WorldWideScience

Sample records for understand toxic risk

  1. Understanding Pesticide Risks: Toxicity and Formulation

    OpenAIRE

    Muntz, Helen; Miller, Rhonda; Alston, Diane

    2016-01-01

    This fact sheet provides information about pesticide risks to human health, primary means of pesticide exposure, standardized measures of pesticide toxicity, pesticide signal words and type of pesticide formulations.

  2. Understanding mechanisms of toxicity: Insights from drug discovery research

    International Nuclear Information System (INIS)

    Houck, Keith A.; Kavlock, Robert J.

    2008-01-01

    Toxicology continues to rely heavily on use of animal testing for prediction of potential for toxicity in humans. Where mechanisms of toxicity have been elucidated, for example endocrine disruption by xenoestrogens binding to the estrogen receptor, in vitro assays have been developed as surrogate assays for toxicity prediction. This mechanistic information can be combined with other data such as exposure levels to inform a risk assessment for the chemical. However, there remains a paucity of such mechanistic assays due at least in part to lack of methods to determine specific mechanisms of toxicity for many toxicants. A means to address this deficiency lies in utilization of a vast repertoire of tools developed by the drug discovery industry for interrogating the bioactivity of chemicals. This review describes the application of high-throughput screening assays as experimental tools for profiling chemicals for potential for toxicity and understanding underlying mechanisms. The accessibility of broad panels of assays covering an array of protein families permits evaluation of chemicals for their ability to directly modulate many potential targets of toxicity. In addition, advances in cell-based screening have yielded tools capable of reporting the effects of chemicals on numerous critical cell signaling pathways and cell health parameters. Novel, more complex cellular systems are being used to model mammalian tissues and the consequences of compound treatment. Finally, high-throughput technology is being applied to model organism screens to understand mechanisms of toxicity. However, a number of formidable challenges to these methods remain to be overcome before they are widely applicable. Integration of successful approaches will contribute towards building a systems approach to toxicology that will provide mechanistic understanding of the effects of chemicals on biological systems and aid in rationale risk assessments

  3. Toxicological Considerations, Toxicity Assessment, and Risk Management of Inhaled Nanoparticles.

    Science.gov (United States)

    Bakand, Shahnaz; Hayes, Amanda

    2016-06-14

    Novel engineered nanoparticles (NPs), nanomaterial (NM) products and composites, are continually emerging worldwide. Many potential benefits are expected from their commercial applications; however, these benefits should always be balanced against risks. Potential toxic effects of NM exposure have been highlighted, but, as there is a lack of understanding about potential interactions of nanomaterials (NMs) with biological systems, these side effects are often ignored. NPs are able to translocate to the bloodstream, cross body membrane barriers effectively, and affect organs and tissues at cellular and molecular levels. NPs may pass the blood-brain barrier (BBB) and gain access to the brain. The interactions of NPs with biological milieu and resulted toxic effects are significantly associated with their small size distribution, large surface area to mass ratio (SA/MR), and surface characteristics. NMs are able to cross tissue and cell membranes, enter into cellular compartments, and cause cellular injury as well as toxicity. The extremely large SA/MR of NPs is also available to undergo reactions. An increased surface area of the identical chemical will increase surface reactivity, adsorption properties, and potential toxicity. This review explores biological pathways of NPs, their toxic potential, and underlying mechanisms responsible for such toxic effects. The necessity of toxicological risk assessment to human health should be emphasised as an integral part of NM design and manufacture.

  4. Toxicological Considerations, Toxicity Assessment, and Risk Management of Inhaled Nanoparticles

    Directory of Open Access Journals (Sweden)

    Shahnaz Bakand

    2016-06-01

    Full Text Available Novel engineered nanoparticles (NPs, nanomaterial (NM products and composites, are continually emerging worldwide. Many potential benefits are expected from their commercial applications; however, these benefits should always be balanced against risks. Potential toxic effects of NM exposure have been highlighted, but, as there is a lack of understanding about potential interactions of nanomaterials (NMs with biological systems, these side effects are often ignored. NPs are able to translocate to the bloodstream, cross body membrane barriers effectively, and affect organs and tissues at cellular and molecular levels. NPs may pass the blood–brain barrier (BBB and gain access to the brain. The interactions of NPs with biological milieu and resulted toxic effects are significantly associated with their small size distribution, large surface area to mass ratio (SA/MR, and surface characteristics. NMs are able to cross tissue and cell membranes, enter into cellular compartments, and cause cellular injury as well as toxicity. The extremely large SA/MR of NPs is also available to undergo reactions. An increased surface area of the identical chemical will increase surface reactivity, adsorption properties, and potential toxicity. This review explores biological pathways of NPs, their toxic potential, and underlying mechanisms responsible for such toxic effects. The necessity of toxicological risk assessment to human health should be emphasised as an integral part of NM design and manufacture.

  5. Protective influence of healthful nutrition on mechanisms of environmental pollutant toxicity and disease risks.

    Science.gov (United States)

    Hoffman, Jessie B; Hennig, Bernhard

    2017-06-01

    Human exposures to environmental contaminants around the world contribute to the global burden of disease and thus require urgent attention. Exploring preventive measures against environmental exposure and disease risk is essential. While a sedentary lifestyle and/or poor dietary habits can exacerbate the deleterious effects resulting from exposure to toxic chemicals, much emerging evidence suggests that positive lifestyle changes (e.g., healthful nutrition) can modulate and/or reduce the toxicity of environmental pollutants. Our work has shown that diets high in anti-inflammatory bioactive food components (e.g., phytochemicals or polyphenols) are possible strategies for modulating and reducing the disease risks associated with exposure to toxic pollutants in the environment. Thus, consuming healthy diets rich in plant-derived bioactive nutrients may reduce the vulnerability to diseases linked to environmental toxic insults. This nutritional paradigm in environmental toxicology requires further study in order to improve our understanding of the relationships between nutrition and other lifestyle modifications and toxicant-induced diseases. © 2017 New York Academy of Sciences.

  6. Human health risk assessment database, "the NHSRC toxicity value database": supporting the risk assessment process at US EPA's National Homeland Security Research Center.

    Science.gov (United States)

    Moudgal, Chandrika J; Garrahan, Kevin; Brady-Roberts, Eletha; Gavrelis, Naida; Arbogast, Michelle; Dun, Sarah

    2008-11-15

    The toxicity value database of the United States Environmental Protection Agency's (EPA) National Homeland Security Research Center has been in development since 2004. The toxicity value database includes a compilation of agent property, toxicity, dose-response, and health effects data for 96 agents: 84 chemical and radiological agents and 12 biotoxins. The database is populated with multiple toxicity benchmark values and agent property information from secondary sources, with web links to the secondary sources, where available. A selected set of primary literature citations and associated dose-response data are also included. The toxicity value database offers a powerful means to quickly and efficiently gather pertinent toxicity and dose-response data for a number of agents that are of concern to the nation's security. This database, in conjunction with other tools, will play an important role in understanding human health risks, and will provide a means for risk assessors and managers to make quick and informed decisions on the potential health risks and determine appropriate responses (e.g., cleanup) to agent release. A final, stand alone MS ACESSS working version of the toxicity value database was completed in November, 2007.

  7. Human health risk assessment database, 'the NHSRC toxicity value database': Supporting the risk assessment process at US EPA's National Homeland Security Research Center

    International Nuclear Information System (INIS)

    Moudgal, Chandrika J.; Garrahan, Kevin; Brady-Roberts, Eletha; Gavrelis, Naida; Arbogast, Michelle; Dun, Sarah

    2008-01-01

    The toxicity value database of the United States Environmental Protection Agency's (EPA) National Homeland Security Research Center has been in development since 2004. The toxicity value database includes a compilation of agent property, toxicity, dose-response, and health effects data for 96 agents: 84 chemical and radiological agents and 12 biotoxins. The database is populated with multiple toxicity benchmark values and agent property information from secondary sources, with web links to the secondary sources, where available. A selected set of primary literature citations and associated dose-response data are also included. The toxicity value database offers a powerful means to quickly and efficiently gather pertinent toxicity and dose-response data for a number of agents that are of concern to the nation's security. This database, in conjunction with other tools, will play an important role in understanding human health risks, and will provide a means for risk assessors and managers to make quick and informed decisions on the potential health risks and determine appropriate responses (e.g., cleanup) to agent release. A final, stand alone MS ACESSS working version of the toxicity value database was completed in November, 2007

  8. Current understanding of microplastics in the environment: Occurrence, fate, risks, and what we should do.

    Science.gov (United States)

    Peng, Jinping; Wang, Jundong; Cai, Liqi

    2017-05-01

    Microplastics pollution has been documented in the global environment, including at sea, in freshwater and in atmospheric fallout. Ingestion of microplastics by multiple kinds of organisms has been reported and has received increasing attention, because microplastics not only act as a source of toxic chemicals but also a sink for toxic chemicals. To better understand the great concerns about microplastics and associated toxic chemicals potential exposed to the organisms ingesting the debris, we should know more about the occurrence, fate, and risks of microplastics in the environment. What we should do depends on this better understanding. Integr Environ Assess Manag 2017;13:476-482. © 2017 SETAC. © 2017 SETAC.

  9. Health risks associated with inhaled nasal toxicants

    NARCIS (Netherlands)

    Feron, VJ; Arts, JHE; Kuper, CF; Slootweg, PJ; Woutersen, RA

    2001-01-01

    Health risks of inhaled nasal toxicants were reviewed with emphasis on chemically induced nasal lesions in humans, sensory irritation, olfactory and trigeminal nerve toxicity, nasal immunopathology and carcinogenesis, nasal responses to chemical mixtures, in vitro models, and nasal dosimetry- and

  10. Understanding environmental health inequalities through comparative intracategorical analysis: racial/ethnic disparities in cancer risks from air toxics in El Paso County, Texas.

    Science.gov (United States)

    Collins, Timothy W; Grineski, Sara E; Chakraborty, Jayajit; McDonald, Yolanda J

    2011-01-01

    This paper contributes to the environmental justice literature by analyzing contextually relevant and racial/ethnic group-specific variables in relation to air toxics cancer risks in a US-Mexico border metropolis at the census block group-level. Results indicate that Hispanics' ethnic status interacts with class, gender and age status to amplify disproportionate risk. In contrast, results indicate that non-Hispanic whiteness attenuates cancer risk disparities associated with class, gender and age status. Findings suggest that a system of white-Anglo privilege shapes the way in which race/ethnicity articulates with other dimensions of inequality to create unequal cancer risks from air toxics. Copyright © 2010 Elsevier Ltd. All rights reserved.

  11. Rethink potential risks of toxic emissions from natural gas and oil mining.

    Science.gov (United States)

    Meng, Qingmin

    2018-09-01

    Studies have showed the increasing environmental and public health risks of toxic emissions from natural gas and oil mining, which have become even worse as fracking is becoming a dominant approach in current natural gas extraction. However, governments and communities often overlook the serious air pollutants from oil and gas mining, which are often quantified lower than the significant levels of adverse health effects. Therefore, we are facing a challenging dilemma: how could we clearly understand the potential risks of air toxics from natural gas and oil mining. This short study aims at the design and application of simple and robust methods to enhance and improve current understanding of the becoming worse toxic air emissions from natural gas and oil mining as fracking is becoming the major approach. Two simple ratios, the min-to-national-average and the max-to-national-average, are designed and applied to each type of air pollutants in a natural gas and oil mining region. The two ratios directly indicate how significantly high a type of air pollutant could be due to natural gas and oil mining by comparing it to the national average records, although it may not reach the significant risks of adverse health effects according to current risk screening methods. The min-to-national-average and the max-to-national-average ratios can be used as a direct and powerful method to describe the significance of air pollution by comparing it to the national average. The two ratios are easy to use for governments, stakeholders, and the public to pay enough attention on the air pollutants from natural gas and oil mining. The two ratios can also be thematically mapped at sampled sites for spatial monitoring, but spatial mitigation and analysis of environmental and health risks need other measurements of environmental and demographic characteristics across a natural gas and oil mining area. Copyright © 2018 Elsevier Ltd. All rights reserved.

  12. Toxicity testing in the 21 century: defining new risk assessment approaches based on perturbation of intracellular toxicity pathways.

    Directory of Open Access Journals (Sweden)

    Sudin Bhattacharya

    Full Text Available The approaches to quantitatively assessing the health risks of chemical exposure have not changed appreciably in the past 50 to 80 years, the focus remaining on high-dose studies that measure adverse outcomes in homogeneous animal populations. This expensive, low-throughput approach relies on conservative extrapolations to relate animal studies to much lower-dose human exposures and is of questionable relevance to predicting risks to humans at their typical low exposures. It makes little use of a mechanistic understanding of the mode of action by which chemicals perturb biological processes in human cells and tissues. An alternative vision, proposed by the U.S. National Research Council (NRC report Toxicity Testing in the 21(st Century: A Vision and a Strategy, called for moving away from traditional high-dose animal studies to an approach based on perturbation of cellular responses using well-designed in vitro assays. Central to this vision are (a "toxicity pathways" (the innate cellular pathways that may be perturbed by chemicals and (b the determination of chemical concentration ranges where those perturbations are likely to be excessive, thereby leading to adverse health effects if present for a prolonged duration in an intact organism. In this paper we briefly review the original NRC report and responses to that report over the past 3 years, and discuss how the change in testing might be achieved in the U.S. and in the European Union (EU. EU initiatives in developing alternatives to animal testing of cosmetic ingredients have run very much in parallel with the NRC report. Moving from current practice to the NRC vision would require using prototype toxicity pathways to develop case studies showing the new vision in action. In this vein, we also discuss how the proposed strategy for toxicity testing might be applied to the toxicity pathways associated with DNA damage and repair.

  13. Food plant toxicants and safety - Risk assessment and regulation of inherent toxicants in plant foods

    DEFF Research Database (Denmark)

    Essers, A.J.A.; Alink, G.M.; Speijers, G.J.A.

    1998-01-01

    The ADI as a tool for risk management and regulation of food additives and pesticide residues is not readily applicable to inherent food plant toxicants: The margin between actual intake and potentially toxic levels is often small; application of the default uncertainty factors used to derive ADI...... values, particularly when extrapolating from animal data, would prohibit the utilisation of the food, which may have an overall beneficial health effect. Levels of inherent toxicants are difficult to control; their complete removal is not always wanted, due to their function for the plant or for human...... health. The health impact of the inherent toxicant is often modified by factors in the food, e.g. the bioavailability from the matrix and interaction with other inherent constituents. Risk-benefit analysis should be made for different consumption scenarios, without the use of uncertainty factors. Crucial...

  14. Nanoparticle interactions with co-existing contaminants: joint toxicity, bioaccumulation and risk.

    Science.gov (United States)

    Deng, Rui; Lin, Daohui; Zhu, Lizhong; Majumdar, Sanghamitra; White, Jason C; Gardea-Torresdey, Jorge L; Xing, Baoshan

    2017-06-01

    With their growing production and application, engineered nanoparticles (NPs) are increasingly discharged into the environment. The released NPs can potentially interact with pre-existing contaminants, leading to biological effects (bioaccumulation and/or toxicity) that are poorly understood. Most studies on NPs focus on single analyte exposure; the existing literature on joint toxicity of NPs and co-existing contaminants is rather limited but beginning to develop rapidly. This is the first review paper evaluating the current state of knowledge regarding the joint effects of NPs and co-contaminants. Here, we review: (1) methods for investigating and evaluating joint effects of NPs and co-contaminants; (2) simultaneous toxicities from NPs co-exposed with organic contaminants, metal/metalloid ions, dissolved organic matter (DOM), inorganic ligands and additional NPs; and (3) the influence of NPs co-exposure on the bioaccumulation of organic contaminants and heavy metal ions, as well as the influence of contaminants on NPs bioaccumulation. In addition, future research needs are discussed so as to better understand risk associated with NPs-contaminant co-exposure.

  15. Food plant toxicants and safety: risk assessment and regulation of inherent toxicants in plant foods.

    NARCIS (Netherlands)

    Essers, A.J.; Alink, G.M.; Speijers, G.J.A.; Alexander, J.; Bouwmeister, P.J.; Brandt, van den P.A.; Ciere, S.; Gry, J.; Herrman, J.; Kuiper, H.A.; Mortby, E.; Renwickn, A.G.

    1998-01-01

    The ADI as a tool for risk management and regulation of food additives and pesticide residues is not readily applicable to inherent food plant toxicants: The margin between actual intake and potentially toxic levels is often small; application of the default uncertainty factors used to derive ADI

  16. Mixtures of toxic agents and attributable risk calculations

    International Nuclear Information System (INIS)

    Seiler, F.A.; Scott, B.R.

    1987-01-01

    Calculations of attributable risks have attracted increasing interest recently. However, these efforts have been limited to mostly one agent, radiation, and no interactions with effects of other toxic agents have been taken into account. This paper outlines a generic approach to the calculation of attributable risks for an exposure to several toxic agents and interaction effects associated with them. In this calculation, the partition of interaction terms between the agents responsible is of particular importance. At present, there are no rules on how to assign equitable shares, so one methodology will be proposed and others discussed briefly. For one example of an assignment, the standard errors of the attributable risks are determined in terms of the uncertainties of the input parameters, thus setting the stage for a comparison of the different shares of responsibility

  17. Toxic-metabolic Risk Factors in Pediatric Pancreatitis: Recommendations for Diagnosis, Management, and Future Research.

    Science.gov (United States)

    Husain, Sohail Z; Morinville, Veronique; Pohl, John; Abu-El-Haija, Maisam; Bellin, Melena D; Freedman, Steve; Hegyi, Peter; Heyman, Melvin B; Himes, Ryan; Ooi, Chee Y; Schwarzenberg, Sarah J; Usatin, Danielle; Uc, Aliye

    2016-04-01

    Pancreatitis in children can result from metabolic and toxic risk factors, but the evidence linking these factors is sparse. We review the evidence for association or causality of these risk factors in pancreatitis, discuss management strategies, and their rationale. We conducted a review of the pediatric pancreatitis literature with respect to the following risk factors: hyperlipidemia, hypercalcemia, chronic renal failure, smoking exposure, alcohol, and medications. Areas of additional research were identified. Hypertriglyceridemia of 1000 mg/dL or greater poses an absolute risk for pancreatitis; persistent elevations of calcium are predisposing. Further research is necessary to determine whether end-stage renal disease leads to increased pancreatitis in children similar to adults. It is unknown whether cigarette smoking exposure, which clearly increases risk in adults, also increases risk in children. The role of alcohol in pediatric pancreatitis, whether direct or modifying, needs to be elucidated. The evidence supporting most cases of medication-induced pancreatitis is poor. Drug structure, improper handling of drug by host, and bystander status may be implicated. Other pancreatitis risk factors must be sought in all cases. The quality of evidence supporting causative role of various toxic and metabolic factors in pediatric pancreatitis is variable. Careful phenotyping is essential, including search for other etiologic risk factors. Directed therapy includes correction/removal of any agent identified, and general supportive measures. Further research is necessary to improve our understanding of these pancreatitis risk factors in children.

  18. [Risk assessment and risk control for occupational exposure to chemical toxicants from an isophorone nitrile device].

    Science.gov (United States)

    Wang, Dejun; Fu, Xiaokuan; Kong, Fanling; Sui, Shaofeng; Jiang, Yuanyuan; Du, Yinglin; Zhou, Jingyang

    2014-06-01

    Risk assessment and risk control for occupational exposure to chemical toxicants were performed on an isophorone nitrile device with an annual production of 5,000 tons, based on improved Singaporean semi-quantitative risk assessment method, with consideration of actual situation in China and in the present project. With the use of engineering analysis and identification of occupational hazards in the improved Singaporean semi-quantitative risk assessment method, hazard rating (HR) and risk assessment were performed on chemical toxicants from an isophorone nitrile device with an annual production of 5,000 tons. The chemical toxicants in the isophorone nitrile device were mainly isophorone, hydrocyanic acid, methanol, phosphoric acid, sodium hydroxide, and sodium cyanide; the HR values were mild hazard (2), extreme hazard (5), mild hazard (2), mild hazard (2), moderate hazard (3), and extreme hazard (5), respectively, and the corresponding exposure rating (ER) values were 2.09, 2.72, 2.76, 1.68, 2.0, and 1.59, respectively. The risk of chemical toxicants in this project was assessed according to the formula Risk = [HR×ER](1/2). Hydrocyanic acid was determined as high risk, sodium hydroxide and sodium cyanide as medium risk, and isophorone, methanol, and phosphoric acid as low risk. Priority in handling of risks was determined by risk rating. The table of risk control measure was established for pre-assessment of occupational hazards. With risk assessment in this study, we concluded that the isophorone nitrile device with 5,000 ton annual production was a high-occupational hazard device. This device is a project of extreme occupational hazard. The improved Singaporean semi-quantitative risk assessment method is a scientific and applicable method, and is especially suitable for pre-evaluation of on-site project with no analogy.

  19. Use of environmental health-risk analysis for managing toxic substances

    International Nuclear Information System (INIS)

    McKone, T.E.

    1985-03-01

    This paper presents a set of simple models used to assess health risks based on toxicity, environmental mobility and persistence. These models use a representative landscape in order to describe the steady-state distribution of arsenic, tritiated water, and TCDD as a result of continuous additions to soil. This information is used to assess potential exposures. Application of the screening model to three chemically different carcinogens reveals that the environmental health risk does not scale with direct measures of toxicity. As estimated here, the environmental health risk of TCDD relative to tritiated water and arsenic is roughly an order of magnitude less than its cancer potency relative to these compounds. The difference is attributable in large part to the immobility of TCDD relative to tritium and the lower persistence of TCDD compared to arsenic. The purpose is to present a simple procedure for using the relative behavior of toxic species under prototype conditions as a basis for risk management. 21 refs., 4 tabs

  20. Consolidating Risk Estimates for Radiation-Induced Complications in Individual Patient: Late Rectal Toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Prior, Phillip; Devisetty, Kiran [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI (United States); Tarima, Sergey S. [Division of Biostatistics, Institute for Health and Society, Medical College of Wisconsin, Milwaukee, WI (United States); Lawton, Colleen A.F. [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI (United States); Semenenko, Vladimir A., E-mail: vsemenenko@mcw.edu [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI (United States)

    2012-05-01

    Purpose: To test the feasibility of a new approach to synthesize published normal tissue complication data using late rectal toxicity in prostate cancer as an example. Methods and Materials: A data survey was performed to identify the published reports on the dose-response relationships for late rectal toxicity. The risk estimates for Grade 1 or greater, Grade 2 or greater, and Grade 3 or greater toxicity were obtained for a test cohort of patients treated at our institution. The influence of the potential factors that might have affected the reported toxicity levels was investigated. The studies that did not conform to the general data trends were excluded, and single, combined risk estimates were derived for each patient and toxicity level. Results: A total of 21 studies of nonoverlapping patient populations were identified. Three studies provided dose-response models for more than one level of toxicity. Of these 21 studies, 6, 14, and 5 were used to derive the initial risk estimates for Grade 1, 2, and 3 or greater toxicity, respectively. A comparison of risk estimates between the studies reporting rectal bleeding and rectal toxicity (bleeding plus other symptoms) or between studies with follow-up <36 months and {>=}36 months did not reveal significant differences (p {>=} .29 for all comparisons). After excluding three reports that did not conform to the general data trends, the combined risk estimates were derived from 5 reports (647 patients), 11 reports (3,369 patients), and 5 reports (1,330 patients) for Grade 1, 2, and 3 or greater toxicity, respectively. Conclusions: The proposed approach is feasible and allows for more systematic use of published dose-response data to estimate the complication risks for the individual patient.

  1. Consolidating Risk Estimates for Radiation-Induced Complications in Individual Patient: Late Rectal Toxicity

    International Nuclear Information System (INIS)

    Prior, Phillip; Devisetty, Kiran; Tarima, Sergey S.; Lawton, Colleen A.F.; Semenenko, Vladimir A.

    2012-01-01

    Purpose: To test the feasibility of a new approach to synthesize published normal tissue complication data using late rectal toxicity in prostate cancer as an example. Methods and Materials: A data survey was performed to identify the published reports on the dose–response relationships for late rectal toxicity. The risk estimates for Grade 1 or greater, Grade 2 or greater, and Grade 3 or greater toxicity were obtained for a test cohort of patients treated at our institution. The influence of the potential factors that might have affected the reported toxicity levels was investigated. The studies that did not conform to the general data trends were excluded, and single, combined risk estimates were derived for each patient and toxicity level. Results: A total of 21 studies of nonoverlapping patient populations were identified. Three studies provided dose–response models for more than one level of toxicity. Of these 21 studies, 6, 14, and 5 were used to derive the initial risk estimates for Grade 1, 2, and 3 or greater toxicity, respectively. A comparison of risk estimates between the studies reporting rectal bleeding and rectal toxicity (bleeding plus other symptoms) or between studies with follow-up <36 months and ≥36 months did not reveal significant differences (p ≥ .29 for all comparisons). After excluding three reports that did not conform to the general data trends, the combined risk estimates were derived from 5 reports (647 patients), 11 reports (3,369 patients), and 5 reports (1,330 patients) for Grade 1, 2, and 3 or greater toxicity, respectively. Conclusions: The proposed approach is feasible and allows for more systematic use of published dose–response data to estimate the complication risks for the individual patient.

  2. Human Health Toxicity Values in Superfund Risk Assessments

    Science.gov (United States)

    This memorandum revises the hierarchy of human health toxicity values generally recommended for use inr isk assessments, originally presented in Risk Assessment Guidance for Superfund Volume I, Part A.

  3. Toxic-Metabolic Risk Factors in Pediatric Pancreatitis: Recommendations for Diagnosis, Management and Future Research

    Science.gov (United States)

    Husain, Sohail Z.; Morinville, Veronique; Pohl, John; Abu-El-Haija, Maisam; Bellin, Melena D.; Freedman, Steve; Hegyi, Peter; Heyman, Melvin B; Himes, Ryan; Ooi, Chee Y.; Schwarzenberg, Sarah Jane; Usatin, Danielle; Uc, Aliye

    2016-01-01

    Objectives Pancreatitis in children can result from metabolic and toxic risk factors, but the evidence linking these factors is sparse. We review the evidence for association or causality of these risk factors in pancreatitis, discuss management strategies and their rationale. Methods We conducted a review of the pediatric pancreatitis literature with respect to the following risk factors: (a) hyperlipidemia, (b) hypercalcemia, (c) chronic renal failure, (d) smoking exposure, (e) alcohol, and (f) medications. Areas of additional research were identified. Results Hypertriglyceridemia of 1000 mg/dl or greater poses an absolute risk for pancreatitis; persistent elevations of calcium are predisposing. Further research is necessary to determine whether end stage renal disease leads to increased pancreatitis in children similar to adults. It is unknown whether cigarette smoking exposure, which clearly increases risk in adults, also increases risk in children. The role of alcohol in pediatric pancreatitis, whether direct or modifying, needs to be elucidated. The evidence supporting most cases of medication-induced pancreatitis is poor. Drug structure, improper handling of drug by host, and by-stander status may be implicated. Other pancreatitis risk factors must be sought in all cases. Conclusions The quality of evidence supporting causative role of various toxic and metabolic factors in pediatric pancreatitis is variable. Careful phenotyping is essential, including search for other etiologic risk factors. Directed therapy includes correction/ removal of any agent identified, and general supportive measures. Further research is necessary to improve our understanding of these pancreatitis risk factors in children. PMID:26594832

  4. Reference manual for toxicity and exposure assessment and risk characterization. CERCLA Baseline Risk Assessment

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-03-01

    The Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA, 1980) (CERCLA or Superfund) was enacted to provide a program for identifying and responding to releases of hazardous substances into the environment. The Superfund Amendments and Reauthorization Act (SARA, 1986) was enacted to strengthen CERCLA by requiring that site clean-ups be permanent, and that they use treatments that significantly reduce the volume, toxicity, or mobility of hazardous pollutants. The National Oil and Hazardous Substances Pollution Contingency Plan (NCP) (USEPA, 1985; USEPA, 1990) implements the CERCLA statute, presenting a process for (1) identifying and prioritizing sites requiring remediation and (2) assessing the extent of remedial action required at each site. The process includes performing two studies: a Remedial Investigation (RI) to evaluate the nature, extent, and expected consequences of site contamination, and a Feasibility Study (FS) to select an appropriate remedial alternative adequate to reduce such risks to acceptable levels. An integral part of the RI is the evaluation of human health risks posed by hazardous substance releases. This risk evaluation serves a number of purposes within the overall context of the RI/FS process, the most essential of which is to provide an understanding of ``baseline`` risks posed by a given site. Baseline risks are those risks that would exist if no remediation or institutional controls are applied at a site. This document was written to (1) guide risk assessors through the process of interpreting EPA BRA policy and (2) help risk assessors to discuss EPA policy with regulators, decision makers, and stakeholders as it relates to conditions at a particular DOE site.

  5. Reference manual for toxicity and exposure assessment and risk characterization. CERCLA Baseline Risk Assessment

    International Nuclear Information System (INIS)

    1995-03-01

    The Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA, 1980) (CERCLA or Superfund) was enacted to provide a program for identifying and responding to releases of hazardous substances into the environment. The Superfund Amendments and Reauthorization Act (SARA, 1986) was enacted to strengthen CERCLA by requiring that site clean-ups be permanent, and that they use treatments that significantly reduce the volume, toxicity, or mobility of hazardous pollutants. The National Oil and Hazardous Substances Pollution Contingency Plan (NCP) (USEPA, 1985; USEPA, 1990) implements the CERCLA statute, presenting a process for (1) identifying and prioritizing sites requiring remediation and (2) assessing the extent of remedial action required at each site. The process includes performing two studies: a Remedial Investigation (RI) to evaluate the nature, extent, and expected consequences of site contamination, and a Feasibility Study (FS) to select an appropriate remedial alternative adequate to reduce such risks to acceptable levels. An integral part of the RI is the evaluation of human health risks posed by hazardous substance releases. This risk evaluation serves a number of purposes within the overall context of the RI/FS process, the most essential of which is to provide an understanding of ''baseline'' risks posed by a given site. Baseline risks are those risks that would exist if no remediation or institutional controls are applied at a site. This document was written to (1) guide risk assessors through the process of interpreting EPA BRA policy and (2) help risk assessors to discuss EPA policy with regulators, decision makers, and stakeholders as it relates to conditions at a particular DOE site

  6. Toxic chemical risk acceptance criteria

    International Nuclear Information System (INIS)

    Craig, D.K.; Davis, J.; Lee, L.; Lein, P.; Omberg, S.

    1992-01-01

    This paper presents recommendations of a subcommittee of the Westinghouse M ampersand 0 Nuclear Facility Safety Committee concerning toxic chemical risk acceptance criteria. Two sets of criteria have been developed, one for use in the hazard classification of facilities, and the second for use in comparing risks in DOE non-reactor nuclear facility Safety Analysis Reports. The Emergency Response Planning Guideline (ERPG) values are intended to provide estimates of concentration ranges for specific chemicals above which exposure would be expected to lead to adverse heath effects of increasing severity for ERPG-1, -2, and -3s. The subcommittee recommends that criteria for hazard class or risk range be based on ERPGs for all chemicals. Probability-based Incremental Cancer Risk (ICR) criteria are recommended for additional analyses of risks from all known or suspected human carcinogens. Criteria are given for both on-site and off-site exposure. The subcommittee also recommends that the 5-minute peak concentration be compared with the relevant criterion with no adjustment for exposure time. Since ERPGs are available for only a limited number of chemicals, the subcommittee has developed a proposed hierarchy of concentration limit parameters for the different criteria

  7. Patients Undergoing Radiation Therapy Are at Risk of Financial Toxicity: A Patient-based Prospective Survey Study.

    Science.gov (United States)

    Palmer, Joshua D; Patel, Tejash T; Eldredge-Hindy, Harriet; Keith, Scott W; Patel, Tapas; Malatesta, Theresa; DiNome, Jessie; Lowther, Anne; Ferguson, Linda; Wagenborg, Sally; Smyles, John; Babaria, Usha; Stabile, Richard; Gressen, Eric; Rudoler, Shari; Fisher, Scot A

    2018-06-01

    Little is known about the financial burden experienced by patients receiving radiation therapy. Furthermore, currently, no financial toxicity screening tools have been validated for use in radiation oncology. Physician surveys were used to gauge provider understanding of treatment costs and their willingness to adopt the use of financial toxicity screening tools. Post-treatment patient surveys were used to investigate the covariates of treatment-induced financial risk. Of the 210 radiation oncologists who completed our survey, 53% reported being "very concerned" with treatment-related costs negatively affecting their patients, and 80% believed that a financial toxicity screening tool would be useful in practice. An analysis of patient surveys using logistic regression found age and cancer site to be the most important variables associated with financial toxicity. Thirty-four patients (22%) experienced financial toxicity related to treatment. The financial toxicities experienced were loss of job (28%), loss of income (24%), difficulty paying their rent or mortgage (20%), difficulty paying for transportation (15%), and difficulty paying for meals (13%). Financial toxicity is an important measure for patients and providers and is experienced by approximately one quarter of patients. Further studies to improve models to predict financial toxicity and how financial toxicity is related to patient outcomes and quality of life are warranted. Copyright © 2018 Elsevier Inc. All rights reserved.

  8. Quantifying risk and accuracy in cancer risk assessment: the process and its role in risk management problem-solving.

    Science.gov (United States)

    Turturro, A; Hart, R W

    1987-01-01

    A better understanding of chemical-induced cancer has led to appreciation of similarities to problems addressed by risk management of radiation-induced toxicity. Techniques developed for cancer risk assessment of toxic substances can be generalized to toxic agents. A recent problem-solving approach for risk management of toxic substances developed for the U.S. Department of Health and Human Services, and the role of risk assessment and how uncertainty should be treated within the context of this approach, is discussed. Finally, two different methods, research into the assumptions underlying risk assessment and the modification of risk assessment/risk management documents, are used to illustrate how the technique can be applied.

  9. Incorporating pharmacokinetic differences between children and adults in assessing children's risks to environmental toxicants

    International Nuclear Information System (INIS)

    Ginsberg, Gary; Hattis, Dale; Sonawane, Babasaheb

    2004-01-01

    Children's risks from environmental toxicant exposure can be affected by pharmacokinetic factors that affect the internal dose of parent chemical or active metabolite. There are numerous physiologic differences between neonates and adults that affect pharmacokinetics including size of lipid, and tissue compartments, organ blood flows, protein binding capacity, and immature function of renal and hepatic systems. These factors combine to decrease the clearance of many therapeutic drugs, which can also be expected to occur with environmental toxicants in neonates. The net effect may be greater or lesser internal dose of active toxicant depending upon how the agent is distributed, metabolized, and eliminated. Child/adult pharmacokinetic differences decrease with increasing postnatal age, but these factors should still be considered in any children's age group, birth through adolescence, for which there is toxicant exposure. Physiologically based pharmacokinetic (PBPK) models can simulate the absorption, distribution, metabolism, and excretion of xenobiotics in both children and adults, allowing for a direct comparison of internal dose and risk across age groups. This review provides special focus on the development of hepatic cytochrome P-450 enzymes (CYPs) in early life and how this information, along with many factors unique to children, can be applied to PBPK models for this receptor population. This review describes a case study involving the development of neonatal PBPK models for the CYP1A2 substrates caffeine and theophylline. These models were calibrated with pharmacokinetic data in neonates and used to help understand key metabolic differences between neonates and adults across these two drugs

  10. In utero exposure to toxic air pollutants and risk of childhood autism.

    Science.gov (United States)

    von Ehrenstein, Ondine S; Aralis, Hilary; Cockburn, Myles; Ritz, Beate

    2014-11-01

    Genetic and environmental factors are believed to contribute to the development of autism, but relatively few studies have considered potential environmental risks. Here, we examine risks for autism in children related to in utero exposure to monitored ambient air toxics from urban emissions. Among the cohort of children born in Los Angeles County, California, 1995-2006, those whose mothers resided during pregnancy in a 5-km buffer around air toxics monitoring stations were included (n = 148,722). To identify autism cases in this cohort, birth records were linked to records of children diagnosed with primary autistic disorder at the California Department of Developmental Services between 1998 and 2009 (n = 768). We calculated monthly average exposures during pregnancy for 24 air toxics selected based on suspected or known neurotoxicity or neurodevelopmental toxicity. Factor analysis helped us identify the correlational structure among air toxics, and we estimated odds ratios (ORs) for autism from logistic regression analyses. Autism risks were increased per interquartile range increase in average concentrations during pregnancy of several correlated toxics mostly loading on 1 factor, including 1,3-butadiene (OR = 1.59 [95% confidence interval = 1.18-2.15]), meta/para-xylene (1.51 [1.26-1.82]), other aromatic solvents, lead (1.49 [1.23-1.81]), perchloroethylene (1.40 [1.09-1.80]), and formaldehyde (1.34 [1.17-1.52]), adjusting for maternal age, race/ethnicity, nativity, education, insurance type, parity, child sex, and birth year. Risks for autism in children may increase following in utero exposure to ambient air toxics from urban traffic and industry emissions, as measured by community-based air-monitoring stations.

  11. Toxicity ratios: Their use and abuse in predicting the risk from induced cancer

    International Nuclear Information System (INIS)

    Mays, C.W.; Taylor, G.N.; Lloyd, R.D.

    1986-01-01

    The toxicity ratio concept assumes the validity of certain relationships. In some examples for bone sarcoma induction, the approximate toxicity of 239 Pu in man can be calculated algebraically from the observed toxicity in the radium-dial painters and the ratio of 239 Pu/ 226 Ra toxicities in suitable laboratory mammals. In a species highly susceptible to bone sarcoma induction, the risk coefficients for both 239 Pu and 226 Ra are elevated, but the toxicity ratio of 239 Pu to 226 Ra tends to be similar to the ratio in resistant species. Among the tested species the toxicity ratio of 239 Pu to 226 Ra ranged from 6 to 22 (a fourfold range), whereas their relative sensitivities to 239 Pu varied by a factor of 150. The toxicity ratio approach can also be used to estimate the actinide risk to man from liver cancer, by comparing to the Thorotrast patients; from lung cancer, by comparing to the uranium miners and the atomic-bomb survivors; and from neutron-induced cancers, by comparing to cancers induced by gamma rays. The toxicity ratio can be used to predict the risk to man from a specific type of cancer that has been reliably induced by a reference radiation in humans and that can be induced by both the reference and the investigated radiation in suitable laboratory animals. 26 refs., 3 figs., 1 tab

  12. Launch Area Toxic Risk Analysis Program (LATRA) Toxicology Review

    National Research Council Canada - National Science Library

    Prince, Joseph

    1996-01-01

    .... Therefore, a literature search of three species of rocket emissions was performed to identify health effects information useful to HQ Space Command for managing the risk from these toxic clouds...

  13. Understand Your Risk for Heart Failure

    Science.gov (United States)

    ... Heart.org Arrhythmia About Arrhythmia Why Arrhythmia Matters Understand Your Risk for Arrhythmia Symptoms, Diagnosis & Monitoring of ... Heart Defects The Impact of Congenital Heart Defects Understand Your Risk for Congenital Heart Defects Symptoms & Diagnosis ...

  14. Risks, risk assessment and risk competence in toxicology.

    Science.gov (United States)

    Stahlmann, Ralf; Horvath, Aniko

    2015-01-01

    Understanding the toxic effects of xenobiotics requires sound knowledge of physiology and biochemistry. The often described lack of understanding pharmacology/toxicology is therefore primarily caused by the general absence of the necessary fundamental knowledge. Since toxic effects depend on exposure (or dosage) assessing the risks arising from toxic substances also requires quantitative reasoning. Typically public discussions nearly always neglect quantitative aspects and laypersons tend to disregard dose-effect-relationships. One of the main reasons for such disregard is the fact that exposures often occur at extremely low concentrations that can only be perceived intellectually but not by the human senses. However, thresholds in the low exposure range are often scientifically disputed. At the same time, ignorance towards known dangers is wide-spread. Thus, enhancing the risk competence of laypersons will have to be initially restricted to increasing the awareness of existing problems.

  15. Understanding Pre-Quantitative Risk in Projects

    Science.gov (United States)

    Cooper, Lynne P.

    2011-01-01

    Standard approaches to risk management in projects depend on the ability of teams to identify risks and quantify the probabilities and consequences of these risks (e.g., the 5 x 5 risk matrix). However, long before quantification does - or even can - occur, and long after, teams make decisions based on their pre-quantitative understanding of risk. These decisions can have long-lasting impacts on the project. While significant research has looked at the process of how to quantify risk, our understanding of how teams conceive of and manage pre-quantitative risk is lacking. This paper introduces the concept of pre-quantitative risk and discusses the implications of addressing pre-quantitative risk in projects.

  16. Undetected Toxicity Risk in Pharmacogenetic Testing for Dihydropyrimidine Dehydrogenase

    Directory of Open Access Journals (Sweden)

    Felicia Stefania Falvella

    2015-04-01

    Full Text Available Fluoropyrimidines, the mainstay agents for the treatment of colorectal cancer, alone or as a part of combination therapies, cause severe adverse reactions in about 10%–30% of patients. Dihydropyrimidine dehydrogenase (DPD, a key enzyme in the catabolism of 5-fluorouracil, has been intensively investigated in relation to fluoropyrimidine toxicity, and several DPD gene (DPYD polymorphisms are associated with decreased enzyme activity and increased risk of fluoropyrimidine-related toxicity. In patients carrying non-functional DPYD variants (c.1905+1G>A, c.1679T>G, c.2846A>T, fluoropyrimidines should be avoided or reduced according to the patients’ homozygous or heterozygous status, respectively. For other common DPYD variants (c.496A>G, c.1129-5923C>G, c.1896T>C, conflicting data are reported and their use in clinical practice still needs to be validated. The high frequency of DPYD polymorphism and the lack of large prospective trials may explain differences in studies’ results. The epigenetic regulation of DPD expression has been recently investigated to explain the variable activity of the enzyme. DPYD promoter methylation and its regulation by microRNAs may affect the toxicity risk of fluoropyrimidines. The studies we reviewed indicate that pharmacogenetic testing is promising to direct personalised dosing of fluoropyrimidines, although further investigations are needed to establish the role of DPD in severe toxicity in patients treated for colorectal cancer.

  17. Risk Levels of Toxic Cyanobacteria in Portuguese Recreational Freshwaters

    Directory of Open Access Journals (Sweden)

    Carina Menezes

    2017-10-01

    Full Text Available Portuguese freshwater reservoirs are important socio-economic resources, namely for recreational use. National legislation concerning bathing waters does not include mandatory levels or guidelines for cyanobacteria and cyanotoxins. This is an issue of concern since cyanotoxin-based evidence is insufficient to change the law, and the collection of scientific evidence has been hampered by the lack of regulatory levels for cyanotoxins in bathing waters. In this work, we evaluate the profile of cyanobacteria and microcystins (MC in eight freshwater reservoirs from the center of Portugal, used for bathing/recreation, in order to determine the risk levels concerning toxic cyanobacteria occurrence. Three of the reservoirs did not pose a risk of MC contamination. However, two reservoirs presented a high risk in 7% of the samples according to the World Health Organization (WHO guidelines for MC in bathing waters (above 20 µg/L. In the remaining three reservoirs, the risk concerning microcystins occurrence was low. However, they exhibited recurrent blooms and persistent contamination with MC up to 4 µg/L. Thus, the risk of exposure to MC and potential acute and/or chronic health outcomes should not be disregarded in these reservoirs. These results contribute to characterize the cyanobacterial blooms profile and to map the risk of toxic cyanobacteria and microcystins occurrence in Portuguese inland waters.

  18. Risks, risk assessment and risk competence in toxicology

    Science.gov (United States)

    Stahlmann, Ralf; Horvath, Aniko

    2015-01-01

    Understanding the toxic effects of xenobiotics requires sound knowledge of physiology and biochemistry. The often described lack of understanding pharmacology/toxicology is therefore primarily caused by the general absence of the necessary fundamental knowledge. Since toxic effects depend on exposure (or dosage) assessing the risks arising from toxic substances also requires quantitative reasoning. Typically public discussions nearly always neglect quantitative aspects and laypersons tend to disregard dose-effect-relationships. One of the main reasons for such disregard is the fact that exposures often occur at extremely low concentrations that can only be perceived intellectually but not by the human senses. However, thresholds in the low exposure range are often scientifically disputed. At the same time, ignorance towards known dangers is wide-spread. Thus, enhancing the risk competence of laypersons will have to be initially restricted to increasing the awareness of existing problems. PMID:26195922

  19. Risks, risk assessment and risk competence in toxicology

    Directory of Open Access Journals (Sweden)

    Stahlmann, Ralf

    2015-07-01

    Full Text Available Understanding the toxic effects of xenobiotics requires sound knowledge of physiology and biochemistry. The often described lack of understanding pharmacology/toxicology is therefore primarily caused by the general absence of the necessary fundamental knowledge. Since toxic effects depend on exposure (or dosage assessing the risks arising from toxic substances also requires quantitative reasoning. Typically public discussions nearly always neglect quantitative aspects and laypersons tend to disregard dose-effect-relationships. One of the main reasons for such disregard is the fact that exposures often occur at extremely low concentrations that can only be perceived intellectually but not by the human senses. However, thresholds in the low exposure range are often scientifically disputed. At the same time, ignorance towards known dangers is wide-spread. Thus, enhancing the risk competence of laypersons will have to be initially restricted to increasing the awareness of existing problems.

  20. The risk of toxic retinopathy in patients on long-term hydroxychloroquine therapy.

    Science.gov (United States)

    Melles, Ronald B; Marmor, Michael F

    2014-12-01

    Hydroxychloroquine sulfate is widely used for the long-term treatment of autoimmune conditions but can cause irreversible toxic retinopathy. Prior estimations of risk were low but were based largely on short-term users or severe retinal toxicity (bull's eye maculopathy). The risk may be much higher because retinopathy can be detected earlier when using more sensitive screening techniques. To reassess the prevalence of and risk factors for hydroxychloroquine retinal toxicity and to determine dosage levels that facilitate safe use of the drug. Retrospective case-control study in an integrated health organization of approximately 3.4 million members among 2361 patients who had used hydroxychloroquine continuously for at least 5 years according to pharmacy records and who were evaluated with visual field testing or spectral-domain optical coherence tomography. Hydroxychloroquine use for at least 5 years. Retinal toxicity as determined by characteristic visual field loss or retinal thinning and photoreceptor damage, as well as statistical measures of risk factors and prevalence. Real body weight predicted risk better than ideal body weight and was used for all calculations. The overall prevalence of hydroxychloroquine retinopathy was 7.5% but varied with daily consumption (odds ratio, 5.67; 95% CI, 4.14-7.79 for >5.0 mg/kg) and with duration of use (odds ratio, 3.22; 95% CI, 2.20-4.70 for >10 years). For daily consumption of 4.0 to 5.0 mg/kg, the prevalence of retinal toxicity remained less than 2% within the first 10 years of use but rose to almost 20% after 20 years of use. Other major risk factors include kidney disease (odds ratio, 2.08; 95% CI, 1.44-3.01) and concurrent tamoxifen citrate therapy (odds ratio, 4.59; 95% CI, 2.05-10.27). These data suggest that hydroxychloroquine retinopathy is more common than previously recognized, especially at high dosages and long duration of use. While no completely safe dosage is identified from this study, daily consumption of

  1. A combined approach to investigate the toxicity of an industrial landfill's leachate: Chemical analyses, risk assessment and in vitro assays

    International Nuclear Information System (INIS)

    Baderna, D.; Maggioni, S.; Boriani, E.; Gemma, S.; Molteni, M.; Lombardo, A.; Colombo, A.; Bordonali, S.; Rotella, G.; Lodi, M.; Benfenati, E.

    2011-01-01

    Solid wastes constitute an important and emerging problem. Landfills are still one of the most common ways to manage waste disposal. The risk assessment of pollutants from landfills is becoming a major environmental issue in Europe, due to the large number of sites and to the importance of groundwater protection. Furthermore, there is lack of knowledge for the environmental, ecotoxicological and toxicological characteristics of most contaminants contained into landfill leacheates. Understanding leachate composition and creating an integrated strategy for risk assessment are currently needed to correctly face the landfill issues and to make projections on the long-term impacts of a landfill, with particular attention to the estimation of possible adverse effects on human health and ecosystem. In the present study, we propose an integrated strategy to evaluate the toxicity of the leachate using chemical analyses, risk assessment guidelines and in vitro assays using the hepatoma HepG2 cells as a model. The approach was applied on a real case study: an industrial waste landfill in northern Italy for which data on the presence of leachate contaminants are available from the last 11 years. Results from our ecological risk models suggest important toxic effects on freshwater fish and small rodents, mainly due to ammonia and inorganic constituents. Our results from in vitro data show an inhibition of cell proliferation by leachate at low doses and cytotoxic effect at high doses after 48 h of exposure. - Research highlights: → We study the toxicity of leachate from a non-hazardous industrial waste landfill. → We perform chemical analyses, risk assessments and in vitro assays on HepG2 cells. → Risk models suggest toxic effects due to ammonia and inorganic constituents. → In vitro assays show that leachate inhibits cell proliferation at low doses. → Leachate can induce cytotoxic effects on HepG2 cells at high doses.

  2. Preliminary analysis of risk factors for late rectal toxicity after helical tomotherapy for prostate cancer

    International Nuclear Information System (INIS)

    Tomita, Natsuo; Soga, Norihito; Ogura, Yuji

    2013-01-01

    The purpose of this study is to examine risk factors for late rectal toxicity for localized prostate cancer patients treated with helical tomotherapy (HT). The patient cohort of this retrospective study was composed of 241 patients treated with HT and followed up regularly. Toxicity levels were scored according to the Radiation Therapy Oncology Group grading scale. The clinical and dosimetric potential factors increasing the risk of late rectal toxicity, such as age, diabetes, anticoagulants, prior abdominal surgery, prescribed dose, maximum dose of the rectum, and the percentage of the rectum covered by 70 Gy (V70), 60 Gy (V60), 40 Gy (V40) and 20 Gy (V20) were compared between ≤ Grade 1 and ≥ Grade 2 toxicity groups using the Student's t-test. Multivariable logistic regression analysis of the factors that appeared to be associated with the risk of late rectal toxicity (as determined by the Student's t-test) was performed. The median follow-up time was 35 months. Late Grade 2-3 rectal toxicity was observed in 18 patients (7.4%). Age, the maximum dose of the rectum, V70 and V60 of the ≥ Grade 2 toxicity group were significantly higher than in those of the ≤ Grade 1 toxicity group (P=0.00093, 0.048, 0.0030 and 0.0021, respectively). No factor was significant in the multivariable analysis. The result of this study indicates that the risk of late rectal toxicity correlates with the rectal volume exposed to high doses of HT for localized prostate cancer. Further follow-up and data accumulation may establish dose-volume modeling to predict rectal complications after HT. (author)

  3. The toxic and radiological risk equivalence approach in UF6 transport

    International Nuclear Information System (INIS)

    Ringot, C.; Hamard, J.

    1988-12-01

    After a brief description of the safety in transport of UF 6 , we discuss the equivalence of the radioactive and chemical risks in UF 6 transport regulations. As the concept of low specific activity appears to be ill-suited for a toxic gas, we propose a quantity of material limit designated T 2 (equivalent to A 2 for radioactive substances) for packagings unable to withstand accident conditions (9 m drop, 800 0 C fire environment for 30 minutes). It is proposed that this limit be chosen for the amount of release acceptable after AIEA tests. Different possible scenarios are described, with fire assumed to be the most severe toxic risk situation

  4. Glyphosate: environmental contamination, toxicity and potential risks to human health via food contamination.

    Science.gov (United States)

    Bai, Shahla Hosseini; Ogbourne, Steven M

    2016-10-01

    Glyphosate has been the most widely used herbicide during the past three decades. The US Environmental Protection Agency (EPA) classifies glyphosate as 'practically non-toxic and not an irritant' under the acute toxicity classification system. This classification is based primarily on toxicity data and due to its unique mode of action via a biochemical pathway that only exists in a small number of organisms that utilise the shikimic acid pathway to produce amino acids, most of which are green plants. This classification is supported by the majority of scientific literature on the toxic effects of glyphosate. However, in 2005, the Food and Agriculture Organisation (FAO) reported that glyphosate and its major metabolite, aminomethylphosphonic acid (AMPA), are of potential toxicological concern, mainly as a result of accumulation of residues in the food chain. The FAO further states that the dietary risk of glyphosate and AMPA is unlikely if the maximum daily intake of 1 mg kg(-1) body weight (bw) is not exceeded. Research has now established that glyphosate can persist in the environment, and therefore, assessments of the health risks associated with glyphosate are more complicated than suggested by acute toxicity data that relate primarily to accidental high-rate exposure. We have used recent literature to assess the possible risks associated with the presence of glyphosate residues in food and the environment.

  5. Using physiology and behaviour to understand the responses of fish early life stages to toxicants.

    Science.gov (United States)

    Sloman, K A; McNeil, P L

    2012-12-01

    The use of early life stages of fishes (embryos and larvae) in toxicity testing has been in existence for a long time, generally utilizing endpoints such as morphological defects and mortality. Behavioural endpoints, however, may represent a more insightful evaluation of the ecological effects of toxicants. Indeed, recent years have seen a considerable increase in the use of behavioural measurements in early life stages reflecting a substantial rise in zebrafish Danio rerio early life-stage toxicity testing and the development of automated behavioural monitoring systems. Current behavioural endpoints identified for early life stages in response to toxicant exposure include spontaneous activity, predator avoidance, capture of live food, shoaling ability and interaction with other individuals. Less frequently used endpoints include measurement of anxiogenic behaviours and cognitive ability, both of which are suggested here as future indicators of toxicant disruption. For many simple behavioural endpoints, there is still a need to link behavioural effects with ecological relevance; currently, only a limited number of studies have addressed this issue. Understanding the physiological mechanisms that underlie toxicant effects on behaviour so early in life has received far less attention, perhaps because physiological measurements can be difficult to carry out on individuals of this size. The most commonly established physiological links with behavioural disruption in early life stages are similar to those seen in juveniles and adults including sensory deprivation (olfaction, lateral line and vision), altered neurogenesis and neurotransmitter concentrations. This review highlights the importance of understanding the integrated behavioural and physiological response of early life stages to toxicants and identifies knowledge gaps which present exciting areas for future research. © 2012 The Authors. Journal of Fish Biology © 2012 The Fisheries Society of the British Isles.

  6. Differential reconstructed gene interaction networks for deriving toxicity threshold in chemical risk assessment

    OpenAIRE

    Yang, Yi; Maxwell, Andrew; Zhang, Xiaowei; Wang, Nan; Perkins, Edward J; Zhang, Chaoyang; Gong, Ping

    2013-01-01

    Background Pathway alterations reflected as changes in gene expression regulation and gene interaction can result from cellular exposure to toxicants. Such information is often used to elucidate toxicological modes of action. From a risk assessment perspective, alterations in biological pathways are a rich resource for setting toxicant thresholds, which may be more sensitive and mechanism-informed than traditional toxicity endpoints. Here we developed a novel differential networks (DNs) appro...

  7. Ionizing radiation-induced DNA damage and repair as a potential biomarker in biodosimetry, cancer risk analysis and for prediction of radiotherapy induced toxicity

    International Nuclear Information System (INIS)

    Satish Rao, B.S.

    2017-01-01

    Lymphocytes isolated from peripheral blood from 100 healthy individuals, 232 cancer patients (cervical, breast cancer and head and neck cancer) irradiated in vitro or in vivo were used for measuring DNA damage and repair. The microscopic method of the γ-H2AX assay was adopted to elucidate the significance of DSB in biodosimetry, cancer risk susceptibility, and normal tissue toxicity prediction. We validated the use of H2AX assay in early triage biodosimetry by using lymphocytes from cervical cancer patients exposed to radiotherapy. Further, the basal and residual damage was significantly higher in cancer individuals compared to the healthy individuals. In cancer patients undergoing radiotherapy, we could able to show the increase in normal tissue toxicity with decreased DSB repair capacity. In conclusion this study indicates the DSB estimation by γ-H2AX foci analysis can serve as a tool to understand the triage of radiation exposed individuals, identifying individuals at cancer risk and normal tissue toxicity

  8. Introduction to Toxicity and Risk Assessment for Project Chemists

    Science.gov (United States)

    2012-03-27

    Toxicity of Hexavalent Chromium  External review complete  EPA will wait until studies underway on carcinogenic mode of action are complete to...finalize the assessment  NJ and Cal values for hex chrome 16 Risk-Based Screening Levels Resident Soil (mg/kg) Resident Water Use (µg/L) DRAFT 0.04

  9. Improving reptile ecological risk assessment: oral and dermal toxicity of pesticides to a common lizard species (Sceloporus occidentalis).

    Science.gov (United States)

    Weir, Scott M; Yu, Shuangying; Talent, Larry G; Maul, Jonathan D; Anderson, Todd A; Salice, Christopher J

    2015-08-01

    Reptiles have been understudied in ecotoxicology, which limits consideration in ecological risk assessments. The goals of the present study were 3-fold: to improve oral and dermal dosing methodologies for reptiles, to generate reptile toxicity data for pesticides, and to correlate reptile and avian toxicity. The authors first assessed the toxicity of different dosing vehicles: 100 μL of water, propylene glycol, and acetone were not toxic. The authors then assessed the oral and dermal toxicity of 4 pesticides following the up-and-down procedure. Neither brodifacoum nor chlorothalonil caused mortality at doses ≤ 1750 μg/g. Under the "neat pesticide" oral exposure, endosulfan (median lethal dose [LD50] = 9.8 μg/g) was more toxic than λ-cyhalothrin (LD50 = 916.5 μg/g). Neither chemical was toxic via dermal exposure. An acetone dosing vehicle increased λ-cyhalothrin toxicity (oral LD50 = 9.8 μg/g; dermal LD50 = 17.5 μg/g), but not endosulfan. Finally, changes in dosing method and husbandry significantly increased dermal λ-cyhalothrin LD50s, which highlights the importance of standardized methods. The authors combined data from the present study with other reptile LD50s to correlate with available avian data. When only definitive LD50s were used in the analysis, a strong correlation was found between avian and reptile toxicity. The results suggest it is possible to build predictive relationships between avian and reptile LD50s. More research is needed, however, to understand trends associated with chemical classes and modes of action. © 2015 SETAC.

  10. Utilizing toxicogenomic data to understand chemical mechanism of action in risk assessment

    Energy Technology Data Exchange (ETDEWEB)

    Wilson, Vickie S., E-mail: wilson.vickie@epa.gov [National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Keshava, Nagalakshmi [National Center for Environmental Assessment, Office of Research and Development, U.S. Environmental Protection Agency, 1200 Pennsylvania Ave., NW, Washington, DC 20460 (United States); Hester, Susan [National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Segal, Deborah; Chiu, Weihsueh [National Center for Environmental Assessment, Office of Research and Development, U.S. Environmental Protection Agency, 1200 Pennsylvania Ave., NW, Washington, DC 20460 (United States); Thompson, Chad M. [ToxStrategies, Inc., 23501 Cinco Ranch Blvd., Suite G265, Katy, TX 77494 (United States); Euling, Susan Y. [National Center for Environmental Assessment, Office of Research and Development, U.S. Environmental Protection Agency, 1200 Pennsylvania Ave., NW, Washington, DC 20460 (United States)

    2013-09-15

    The predominant role of toxicogenomic data in risk assessment, thus far, has been one of augmentation of more traditional in vitro and in vivo toxicology data. This article focuses on the current available examples of instances where toxicogenomic data has been evaluated in human health risk assessment (e.g., acetochlor and arsenicals) which have been limited to the application of toxicogenomic data to inform mechanism of action. This article reviews the regulatory policy backdrop and highlights important efforts to ultimately achieve regulatory acceptance. A number of research efforts on specific chemicals that were designed for risk assessment purposes have employed mechanism or mode of action hypothesis testing and generating strategies. The strides made by large scale efforts to utilize toxicogenomic data in screening, testing, and risk assessment are also discussed. These efforts include both the refinement of methodologies for performing toxicogenomics studies and analysis of the resultant data sets. The current issues limiting the application of toxicogenomics to define mode or mechanism of action in risk assessment are discussed together with interrelated research needs. In summary, as chemical risk assessment moves away from a single mechanism of action approach toward a toxicity pathway-based paradigm, we envision that toxicogenomic data from multiple technologies (e.g., proteomics, metabolomics, transcriptomics, supportive RT-PCR studies) can be used in conjunction with one another to understand the complexities of multiple, and possibly interacting, pathways affected by chemicals which will impact human health risk assessment.

  11. Utilizing toxicogenomic data to understand chemical mechanism of action in risk assessment

    International Nuclear Information System (INIS)

    Wilson, Vickie S.; Keshava, Nagalakshmi; Hester, Susan; Segal, Deborah; Chiu, Weihsueh; Thompson, Chad M.; Euling, Susan Y.

    2013-01-01

    The predominant role of toxicogenomic data in risk assessment, thus far, has been one of augmentation of more traditional in vitro and in vivo toxicology data. This article focuses on the current available examples of instances where toxicogenomic data has been evaluated in human health risk assessment (e.g., acetochlor and arsenicals) which have been limited to the application of toxicogenomic data to inform mechanism of action. This article reviews the regulatory policy backdrop and highlights important efforts to ultimately achieve regulatory acceptance. A number of research efforts on specific chemicals that were designed for risk assessment purposes have employed mechanism or mode of action hypothesis testing and generating strategies. The strides made by large scale efforts to utilize toxicogenomic data in screening, testing, and risk assessment are also discussed. These efforts include both the refinement of methodologies for performing toxicogenomics studies and analysis of the resultant data sets. The current issues limiting the application of toxicogenomics to define mode or mechanism of action in risk assessment are discussed together with interrelated research needs. In summary, as chemical risk assessment moves away from a single mechanism of action approach toward a toxicity pathway-based paradigm, we envision that toxicogenomic data from multiple technologies (e.g., proteomics, metabolomics, transcriptomics, supportive RT-PCR studies) can be used in conjunction with one another to understand the complexities of multiple, and possibly interacting, pathways affected by chemicals which will impact human health risk assessment

  12. Toxic releases and risk disparity: a spatiotemporal model of industrial ecology and social empowerment.

    Science.gov (United States)

    Aoyagi, Hannah; Ogunseitan, Oladele A

    2015-06-02

    Information-based regulations (IBRs) are founded on the theoretical premise that public participation in accomplishing policy goals is empowered by open access to information. Since its inception in 1988, the Toxics Release Inventory (TRI) has provided the framework and regulatory impetus for the compilation and distribution of data on toxic releases associated with industrial development, following the tenets of IBR. As TRI emissions are reputed to disproportionately affect low-income communities, we investigated how demographic characteristics are related to change in TRI emissions and toxicity risks between 1989 and 2002, and we sought to identify factors that predict these changes. We used local indicators of spatial association (LISA) maps and spatial regression techniques to study risk disparity in the Los Angeles urban area. We also surveyed 203 individuals in eight communities in the same region to measure the levels of awareness of TRI, attitudes towards air pollution, and general environmental risk. We discovered, through spatial lag models, that changes in gross and toxic emissions are related to community ethnic composition, poverty level, home ownership, and base 1989 emissions (R-square=0.034-0.083). We generated a structural equation model to explain the determinants of social empowerment to act on the basis of environmental information. Hierarchical confirmatory factor analysis (HCFA) supports the theoretical model that individual empowerment is predicted by risk perception, worry, and awareness (Chi-square=63.315, p=0.022, df=42). This study provides strong evidence that spatiotemporal changes in regional-scale environmental risks are influenced by individual-scale empowerment mediated by IBRs.

  13. Toxic Releases and Risk Disparity: A Spatiotemporal Model of Industrial Ecology and Social Empowerment

    Directory of Open Access Journals (Sweden)

    Hannah Aoyagi

    2015-06-01

    Full Text Available Information-based regulations (IBRs are founded on the theoretical premise that public participation in accomplishing policy goals is empowered by open access to information. Since its inception in 1988, the Toxics Release Inventory (TRI has provided the framework and regulatory impetus for the compilation and distribution of data on toxic releases associated with industrial development, following the tenets of IBR. As TRI emissions are reputed to disproportionately affect low-income communities, we investigated how demographic characteristics are related to change in TRI emissions and toxicity risks between 1989 and 2002, and we sought to identify factors that predict these changes. We used local indicators of spatial association (LISA maps and spatial regression techniques to study risk disparity in the Los Angeles urban area. We also surveyed 203 individuals in eight communities in the same region to measure the levels of awareness of TRI, attitudes towards air pollution, and general environmental risk. We discovered, through spatial lag models, that changes in gross and toxic emissions are related to community ethnic composition, poverty level, home ownership, and base 1989 emissions (R-square = 0.034–0.083. We generated a structural equation model to explain the determinants of social empowerment to act on the basis of environmental information. Hierarchical confirmatory factor analysis (HCFA supports the theoretical model that individual empowerment is predicted by risk perception, worry, and awareness (Chi-square = 63.315, p = 0.022, df = 42. This study provides strong evidence that spatiotemporal changes in regional-scale environmental risks are influenced by individual-scale empowerment mediated by IBRs.

  14. Potentials and limitations of hazard indices for the determination of risk potentials of disposed toxic wastes

    International Nuclear Information System (INIS)

    Kirchner, Gerald

    1989-01-01

    Hazard indices are often used for the determination of risk potentials arising from the geological disposal of toxic wastes. They are based on simplified models for the calculation of potential health effects caused by the wastes. The attractiveness of hazard indices lies in their simplicity which nevertheless results in reliable data on necessary isolation times and the most toxic nuclides of a waste. They also make possible comparisons of the potential risks of different wastes. After a discussion of the processes that control the behavior of toxic wastes in the environment after a failure of the geological barriers, a new hazard index is presented. Originally developed for nuclear wastes, it is the first which involves the joint consideration of the composition of a waste, the probability for transport of waste nuclides to man, their toxicity, and the time-dependent changes of the risk potentials which are caused by radioactive buildup and decay processes after the waste has entered the biosphere. The new hazard index makes possible the calculation of risk potentials at a given time of release and time period of concern thereafter. Sample calculations for different nuclear wastes show the importance of the model improvements on resulting time-dependent risk potentials. Applicability of the new hazard index to non-nuclear wastes is described. Potentials and limitations of comparative risk assessments using hazard indices are discussed. (author)

  15. Severe Pulmonary Toxicity After Myeloablative Conditioning Using Total Body Irradiation: An Assessment of Risk Factors

    International Nuclear Information System (INIS)

    Kelsey, Chris R.; Horwitz, Mitchell E.; Chino, Junzo P.; Craciunescu, Oana; Steffey, Beverly; Folz, Rodney J.; Chao, Nelson J.; Rizzieri, David A.; Marks, Lawrence B.

    2011-01-01

    Purpose: To assess factors associated with severe pulmonary toxicity after myeloablative conditioning using total body irradiation (TBI) followed by allogeneic stem cell transplantation. Methods and Materials: A total of 101 adult patients who underwent TBI-based myeloablative conditioning for hematologic malignancies at Duke University between 1998 and 2008 were reviewed. TBI was combined with high-dose cyclophosphamide, melphalan, fludarabine, or etoposide, depending on the underlying disease. Acute pulmonary toxicity, occurring within 90 days of transplantation, was scored using Common Terminology Criteria for Adverse Events version 3.0. Actuarial overall survival and the cumulative incidence of acute pulmonary toxicity were calculated via the Kaplan-Meier method and compared using a log-rank test. A binary logistic regression analysis was performed to assess factors independently associated with acute severe pulmonary toxicity. Results: The 90-day actuarial risk of developing severe (Grade 3-5) pulmonary toxicity was 33%. Actuarial survival at 90 days was 49% in patients with severe pulmonary toxicity vs. 94% in patients without (p < 0.001). On multivariate analysis, the number of prior chemotherapy regimens was the only factor independently associated with development of severe pulmonary toxicity (odds ratio, 2.7 per regimen). Conclusions: Severe acute pulmonary toxicity is prevalent after TBI-based myeloablative conditioning regimens, occurring in approximately 33% of patients. The number of prior chemotherapy regimens appears to be an important risk factor.

  16. Predicted risks of radiogenic cardiac toxicity in two pediatric patients undergoing photon or proton radiotherapy

    International Nuclear Information System (INIS)

    Zhang, Rui; Howell, Rebecca M; Homann, Kenneth; Giebeler, Annelise; Taddei, Phillip J; Mahajan, Anita; Newhauser, Wayne D

    2013-01-01

    Hodgkin disease (HD) and medulloblastoma (MB) are common malignancies found in children and young adults, and radiotherapy is part of the standard treatment. It was reported that these patients who received radiation therapy have an increased risk of cardiovascular late effects. We compared the predicted risk of developing radiogenic cardiac toxicity after photon versus proton radiotherapies for a pediatric patient with HD and a pediatric patient with MB. In the treatment plans, each patient’s heart was contoured in fine detail, including substructures of the pericardium and myocardium. Risk calculations took into account both therapeutic and stray radiation doses. We calculated the relative risk (RR) of cardiac toxicity using a linear risk model and the normal tissue complication probability (NTCP) values using relative seriality and Lyman models. Uncertainty analyses were also performed. The RR values of cardiac toxicity for the HD patient were 7.27 (proton) and 8.37 (photon), respectively; the RR values for the MB patient were 1.28 (proton) and 8.39 (photon), respectively. The predicted NTCP values for the HD patient were 2.17% (proton) and 2.67% (photon) for the myocardium, and were 2.11% (proton) and 1.92% (photon) for the whole heart. The predicted ratios of NTCP values (proton/photon) for the MB patient were much less than unity. Uncertainty analyses revealed that the predicted ratio of risk between proton and photon therapies was sensitive to uncertainties in the NTCP model parameters and the mean radiation weighting factor for neutrons, but was not sensitive to heart structure contours. The qualitative findings of the study were not sensitive to uncertainties in these factors. We conclude that proton and photon radiotherapies confer similar predicted risks of cardiac toxicity for the HD patient in this study, and that proton therapy reduced the predicted risk for the MB patient in this study

  17. Potentially toxic elements in soil of the Khyber Pakhtunkhwa province and Tribal areas, Pakistan: evaluation for human and ecological risk assessment.

    Science.gov (United States)

    Saddique, Umar; Muhammad, Said; Tariq, Mohsin; Zhang, Hua; Arif, Mohammad; Jadoon, Ishtiaq A K; Khattak, Nimat Ullah

    2018-03-22

    Potentially toxic elements (PTEs) contaminations in the soil ecosystem are considered as extremely hazardous due to toxicity, persistence and bioaccumulative nature. Therefore, this study was aimed to summarize the results of published PTEs in soil of Khyber Pakhtunkhwa and Tribal areas, Pakistan. Results were evaluated for the pollution quantification factors, including contamination factor (CF), pollution load index (PLI), ecological risk index (ERI) and human health risk assessment. The highest CF (797) and PLI (7.35) values were observed for Fe and ERI (857) values for Cd. Soil PTEs concentrations were used to calculate the human exposure for the risk assessment, including chronic or non-carcinogenic risks such as the hazard quotient (HQ) and carcinogenic or cancer risk (CR). The values of HQ were > 1 for the Cd, Co and Cr in Khyber Pakhtunkhwa and Tribal areas. Tribal areas showed higher values of ERI, HQ, and CR as compared to the Khyber Pakhtunkhwa that were attributed to the mining activities, weathering and erosion of mafic and ultramafic bedrocks hosting ophiolites. This study strongly recommends that best control measures need to be taken for soil PTEs with the intent to alleviate any continuing potential threat to the human health, property and environment, which otherwise could enter ecosystem and ultimately the living beings. Further studies are recommended to combat the soil PTEs concentrations and toxicity in the Tribal areas for a best picture of understanding the element effects on human, and environment can be achieved that will lead to a sustainable ecological harmony.

  18. Metal Oxide Nanomaterial QNAR Models: Available Structural Descriptors and Understanding of Toxicity Mechanisms

    Directory of Open Access Journals (Sweden)

    Jiali Ying

    2015-10-01

    Full Text Available Metal oxide nanomaterials are widely used in various areas; however, the divergent published toxicology data makes it difficult to determine whether there is a risk associated with exposure to metal oxide nanomaterials. The application of quantitative structure activity relationship (QSAR modeling in metal oxide nanomaterials toxicity studies can reduce the need for time-consuming and resource-intensive nanotoxicity tests. The nanostructure and inorganic composition of metal oxide nanomaterials makes this approach different from classical QSAR study; this review lists and classifies some structural descriptors, such as size, cation charge, and band gap energy, in recent metal oxide nanomaterials quantitative nanostructure activity relationship (QNAR studies and discusses the mechanism of metal oxide nanomaterials toxicity based on these descriptors and traditional nanotoxicity tests.

  19. Risk associated with toxic blooms of marine phytoplankton functional groups on Artemia franciscana

    Directory of Open Access Journals (Sweden)

    Ana D’ors

    2014-08-01

    Full Text Available Objective: To study mortality of copepod Artemia franciscana against the occurrence of harmful marine algae and possible toxicological changes exhibited by binary and tertiary combinations of these harmful algae toxins. Methods: Tweenty four hours acute toxicity assays were performed with selected concentrations of Alexandrium minutum, Prorocentrum lima and Nitzschia N1c1 living cells. Additionally, the results were analyzed using the median-effect/combination index (CI-isobologram equation to assess possible changes in the toxic effect induced by phytoplankton functional groups. Results: Biotoxin equivalent values obtained by immunodetection were (2.12±0.10, (8.60±1.30 and (4.32±1.67 pg/cell for saxitoxin, okadaic acid and domoic acid, respectively. The 24-h LC50 values estimated to saxitoxin and okadaic acid equivalents were 4.06 and 6.27 µg/L, significantly below the value obtained for Nitzschia N1c1, which was established at 467.33 µg/L. CI analysis applied on phytoplankton assemblages showed that both ternary mixture as the binary combinations exhibited antagonic action on toxic effects in Artemia nauplii, which were significantly lower than the toxic effect exhibited by each species studied. Conclusions: These results show that, although these harmful algae represent a serious risk to estuarine zooplankton community, the presence of phytoplankton functional groups within the same bloom can reduce the potential risk compared to the expected risk when each of the phytoplankton groups are evaluated individually.

  20. Lead Toxicity in the Pediatric Patient with Sickle Cell Disease: Unique Risks and Management.

    Science.gov (United States)

    Jung, Josephine Misun; Peddinti, Radhika

    2018-01-01

    Lead toxicity is the result of lead ingestion, one of the most common ingestions in the pediatric population. Nationwide and statewide efforts to recognize and curtail this epidemic have led to declining rates of toxicity. In patients with sickle cell disease (SCD), lead toxicity can be an elusive diagnosis due to overlapping symptom profiles, and inconsistent follow-up with a primary care physician can make the diagnosis even more difficult. In this article, two illustrative cases of lead toxicity in patients with SCD are described. The discussion reviews the current risk factors, screening, and inpatient management of lead toxicity, as well as describing the unique and sometimes confounding presentations of lead toxicity versus sickle cell crisis. [Pediatr Ann. 2018;47(1):e36-e40.]. Copyright 2018, SLACK Incorporated.

  1. Perceptions of risk: understanding cardiovascular disease

    Directory of Open Access Journals (Sweden)

    Ruth Webster

    2010-09-01

    Full Text Available Ruth Webster1, Emma Heeley21Cardiovascular Division, 2Neurological and Mental Health Division, The George Institute for International Health, Camperdown, NSW, AustraliaAbstract: Cardiovascular disease (CVD is still the leading cause of death and disability worldwide despite the availability of well-established and effective preventive options. Accurate perception of a patient’s risk by both the patient and the doctors is important as this is one of the components that determine health-related behavior. Doctors tend to not use cardiovascular (CV risk calculators and underestimate the absolute CV risk of their patients. Patients show optimistic bias when considering their own risk and consistently underestimate it. Poor patient health literacy and numeracy must be considered when thinking about this problem. Patients must possess a reasonably high level of understanding of numerical processes when doctors discuss risk, a level that is not possessed by large numbers of the population. In order to overcome this barrier, doctors need to utilize various tools including the appropriate use of visual aids to accurately communicate risk with their patients. Any intervention has been shown to be better than nothing in improving health understanding. The simple process of repeatedly conveying risk information to a patient has been shown to improve accuracy of risk perception. Doctors need to take responsibility for the accurate assessment and effective communication of CV risk in their patients in order to improve patient uptake of cardioprotective lifestyle choices and preventive medications.Keywords: risk perception, cardiovascular disease, cardioprotective lifestyle

  2. Immunotoxicity, genotoxicity and epigenetic toxicity of nanomaterials: New strategies for toxicity testing?

    Science.gov (United States)

    Dusinska, Maria; Tulinska, Jana; El Yamani, Naouale; Kuricova, Miroslava; Liskova, Aurelia; Rollerova, Eva; Rundén-Pran, Elise; Smolkova, Bozena

    2017-11-01

    The unique properties of nanomaterials (NMs) are beneficial in numerous industrial and medical applications. However, they could also induce unintended effects. Thus, a proper strategy for toxicity testing is essential in human hazard and risk assessment. Toxicity can be tested in vivo and in vitro; in compliance with the 3Rs, alternative strategies for in vitro testing should be further developed for NMs. Robust, standardized methods are of great importance in nanotoxicology, with comprehensive material characterization and uptake as an integral part of the testing strategy. Oxidative stress has been shown to be an underlying mechanism of possible toxicity of NMs, causing both immunotoxicity and genotoxicity. For testing NMs in vitro, a battery of tests should be performed on cells of human origin, either cell lines or primary cells, in conditions as close as possible to an in vivo situation. Novel toxicity pathways, particularly epigenetic modification, should be assessed along with conventional toxicity testing methods. However, to initiate epigenetic toxicity screens for NM exposure, there is a need to better understand their adverse effects on the epigenome, to identify robust and reproducible causal links between exposure, epigenetic changes and adverse phenotypic endpoints, and to develop improved assays to monitor epigenetic toxicity. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  3. Incidence and risk of hematologic toxicities in cancer patients treated with regorafenib.

    Science.gov (United States)

    Zhao, Bin; Zhao, Hong

    2017-11-07

    Regorafenib, an oral vascular endothelial growth factor receptor tyrosine-kinase inhibitor, has been approved for the treatment of several malignancies. As a non-traditional cytotoxic chemotherapeutic agent, regorafenib is often associated with hematologic toxicities. Here we searched PubMed and Embase up to June 2017 for relevant clinical trials. Eligible studies include trials in which subjects treated with 160 mg of regorafenib daily during the first 21 days of each 28-day cycle, and adequate safety data profile reporting thrombocytopenia, anemia, neutropenia and leucopenia. Statistical analyses were conducted to calculate the overall incidences, relative risks (RRs) and their 95% confidence intervals (CIs). A total of 2,341 subjects from 16 trials were included in the present studies. The incidences of regorafenib associated all-grade and high-grade hematologic toxicities were: thrombocytopenia, 22% and 3%; anemia, 20% and 3%; neutropenia, 10% and 2%, and leucopenia, 13% and 2%, respectively. Regorafenib-treated subjects had a significant increased risk of all-grade (RR=6.35; 95% CI, 3.19-12.64) and high-grade (RR=6.27; 95% CI, 1.69-23.26) thrombocytopenia, all-grade (RR=2.76; 95% CI, 1.63-4.68) and high-grade (RR=5.38; 95% CI, 1.60-18.06) anemia. Our results suggested that regorafenib therapy was associated with significantly increased risks of hematological toxicities, and hematologic monitoring at regular intervals should be advised to clinician.

  4. Particle size: a missing factor in risk assessment of human exposure to toxic chemicals in settled indoor dust.

    Science.gov (United States)

    Cao, Zhi-Guo; Yu, Gang; Chen, Yong-Shan; Cao, Qi-Ming; Fiedler, Heidelore; Deng, Shu-Bo; Huang, Jun; Wang, Bin

    2012-11-15

    For researches on toxic chemicals in settled indoor dust, selection of dust fraction is a critical influencing factor to the accuracy of human exposure risk assessment results. However, analysis of the selection of dust fraction in recent studies revealed that there is no consensus. This study classified and presented researches on distribution of toxic chemicals according to dust particle size and on relationship between dust particle size and human exposure possibility. According to the literature, beyond the fact that there were no consistent conclusions on particle size distribution of adherent fraction, dust with particle size less than 100 μm should be paid more attention and that larger than 250 μm is neither adherent nor proper for human exposure risk assessment. Calculation results based on literature data show that with different selections of dust fractions, analytical results of toxic chemicals would vary up to 10-fold, which means that selecting dust fractions arbitrarily will lead to large errors in risk assessment of human exposure to toxic chemicals in settled dust. Taking into account the influence of dust particle size on risk assessment of human exposure to toxic chemicals, a new methodology for risk assessment of human exposure to toxic chemicals in settled indoor dust is proposed and human exposure parameter systems to settled indoor dust are advised to be established at national and regional scales all over the world. Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. Mode of Action Frameworks in Toxicity Testing and Chemical Risk Assessment

    NARCIS (Netherlands)

    Meek, B.

    2009-01-01

    Recently, legislative mandates worldwide are requiring systematic consideration of much larger numbers of chemicals. This necessitates more efficient and effective toxicity testing, as a basis to be more predictive in a risk assessment context. This in turn requires much more emphasis early in the

  6. Calculating background levels for ecological risk parameters in toxic harbor sediment

    Science.gov (United States)

    Leadon, C.J.; McDonnell, T.R.; Lear, J.; Barclift, D.

    2007-01-01

    Establishing background levels for biological parameters is necessary in assessing the ecological risks from harbor sediment contaminated with toxic chemicals. For chemicals in sediment, the term contaminated is defined as having concentrations above background and significant human health or ecological risk levels. For biological parameters, a site could be considered contaminated if levels of the parameter are either more or less than the background level, depending on the specific parameter. Biological parameters can include tissue chemical concentrations in ecological receptors, bioassay responses, bioaccumulation levels, and benthic community metrics. Chemical parameters can include sediment concentrations of a variety of potentially toxic chemicals. Indirectly, contaminated harbor sediment can impact shellfish, fish, birds, and marine mammals, and human populations. This paper summarizes the methods used to define background levels for chemical and biological parameters from a survey of ecological risk investigations of marine harbor sediment at California Navy bases. Background levels for regional biological indices used to quantify ecological risks for benthic communities are also described. Generally, background stations are positioned in relatively clean areas exhibiting the same physical and general chemical characteristics as nearby areas with contaminated harbor sediment. The number of background stations and the number of sample replicates per background station depend on the statistical design of the sediment ecological risk investigation, developed through the data quality objective (DQO) process. Biological data from the background stations can be compared to data from a contaminated site by using minimum or maximum background levels or comparative statistics. In Navy ecological risk assessments (ERA's), calculated background levels and appropriate ecological risk screening criteria are used to identify sampling stations and sites with contaminated

  7. Toxicity of Transition Metal Oxide Nanoparticles: Recent Insights from in vitro Studies

    Directory of Open Access Journals (Sweden)

    Robert S. Aronstam

    2010-10-01

    Full Text Available Nanotechnology has evolved to play a prominent role in our economy. Increased use of nanomaterials poses potential human health risk. It is therefore critical to understand the nature and origin of the toxicity imposed by nanomaterials (nanotoxicity. In this article we review the toxicity of the transition metal oxides in the 4th period that are widely used in industry and biotechnology. Nanoparticle toxicity is compellingly related to oxidative stress and alteration of calcium homeostasis, gene expression, pro-inflammatory responses, and cellular signaling events. The precise physicochemical properties that dictate the toxicity of nanoparticles have yet to be defined, but may include element-specific surface catalytic activity (e.g., metallic, semiconducting properties, nanoparticle uptake, or nanoparticle dissolution. These in vitro studies substantially advance our understanding in mechanisms of toxicity, which may lead to safer design of nanomaterials.

  8. The prevalence of toxic hotspots in former Soviet countries.

    Science.gov (United States)

    Sharov, Petr; Dowling, Russell; Gogishvili, Megi; Jones, Barbara; Caravanos, Jack; McCartor, Andrew; Kashdan, Zachary; Fuller, Richard

    2016-04-01

    Using a global database of contaminated sites, toxic hotspots in eight former Soviet countries were analyzed to identify the prevalence, types and sources of toxic pollution, as well as their associated potential public health impacts. For this analysis, polluted sites in Armenia, Azerbaijan, Kazakhstan, Kyrgyzstan, Russia, Tajikistan, Ukraine, and Uzbekistan were compiled and analyzed. The levels of contamination of seven key pollutants were assessed in each country. 424 contaminated sites were identified using data from Blacksmith Institute. Pesticides, lead (Pb), radioactive metals, arsenic (As), mercury (Hg), chromium (Cr), and cadmium (Cd) were the most commonly identified key pollutants. Collectively, these sites pose health risks to an estimated 6.2 million residents. The existing data on toxic hotspots in former Soviet countries likely captures only a small percentage of actual contaminated sites, but suggests potentially severe public health consequences. Additional assessments are needed to understand the risks posed by toxic pollution in the region. Copyright © 2016. Published by Elsevier Ltd.

  9. Concentrations, sources and human health risk of inhalation exposure to air toxics in Edmonton, Canada.

    Science.gov (United States)

    Bari, Md Aynul; Kindzierski, Warren B

    2017-04-01

    With concern about levels of air pollutants in recent years in the Capital Region of Alberta, an investigation of ambient concentrations, sources and potential human health risk of hazardous air pollutants (HAPs) or air toxics was undertaken in the City of Edmonton over a 5-year period (2009-2013). Mean concentrations of individual HAPs in ambient air including volatile organic compounds (VOCs), polycyclic aromatic hydrocarbons (PAHs) and trace metals ranged from 0.04 to 1.73 μg/m 3 , 0.01-0.54 ng/m 3 , and 0.05-3.58 ng/m 3 , respectively. Concentrations of benzene, naphthalene, benzo(a)pyrene (BaP), arsenic, manganese and nickel were far below respective annual Alberta Ambient Air Quality Objectives. Carcinogenic and non-carcinogenic risk of air toxics were also compared with risk levels recommended by regulatory agencies. Positive matrix factorization identified six air toxics sources with traffic as the dominant contributor to total HAPs (4.33 μg/m 3 , 42%), followed by background/secondary organic aerosol (SOA) (1.92 μg/m 3 , 25%), fossil fuel combustion (0.92 μg/m 3 , 11%). On high particulate air pollution event days, local traffic was identified as the major contributor to total HAPs compared to background/SOA and fossil fuel combustion. Carcinogenic risk values of traffic, background/SOA and metals industry emissions were above the USEPA acceptable level (1 × 10 -6 ), but below a tolerable risk (1 × 10 -4 ) and Alberta benchmark (1 × 10 -5 ). These findings offer useful preliminary information about current ambient air toxics levels, dominant sources and their potential risk to public health; and this information can support policy makers in the development of appropriate control strategies if required. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Perceptions of environmental health risks among residents in the "Toxic Doughnut": opportunities for risk screening and community mobilization.

    Science.gov (United States)

    White, Brandi M; Hall, Eric S

    2015-12-10

    Surrounded by landfills, and toxic and hazardous facilities, Altgeld Gardens is located in a "toxic doughnut". With high rates of environmentally-related conditions, residents have called for a community-based environmental health assessment to improve overall health in their community. The purpose of this study was to investigate the attitudes and beliefs of environmental health risks of Altgeld's residents which would assist community organizing efforts and provide the groundwork for a community-based environmental health assessment. A questionnaire was designed and administered to 42 Altgeld residents who also participated in focus groups to assess their perceptions of environmental health risks. All participants were Altgeld residents for at least two years and were fairly representative of the broader community. Physical and social hazards were primarily identified as posing risks to participants' family and the broader community. Physical hazards included the dumping of hazardous waste and landfills; social hazards were crime and drugs. These findings have been useful in community organizing efforts and in program planning for local community-based organizations and public health agencies. The results have also been used to prioritize health and environmental risk issues impacting the community.

  11. Systemic Lupus Erythematosus, Radiotherapy, and the Risk of Acute and Chronic Toxicity: The Mayo Clinic Experience

    International Nuclear Information System (INIS)

    Pinn, Melva E.; Gold, Douglas G. M.; Petersen, Ivy A.; Osborn, Thomas G.; Brown, Paul D.; Miller, Robert C.

    2008-01-01

    Purpose: To determine the acute and chronic toxic effects of radiotherapy in patients with systemic lupus erythematosus (SLE). Methods and Materials: Medical records of 21 consecutive patients with SLE, who had received 34 courses of external beam radiotherapy and one low-dose-rate prostate implant, were retrospectively reviewed. Patients with discoid lupus erythematosus were excluded. Results: Median survival was 2.3 years and median follow-up 5.6 years. Eight (42%) of 19 patients evaluable for acute toxicity during radiotherapy experienced acute toxicity of Grade 1 or greater, and 4 (21%) had acute toxicity of Grade 3 or greater. The 5- and 10-year incidence of chronic toxicity of Grade 1 or greater was 45% (95% confidence interval [CI], 22-72%) and 56% (95% CI, 28-81%), respectively. The 5- and 10-year incidence of chronic toxicity of Grade 3 or greater was 28% (95% CI, 18-60%) and 40% (95% CI, 16-72%), respectively. Univariate analysis showed that chronic toxicity of Grade 1 or greater correlated with SLE renal involvement (p < 0.006) and possibly with the presence of five or more American Rheumatism Association criteria (p < 0.053). Chronic toxicity of Grade 3 or greater correlated with an absence of photosensitivity (p < 0.02), absence of arthritis (p < 0.03), and presence of a malar rash (p < 0.04). Conclusions: The risk of acute and chronic toxicity in patients with SLE who received radiotherapy was moderate but was not prohibitive of the use of radiotherapy. Patients with more advanced SLE may be at increased risk for chronic toxicity

  12. Do we actually understand how people perceive risk?

    Energy Technology Data Exchange (ETDEWEB)

    Bochud, Francois O.

    2016-11-01

    The best way to understand how people perceive radiation risk is to not consider them as fundamentally different from experts, but rather, to consider how we, as experts, naturally react when we are confronted with a risk and how we like to be treated. Do we have to alter our language to make it understandable by members of the public?.

  13. Proteomic Assessment of Biochemical Pathways That Are Critical to Nickel-Induced Toxicity Responses in Human Epithelial Cells

    Science.gov (United States)

    Understanding the mechanisms underlying toxicity initiated by nickel, a ubiquitous environmental contaminant and known human carcinogen is necessary for proper assessment of its risks to human and environment. Among a variety of toxic mechanisms, disruption of protein responses a...

  14. Personal care product preservatives: risk assessment and mixture toxicities with an industrial wastewater.

    Science.gov (United States)

    Carbajo, Jose B; Perdigón-Melón, Jose A; Petre, Alice L; Rosal, Roberto; Letón, Pedro; García-Calvo, Eloy

    2015-04-01

    The aquatic toxicity of eight preservatives frequently used in personal care products (PCPs) (iodopropynyl butylcarbamate, bronopol, diazolidinyl urea, benzalkonium chloride, zinc pyrithione, propylparaben, triclosan and a mixture of methylchloroisothiazolinone and methylisothiazolinone) was assessed by means of two different approaches: a battery of bioassays composed of single species tests of bacteria (Vibrio fischeri and Pseudomonas putida) and protozoa (Tetrahymena thermophila), and a whole biological community resazurin-based assay using activated sludge. The tested preservatives showed considerable toxicity in the studied bioassays, but with a marked difference in potency. In fact, all biocides except propylparaben and diazolidinyl urea had EC50 values lower than 1 mg L(-1) in at least one assay. Risk quotients for zinc pyrithione, benzalkonium chloride, iodopropynyl butylcarbamate and triclosan as well as the mixture of the studied preservatives exceeded 1, indicating a potential risk for the process performance and efficiency of municipal sewage treatment plants (STPs). These four single biocides explained more than 95% of the preservative mixture risk in all bioassays. Each individual preservative was also tested in combination with an industrial wastewater (IWW) from a cosmetics manufacturing facility. The toxicity assessment was performed on binary mixtures (preservative + IWW) and carried out using the median-effect principle, which is a special case of the concept of Concentration Addition (CA). Almost 70% of all experiments resulted in EC50 values within a factor of 2 of the values predicted by the median-effect principle (CI values between 0.5 and 2). The rest of the mixtures whose toxicity was mispredicted by CA were assessed with the alternative concept of Independent Action (IA), which showed higher predictive power for the biological community assay. Therefore, the concept used to accurately predict the toxicity of mixtures of a preservative

  15. "Incorporating epigenetic data into the risk assessment process for the toxic metals arsenic, cadmium, chromium, lead, and mercury: strategies and challenges."

    Directory of Open Access Journals (Sweden)

    Paul eRay

    2014-07-01

    Full Text Available Exposure to toxic metals poses a serious human health hazard based on ubiquitous environmental presence, the extent of exposure, and the toxicity and disease states associated with exposure. This global health issue warrants accurate and reliable models derived from the risk assessment process to predict disease risk in populations. There has been considerable interest recently in the impact of environmental toxicants such as toxic metals on the epigenome. Epigenetic modifications are somatically inherited alterations to an individual’s genome without a change in the DNA sequence, and include, but are not limited to, three commonly studied alterations: DNA methylation, histone modification, and non-coding RNA expression. Given the role of epigenetic alterations in regulating gene and thus protein expression, there is the potential for the integration of toxic metal-induced epigenetic alterations as informative factors in the risk assessment process. In the present review, epigenetic alterations induced by five high priority toxic metals/metalloids are prioritized for analysis and their possible inclusion into the risk assessment process is discussed.

  16. Toxic effects of fluoride on organisms.

    Science.gov (United States)

    Zuo, Huan; Chen, Liang; Kong, Ming; Qiu, Lipeng; Lü, Peng; Wu, Peng; Yang, Yanhua; Chen, Keping

    2018-04-01

    Accumulation of excess fluoride in the environment poses serious health risks to plants, animals, and humans. This endangers human health, affects organism growth and development, and negatively impacts the food chain, thereby affecting ecological balance. In recent years, numerous studies focused on the molecular mechanisms associated with fluoride toxicity. These studies have demonstrated that fluoride can induce oxidative stress, regulate intracellular redox homeostasis, and lead to mitochondrial damage, endoplasmic reticulum stress and alter gene expression. This paper reviews the present research on the potential adverse effects of overdose fluoride on various organisms and aims to improve our understanding of fluoride toxicity. Copyright © 2018 Elsevier Inc. All rights reserved.

  17. Assessing plant protection practices using pressure indicator and toxicity risk indicators: analysis of therelationship between these indicators for improved risk management, application in viticulture.

    Science.gov (United States)

    Oussama, Mghirbi; Kamel, Ellefi; Philippe, Le Grusse; Elisabeth, Mandart; Jacques, Fabre; Habiba, Ayadi; Jean-Paul, Bord

    2015-06-01

    The excessive use of plant protection products (PPPs) has given rise to issues of public and environmental health because of their toxicity. Reducing the use of toxic PPPs and replacing them with products that are less toxic for human health and the environment have become socially, environmentally and economically indispensable. In this article, we assess the plant protection practices of a small group of winegrowers practicing "integrated agriculture" in the south of France, in order to measure the benefit of using toxicity risk indicators as a decision-support tool for different players in land management. An analysis of plant protection practices using indicators of the risk to operator health and the environment (IRSA, IRTE), together with a frequency-of-treatment indicator (TFI), enabled us to (i) show the variability of these indicators depending on the production system and farmers' pesticide use strategies and (ii) calculate correlations between these indicators. This analysis of plant protection practices at different scales (farm, field), carried out in collaboration with the growers, enabled us to perform an initial validation of decision-support tools for determining risk management strategies regarding the use of pesticides.

  18. Toxicities and risk assessment of heavy metals in sediments of Taihu Lake, China, based on sediment quality guidelines.

    Science.gov (United States)

    Zhang, Yanfeng; Han, Yuwei; Yang, Jinxi; Zhu, Lingyan; Zhong, Wenjue

    2017-12-01

    The occurrence, toxicities, and ecological risks of five heavy metals (Pb, Cu, Cd, Zn and Ni) in the sediment of Taihu Lake were investigated in this study. To evaluate the toxicities caused by the heavy metals, the toxicities induced by organic contaminants and ammonia in the sediments were screened out with activated carbon and zeolite. The toxicities of heavy metals in sediments were tested with benthic invertebrates (tubificid and chironomid). The correlations between toxicity of sediment and the sediment quality guidelines (SQGs) derived previously were evaluated. There were significant correlations (pheavy metals based on SQGs, indicating that threshold effect level (TEL) and probable effect level (PEL) were reliable to predict the toxicities of heavy metals in the sediments of Taihu Lake. By contrast, the method based on acid volatile sulfides (AVS) and simultaneously extracted metals (SEM), such as ∑SEM/AVS and ∑SEM-AVS, did not show correlations with the toxicities. Moreover, the predictive ability of SQGs was confirmed by a total predicting accuracy of 77%. Ecological risk assessment based on TELs and PELs showed that the contaminations of Pb, Cu, Cd and Zn in the sediments of Taihu Lake were at relatively low or medium levels. The risks caused by heavy metals in the sediments of northern bay of the lake, which received more wastewater discharge from upper stream, were higher than other area of the lake. Copyright © 2017. Published by Elsevier B.V.

  19. The approach of toxic and radiological risk equivalence in UF6 transport

    International Nuclear Information System (INIS)

    Ringot, C.; Hamard, J.

    1989-01-01

    After a brief description of the present situation concerning the safety of the transport of UF6 and the new regulation project which is being developed under the behalf of IAEA, the equivalence of radioactive and chemical risks is considered for UF6 transport regulations. The concept of low specific activity appearing misfitting to toxic gas, it is proposed a quantity limit of material, T 2 (equivalent to A 2 for radioactive materials), for packagings which do not resist to accidental conditions, (9 m drop, 800 0 C, 30 minutes fire environment). It is proposed that this limit is chosen as the release rate which is acceptable after the IAEA tests for packages having a capacity higher than T 2 kilograms. The fire being considered as the most severe situation for the toxic risk, different possible scenarios are described. This approach of risk equivalence leads to impose that the packaging resists a 800 0 C - 30 minutes fire and that in this condition the release is less than T 2 . The problem of the behaviour of the shell and the openings (in particular the valve) is raised in this context [fr

  20. Supplementing quantitative risk assessments with a stage addressing the risk understanding of the decision maker

    International Nuclear Information System (INIS)

    Aven, Terje

    2016-01-01

    A quantitative probabilistic risk assessment produces a conditional risk description given the knowledge of the analysts (formulated to a large extent through assumptions). However, important aspects of the risk may be concealed in the background knowledge of the analyst and the assumptions. This paper discusses this issue, the main purpose being to present a two-stage risk assessment approach where the second stage addresses the risk understanding of the decision maker. This second-stage is to a large extent qualitative. The approach is novel with its separation between the analysts' conditional risk descriptions using probability judgments, and the decision maker's risk understanding. The approach aims at improving the use of risk assessment in practical decision making by ensuring that the results of the risk assessments are properly interpreted and the key aspects of risk, uncertainty and knowledge are brought to attention for the decision makers. Examples are used to illustrate the approach. - Highlights: • A quantitative risk assessment produces a conditional risk description. • The decision maker (DM) needs to address risk beyond this description. • The paper presents a related two-stage process, covering analyst and DM judgments. • The second stage relates to the DM's risk understanding. • Strength of knowledge judgments are included in both stages.

  1. The molecular basis of simple relationships between exposure concentration and toxic effects with time.

    Science.gov (United States)

    Tennekes, Henk A; Sánchez-Bayo, Francisco

    2013-07-05

    Understanding the toxicity of chemicals to organisms requires considering the molecular mechanisms involved as well as the relationships between exposure concentration and toxic effects with time. Our current knowledge about such relationships is mainly explained from a toxicodynamic and toxicokinetic perspective. This paper re-introduces an old approach that takes into account the biochemical mode of action and their resulting biological effects over time of exposure. Empirical evidence demonstrates that the Druckrey-Küpfmüller toxicity model, which was validated for chemical carcinogens in the early 1960s, is also applicable to a wide range of toxic compounds in ecotoxicology. According to this model, the character of a poison is primarily determined by the reversibility of critical receptor binding. Chemicals showing irreversible or slowly reversible binding to specific receptors will produce cumulative effects with time of exposure, and whenever the effects are also irreversible (e.g. death) they are reinforced over time; these chemicals have time-cumulative toxicity. Compounds having non-specific receptor binding, or involving slowly reversible binding to some receptors that do not contribute to toxicity, may also be time-dependent; however, their effects depend primarily on the exposure concentration, with time playing a minor role. Consequently, the mechanism of toxic action has important implications for risk assessment. Traditional risk approaches cannot predict the impacts of toxicants with time-cumulative toxicity in the environment. New assessment procedures are needed to evaluate the risk that the latter chemicals pose on humans and the environment. An example is shown to explain how the risk of time-dependent toxicants is underestimated when using current risk assessment protocols. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  2. Limitations of the toxic equivalency factor (TEF) approach for risk assessment of halogenated aromatic hydrocarbons

    Energy Technology Data Exchange (ETDEWEB)

    Safe, S. [Texas A and M Univ., College Station, TX (United States). Dept. of Veterinary Physiology and Pharmacology

    1995-12-31

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and related halogenated aromatic hydrocarbons (HAHs) are present as complex mixtures of polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs) and biphenyls (PCBs) in most environmental matrices. Risk management of these mixtures utilize the toxic equivalency factor (TEF) approach in which the TCDD (dioxin) or toxic equivalents of a mixture is a summation of the congener concentration (Ci) times TEF{sub i} (potency relative to TCDD) where. TEQ{sub mixture} = {Sigma}[Cil] {times} TEF{sub i}. TEQs are determined only for those HAHs which are aryl hydrocarbon (Ah) receptor agonists and this approach assumes that the toxic or biochemical effects of individual compounds in a mixture are additive. Several in vivo and in vitro laboratory and field studies with different HAH mixtures have been utilized to validate the TEF approach. For some responses, the calculated toxicities of PCDD/PCDF and PCB mixtures predict the observed toxic potencies. However, for fetal cleft palate and immunotoxicity in mice, nonadditive (antagonistic) responses are observed using complex PCB mixtures or binary mixtures containing an Ah receptor agonist with 2,2{prime},4,4{prime},5,5{prime}-hexachlorobiphenyl (PCB153). The potential interactive effects of PCBs and other dietary Ah receptor antagonist suggest that the TEF approach for risk management of HAHs requires further refinement and should be used selectively.

  3. An empirical study of the toxic capsule crisis in China: risk perceptions and behavioral responses.

    Science.gov (United States)

    Feng, Tianjun; Keller, L Robin; Wu, Ping; Xu, Yifan

    2014-04-01

    The outbreak of the toxic capsule crisis during April 2012 aroused widespread public concern about the risk of chromium-contaminated capsules and drug safety in China. In this article, we develop a conceptual model to investigate risk perceptions of the pharmaceutical drug capsules and behavioral responses to the toxic capsule crisis and the relationship between associated factors and these two variables. An online survey was conducted to test the model, including questions on the measures of perceived efficacy of the countermeasures, trust in the State FDA (Food and Drug Administration), trust in the pharmaceutical companies, trust in the pharmaceutical capsule producers, risk perception, concern, need for information, information seeking, and risk avoidance. In general, participants reported higher levels of risk perception, concern, and risk avoidance, and lower levels of trust in the three different stakeholders. The results from the structural equation modeling procedure suggest that perceived efficacy of the countermeasures is a predictor of each of the three trust variables; however, only trust in the State FDA has a dampening impact on risk perception. Both risk perception and information seeking are significant determinants of risk avoidance. Risk perception is also positively related to concern. Information seeking is positively related to both concern and need for information. The theoretical and policy implications are also discussed. © 2013 Society for Risk Analysis.

  4. Identifying Toxic Impacts of Metals Potentially Released during Deep-Sea Mining—A Synthesis of the Challenges to Quantifying Risk

    Directory of Open Access Journals (Sweden)

    Chris Hauton

    2017-11-01

    Full Text Available In January 2017, the International Seabed Authority released a discussion paper on the development of Environmental Regulations for deep-sea mining (DSM within the Area Beyond National Jurisdiction (the “Area”. With the release of this paper, the prospect for commercial mining in the Area within the next decade has become very real. Moreover, within nations' Exclusive Economic Zones, the exploitation of deep-sea mineral ore resources could take place on very much shorter time scales and, indeed, may have already started. However, potentially toxic metal mixtures may be released at sea during different stages of the mining process and in different physical phases (dissolved or particulate. As toxicants, metals can disrupt organism physiology and performance, and therefore may impact whole populations, leading to ecosystem scale effects. A challenge to the prediction of toxicity is that deep-sea ore deposits include complex mixtures of minerals, including potentially toxic metals such as copper, cadmium, zinc, and lead, as well as rare earth elements. Whereas the individual toxicity of some of these dissolved metals has been established in laboratory studies, the complex and variable mineral composition of seabed resources makes the a priori prediction of the toxic risk of DSM extremely challenging. Furthermore, although extensive data quantify the toxicity of metals in solution in shallow-water organisms, these may not be representative of the toxicity in deep-sea organisms, which may differ biochemically and physiologically and which will experience those toxicants under conditions of low temperature, high hydrostatic pressure, and potentially altered pH. In this synthesis, we present a summation of recent advances in our understanding of the potential toxic impacts of metal exposure to deep-sea meio- to megafauna at low temperature and high pressure, and consider the limitation of deriving lethal limits based on the paradigm of exposure to

  5. Risk perception: expert opinion versus public understanding

    International Nuclear Information System (INIS)

    Brown, Jennifer

    1987-01-01

    A research project looking at the public's attitudes towards the siting of radioactive waste depositories is reported. The risk perception studies seek to compare expert and lay understanding of risk. Adverse public reactions to risk can only be understood if it is known how people relate to risks in their everyday or working lives. Social trends and experiences are important, for example, the adverse public opinion on the siting of nuclear waste facilities. A number of elements have been identified as common to different risk areas such as chemicals, drugs, food or radioactive waste. These are the clashing of values, polarization of beliefs or clashes of interest. (UK)

  6. The risk of contamination of food with toxic substances present in animal feed

    NARCIS (Netherlands)

    Kan, C.A.; Meijer, G.A.L.

    2007-01-01

    Toxic substances such as dioxins, mycotoxins, heavy metals, pesticides, veterinary drugs and polycyclic aromatic hydrocarbons are almost ubiquitous in the environment. Thus, they are also present in ingredients for animal feed. Adequate risk management depends on knowledge of absorption, metabolism,

  7. The Role of Biomarkers in Decreasing Risk of Cardiac Toxicity after Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Christine Henri

    2016-01-01

    Full Text Available With the improvement of cancer therapy, survival related to malignancy has improved, but the prevalence of long-term cardiotoxicity has also increased. Cancer therapies with known cardiac toxicity include anthracyclines, biologic agents (trastuzumab, and multikinase inhibitors (sunitinib. The most frequent presentation of cardiac toxicity is dilated cardiomyopathy associated with poorest prognosis. Monitoring of cardiac toxicity is commonly performed by assessment of left ventricular (LV ejection fraction, which requires a significant amount of myocardial damage to allow detection of cardiac toxicity. Accordingly, this creates the impetus to search for more sensitive and reproducible biomarkers of cardiac toxicity after cancer therapy. Different biomarkers have been proposed to that end, the most studied ones included troponin release resulting from cardiomyocyte damage and natriuretic peptides reflecting elevation in LV filling pressure and wall stress. Increase in the levels of troponin and natriuretic peptides have been correlated with cumulative dose of anthracycline and the degree of LV dysfunction. Troponin is recognized as a highly efficient predictor of early and chronic cardiac toxicity, but there remains some debate regarding the clinical usefulness of the measurement of natriuretic peptides because of divergent results. Preliminary data are available for other biomarkers targeting inflammation, endothelial dysfunction, myocardial ischemia, and neuregulin-1. The purpose of this article is to review the available data to determine the role of biomarkers in decreasing the risk of cardiac toxicity after cancer therapy.

  8. Trichothecenes: structure-toxic activity relationships.

    Science.gov (United States)

    Wu, Qinghua; Dohnal, Vlastimil; Kuca, Kamil; Yuan, Zonghui

    2013-07-01

    Trichothecenes comprise a large family of structurally related toxins mainly produced by fungi belonging to the genus Fusarium. Among trichothecenes, type A and type B are of the most concern due to their broad and highly toxic nature. In order to address structure-activity relationships (SAR) of trichothecenes, relationships between structural features and biological effects of trichothecene mycotoxins in mammalian systems are summarized in this paper. The double bond between C-9-C-10 and the 12,13-epoxide ring are essential structural features for trichothecene toxicity. Removal of these groups results in a complete loss of toxicity. A hydroxyl group at C-3 enhances trichothecene toxicity, while this activity decreases gradually when C-3 is substituted with either hydrogen or an acetoxy group. The presence of a hydroxyl group at C-4 promotes slightly lower toxicity than an acetoxy group at the same position. The toxicity for type B trichothecenes decreases if the substituent at C-4 is changed from acetoxy to hydroxyl or hydrogen at C-4 position. The presence of hydroxyl and hydrogen groups on C-15 decreases the trichothecene toxicity in comparison with an acetoxy group attached to this carbon. Trichothecenes toxicity increases when a macrocyclic ring exists between the C-4 and C-15. At C-8 position, an oxygenated substitution at C-8 is essential for trichothecene toxicity, indicating a decrease in the toxicity if substituent change from isovaleryloxy through hydrogen to the hydroxyl group. The presence of a second epoxy ring at C-7-C-8 reduces the toxicity, whereas epoxidation at C-9-C-10 of some macrocyclic trichothecenes increases the activity. Conjugated trichothecenes could release their toxic precursors after hydrolysis in animals, and present an additional potential risk. The SAR study of trichothecenes should provide some crucial information for a better understanding of trichothecene chemical and biological properties in food contamination.

  9. Scenario-targeted toxicity assessment through multiple endpoint bioassays in a soil posing unacceptable environmental risk according to regulatory screening values.

    Science.gov (United States)

    Rodriguez-Ruiz, A; Etxebarria, J; Boatti, L; Marigómez, I

    2015-09-01

    Lanestosa is a chronically polluted site (derelict mine) where the soil (Lanestosa (LA) soil) exceeds screening values (SVs) of regulatory policies in force (Basque Country; Europe) for Zn, Pb and Cd. A scenario-targeted toxicity assessment was carried out on the basis of a multi-endpoint bioassay approach. Acute and chronic toxicity bioassays were conducted with selected test species (Vibrio fischeri, Dictyostelium discoideum, Lactuca sativa, Raphanus sativus and Eisenia fetida) in combination with chemical analysis of soils and elutriates and with bioaccumulation studies in earthworms. Besides, the toxicity profile was compared with that of the mine runoff (RO) soil and of a fresh artificially polluted soil (LAAPS) resembling LA soil pollutant profile. Extractability studies in LA soil revealed that Pb, Zn and Cd were highly available for exchange and/or release into the environment. Indeed, Pb and Zn were accumulated in earthworms and LA soil resulted to be toxic. Soil respiration, V. fischeri, vegetative and developmental cycles of D. discoideum and survival and juvenile production of E. fetida were severely affected. These results confirmed that LA soil had unacceptable environmental risk and demanded intervention. In contrast, although Pb and Zn concentrations in RO soil revealed also unacceptable risk, both metal extractability and toxicity were much lower than in LA soil. Thus, within the polluted site, the need for intervention varied between areas that posed dissimilar risk. Besides, since LAAPS, with a high exchangeable metal fraction, was the most toxic, ageing under in situ natural conditions seemingly contributed to attenuate LA soil risk. As a whole, combining multi-endpoint bioassays with scenario-targeted analysis (including leaching and ageing) provides reliable risk assessment in soils posing unacceptable environmental risk according to SVs, which is useful to optimise the required intervention measures.

  10. Risk of Late Toxicity in Men Receiving Dose-Escalated Hypofractionated Intensity Modulated Prostate Radiation Therapy: Results From a Randomized Trial

    Energy Technology Data Exchange (ETDEWEB)

    Hoffman, Karen E., E-mail: khoffman1@mdanderson.org; Voong, K. Ranh; Pugh, Thomas J.; Skinner, Heath; Levy, Lawrence B.; Takiar, Vinita; Choi, Seungtaek; Du, Weiliang; Frank, Steven J.; Johnson, Jennifer; Kanke, James; Kudchadker, Rajat J.; Lee, Andrew K.; Mahmood, Usama; McGuire, Sean E.; Kuban, Deborah A.

    2014-04-01

    Objective: To report late toxicity outcomes from a randomized trial comparing conventional and hypofractionated prostate radiation therapy and to identify dosimetric and clinical parameters associated with late toxicity after hypofractionated treatment. Methods and Materials: Men with localized prostate cancer were enrolled in a trial that randomized men to either conventionally fractionated intensity modulated radiation therapy (CIMRT, 75.6 Gy in 1.8-Gy fractions) or to dose-escalated hypofractionated IMRT (HIMRT, 72 Gy in 2.4-Gy fractions). Late (≥90 days after completion of radiation therapy) genitourinary (GU) and gastrointestinal (GI) toxicity were prospectively evaluated and scored according to modified Radiation Therapy Oncology Group criteria. Results: 101 men received CIMRT and 102 men received HIMRT. The median age was 68, and the median follow-up time was 6.0 years. Twenty-eight percent had low-risk, 71% had intermediate-risk, and 1% had high-risk disease. There was no difference in late GU toxicity in men treated with CIMRT and HIMRT. The actuarial 5-year grade ≥2 GU toxicity was 16.5% after CIMRT and 15.8% after HIMRT (P=.97). There was a nonsignificant numeric increase in late GI toxicity in men treated with HIMRT compared with men treated with CIMRT. The actuarial 5-year grade ≥2 GI toxicity was 5.1% after CIMRT and 10.0% after HIMRT (P=.11). In men receiving HIMRT, the proportion of rectum receiving 36.9 Gy, 46.2 Gy, 64.6 Gy, and 73.9 Gy was associated with the development of late GI toxicity (P<.05). The 5-year actuarial grade ≥2 GI toxicity was 27.3% in men with R64.6Gy ≥ 20% but only 6.0% in men with R64.6Gy < 20% (P=.016). Conclusions: Dose-escalated IMRT using a moderate hypofractionation regimen (72 Gy in 2.4-Gy fractions) can be delivered safely with limited grade 2 or 3 late toxicity. Minimizing the proportion of rectum that receives moderate and high dose decreases the risk of late rectal toxicity after this

  11. Risk of Late Toxicity in Men Receiving Dose-Escalated Hypofractionated Intensity Modulated Prostate Radiation Therapy: Results From a Randomized Trial

    International Nuclear Information System (INIS)

    Hoffman, Karen E.; Voong, K. Ranh; Pugh, Thomas J.; Skinner, Heath; Levy, Lawrence B.; Takiar, Vinita; Choi, Seungtaek; Du, Weiliang; Frank, Steven J.; Johnson, Jennifer; Kanke, James; Kudchadker, Rajat J.; Lee, Andrew K.; Mahmood, Usama; McGuire, Sean E.; Kuban, Deborah A.

    2014-01-01

    Objective: To report late toxicity outcomes from a randomized trial comparing conventional and hypofractionated prostate radiation therapy and to identify dosimetric and clinical parameters associated with late toxicity after hypofractionated treatment. Methods and Materials: Men with localized prostate cancer were enrolled in a trial that randomized men to either conventionally fractionated intensity modulated radiation therapy (CIMRT, 75.6 Gy in 1.8-Gy fractions) or to dose-escalated hypofractionated IMRT (HIMRT, 72 Gy in 2.4-Gy fractions). Late (≥90 days after completion of radiation therapy) genitourinary (GU) and gastrointestinal (GI) toxicity were prospectively evaluated and scored according to modified Radiation Therapy Oncology Group criteria. Results: 101 men received CIMRT and 102 men received HIMRT. The median age was 68, and the median follow-up time was 6.0 years. Twenty-eight percent had low-risk, 71% had intermediate-risk, and 1% had high-risk disease. There was no difference in late GU toxicity in men treated with CIMRT and HIMRT. The actuarial 5-year grade ≥2 GU toxicity was 16.5% after CIMRT and 15.8% after HIMRT (P=.97). There was a nonsignificant numeric increase in late GI toxicity in men treated with HIMRT compared with men treated with CIMRT. The actuarial 5-year grade ≥2 GI toxicity was 5.1% after CIMRT and 10.0% after HIMRT (P=.11). In men receiving HIMRT, the proportion of rectum receiving 36.9 Gy, 46.2 Gy, 64.6 Gy, and 73.9 Gy was associated with the development of late GI toxicity (P<.05). The 5-year actuarial grade ≥2 GI toxicity was 27.3% in men with R64.6Gy ≥ 20% but only 6.0% in men with R64.6Gy < 20% (P=.016). Conclusions: Dose-escalated IMRT using a moderate hypofractionation regimen (72 Gy in 2.4-Gy fractions) can be delivered safely with limited grade 2 or 3 late toxicity. Minimizing the proportion of rectum that receives moderate and high dose decreases the risk of late rectal toxicity after this

  12. From Classical Toxicology to Tox21: Some Critical Conceptual and Technological Advances in the Molecular Understanding of the Toxic Response Beginning From the Last Quarter of the 20th Century.

    Science.gov (United States)

    Choudhuri, Supratim; Patton, Geoffrey W; Chanderbhan, Ronald F; Mattia, Antonia; Klaassen, Curtis D

    2018-01-01

    Toxicology has made steady advances over the last 60+ years in understanding the mechanisms of toxicity at an increasingly finer level of cellular organization. Traditionally, toxicological studies have used animal models. However, the general adoption of the principles of 3R (Replace, Reduce, Refine) provided the impetus for the development of in vitro models in toxicity testing. The present commentary is an attempt to briefly discuss the transformation in toxicology that began around 1980. Many genes important in cellular protection and metabolism of toxicants were cloned and characterized in the 80s, and gene expression studies became feasible, too. The development of transgenic and knockout mice provided valuable animal models to investigate the role of specific genes in producing toxic effects of chemicals or protecting the organism from the toxic effects of chemicals. Further developments in toxicology came from the incorporation of the tools of "omics" (genomics, proteomics, metabolomics, interactomics), epigenetics, systems biology, computational biology, and in vitro biology. Collectively, the advances in toxicology made during the last 30-40 years are expected to provide more innovative and efficient approaches to risk assessment. A goal of experimental toxicology going forward is to reduce animal use and yet be able to conduct appropriate risk assessments and make sound regulatory decisions using alternative methods of toxicity testing. In that respect, Tox21 has provided a big picture framework for the future. Currently, regulatory decisions involving drugs, biologics, food additives, and similar compounds still utilize data from animal testing and human clinical trials. In contrast, the prioritization of environmental chemicals for further study can be made using in vitro screening and computational tools. Published by Oxford University Press on behalf of the Society of Toxicology 2017. This work is written by US Government employees and is in the

  13. Exposure to sennoside-digoxin interaction and risk of digoxin toxicity: a population-based nested case-control study.

    Science.gov (United States)

    Wang, Meng-Ting; Li, I-Hsun; Lee, Wan-Ju; Huang, Tien-Yu; Leu, Hsin-Bang; Chan, Agnes L F

    2011-11-01

    Digoxin is an important medication for heart failure (HF) patients and sennosides are widely used to treat constipation. Recently, safety concerns have been raised about a possible interaction between sennosides and digoxin, an issue that has not been studied empirically. This study therefore aimed to evaluate whether exposure to sennoside-digoxin interaction is associated with an increased risk of digoxin toxicity. This was a population-based nested case-control study that analysed data obtained from the Taiwan National Health Insurance Research Database between 1 January 2001 and 31 December 2004. All HF patients treated with digoxin for the first time were included as the study cohort. Of these, cases were identified as subjects hospitalized for digoxin toxicity (International Classification of Diseases, Ninth Revision, Clinical Modification, ICD-9-CM 972.1), and matched to randomly selected controls. Use of sennosides was compared between the two groups. Odds ratios (ORs) were employed to quantify the risk associated with exposure to sennoside-digoxin interaction by conditional logistic regression. The study cohort comprised 222,527 HF patients, of whom 524 were identified as cases and 2,502 as matched controls. Use of sennosides during the 14 days preceding the index date was found to be associated with a 1.61-fold increased risk of digoxin toxicity [95% confidence interval (CI) = 1.15, 2.25]. Additionally, a greater risk was observed for sennosides prescribed at an average daily dose ≥ 24 mg (adjusted OR = 1.93; 95% CI = 1.27, 2.94). The combined use of sennosides and digoxin was found to be associated with a modest increased risk of digoxin toxicity in HF patients.

  14. Late renal toxicity of treatment for childhood malignancy: risk factors, long-term outcomes, and surveillance.

    Science.gov (United States)

    Skinner, Roderick

    2018-02-01

    Chronic glomerular and tubular nephrotoxicity is reported in 20-50% and 20-25%, respectively, of children and adolescents treated with ifosfamide and 60-80% and 10-30%, respectively, of those given cisplatin. Up to 20% of children display evidence of chronic glomerular damage after unilateral nephrectomy for a renal tumour. Overall, childhood cancer survivors have a ninefold higher risk of developing renal failure compared with their siblings. Such chronic nephrotoxicity may have multiple causes, including chemotherapy, radiotherapy exposure to kidneys, renal surgery, supportive care drugs and tumour-related factors. These cause a wide range of chronic glomerular and tubular toxicities, often with potentially severe clinical sequelae. Many risk factors for developing nephrotoxicity, mostly patient and treatment related, have been described, but we remain unable to predict all episodes of renal damage. This implies that other factors may be involved, such as genetic polymorphisms influencing drug metabolism. Although our knowledge of the long-term outcomes of chronic nephrotoxicity is increasing, there is still much to learn, including how we can optimally predict or achieve early detection of nephrotoxicity. Greater understanding of the pathogenesis of nephrotoxicity is needed before its occurrence can be prevented.

  15. Chemical concentrations, exposures, health risks by census tract from National Scale Air Toxics Assessment (NATA)

    Data.gov (United States)

    U.S. Environmental Protection Agency — Chemical concentrations, exposures, health risks by census tract for the United States from National Scale Air Toxics Assessment (NATA). This dataset is associated...

  16. The prevalence of toxic hotspots in former Soviet countries

    International Nuclear Information System (INIS)

    Sharov, Petr; Dowling, Russell; Gogishvili, Megi; Jones, Barbara; Caravanos, Jack; McCartor, Andrew; Kashdan, Zachary; Fuller, Richard

    2016-01-01

    Using a global database of contaminated sites, toxic hotspots in eight former Soviet countries were analyzed to identify the prevalence, types and sources of toxic pollution, as well as their associated potential public health impacts. For this analysis, polluted sites in Armenia, Azerbaijan, Kazakhstan, Kyrgyzstan, Russia, Tajikistan, Ukraine, and Uzbekistan were compiled and analyzed. The levels of contamination of seven key pollutants were assessed in each country. 424 contaminated sites were identified using data from Blacksmith Institute. Pesticides, lead (Pb), radioactive metals, arsenic (As), mercury (Hg), chromium (Cr), and cadmium (Cd) were the most commonly identified key pollutants. Collectively, these sites pose health risks to an estimated 6.2 million residents. The existing data on toxic hotspots in former Soviet countries likely captures only a small percentage of actual contaminated sites, but suggests potentially severe public health consequences. Additional assessments are needed to understand the risks posed by toxic pollution in the region. - Highlights: • Pollution in 8 former Soviet countries poses a health risk to 6.2 million residents. • The most commonly found key pollutants are pesticides, lead, arsenic, and cadmium. • The majority of sites can be traced to Soviet legacy pollution. - 424 sites were identified in the analysis. Pesticides, Pb, radioactive metals, As, Hg, Cr, and Cd were the most common key pollutants, collectively affecting 6.2 million people.

  17. Evaluation of nano-specific toxicity of zinc oxide, copper oxide, and silver nanoparticles through toxic ratio

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Weicheng; Liu, Xiawei; Bao, Shaopan; Xiao, Bangding; Fang, Tao, E-mail: fangt@ihb.ac.cn [Chinese Academy of Sciences, Institute of Hydrobiology (China)

    2016-12-15

    For safety and environmental risk assessments of nanomaterials (NMs) and to provide essential toxicity data, nano-specific toxicities, or excess toxicities, of ZnO, CuO, and Ag nanoparticles (NPs) (20, 20, and 30 nm, respectively) to Escherichia coli and Saccharomyces cerevisiae in short-term (6 h) and long-term (48 h) bioassays were quantified based on a toxic ratio. ZnO NPs exhibited no nano-specific toxicities, reflecting similar toxicities as ZnO bulk particles (BPs) (as well as zinc salt). However, CuO and Ag NPs yielded distinctly nano-specific toxicities when compared with their BPs. According to their nano-specific toxicities, the capability of these NPs in eliciting hazardous effects on humans and the environment was as follows: CuO > Ag > ZnO NPs. Moreover, long-term bioassays were more sensitive to nano-specific toxicity than short-term bioassays. Overall, nano-specific toxicity is a meaningful measurement to evaluate the environmental risk of NPs. The log T{sub e}{sup particle} value is a useful parameter for quantifying NP nano-specific toxicity and enabling comparisons of international toxicological data. Furthermore, this value could be used to determine the environmental risk of NPs.

  18. Individualized toxicity-titrated 6-mercaptopurine increments during high-dose methotrexate consolidation treatment of lower risk childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Frandsen, Thomas Leth; Abrahamsson, Jonas; Lausen, Birgitte Frederiksen

    2011-01-01

    This study explored the feasibility and toxicity of individualized toxicity-titrated 6-mercaptopurine (6MP) dose increments during post-remission treatment with High-dose methotrexate (HDM) (5000 mg/m2, ×3) in 38 patients with Childhood (ALL). Patients were increased in steps of 25 mg 6MP/m2 per...... the remaining patients (P = 0·03). This study shows individualized toxicity-titrated 6MP dosing during consolidation is feasible without increased risk of toxicity....

  19. Toxic chemicals: risk prevention through use reduction

    National Research Council Canada - National Science Library

    Higgins, Thomas E; Sachdev, Jayanti A; Engleman, Stephen A

    2011-01-01

    ... on the actual toxicity of chemicals currently in use, discusses variables that contribute to the relative toxicity of a substance, compares alternate emphases in existing programs for reducing environmental...

  20. Potential risks of metal toxicity in contaminated sediments of Deule river in Northern France

    International Nuclear Information System (INIS)

    Lourino-Cabana, Beatriz; Lesven, Ludovic; Charriau, Adeline; Billon, Gabriel; Ouddane, Baghdad; Boughriet, Abdel

    2011-01-01

    Research highlights: → A historical environmental pollution is evidenced with reference to background levels. → Sedimentary trace metals partitioning is examined under undisturbed conditions. → Anoxia and diagenetic processes induce geochemical and mineralogical variabilities. → Do metals present in particles and pore waters exhibit a potential toxicity risk? → Behaviour of binding fractions contributes to trace metals scavenging. - Abstract: The aim of this paper was to evaluate the potential sediment cumulative damage and toxicity due to metal contamination in a polluted zone of Deule river (in northern France) from nearby two smelters. Metal-enrichment factors and geoaccumulation indices measured with sediment depth revealed that - compared to background levels either in local reference soils or in world rivers sediments/suspended particulate matter - Cd contributed to the highest pollution levels, followed by Zn, Pb and to a much lesser extent Cu and Ni. A comparison of the vertical distribution of AVS (acid volatile sulfides), SEM (simultaneously extracted metals), TMC (total metal concentrations), TOC (total organic carbon) and interstitial water-metal concentrations in the sediment allowed us to highlight the extent of toxicity caused by Cd, Pb, Zn, Ni and Cu and to raise the possibility of their association with certain geochemical phases. To assess the actual environmental impacts of these metals in Deule river, numerical sediment quality guidelines were further used in the present work. Sedimentary Pb, Zn, and Cd contents largely exceeded PEC (probable effect concentration) values reported as consensus-based sediment quality guidelines for freshwater ecosystems. As for risks of toxicity from pore waters, metal concentrations reached their maxima at the surficial layers of the sediment (1-3 cm) and IWCTU (Interstitial Water Criteria Toxicity Unit) observed for Pb and to a lesser extent Cd, violated the corresponding water quality data recommended

  1. Toxicity risk of insecticides to the insect egg parasitoid Trichogramma evanescens Westwood (Hymenoptera: Trichogrammatidae).

    Science.gov (United States)

    Wang, Yanhua; Wu, Changxing; Cang, Tao; Yang, Lizhi; Yu, Weihua; Zhao, Xueping; Wang, Qiang; Cai, Leiming

    2014-03-01

    Natural populations of Trichogramma evanescens contribute to the control of lepidopterous pests. The toxic effects of insecticides have been extensively reported on trichogrammatids, but are largely unknown on T. evanescens. In this study, the toxicities of seven classes of chemicals against the parasitoid were investigated. Among these classes, organophosphates and carbamates exhibited the highest levels of intrinsic toxicity, with LC50 values ranging from 0.025 (0.023-0.028) to 2.20 (1.71-3.09) and from 0.040 (0.032-0.053) to 1.84 (1.53-2.30) mg AI L(-1) respectively. Among the phenylpyrazoles, only ethiprole can be considered to be less toxic in the group. Avermectins, pyrethroids and neonicotinoids were less toxic, with LC50 values ranging from 1.29 to 2.57, from 2.26 to 14.03 and from 1.12 to 239.1 mg AI L(-1) respectively. In contrast, insect growth regulators (IGRs) showed the lowest toxicity to the parasitoid, with LC50 values ranging from 3383 (2406-5499) to 5650 (4228-8579) mg AI L(-1) . The results of risk quotient analysis indicated that neonicotinoids, avermectins, pyrethroids and IGRs were less hazardous, but phenylpyrazoles (except for ethiprole), organophosphates and carbamates were slightly to moderately or dangerously toxic to T. evanescens. The present results provide informative data for implementing biological and chemical control strategies in integrated pest management of lepidopterans. © 2013 Society of Chemical Industry.

  2. Evaluation of metals, metalloids, and ash mixture toxicity using sediment toxicity testing.

    Science.gov (United States)

    Stojak, Amber; Bonnevie, Nancy L; Jones, Daniel S

    2015-01-01

    In December 2008, a release of 4.1 million m(3) of coal ash from the Tennessee Valley Authority Kingston Fossil Plant occurred. Ash washed into the Emory River and migrated downstream into the Clinch and Tennessee Rivers. A Baseline Ecological Risk Assessment evaluated risks to ecological receptors from ash in the river system post-dredging. This article describes the approach used and results from sediment toxicity tests, discussing any causal relationships between ash, metals, and toxicity. Literature is limited in the realm of aquatic coal combustion residue (CCR) exposures and the potential magnitude of effects on benthic invertebrates. Sediment samples along a spectrum of ash content were used in a tiered toxicity testing approach and included a combination of 10 day sediment toxicity acute tests and longer-term, partial life cycle "definitive" tests with 2 species (Hyalella azteca and Chironomus dilutus). Arsenic, and to a lesser extent Se, in the ash was the most likely toxicant causing observed effects in the laboratory toxicity tests. Sites in the Emory River with the greatest statistical and biologically significant effects had As concentrations in sediments twice the probable effects concentration of 33 mg/kg. These sites contained greater than 50% ash. Sites with less than approximately 50% ash in sediments exhibited fewer significant toxic responses relative to the reference sediment in the laboratory. The results discussed here present useful evidence of only limited effects occurring from a worst-case exposure pathway. These results provided a valuable line of evidence for the overall assessment of risks to benthic invertebrates and to other ecological receptors, and were crucial to risk management and development of project remediation goals. © 2014 SETAC.

  3. Predicting molybdenum toxicity to higher plants: Estimation of toxicity threshold values

    Energy Technology Data Exchange (ETDEWEB)

    McGrath, S.P., E-mail: steve.mcgrath@bbsrc.ac.u [Soil Science Department, Centre for Soils and Ecosystems Function, Rothamsted Research, Harpenden, Hertfordshire AL5 2JQ (United Kingdom); Mico, C.; Zhao, F.J.; Stroud, J.L. [Soil Science Department, Centre for Soils and Ecosystems Function, Rothamsted Research, Harpenden, Hertfordshire AL5 2JQ (United Kingdom); Zhang, H.; Fozard, S. [Division of Environmental Science, Lancaster University, Lancaster LA1 4YQ (United Kingdom)

    2010-10-15

    Four plant species (oilseed rape, Brassica napus L.; red clover, Trifolium pratense L.; ryegrass, Lolium perenne L.; and tomato, Lycopersicon esculentum L.) were tested on ten soils varying widely in soil properties to assess molybdenum (Mo) toxicity. A larger range (66-fold-609-fold) of added Mo concentrations resulting in 50% inhibition of yield (ED{sub 50}) was found among soils than among plant species (2-fold-38-fold), which illustrated that the soils differed widely in the expression of Mo toxicity. Toxicity thresholds based on soil solution Mo narrowed the variation among soils compared to thresholds based on added Mo concentrations. We conclude that plant bioavailability of Mo in soil depends on Mo solubility, but this alone did not decrease the variability in observed toxicity enough to be used in risk assessment and that other soil properties influencing Mo toxicity to plants need to be considered. - Mo toxicity thresholds varied widely in different soils and therefore soil properties need to be taken into account in order to assess the risk of Mo exposure.

  4. Understanding the tolerance of the industrial yeast Saccharomyces cerevisiae against a major class of toxic aldehyde compounds.

    Science.gov (United States)

    Liu, ZongLin Lewis

    2018-07-01

    Development of the next-generation biocatalyst is vital for fermentation-based industrial applications and a sustainable bio-based economy. Overcoming the major class of toxic compounds associated with lignocellulose-to-biofuels conversion is one of the significant challenges for new strain development. A significant number of investigations have been made to understand mechanisms of the tolerance for industrial yeast. It is humbling to learn how complicated the cell's response to the toxic chemicals is and how little we have known about yeast tolerance in the universe of the living cell. This study updates our current knowledge on the tolerance of industrial yeast against aldehyde inhibitory compounds at cellular, molecular and the genomic levels. It is comprehensive yet specific based on reproducible evidence and cross confirmed findings from different investigations using varied experimental approaches. This research approaches a rational foundation toward a more comprehensive understanding on the yeast tolerance. Discussions and perspectives are also proposed for continued exploring the puzzle of the yeast tolerance to aid the next-generation biocatalyst development.

  5. Implementing Toxicity Testing in the 21st Century (TT21C): Making safety decisions using toxicity pathways, and progress in a prototype risk assessment

    International Nuclear Information System (INIS)

    Adeleye, Yeyejide; Andersen, Melvin; Clewell, Rebecca; Davies, Michael; Dent, Matthew; Edwards, Sue; Fowler, Paul; Malcomber, Sophie; Nicol, Beate; Scott, Andrew; Scott, Sharon; Sun, Bin; Westmoreland, Carl; White, Andrew; Zhang, Qiang; Carmichael, Paul L.

    2015-01-01

    Risk assessment methodologies in toxicology have remained largely unchanged for decades. The default approach uses high dose animal studies, together with human exposure estimates, and conservative assessment (uncertainty) factors or linear extrapolations to determine whether a specific chemical exposure is ‘safe’ or ‘unsafe’. Although some incremental changes have appeared over the years, results from all new approaches are still judged against this process of extrapolating high-dose effects in animals to low-dose exposures in humans. The US National Research Council blueprint for change, entitled Toxicity Testing in the 21st Century: A Vision and Strategy called for a transformation of toxicity testing from a system based on high-dose studies in laboratory animals to one founded primarily on in vitro methods that evaluate changes in normal cellular signalling pathways using human-relevant cells or tissues. More recently, this concept of pathways-based approaches to risk assessment has been expanded by the description of ‘Adverse Outcome Pathways’ (AOPs). The question, however, has been how to translate this AOP/TT21C vision into the practical tools that will be useful to those expected to make safety decisions. We have sought to provide a practical example of how the TT21C vision can be implemented to facilitate a safety assessment for a commercial chemical without the use of animal testing. To this end, the key elements of the TT21C vision have been broken down to a set of actions that can be brought together to achieve such a safety assessment. Such components of a pathways-based risk assessment have been widely discussed, however to-date, no worked examples of the entire risk assessment process exist. In order to begin to test the process, we have taken the approach of examining a prototype toxicity pathway (DNA damage responses mediated by the p53 network) and constructing a strategy for the development of a pathway based risk assessment for a

  6. Implementing Toxicity Testing in the 21st Century (TT21C): Making safety decisions using toxicity pathways, and progress in a prototype risk assessment.

    Science.gov (United States)

    Adeleye, Yeyejide; Andersen, Melvin; Clewell, Rebecca; Davies, Michael; Dent, Matthew; Edwards, Sue; Fowler, Paul; Malcomber, Sophie; Nicol, Beate; Scott, Andrew; Scott, Sharon; Sun, Bin; Westmoreland, Carl; White, Andrew; Zhang, Qiang; Carmichael, Paul L

    2015-06-05

    Risk assessment methodologies in toxicology have remained largely unchanged for decades. The default approach uses high dose animal studies, together with human exposure estimates, and conservative assessment (uncertainty) factors or linear extrapolations to determine whether a specific chemical exposure is 'safe' or 'unsafe'. Although some incremental changes have appeared over the years, results from all new approaches are still judged against this process of extrapolating high-dose effects in animals to low-dose exposures in humans. The US National Research Council blueprint for change, entitled Toxicity Testing in the 21st Century: A Vision and Strategy called for a transformation of toxicity testing from a system based on high-dose studies in laboratory animals to one founded primarily on in vitro methods that evaluate changes in normal cellular signalling pathways using human-relevant cells or tissues. More recently, this concept of pathways-based approaches to risk assessment has been expanded by the description of 'Adverse Outcome Pathways' (AOPs). The question, however, has been how to translate this AOP/TT21C vision into the practical tools that will be useful to those expected to make safety decisions. We have sought to provide a practical example of how the TT21C vision can be implemented to facilitate a safety assessment for a commercial chemical without the use of animal testing. To this end, the key elements of the TT21C vision have been broken down to a set of actions that can be brought together to achieve such a safety assessment. Such components of a pathways-based risk assessment have been widely discussed, however to-date, no worked examples of the entire risk assessment process exist. In order to begin to test the process, we have taken the approach of examining a prototype toxicity pathway (DNA damage responses mediated by the p53 network) and constructing a strategy for the development of a pathway based risk assessment for a specific

  7. Anticoagulant rodenticide toxicity to non-target wildlife under controlled exposure conditions

    Science.gov (United States)

    Rattner, Barnett A.; Mastrota, F. Nicholas; van den Brink, Nico; Elliott, J.; Shore, R.; Rattner, B.

    2018-01-01

    Much of our understanding of anticoagulant rodenticide toxicity to non-target wildlife has been derived from molecular through whole animal research and registration studies in domesticated birds and mammals, and to a lesser degree from trials with captive wildlife. Using these data, an adverse outcome pathway identifying molecular initiating and anchoring events (inhibition of vitamin K epoxide reductase, failure to activate clotting factors), and established and plausible linkages (coagulopathy, hemorrhage, anemia, reduced fitness) associated with toxicity, is presented. Controlled exposure studies have demonstrated that second-generation anticoagulant rodenticides (e.g., brodifacoum) are more toxic than first- and intermediate-generation compounds (e.g., warfarin, diphacinone), however the difference in potency is diminished when first- and intermediate-generation compounds are administered on multiple days. Differences in species sensitivity are inconsistent among compounds. Numerous studies have compared mortality rate of predators fed prey or tissue containing anticoagulant rodenticides. In secondary exposure studies in birds, brodifacoum appears to pose the greatest risk, with bromadiolone, difenacoum, flocoumafen and difethialone being less hazardous than brodifacoum, and warfarin, coumatetralyl, coumafuryl, chlorophacinone and diphacinone being even less hazardous. In contrast, substantial mortality was noted in secondary exposure studies in mammals ingesting prey or tissue diets containing either second- or intermediate-generation compounds. Sublethal responses (e.g., prolonged clotting time, reduced hematocrit and anemia) have been used to study the sequelae of anticoagulant intoxication, and to some degree in the establishment of toxicity thresholds or toxicity reference values. Surprisingly few studies have undertaken histopathological evaluations to identify cellular lesions and hemorrhage associated with anticoagulant rodenticide exposure in non

  8. Prostate cancer and toxicity from critical use exemptions of methyl bromide: Environmental protection helps protect against human health risks

    Directory of Open Access Journals (Sweden)

    Budnik Lygia T

    2012-01-01

    Full Text Available Abstract Background Although ozone-depleting methyl bromide was destined for phase-out by 2005, it is still widely applied as a consequence of various critical-use-exemptions and mandatory international regulations aiming to restrict the spread of pests and alien species (e.g. in globalized transport and storage. The withdrawal of methyl bromide because of its environmental risk could fortuitously help in the containment of its human toxicity. Methods We performed a systematic review of the literature, including in vitro toxicological and epidemiological studies of occupational and community exposure to the halogenated hydrocarbon pesticide methyl bromide. We focused on toxic (especially chronic or carcinogenic effects from the use of methyl bromide, on biomonitoring data and reference values. Eligible epidemiological studies were subjected to meta-analysis. Results Out of the 542 peer reviewed publications between 1990-2011, we found only 91 referring to toxicity of methyl bromide and 29 using the term "carcinogenic", "neoplastic" or "mutagenic". Several studies provide new additional data pertaining to the mechanistic aspects of methyl bromide toxicity. Few studies have performed a detailed exposure assessment including biomonitoring. Three evaluated epidemiological studies assessed a possible association between cancer and methyl bromide. Overall, exposure to methyl bromide is associated with an increased risk of prostate cancer OR, 1.21; 95% CI (0,98-1.49, P = 0.076. Two epidemiological studies have analyzed environmental, non-occupational exposure to methyl bromide providing evidence for its health risk to the general public. None of the epidemiological studies addressed its use as a fumigant in freight containers, although recent field and case reports do refer to its toxic effects associated with its use in shipping and storage. Conclusions Both the epidemiological evidence and toxicological data suggest a possible link between methyl

  9. Potentially Toxic Elements and Health Risk Assessment in Farmland Systems around High-Concentrated Arsenic Coal Mining in Xingren, China

    Directory of Open Access Journals (Sweden)

    Ying-ju Li

    2018-01-01

    Full Text Available The health risk of potentially toxic elements (PTEs via contamination of the food chain has attracted widespread concern. The aim of this study is to evaluate the effects of PTEs in environment and human body (fingernail, hair, and blood of people living in agricultural soil near arsenic coal mining areas in Xingren County (Guizhou, southwest China. 89 crop samples which included vegetables, rice, maize, and coix seed and their corresponding soils and 17 local surface water and biological tissue samples (41 × 3 in near arsenic coal mining areas were collected, and the concentrations of potentially toxic elements (As, Cd, Cu, Cr, and Pb in all the samples were determined. The health risk assessment methods developed by the United States Environmental Protection Agency were employed to explore the potential health hazards of PTEs in soils growing crops. Results showed that 4 toxic elements, Cd, Cu, As, and Cr, were found to have different degrees of contamination in soils in the studied area. The total concentration of toxic elements (As, Cr, Cu, and Pb in fingernail, hair, and blood samples were 90.50, 69.31, and 6.90 mg·kg−1, respectively. Fingernail samples from females were more likely to show exposure to trace metals compared to males. As the age of the subject increased, the concentration of As also increased in all three biological samples. The risk assessment for the mean hazard index value from the consumption of local food crops was 14.81, indicating that consumers may experience adverse, noncarcinogenic health effects. The estimated mean total cancer risk value of was 5.3 × 10−3, which was approximately 10 to 1000 times higher than the acceptable range of 10−6–10−4, indicating serious carcinogenic risks for local people consuming crops from the area. This study provides evidence that local residents in this study area may be at a high risk of disease caused from toxic element exposure.

  10. Preliminary Assessment of Health Risks of Potentially Toxic Elements in Settled Dust over Beijing Urban Area

    Directory of Open Access Journals (Sweden)

    Dejun Wan

    2016-05-01

    Full Text Available To examine levels, health risks, sources, and spatial distributions of potentially toxic elements in settled dust over Beijing urban area, 62 samples were collected mostly from residential building outdoor surfaces, and their <63 μm fractions were measured for 12 potentially toxic elements. The results show that V, Cr, Mn, Co, Ni, and Ba in dust are from predominantly natural sources, whereas Cu, Zn, As, Cd, Sb, and Pb mostly originate from anthropogenic sources. Exposure to these elements in dust has significant non-cancer risks to children but insignificant to adults. Cancer risks of Cr, Co, Ni, As, and Cd via inhalation and dermal contact are below the threshold of 10−6–10−4 but As via dust ingestion shows a tolerable risk. The non-cancer risks to children are contributed mainly (75% by As, Pb, and Sb, and dominantly (92% via dust ingestion, with relatively higher risks mainly occurring in the eastern and northeastern Beijing urban areas. Although Cd, Zn, and Cu in dust are heavily affected by anthropogenic sources, their health risks are insignificant. Source appointments suggest that coal burning emissions, the dominant source of As, are likely the largest contributors to the health risk, and traffic-related and industrial emissions are also important because they contribute most of the Pb and Sb in dust.

  11. Health risks in international container and bulk cargo transport due to volatile toxic compounds.

    Science.gov (United States)

    Baur, Xaver; Budnik, Lygia Therese; Zhao, Zhiwei; Bratveit, Magne; Djurhuus, Rune; Verschoor, Louis; Rubino, Federico Maria; Colosio, Claudio; Jepsen, Jorgen R

    2015-01-01

    To ensure the preservation and quality of the goods, physical (i.e. radiation) or chemical pest control is needed. The dark side of such consents may bear health risks in international transport and production sharing. In fact, between 10% and 20% of all containers arriving European harbors were shown to contain volatile toxic substances above the exposure limit values. Possible exposure to these toxic chemicals may occur not only for the applicators but also the receiver by off gassing from products, packing materials or transport units like containers. A number of intoxications, some with lethal outcome, occur not only during the fumigation, but also during freight transport (on bulk carriers and other transport vessels), as well as in the logistic lines during loading and unloading. Risk occupations include dock-workers, seafarers, inspectors, as well as the usually uninformed workers of importing enterprises that unload the products. Bystanders as well as vulnerable consumers may also be at risk. Ongoing studies focus on the release of these toxic volatile substances from various goods. It was shown that the half-lives of the off-gassing process range between minutes and months, depending on the toxic substance, its chemical reactivity, concentration, the temperature, the contaminated matrix (goods and packing materials), and the packing density in the transport units. Regulations on declaration and handling dangerous goods are mostly not followed. It is obvious that this hazardous situation in freight transport urgently requires preventive steps. In order to improve awareness and relevant knowledge there is a need for more comprehensive information on chemical hazards and a broader implementation of the already existing regulations and guidelines, such as those from ILO, IMO, and national authorities. It is also necessary to have regular controls by the authorities on a worldwide scale, which should be followed by sanctions in case of disregarding regulations

  12. Animal data on plutonium toxicity

    International Nuclear Information System (INIS)

    Thompson, R.C.

    1975-01-01

    Animal data are necessary in the assessment of plutonium toxicity since it is unlikely that the necessary information on effects from humans will be obtained. Experiments on animals must be designed to provide understanding of the mechanisms at work if the results are to be applied to man since it is a statistical impossibility to design experiments to measure directly the low levels of risk that are of concern. Cancer induction appears to be the risk of greatest concern with the lung and bone apparently the most susceptible organs, depending upon the method of administration. Current limitations on these organs do not appear to have the safety margin formerly believed and there are some uncertainties in the extrapolation from animal data to man. (author)

  13. Adjuvant chemotherapy and risk of gastrointestinal, hematologic, and cardiac toxicities in elderly patients with stage III colon cancer.

    Science.gov (United States)

    Hu, Chung-Yuan; Chan, Wenyaw; Delclos, George P; Du, Xianglin L

    2012-06-01

    Randomized trials have established the effectiveness of 5-fluorouracil-based adjuvant chemotherapy for stage III resectable colon cancer but the toxicity has not been well established outside the trial setting. The objective of this study was to estimate the risk of various toxicity-related endpoints among the elderly patients. Patients diagnosed with stage III colon cancer in 1991 to 2005 were identified from the Surveillance, Epidemiology, and End Results-Medicare database. Chemotherapy use within 3 months after tumor resection was identified from submitted claims. We reported the 3-month cumulative incidence rate (CIR) for gastrointestinal and hematologic toxicities. The risk of ischemic heart disease in relation to chemotherapy use and length was assessed using Cox regression models, stratified by age and comorbidity subgroups. Of the 12,099 patients, 63.9% (n=7740) received adjuvant chemotherapy. Common gastrointestinal and hematologic toxicities among chemotherapy group include volume depletion disorder (CIR=9.1%), agranulocytosis (CIR=3.4%), diarrhea (CIR=2.4%), nausea and vomiting (CIR=2.3%). Chemotherapy use was significantly associated with the onset of these toxicities [hazard ratio (HR)=2.76; 95% confidence interval (95% CI)=2.42-3.15]. The risk of ischemic heart disease was slightly associated with chemotherapy use (HR=1.08, 95% CI=0.96-1.22), but significant only among patients aged colon cancer. On account of the effects of these side effects on treatment discontinuation, rehospitalization, and overall health status, some close monitoring and preventive measures may be emphasized to maximize the benefits of adjuvant chemotherapy.

  14. Using quantitative structure-activity relationships (QSAR) to predict toxic endpoints for polycyclic aromatic hydrocarbons (PAH).

    Science.gov (United States)

    Bruce, Erica D; Autenrieth, Robin L; Burghardt, Robert C; Donnelly, K C; McDonald, Thomas J

    2008-01-01

    Quantitative structure-activity relationships (QSAR) offer a reliable, cost-effective alternative to the time, money, and animal lives necessary to determine chemical toxicity by traditional methods. Additionally, humans are exposed to tens of thousands of chemicals in their lifetimes, necessitating the determination of chemical toxicity and screening for those posing the greatest risk to human health. This study developed models to predict toxic endpoints for three bioassays specific to several stages of carcinogenesis. The ethoxyresorufin O-deethylase assay (EROD), the Salmonella/microsome assay, and a gap junction intercellular communication (GJIC) assay were chosen for their ability to measure toxic endpoints specific to activation-, induction-, and promotion-related effects of polycyclic aromatic hydrocarbons (PAH). Shape-electronic, spatial, information content, and topological descriptors proved to be important descriptors in predicting the toxicity of PAH in these bioassays. Bioassay-based toxic equivalency factors (TEF(B)) were developed for several PAH using the quantitative structure-toxicity relationships (QSTR) developed. Predicting toxicity for a specific PAH compound, such as a bioassay-based potential potency (PP(B)) or a TEF(B), is possible by combining the predicted behavior from the QSTR models. These toxicity estimates may then be incorporated into a risk assessment for compounds that lack toxicity data. Accurate toxicity predictions are made by examining each type of endpoint important to the process of carcinogenicity, and a clearer understanding between composition and toxicity can be obtained.

  15. Toxicity risk of non-target organs at risk receiving low-dose radiation: case report

    International Nuclear Information System (INIS)

    Shueng, Pei-Wei; Lin, Shih-Chiang; Chang, Hou-Tai; Chong, Ngot-Swan; Chen, Yu-Jen; Wang, Li-Ying; Hsieh, Yen-Ping; Hsieh, Chen-Hsi

    2009-01-01

    The spine is the most common site for bone metastases. Radiation therapy is a common treatment for palliation of pain and for prevention or treatment of spinal cord compression. Helical tomotherapy (HT), a new image-guided intensity modulated radiotherapy (IMRT), delivers highly conformal dose distributions and provides an impressive ability to spare adjacent organs at risk, thus increasing the local control of spinal column metastases and decreasing the potential risk of critical organs under treatment. However, there are a lot of non-target organs at risk (OARs) occupied by low dose with underestimate in this modern rotational IMRT treatment. Herein, we report a case of a pathologic compression fracture of the T9 vertebra in a 55-year-old patient with cholangiocarcinoma. The patient underwent HT at a dose of 30 Gy/10 fractions delivered to T8-T10 for symptom relief. Two weeks after the radiotherapy had been completed, the first course of chemotherapy comprising gemcitabine, fluorouracil, and leucovorin was administered. After two weeks of chemotherapy, however, the patient developed progressive dyspnea. A computed tomography scan of the chest revealed an interstitial pattern with traction bronchiectasis, diffuse ground-glass opacities, and cystic change with fibrosis. Acute radiation pneumonitis was diagnosed. Oncologists should be alert to the potential risk of radiation toxicities caused by low dose off-targets and abscopal effects even with highly conformal radiotherapy

  16. Toxic metals in tissues of fishes from the Black Sea and associated human health risk exposure.

    Science.gov (United States)

    Plavan, Gabriel; Jitar, Oana; Teodosiu, Carmen; Nicoara, Mircea; Micu, Dragos; Strungaru, Stefan-Adrian

    2017-03-01

    The anthropogenic activities in the Black Sea area are responsible for toxic metal contamination of sea food products. In this study, several toxic metals: cadmium, lead, nickel, chromium, and copper were quantified in different tissues (digestive tract, muscle, skeleton, skin) of nine fish species (Neogobius melanostomus, Belone belone, Solea solea, Trachurus mediterraneus ponticus, Sardina pilchardus, Engraulis encrasicolus, Pomatomus saltatrix, Sprattus sprattus, Scorpaena porcus) by using atomic absorption spectrometer with a high-resolution continuum source and graphite furnace technique (HR-CS GF-AAS), and the risk of fish meat consumption by the young human population was evaluated. These metals are used in high amounts in industries located near the coastline such as shipyard construction and industrial plants. Toxic metal accumulation depends on fish feeding behavior, abiotic conditions, metal chemistry, and animal physiology. For instance, cadmium was measured in the muscle of the investigated species and average values of 0.0008-0.0338 mg kg -1 were obtained. The lowest average value of this metal was measured at benthic species N. melanostomus and the highest at the pelagic predator T. mediterraneus ponticus. Generally, the highest metal concentration was measured in the digestive tract that has the role of biofilter for these contaminants. The risk of contamination is significantly reduced by avoiding the consumption of certain fish tissues (digestive tract and skin for copper and skeleton for nickel). An estimation of the dietary metal intake to young consumers was realized for each of the studied species of fish from Romanian, Bulgarian, and Turkish waters, during the period 2001-2014 in order to evaluate the risks of chronic exposure in time due to metal toxicity. This estimation is important for the prevention of chronic exposure due to metal toxicity. Food exposure to studied metals showed a negative trend for Romania, Turkey, and Bulgaria based

  17. Emerging contaminants in Belgian marine waters: single toxicant and mixture risks of pharmaceuticals.

    Science.gov (United States)

    Claessens, Michiel; Vanhaecke, Lynn; Wille, Klaas; Janssen, Colin R

    2013-06-15

    Knowledge on the effects of pharmaceuticals on aquatic marine ecosystems is limited. The aim of this study was therefore to establish the effect thresholds of pharmaceutical compounds occurring in the Belgian marine environment for the marine diatom Phaeodactylum tricornutum, and subsequently perform an environmental risk assessment for these substances. Additionally, a screening-level risk assessment was performed for the pharmaceutical mixtures. No immediate risk for acute toxic effects of these compounds on P. tricornutum were apparent at the concentrations observed in the Belgian marine environment. In two Belgian coastal harbours however, a potential chronic risk was observed for the β-blocker propranolol. No additional risks arising from the exposure to mixtures of pharmaceuticals present in the sampling area could be detected. However, as risk characterization ratios for mixtures of up to 0.5 were observed, mixture effects could emerge should more compounds be taken into account. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Nanotoxicity: challenging the myth of nano-specific toxicity.

    Science.gov (United States)

    Donaldson, Ken; Poland, Craig A

    2013-08-01

    The analysis of nanoparticle (NP) hazard is currently a major research pre-occupation for particle toxicologists since there is a pressing requirement for a comprehensive understanding of nanoparticle hazard because of the wide spectrum of NP varying in composition, shape and size that require testing for risk assessment. The Biologically Effective Doses (BEDs) of nanoparticles, the dose entity that drives toxicity include charge, solubility, contaminants, shape and the ability to translocate from the site of deposition in the lungs. We point out here that all of these modes of toxicity are relevant and described for conventional pathogenic particles. There is no evidence that particles below 100nm, the threshold definition of a NP, show any step-change in their hazard meaning that there is no evidence of novel 'nano-specific hazard'. Therefore conventional particle toxicology data are useful and relevant to the determination of the nanoparticle hazard. Emphasis away from 'nano-specific effects' and the availability of hazard data from conventional particles will focus limited resource towards a full understanding of the NP hazard. This will lead to improved ability to identify and test for their effects and measure their toxicokinetics and so contribute to their risk assessment. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. Use of genomic data in risk assessment case study: I. Evaluation of the dibutyl phthalate male reproductive development toxicity data set

    Energy Technology Data Exchange (ETDEWEB)

    Makris, Susan L., E-mail: makris.susan@epa.gov [U.S. Environmental Protection Agency, National Center for Environmental Assessment, Office of Research and Development, (Mail code 8623P), 1200 Pennsylvania Ave., NW, Washington, DC 20460 (United States); Euling, Susan Y. [U.S. Environmental Protection Agency, National Center for Environmental Assessment, Office of Research and Development, (Mail code 8623P), 1200 Pennsylvania Ave., NW, Washington, DC 20460 (United States); Gray, L. Earl [U.S. Environmental Protection Agency, National Health and Environmental Effects Research Laboratory, Office of Research and Development, (MD-72), Highway 54, Research Triangle Park, NC 27711 (United States); Benson, Robert [U.S. Environmental Protection Agency, Region 8, (Mail code 8P-W), 1595 Wynkoop Street, Denver, CO 80202 (United States); Foster, Paul M.D. [National Toxicology Program, National Institute of Environmental Health Sciences, P.O. Box 12233 (MD K2-12), Research Triangle Park, NC 27709 (United States)

    2013-09-15

    A case study was conducted, using dibutyl phthalate (DBP), to explore an approach to using toxicogenomic data in risk assessment. The toxicity and toxicogenomic data sets relative to DBP-related male reproductive developmental outcomes were considered conjointly to derive information about mode and mechanism of action. In this manuscript, we describe the case study evaluation of the toxicological database for DBP, focusing on identifying the full spectrum of male reproductive developmental effects. The data were assessed to 1) evaluate low dose and low incidence findings and 2) identify male reproductive toxicity endpoints without well-established modes of action (MOAs). These efforts led to the characterization of data gaps and research needs for the toxicity and toxicogenomic studies in a risk assessment context. Further, the identification of endpoints with unexplained MOAs in the toxicity data set was useful in the subsequent evaluation of the mechanistic information that the toxicogenomic data set evaluation could provide. The extensive analysis of the toxicology data set within the MOA context provided a resource of information for DBP in attempts to hypothesize MOAs (for endpoints without a well-established MOA) and to phenotypically anchor toxicogenomic and other mechanistic data both to toxicity endpoints and to available toxicogenomic data. This case study serves as an example of the steps that can be taken to develop a toxicological data source for a risk assessment, both in general and especially for risk assessments that include toxicogenomic data.

  20. Rectal toxicity profile after transperineal interstitial permanent prostate brachytherapy: Use of a comprehensive toxicity scoring system and identification of rectal dosimetric toxicity predictors

    International Nuclear Information System (INIS)

    Shah, Jinesh N.; Ennis, Ronald D.

    2006-01-01

    Purpose: To better understand rectal toxicity after prostate brachytherapy, we employed the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE version 3.0), a comprehensive system with distinct and separately reported gastrointestinal adverse event items (unlike Radiation Therapy Oncology Group morbidity scoring), to evaluate item-specific postimplant rectal toxicities. Methods and Materials: We analyzed 135 patients treated with brachytherapy ± hormonal therapy, using CTCAE v3.0 to score acute/late rectal toxicities (median follow-up, 41 months). Dosimetric parameters were evaluated for ability to predict toxicities. Results: Use of CTCAE yielded a novel rectal toxicity profile consisting of diarrhea, incontinence, urgency, proctitis, pain, spasms, and hemorrhage event rates. No item had a 25 (percent of rectal volume receiving 25% of prescribed prostate dose) ≤ 25% vs. 60% for %V 25 > 25% (p 1 ≤ 40% vs. 44% for %V 1 > 40% (p = 0.007). Conclusions: A comprehensive understanding of item-specific postimplant rectal toxicities was obtained using CTCAE. Rectal %V 25 > 25% and %V 1 > 40% predicted worse late diarrhea and maximum toxicity, respectively

  1. Overview of toxicity data and risk assessment methods for evaluating the chemical effects of depleted uranium compounds

    International Nuclear Information System (INIS)

    Hartmann, H.M.; Monette, F.A.; Avci, H.I.

    2000-01-01

    In the United States, depleted uranium is handled or used in several chemical forms by both governmental agencies and private industry (primarily companies producing and machining depleted uranium metal for military applications). Human exposure can occur as a result of handling these compounds, routine low-level effluent releases to the environment from processing facilities, or materials being accidentally released from storage locations or during processing or transportation. Exposure to uranium can result in both chemical and radiological toxicity, but in most instances chemical toxicity is of greater concern. This article discusses the chemical toxic effects from human exposure to depleted uranium compounds that are likely to be handled during the long-term management and use of depleted uranium hexafluoride (UF 6 ) inventories in the United States. It also reviews representative publications in the toxicological literature to establish appropriate reference values for risk assessments. Methods are described for evaluating chemical toxicity caused by chronic low-level exposure and acute exposure. Example risk evaluations are provided for illustration. Preliminary results indicate that chemical effects of chronic exposure to uranium compounds under normal operating conditions would be negligibly small. Results also show that acute exposures under certain accident conditions could cause adverse chemical effects among the populations exposed.

  2. Some approaches to understanding public perceptions of risk

    International Nuclear Information System (INIS)

    Greer-Wootten, B.

    1981-01-01

    The debate on nuclear power contains a central set of arguments that can be related, by and large, to differences in the meaning of risk assessment for various concerned publics. At an earlier point in time the arguments largely concerned power production (reactor safety), but now most components of the nuclear fuel cycle are subject to risk perceptions. The strongest levels of public concern over time have focussed on waste management, and in this area illustrates most clearly the gaps between the assessments of the technical community and those of the publics. In order to understand such gaps, a theoretical framework is necessary. The broadest scope for such a framework is found in the I.I.A.S.A. - I.A.E.A. model developed by H.J. Otway, with its three interrelated components of risk estimation (technical), risk evaluation (public) and risk management. The model is described in this paper, as well as a number of empirical studies that derive from it and attempt to measure public perceptions of risks. These studies are then compared to several alternative explanations: the use of public opinion surveys; risk rating tasks based on psychologicl theory; the structure of arguments used by members of the public in qualitative focus group discussions; and a model of local community conflict derived from the content analysis of newspapers. Throughout the discussion, examples are taken wherever possible, from recent Canadian studies, in which the effects of major incidents (such as T.M.I., the Mississauga derailment, the Blind River refinery siting controversy, etc.) become apparent. It is suggested that our understanding of public perceptions of risks cannot be divorced from the set of broad societal concerns evidenced in the I.I.A.S.A. - I.A.E.A. model, and that the crucial elements of this approach are seen in its emphasis on the decision-making process

  3. Chemotherapy Toxicity Risk Score for Treatment Decisions in Older Adults with Advanced Solid Tumors.

    Science.gov (United States)

    Nishijima, Tomohiro F; Deal, Allison M; Williams, Grant R; Sanoff, Hanna K; Nyrop, Kirsten A; Muss, Hyman B

    2018-05-01

    The decision whether to treat older adults with advanced cancer with standard therapy (ST) or reduced therapy (RT) is complicated by heterogeneity in aging. We assessed the potential utility of the chemotherapy toxicity risk score (CTRS) [J Clin Oncol 2011;29:3457-3465] for treatment decisions in older adults. This was a prospective observational study of patients aged ≥65 years receiving first-line chemotherapy for advanced cancer for which combination chemotherapy is the standard of care. Patients were categorized as high risk (CTRS ≥10), for whom RT (dose-reduced combination or single-agent chemotherapy) is deemed appropriate, or nonhigh risk (CTRS statistic. Fifty-eight patients (median age, 71 years) were enrolled. Thirty-eight patients received ST (21 had CTRS advanced solid tumors receiving first-line chemotherapy was assessed. Little agreement was found between chemotherapy treatment decisions based on the clinical impression versus what was recommended based on the CTRS. Among patients treated with standard-dose combination chemotherapy, patients with CTRS ≥10 had a very high incidence of grade 3-4 toxicities and hospitalization, which was significantly greater than that of patients with a low CTRS (<10). These findings suggest that the addition of CTRS to the clinical impression has a potential to improve treatment decisions. © AlphaMed Press 2018.

  4. Toxicant emissions from hazardous wastes in landfills - implications for disposal risk management decisions

    International Nuclear Information System (INIS)

    Assmuth, T.W.

    1991-01-01

    The environmental impacts and risks of hazardous wastes disposed in Finnish landfills were assessed in a 5-yr field study. By systematic analysis of the acquired information, the toxicological impacts and risks of landfills seem as a whole small when compared with those caused by other kinds of environmental toxicants. Locally more significant risks arise, and may be difficult to manage. Scientific information on risk factors and their development is as yet insufficient, and additional research and monitoring are needed. Since uncertainties will remain, the prevention and control of risks, e.g. by improved hazardous waste management and disposal, are advocated by safety principles, but are made difficult by many technical and societal factors. Control strategies and remedial actions should thus be based on more comprehensive, comparative risk assessments and improved decision methods. Ethical, political and methodological issues in the management of hazardous waste disposal are discussed, with special reference to the interaction of science with regulatory decision-making related to the risks of old chemical waste sites. (44 refs.) (au)

  5. Treatment of primary liver tumors with Yttrium-90 microspheres (TheraSphere) in high risk patients: analysis of survival and toxicities.

    Science.gov (United States)

    Reardon, Kelli A; McIntosh, Alyson F; Shilling, A Tanner; Hagspiel, Klaus D; Al-Osaimi, Abdullah; Berg, Carl; Caldwell, Stephen H; Northup, Patrick G; Angle, Fritz; Mulder, Robert; Rich, Tyvin A

    2009-02-01

    This retrospective study was undertaken to obtain information regarding the survival and toxicities after Yttrium-90 microspheres treatment in patients with primary liver malignancies. Baseline, treatment, and follow-up data were collected and analyzed for 21 patients treated with Yttrium-90 microspheres. Survival analysis was then performed. The results of this study showed that median survival for all the patients was 120 days. Twenty of 21 patients were categorized as high-risk with a median survival of 114 days. It was also found that one high-risk patient has survived 858 days with no recurrence of disease. Acute grade 3-5 toxicities were recorded for nine patients and consisted of elevations in AST and bilirubin, thrombocytopenia, abdominal pain, ascites, nausea, fatigue, and death. This study concluded that Yttrium-90 is a low-toxicity, outpatient alternative for individuals with liver cancer and without many options. The maximal value, however, may lie in the treatment of low-risk patients.

  6. Dose-Escalated Hypofractionated Intensity-Modulated Radiotherapy in High-Risk Carcinoma of the Prostate: Outcome and Late Toxicity

    Directory of Open Access Journals (Sweden)

    David Thomson

    2012-01-01

    Results. Median followup was 84 months. Five-year overall survival (OS was 83% and biochemical progression-free survival (bPFS was 50% for 57 Gy. Five-year OS was 75% and bPFS 58% for 60 Gy. At 7 years, toxicity by RTOG criteria was acceptable with no grade 3 or above toxicity. Compared with baseline, there was no significant change in urinary symptoms at 2 or 7 years. Bowel symptoms were stable between 2 and 7 years. All patients continued to have significant sexual dysfunction. Conclusion. In high-risk prostate cancer, dose-escalated hypofractionated radiotherapy using IMRT results in encouraging outcomes and acceptable late toxicity.

  7. Distribution, relationship, and risk assessment of toxic heavy metals in walnuts and growth soil.

    Science.gov (United States)

    Han, Yongxiang; Ni, Zhanglin; Li, Shiliang; Qu, Minghua; Tang, Fubin; Mo, Runhong; Ye, Caifen; Liu, Yihua

    2018-04-14

    Walnut is one of the most popular nuts worldwide and contains various mineral nutrients. Little is known, however, about the relationship between toxic heavy metals in walnuts and growth soil. In this study, we investigated the distribution, relationship, and risk assessment of five toxic heavy metals-lead (Pb), arsenic (As), chromium (Cr), cadmium (Cd), and mercury (Hg)-in walnuts and growth soil in the main production areas of China. The results showed that the main heavy metal pollution in walnut and soil was Pb and Cd. Regionally, positive relationships existed between heavy metals and the pH and organic matter of soil. In addition, we observed a notable uptake effect between walnut and growth soil. In this study, we found a significant correlation (r = 0.786, P toxic heavy metal pollution in walnuts and growth soil could be helpful to screen suitable planting sites to prevent and control heavy metal pollution and improve the quality and safety of walnut.

  8. Joint Estimation of Cardiac Toxicity and Recurrence Risks After Comprehensive Nodal Photon Versus Proton Therapy for Breast Cancer

    DEFF Research Database (Denmark)

    Stick, Line B; Yu, Jen; Maraldo, Maja V

    2017-01-01

    PURPOSE: The study aims to perform joint estimation of the risk of recurrence caused by inadequate radiation dose coverage of lymph node targets and the risk of cardiac toxicity caused by radiation exposure to the heart. Delivered photon plans are compared with realistic proton plans, thereby pro...

  9. Risk and toxicity assessments of heavy metals in sediments and fishes from the Yangtze River and Taihu Lake, China.

    Science.gov (United States)

    Fu, Jie; Hu, Xin; Tao, Xiancong; Yu, Hongxia; Zhang, Xiaowei

    2013-11-01

    Heavy metal pollution is one of the most serous environmental issues globally. To evaluate the metal pollution in Jiangsu Province of China, the total concentrations of heavy metals in sediments and fishes from the Yangtze River and Taihu Lake were analyzed. Ecological risk of sediments and human health risk of fish consumption were assessed respectively. Furthermore, toxicity of samples on expression of the stress responsive genes was evaluated using microbial live cell-array method. The results showed that the heavy metals concentrations in sediments from the Yangtze River were much higher than those in sediments from the Taihu Lake. However, the fishes from the Taihu Lake had higher concentrations of heavy metals than fishes from the Yangtze River. Ecological risk evaluation showed that the heavy metal contaminants in sediments from the Yangtze River posed higher risk of adverse ecological effects, while sediments from the study areas of Taihu Lake were relatively safe. Health risk assessment suggested that the heavy metals in fishes of both Yangtze River and Taihu Lake might have risk of adverse health effects to human. The toxicity assessment indicated that the heavy metals in these sediments and fishes showed transcriptional effects on the selected 21 stress responsive genes, which were involved in the pathways of DNA damage response, chemical stress, and perturbations of electron transport. Together, this field investigation combined with chemical analysis, risk assessment and toxicity bioassay would provide useful information on the heavy metal pollution in Jiangsu Province. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. Daily Aspirin Therapy: Understand the Benefits and Risks

    Science.gov (United States)

    Daily aspirin therapy: Understand the benefits and risks Daily aspirin therapy can be a lifesaving option, but it's not ... everyone. Get the facts before considering a daily aspirin. By Mayo Clinic Staff Daily aspirin therapy may ...

  11. Rs895819 in MIR27A improves the predictive value of DPYD variants to identify patients at risk of severe fluoropyrimidine-associated toxicity.

    Science.gov (United States)

    Meulendijks, Didier; Henricks, Linda M; Amstutz, Ursula; Froehlich, Tanja K; Largiadèr, Carlo R; Beijnen, Jos H; de Boer, Anthonius; Deenen, Maarten J; Cats, Annemieke; Schellens, Jan H M

    2016-06-01

    The objective of this study was to determine whether genotyping of MIR27A polymorphisms rs895819A>G and rs11671784C>T can be used to improve the predictive value of DPYD variants to identify patients at risk of severe fluoropyrimidine-associated toxicity (FP-toxicity). Patients treated previously in a prospective study with fluoropyrimidine-based chemotherapy were genotyped for rs895819 and rs11671784, and DPYD c.2846A>T, c.1679T>G, c.1129-5923C>G and c.1601G>A. The predictive value of MIR27A variants for early-onset grade ≥3 FP-toxicity, alone or in combination with DPYD variants, was tested in multivariable logistic regression models. Random-effects meta-analysis was performed, including previously published data. A total of 1,592 patients were included. Allele frequencies of rs895819 and rs11671784 were 0.331 and 0.020, respectively. In DPYD wild-type patients, MIR27A variants did not affect risk of FP-toxicity (OR 1.3 for ≥1 variant MIR27A allele vs. none, 95% CI: 0.87-1.82, p = 0.228). In contrast, in patients carrying DPYD variants, the presence of ≥1 rs895819 variant allele was associated with increased risk of FP-toxicity (OR 4.9, 95% CI: 1.24-19.7, p = 0.023). Rs11671784 was not associated with FP-toxicity (OR 2.9, 95% CI: 0.47-18.0, p = 0.253). Patients carrying a DPYD variant and rs895819 were at increased risk of FP-toxicity compared to patients wild type for rs895819 and DPYD (OR 2.4, 95% CI: 1.27-4.37, p = 0.007), while patients with a DPYD variant but without a MIR27A variant were not (OR 0.3 95% CI: 0.06-1.17, p = 0.081). In meta-analysis, rs895819 remained significantly associated with FP-toxicity in DPYD variant allele carriers, OR 5.4 (95% CI: 1.83-15.7, p = 0.002). This study demonstrates the clinical validity of combined MIR27A/DPYD screening to identify patients at risk of severe FP-toxicity. © 2016 UICC.

  12. Preparing for Local Adaptation: Understanding Flood Risk Perceptions in Pittsburgh

    Science.gov (United States)

    Klima, K.; Wong-Parodi, G.

    2015-12-01

    The City of Pittsburgh experiences numerous floods every year. Aging and insufficient infrastructure contribute to flash floods and to over 20 billion gallons of combined sewer overflows annually, contaminating Pittsburgh's streets, basements, and waterways. Climate change is expected to further exacerbate this problem by causing more intense and more frequent extreme precipitation events in Western Pennsylvania. For a stormwater adaptation plan to be implemented effectively, the City will need informed public support. One way to achieve public understanding and support is through effective communication of the risks, benefits, and uncertainties of local flooding hazards and adaptation methods. In order to develop these communications effectively, the city and its partners will need to know what knowledge and attitudes the residents of Pittsburgh already hold about flood risks. Here we seek to (1) identify Pittsburgh residents' knowledge level, risk perception and attitudes towards flooding and storm water management, and (2) pre-test communications meant to inform and empower Pittsburghers about flood risks and adaptation strategies. We conduct a city-wide survey of 10,000 Pittsburgh renters and homeowners from four life situations: high risk, above poverty; high-risk, below poverty; low risk, above poverty; and low-risk, below poverty. Mixed media recruitment strategies (online and paper-based solicitations guided/organized by community organizations) assist in reaching all subpopulations. Preliminary results suggest participants know what stormwater runoff is, but have a weak understanding of how stormwater interacts with natural and built systems. Furthermore, although participants have a good understanding of the difference between green and gray infrastructure, this does not translate into a change in their willingness to pay for green infrastructure adaptation. This suggests additional communications about flood risks and adaptation strategies.

  13. Human health risk assessment based on toxicity characteristic leaching procedure and simple bioaccessibility extraction test of toxic metals in urban street dust of Tianjin, China.

    Directory of Open Access Journals (Sweden)

    Binbin Yu

    Full Text Available The potential ecological and human health risk related with urban street dust from urban areas of Tianjin, China was quantitatively analyzed using the method of toxicity characteristic leaching procedure (TCLP and simple bioaccessibility extraction test (SBET. In the study, Hakason index, Nemerow index (P, the hazard index (HI and the cancer risk index (RI were calculated to assess the potential risk. The sequence of potential ecological risk based on Hakason index was arsenic (As > cadmium (Cd > lead (Pb > copper (Cu > chromium (Cr, in particular, As and Cd were regarded as high polluted metals. While the results of extraction of TCLP were assessed using P, the sequence was As > Pb > Cd > Cr > Cu, which mean that As and Pb should be low polluted, and Cd, Cr and Cu would barely not polluted. For human health, total carcinogenic risk for children and adults was 2.01 × 10(-3 and 1.05 × 10(-3, respectively. This could be considered to be intolerable in urban street dust exposure. The sequence in the hazard quotient (HQ of each element was As > Cr > Pb > Cu > Cd. The HI value of these toxic metals in urban street dust for children and adults was 5.88 × 10(-1 and 2.80 × 10(-1, respectively. According to the characters of chemistry, mobility, and bioavailability of metals in urban street dust, we estimated the hazards on the environment and human health, which will help us to get more reasonable information for risk management of metals in urban environment.

  14. Neurodevelopmental toxicity risks due to occupational exposure to industrial chemicals during pregnancy

    DEFF Research Database (Denmark)

    Julvez, Jordi; Grandjean, Philippe

    2009-01-01

    Exposure to neurotoxic chemicals is of particular concern when it occurs during early development. The immature brain is highly vulnerable prenatally and is therefore at risk due to occupational exposures incurred by pregnant women. A systematic search of the literature has been performed...... by occupational health researchers and practitioners from the need to protect pregnant workers. Due to the vulnerability of the brain during early development, a precautionary approach to neurodevelopmental toxicity needs to be applied in occupational health....

  15. Evaluation of the toxic effect of endocrine disruptor Bisphenol A (BPA) in the acute and chronic toxicity tests with Pomacea lineata gastropod.

    Science.gov (United States)

    de Andrade, André Lucas Correa; Soares, Priscila Rafaela Leão; da Silva, Stephannie Caroline Barros Lucas; da Silva, Marília Cordeiro Galvão; Santos, Thamiris Pinheiro; Cadena, Marilia Ribeiro Sales; Soares, Pierre Castro; Cadena, Pabyton Gonçalves

    2017-07-01

    Bisphenol A (BPA) is a plasticizer and a risk when it interacts with organisms, and can cause changes in the development and reproduction of them. This study aimed to evaluate the effects of BPA, by acute and chronic toxicity tests with neonates and adults of Pomacea lineata. Adults and neonates were divided into groups exposed to BPA (1-20mg/L), or 17β-estradiol (1mg/L) and control in the acute and chronic toxicity tests. Behavior, heart rate, reproduction and hemolymph biochemical analysis were measured. In the acute toxicity test, the 96-h LC 50 with adults was 11.09 and with neonates was 3.14mg/L. In this test, it was observed lethargic behavior and an increase of 77.6% of aspartate aminotransferase in the adults' hemolymph (ptest, it was observed behaviors associated with reproduction, as Copulate, in the groups exposed to BPA. The results that were found in this study proved that BPA is a potentially toxic agent to Pomacea lineata according to biological parameters evaluated. These data contribute to the understanding of BPA toxic effects' in the aquatic invertebrates. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Informing people about radiation risks: a review of obstacles to public understanding and effective risk communication

    International Nuclear Information System (INIS)

    Covello, V.T.

    1988-01-01

    This paper reviews the literature on informing people about radiation risks. The paper focuses on obstacles to public understanding and effective risk communication. The paper concludes with a set of guidelines for communicating information about radiation risks to the public. The paper also includes an appendix that reviews the literature on one of the most important tools for communicating information about radiation risks: risk comparisons

  17. Evaluation of toxicity risks in farmers exposed to pesticides in an agricultural community in Concórdia, Santa Catarina State, Brazil - doi: 10.4025/actascihealthsci.v35i1.11227

    Directory of Open Access Journals (Sweden)

    Alexandre Meneghello Fuentefria

    2013-03-01

    Full Text Available There has been an increase during recent years in the use of pesticides in agricultural activities to improve productivity, reduce labor costs and increase profits. On the other hand, the use of pesticides in excess or without adequate biosafety practices could lead to serious harm to human health. Current research evaluated toxicity risks in the case of 50 agricultural workers from the São Paulo Rural Community in the municipality of Concordia, Santa Catarina State, Brazil, who were exposed to pesticides. The questionnaire with open- and closed-ended questions revealed that there are several situations and procedures that expose most farm workers to toxicity risks since they do not have a clear understanding of biosafety measures or suitable knowledge on the products they use. Since a lack of information on pesticides exists, there is strong evidence for measures to inform and raise consciousness so that agricultural workers may exercise self-care in handling pesticides.  

  18. Clinical Validity, Understandability, and Actionability of Online Cardiovascular Disease Risk Calculators: Systematic Review.

    Science.gov (United States)

    Bonner, Carissa; Fajardo, Michael Anthony; Hui, Samuel; Stubbs, Renee; Trevena, Lyndal

    2018-02-01

    Online health information is particularly important for cardiovascular disease (CVD) prevention, where lifestyle changes are recommended until risk becomes high enough to warrant pharmacological intervention. Online information is abundant, but the quality is often poor and many people do not have adequate health literacy to access, understand, and use it effectively. This project aimed to review and evaluate the suitability of online CVD risk calculators for use by low health literate consumers in terms of clinical validity, understandability, and actionability. This systematic review of public websites from August to November 2016 used evaluation of clinical validity based on a high-risk patient profile and assessment of understandability and actionability using Patient Education Material Evaluation Tool for Print Materials. A total of 67 unique webpages and 73 unique CVD risk calculators were identified. The same high-risk patient profile produced widely variable CVD risk estimates, ranging from as little as 3% to as high as a 43% risk of a CVD event over the next 10 years. One-quarter (25%) of risk calculators did not specify what model these estimates were based on. The most common clinical model was Framingham (44%), and most calculators (77%) provided a 10-year CVD risk estimate. The calculators scored moderately on understandability (mean score 64%) and poorly on actionability (mean score 19%). The absolute percentage risk was stated in most (but not all) calculators (79%), and only 18% included graphical formats consistent with recommended risk communication guidelines. There is a plethora of online CVD risk calculators available, but they are not readily understandable and their actionability is poor. Entering the same clinical information produces widely varying results with little explanation. Developers need to address actionability as well as clinical validity and understandability to improve usefulness to consumers with low health literacy.

  19. Caffeine intake, toxicity and dependence and lifetime risk for psychiatric and substance use disorders: an epidemiologic and co-twin control analysis.

    Science.gov (United States)

    Kendler, Kenneth S; Myers, John; O Gardner, Charles

    2006-12-01

    Although caffeine is the most commonly used psychoactive substance and often produces symptoms of toxicity and dependence, little is known, especially in community samples, about the association between caffeine use, toxicity and dependence and risk for common psychiatric and substance use disorders. Assessments of lifetime maximal caffeine use and symptoms of caffeine toxicity and dependence were available on over 3600 adult twins ascertained from the population-based Virginia Twin Registry. Lifetime histories of major depression (MD), generalized anxiety disorder (GAD) and panic disorder, alcohol dependence, adult antisocial behavior and cannabis and cocaine abuse/dependence were obtained at personal interview. Logistic regression analyses in the entire sample and within monozygotic (MZ) twin pairs were conducted in SAS. In the entire sample, measures of maximal caffeine use, heavy caffeine use, and caffeine-related toxicity and dependence were significantly and positively associated with all seven psychiatric and substance use disorders. However, within MZ twin pairs, controlling for genetic and family environmental factors, these associations, while positive, were all non-significant. These results were similar when excluding twins who denied regular caffeine use. Maximal lifetime caffeine intake and caffeine-associated toxicity and dependence are moderately associated with risk for a wide range of psychiatric and substance use disorders. Analyses of these relationships within MZ twin pairs suggest that most of the observed associations are not causal. Rather, familial factors, which are probably in part genetic, predispose to both caffeine intake, toxicity and dependence and the risk for a broad array of internalizing and externalizing disorders.

  20. A systems-level approach for investigating organophosphorus pesticide toxicity.

    Science.gov (United States)

    Zhu, Jingbo; Wang, Jing; Ding, Yan; Liu, Baoyue; Xiao, Wei

    2018-03-01

    The full understanding of the single and joint toxicity of a variety of organophosphorus (OP) pesticides is still unavailable, because of the extreme complex mechanism of action. This study established a systems-level approach based on systems toxicology to investigate OP pesticide toxicity by incorporating ADME/T properties, protein prediction, and network and pathway analysis. The results showed that most OP pesticides are highly toxic according to the ADME/T parameters, and can interact with significant receptor proteins to cooperatively lead to various diseases by the established OP pesticide -protein and protein-disease networks. Furthermore, the studies that multiple OP pesticides potentially act on the same receptor proteins and/or the functionally diverse proteins explained that multiple OP pesticides could mutually enhance toxicological synergy or additive on a molecular/systematic level. To the end, the integrated pathways revealed the mechanism of toxicity of the interaction of OP pesticides and elucidated the pathogenesis induced by OP pesticides. This study demonstrates a systems-level approach for investigating OP pesticide toxicity that can be further applied to risk assessments of various toxins, which is of significant interest to food security and environmental protection. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Model-based approach for quantitative estimates of skin, heart, and lung toxicity risk for left-side photon and proton irradiation after breast-conserving surgery.

    Science.gov (United States)

    Tommasino, Francesco; Durante, Marco; D'Avino, Vittoria; Liuzzi, Raffaele; Conson, Manuel; Farace, Paolo; Palma, Giuseppe; Schwarz, Marco; Cella, Laura; Pacelli, Roberto

    2017-05-01

    Proton beam therapy represents a promising modality for left-side breast cancer (BC) treatment, but concerns have been raised about skin toxicity and poor cosmesis. The aim of this study is to apply skin normal tissue complication probability (NTCP) model for intensity modulated proton therapy (IMPT) optimization in left-side BC. Ten left-side BC patients undergoing photon irradiation after breast-conserving surgery were randomly selected from our clinical database. Intensity modulated photon (IMRT) and IMPT plans were calculated with iso-tumor-coverage criteria and according to RTOG 1005 guidelines. Proton plans were computed with and without skin optimization. Published NTCP models were employed to estimate the risk of different toxicity endpoints for skin, lung, heart and its substructures. Acute skin NTCP evaluation suggests a lower toxicity level with IMPT compared to IMRT when the skin is included in proton optimization strategy (0.1% versus 1.7%, p < 0.001). Dosimetric results show that, with the same level of tumor coverage, IMPT attains significant heart and lung dose sparing compared with IMRT. By NTCP model-based analysis, an overall reduction in the cardiopulmonary toxicity risk prediction can be observed for all IMPT compared to IMRT plans: the relative risk reduction from protons varies between 0.1 and 0.7 depending on the considered toxicity endpoint. Our analysis suggests that IMPT might be safely applied without increasing the risk of severe acute radiation induced skin toxicity. The quantitative risk estimates also support the potential clinical benefits of IMPT for left-side BC irradiation due to lower risk of cardiac and pulmonary morbidity. The applied approach might be relevant on the long term for the setup of cost-effectiveness evaluation strategies based on NTCP predictions.

  2. Understanding the Strategies to Overcome Phosphorus–Deficiency and Aluminum–Toxicity by Ryegrass Endophytic and Rhizosphere Phosphobacteria

    Directory of Open Access Journals (Sweden)

    Patricio J. Barra

    2018-06-01

    Full Text Available Phosphobacteria, secreting organic acids and phosphatases, usually favor plant performance in acidic soils by increasing phosphorus (P availability and aluminum (Al complexing. However, it is not well-known how P-deficiency and Al-toxicity affect the phosphobacteria physiology. Since P and Al problems often co-occur in acidic soils, we have therefore proposed the evaluation of the single and combined effects of P-deficiency and Al-toxicity on growth, organic acids secretion, malate dehydrogenase (mdh gene expression, and phosphatase activity of five Al-tolerant phosphobacteria previously isolated from ryegrass. These phosphobacteria were identified as Klebsiella sp. RC3, Stenotrophomona sp. RC5, Klebsiella sp. RCJ4, Serratia sp. RCJ6, and Enterobacter sp. RJAL6. The strains were cultivated in mineral media modified to obtain (i high P in absence of Al–toxicity, (ii high P in presence of Al–toxicity, (iii low P in absence of Al–toxicity, and (iv low P in presence of Al–toxicity. High and low P were obtained by adding KH2PO4 at final concentration of 1.4 and 0.05 mM, respectively. To avoid Al precipitation, AlCl3 × 6H2O was previously complexed to citric acid (sole carbon source in concentrations of 10 mM. The secreted organic acids were identified and quantified by HPLC, relative mdh gene expression was determined by qRT-PCR and phosphatase activity was colorimetrically determined using p-nitrophenyl phosphate as substrate. Our results revealed that although a higher secretion of all organic acids was achieved under P–deficiency, the patterns of organic acids secretion were variable and dependent on treatment and strain. The organic acid secretion is exacerbated when Al was added into media, particularly in the form of malic and citric acid. The mdh gene expression was significantly up–regulated by the strains RC3, RC5, and RCJ6 under P–deficiency and Al–toxicity. In general, Al–tolerant phosphobacteria under P deficiency

  3. Toxicity identification evaluation methods for identification of toxicants in refinery effluents

    International Nuclear Information System (INIS)

    Barten, K.A.; Mount, D.R.; Hackett, J.R.

    1993-01-01

    During the last five years, the authors have used Toxicity Identification Evaluation (TIE) methods to characterize and identify the source(s) of toxicity in effluents from dozens of municipal and industrial facilities. In most cases, specific chemicals responsible for toxicity have been identified. Although generally successful, the initial experience was that for several refinery effluents, they were able only to qualitatively characterize the presence of organic toxicants; standard toxicant identification procedures were not able to isolate specific organic chemicals. They believe that organic toxicity in these refinery effluents is caused by multiple organic compounds rather than by just a few; evidence for this includes an inability to isolate toxicity in a small number of fractions using liquid chromatography and the presence of very large numbers of compounds in isolated fractions. There is also evidence that the toxicant(s) may be ionic, in that the toxicity of whole effluent and isolated fractions often show increasing toxicity with decreasing pH. Finally, positive-pressure filtration has also reduced toxicity in some samples. In this presentation the authors summarize their experiences with refinery effluents, focusing on typical patterns they have observed and alternative procedures they have used to better understand the nature of these toxicants

  4. [Occupational toxic exposure in the pregnant woman. 1: principles fo individual risk assessment ].

    Science.gov (United States)

    Testud, F; Lambert-Chhum, R; Bellemin, B; Descotes, J

    2001-12-01

    Many women of childbearing age are occupationally exposed to chemicals and concerned with the ensuing risk when pregnant. To describe the principles of individual risk assessment to be applied in pregnant women or women wishing to become pregnant that are exposed to chemicals at the workplace. Each request for risk assessment is based on a comprehensive review of the hazards of the handled products together with a thorough evaluation of the actual exposure at the workplace. A toxicological advice is then written to the gynecologist or the general practitioner in charge of the patient. When the exposure is estimated to be hazardous for the pregnancy, either total withdrawal, avoidance of certain activities or improvements of individual protective devices are recommended. The outcome of the pregnancy is systematically followed-up. An objective assessment of toxic risks in pregnant women exposed to chemicals at the workplace can be done. Thus, patients who must be withdrawn or benefit from improvements of their workstation can be selected.

  5. Toxicovigilance: A new approach for the hazard identification and risk assessment of toxicants in human beings

    International Nuclear Information System (INIS)

    Descotes, Jacques; Testud, Francois

    2005-01-01

    The concept of toxicovigilance encompasses the active detection, validation and follow-up of clinical adverse events related to toxic exposures in human beings. Poison centers are key players in this function as poisoning statistics are essential to define the cause, incidence and severity of poisonings occurring in the general population. In addition, the systematic search for unexpected shifts in the recorded causes of poisonings, e.g., following the introduction of a new product, or change in the formulation or recommended use of an old product, allows for a rapid detection of potential adverse health consequences and the implementation of preventive or corrective measures. However, toxicovigilance is genuinely a medical and not only a statistical approach of human toxicity issues. In contrast to epidemiology, toxicovigilance is based on the in-depth medical assessment of acute or chronic intoxications on an individual basis, which requires detailed information that poison centers can rarely obtain via emergency telephone calls and that epidemiologists cannot collect or process. Validation of this medical information must primarily be based on toxicological expertise to help identify causal links between otherwise unexplained pathological conditions and documented toxic exposures. Thus, toxicovigilance can contribute to hazard identification and risk assessment by providing medically validated data which are often overlooked in the process of risk assessment. So far, very few structured toxicovigilance systems have been set up and hopefully national and international initiatives will bridge this gap in our knowledge of the toxicity of many chemicals and commercial products in human beings

  6. Toxicovigilance: a new approach for the hazard identification and risk assessment of toxicants in human beings.

    Science.gov (United States)

    Descotes, Jacques; Testud, François

    2005-09-01

    The concept of toxicovigilance encompasses the active detection, validation and follow-up of clinical adverse events related to toxic exposures in human beings. Poison centers are key players in this function as poisoning statistics are essential to define the cause, incidence and severity of poisonings occurring in the general population. In addition, the systematic search for unexpected shifts in the recorded causes of poisonings, e.g., following the introduction of a new product, or change in the formulation or recommended use of an old product, allows for a rapid detection of potential adverse health consequences and the implementation of preventive or corrective measures. However, toxicovigilance is genuinely a medical and not only a statistical approach of human toxicity issues. In contrast to epidemiology, toxicovigilance is based on the in-depth medical assessment of acute or chronic intoxications on an individual basis, which requires detailed information that poison centers can rarely obtain via emergency telephone calls and that epidemiologists cannot collect or process. Validation of this medical information must primarily be based on toxicological expertise to help identify causal links between otherwise unexplained pathological conditions and documented toxic exposures. Thus, toxicovigilance can contribute to hazard identification and risk assessment by providing medically validated data which are often overlooked in the process of risk assessment. So far, very few structured toxicovigilance systems have been set up and hopefully national and international initiatives will bridge this gap in our knowledge of the toxicity of many chemicals and commercial products in human beings.

  7. Insights into aquatic toxicities of the antibiotics oxytetracycline and ciprofloxacin in the presence of metal: Complexation versus mixture

    International Nuclear Information System (INIS)

    Zhang Yu; Cai Xiyun; Lang Xianming; Qiao Xianliang; Li Xuehua; Chen Jingwen

    2012-01-01

    Co-contamination of ligand-like antibiotics (e.g., tetracyclines and quinolones) and heavy metals prevails in the environment, and thus the complexation between them is involved in environmental risks of antibiotics. To understand toxicological significance of the complex, effects of metal coordination on antibiotics' toxicity were investigated. The complexation of two antibiotics, oxytetracycline and ciprofloxacin, with three heavy metals, copper, zinc, and cadmium, was verified by spectroscopic techniques. The antibiotics bound metals via multiple coordination sites and rendered a mixture of various complexation speciations. Toxicity analysis indicated that metal coordination did modify the toxicity of the antibiotics and that antibiotic, metal, and their complex acted primarily as concentration addition. Comparison of EC 50 values revealed that the complex commonly was highest toxic and predominately correlated in toxicity to the mixture. Finally, environmental scenario analysis demonstrated that ignoring complexation would improperly classify environmental risks of the antibiotics. - Highlights: ► The complex of antibiotic with metal is a mixture of various complexation modes. ► Antibiotic and metal act as various combined interactions when their complexation is ignored. ► Antibiotic, metal, and their complex act as concentration addition interaction. ► Complex commonly is the highest toxicant. ► Neglecting complexation renders improper classification of risks for antibiotics. - Antibiotic, heavy metal and their complex act primarily as concentration addition interaction and the complex commonly is highest toxic.

  8. Air toxics concentrations, source identification, and health risks: An air pollution hot spot in southwest Memphis, TN

    Science.gov (United States)

    Jia, Chunrong; Foran, Jeffery

    2013-12-01

    Southwest Memphis is a residential region surrounded by fossil fuel burning, steel, refining, and food processing industries, and considerable mobile sources whose emissions may pose adverse health risks to local residents. This study characterizes cancer and non-cancer risks resulting from exposure to ambient air toxics in southwest Memphis. Air toxics samples were collected at a central location every 6 days from June 5, 2008 to January 8, 2010. Volatile organic compounds (VOCs) were collected in evacuated stainless-steel canisters and aldehydes by DNPH cartridges, and samples were analyzed for 73 target compounds. A total of 60 compounds were detected and 39 were found in over 86% of the samples. Mean concentrations of many compounds were higher than those measured in many industrial communities throughout the U.S. The cumulative cancer risk associated with exposure to 13 carcinogens found in southwest Memphis air was 2.3 × 10-4, four times higher than the national average of 5.0 × 10-5. Three risk drivers were identified: benzene, formaldehyde, and acrylonitrile, which contributed 43%, 19%, and 14% to the cumulative risk, respectively. This is the first field study to confirm acrylonitrile as a potential risk driver. Mobile, secondary, industrial, and background sources contributed 57%, 24%, 14%, and 5% of the risk, respectively. The results of this study indicate that southwest Memphis, a region of significant income, racial, and social disparities, is also a region under significant environmental stress compared with surrounding areas and communities.

  9. Does Bleomycin Lung Toxicity Increase the Risk of Radiation Pneumonitis in Hodgkin Lymphoma?

    International Nuclear Information System (INIS)

    Abou Yehia, Zeinab; Mikhaeel, George N.; Smith, Grace; Pinnix, Chelsea C.; Milgrom, Sarah A.; Tang, Chad; Jiang, Wen; Fanale, Michelle A.; Oki, Yasuhiro; Shank, JoAnn H.; Horace, Trisha; Reddy, Jay; Akhtari, Mani; Gunther, Jillian R.; Suki, Tina; Allen, Pamela K.; Turner, Shryll; Mawlawi, Osama; Dabaja, Bouthaina S.

    2016-01-01

    Purpose: Bleomycin pulmonary toxicity (BPT) is a well-known complication of treatment in patients with Hodgkin lymphoma (HL). We undertook the present study to investigate the risk of radiation pneumonitis (RP) in the setting of BPT and to determine the need for delay or omission of radiation therapy (RT) in these patients. Methods and Materials: We identified 123 HL patients treated with ABVD (Adriamycin, bleomycin, vinblastine, dacarbazine) followed by RT to the chest from January 2009 to December 2014. The medical records were reviewed for clinical, pathologic, and treatment information and toxicities. Our primary outcome was RP of any grade. Univariate and multivariate analyses were used to assess the association of BPT, baseline patient characteristics, and treatment variables with the incidence of RP. Results: A total of 123 patients were included, of whom 99 (80%) received consolidation intensity modulated RT after ABVD treatment. We identified 31 patients (25.2%) with BPT after frontline ABVD. Seventeen patients (13.8%) developed RP a median of 8 weeks (range 1-39) after RT completion. BPT did not correlate with the risk of developing RP (P=.36). We evaluated the RP outcomes with respect to the bleomycin to RT interval (≤6 weeks vs >6 weeks), and we found that this interval did not predict for RP risk (P=.60). Dosimetric parameters such as the volume covered by 5 Gy and the mean lung dose were analyzed. A volume covered by 5 Gy of >55% and mean lung dose >13.5 Gy increased the risk of RP by 1.14-fold (P=.002) and 4.24-fold (P=.007), respectively. Conclusions: The results of our study suggest that BPT does not increase the risk of developing RP. Furthermore, RT initiation does not need to be delayed after chemotherapy, except to allow for the completion of steroid therapy or clinical recovery from BPT.

  10. Does Bleomycin Lung Toxicity Increase the Risk of Radiation Pneumonitis in Hodgkin Lymphoma?

    Energy Technology Data Exchange (ETDEWEB)

    Abou Yehia, Zeinab [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Mikhaeel, George N. [Department of Clinical Oncology, Guy' s & St Thomas' Hospital, London (United Kingdom); Smith, Grace; Pinnix, Chelsea C.; Milgrom, Sarah A.; Tang, Chad; Jiang, Wen [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Fanale, Michelle A.; Oki, Yasuhiro [Department of Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Shank, JoAnn H.; Horace, Trisha; Reddy, Jay [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Akhtari, Mani [Department of Radiation Oncology, The University of Texas Medical Branch Hospitals, Galveston, Texas (United States); Gunther, Jillian R. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Suki, Tina [The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Allen, Pamela K.; Turner, Shryll [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Mawlawi, Osama [Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Dabaja, Bouthaina S., E-mail: bdabaja@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2016-12-01

    Purpose: Bleomycin pulmonary toxicity (BPT) is a well-known complication of treatment in patients with Hodgkin lymphoma (HL). We undertook the present study to investigate the risk of radiation pneumonitis (RP) in the setting of BPT and to determine the need for delay or omission of radiation therapy (RT) in these patients. Methods and Materials: We identified 123 HL patients treated with ABVD (Adriamycin, bleomycin, vinblastine, dacarbazine) followed by RT to the chest from January 2009 to December 2014. The medical records were reviewed for clinical, pathologic, and treatment information and toxicities. Our primary outcome was RP of any grade. Univariate and multivariate analyses were used to assess the association of BPT, baseline patient characteristics, and treatment variables with the incidence of RP. Results: A total of 123 patients were included, of whom 99 (80%) received consolidation intensity modulated RT after ABVD treatment. We identified 31 patients (25.2%) with BPT after frontline ABVD. Seventeen patients (13.8%) developed RP a median of 8 weeks (range 1-39) after RT completion. BPT did not correlate with the risk of developing RP (P=.36). We evaluated the RP outcomes with respect to the bleomycin to RT interval (≤6 weeks vs >6 weeks), and we found that this interval did not predict for RP risk (P=.60). Dosimetric parameters such as the volume covered by 5 Gy and the mean lung dose were analyzed. A volume covered by 5 Gy of >55% and mean lung dose >13.5 Gy increased the risk of RP by 1.14-fold (P=.002) and 4.24-fold (P=.007), respectively. Conclusions: The results of our study suggest that BPT does not increase the risk of developing RP. Furthermore, RT initiation does not need to be delayed after chemotherapy, except to allow for the completion of steroid therapy or clinical recovery from BPT.

  11. Differential reconstructed gene interaction networks for deriving toxicity threshold in chemical risk assessment.

    Science.gov (United States)

    Yang, Yi; Maxwell, Andrew; Zhang, Xiaowei; Wang, Nan; Perkins, Edward J; Zhang, Chaoyang; Gong, Ping

    2013-01-01

    Pathway alterations reflected as changes in gene expression regulation and gene interaction can result from cellular exposure to toxicants. Such information is often used to elucidate toxicological modes of action. From a risk assessment perspective, alterations in biological pathways are a rich resource for setting toxicant thresholds, which may be more sensitive and mechanism-informed than traditional toxicity endpoints. Here we developed a novel differential networks (DNs) approach to connect pathway perturbation with toxicity threshold setting. Our DNs approach consists of 6 steps: time-series gene expression data collection, identification of altered genes, gene interaction network reconstruction, differential edge inference, mapping of genes with differential edges to pathways, and establishment of causal relationships between chemical concentration and perturbed pathways. A one-sample Gaussian process model and a linear regression model were used to identify genes that exhibited significant profile changes across an entire time course and between treatments, respectively. Interaction networks of differentially expressed (DE) genes were reconstructed for different treatments using a state space model and then compared to infer differential edges/interactions. DE genes possessing differential edges were mapped to biological pathways in databases such as KEGG pathways. Using the DNs approach, we analyzed a time-series Escherichia coli live cell gene expression dataset consisting of 4 treatments (control, 10, 100, 1000 mg/L naphthenic acids, NAs) and 18 time points. Through comparison of reconstructed networks and construction of differential networks, 80 genes were identified as DE genes with a significant number of differential edges, and 22 KEGG pathways were altered in a concentration-dependent manner. Some of these pathways were perturbed to a degree as high as 70% even at the lowest exposure concentration, implying a high sensitivity of our DNs approach

  12. Cancer risk assessments and environmental regulation

    International Nuclear Information System (INIS)

    Scroggin, D.G.

    1990-01-01

    Governmental regulation of toxic substances, such as carcinogens and radiation, prompts both legal and scientific controversies. Industry, environmental activist groups, government regulators, and the general public are all concerned with the question of how environmental risk to public health is to be measured and what level of risk warrants government action under the environmental laws. Several recent events shed light on the fundamental scientific and legal problems inherent in such regulation, and these events may affect the direction of future developments. These events include implementation of generic Risk Assessment Guidelines by the US EPA, litigation challenging EPA's regulation of carcinogenic substances, new scientific understanding of the relative risks from human exposure to natural and man-made sources, and the continuing growth of toxic tort litigation in which victims of cancer seek large damages from industrial emitters of pollution

  13. Joint Estimation of Cardiac Toxicity and Recurrence Risks After Comprehensive Nodal Photon Versus Proton Therapy for Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Stick, Line B., E-mail: line.bjerregaard.stick@regionh.dk [Department of Clinical Oncology, Rigshospitalet, University of Copenhagen, Copenhagen (Denmark); Niels Bohr Institute, Faculty of Science, University of Copenhagen, Copenhagen (Denmark); Yu, Jen [Maryland Proton Treatment Center, University of Maryland School of Medicine, Baltimore, Maryland (United States); Maraldo, Maja V. [Department of Clinical Oncology, Rigshospitalet, University of Copenhagen, Copenhagen (Denmark); Aznar, Marianne C. [Department of Clinical Oncology, Rigshospitalet, University of Copenhagen, Copenhagen (Denmark); Nuffield Department of Population Health, University of Oxford, Oxford (United Kingdom); Pedersen, Anders N. [Department of Clinical Oncology, Rigshospitalet, University of Copenhagen, Copenhagen (Denmark); Bentzen, Søren M. [Department of Clinical Oncology, Rigshospitalet, University of Copenhagen, Copenhagen (Denmark); Maryland Proton Treatment Center, University of Maryland School of Medicine, Baltimore, Maryland (United States); Greenebaum Comprehensive Cancer Center and Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, Maryland (United States); Vogelius, Ivan R. [Department of Clinical Oncology, Rigshospitalet, University of Copenhagen, Copenhagen (Denmark)

    2017-03-15

    Purpose: The study aims to perform joint estimation of the risk of recurrence caused by inadequate radiation dose coverage of lymph node targets and the risk of cardiac toxicity caused by radiation exposure to the heart. Delivered photon plans are compared with realistic proton plans, thereby providing evidence-based estimates of the heterogeneity of treatment effects in consecutive cases for the 2 radiation treatment modalities. Methods and Materials: Forty-one patients referred for postlumpectomy comprehensive nodal photon irradiation for left-sided breast cancer were included. Comparative proton plans were optimized by a spot scanning technique with single-field optimization from 2 en face beams. Cardiotoxicity risk was estimated with the model of Darby et al, and risk of recurrence following a compromise of lymph node coverage was estimated by a linear dose-response model fitted to the recurrence data from the recently published EORTC (European Organisation for Research and Treatment of Cancer) 22922/10925 and NCIC-CTG (National Cancer Institute of Canada Clinical Trials Group) MA.20 randomized controlled trials. Results: Excess absolute risk of cardiac morbidity was small with photon therapy at an attained age of 80 years, with median values of 1.0% (range, 0.2%-2.9%) and 0.5% (range, 0.03%-1.0%) with and without cardiac risk factors, respectively, but even lower with proton therapy (0.13% [range, 0.02%-0.5%] and 0.06% [range, 0.004%-0.3%], respectively). The median estimated excess absolute risk of breast cancer recurrence after 10 years was 0.10% (range, 0.0%-0.9%) with photons and 0.02% (range, 0.0%-0.07%) with protons. The association between age of the patient and benefit from proton therapy was weak, almost non-existing (Spearman rank correlations of −0.15 and −0.30 with and without cardiac risk factors, respectively). Conclusions: Modern photon therapy yields limited risk of cardiac toxicity in most patients, but proton therapy can reduce the

  14. Efforts to standardize wildlife toxicity values remain unrealized.

    Science.gov (United States)

    Mayfield, David B; Fairbrother, Anne

    2013-01-01

    Wildlife toxicity reference values (TRVs) are routinely used during screening level and baseline ecological risk assessments (ERAs). Risk assessment professionals often adopt TRVs from published sources to expedite risk analyses. The US Environmental Protection Agency (USEPA) developed ecological soil screening levels (Eco-SSLs) to provide a source of TRVs that would improve consistency among risk assessments. We conducted a survey and evaluated more than 50 publicly available, large-scale ERAs published in the last decade to evaluate if USEPA's goal of uniformity in the use of wildlife TRVs has been met. In addition, these ERAs were reviewed to understand current practices for wildlife TRV use and development within the risk assessment community. The use of no observed and lowest observed adverse effect levels culled from published compendia was common practice among the majority of ERAs reviewed. We found increasing use over time of TRVs established in the Eco-SSL documents; however, Eco-SSL TRV values were not used in the majority of recent ERAs and there continues to be wide variation in TRVs for commonly studied contaminants (e.g., metals, pesticides, PAHs, and PCBs). Variability in the toxicity values was driven by differences in the key studies selected, dose estimation methods, and use of uncertainty factors. These differences result in TRVs that span multiple orders of magnitude for many of the chemicals examined. This lack of consistency in TRV development leads to highly variable results in ecological risk assessments conducted throughout the United States. Copyright © 2012 SETAC.

  15. Predicting the risk of toxic blooms of golden alga from cell abundance and environmental covariates

    Science.gov (United States)

    Patino, Reynaldo; VanLandeghem, Matthew M.; Denny, Shawn

    2016-01-01

    Golden alga (Prymnesium parvum) is a toxic haptophyte that has caused considerable ecological damage to marine and inland aquatic ecosystems worldwide. Studies focused primarily on laboratory cultures have indicated that toxicity is poorly correlated with the abundance of golden alga cells. This relationship, however, has not been rigorously evaluated in the field where environmental conditions are much different. The ability to predict toxicity using readily measured environmental variables and golden alga abundance would allow managers rapid assessments of ichthyotoxicity potential without laboratory bioassay confirmation, which requires additional resources to accomplish. To assess the potential utility of these relationships, several a priori models relating lethal levels of golden alga ichthyotoxicity to golden alga abundance and environmental covariates were constructed. Model parameters were estimated using archived data from four river basins in Texas and New Mexico (Colorado, Brazos, Red, Pecos). Model predictive ability was quantified using cross-validation, sensitivity, and specificity, and the relative ranking of environmental covariate models was determined by Akaike Information Criterion values and Akaike weights. Overall, abundance was a generally good predictor of ichthyotoxicity as cross validation of golden alga abundance-only models ranged from ∼ 80% to ∼ 90% (leave-one-out cross-validation). Environmental covariates improved predictions, especially the ability to predict lethally toxic events (i.e., increased sensitivity), and top-ranked environmental covariate models differed among the four basins. These associations may be useful for monitoring as well as understanding the abiotic factors that influence toxicity during blooms.

  16. Eco-toxicity and human estrogenic exposure risks from "·OH-initiated photochemical transformation of four phthalates in water: A computational study

    International Nuclear Information System (INIS)

    Gao, Yanpeng; An, Taicheng; Ji, Yuemeng; Li, Guiying; Zhao, Cunyuan

    2015-01-01

    Transformation products (TPs) of emerging organic contaminates (EOCs) in water are still rarely considered in environmental risk assessment, although some have been found to be concern. "·OH is believed as an important reactive species both in indirect phototransformation and advanced oxidation technology. Thus, eco-toxicity and human estrogenic exposure risks of four phthalates and TPs during the "·OH-initiated photochemical process were investigated using computational approach. Four phthalates can be degraded through "·OH-addition and H-transfer pathways. The "·OH-addition TPs were predominant for dimethyl phthalates, while H-transfer TPs were predominant for other three phthalates. Compared with phthalates, "·OH-addition TPs (o-OH-phthalates) were one level more toxic to aquatic organisms, and m-OH-phthalates exhibit higher estrogenic activity. Although H-transfer TPs were less harmful than "·OH-addition TPs, some of them still have aquatic toxicity and estrogenic activity. Therefore, more attentions should be paid to photochemical TPs and original EOCs, particularly those exhibiting high estrogenic activity to humans. - Highlights: • Phthalates can be degraded with "·OH-addition and H-transfer pathways. • "·OH-addition products are mainly formed during DMP transformation. • H-transfer products were predominant for the transformation of DEP, DPP and DBP. • o-"·OH-addition products have greater eco-toxicity than corresponding phthalates. • m-"·OH-addition products have higher estrogenic activity than corresponding phthalates. - Computational approach could provide valuable information on the mechanisms, kinetics, eco-toxicity as well as human estrogenic exposure risks of EOCs and their transformation products.

  17. A Framework for Understanding Uncertainty in Seismic Risk Assessment.

    Science.gov (United States)

    Foulser-Piggott, Roxane; Bowman, Gary; Hughes, Martin

    2017-10-11

    A better understanding of the uncertainty that exists in models used for seismic risk assessment is critical to improving risk-based decisions pertaining to earthquake safety. Current models estimating the probability of collapse of a building do not consider comprehensively the nature and impact of uncertainty. This article presents a model framework to enhance seismic risk assessment and thus gives decisionmakers a fuller understanding of the nature and limitations of the estimates. This can help ensure that risks are not over- or underestimated and the value of acquiring accurate data is appreciated fully. The methodology presented provides a novel treatment of uncertainties in input variables, their propagation through the model, and their effect on the results. The study presents ranges of possible annual collapse probabilities for different case studies on buildings in different parts of the world, exposed to different levels of seismicity, and with different vulnerabilities. A global sensitivity analysis was conducted to determine the significance of uncertain variables. Two key outcomes are (1) that the uncertainty in ground-motion conversion equations has the largest effect on the uncertainty in the calculation of annual collapse probability; and (2) the vulnerability of a building appears to have an effect on the range of annual collapse probabilities produced, i.e., the level of uncertainty in the estimate of annual collapse probability, with less vulnerable buildings having a smaller uncertainty. © 2017 Society for Risk Analysis.

  18. Facilitating Shared Understandings of Risk

    DEFF Research Database (Denmark)

    Mitchell, Robb

    This thesis contributes an identification of a key mechanism and its constituent qualities, for facilitating shared understandings of risk. Globalisation and the pace of technological change increases the uncertainties of decision making within many design and innovation practices. Accordingly......, the focus of participatory workshops has expanded towards addressing broader questions of strategy, business models and other organizational and inter-organisational issues. To develop effective partnerships across the boundaries separating companies, I argue that is necessary for those involved to gain...... or proxy for absent others, 4) an incomplete comic with which children could contribute sketched ideas to a design process 5) a table top tool kits for discussing business relationship issues and 5) a number of bespoke interactive sculpture-like artifacts for provoking insights concerning business dilemmas...

  19. Determination of toxic metals, trace and essentials, and macronutrients in Sarpa salpa and Chelon labrosus: risk assessment for the consumers.

    Science.gov (United States)

    Afonso, Aridani; Gutiérrez, Angel J; Lozano, Gonzalo; González-Weller, Dailos; Rubio, Carmen; Caballero, José M; Hardisson, Arturo; Revert, Consuelo

    2017-04-01

    Due to increased environmental pollution, monitoring of contaminants in the environment and marine organisms is a fundamental tool for assessing the existence of risk from their consumption to human health. The levels of toxic heavy metals (Cd, Pb, and Al), trace and essential metals (B, Ba, Co, Cu, Cr, Fe, Li, Mn, Mo, Ni, Sr, V, and Zn), and macronutrients (Ca, K, Mg, Na) in two species of fish for human consumption were quantified in the present study. Eighty samples of muscle tissue and 80 samples of liver tissue belonging to two species of Osteichthyes fish; Sarpa salpa and Chelon labrosus were analyzed. The studied specimens were caught on the northern coast of Gran Canaria (Canary Islands) with fishing rods. As they caught from the shore, they are suitable samples for assessing the toxic levels of representative species caught by local amateur fishermen. The results show that both species are fit for human consumption since they have toxic levels of heavy metals (Cd, Pb, and Al) which are below the maximum established levels; however, the toxic levels of the liver samples are several orders of magnitude higher than the muscle samples, so we discourage their regular consumption. The risk assessment indicated that the two species of fish are safe for the average consumer; however, if the livers of these species are consumed, there could be risks because they exceed the PTWI for Pb and the TWI for Cd.

  20. Cyanotoxins: producing organisms, occurrence, toxicity, mechanism of action and human health toxicological risk evaluation.

    Science.gov (United States)

    Buratti, Franca M; Manganelli, Maura; Vichi, Susanna; Stefanelli, Mara; Scardala, Simona; Testai, Emanuela; Funari, Enzo

    2017-03-01

    Cyanobacteria were present on the earth 3.5 billion years ago; since then they have colonized almost all terrestrial and aquatic ecosystems. They produce a high number of bioactive molecules, among which some are cyanotoxins. Cyanobacterial growth at high densities, forming blooms, is increasing in extension and frequency, following anthropogenic activities and climate changes, giving rise to some concern for human health and animal life exposed to cyanotoxins. Numerous cases of lethal poisonings have been associated with cyanotoxins ingestion in wild animal and livestock. In humans few episodes of lethal or severe human poisonings have been recorded after acute or short-term exposure, but the repeated/chronic exposure to low cyanotoxin levels remains a critical issue. The properties of the most frequently detected cyanotoxins (namely, microcystins, nodularins, cylindrospermopsin and neurotoxins) are here critically reviewed, describing for each toxin the available information on producing organisms, biosynthesis/genetic and occurrence, with a focus on the toxicological profile (including kinetics, acute systemic toxicity, mechanism and mode of action, local effects, repeated toxicity, genotoxicity, carcinogenicity, reproductive toxicity; human health effects and epidemiological studies; animal poisoning) with the derivation of health-based values and considerations on the risks for human health.

  1. Insights into aquatic toxicities of the antibiotics oxytetracycline and ciprofloxacin in the presence of metal: Complexation versus mixture

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Zhang [Key Laboratory of Industrial Ecology and Environmental Engineering (Ministry of Education), School of Environmental Science and Technology, Dalian University of Technology, Dalian 116024 (China); Cai Xiyun, E-mail: xiyuncai@dlut.edu.cn [Key Laboratory of Industrial Ecology and Environmental Engineering (Ministry of Education), School of Environmental Science and Technology, Dalian University of Technology, Dalian 116024 (China); Xianming, Lang [Liaoning Academy of Environmental Sciences, Shenyang 110031 (China); Xianliang, Qiao; Xuehua, Li; Jingwen, Chen [Key Laboratory of Industrial Ecology and Environmental Engineering (Ministry of Education), School of Environmental Science and Technology, Dalian University of Technology, Dalian 116024 (China)

    2012-07-15

    Co-contamination of ligand-like antibiotics (e.g., tetracyclines and quinolones) and heavy metals prevails in the environment, and thus the complexation between them is involved in environmental risks of antibiotics. To understand toxicological significance of the complex, effects of metal coordination on antibiotics' toxicity were investigated. The complexation of two antibiotics, oxytetracycline and ciprofloxacin, with three heavy metals, copper, zinc, and cadmium, was verified by spectroscopic techniques. The antibiotics bound metals via multiple coordination sites and rendered a mixture of various complexation speciations. Toxicity analysis indicated that metal coordination did modify the toxicity of the antibiotics and that antibiotic, metal, and their complex acted primarily as concentration addition. Comparison of EC{sub 50} values revealed that the complex commonly was highest toxic and predominately correlated in toxicity to the mixture. Finally, environmental scenario analysis demonstrated that ignoring complexation would improperly classify environmental risks of the antibiotics. - Highlights: Black-Right-Pointing-Pointer The complex of antibiotic with metal is a mixture of various complexation modes. Black-Right-Pointing-Pointer Antibiotic and metal act as various combined interactions when their complexation is ignored. Black-Right-Pointing-Pointer Antibiotic, metal, and their complex act as concentration addition interaction. Black-Right-Pointing-Pointer Complex commonly is the highest toxicant. Black-Right-Pointing-Pointer Neglecting complexation renders improper classification of risks for antibiotics. - Antibiotic, heavy metal and their complex act primarily as concentration addition interaction and the complex commonly is highest toxic.

  2. A bioethical perspective on risk assessment models for managing toxic wastes, radioactive or non-radioactive

    International Nuclear Information System (INIS)

    Maxey, M.N.

    1982-01-01

    In the interest of developing an adequate and consistent bioethical perspective for reflecting on the ethical issues raised by toxic wastes, this brief paper focuses on the question of whether or not public opposition to past and proposed methods for waste management has been induced as much by technical incompetance as by deficiencies in using risk models for bioethical problem definitions

  3. Toxicity of Atorvastatin on Pancreas Mitochondria: A Justification for Increased Risk of Diabetes Mellitus.

    Science.gov (United States)

    Sadighara, Melina; Amirsheardost, Zahra; Minaiyan, Mohsen; Hajhashemi, Valiollah; Naserzadeh, Parvaneh; Salimi, Ahmad; Seydi, Enayatollah; Pourahmad, Jalal

    2017-02-01

    Statins (including atorvastatin) are a widely used class of drugs, and like all medications, they have a potential for adverse effects. Recently, it has been shown that statins also exert side effects on the pancreas. In vitro studies have suggested that this class of drugs induced a reduction in insulin secretion. Also, the use of statins is associated with a raised risk of diabetes mellitus (DM), but the mechanisms underlying statin-induced diabetes are poorly known. Literature data indicate that several statins are able to induce apoptosis signalling. This study was designed to examine the mechanism of atorvastatin on mitochondria obtained from rat pancreas. In our study, mitochondria were obtained from the pancreas and then exposed to atorvastatin and vehicle to investigate probable toxic effects. The results showed that atorvastatin (25, 50, 75, 100 and 125 μM) increased reactive oxygen species (ROS) production, mitochondrial swelling, collapse of mitochondrial membrane potential and cytochrome c release, the orchestrating factor for mitochondria-mediated apoptosis signalling. Atorvastatin also reduced the ATP levels. These results propose that the toxicity of atorvastatin on pancreas mitochondria is a key point for drug-induced apoptotic cell loss in the pancreas and therefore a justification for increased risk of DM. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  4. Financial disclosure and toxic products: encouraging wall street to anticipate product risk and exercise precaution.

    Science.gov (United States)

    Lewis, Sanford; Byrne, Margaret

    2009-01-01

    Amidst discussion by policymakers about how regulators' failure to ensure disclosure of risks contributed to the current financial crisis, we assess how emerging product toxicity risks are addressed in companies' financial reports. Will corporations blindside investors with "the next asbestos?" Existing disclosures are found lacking in the specificity needed to forewarn of liabilities and reputational damage from the use of potentially harmful materials-from nanotechnologies, to asthmagens, to perfluorinated compounds. Improved standards could protect investors while also enhancing corporate incentives to use safer materials. Reforms by the Securities and Exchange Commission and the Financial Accounting Standards Board are recommended.

  5. Diethylene glycol-induced toxicities show marked threshold dose response in rats

    Energy Technology Data Exchange (ETDEWEB)

    Landry, Greg M., E-mail: Landry.Greg@mayo.edu [Department of Pharmacology, Toxicology, & Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA (United States); Dunning, Cody L., E-mail: cdunni@lsuhsc.edu [Department of Pharmacology, Toxicology, & Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA (United States); Abreo, Fleurette, E-mail: fabreo@lsuhsc.edu [Department of Pathology, Louisiana State University Health Sciences Center, Shreveport, LA (United States); Latimer, Brian, E-mail: blatim@lsuhsc.edu [Department of Pharmacology, Toxicology, & Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA (United States); Orchard, Elysse, E-mail: eorcha@lsuhsc.edu [Department of Pharmacology, Toxicology, & Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA (United States); Division of Animal Resources, Louisiana State University Health Sciences Center, Shreveport, LA (United States); McMartin, Kenneth E., E-mail: kmcmar@lsuhsc.edu [Department of Pharmacology, Toxicology, & Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA (United States)

    2015-02-01

    Diethylene glycol (DEG) exposure poses risks to human health because of widespread industrial use and accidental exposures from contaminated products. To enhance the understanding of the mechanistic role of metabolites in DEG toxicity, this study used a dose response paradigm to determine a rat model that would best mimic DEG exposure in humans. Wistar and Fischer-344 (F-344) rats were treated by oral gavage with 0, 2, 5, or 10 g/kg DEG and blood, kidney and liver tissues were collected at 48 h. Both rat strains treated with 10 g/kg DEG had equivalent degrees of metabolic acidosis, renal toxicity (increased BUN and creatinine and cortical necrosis) and liver toxicity (increased serum enzyme levels, centrilobular necrosis and severe glycogen depletion). There was no liver or kidney toxicity at the lower DEG doses (2 and 5 g/kg) regardless of strain, demonstrating a steep threshold dose response. Kidney diglycolic acid (DGA), the presumed nephrotoxic metabolite of DEG, was markedly elevated in both rat strains administered 10 g/kg DEG, but no DGA was present at 2 or 5 g/kg, asserting its necessary role in DEG-induced toxicity. These results indicate that mechanistically in order to produce toxicity, metabolism to and significant target organ accumulation of DGA are required and that both strains would be useful for DEG risk assessments. - Highlights: • DEG produces a steep threshold dose response for kidney injury in rats. • Wistar and F-344 rats do not differ in response to DEG-induced renal injury. • The dose response for renal injury closely mirrors that for renal DGA accumulation. • Results demonstrate the importance of DGA accumulation in producing kidney injury.

  6. Hypofractionated Accelerated Radiotherapy Using Concomitant Intensity-Modulated Radiotherapy Boost Technique for Localized High-Risk Prostate Cancer: Acute Toxicity Results

    International Nuclear Information System (INIS)

    Lim, Tee S.; Cheung, Patrick; Loblaw, D. Andrew; Morton, Gerard; Sixel, Katharina E.; Pang, Geordi; Basran, Parminder; Zhang Liying; Tirona, Romeo; Szumacher, Ewa; Danjoux, Cyril; Choo, Richard; Thomas, Gillian

    2008-01-01

    Purpose: To evaluate the acute toxicities of hypofractionated accelerated radiotherapy (RT) using a concomitant intensity-modulated RT boost in conjunction with elective pelvic nodal irradiation for high-risk prostate cancer. Methods and Materials: This report focused on 66 patients entered into this prospective Phase I study. The eligible patients had clinically localized prostate cancer with at least one of the following high-risk features (Stage T3, Gleason score ≥8, or prostate-specific antigen level >20 ng/mL). Patients were treated with 45 Gy in 25 fractions to the pelvic lymph nodes using a conventional four-field technique. A concomitant intensity-modulated radiotherapy boost of 22.5 Gy in 25 fractions was delivered to the prostate. Thus, the prostate received 67.5 Gy in 25 fractions within 5 weeks. Next, the patients underwent 3 years of adjuvant androgen ablative therapy. Acute toxicities were assessed using the Common Terminology Criteria for Adverse Events, version 3.0, weekly during treatment and at 3 months after RT. Results: The median patient age was 71 years. The median pretreatment prostate-specific antigen level and Gleason score was 18.7 ng/L and 8, respectively. Grade 1-2 genitourinary and gastrointestinal toxicities were common during RT but most had settled at 3 months after treatment. Only 5 patients had acute Grade 3 genitourinary toxicity, in the form of urinary incontinence (n = 1), urinary frequency/urgency (n = 3), and urinary retention (n = 1). None of the patients developed Grade 3 or greater gastrointestinal or Grade 4 or greater genitourinary toxicity. Conclusion: The results of the present study have indicated that hypofractionated accelerated RT with a concomitant intensity-modulated RT boost and pelvic nodal irradiation is feasible with acceptable acute toxicity

  7. Novel view on predicting acute toxicity: Decomposing toxicity data in species vulnerability and chemical potency.

    NARCIS (Netherlands)

    Jager, D.T.; Posthuma, L.; Zwart, D.D.; van de Meent, D.

    2007-01-01

    Chemical risk assessment usually applies empirical methods to predict toxicant effects on different species. We propose a more mechanism-oriented approach, and introduce a method to decompose toxicity data in a contribution from the chemical (potency) and from the exposed species (vulnerability). We

  8. A possible early sign of hydroxychloroquine macular toxicity.

    Science.gov (United States)

    Brandao, Livia M; Palmowski-Wolfe, Anja M

    2016-02-01

    and daily dosages were under the high-risk parameters for screening and the averages reported in studies. As ganglion cell analysis has only recently become available, further studies are needed to understand toxicity mechanisms and maybe review screening recommendations.

  9. Evaluation of the Possible Sources and Controlling Factors of Toxic Metals/Metalloids in the Florida Everglades and Their Potential Risk of Exposure.

    Science.gov (United States)

    Li, Yanbin; Duan, Zhiwei; Liu, Guangliang; Kalla, Peter; Scheidt, Daniel; Cai, Yong

    2015-08-18

    The Florida Everglades is an environmentally sensitive wetland ecosystem with a number of threatened and endangered fauna species susceptible to the deterioration of water quality. Several potential toxic metal sources exist in the Everglades, including farming, atmospheric deposition, and human activities in urban areas, causing concerns of potential metal exposure risks. However, little is known about the pollution status of toxic metals/metalloids of potential concern, except for Hg. In this study, eight toxic metals/metalloids (Cd, Cr, Pb, Ni, Cu, Zn, As, and Hg) in Everglades soils were investigated in both dry and wet seasons. Pb, Cr, As, Cu, Cd, and Ni were identified to be above Florida SQGs (sediment quality guidelines) at a number of sampling sites, particularly Pb, which had a level of potential risk to organisms similar to that of Hg. In addition, a method was developed for quantitative source identification and controlling factor elucidation of toxic metals/metalloids by introducing an index, enrichment factor (EF), in the conventional multiple regression analysis. EFs represent the effects of anthropogenic sources on metals/metalloids in soils. Multiple regression analysis showed that Cr and Ni were mainly controlled by anthropogenic loading, whereas soil characteristics, in particular natural organic matter (NOM), played a more important role for Hg, As, Cd, and Zn. NOM may control the distribution of these toxic metals/metalloids by affecting their mobility in soils. For Cu and Pb, the effects of EFs and environmental factors are comparable, suggesting combined effects of loading and soil characteristics. This study is the first comprehensive research with a vast amount of sampling sites on the distribution and potential risks of toxic metals/metalloids in the Everglades. The finding suggests that in addition to Hg other metals/metalloids could also potentially be an environmental problem in this wetland ecosystem.

  10. Toxicity profile of labile preservative bronopol in water: The role of more persistent and toxic transformation products

    International Nuclear Information System (INIS)

    Cui Na; Zhang Xiaoxiang; Xie Qing; Wang Se; Chen Jingwen; Huang Liping; Qiao Xianliang; Li Xuehua; Cai Xiyun

    2011-01-01

    Transformation products usually differ in environmental behaviors and toxicological properties from the parent contaminants, and probably cause potential risks to the environment. Toxicity evolution of a labile preservative, bronopol, upon primary aquatic degradation processes was investigated. Bronopol rapidly hydrolyzed in natural waters, and primarily produced more stable 2-bromo-2-nitroethanol (BNE) and bromonitromethane (BNM). Light enhanced degradation of the targeted compounds with water site specific photoactivity. The bond order analysis theoretically revealed that the reversible retroaldol reactions were primary degradation routes for bronopol and BNE. Judging from toxicity assays and the relative pesticide toxicity index, these degradation products (i.e., BNE and BNM), more persistent and higher toxic than the parent, probably accumulated in natural waters and resulted in higher or prolonging adverse impacts. Therefore, these transformation products should be included into the assessment of ecological risks of non-persistent and low toxic chemicals such as the preservative bronopol. - The preservative bronopol is non-persistent and low toxic, but some transformation products can cause higher or prolonging adverse impacts.

  11. Toxicity profile of labile preservative bronopol in water: The role of more persistent and toxic transformation products

    Energy Technology Data Exchange (ETDEWEB)

    Cui Na; Zhang Xiaoxiang; Xie Qing; Wang Se; Chen Jingwen; Huang Liping; Qiao Xianliang; Li Xuehua [Key Laboratory of Industrial Ecology and Environmental Engineering (Ministry of Education), School of Environmental Science and Technology, Dalian University of Technology, Dalian 116024 (China); Cai Xiyun, E-mail: xiyuncai@dlut.edu.c [Key Laboratory of Industrial Ecology and Environmental Engineering (Ministry of Education), School of Environmental Science and Technology, Dalian University of Technology, Dalian 116024 (China)

    2011-02-15

    Transformation products usually differ in environmental behaviors and toxicological properties from the parent contaminants, and probably cause potential risks to the environment. Toxicity evolution of a labile preservative, bronopol, upon primary aquatic degradation processes was investigated. Bronopol rapidly hydrolyzed in natural waters, and primarily produced more stable 2-bromo-2-nitroethanol (BNE) and bromonitromethane (BNM). Light enhanced degradation of the targeted compounds with water site specific photoactivity. The bond order analysis theoretically revealed that the reversible retroaldol reactions were primary degradation routes for bronopol and BNE. Judging from toxicity assays and the relative pesticide toxicity index, these degradation products (i.e., BNE and BNM), more persistent and higher toxic than the parent, probably accumulated in natural waters and resulted in higher or prolonging adverse impacts. Therefore, these transformation products should be included into the assessment of ecological risks of non-persistent and low toxic chemicals such as the preservative bronopol. - The preservative bronopol is non-persistent and low toxic, but some transformation products can cause higher or prolonging adverse impacts.

  12. Advances in exposure and toxicity assessment of particulate matter: An overview of presentations at the 2009 Toxicology and Risk Assessment Conference

    International Nuclear Information System (INIS)

    Gunasekar, Palur G.; Stanek, Lindsay W.

    2011-01-01

    The 2009 Toxicology and Risk Assessment Conference (TRAC) session on 'Advances in Exposure and Toxicity Assessment of Particulate Matter' was held in April 2009 in West Chester, OH. The goal of this session was to bring together toxicology, geology and risk assessment experts from the Department of Defense and academia to examine issues in exposure assessment and report on recent epidemiological findings of health effects associated with particulate matter (PM) exposure. Important aspects of PM exposure research are to detect and monitor low levels of PM with various chemical compositions and to assess the health risks associated with these exposures. As part of the overall theme, some presenters discussed collection methods for sand and dust from Iraqi and Afghanistan regions, health issues among deployed personnel, and future directions for risk assessment research among these populations. The remaining speakers focused on the toxicity of ultrafine PM and the characterization of aerosols generated during ballistic impacts of tungsten heavy alloys.

  13. Toxic Stress: Effects, Prevention and Treatment

    Directory of Open Access Journals (Sweden)

    Hillary A. Franke

    2014-11-01

    Full Text Available Children who experience early life toxic stress are at risk of long-term adverse health effects that may not manifest until adulthood. This article briefly summarizes the findings in recent studies on toxic stress and childhood adversity following the publication of the American Academy of Pediatrics (AAP Policy Report on the effects of toxic stress. A review of toxic stress and its effects is described, including factors of vulnerability, resilience, and the relaxation response. An integrative approach to the prevention and treatment of toxic stress necessitates individual, community and national focus.

  14. Medical Applications and Toxicities of Gallium Compounds

    Directory of Open Access Journals (Sweden)

    Christopher R. Chitambar

    2010-05-01

    Full Text Available Over the past two to three decades, gallium compounds have gained importance in the fields of medicine and electronics. In clinical medicine, radioactive gallium and stable gallium nitrate are used as diagnostic and therapeutic agents in cancer and disorders of calcium and bone metabolism. In addition, gallium compounds have displayed anti-inflammatory and immunosuppressive activity in animal models of human disease while more recent studies have shown that gallium compounds may function as antimicrobial agents against certain pathogens. In a totally different realm, the chemical properties of gallium arsenide have led to its use in the semiconductor industry. Gallium compounds, whether used medically or in the electronics field, have toxicities. Patients receiving gallium nitrate for the treatment of various diseases may benefit from such therapy, but knowledge of the therapeutic index of this drug is necessary to avoid clinical toxicities. Animals exposed to gallium arsenide display toxicities in certain organ systems suggesting that environmental risks may exist for individuals exposed to this compound in the workplace. Although the arsenic moiety of gallium arsenide appears to be mainly responsible for its pulmonary toxicity, gallium may contribute to some of the detrimental effects in other organs. The use of older and newer gallium compounds in clinical medicine may be advanced by a better understanding of their mechanisms of action, drug resistance, pharmacology, and side-effects. This review will discuss the medical applications of gallium and its mechanisms of action, the newer gallium compounds and future directions for development, and the toxicities of gallium compounds in current use.

  15. Assessment of microplastic toxicity to embryonic development of the sea urchin Lytechinus variegatus (Echinodermata: Echinoidea).

    Science.gov (United States)

    Nobre, C R; Santana, M F M; Maluf, A; Cortez, F S; Cesar, A; Pereira, C D S; Turra, A

    2015-03-15

    Apart from the physiological impacts on marine organisms caused by ingesting microplastics, the toxicity caused by substances leaching from these particles into the environment requires investigation. To understand this potential risk, we evaluated the toxicity of virgin (raw) and beach-stranded plastic pellets to the development of embryos of Lytechinus variegatus, simulating transfers of chemical compounds to interstitial water and water column by assays of pellet-water interface and elutriate, respectively. Both assays showed that virgin pellets had toxic effects, increasing anomalous embryonic development by 58.1% and 66.5%, respectively. The toxicity of stranded pellets was lower than virgin pellets, and was observed only for pellet-water interface assay. These results show that (i) plastic pellets act as a vector of pollutants, especially for plastic additives found on virgin particles; and that (ii) the toxicity of leached chemicals from pellets depends on the exposure pathway and on the environmental compartment in which pellets accumulate. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Understanding safety and production risks in rail engineering planning and protection.

    Science.gov (United States)

    Wilson, John R; Ryan, Brendan; Schock, Alex; Ferreira, Pedro; Smith, Stuart; Pitsopoulos, Julia

    2009-07-01

    Much of the published human factors work on risk is to do with safety and within this is concerned with prediction and analysis of human error and with human reliability assessment. Less has been published on human factors contributions to understanding and managing project, business, engineering and other forms of risk and still less jointly assessing risk to do with broad issues of 'safety' and broad issues of 'production' or 'performance'. This paper contains a general commentary on human factors and assessment of risk of various kinds, in the context of the aims of ergonomics and concerns about being too risk averse. The paper then describes a specific project, in rail engineering, where the notion of a human factors case has been employed to analyse engineering functions and related human factors issues. A human factors issues register for potential system disturbances has been developed, prior to a human factors risk assessment, which jointly covers safety and production (engineering delivery) concerns. The paper concludes with a commentary on the potential relevance of a resilience engineering perspective to understanding rail engineering systems risk. Design, planning and management of complex systems will increasingly have to address the issue of making trade-offs between safety and production, and ergonomics should be central to this. The paper addresses the relevant issues and does so in an under-published domain - rail systems engineering work.

  17. Health risks in international container and bulk cargo transport due to volatile toxic compounds

    DEFF Research Database (Denmark)

    Baur, Xaver; Budnik, Lygia T; Zhao, Zhiwei

    2015-01-01

    To ensure the preservation and quality of the goods, physical (i.e. radiation) or chemical pest control is needed. The dark side of such consents may bear health risks in international transport and production sharing. In fact, between 10% and 20% of all containers arriving European harbors were...... with lethal outcome, occur not only during the fumigation, but also during freight transport (on bulk carriers and other transport vessels), as well as in the logistic lines during loading and unloading. Risk occupations include dock-workers, seafarers, inspectors, as well as the usually uninformed workers...... of importing enterprises that unload the products. Bystanders as well as vulnerable consumers may also be at risk. Ongoing studies focus on the release of these toxic volatile substances from various goods. It was shown that the half-lives of the off-gassing process range between minutes and months, depending...

  18. FLUORIDE TOXICITY – A HARSH REALITY

    OpenAIRE

    Bandlapalli Pavani; Mandava Ragini; David Banji; Otilia J F Banji; N Gouri Pratusha

    2011-01-01

    There are many incidents of fluoride toxicity whether it is acute or chronic. Fluoride toxicity is an environmental hazard which arises from the upper layers of geological crust and is dissolved in water. Prolonged drinking of such water causes chronic fluoride toxicity. Use of fluoride containing compounds for various purposes such as dental products, metal, glass, refrigerator and chemical industries act as a source of fluoride poisoning and increase the risk of toxicity. This review reflec...

  19. [MANAGEMENT OF HEALTHCARE WASTE IN THE HOSPITAL SETTING. UNDERSTANDING RISK MANAGEMENT].

    Science.gov (United States)

    Galimany-Masclans, Jordi; Torres-Egea, Pilar; Sancho-Agredano, Raúl; Girbau-García, Ma Rosa; Fabrellas, Núria; Torrens-Garcia, Ma Llum; Martínez-Estalella, Gemma

    2015-05-01

    The sanitary waste represents a potential hazard for health workers. Given the high risk of infection in labor accidents, the correct management of sanitary waste minimizes this risk and improves labor and environment conditions. To identify risk perception with health professionals in relation to the advanced sorting and management of healthcare waste (HW). The current study is a descriptive, cross-sectional. The sample size was 177 health workers (nurse assistants, nurses, physicians, lab technicians) from three hospitals in Barcelona (Catalonia). Homemade questionnaire and questions with a free and spontaneous association and incomplete sentences were used to analyze labor variables, perception of risk and personal security through a Likert scale. Using a score from 1 (the lowest perception of risk) to 5 (the high perception of risk) to assess the risk perception, the average value for nurse assistants, nurses, physicians, and lab technicians was 3.71, 3.75, 3.83 and 4.03, respectively. Referring to items with free and spontaneous response association, 44.8% of workers consider HW as a biohazard, 29.6% consider it as waste material, 22.1% state that it must be managed properly and 3.5% described it as unknown residues. The results suggest that all health professionals generally have a perception of high risk. The lab technicians have a higher perception of the real risk of inadequate management of HW A 63.2% report that everyone has to make a proper management to preserve their occupational health; the 59% consider that the HW are a biological risk to the general population and only the 47.8% that are harmful to public health. Although it should be noted that only 44.8% think that HW are toxic and dangerous.

  20. Comprehensive assessment of toxic chemical pollutants at Trombay region

    International Nuclear Information System (INIS)

    Sahu, S.K.; Saradhi, I.V.; Raghunath, R.; Pandit, G.G.; Puranik, V.D.

    2006-04-01

    Anthropogenic activities like industrial production and transportation, a wide range of chemical pollutants such as trace and toxic metals, pesticides, polycyclic aromatic hydrocarbons etc. eventually found their way into various environmental compartments. These pollutants get distributed among soil, water bodies, air and if left unattended can cause serious health risk to all exposed ecosystem components including human beings. These compounds may produce immediate toxicity to ecosystems or exhibit long term effects such as mutagenicity, carcinogenicity or biomagnify (concentrations of pollutant increase per unit body weight) in higher trophic organism of the food chain. Thus regular monitoring of these toxic chemicals in all the environmental matrices is unquestionably essential for reclaiming our natural resources. This report describes some of the activities of Environmental Assessment Division which are having direct relevance to the public health and regulatory bodies. Extensive studies were carried out in our laboratories for the Trombay site, over the years; on the organic as well as inorganic pollution in the environment to understand inter compartmental behaviour of these chemical pollutants. In this report attempt has been made to compare the data on various toxic chemical pollutants that are being monitored regularly at Trombay site and their levels are compared with existing regulations. For monitoring, methodologies have been standardized for characterization of toxic chemical pollutants using different analytical techniques. Regular sample collection from different environmental matrices has been done. Sample analysis has been carried out using different analytical instruments such as high performance liquid chromatograph, ion chromatograph, gas chromatograph, atomic absorption spectrophotometer, and differential pulse anodic stripping voltammetry. Major portion of the study covers Air quality monitoring of toxic chemical pollutants, as the other

  1. Chronic toxicity risk after radiotherapy for patients with systemic sclerosis (systemic scleroderma) or systemic lupus erythematosus: Association with connective tissue disorder severity

    International Nuclear Information System (INIS)

    Gold, Douglas G.; Miller, Robert C.; Pinn, Melva E.; Osborn, Thomas G.; Petersen, Ivy A.; Brown, Paul D.

    2008-01-01

    No method reliably identifies which patients with connective tissue disorders are at greatest risk of radiotherapy-related complications. Building on our prior experience, we postulated that disease severity, as measured by the number of organ systems involved, may predict chronic radiation toxicity risk

  2. A Novel Method for Predicting Late Genitourinary Toxicity After Prostate Radiation Therapy and the Need for Age-Based Risk-Adapted Dose Constraints

    International Nuclear Information System (INIS)

    Ahmed, Awad A.; Egleston, Brian; Alcantara, Pino; Li, Linna; Pollack, Alan; Horwitz, Eric M.; Buyyounouski, Mark K.

    2013-01-01

    Background: There are no well-established normal tissue sparing dose–volume histogram (DVH) criteria that limit the risk of urinary toxicity from prostate radiation therapy (RT). The aim of this study was to determine which criteria predict late toxicity among various DVH parameters when contouring the entire solid bladder and its contents versus the bladder wall. The area under the histogram curve (AUHC) was also analyzed. Methods and Materials: From 1993 to 2000, 503 men with prostate cancer received 3-dimensional conformal RT (median follow-up time, 71 months). The whole bladder and the bladder wall were contoured in all patients. The primary endpoint was grade ≥2 genitourinary (GU) toxicity occurring ≥3 months after completion of RT. Cox regressions of time to grade ≥2 toxicity were estimated separately for the entire bladder and bladder wall. Concordance probability estimates (CPE) assessed model discriminative ability. Before training the models, an external random test group of 100 men was set aside for testing. Separate analyses were performed based on the mean age (≤ 68 vs >68 years). Results: Age, pretreatment urinary symptoms, mean dose (entire bladder and bladder wall), and AUHC (entire bladder and bladder wall) were significant (P 68 years. Conclusion: The AUHC method based on bladder wall volumes was superior for predicting late GU toxicity. Age >68 years was associated with late grade ≥2 GU toxicity, which suggests that risk-adapted dose constraints based on age should be explored

  3. In vitro bioassays reveal that additives are significant contributors to the toxicity of commercial household pesticides.

    Science.gov (United States)

    van de Merwe, Jason P; Neale, Peta A; Melvin, Steven D; Leusch, Frederic D L

    2018-06-01

    Pesticides commonly used around households can contain additives of unknown concentrations and toxicity. Given the likelihood of these chemicals washing into urban waterways, it is important to understand the effects that these additives may have on aquatic organisms. The aim of this study was to compare the toxicity of commercially available household pesticides to that of the active ingredient(s) alone. The toxicity of five household pesticides (three herbicides and two insecticides) was investigated using a bacterial cytotoxicity bioassay and an algal photosynthesis bioassay. The commercial products were up to an order of magnitude more toxic than the active ingredient(s) alone. In addition, two commercial products with the same listed active ingredients in the same ratio had a 600× difference in potency. These results clearly demonstrate that additives in commercial formulations are significant contributors to the toxicity of household pesticides. The toxicity of pesticides in aquatic systems is therefore likely underestimated by conventional chemical monitoring and risk assessment when only the active ingredients are considered. Regulators and customers should require more clarity from pesticide manufacturers about the nature and concentrations of not only the active ingredients, but also additives used in commercial formulations. In addition, monitoring programmes and chemical risk assessments schemes should develop a structured approach to assessing the toxic effects of commercial formulations, including additives, rather than simply those of the listed active ingredients. Copyright © 2018. Published by Elsevier B.V.

  4. Informed consent in contrast-enhanced CT. Understanding of risks and identification of possible prognostic factors

    International Nuclear Information System (INIS)

    Roehrl, S.; Dendl, L.M.; Scharf, G.; Stroszczynski, C.; Schreyer, A.G.; Zeman, F.

    2015-01-01

    Aim of our study was to assess understanding of risks associated with intravascular application of contrast media in patients undergoing CT examination. We wanted to evaluate epidemiologic and socio-economic prognostic factors for a higher understanding of risks. Additionally, we evaluated a possible correlation between an extensive, outcome-oriented oral informed consent and better understanding of risks. 120 patients distributed in 2 study arms participated in this prospective study. In study arm I, the treating physician was not informed that his patients participated in a study whereas the physician in study arm II knew about the survey. After the informed consent we performed a standardized, semi-structured interview to enquire the 3 most frequent risks of intravascular application of contrast agents (anaphylactoid reactions, nephropathy and thyrotoxic crisis) and epidemiologic data. The understanding of the risks was evaluated using a 6 point scale. Patients scored 3.73 points in study arm I and 4.93 points in arm II on average. The statistical difference between both study arms was highly significant (p < 0.001). In a combined logistic regression analysis, only ''higher education'' (p = 0.001) and participation in study arm II (p =0.001) showed a significant connection to a better understanding of risks. Patients profit from an outcome-oriented and individualized informed consent. Due to the significant correlation between educational level and understanding of risks, informed consent should be adjusted to the educational status of the individual patient, e.g. by using didactic aids or individualized information sheets.

  5. Toxic chemicals: risk prevention through use reduction

    National Research Council Canada - National Science Library

    Higgins, Thomas E; Sachdev, Jayanti A; Engleman, Stephen A

    2011-01-01

    "Catastrophic events such as the Bhopal, India tragedy and rising incidences of cancer in areas neighboring industrial facilities have heightened concern over the use of toxic chemicals in manufacturing and industry...

  6. Emerging systems biology approaches in nanotoxicology: Towards a mechanism-based understanding of nanomaterial hazard and risk

    Energy Technology Data Exchange (ETDEWEB)

    Costa, Pedro M.; Fadeel, Bengt, E-mail: Bengt.Fadeel@ki.se

    2016-05-15

    Engineered nanomaterials are being developed for a variety of technological applications. However, the increasing use of nanomaterials in society has led to concerns about their potential adverse effects on human health and the environment. During the first decade of nanotoxicological research, the realization has emerged that effective risk assessment of the multitudes of new nanomaterials would benefit from a comprehensive understanding of their toxicological mechanisms, which is difficult to achieve with traditional, low-throughput, single end-point oriented approaches. Therefore, systems biology approaches are being progressively applied within the nano(eco)toxicological sciences. This novel paradigm implies that the study of biological systems should be integrative resulting in quantitative and predictive models of nanomaterial behaviour in a biological system. To this end, global ‘omics’ approaches with which to assess changes in genes, proteins, metabolites, etc. are deployed allowing for computational modelling of the biological effects of nanomaterials. Here, we highlight omics and systems biology studies in nanotoxicology, aiming towards the implementation of a systems nanotoxicology and mechanism-based risk assessment of nanomaterials. - Highlights: • Systems nanotoxicology is a multi-disciplinary approach to quantitative modelling. • Transcriptomics, proteomics and metabolomics remain the most common methods. • Global “omics” techniques should be coupled to computational modelling approaches. • The discovery of nano-specific toxicity pathways and biomarkers is a prioritized goal. • Overall, experimental nanosafety research must endeavour reproducibility and relevance.

  7. Emerging systems biology approaches in nanotoxicology: Towards a mechanism-based understanding of nanomaterial hazard and risk

    International Nuclear Information System (INIS)

    Costa, Pedro M.; Fadeel, Bengt

    2016-01-01

    Engineered nanomaterials are being developed for a variety of technological applications. However, the increasing use of nanomaterials in society has led to concerns about their potential adverse effects on human health and the environment. During the first decade of nanotoxicological research, the realization has emerged that effective risk assessment of the multitudes of new nanomaterials would benefit from a comprehensive understanding of their toxicological mechanisms, which is difficult to achieve with traditional, low-throughput, single end-point oriented approaches. Therefore, systems biology approaches are being progressively applied within the nano(eco)toxicological sciences. This novel paradigm implies that the study of biological systems should be integrative resulting in quantitative and predictive models of nanomaterial behaviour in a biological system. To this end, global ‘omics’ approaches with which to assess changes in genes, proteins, metabolites, etc. are deployed allowing for computational modelling of the biological effects of nanomaterials. Here, we highlight omics and systems biology studies in nanotoxicology, aiming towards the implementation of a systems nanotoxicology and mechanism-based risk assessment of nanomaterials. - Highlights: • Systems nanotoxicology is a multi-disciplinary approach to quantitative modelling. • Transcriptomics, proteomics and metabolomics remain the most common methods. • Global “omics” techniques should be coupled to computational modelling approaches. • The discovery of nano-specific toxicity pathways and biomarkers is a prioritized goal. • Overall, experimental nanosafety research must endeavour reproducibility and relevance.

  8. Hazard and risk of herbicides for marine microalgae

    NARCIS (Netherlands)

    Sjollema, S.B.; Martínez-García, G.; van der Geest, H.G.; Kraak, M.H.S.; Booij, P.; Vethaak, A.D.; Admiraal, W.

    2014-01-01

    Due to their specific effect on photosynthesis, herbicides pose a potential threat to coastal and estuarine microalgae. However, comprehensive understanding of the hazard and risk of these contaminants is currently lacking. Therefore the aim of the present study was to investigate the toxic effects

  9. Source contribution and risk assessment of airborne toxic metals by neutron activation analysis in Taejeon industrial complex area - Concentration analysis and health risk assessment of airborne toxic metals in Taejeon 1,2 industrial Complex

    Energy Technology Data Exchange (ETDEWEB)

    Lee, J. H.; Jang, M. S.; Nam, B. H.; Yun, M. J. [Chungnam National Univ., Taejeon (Korea)

    2000-04-01

    The study centers on one-year continual concentration analysis using ICP-MS and on health risk assessment of 15 airborne toxic metals in Taejeon 1,2 industrial complex. About 1-year arithmetic mean of human carcinogen, arsenic, hexavalent chromium and nickel subsulfide is 6.05, 2.40 and 2.81 ng/m{sup 3} while the mean of probable human carcinogen, beryllium, cadmium and lead is 0.06, 3.92, 145.99 ng/m{sup 3}, respectively. And the long-term arithmetic mean concentration of non-carcinogenic metal, manganese is 44.60 ng/m{sup 3}. The point risk estimate for the inhalation of carcinogenic metals is 7.0 X10{sup -5}, which is higher than a risk standard of 10{sup -5}. The risk from human carcinogens is 6.2X10{sup -5}, while that from probable human carcinogens is 8.0X10{sup -6}, respectively. About 86 % of the cancer risk is due to the inhalation of human carcinogens, arsenic and hexavalent chromium. Thus, it is necessary to properly manage both arsenic and hexavalent chromium risk in Taejeon 1,2 industrial complex. 37 refs., 13 figs., 9 tabs. (Author)

  10. Risk perception: expert opinion versus public understanding. [Of radioactive waste repositories

    Energy Technology Data Exchange (ETDEWEB)

    Brown, J

    1987-02-01

    A research project looking at the public's attitudes towards the siting of radioactive waste depositories is reported. The risk perception studies seek to compare expert and lay understanding of risk. Adverse public reactions to risk can only be understood if it is known how people relate to risks in their everyday or working lives. Social trends and experiences are important, for example, the adverse public opinion on the siting of nuclear waste facilities. A number of elements have been identified as common to different risk areas such as chemicals, drugs, food or radioactive waste. These are the clashing of values, polarization of beliefs or clashes of interest.

  11. Pollutants, human health and the environment - A risk-based approach

    International Nuclear Information System (INIS)

    Plant, Jane A; Bone, James; Ragnarsdottir, Kristin Vala; Voulvoulis, Nickalaos

    2011-01-01

    Over the last 50 a there has been mounting unease about the risk of synthetic chemicals to human health. Publication of Rachel Carson's Silent Spring in 1962 catalyzed public concern about chemicals. There is now a vast range of synthetic substances in the environment and their potential cocktail as well as the effects of chronic exposure is of concern. Concerns about pollution are not restricted to toxic chemicals, with radioactivity being an issue that continues to be emotive, and exposure to substances such as particulates has been seen to cause health problems. Improved understanding of chemical risks to the environment and human health suggest that a precautionary approach is adopted, with new approaches demonstrating how nature uses thousands of sustainable, non-toxic processes, which can be copied by industry. Policy has evolved from the prevention of local pollution to the holistic management of environmental quality. Regulation is now increasingly underpinned by risk assessment and responsibility for understanding and managing chemical risk is being transferred progressively to manufacturers and users. There is now an increased emphasis on individual responsibilities which requires a debate about the risks and benefits of chemicals in which all members of society can participate.

  12. Does cytochrome P450 liver isoenzyme induction increase the risk of liver toxicity after paracetamol overdose?

    Directory of Open Access Journals (Sweden)

    Kalsi SS

    2011-10-01

    Full Text Available Sarbjeet S Kalsi1,2, David M Wood2–4, W Stephen Waring5, Paul I Dargan2–4 1Emergency Department, 2Clinical Toxicology, Guy's and St Thomas' NHS Foundation Trust, London; 3King's Health Partners, 4King's College London, London; 5York Teaching Hospital NHS Foundation Trust, York, UK Abstract: Paracetamol (acetaminophen, N-acetyl-p-aminophenol, 4-hydroxyacetanilide is the most common cause of acute liver failure in developed countries. There are a number of factors which potentially impact on the risk of an individual developing hepatotoxicity following an acute paracetamol overdose. These include the dose of paracetamol ingested, time to presentation, decreased liver glutathione, and induction of cytochrome P450 (CYP isoenzymes responsible for the metabolism of paracetamol to its toxic metabolite N-acetyl-p-benzoquinoneimine (NAPQI. In this paper, we review the currently published literature to determine whether induction of relevant CYP isoenzymes is a risk factor for hepatotoxicity in patients with acute paracetamol overdose. Animal and human in vitro studies have shown that the CYP isoenzyme responsible for the majority of human biotransformation of paracetamol to NAPQI is CYP2E1 at both therapeutic and toxic doses of paracetamol. Current UK treatment guidelines suggest that patients who use a number of drugs therapeutically should be treated as “high-risk” after paracetamol overdose. However, based on our review of the available literature, it appears that the only drugs for which there is evidence of the potential for an increased risk of hepatotoxicity associated with paracetamol overdose are phenobarbital, primidone, isoniazid, and perhaps St John's wort. There is no evidence that other drugs often quoted as increasing risk, such as carbamazepine, phenytoin, primidone, rifampicin, rifabutin, efavirenz, or nevirapine, should be considered risk factors for hepatotoxicity in patients presenting with acute paracetamol overdose. Keywords

  13. Preparing for local adaptation: Understanding flood risk perceptions in Pittsburgh

    Science.gov (United States)

    Wong-Parodi, G.; Klima, K.

    2016-12-01

    In cities such as Pittsburgh, aging and insufficient infrastructure contributes to flashfloods and numerous combined sewer overflows annually, contaminating streets, basements and waterways. Climate change is expected to further exacerbate this problem by causing more intense and more frequent extreme events in Western Pennsylvania. For a storm water adaptation plan to be implemented successfully, the City of Pittsburgh will need informed public support. One way to achieve public understanding and support is through effective communication of the risks, benefits, and uncertainties of local flooding hazards and adaptation methods. In order to develop risk communications effectively, the City and its partners will need to know what knowledge and attitudes the residents of Pittsburgh already hold about flood risks. To that end we surveyed 1,376 Pittsburgh residents on a variety of flood risk topics through an online or paper survey in Fall 2015. On balance, residents were relatively knowledgeable about storm water and see the City's current infrastructure as being inadequate to meet future risk. Moreover, they see the risk of runoff events as increasing and especially among those who live in hazardous flood areas. Residents expressed interest in having a dedicated fund to deal with runoff events. Among those queried about their willingness-to-pay, those asked to pay $15 were most interested in a dedicated fund and for green infrastructure (as opposed to gray infrastructure) in particular. Finally, while most residents favored green infrastructure in terms of its attractiveness and perceived affects on mitigating climate change many did not see it as effective at addressing flooding as gray infrastructure. We found people understand the risk and are open to doing something about it. However, more guidance and information on appropriate ways to adapt locally in terms that make sense to residents could enhance informed support for adaptation measures.

  14. Understanding operational risk capital approximations: First and second orders

    Directory of Open Access Journals (Sweden)

    Gareth W. Peters

    2013-07-01

    Full Text Available We set the context for capital approximation within the framework of the Basel II / III regulatory capital accords. This is particularly topical as the Basel III accord is shortly due to take effect. In this regard, we provide a summary of the role of capital adequacy in the new accord, highlighting along the way the significant loss events that have been attributed to the Operational Risk class that was introduced in the Basel II and III accords. Then we provide a semi-tutorial discussion on the modelling aspects of capital estimation under a Loss Distributional Approach (LDA. Our emphasis is to focuss on the important loss processes with regard to those that contribute most to capital, the so called “high consequence, low frequency" loss processes. This leads us to provide a tutorial overview of heavy tailed loss process modelling in OpRisk under Basel III, with discussion on the implications of such tail assumptions for the severity model in an LDA structure. This provides practitioners with a clear understanding of the features that they may wish to consider when developing OpRisk severity models in practice. From this discussion on heavy tailed severity models, we then develop an understanding of the impact such models have on the right tail asymptotics of the compound loss process and we provide detailed presentation of what are known as first and second order tail approximations for the resulting heavy tailed loss process. From this we develop a tutorial on three key families of risk measures and their equivalent second order asymptotic approximations: Value-at-Risk (Basel III industry standard; Expected Shortfall (ES and the Spectral Risk Measure. These then form the capital approximations. We then provide a few example case studies to illustrate the accuracy of these asymptotic captial approximations, the rate of the convergence of the assymptotic result as a function of the LDA frequency and severity model parameters, the sensitivity

  15. A Model for Understanding the Genetic Basis for Disparity in Prostate Cancer Risk

    Science.gov (United States)

    2017-10-01

    AWARD NUMBER: W81XWH-15-1-0529 TITLE: A Model for Understanding the Genetic Basis for Disparity in Prostate Cancer Risk PRINCIPAL INVESTIGATOR...AND SUBTITLE A Model for Understanding the Genetic Basis for Disparity in Prostate Cancer Risk 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-15-1...STATEMENT Approved for Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Prostate cancer is the most commonly diagnosed cancer in

  16. Toxicity report of once weekly radiation therapy for low-risk prostate adenocarcinoma: preliminary results of a phase I/II trial

    International Nuclear Information System (INIS)

    Menkarios, Cathy; Fortin, Bernard; Lambert, Carole; Vigneault, Éric; Brochet, Nicolas; Nguyen, David HA; Bahary, Jean-Paul; Jolicoeur, Marjory; Beauchemin, Marie-Claude; Villeneuve, Hugo; Van Nguyen, Thu

    2011-01-01

    Increasing clinical data supports a low α/β ratio for prostate adenocarcinoma, potentially lower than that of surrounding normal tissues. A hypofractionated, weekly radiation therapy (RT) schedule should result in improved tumour control, reduced acute toxicity, and similar or decreased late effects. We report the toxicity profile of such treatment. We conducted a multi-institution phase I/II trial of three-dimensional conformal radiation therapy (3D-CRT) for favourable-risk prostate cancer (T1a-T2a, Gleason ≤ 6 and PSA < 10 ng/ml). RT consisted of 45 Gy in nine 5 Gy fractions, once weekly. Primary end-points were feasibility and late gastrointestinal (GI) toxicity (RTOG scale), while secondary end-points included acute GI toxicity, acute and late genitourinary (GU) toxicity, biochemical control, and survival. Between 2006 and 2008, 80 patients were treated. No treatment interruptions occurred. The median follow-up is 33 months (range: 20-51). Maximal grade 1, 2, and 3 acute (< 3 months) GU toxicity was 29%, 31% and 5% respectively (no grade 4). Acute GI grade 1 toxicity was reported in 30% while grade 2 occurred in 14% (no grade 3 or 4). Crude late grade ≥ 3 toxicity rates at 31 months were 2% for both GU and GI toxicity. Cumulative late grade ≥ 3 GI toxicity at 3 years was 11%. Two patients had PSA failure according to the Phoenix definition. The three-year actuarial biochemical control rate is 97%. Weekly RT with 45 Gy in 9 fractions is feasible and results in comparable toxicity. Long term tumour control and survival remain to be assessed

  17. Discursive junctions in flood risk governance - A comparative understanding in six European countries.

    Science.gov (United States)

    Kaufmann, Maria; Wiering, Mark

    2017-07-01

    Flood risks are managed differently across Europe. While a number of research studies aim to understand these differences, they tend to pay little attention to the social constructionist aspects of flood risk governance, i.e. the meaning that societies give to flood risk and governance. This paper aims to address this gap by understanding differences in flood risk management approaches (FRMA) from a discursive-institutional perspective. Based on this perspective, an analytical framework was developed to systematically analyse and compare discourses pertaining to flood risk and its governance in six European member states (England (the United Kingdom), Flanders (Belgium), France, the Netherlands, Poland and Sweden). Correspondingly, this paper demonstrates how the hegemonic discursive-institutional patterns of flood risk governance differ between the six European countries. These differences may influence the capability of countries to learn from each other, adopt new FRMAs or cooperate with each other. Moreover, the paper argues that differences in discourses partially account for the differences in FRMAs between countries, combined with other factors. Additionally, broader implications are discussed. For example, the research findings imply that some discourses tend to favour or disfavour other discourses, and that they additionally also tend to favour particular FRMAs; e.g. the flood risk discourse pertaining to high manageability of risks seems to favour a governance discourse of collectivity and central governance. The different insights imply that further research is necessary to understand the complex interaction of discourses and institutional arrangements. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Pharmaceuticals and personal care products in waters: occurrence, toxicity, and risk.

    Science.gov (United States)

    Cizmas, Leslie; Sharma, Virender K; Gray, Cole M; McDonald, Thomas J

    2015-12-01

    Pharmaceuticals and personal care products (PPCP) are compounds with special physical and chemical properties that address the care of animal and human health. PPCP have been detected in surface water and wastewater in the ng/L to µg/L concentration range worldwide. PPCP ecotoxicity has been studied in a variety of organisms, and multiple methods have been used to assess the risk of PPCP in the environment to ecological health. Here we review the occurrence, effects, and risk assessment of PPCP in aquatic systems, as well as the sustainability of current methods for managing PPCP contamination in aquatic systems. The major points are the following: (1) a number of PPCP present potential concerns at environmentally relevant concentrations. PPCP mixtures may produce synergistic toxicity. (2) Various methods have been used for the ecological risk assessment of PPCP in aquatic systems. There are similarities in these methods, but no consensus has emerged regarding best practices for the ecological risk assessment of these compounds. (3) Human health risk assessments of PPCP contamination in aquatic systems have generally indicated little cause for concern. However, there is a lack of information regarding whether antibiotic contamination in wastewater and aquatic systems could lead to an increase in clinically relevant antibiotic-resistant bacteria and antibiotic-resistant genes. (4) Over the next century, the combination of increasing global population size and potential droughts may result in reduced water availability, increased need for water reuse, and increasing concentrations of PPCP in wastewaters. The current wastewater treatment methods do not remove all PPCP effectively. This, coupled with the possibility that antibiotics may promote the development of antibiotic-resistant bacteria and antibiotic-resistant genes, leads to concerns about the sustainability of global water supplies.

  19. Communicating global cardiovascular risk: are icon arrays better than numerical estimates in improving understanding, recall and perception of risk?

    Science.gov (United States)

    Ruiz, Jorge G; Andrade, Allen D; Garcia-Retamero, Rocio; Anam, Ramanakumar; Rodriguez, Remberto; Sharit, Joseph

    2013-12-01

    Experts recommend that adults have their global cardiovascular risk assessed. We investigated whether icon arrays increase understanding, recall, perception of CVR, and behavioral intent as compared with numerical information. Male outpatient veterans, at an intermediate to high cardiovascular risk participated in a randomized controlled trial of a computer tutorial presenting individualized risk. Message format was presented in 3 formats: percentages, frequencies, and frequencies with icon arrays. We assessed understanding immediately (T1) and recall at 20 min (T2) and 2 weeks (T3) after the intervention. We assessed perceptions of importance/seriousness, intent to adhere, and self-efficacy at T1. Self-reported adherence was assessed at T3. One-hundred and twenty male veterans participated. Age, education, race, health literacy and numeracy were comparable at baseline. There were no differences in understanding at T1 [p = .31] and recall at T3 [p = .10]. Accuracy was inferior with frequencies with icon arrays than percentages or frequencies at T2 [p ≤ .001]. There were no differences in perception of seriousness and importance for heart disease, behavioral intent, self-efficacy, actual adherence and satisfaction. Icon arrays may impair short-term recall of CVR. Icon arrays will not necessarily result in better understanding and recall of medical risk in all patients. Published by Elsevier Ireland Ltd.

  20. Mycophenolate fetal toxicity and risk evaluation and mitigation strategies.

    Science.gov (United States)

    Kim, M; Rostas, S; Gabardi, S

    2013-06-01

    The mycophenolic acid (MPA) preparations are one of the most commonly used immunosuppressants in the United States. However, these agents carry a black box warning regarding their use during pregnancy due to an association with increased risk of miscarriage and congenital defects. To ensure that the benefits of MPA outweigh the risks, the Food and Drug Administration (FDA) required all manufacturers of MPA products to propose risk evaluation and mitigation strategies (REMS). Four years after initially calling for proposals, the FDA approved a single shared REMS system in September 2012. The elements of the MPA REMS include a medication guide and elements to assure safe use (ETASU). The medication guide, which was previously FDA-approved in 2008, should continue to be distributed to patients, and the ETASU requires physicians to complete training and obtain patient signatures on the "Patient-Prescriber Acknowledgement Form." A single, national, voluntary pregnancy registry is available, and pregnant patients should be encouraged to participate. Although the impact of the MPA REMS on clinical practice is not clear, it is a step toward increasing the understanding of fetal risks with MPA products among patients and possibly practitioners. © Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.

  1. Understanding the nature of nuclear power plant risk

    International Nuclear Information System (INIS)

    Denning, R. S.

    2012-01-01

    This paper describes the evolution of understanding of severe accident consequences from the non-mechanistic assumptions of WASH-740 to WASH-1400, NUREG-1150, SOARCA and today in the interpretation of the consequences of the accident at Fukushima. As opposed to the general perception, the radiological human health consequences to members of the Japanese public from the Fukushima accident will be small despite meltdowns at three reactors and loss of containment integrity. In contrast, the radiation-related societal impacts present a substantial additional economic burden on top of the monumental task of economic recovery from the nonnuclear aspects of the earthquake and tsunami damage. The Fukushima accident provides additional evidence that we have mis-characterized the risk of nuclear power plant accidents to ourselves and to the public. The human health risks are extremely small even to people living next door to a nuclear power plant. The principal risk associated with a nuclear power plant accident involves societal impacts: relocation of people, loss of land use, loss of contaminated products, decontamination costs and the need for replacement power. Although two of the three probabilistic safety goals of the NRC address societal risk, the associated quantitative health objectives in reality only address individual human health risk. This paper describes the types of analysis that would address compliance with the societal goals. (authors)

  2. Improvement in toxicity in high risk prostate cancer patients treated with image-guided intensity-modulated radiotherapy compared to 3D conformal radiotherapy without daily image guidance

    International Nuclear Information System (INIS)

    Sveistrup, Joen; Rosenschöld, Per Munck af; Deasy, Joseph O; Oh, Jung Hun; Pommer, Tobias; Petersen, Peter Meidahl; Engelholm, Svend Aage

    2014-01-01

    Image-guided radiotherapy (IGRT) facilitates the delivery of a very precise radiation dose. In this study we compare the toxicity and biochemical progression-free survival between patients treated with daily image-guided intensity-modulated radiotherapy (IG-IMRT) and 3D conformal radiotherapy (3DCRT) without daily image guidance for high risk prostate cancer (PCa). A total of 503 high risk PCa patients treated with radiotherapy (RT) and endocrine treatment between 2000 and 2010 were retrospectively reviewed. 115 patients were treated with 3DCRT, and 388 patients were treated with IG-IMRT. 3DCRT patients were treated to 76 Gy and without daily image guidance and with 1–2 cm PTV margins. IG-IMRT patients were treated to 78 Gy based on daily image guidance of fiducial markers, and the PTV margins were 5–7 mm. Furthermore, the dose-volume constraints to both the rectum and bladder were changed with the introduction of IG-IMRT. The 2-year actuarial likelihood of developing grade > = 2 GI toxicity following RT was 57.3% in 3DCRT patients and 5.8% in IG-IMRT patients (p < 0.001). For GU toxicity the numbers were 41.8% and 29.7%, respectively (p = 0.011). On multivariate analysis, 3DCRT was associated with a significantly increased risk of developing grade > = 2 GI toxicity compared to IG-IMRT (p < 0.001, HR = 11.59 [CI: 6.67-20.14]). 3DCRT was also associated with an increased risk of developing GU toxicity compared to IG-IMRT. The 3-year actuarial biochemical progression-free survival probability was 86.0% for 3DCRT and 90.3% for IG-IMRT (p = 0.386). On multivariate analysis there was no difference in biochemical progression-free survival between 3DCRT and IG-IMRT. The difference in toxicity can be attributed to the combination of the IMRT technique with reduced dose to organs-at-risk, daily image guidance and margin reduction

  3. Overview of Provisional Peer-Reviewed Toxicity Values (PPRTVs), Alternative Methods in Human Health Risk Assessment, and the RapidTox Dashboard

    Science.gov (United States)

    This poster provides an overview of three key lines of ongoing work at EPA/ORD/NCEA-CIN: Provisional Peer-Reviewed Toxicity Values (PPRTVs), Alternative Methods in Human Health Risk Assessment, and the RapidTox Dashboard collaboration.

  4. Minimizing employee exposure to toxic chemical releases

    International Nuclear Information System (INIS)

    Plummer, R.W.; Stobbe, T.J.; Mogensen, J.E.; Jeram, L.K.

    1987-01-01

    This book describes procedures for minimizing employee exposure to toxic chemical releases and suggested personal protective equipment (PPE) to be used in the event of such chemical release. How individuals, employees, supervisors, or companies perceive the risks of chemical exposure (risk meaning both probability of exposure and effect of exposure) determines to a great extent what precautions are taken to avoid risk. In Part I, the authors develop and approach which divides the project into three phases: kinds of procedures currently being used; the types of toxic chemical release accidents and injuries that occur; and, finally, integration of this information into a set of recommended procedures which should decrease the likelihood of a toxic chemical release and, if one does occur, will minimize the exposure and its severity to employees. Part II covers the use of personal protective equipment. It addresses the questions: what personal protective equipment ensembles are used in industry in situations where the release of a toxic or dangerous chemical may occur or has occurred; and what personal protective equipment ensembles should be used in these situations

  5. Dose-dependent transitions in mechanisms of toxicity

    International Nuclear Information System (INIS)

    Slikker, William; Andersen, Melvin E.; Bogdanffy, Matthew S.; Bus, James S.; Cohen, Steven D.; Conolly, Rory B.; David, Raymond M.; Doerrer, Nancy G.; Dorman, David C.; Gaylor, David W.; Hattis, Dale; Rogers, John M.; Woodrow Setzer, R.; Swenberg, James A.; Wallace, Kendall

    2004-01-01

    Scientists and decision makers from all sectors agree that risk assessments should be based on the best available science. Several years ago, the Health and Environmental Sciences Institute (HESI), a global branch of the International Life Sciences Institute (ILSI), identified the need for better scientific understanding of dose-dependent transitions in mechanisms of toxicity as one avenue by which the best and latest science can be integrated into the decision making process. In July 2001, the HESI Project Committee on Dose-Dependent Transitions in Mechanisms of Toxicity established a group of academic, government, and industry scientists to engage in active technical discourse on the issue of dose-dependent transitions in mechanisms of toxicity. Over the next 18 months, case studies were examined. These case studies included acetaminophen, butadiene, ethylene glycol, formaldehyde, manganese, methylene chloride, the peroxisome proliferator-activated receptor, progesterone/hydroxyflutamide, propylene oxide, vinyl acetate, vinyl chloride, vinylidene chloride, and zinc (Slikker, W., Jr., Andersen, M.E., Bogdanffy, M.S., Bus, J.S., Cohen, S.D., Conolly, R.B., David, R.M., Doerrer, N.G., Dorman, D.C., Gaylor, D.W., Hattis, D., Rogers, J.M., Setzer, R.W., Swenberg, J.A., Wallace, K., 2004. Dose-dependent transitions in mechanisms of toxicity: case studies. Toxicol. Appl. Pharmacol. 201(3), 226-294 (this issue)). The HESI Project Committee sponsored two technical workshops in 2003. The first of these workshops took place on February 12-13, 2003, and was co-sponsored by the Agency for Toxic Substances and Disease Registry, the American Chemistry Council, the National Institute of Environmental Health Sciences, the Society of Toxicology, and the U.S. Environmental Protection Agency. Additional support was provided by Health Canada. Invited experts from government, academia, and industry provided scientific perspectives and recommendations at the workshop. The purpose of

  6. Spray Toxicity and Risk Potential of 42 Commonly Used Formulations of Row Crop Pesticides to Adult Honey Bees (Hymenoptera: Apidae).

    Science.gov (United States)

    Zhu, Yu Cheng; Adamczyk, John; Rinderer, Thomas; Yao, Jianxiu; Danka, Robert; Luttrell, Randall; Gore, Jeff

    2015-12-01

    To combat an increasing abundance of sucking insect pests, >40 pesticides are currently recommended and frequently used as foliar sprays on row crops, especially cotton. Foraging honey bees may be killed when they are directly exposed to foliar sprays, or they may take contaminated pollen back to hives that maybe toxic to other adult bees and larvae. To assess acute toxicity against the honey bee, we used a modified spray tower to simulate field spray conditions to include direct whole-body exposure, inhalation, and continuing tarsal contact and oral licking after a field spray. A total of 42 formulated pesticides, including one herbicide and one fungicide, were assayed for acute spray toxicity to 4-6-d-old workers. Results showed significantly variable toxicities among pesticides, with LC50s ranging from 25 to thousands of mg/liter. Further risk assessment using the field application concentration to LC1 or LC99 ratios revealed the risk potential of the 42 pesticides. Three pesticides killed less than 1% of the worker bees, including the herbicide, a miticide, and a neonicotinoid. Twenty-six insecticides killed more than 99% of the bees, including commonly used organophosphates and neonicotinoids. The remainder of the 13 chemicals killed from 1-99% of the bees at field application rates. This study reveals a realistic acute toxicity of 42 commonly used foliar pesticides. The information is valuable for guiding insecticide selection to minimize direct killing of foraging honey bees, while maintaining effective control of field crop pests. Published by Oxford University Press [on behalf of Entomological Society of America] 2015. This work is written by US Government employees and is in the public domain in the US.

  7. Toxic metals in cigarettes and human health risk assessment associated with inhalation exposure.

    Science.gov (United States)

    Benson, Nsikak U; Anake, Winifred U; Adedapo, Adebusayo E; Fred-Ahmadu, Omowunmi H; Ayejuyo, Olusegun O

    2017-11-08

    This study evaluated the concentrations of cadmium (Cd), copper (Cu), iron (Fe), manganese (Mn), lead (Pb), and zinc (Zn) in 10 branded cigarettes commonly consumed in Nigeria. Chemical sequential extraction method and pseudo-total metal digestion procedure were used for extraction of metals from filler tobacco and filter samples. Samples were analyzed using flame atomic absorption spectrometry (FAAS). The filler tobacco of cigarettes had Cd, Cu, Fe, Mn, Pb, and Zn concentrations in the ranges of 5.90-7.94, 18.26-34.94, 192.61-3494.05, 44.67-297.69, 17.21-74.78, and 47.02-167.31 μg/cigarette, respectively. The minimum and maximum concentrations in the filter samples were 8.67-12.34 μg/g of Cd, 1.77-36.48 μg/g of Cu, 1.83-15.27 μg/g of Fe, 3.82-7.44 μg/g of Mn, 4.09-13.78 μg/g of Pb, and 30.07-46.70 μg/g of Zn. The results of this study showed that the concentrations of heavy metals in the filler tobacco samples were consistently higher than those obtained for the cigarette filters except for Cd. Toxic metals were largely found in the most labile chemical fractions. Moderate to very high risks are found associated with potential exposure to Cd and Pb. The carcinogenic risks posed by Cd and Pb ranged between 1.87E-02 and 2.52E-02, 1.05E-03 and 4.76E-03, respectively, while the non-carcinogenic risk estimates for Cd and Pb were greater than 1.0 (HI > 1). Toxic metals in cigarette may have significant carcinogenic and non-carcinogenic health effects associated with inhalation exposure. Continuous monitoring and regulations of the ingredients of imported and locally produced tobacco products are advocated.

  8. Pictorial Health Warning Label Content and Smokers' Understanding of Smoking-Related Risks--A Cross-Country Comparison

    Science.gov (United States)

    Swayampakala, Kamala; Thrasher, James F.; Hammond, David; Yong, Hua-Hie; Bansal-Travers, Maansi; Krugman, Dean; Brown, Abraham; Borland, Ron; Hardin, James

    2015-01-01

    The aim of the present study was to assess smokers' level of agreement with smoking-related risks and toxic tobacco constituents relative to inclusion of these topics on health warning labels (HWLs). 1000 adult smokers were interviewed between 2012 and 2013 from online consumer panels of adult smokers from each of the three countries: Australia…

  9. Potential Occupational Risks Associated with Pulmonary Toxicity of Carbon Nanotubes.

    Science.gov (United States)

    Manke, Amruta; Luanpitpong, Sudjit; Rojanasakul, Yon

    Given their remarkable properties, carbon nanotubes (CNTs) have made their way through various industrial and medicinal applications and the overall production of CNTs is expected to grow rapidly in the next few years, thus requiring an additional recruitment of workers. However, their unique applications and desirable properties are fraught with concerns regarding occupational exposure. The concern about worker exposure to CNTs arises from the results of recent animal studies. Short-term and sub-chronic exposure studies in rodents have shown consistent adverse health effects such as pulmonary inflammation, granulomas, fibrosis, genotoxicity and mesothelioma after inhalation or instillation of several types of CNTs. Furthermore, physicochemical properties of CNTs such as dispersion, functionalization and particle size can significantly affect their pulmonary toxicity. Risk estimates from animal studies necessitate implementation of protective measures to limit worker exposure to CNTs. Information on workplace exposure is very limited, however, studies have reported that CNTs can be aerosolized and attain respirable airborne levels during synthesis and processing activities in the workplace. Quantitative risk assessments from sub-chronic animal studies recommend the health-based need to reduce exposures below the recommended exposure limit of 1 µg/m 3 . Practice of prevention measures including the use of engineering controls, personal protective equipment, health surveillance program, safe handling and use, as well as worker training can significantly minimize worker exposure and improve worker health and safety.

  10. Improvement of mutual understanding in risk communication by application of a debate support system

    International Nuclear Information System (INIS)

    Shimoda, Hiroshi; Matsuda, Koji; Ishii, Hirotake; Yoshikawa, Hidekazu

    2010-01-01

    Given the recent problem of climate change, nuclear power has become perhaps the world's most important energy source. In Japan, however, it is difficult to build new nuclear facilities. One of the reasons for such difficulty lies in problems in risk communication. In this study, a support method has been proposed to improve mutual understanding in risk communication. The authors paid especial attention at the learning effect of debating and the benefits of employing a debate support system. A laboratory experiment including 30 university students was conducted in order to evaluate the proposed method. Results showed that the use of the system could improve mutual understanding especially with respect to the factors of risk 'reduction measures' and 'accident management'. In addition, it was found that using the system and debating from 'opposite positions' could improve subjective mutual understanding; however, this practice showed no effectiveness in terms of improving objective mutual understanding. (author)

  11. Computational systems biology and dose-response modeling in relation to new directions in toxicity testing.

    Science.gov (United States)

    Zhang, Qiang; Bhattacharya, Sudin; Andersen, Melvin E; Conolly, Rory B

    2010-02-01

    The new paradigm envisioned for toxicity testing in the 21st century advocates shifting from the current animal-based testing process to a combination of in vitro cell-based studies, high-throughput techniques, and in silico modeling. A strategic component of the vision is the adoption of the systems biology approach to acquire, analyze, and interpret toxicity pathway data. As key toxicity pathways are identified and their wiring details elucidated using traditional and high-throughput techniques, there is a pressing need to understand their qualitative and quantitative behaviors in response to perturbation by both physiological signals and exogenous stressors. The complexity of these molecular networks makes the task of understanding cellular responses merely by human intuition challenging, if not impossible. This process can be aided by mathematical modeling and computer simulation of the networks and their dynamic behaviors. A number of theoretical frameworks were developed in the last century for understanding dynamical systems in science and engineering disciplines. These frameworks, which include metabolic control analysis, biochemical systems theory, nonlinear dynamics, and control theory, can greatly facilitate the process of organizing, analyzing, and understanding toxicity pathways. Such analysis will require a comprehensive examination of the dynamic properties of "network motifs"--the basic building blocks of molecular circuits. Network motifs like feedback and feedforward loops appear repeatedly in various molecular circuits across cell types and enable vital cellular functions like homeostasis, all-or-none response, memory, and biological rhythm. These functional motifs and associated qualitative and quantitative properties are the predominant source of nonlinearities observed in cellular dose response data. Complex response behaviors can arise from toxicity pathways built upon combinations of network motifs. While the field of computational cell

  12. Mechanisms of Phosphine Toxicity

    Directory of Open Access Journals (Sweden)

    Nisa S. Nath

    2011-01-01

    Full Text Available Fumigation with phosphine gas is by far the most widely used treatment for the protection of stored grain against insect pests. The development of high-level resistance in insects now threatens its continued use. As there is no suitable chemical to replace phosphine, it is essential to understand the mechanisms of phosphine toxicity to increase the effectiveness of resistance management. Because phosphine is such a simple molecule (PH3, the chemistry of phosphorus is central to its toxicity. The elements above and below phosphorus in the periodic table are nitrogen (N and arsenic (As, which also produce toxic hydrides, namely, NH3 and AsH3. The three hydrides cause related symptoms and similar changes to cellular and organismal physiology, including disruption of the sympathetic nervous system, suppressed energy metabolism and toxic changes to the redox state of the cell. We propose that these three effects are interdependent contributors to phosphine toxicity.

  13. Sarcopenic obesity: A probable risk factor for dose limiting toxicity during neo-adjuvant chemotherapy in oesophageal cancer patients.

    Science.gov (United States)

    Anandavadivelan, Poorna; Brismar, Torkel B; Nilsson, Magnus; Johar, Asif M; Martin, Lena

    2016-06-01

    Profound weight loss and malnutrition subsequent to severe dysphagia and cancer cachexia are cardinal symptoms in oesophageal cancer (OC). Low muscle mass/sarcopenia has been linked to toxicity during neo-adjuvant therapy in other cancers, with worser effects in sarcopenic obesity. In this study the association between sarcopenia and/or sarcopenic obesity and dose limiting toxicity (DLT) during cycle one chemotherapy in resectable OC patients was evaluated. Body composition was assessed from computed tomography scans of 72 consecutively diagnosed OC patients. Lean body mass and body fat mass were estimated. Patients were grouped as sarcopenic or non-sarcopenic based on pre-defined gender-specific cut-offs for sarcopenia, and as underweight/normal (BMI sarcopenia combined with overweight and obesity. DLT was defined as temporary reduction/delay or permanent discontinuation of drugs due to adverse effects. Odds ratios for developing toxicity were ascertained using multiple logistic regression. Of 72 patients, 85% (n = 61) were males. Sarcopenia and sarcopenic obesity were present in 31 (43%) and 10 (14%), respectively, prior to chemotherapy. Sarcopenic patients had significantly lower adipose tissue index (p = 0.02) compared to non-sarcopenic patients. Patients with DLT (n = 24) had lower skeletal muscle mass (p = 0.04) than those without DLT. Sarcopenic patients (OR = 2.47; 95% CI: 0.88-6.93) showed a trend towards increased DLT risk (p < 0.10). Logistic regression with BMI as an interaction term indicated higher DLT risk in sarcopenic patients with normal BMI (OR = 1.60; 95% CI 0.30-8.40), but was non-significant. In the sarcopenic obese, risk of DLT increased significantly (OR = 5.54; 95% CI 1.12-27.44). Sarcopenic and sarcopenic obese OC patients may be at a higher risk for developing DLT during chemotherapy compared to non-sarcopenic OC patients. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All

  14. Toxic releases from power plants

    International Nuclear Information System (INIS)

    Rubin, E.S.

    1999-01-01

    Beginning in 1998, electric power plants burning coal or oil must estimate and report their annual releases of toxic chemicals listed in the Toxics Release Inventory (TRI) published by the US Environmental Protection Agency (EPA). This paper identifies the toxic chemicals of greatest significance for the electric utility sector and develops quantitative estimates of the toxic releases reportable to the TRI for a representative coal-fired power plant. Key factors affecting the magnitude and types of toxic releases for individual power plants also are discussed. A national projection suggests that the magnitude of electric utility industry releases will surpass those of the manufacturing industries which current report to the TRI. Risk communication activities at the community level will be essential to interpret and provide context for the new TRI results

  15. Brand switching and toxic chemicals in cigarette smoke: A national study.

    Science.gov (United States)

    Mendel, Jennifer R; Baig, Sabeeh A; Hall, Marissa G; Jeong, Michelle; Byron, M Justin; Morgan, Jennifer C; Noar, Seth M; Ribisl, Kurt M; Brewer, Noel T

    2018-01-01

    US law requires disclosure of quantities of toxic chemicals (constituents) in cigarette smoke by brand and sub-brand. This information may drive smokers to switch to cigarettes with lower chemical quantities, under the misperception that doing so can reduce health risk. We sought to understand past brand-switching behavior and whether learning about specific chemicals in cigarette smoke increases susceptibility to brand switching. Participants were US adult smokers surveyed by phone (n = 1,151, probability sample) and online (n = 1,561, convenience sample). Surveys assessed whether smokers had ever switched cigarette brands or styles to reduce health risk and about likelihood of switching if the smoker learned their brand had more of a specific chemical than other cigarettes. Chemicals presented were nicotine, carbon monoxide, lead, formaldehyde, arsenic, and ammonia. Past brand switching to reduce health risk was common among smokers (43% in phone survey, 28% in online survey). Smokers who were female, over 25, and current "light" cigarette users were more likely to have switched brands to reduce health risks (all p brand switching based on information about particular chemicals. In both samples, lead, formaldehyde, arsenic, and ammonia led to more susceptibility to switch than nicotine (all p brands or styles to reduce health risks. The majority said they might or would definitely switch brands if they learned their cigarettes had more of a toxic chemical than other brands. Brand switching is a probable unintended consequence of communications that show differences in smoke chemicals between brands.

  16. Chemical warfare agent and biological toxin-induced pulmonary toxicity: could stem cells provide potential therapies?

    Science.gov (United States)

    Angelini, Daniel J; Dorsey, Russell M; Willis, Kristen L; Hong, Charles; Moyer, Robert A; Oyler, Jonathan; Jensen, Neil S; Salem, Harry

    2013-01-01

    Chemical warfare agents (CWAs) as well as biological toxins present a significant inhalation injury risk to both deployed warfighters and civilian targets of terrorist attacks. Inhalation of many CWAs and biological toxins can induce severe pulmonary toxicity leading to the development of acute lung injury (ALI) as well as acute respiratory distress syndrome (ARDS). The therapeutic options currently used to treat these conditions are very limited and mortality rates remain high. Recent evidence suggests that human stem cells may provide significant therapeutic options for ALI and ARDS in the near future. The threat posed by CWAs and biological toxins for both civilian populations and military personnel is growing, thus understanding the mechanisms of toxicity and potential therapies is critical. This review will outline the pulmonary toxic effects of some of the most common CWAs and biological toxins as well as the potential role of stem cells in treating these types of toxic lung injuries.

  17. Classification of baseline toxicants for QSAR predictions to replace fish acute toxicity studies.

    Science.gov (United States)

    Nendza, Monika; Müller, Martin; Wenzel, Andrea

    2017-03-22

    Fish acute toxicity studies are required for environmental hazard and risk assessment of chemicals by national and international legislations such as REACH, the regulations of plant protection products and biocidal products, or the GHS (globally harmonised system) for classification and labelling of chemicals. Alternative methods like QSARs (quantitative structure-activity relationships) can replace many ecotoxicity tests. However, complete substitution of in vivo animal tests by in silico methods may not be realistic. For the so-called baseline toxicants, it is possible to predict the fish acute toxicity with sufficient accuracy from log K ow and, hence, valid QSARs can replace in vivo testing. In contrast, excess toxicants and chemicals not reliably classified as baseline toxicants require further in silico, in vitro or in vivo assessments. Thus, the critical task is to discriminate between baseline and excess toxicants. For fish acute toxicity, we derived a scheme based on structural alerts and physicochemical property thresholds to classify chemicals as either baseline toxicants (=predictable by QSARs) or as potential excess toxicants (=not predictable by baseline QSARs). The step-wise approach identifies baseline toxicants (true negatives) in a precautionary way to avoid false negative predictions. Therefore, a certain fraction of false positives can be tolerated, i.e. baseline toxicants without specific effects that may be tested instead of predicted. Application of the classification scheme to a new heterogeneous dataset for diverse fish species results in 40% baseline toxicants, 24% excess toxicants and 36% compounds not classified. Thus, we can conclude that replacing about half of the fish acute toxicity tests by QSAR predictions is realistic to be achieved in the short-term. The long-term goals are classification criteria also for further groups of toxicants and to replace as many in vivo fish acute toxicity tests as possible with valid QSAR

  18. Improving ecological risk assessment of persistent, bioaccumulative, and toxic (PBT) chemicals by using an integrated modeling system - An example assessing chloroparaffins in riverine environments.

    Science.gov (United States)

    Chemical risk assessment (CRA) is primarily carried out at the screening level relying on empirical relationships between chemical properties and tested toxicity effects. Ultimately, risk to aquatic ecosystems is strongly dependent on actual exposure, which depends on chemical pr...

  19. Toward understanding the active SETI debate: Insights from risk communication and perception

    Science.gov (United States)

    Korbitz, Adam

    2014-12-01

    Insights from the robust field of risk communication and perception have to date been almost totally absent from the policy debate regarding the relative risks and merits of Active SETI or Messaging to Extraterrestrial Intelligence (METI). For many years, the practice (or proposed practice) of Active SETI has generated a vigorous and sometimes heated policy debate within the scientific community. There have also been some negative reactions in the media toward the activities of those engaged in Active SETI. Risk communication is a scientific approach to communication regarding situations involving potentially sensitive or controversial situations in which there may be high public concern and low public trust. The discipline has found wide acceptance and utility in fields such as public health, industrial regulation and environmental protection. Insights from the scientific field of risk communication (such as omission bias, loss aversion, the availability heuristic, probability neglect, and the general human preference for voluntary over involuntary risks) may help those who have participated in either side of the debate over Active SETI to better understand why the debate has taken on this posture. Principles of risk communication and risk perception may also help those engaged in Active SETI to communicate more effectively with other scientists, the public, with the media, and with policy makers regarding their activities and to better understand and respond to concerns expressed regarding the activity.

  20. The developmental toxicity of perfluoroalkyl acids and their derivatives

    International Nuclear Information System (INIS)

    Lau, Christopher; Butenhoff, John L.; Rogers, John M.

    2004-01-01

    Perfluoroalkyl acids such as perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) have applications in numerous industrial and consumer products. Although the toxicology of some of these compounds has been investigated in the past, the widespread prevalence of PFOS and PFOA in humans, as demonstrated in recent bio-monitoring studies, has drawn considerable interest from the public and regulatory agencies as well as renewed efforts to better understand the hazards that may be inherent in these compounds. This review provides a brief overview of the perfluoroalkyl chemicals and a summary of the available information on the developmental toxicity of the eight-carbon compounds, PFOS and PFOA. Although the teratological potentials of some of these chemicals had been studied in the past and the findings were generally unremarkable, results from recent postnatal studies on developmental and reproductive indices have prompted consideration of their relevance to human health risk. Based on current understanding of the developmental effects of PFOS and PFOA in rodents, several avenues of research are suggested that would further support the risk assessment of these perfluorinated organic chemicals

  1. Mixture toxicity of wood preservative products in the fish embryo toxicity test.

    Science.gov (United States)

    Coors, Anja; Dobrick, Jan; Möder, Monika; Kehrer, Anja

    2012-06-01

    Wood preservative products are used globally to protect wood from fungal decay and insects. We investigated the aquatic toxicity of five commercial wood preservative products, the biocidal active substances and some formulation additives contained therein, as well as six generic binary mixtures of the active substances in the fish embryo toxicity test (FET). Median lethal concentrations (LC50) of the single substances, the mixtures, and the products were estimated from concentration-response curves and corrected for concentrations measured in the test medium. The comparison of the experimentally observed mixture toxicity with the toxicity predicted by the concept of concentration addition (CA) showed less than twofold deviation for all binary mixtures of the active substances and for three of the biocidal products. A more than 60-fold underestimation of the toxicity of the fourth product by the CA prediction was detected and could be explained fully by the toxicity of one formulation additive, which had been labeled as a hazardous substance. The reason for the 4.6-fold underestimation of toxicity of the fifth product could not be explained unambiguously. Overall, the FET was found to be a suitable screening tool to verify whether the toxicity of formulated wood preservatives can reliably be predicted by CA. Applied as a quick and simple nonanimal screening test, the FET may support approaches of applying component-based mixture toxicity predictions within the environmental risk assessment of biocidal products, which is required according to European regulations. Copyright © 2012 SETAC.

  2. Understanding risk appetite : what is it, what pressures shape it and how is it institutionalized

    OpenAIRE

    Baunan, Håvard; Berge, Joel

    2016-01-01

    The purpose of this thesis is to understand the concept of risk appetite in terms of what it is, what institutional pressures influence it, and how it is institutionalized in an organization. We try to understand what risk appetite is by examining the most influential enterprise risk management frameworks, reports from practitioners, and scholarly research on the topic. Through a case study of a large and complex Norwegian organization, we seek to explain what influences and in...

  3. Use of Segregation Indices, Townsend Index, and Air Toxics Data to Assess Lifetime Cancer Risk Disparities in Metropolitan Charleston, South Carolina, USA

    Directory of Open Access Journals (Sweden)

    LaShanta J. Rice

    2014-05-01

    Full Text Available Background: Studies have demonstrated a relationship between segregation and level of education, occupational opportunities, and risk behaviors, yet a paucity of research has elucidated the association between racial residential segregation, socioeconomic deprivation, and lifetime cancer risk. Objectives: We examined estimated lifetime cancer risk from air toxics by racial composition, segregation, and deprivation in census tracts in Metropolitan Charleston. Methods: Segregation indices were used to measure the distribution of groups of people from different races within neighborhoods. The Townsend Index was used to measure economic deprivation in the study area. Poisson multivariate regressions were applied to assess the association of lifetime cancer risk with segregation indices and Townsend Index along with several sociodemographic measures. Results: Lifetime cancer risk from all pollution sources was 28 persons/million for half of the census tracts in Metropolitan Charleston. Isolation Index and Townsend Index both showed significant correlation with lifetime cancer risk from different sources. This significance still holds after adjusting for other sociodemographic measures in a Poisson regression, and these two indices have stronger effect on lifetime cancer risk compared to the effects of sociodemographic measures. Conclusions: We found that material deprivation, measured by the Townsend Index and segregation measured by the Isolation index, introduced high impact on lifetime cancer risk by air toxics at the census tract level.

  4. A comparative assessment of the acute inhalation toxicity of vanadium compounds.

    Science.gov (United States)

    Rajendran, N; Seagrave, J C; Plunkett, L M; MacGregor, J A

    2016-11-01

    Vanadium compounds have become important in industrial processes, resulting in workplace exposure potential and are present in ambient air as a result of fossil fuel combustion. A series of acute nose-only inhalation toxicity studies was conducted in both rats and mice in order to obtain comparative data on the acute toxicity potential of compounds used commercially. V 2 O 3 , V 2 O 4 , and V 2 O 5 , which have different oxidation states (+3, +4, +5, respectively), were delivered as micronized powders; the highly water-soluble and hygroscopic VOSO 4 (+4) could not be micronized and was instead delivered as a liquid aerosol from an aqueous solution. V 2 O 5 was the most acutely toxic micronized powder in both species. Despite its lower overall percentage vanadium content, a liquid aerosol of VOSO 4 was more toxic than the V 2 O 5 particles in mice, but not in rats. These data suggest that an interaction of characteristics, i.e., bioavailability, solubility and oxidation state, as well as species sensitivity, likely affect the toxicity potential of vanadium compounds. Based on clinical observations and gross necropsy findings, the lung appeared to be the target organ for all compounds. The level of hazard posed will depend on the specific chemical form of the vanadium. Future work to define the inhalation toxicity potential of vanadium compounds of various oxidation states after repeated exposures will be important in understanding how the physico-chemical and biological characteristics of specific vanadium compounds interact to affect toxicity potential and the potential risks posed to human health.

  5. Developmental toxicity of PAH mixtures in fish early life stages. Part II: adverse effects in Japanese medaka.

    Science.gov (United States)

    Le Bihanic, Florane; Clérandeau, Christelle; Le Menach, Karyn; Morin, Bénédicte; Budzinski, Hélène; Cousin, Xavier; Cachot, Jérôme

    2014-12-01

    In aquatic environments, polycyclic aromatic hydrocarbons (PAHs) mostly occur as complex mixtures, for which risk assessment remains problematic. To better understand the effects of PAH mixture toxicity on fish early life stages, this study compared the developmental toxicity of three PAH complex mixtures. These mixtures were extracted from a PAH-contaminated sediment (Seine estuary, France) and two oils (Arabian Light and Erika). For each fraction, artificial sediment was spiked at three different environmental concentrations roughly equivalent to 0.5, 4, and 10 μg total PAH g(-1) dw. Japanese medaka embryos were incubated on these PAH-spiked sediments throughout their development, right up until hatching. Several endpoints were recorded at different developmental stages, including acute endpoints, morphological abnormalities, larvae locomotion, and genotoxicity (comet and micronucleus assays). The three PAH fractions delayed hatching, induced developmental abnormalities, disrupted larvae swimming activity, and damaged DNA at environmental concentrations. Differences in toxicity levels, likely related to differences in PAH proportions, were highlighted between fractions. The Arabian Light and Erika petrogenic fractions, containing a high proportion of alkylated PAHs and low molecular weight PAHs, were more toxic to Japanese medaka early life stages than the pyrolytic fraction. This was not supported by the toxic equivalency approach, which appeared unsuitable for assessing the toxicity of the three PAH fractions to fish early life stages. This study highlights the potential risks posed by environmental mixtures of alkylated and low molecular weight PAHs to early stages of fish development.

  6. Lower tier toxicity risk assessment of agriculture pesticides detected on the Río Madre de Dios watershed, Costa Rica

    NARCIS (Netherlands)

    Arias-Andrés, M.; Rämö, R.; Mena Torres, F.; Ugalde, R.; Grandas, L.; Ruepert, C.; Castillo, L.E.; Den Brink, van P.J.; Gunnarsson, J.S.

    2016-01-01

    Costa Rica is a tropical country with one of the highest biodiversity on Earth. It also has an intensive agriculture, and pesticide runoff from banana and pineapple plantations may cause a high toxicity risk to non-target species in rivers downstream the plantations. We performed a first tier

  7. Petroleum Hydrocarbon Mixture Toxicity and a Trait Based Approach to Soil Invertebrate Species for Site Specific Risk Assessments.

    Science.gov (United States)

    Gainer, Amy; Cousins, Mark; Hogan, Natacha; Siciliano, Steven D

    2018-05-05

    Although petroleum hydrocarbons (PHCs) released to the environment typically occur as mixtures, PHC remediation guidelines often reflect individual substance toxicity. It is well documented that groups of aliphatic PHCs act via the same mechanism of action, nonpolar narcosis and, theoretically, concentration addition mixture toxicity principles apply. To assess this theory, ten standardized acute and chronic soil invertebrate toxicity tests on a range of organisms (Eisenia fetida, Lumbricus terrestris, Enchytraeus crypticus, Folsomia candida, Oppia nitens and Hypoaspis aculeifer) were conducted with a refined PHC binary mixture. Reference models for concentration addition and independent action were applied to the mixture toxicity data with consideration of synergism, antagonism and dose level toxicity. Both concentration addition and independent action, without further interactions, provided the best fit with observed response to the mixture. Individual fraction effective concentration values were predicted from optimized, fitted reference models. Concentration addition provided a better estimate than independent action of individual fraction effective concentrations based on comparison with available literature and species trends observed in toxic responses to the mixture. Interspecies differences in standardized laboratory soil invertebrate species responses to PHC contaminated soil was reflected in unique traits. Diets that included soil, large body size, permeable cuticle, low lipid content, lack of ability to molt and no maternal transfer were traits linked to a sensitive survival response to PHC contaminated soil in laboratory tests. Traits linked to sensitive reproduction response in organisms tested were long life spans with small clutch sizes. By deriving single fraction toxicity endpoints considerate of mixtures, we reduce resources and time required in conducting site specific risk assessments for the protection of soil organism's exposure pathway. This

  8. Genomics and the prediction of xenobiotic toxicity

    International Nuclear Information System (INIS)

    Meyer, Urs-A.; Gut, Josef

    2002-01-01

    The systematic identification and functional analysis of human genes is revolutionizing the study of disease processes and the development and rational use of drugs. It increasingly enables medicine to make reliable assessments of the individual risk to acquire a particular disease, raises the number and specificity of drug targets and explains interindividual variation of the effectiveness and toxicity of drugs. Mutant alleles at a single gene locus for more than 20 drug metabolizing enzymes are some of the best studied individual risk factors for adverse drug reactions and xenobiotic toxicity. Increasingly, genetic polymorphisms of transporter and receptor systems are also recognized as causing interindividual variation in drug response and drug toxicity. However, pharmacogenetic and toxicogenetic factors rarely act alone; they produce a phenotype in concert with other variant genes and with environmental factors. Environmental factors may affect gene expression in many ways. For instance, numerous drugs induce their own and the metabolism of other xenobiotics by interacting with nuclear receptors such as AhR, PPAR, PXR and CAR. Genomics is providing the information and technology to analyze these complex situations to obtain individual genotypic and gene expression information to assess the risk of toxicity

  9. Understanding gaps between the risk perceptions of wildland-urban interface (WUI) residents and wildfire professionals

    Science.gov (United States)

    James R. Meldrum; Patricia A. Champ; Hannah Brenkert-Smith; Travis Warziniack; Christopher M. Barth; Lilia C. Falk

    2015-01-01

    Research across a variety of risk domains finds that the risk perceptions of professionals and the public differ. Such risk perception gaps occur if professionals and the public understand individual risk factors differently or if they aggregate risk factors into overall risk differently. The nature of such divergences, whether based on objective inaccuracies or on...

  10. Future research needs associated with the assessment of potential human health risks from exposure to toxic ambient air pollutants

    DEFF Research Database (Denmark)

    Möller, Lennart; Schuetzle, Dennis; Autrup, Herman

    1994-01-01

    of identification and quantification of toxics in source emissions and ambient air, atmospheric transport and chemistry, exposure level assessment, the development of improved in vitro bioassays, biomarker development, the development of more accurate epidemiological methodologies, and risk quantification...... techniques. Studies are described that will be necessary to assess and reduce the level of uncertainties associated with each step of the risk assessment process. International collaborative research efforts between industry and government organizations are recommended as the most effective way to carry out...

  11. Risk of severe hematologic toxicities in cancer patients treated with PARP inhibitors: results of monotherapy and combination therapy trials

    Directory of Open Access Journals (Sweden)

    Alecu I

    2018-02-01

    Full Text Available Iulian Alecu, Tsveta Milenkova, Simon R Turner Research and Development, AstraZeneca UK Limited, Cambridge, UKThe tolerability profile of PARP inhibitors often includes hematologic toxicities, and the characterization of these adverse events is important to allow effective management by clinicians. Zhou et al1 recently carried out a meta-analysis of the incidence and relative risks of severe neutropenia, thrombocytopenia, and anemia events in 12 randomized controlled trials of PARP inhibitors, either as monotherapy or in combination with chemotherapy or radiotherapy. The authors concluded that olaparib resulted in a higher incidence of severe (common terminology criteria for adverse events [CTCAE] grade $3 neutropenia when compared with niraparib and veliparib; however, these conclusions are based on inappropriate and incomplete comparisons of hematologic toxicity with olaparib or veliparib in combination with myelotoxic chemotherapy versus niraparib monotherapy. While both monotherapy and combination therapy olaparib studies are discussed in the paper, the neutropenia analysis is based on olaparib data solely from studies in combination with paclitaxel or paclitaxel plus carboplatin. In order to inform the practicing clinician of the relative risk of hematologic toxicity associated with different PARP inhibitors, direct comparison needs to be conducted based on monotherapy, where applicable, as per the approved drug indication, otherwise the reader is given misleading information.View the original paper by Zhou et al.

  12. Assessing reproductive toxicity of two environmental toxicants with a novel in vitro human spermatogenic model

    Directory of Open Access Journals (Sweden)

    Charles A. Easley, IV

    2015-05-01

    Full Text Available Environmental influences and insults by reproductive toxicant exposure can lead to impaired spermatogenesis or infertility. Understanding how toxicants disrupt spermatogenesis is critical for determining how environmental factors contribute to impaired fertility. While current animal models are available, understanding of the reproductive toxic effects on human fertility requires a more robust model system. We recently demonstrated that human pluripotent stem cells can differentiate into spermatogonial stem cells/spermatogonia, primary and secondary spermatocytes, and haploid spermatids; a model that mimics many aspects of human spermatogenesis. Here, using this model system, we examine the effects of 2-bromopropane (2-BP and 1,2,dibromo-3-chloropropane (DBCP on in vitro human spermatogenesis. 2-BP and DBCP are non-endocrine disrupting toxicants that are known to impact male fertility. We show that acute treatment with either 2-BP or DBCP induces a reduction in germ cell viability through apoptosis. 2-BP and DBCP affect viability of different cell populations as 2-BP primarily reduces spermatocyte viability, whereas DBCP exerts a much greater effect on spermatogonia. Acute treatment with 2-BP or DBCP also reduces the percentage of haploid spermatids. Both 2-BP and DBCP induce reactive oxygen species (ROS formation leading to an oxidized cellular environment. Taken together, these results suggest that acute exposure with 2-BP or DBCP causes human germ cell death in vitro by inducing ROS formation. This system represents a unique platform for assessing human reproductive toxicity potential of various environmental toxicants in a rapid, efficient, and unbiased format.

  13. Toxic urban waste's assault on cardiovascular risk

    Directory of Open Access Journals (Sweden)

    M.L. De Rosa

    2015-03-01

    Full Text Available A cardiovascular health survey of 1203 persons in households located near the hazardous waste disposal sites and in a reference community, was conducted from 2009 until today to assess whether rates of adverse cardiovascular health outcomes were elevated among persons living near the sites. Data included medical records of reported cardiovascular disease certificates and hospital admission for cardiovascular diseases from hospital database. The study areas appeared similar with respect to mortality, cancer incidence, and pregnancy outcomes. In contrast, rate ratios were greater than 1.5 for 2 of 19 reported diseases, i.e., angina pectoris, and strokes. The apparent broad-based elevation in reported diseases and symptoms may reflect increased perception or recall of conditions by respondents living near the sites. Our study found that cardiovascular risk is associated only with PM2.5 concentrations, derived from uncontrolled burning of municipal solid waste in particular sites of our country. Their analysis demonstrated a relationship between increased levels of eventual fine particulate pollution and higher rates of death and complications from cardiovascular and cerebrovascular diseases. Management of solid waste releases a number of toxic substances, most in small quantities and at extremely low levels. Because of the wide range of pollutants, the different pathways of exposure, long-term low-level exposure, and the potential for synergism among the pollutants, concerns remain about potential health effects but there are many uncertainties involved in the assessment. Future community-based health studies should include medical and psychosocial assessment instruments sufficient to distinguish between changes in health status and effects of resident reporting tendency.

  14. Potential risks from UV/H2O2 oxidation and UV photocatalysis: A review of toxic, assimilable, and sensory-unpleasant transformation products.

    Science.gov (United States)

    Wang, Wen-Long; Wu, Qian-Yuan; Huang, Nan; Xu, Zi-Bin; Lee, Min-Yong; Hu, Hong-Ying

    2018-05-15

    UV based advanced oxidation processes (UV-AOPs) that efficiently eliminate organic pollutants during water treatment have been the subject of numerous investigations. Most organic pollutants are not completely mineralized during UV-AOPs but are partially oxidized into transformation products (TPs), thereby adding complexity to the treated water and posing risks to humans, ecological systems, and the environment. While the degradation kinetics and mechanisms of pollutants have been widely documented, there is little information about the risks associated with TPs. In this review, we have collated recent knowledge about the harmful TPs that are generated in UV/H 2 O 2 and UV photocatalysis, two UV-AOPs that have been studied extensively. Toxic and assimilable TPs were ubiquitously observed in more than 80% of UV-AOPs of organic pollutants, of which the toxicity and assimilability levels changed with variations in the reaction conditions, such as the UV fluence and oxidant dosage. Previous studies and modeling assessments showed that toxic and assimilable TPs may be generated during hydroxylation, dealkylation, decarboxylation, and deamination. Among various reactions, TPs generated from dealkylation and decarboxylation were generally less and more toxic than the parent pollutants, respectively; TPs generated from decarboxylation and deamination were generally less and more assimilable than the parent pollutants, respectively. There is also potential concern about the sensory-unpleasant TPs generated by oxidations and subsequent metabolism of microorganisms. In this overview, we stress the need to include both the concentrations of organic pollutants and the evaluations of the risks from TPs for the quality assessments of the water treated by UV-AOPs. Copyright © 2018 Elsevier Ltd. All rights reserved.

  15. Lung Deposition Analyses of Inhaled Toxic Aerosols in Conventional and Less Harmful Cigarette Smoke: A Review

    Directory of Open Access Journals (Sweden)

    Yu Feng

    2013-09-01

    Full Text Available Inhaled toxic aerosols of conventional cigarette smoke may impact not only the health of smokers, but also those exposed to second-stream smoke, especially children. Thus, less harmful cigarettes (LHCs, also called potential reduced exposure products (PREPs, or modified risk tobacco products (MRTP have been designed by tobacco manufacturers to focus on the reduction of the concentration of carcinogenic components and toxicants in tobacco. However, some studies have pointed out that the new cigarette products may be actually more harmful than the conventional ones due to variations in puffing or post-puffing behavior, different physical and chemical characteristics of inhaled toxic aerosols, and longer exposure conditions. In order to understand the toxicological impact of tobacco smoke, it is essential for scientists, engineers and manufacturers to develop experiments, clinical investigations, and predictive numerical models for tracking the intake and deposition of toxicants of both LHCs and conventional cigarettes. Furthermore, to link inhaled toxicants to lung and other diseases, it is necessary to determine the physical mechanisms and parameters that have significant impacts on droplet/vapor transport and deposition. Complex mechanisms include droplet coagulation, hygroscopic growth, condensation and evaporation, vapor formation and changes in composition. Of interest are also different puffing behavior, smoke inlet conditions, subject geometries, and mass transfer of deposited material into systemic regions. This review article is intended to serve as an overview of contributions mainly published between 2009 and 2013, focusing on the potential health risks of toxicants in cigarette smoke, progress made in different approaches of impact analyses for inhaled toxic aerosols, as well as challenges and future directions.

  16. Understanding environmental pollution: a primer. 2nd ed.

    Energy Technology Data Exchange (ETDEWEB)

    Marquita K. Hill [University of Maine, Orono, MN (United States)

    2004-08-15

    The book moves from the definition of pollution and how pollutants behave, to air and water pollution basics, pollution and global change, solid waste, and pollution in the home. It also discusses persistent and bioaccumulative chemicals, and pesticides, and it places greater stress on global pollutants. The relationship between energy generation and use, and pollution is stressed, as well as the importance of going beyond pollution control, to pollution prevention. Impacts on human and environmental health are emphasized throughout. Contents are: 1. Understanding pollution; 2. Reducing pollution; 3. Chemical toxicity; 4. Chemical exposures and risk assessment; 5. Ambient air pollution; 6. Acid deposition; 7. Global climate change; 8. Stratispheric ozone depletion; 9. Water pollution; 10. Drinking water; 11. Solid waste; 12. Hazardous waste; 13. Energy; 14. Persistent, bioaccumulative and toxic; 15. Metals; 16. Pesticides; 17. Pollution at home; and 18. Zero waste, zero emissions. 69 figs., 42 tabs.

  17. Improving toxicity assessment of pesticide mixtures: the use of polar passive sampling devices extracts in microalgae toxicity tests

    Directory of Open Access Journals (Sweden)

    Sandra KIM TIAM

    2016-09-01

    Full Text Available Complexity of contaminants exposure needs to be taking in account for an appropriate evaluation of risks related to mixtures of pesticides released in the ecosystems. Toxicity assessment of such mixtures can be made through a variety of toxicity tests reflecting different level of biological complexity. This paper reviews the recent developments of passive sampling techniques for polar compounds, especially Polar Organic Chemical Integrative Samplers (POCIS and Chemcatcher® and the principal assessment techniques using microalgae in laboratory experiments. The progresses permitted by the coupled use of such passive samplers and ecotoxicology testing as well as their limitations are presented. Case studies combining passive sampling devices (PSD extracts and toxicity assessment toward microorganisms at different biological scales from single organisms to communities level are presented. These case studies, respectively aimed i at characterizing the toxic potential of waters using dose-response curves, and ii at performing microcosm experiments with increased environmental realism in the toxicant exposure in term of cocktail composition and concentration. Finally perspectives and limitations of such approaches for future applications in the area of environmental risk assessment are discussed.

  18. Do oil dispersants make spilled oil more toxic to fish?

    International Nuclear Information System (INIS)

    Hodson, P.

    2010-01-01

    The Deepwater Horizon blowout in the Gulf of Mexico was the world's largest oil spill in terms of duration and volume spilled. Clean-up operations, which involved the continuous and wide-spread use of oil dispersant at the surface and at the seabed discharge point at 1500 metres depth, gave rise to public concern about dispersant toxicity. Reports from the United States Environmental Protection Agency (EPA) claimed little difference in acute toxicity to marine fish and invertebrate species among commonly available dispersants and between dispersed and non-dispersed Louisiana Sweet Crude. Technically, the toxicity of waterborne hydrocarbons does not vary with chemical dispersion. However, the EPA omitted any consideration of loading, and misled the public about the risks of dispersant use in oil clean-up. This study examined the chronic toxicity of dispersed oil to fish embryos. The study revealed that toxicity expressed as oil loading increases by a factor of 10 to 1000 times with dispersion, largely because 10 to 1000 times more oil enters the water column. Since the action of dispersant is on the exposure component of the risk equation, not on the potency of the toxic components of oil, then the risk of oil toxicity to fish increases an equivalent amount.

  19. Arsenic, lead, mercury and cadmium: Toxicity, levels in breast milk and the risks for breastfed infants

    International Nuclear Information System (INIS)

    Rebelo, Fernanda Maciel; Caldas, Eloisa Dutra

    2016-01-01

    Metals are ubiquitous in nature, being found in all environmental compartments, and have a variety of applications in human activities. Metals are transferred by maternal blood to the fetus via the placenta, and exposure continues throughout life. For the general population, exposure comes mainly from water and food consumption, including breast milk. In this paper, we reviewed studies on the toxicity of arsenic, lead, mercury and cadmium, the toxic metals of most concern to human health, focusing on the potential risks to newborns and infants. A total of 75 studies published since 2000 reporting the levels of these metals in breast milk were reviewed. Lead was the metal most investigated in breast milk (43 studies), and for which the highest levels were reported (up to 1515 µg/L). Arsenic was the least investigated (18 studies), with higher levels reported for breast milk (up to 149 µg/L) collected in regions with high arsenic concentrations in water (>10 µg/L). Data from 34 studies on mercury showed that levels in breast milk were generally higher in populations with high fish consumption, where it may be present mainly as MeHg. Cadmium levels in breast milk were the lowest, with means <2 µg/L in most of the 29 studies reviewed. Results of risk assessments indicated that the intake of arsenic, lead and mercury by infants through breastfeeding can be considered a health concern in most regions of the world. Although the potential risks to infants are mostly outweighed by the benefits of breast milk consumption, it is essential that contaminants be continuously monitored, especially in the most critical regions, and that measures be implemented by health authorities to reduce exposure of newborns and infants to these metals, and thus avoid unnecessary health risks. - Highlights: • Review of 75 studies that analyzed arsenic, lead, mercury and/or cadmium levels. • Higher levels of arsenic found in India; of mercury found in Brazil. • Lead was the most

  20. Arsenic, lead, mercury and cadmium: Toxicity, levels in breast milk and the risks for breastfed infants

    Energy Technology Data Exchange (ETDEWEB)

    Rebelo, Fernanda Maciel [Brazilian Health Surveillance Agency, University of Brasilia, 70910-900 Brasilia, DF (Brazil); Caldas, Eloisa Dutra, E-mail: eloisa@unb.br [Laboratory of Toxicology, Department of Pharmacy, University of Brasilia, 70910-900 Brasilia, DF (Brazil)

    2016-11-15

    Metals are ubiquitous in nature, being found in all environmental compartments, and have a variety of applications in human activities. Metals are transferred by maternal blood to the fetus via the placenta, and exposure continues throughout life. For the general population, exposure comes mainly from water and food consumption, including breast milk. In this paper, we reviewed studies on the toxicity of arsenic, lead, mercury and cadmium, the toxic metals of most concern to human health, focusing on the potential risks to newborns and infants. A total of 75 studies published since 2000 reporting the levels of these metals in breast milk were reviewed. Lead was the metal most investigated in breast milk (43 studies), and for which the highest levels were reported (up to 1515 µg/L). Arsenic was the least investigated (18 studies), with higher levels reported for breast milk (up to 149 µg/L) collected in regions with high arsenic concentrations in water (>10 µg/L). Data from 34 studies on mercury showed that levels in breast milk were generally higher in populations with high fish consumption, where it may be present mainly as MeHg. Cadmium levels in breast milk were the lowest, with means <2 µg/L in most of the 29 studies reviewed. Results of risk assessments indicated that the intake of arsenic, lead and mercury by infants through breastfeeding can be considered a health concern in most regions of the world. Although the potential risks to infants are mostly outweighed by the benefits of breast milk consumption, it is essential that contaminants be continuously monitored, especially in the most critical regions, and that measures be implemented by health authorities to reduce exposure of newborns and infants to these metals, and thus avoid unnecessary health risks. - Highlights: • Review of 75 studies that analyzed arsenic, lead, mercury and/or cadmium levels. • Higher levels of arsenic found in India; of mercury found in Brazil. • Lead was the most

  1. Alternative approaches for identifying acute systemic toxicity: Moving from research to regulatory testing.

    Science.gov (United States)

    Hamm, Jon; Sullivan, Kristie; Clippinger, Amy J; Strickland, Judy; Bell, Shannon; Bhhatarai, Barun; Blaauboer, Bas; Casey, Warren; Dorman, David; Forsby, Anna; Garcia-Reyero, Natàlia; Gehen, Sean; Graepel, Rabea; Hotchkiss, Jon; Lowit, Anna; Matheson, Joanna; Reaves, Elissa; Scarano, Louis; Sprankle, Catherine; Tunkel, Jay; Wilson, Dan; Xia, Menghang; Zhu, Hao; Allen, David

    2017-06-01

    Acute systemic toxicity testing provides the basis for hazard labeling and risk management of chemicals. A number of international efforts have been directed at identifying non-animal alternatives for in vivo acute systemic toxicity tests. A September 2015 workshop, Alternative Approaches for Identifying Acute Systemic Toxicity: Moving from Research to Regulatory Testing, reviewed the state-of-the-science of non-animal alternatives for this testing and explored ways to facilitate implementation of alternatives. Workshop attendees included representatives from international regulatory agencies, academia, nongovernmental organizations, and industry. Resources identified as necessary for meaningful progress in implementing alternatives included compiling and making available high-quality reference data, training on use and interpretation of in vitro and in silico approaches, and global harmonization of testing requirements. Attendees particularly noted the need to characterize variability in reference data to evaluate new approaches. They also noted the importance of understanding the mechanisms of acute toxicity, which could be facilitated by the development of adverse outcome pathways. Workshop breakout groups explored different approaches to reducing or replacing animal use for acute toxicity testing, with each group crafting a roadmap and strategy to accomplish near-term progress. The workshop steering committee has organized efforts to implement the recommendations of the workshop participants. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Esophageal Toxicity From High-Dose, Single-Fraction Paraspinal Stereotactic Radiosurgery

    International Nuclear Information System (INIS)

    Cox, Brett W.; Jackson, Andrew; Hunt, Margie; Bilsky, Mark; Yamada, Yoshiya

    2012-01-01

    Purpose: To report the esophageal toxicity from single-fraction paraspinal stereotactic radiosurgery (SRS) and identify dosimetric and clinical risk factors for toxicity. Methods and Materials: A total of 204 spinal metastases abutting the esophagus (182 patients) were treated with high-dose single-fraction SRS during 2003-2010. Toxicity was scored using the National Cancer Institute Common Toxicity Criteria for Adverse Events, version 4.0. Dose-volume histograms were combined to generate a comprehensive atlas of complication incidence that identifies risk factors for toxicity. Correlation of dose-volume factors with esophageal toxicity was assessed using Fisher’s exact test and logistic regression. Clinical factors were correlated with toxicity. Results: The median dose to the planning treatment volume was 24 Gy. Median follow-up was 12 months (range, 3-81). There were 31 (15%) acute and 24 (12%) late esophageal toxicities. The rate of grade ≥3 acute or late toxicity was 6.8% (14 patients). Fisher’s exact test resulted in significant median splits for grade ≥3 toxicity at V12 = 3.78 cm 3 (relative risk [RR] 3.7, P=.05), V15 = 1.87 cm 3 (RR 13, P=.0013), V20 = 0.11 cm 3 (RR 6, P=0.01), and V22 = 0.0 cm 3 (RR 13, P=.0013). The median split for D2.5 cm 3 (14.02 Gy) was also a significant predictor of toxicity (RR 6; P=.01). A highly significant logistic regression model was generated on the basis of D2.5 cm 3 . One hundred percent (n = 7) of grade ≥4 toxicities were associated with radiation recall reactions after doxorubicin or gemcitabine chemotherapy or iatrogenic manipulation of the irradiated esophagus. Conclusions: High-dose, single-fraction paraspinal SRS has a low rate of grade ≥3 esophageal toxicity. Severe esophageal toxicity is minimized with careful attention to esophageal doses during treatment planning. Iatrogenic manipulation of the irradiated esophagus and systemic agents classically associated with radiation recall reactions are

  3. Future research needs associated with the assessment of potential human health risks from exposure to toxic ambient air pollutants

    DEFF Research Database (Denmark)

    Möller, Lennart; Schuetzle, Dennis; Autrup, Herman

    1994-01-01

    of identification and quantification of toxics in source emissions and ambient air, atmospheric transport and chemistry, exposure level assessment, the development of improved in vitro bioassays, biomarker development, the development of more accurate epidemiological methodologies, and risk quantification......This paper presents key conclusions and future research needs from a Workshop on the Risk Assessment of Urban Air, Emissions, Exposure, Risk Identification, and Quantification, which was held in Stockholm during June 1992 by 41 participants from 13 countries. Research is recommended in the areas...... techniques. Studies are described that will be necessary to assess and reduce the level of uncertainties associated with each step of the risk assessment process. International collaborative research efforts between industry and government organizations are recommended as the most effective way to carry out...

  4. Exposure to toxicants in soil and bottom ash deposits in Agbogbloshie, Ghana: human health risk assessment.

    Science.gov (United States)

    Obiri, S; Ansa-Asare, O D; Mohammed, S; Darko, H F; Dartey, A G

    2016-10-01

    Recycling of e-waste using informal or crude techniques poses serious health risk not only to the workers but also to the environment as whole. It is against this background that this paper sought to measure health risk faced by informal e-waste workers from exposure to toxicants such as lead, cadmium, chromium, copper, arsenic, tin, zinc and cobalt via oral and dermal contact with bottom ash and soil. Using random sampling techniques, 3 separate sites each (where burning and manual dismantling of e-wastes are usually carried) were identified, and a total of 402 samples were collected. The samples were analysed using standard methods for chemical analysis prescribed by the American Water Works Association (AWWA). Concentrations of Pb, Cd, Cr, Cu, As, Sn, Zn and Co in bottom ash samples from location ASH1 are 5388 ± 0.02 mg/kg (Pb), 2.39 ± 0.01 mg/kg (Cd), 42 ± 0.05 mg/kg (Cr), 7940 ± 0.01 mg/kg (Cu), 20 ± 0.07 mg/kg (As), 225 ± 0.04 mg/kg (Sn), 276 ± 0.04 mg/kg (Zn) and 123 ± 0.04 mg/kg (Co), while concentrations of the aforementioned toxicants in soil samples at location ASG1 are as follows: 1685 ± 0.14 mg/kg (Pb), 26.89 ± 0.30 mg/kg (Cd), 36.86 ± 0.02 mg/kg (Cr), 1427 ± 0.08 mg/kg (Cu), 1622 ± 0.12 mg/kg (As), 234 ± 0.25 mg/kg (Sn), 783 ± 0.31 mg/kg (Zn) and 135 ± 0.01 mg/kg (Co); used as input parameters in assessing health risk faced by workers. The results of cancer health risk faced by e-waste workers due to accidental ingestion of As in bottom ash at ASH1 is 4.3 × 10 -3 (CTE) and 6.5 × 10 -2 (RME), i.e. approximately 4 out of 1000 e-waste workers are likely to suffer from cancer-related diseases via central tendency exposure (CTE parameters), and 7 out of every 100 e-waste worker is also likely to suffer from cancer cases by reasonable maximum exposure (RME) parameters, respectively. The cancer health risk results for the other sampling sites were found to have exceeded the acceptable

  5. Does Your Heart Forecast help practitioner understanding and confidence with cardiovascular disease risk communication?

    Science.gov (United States)

    Wells, Sue; Kerr, Andrew; Broadbent, Elizabeth; MacKenzie, Craig; Cole, Karl; McLachlan, Andy

    2011-03-01

    Explaining what cardiovascular disease (CVD) risk means and engaging in shared decision-making regarding risk factor modification is challenging. An electronic CVD risk visualisation tool containing multiple risk communication strategies (Your Heart Forecast) was designed in 2009. To assess whether this tool facilitated explaining CVD risk to primary care patients. Health professionals who accessed a Primary Health Organisation website or who attended educational peer groups over a three-month period were invited to complete questionnaires before and after viewing a four-minute video about the tool. Respondents were asked to make an informed guess of the CVD risk of a 35-year-old patient (actual CVD risk 5%) and rate the following sentence as being true or false: 'If there were 100 people like Mr Andrews, five would go on to have a cardiac event in the next five years.' They also were asked to rank their understanding of CVD risk and confidence in explaining the concept to patients. Fifty health professionals (37 GPs, 12 practice nurses, one other) completed before and after questionnaires. Respondents' CVD risk estimates pre-video ranged from confidence in explaining risk reduced in range and shifted towards greater efficacy. Whether this tool facilitates discussions of CVD risk with patients and improves patient understanding and lifestyle behaviour needs to be evaluated in a randomised trial.

  6. Enantioselective developmental toxicity and immunotoxicity of pyraclofos toward zebrafish (Danio rerio)

    Energy Technology Data Exchange (ETDEWEB)

    Zhuang, Shulin, E-mail: shulin@zju.edu.cn [Institute of Environmental Science, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058 (China); Zhejiang Provincial Key Laboratory of Organic Pollution Process and Control, Hangzhou 310058 (China); Zhang, Zhisheng [Institute of Environmental Science, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058 (China); Zhang, Wenjing; Bao, Lingling [Institute of Environmental Science, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058 (China); Zhejiang Provincial Key Laboratory of Organic Pollution Process and Control, Hangzhou 310058 (China); Xu, Chao, E-mail: chaoxu@zjut.edu.cn [Research Center of Environmental Science, College of Biological and Environmental Engineering, Zhejiang University of Technology, Hangzhou 310032 (China); Zhang, Hu [Institute of Quality and Standard for Agro-products, Zhejiang Academy of Agricultural Sciences, Hangzhou 210021 (China)

    2015-02-15

    Highlights: • Pyraclofos has significant enantioselective aquatic toxicities to zebrafish. • Pyraclofos induces time- and concentration-dependent developmental toxicity and immunotoxicity. • The mRNA level of IL-1β gene was significantly up-regulated by pyraclofos. • Pyraclofos binds potently to IL-1β, potentially affecting IL-1β-dependent proinflammatory signal transduction. • Our in vitro and in silico studies help to understand the molecular basis for aquatic toxicity of pyraclofos. - Abstract: Pyraclofos, a relatively new organophosphorus pesticide, has shown potential ecotoxicities, however, its aquatic toxicity, especially enantioselective aquatic toxicity, remains largely unknown. Using zebrafish (Danio rerio) as a preeminent vertebrate aquatic model, the enantioselective differences in the developmental toxicity and immunotoxicity of pyraclofos were evaluated. Following 96-h exposure, pyraclofos enantiomers exhibited acute toxicity and showed lethal concentration 50 of 2.23 and 3.99 mg/L for (R)-Pyraclofos and (S)-Pyraclofos, respectively. Exposure to pyraclofos caused time- and concentration-dependent malformations such as pericardial edema, yolk sac edema, crooked bodies and hatching during the embryonic development, with markedly higher percentages of malformation at higher concentrations. The concentration-dependent immunotoxicity to zebrafish embryo exposed to low level pyraclofos was induced with significant up-regulation of mRNA levels of immune-related interleukin-1β (IL-1β) gene. (R)-Pyraclofos was consistently more toxic than (S)-Pyraclofos for the acute toxicity, developmental toxicity and immunotoxicity to zebrafish. Molecular dynamics simulations revealed that at the atomic level, (R)-Pyraclofos binds more potently to IL-1β protein than (S)-Pyraclofos. This enantioselective binding is mainly contributed by the distinct binding mode of pyraclofos enantiomers and their electrostatic interactions with IL-1β, which potentially

  7. Enantioselective developmental toxicity and immunotoxicity of pyraclofos toward zebrafish (Danio rerio)

    International Nuclear Information System (INIS)

    Zhuang, Shulin; Zhang, Zhisheng; Zhang, Wenjing; Bao, Lingling; Xu, Chao; Zhang, Hu

    2015-01-01

    Highlights: • Pyraclofos has significant enantioselective aquatic toxicities to zebrafish. • Pyraclofos induces time- and concentration-dependent developmental toxicity and immunotoxicity. • The mRNA level of IL-1β gene was significantly up-regulated by pyraclofos. • Pyraclofos binds potently to IL-1β, potentially affecting IL-1β-dependent proinflammatory signal transduction. • Our in vitro and in silico studies help to understand the molecular basis for aquatic toxicity of pyraclofos. - Abstract: Pyraclofos, a relatively new organophosphorus pesticide, has shown potential ecotoxicities, however, its aquatic toxicity, especially enantioselective aquatic toxicity, remains largely unknown. Using zebrafish (Danio rerio) as a preeminent vertebrate aquatic model, the enantioselective differences in the developmental toxicity and immunotoxicity of pyraclofos were evaluated. Following 96-h exposure, pyraclofos enantiomers exhibited acute toxicity and showed lethal concentration 50 of 2.23 and 3.99 mg/L for (R)-Pyraclofos and (S)-Pyraclofos, respectively. Exposure to pyraclofos caused time- and concentration-dependent malformations such as pericardial edema, yolk sac edema, crooked bodies and hatching during the embryonic development, with markedly higher percentages of malformation at higher concentrations. The concentration-dependent immunotoxicity to zebrafish embryo exposed to low level pyraclofos was induced with significant up-regulation of mRNA levels of immune-related interleukin-1β (IL-1β) gene. (R)-Pyraclofos was consistently more toxic than (S)-Pyraclofos for the acute toxicity, developmental toxicity and immunotoxicity to zebrafish. Molecular dynamics simulations revealed that at the atomic level, (R)-Pyraclofos binds more potently to IL-1β protein than (S)-Pyraclofos. This enantioselective binding is mainly contributed by the distinct binding mode of pyraclofos enantiomers and their electrostatic interactions with IL-1β, which potentially

  8. Occurrence and risk assessment of potentially toxic elements and typical organic pollutants in contaminated rural soils.

    Science.gov (United States)

    Xu, Yongfeng; Dai, Shixiang; Meng, Ke; Wang, Yuting; Ren, Wenjie; Zhao, Ling; Christie, Peter; Teng, Ying

    2018-07-15

    The residual levels and risk assessment of several potentially toxic elements (PTEs), phthalate esters (PAEs) and polycyclic aromatic hydrocarbons (PAHs) in rural soils near different types of pollution sources in Tianjin, China, were studied. The soils were found to be polluted to different extents with PTEs, PAEs and PAHs from different pollution sources. The soil concentrations of chromium (Cr), nickel (Ni), di-n-butyl phthalate (DnBP), acenaphthylene (Any) and acenaphthene (Ane) were higher than their corresponding regulatory reference limits. The health risk assessment model used to calculate human exposure indicates that both non-carcinogenic and carcinogenic risks from selected pollutants were generally acceptable or close to acceptable. Different types of pollution sources and soil physicochemical properties substantially affected the soil residual concentrations of and risks from these pollutants. PTEs in soils collected from agricultural lands around industrial and residential areas and organic pollutants (PAEs and PAHs) in soils collected from agricultural areas around livestock breeding were higher than those from other types of pollution sources and merit long-term monitoring. Copyright © 2018 Elsevier B.V. All rights reserved.

  9. Experts’ understandings of drinking water risk management in a climate change scenario

    Directory of Open Access Journals (Sweden)

    Åsa Boholm

    2017-01-01

    Full Text Available The challenges for society presented by climate change are complex and demanding. This paper focuses on one particular resource of utmost necessity and vulnerability to climate change: namely, the provisioning of safe drinking water. From a critical perspective on the role of expertise in risk debates, this paper looks at how Swedish experts understand risk to drinking water in a climate change scenario and how they reason about challenges to risk management and adaptation strategies. The empirical material derives from ten in-depth semi-structured interviews with experts, employed both at government agencies and at universities, and with disciplinary backgrounds in a variety of fields (water engineering, planning, geology and environmental chemistry. The experts understand risk factors affecting both drinking water quality and availability as complex and systemically interrelated. A lack of political saliency of drinking water as a public service is identified as an obstacle to the development of robust adaptation strategies. Another area of concern relates to the geographical, organizational and institutional boundaries (regulatory, political and epistemological between the plethora of public actors with partly overlapping and sometimes unclear responsibilities for the provisioning of safe drinking water. The study concludes that climate change adaptation regarding drinking water provisioning will require a new integration of the knowledge of systemic risk relations, in combination with more efficient agency collaboration based on a clear demarcation of responsibility between actors.

  10. 2011 NATA - Air Toxics Monitors

    Data.gov (United States)

    U.S. Environmental Protection Agency — This dataset includes annual (2005 - 2013) statistics of measured ambient air toxics concentrations (in micrograms per cubic meter) and associated risk estimates for...

  11. Acute Toxicity and Ecological Risk Assessment of Benzophenone and N,N-Diethyl-3 Methylbenzamide in Personal Care Products

    Directory of Open Access Journals (Sweden)

    Hong-Qin Sun

    2016-09-01

    Full Text Available Benzophenone (BP and N,N-diethyl-3-methylbenzamide (DEET are two chemicals often used in personal care products (PCPs. There is a lack of systematic ecotoxicological evaluations about the two chemicals to aquatic organisms. In the present study, the acute toxic effects on Chlorella vulgaris, Daphnia Magana, and Brachydanio rerio were tested and the ecotoxicological risks were evaluated. For BP, the 96-h half-maximal effective concentration (EC50 on C. vulgaris was 6.86 mg/L; the 24-h median lethal concentration (LC50 on D. magana was 7.63 mg/L; the 96-h LC50 on B. rerio was 14.73 mg/L. For DEET, those were 270.72 mg/L, 40.74 mg/L, and 109.67 mg/L, respectively. The mixture toxicity of BP and DEET, on C. vulgaris, D. magana, and B. rerio all showed an additive effect. The induced predicted no-effect concentrations (PNECs for BP and DEET by assessment factor (AF method are 0.003 mg/L and 0.407 mg/L, respectively. Both are lower than the concentrations detected from environment at present, verifying that BP and DEET are low-risk chemicals to the environment.

  12. Discrimination of uranium chemo-toxic and radio-toxic effects: definition of biological markers for evaluating professional risks in nuclear industry

    International Nuclear Information System (INIS)

    Darolles, Carine

    2010-01-01

    Uranium (U) is a heavy metal that is also considered as an alpha emitter. Thus the origin of U toxicity is both chemical and radiological. The identification of bio-markers to discriminate chemical and radiological toxicity for a given U compound is required to assess accurately the health effects of isotopic mixtures such as depleted U in 235 U with a low specific activity. Data from the literature show that the best candidates are cytogenetic markers. In the present work, the assessment of bio-markers of U contamination was performed on three cellular models (mouse fibroblasts, rat lymphocytes and human lymphocytes) that were exposed to different isotopic mixtures of U. The cytokinesis-block micronucleus (MN) centromere assay was performed to discriminate the chemo-toxic and radio-toxic effects of U. This study showed that the evaluation of micronuclei in bi-nucleated cells could not assess U genotoxicity accurately. Instead, the assessment of centromere-negative micronuclei and nucleo-plasmic bridges correlated with the radio-toxic effects of U. The evaluation of centromere-positive micronuclei and micronuclei in mono-nucleated cells correlated with the chemo-toxic effects of U. These cytogenetic markers should be validated on different biological models and could be proposed to discriminate radiological and chemical toxicity of a given isotopic mixture of U. These four cytogenetic markers could be a useful complement of the classical dosimetric bio-markers for the assessment of internal uranium contamination. (author)

  13. Environmentally induced epigenetic toxicity: potential public health concerns.

    Science.gov (United States)

    Marczylo, Emma L; Jacobs, Miriam N; Gant, Timothy W

    2016-09-01

    Throughout our lives, epigenetic processes shape our development and enable us to adapt to a constantly changing environment. Identifying and understanding environmentally induced epigenetic change(s) that may lead to adverse outcomes is vital for protecting public health. This review, therefore, examines the present understanding of epigenetic mechanisms involved in the mammalian life cycle, evaluates the current evidence for environmentally induced epigenetic toxicity in human cohorts and rodent models and highlights the research considerations and implications of this emerging knowledge for public health and regulatory toxicology. Many hundreds of studies have investigated such toxicity, yet relatively few have demonstrated a mechanistic association among specific environmental exposures, epigenetic changes and adverse health outcomes in human epidemiological cohorts and/or rodent models. While this small body of evidence is largely composed of exploratory in vivo high-dose range studies, it does set a precedent for the existence of environmentally induced epigenetic toxicity. Consequently, there is worldwide recognition of this phenomenon, and discussion on how to both guide further scientific research towards a greater mechanistic understanding of environmentally induced epigenetic toxicity in humans, and translate relevant research outcomes into appropriate regulatory policies for effective public health protection.

  14. Marine pollution in the Libyan coastal area: Environmental and risk assessment.

    Science.gov (United States)

    Bonsignore, Maria; Salvagio Manta, Daniela; Al-Tayeb Sharif, Ehab A; D'Agostino, Fabio; Traina, Anna; Quinci, Enza Maria; Giaramita, Luigi; Monastero, Calogera; Benothman, Mohamed; Sprovieri, Mario

    2018-03-01

    A comprehensive assessment of the potential adverse effects on environment and human health generated by the inputs of chemicals from the most important Libyan petrochemical plant is presented. Ecotoxicological risk associated with the presence of As, Hg, Ni, Zn and PAHs in marine sediments is low or moderate, with a probability of toxicity for ecosystem <9% and <20% for heavy metals and PAHs respectively. However, surface sediments result strongly enriched in Hg and As of anthropogenic origin. Investigation of metals in fish allowed to assess potential risks for human populations via fish intake. Target hazard quotients values indicate potential risk associated to toxic metals exposure by fish consumption and lifetime cancer risk (TR) values highlight a potential carcinogen risk associated to As intake. Noteworthy, the presented results provide an unprecedented environmental dataset in an area where the availability of field data is very scant, for a better understanding of anthropogenic impacts at Mediterranean scale. Copyright © 2018 Elsevier Ltd. All rights reserved.

  15. Improvement in toxicity in high risk prostate cancer patients treated with image-guided intensity-modulated radiotherapy compared to 3D conformal radiotherapy without daily image guidance.

    Science.gov (United States)

    Sveistrup, Joen; af Rosenschöld, Per Munck; Deasy, Joseph O; Oh, Jung Hun; Pommer, Tobias; Petersen, Peter Meidahl; Engelholm, Svend Aage

    2014-02-04

    Image-guided radiotherapy (IGRT) facilitates the delivery of a very precise radiation dose. In this study we compare the toxicity and biochemical progression-free survival between patients treated with daily image-guided intensity-modulated radiotherapy (IG-IMRT) and 3D conformal radiotherapy (3DCRT) without daily image guidance for high risk prostate cancer (PCa). A total of 503 high risk PCa patients treated with radiotherapy (RT) and endocrine treatment between 2000 and 2010 were retrospectively reviewed. 115 patients were treated with 3DCRT, and 388 patients were treated with IG-IMRT. 3DCRT patients were treated to 76 Gy and without daily image guidance and with 1-2 cm PTV margins. IG-IMRT patients were treated to 78 Gy based on daily image guidance of fiducial markers, and the PTV margins were 5-7 mm. Furthermore, the dose-volume constraints to both the rectum and bladder were changed with the introduction of IG-IMRT. The 2-year actuarial likelihood of developing grade > = 2 GI toxicity following RT was 57.3% in 3DCRT patients and 5.8% in IG-IMRT patients (p analysis, 3DCRT was associated with a significantly increased risk of developing grade > = 2 GI toxicity compared to IG-IMRT (p analysis there was no difference in biochemical progression-free survival between 3DCRT and IG-IMRT. The difference in toxicity can be attributed to the combination of the IMRT technique with reduced dose to organs-at-risk, daily image guidance and margin reduction.

  16. Acute aquatic toxicity of tire and road wear particles to alga, daphnid, and fish.

    Science.gov (United States)

    Marwood, Christopher; McAtee, Britt; Kreider, Marisa; Ogle, R Scott; Finley, Brent; Sweet, Len; Panko, Julie

    2011-11-01

    Previous studies have indicated that tire tread particles are toxic to aquatic species, but few studies have evaluated the toxicity of such particles using sediment, the likely reservoir of tire wear particles in the environment. In this study, the acute toxicity of tire and road wear particles (TRWP) was assessed in Pseudokirchneriella subcapita, Daphnia magna, and Pimephales promelas using a sediment elutriate (100, 500, 1000 or 10000 mg/l TRWP). Under standard test temperature conditions, no concentration response was observed and EC/LC(50) values were greater than 10,000 mg/l. Additional tests using D. magna were performed both with and without sediment in elutriates collected under heated conditions designed to promote the release of chemicals from the rubber matrix to understand what environmental factors may influence the toxicity of TRWP. Toxicity was only observed for elutriates generated from TRWP leached under high-temperature conditions and the lowest EC/LC(50) value was 5,000 mg/l. In an effort to identify potential toxic chemical constituent(s) in the heated leachates, toxicity identification evaluation (TIE) studies and chemical analysis of the leachate were conducted. The TIE coupled with chemical analysis (liquid chromatography/mass spectrometry/mass spectrometry [LC/MS/MS] and inductively coupled plasma/mass spectrometry [ICP/MS]) of the leachate identified zinc and aniline as candidate toxicants. However, based on the high EC/LC(50) values and the limited conditions under which toxicity was observed, TRWP should be considered a low risk to aquatic ecosystems under acute exposure scenarios.

  17. Toxicity after intensity-modulated, image-guided radiotherapy for prostate cancer

    International Nuclear Information System (INIS)

    Flentje, Michael; Guckenberger, Matthias; Ok, Sami; Polat, Buelent; Sweeney, Reinhart A.

    2010-01-01

    Purpose: To evaluate toxicity after dose-escalated radiotherapy for prostate cancer using intensity-modulated treatment planning (IMRT) and image-guided treatment (IGRT) delivery. Patients and Methods: 100 patients were treated with simultaneous integrated boost (SIB) IMRT for prostate cancer: doses of 76.23 Gy and 60 Gy in 33 fractions were prescribed to the prostate and the seminal vesicles, respectively, for intermediate- and high-risk patients (n = 74). The total dose was 73.91 Gy in 32 fractions for low-risk patients and after transurethral resection of the prostate (n = 26). The pelvic lymphatics were treated with 46 Gy in 25 fractions in patients with high risk of lymph node metastases using an SIB to the prostate (n = 25). IGRT was practiced with cone-beam computed tomography. Acute and late gastrointestinal (GI) and genitourinary (GU) toxicity was evaluated prospectively (CTCAE v3.0). Results: Treatment was completed as planned by all patients. Acute GI and GU toxicity grade ≥ 2 was observed in 12% and 42% of the patients, respectively, with 4% suffering from GU toxicity grade 3. 6 weeks after treatment, the incidence of acute toxicity grade ≥ 2 had decreased to 12%. With a median follow-up of 26 months, late GI and GU toxicity grade ≥ 2 was seen in 1.5% and 7.7% of the patients at 24 months. Four patients developed late toxicity grade 3 (GI n = 1; GU n = 3). Presence of acute GI and GU toxicity was significantly associated with late GI (p = 0.0007) and GU toxicity (p = 0.006). Conclusion: High-dose radiotherapy for prostate cancer using IMRT and IGRT resulted in low rates of acute toxicity and preliminary results of late toxicity are promising. (orig.)

  18. Toxicity after intensity-modulated, image-guided radiotherapy for prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Flentje, Michael [Dept. of Radiotherapy, Univ. Hospital Wuerzburg (Germany); Guckenberger, Matthias; Ok, Sami; Polat, Buelent; Sweeney, Reinhart A.

    2010-10-15

    Purpose: To evaluate toxicity after dose-escalated radiotherapy for prostate cancer using intensity-modulated treatment planning (IMRT) and image-guided treatment (IGRT) delivery. Patients and Methods: 100 patients were treated with simultaneous integrated boost (SIB) IMRT for prostate cancer: doses of 76.23 Gy and 60 Gy in 33 fractions were prescribed to the prostate and the seminal vesicles, respectively, for intermediate- and high-risk patients (n = 74). The total dose was 73.91 Gy in 32 fractions for low-risk patients and after transurethral resection of the prostate (n = 26). The pelvic lymphatics were treated with 46 Gy in 25 fractions in patients with high risk of lymph node metastases using an SIB to the prostate (n = 25). IGRT was practiced with cone-beam computed tomography. Acute and late gastrointestinal (GI) and genitourinary (GU) toxicity was evaluated prospectively (CTCAE v3.0). Results: Treatment was completed as planned by all patients. Acute GI and GU toxicity grade {>=} 2 was observed in 12% and 42% of the patients, respectively, with 4% suffering from GU toxicity grade 3. 6 weeks after treatment, the incidence of acute toxicity grade {>=} 2 had decreased to 12%. With a median follow-up of 26 months, late GI and GU toxicity grade {>=} 2 was seen in 1.5% and 7.7% of the patients at 24 months. Four patients developed late toxicity grade 3 (GI n = 1; GU n = 3). Presence of acute GI and GU toxicity was significantly associated with late GI (p = 0.0007) and GU toxicity (p = 0.006). Conclusion: High-dose radiotherapy for prostate cancer using IMRT and IGRT resulted in low rates of acute toxicity and preliminary results of late toxicity are promising. (orig.)

  19. Air toxics regulatory issues facing urban settings

    Energy Technology Data Exchange (ETDEWEB)

    Olden, K.; Guthrie, J. [National Institute of Environmental Health Sciences, Research Triangle Park, NC (United States)

    1996-10-01

    Biomarker research does not exist in isolation. Its usefulness can only be realized when it is translated into prevention strategies to protect public health. In the context of air toxics, these prevention strategies begin with the development of regulatory standards derived from risk assessment schemes. The Clean Air Act Amendments of 1990 list 189 air toxics, including many volatile organics, metals, and pesticides. The National Institute of Environmental Health Sciences (NIEHS), through its affiliation with the National Toxicology Program, has generated toxicity and carcinogenicity data on more than 100 of these air toxics. The NIEHS extramural and intramural research portfolios support a variety of projects that develop and validate biomarkers for use in environmental health science and risk assessment. Biomarkers have a tremendous potential in the areas of regulating air toxics and protecting public health. Risk assessors need data provided by biomarkers of exposure, biomarkers of close/pharmacokinetics, biomarkers of susceptibility or individual variability, and biomarkers of effects. The greatest benefit would be realized if biomarkers could be employed in four areas of primary and secondary prevention. The first is the use of biomarkers to enhance extrapolation of animal data to human exposure situations in establishing risk standards. The second is the use of biomarkers that assess noncancer, as well as cancer, end points. Important health end points include pulmonary dysfunction, immunotoxicity, and neurotoxicity. Third, biomarkers that serve as early warning signs to detect intermediate effects would enhance our ability to design timely and cost-effective intervention strategies. Finally, biomarkers used to evaluate the effectiveness of intervention strategies both in clinical and regulatory settings, would enable us to ensure that programs designed to protect public health do, in fact, achieve the desired outcome. 9 refs., 2 tabs.

  20. Development of QSAR models using artificial neural network analysis for risk assessment of repeated-dose, reproductive, and developmental toxicities of cosmetic ingredients.

    Science.gov (United States)

    Hisaki, Tomoka; Aiba Née Kaneko, Maki; Yamaguchi, Masahiko; Sasa, Hitoshi; Kouzuki, Hirokazu

    2015-04-01

    Use of laboratory animals for systemic toxicity testing is subject to strong ethical and regulatory constraints, but few alternatives are yet available. One possible approach to predict systemic toxicity of chemicals in the absence of experimental data is quantitative structure-activity relationship (QSAR) analysis. Here, we present QSAR models for prediction of maximum "no observed effect level" (NOEL) for repeated-dose, developmental and reproductive toxicities. NOEL values of 421 chemicals for repeated-dose toxicity, 315 for reproductive toxicity, and 156 for developmental toxicity were collected from Japan Existing Chemical Data Base (JECDB). Descriptors to predict toxicity were selected based on molecular orbital (MO) calculations, and QSAR models employing multiple independent descriptors as the input layer of an artificial neural network (ANN) were constructed to predict NOEL values. Robustness of the models was indicated by the root-mean-square (RMS) errors after 10-fold cross-validation (0.529 for repeated-dose, 0.508 for reproductive, and 0.558 for developmental toxicity). Evaluation of the models in terms of the percentages of predicted NOELs falling within factors of 2, 5 and 10 of the in-vivo-determined NOELs suggested that the model is applicable to both general chemicals and the subset of chemicals listed in International Nomenclature of Cosmetic Ingredients (INCI). Our results indicate that ANN models using in silico parameters have useful predictive performance, and should contribute to integrated risk assessment of systemic toxicity using a weight-of-evidence approach. Availability of predicted NOELs will allow calculation of the margin of safety, as recommended by the Scientific Committee on Consumer Safety (SCCS).

  1. Toxic Mixtures in Time-The Sequence Makes the Poison.

    Science.gov (United States)

    Ashauer, Roman; O'Connor, Isabel; Escher, Beate I

    2017-03-07

    "The dose makes the poison". This principle assumes that once a chemical is cleared out of the organism (toxicokinetic recovery), it no longer has any effect. However, it overlooks the other process of re-establishing homeostasis, toxicodynamic recovery, which can be fast or slow depending on the chemical. Therefore, when organisms are exposed to two toxicants in sequence, the toxicity can differ if their order is reversed. We test this hypothesis with the freshwater crustacean Gammarus pulex and four toxicants that act on different targets (diazinon, propiconazole, 4,6-dinitro-o-cresol, 4-nitrobenzyl chloride). We found clearly different toxicity when the exposure order of two toxicants was reversed, while maintaining the same dose. Slow toxicodynamic recovery caused carry-over toxicity in subsequent exposures, thereby resulting in a sequence effect-but only when toxicodynamic recovery was slow relative to the interval between exposures. This suggests that carry-over toxicity is a useful proxy for organism fitness and that risk assessment methods should be revised as they currently could underestimate risk. We provide the first evidence that carry-over toxicity occurs among chemicals acting on different targets and when exposure is several days apart. It is therefore not only the dose that makes the poison but also the exposure sequence.

  2. Nomogram to predict rectal toxicity following prostate cancer radiotherapy.

    Directory of Open Access Journals (Sweden)

    Jean-Bernard Delobel

    Full Text Available To identify predictors of acute and late rectal toxicity following prostate cancer radiotherapy (RT, while integrating the potential impact of RT technique, dose escalation, and moderate hypofractionation, thus enabling us to generate a nomogram for individual prediction.In total, 972 patients underwent RT for localized prostate cancer, to a total dose of 70 Gy or 80 Gy, using two different fractionations (2 Gy or 2.5 Gy/day, by means of several RT techniques (3D conformal RT [3DCRT], intensity-modulated RT [IMRT], or image-guided RT [IGRT]. Multivariate analyses were performed to identify predictors of acute and late rectal toxicity. A nomogram was generated based on the logistic regression model used to predict the 3-year rectal toxicity risk, with its accuracy assessed by dividing the cohort into training and validation subgroups.Mean follow-up for the entire cohort was 62 months, ranging from 6 to 235. The rate of acute Grade ≥2 rectal toxicity was 22.2%, decreasing when combining IMRT and IGRT, compared to 3DCRT (RR = 0.4, 95%CI: 0.3-0.6, p<0.01. The 5-year Grade ≥2 risks for rectal bleeding, urgency/tenesmus, diarrhea, and fecal incontinence were 9.9%, 4.5%, 2.8%, and 0.4%, respectively. The 3-year Grade ≥2 risk for overall rectal toxicity increased with total dose (p<0.01, RR = 1.1, 95%CI: 1.0-1.1 and dose per fraction (2Gy vs. 2.5Gy (p = 0.03, RR = 3.3, 95%CI: 1.1-10.0, and decreased when combining IMRT and IGRT (RR = 0.50, 95% CI: 0.3-0.8, p<0.01. Based on these three parameters, a nomogram was generated.Dose escalation and moderate hypofractionation increase late rectal toxicity. IMRT combined with IGRT markedly decreases acute and late rectal toxicity. Performing combined IMRT and IGRT can thus be envisaged for dose escalation and moderate hypofractionation. Our nomogram predicts the 3-year rectal toxicity risk by integrating total dose, fraction dose, and RT technique.

  3. A framework for understanding risk perception, explored from the perspective of the water practitioner.

    Science.gov (United States)

    Dobbie, Meredith Frances; Brown, Rebekah Ruth

    2014-02-01

    Sustainable urban water systems are likely to be hybrids of centralized and decentralized infrastructure, managed as an integrated system in water-sensitive cities. The technology for many of these systems is available. However, social and institutional barriers, which can be understood as deeply embedded risk perceptions, have impeded their implementation. Risk perceptions within the water sector are often unrecognized or unacknowledged, despite their role in risk management generally in informing value judgments and specifically in ranking risks to achieve management objectives. There has been very little examination of the role of these risk perceptions in advancing more sustainable water supply management through the adoption of alternative sources. To address this gap, this article presents a framework that can be used as a tool for understanding risk perceptions. The framework is built on the relational theory of risk and presents the range of human phenomena that might influence the perception of an "object at risk" in relation to a "risk object." It has been synthesized from a critical review of theoretical, conceptual, and empirical studies of perception broadly and risk perception specifically, and interpreted in relation to water practitioners. For a water practitioner, the risk object might be an alternative water system, a component, a process, or a technology, and the object at risk could be public or environmental health, profitability, or professional reputation. This framework has two important functions: to allow practitioners to understand their own and others' risk perceptions, which might differ, and to inform further empirical research. © 2013 Society for Risk Analysis.

  4. Nanomedicine and epigenome. Possible health risks.

    Science.gov (United States)

    Smolkova, Bozena; Dusinska, Maria; Gabelova, Alena

    2017-11-01

    Nanomedicine is an emerging field that combines knowledge of nanotechnology and material science with pharmaceutical and biomedical sciences, aiming to develop nanodrugs with increased efficacy and safety. Compared to conventional therapeutics, nanodrugs manifest higher stability and circulation time, reduced toxicity and improved targeted delivery. Despite the obvious benefit, the accumulation of imaging agents and nanocarriers in the body following their therapeutic or diagnostic application generates concerns about their safety for human health. Numerous toxicology studies have demonstrated that exposure to nanomaterials (NMs) might pose serious risks to humans. Epigenetic modifications, representing a non-genotoxic mechanism of toxicant-induced health effects, are becoming recognized as playing a potential causative role in the aetiology of many diseases including cancer. This review i) provides an overview of recent advances in medical applications of NMs and ii) summarizes current evidence on their possible epigenetic toxicity. To discern potential health risks of NMs, since current data are mostly based upon in vitro and animal models, a better understanding of functional relationships between NM exposure, epigenetic deregulation and phenotype is required. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Potential fluoride toxicity from oral medicaments: A review.

    Science.gov (United States)

    Ullah, Rizwan; Zafar, Muhammad Sohail; Shahani, Nazish

    2017-08-01

    The beneficial effects of fluoride on human oral health are well studied. There are numerous studies demonstrating that a small amount of fluoride delivered to the oral cavity decreases the prevalence of dental decay and results in stronger teeth and bones. However, ingestion of fluoride more than the recommended limit leads to toxicity and adverse effects. In order to update our understanding of fluoride and its potential toxicity, we have described the mechanisms of fluoride metabolism, toxic effects, and management of fluoride toxicity. The main aim of this review is to highlight the potential adverse effects of fluoride overdose and poorly understood toxicity. In addition, the related clinical significance of fluoride overdose and toxicity has been discussed.

  6. Individualized toxicity-titrated 6-mercaptopurine increments during high-dose methotrexate consolidation treatment of lower risk childhood acute lymphoblastic leukaemia. A Nordic Society of Paediatric Haematology and Oncology (NOPHO) pilot study

    DEFF Research Database (Denmark)

    Frandsen, Thomas L; Abrahamsson, Jonas; Lausen, Birgitte

    2011-01-01

    This study explored the feasibility and toxicity of individualized toxicity-titrated 6-mercaptopurine (6MP) dose increments during post-remission treatment with High-dose methotrexate (HDM) (5000 mg/m(2), ×3) in 38 patients with Childhood (ALL). Patients were increased in steps of 25 mg 6MP/m(2...... the remaining patients (P = 0·03). This study shows individualized toxicity-titrated 6MP dosing during consolidation is feasible without increased risk of toxicity....

  7. Rapid screening of aquatic toxicity of several metal-based nanoparticles using the MetPLATE™ bioassay

    International Nuclear Information System (INIS)

    Pokhrel, Lok R.; Silva, Thilini; Dubey, Brajesh; El Badawy, Amro M.; Tolaymat, Thabet M.; Scheuerman, Phillip R.

    2012-01-01

    Current understanding of potential toxicity of engineered nanomaterials to aquatic microorganisms is limited for risk assessment and management. Here we evaluate if the MetPLATE™ test can be used as an effective and rapid screening tool to test for potential aquatic toxicity of various metal-based nanoparticles (NPs). The MetPLATE bioassay is a heavy metal sensitive test based on β-galactosidase activity in Escherichia coli. Five different types of metal-based NPs were screened for toxicity: (1) citrate coated nAg (Citrate-nanosilver), (2) polyvinylpyrrolidone coated nAg (PVP-nAg), (3) uncoated nZnO, (4) uncoated nTiO 2 and (5) 1-Octadecylamine coated CdSe Quantum Dots (CdSe QDs); and compared with their corresponding ionic salt toxicity. Citrate-nAg was further fractionated into clean Citrate-nAg, unclean Citrate-nAg and permeate using a tangential flow filtration (TFF) system to eliminate residual ions and impurities from the stock Citrate-nAg suspension and also to differentiate between ionic- versus nano-specific toxicity. Our results showed that nAg, nZnO and CdSe QDs were less toxic than their corresponding ionic salts tested, while nano- or ionic form of TiO 2 was not toxic as high as 2.5 g L −1 to the MetPLATE™ bacteria. Although coating-dependent toxicity was noticeable between two types of Ag NPs evaluated, particle size and surface charge were not adequate to explain the observed toxicity; hence, the toxicity appeared to be material-specific. Overall, the toxicity followed the trend: CdCl 2 > AgNO 3 > PVP-nAg > unclean Citrate-nAg > clean Citrate-nAg > ZnSO 4 > nZnO > CdSe QDs > nTiO 2 /TiO 2 . These results indicate that an evaluation of β-galactosidase inhibition in MetPLATE™ E. coli can be an important consideration for rapid screening of metal-based NP toxicity, and should facilitate ecological risk assessment of these emerging contaminants. - Highlights: ► MetPLATE bioassay was evaluated as a rapid screening tool for nanotoxicity.

  8. Ecological risk assessment of toxic organic pollutant and heavy metals in water and sediment from a landscape lake in Tianjin City, China.

    Science.gov (United States)

    Zhang, Ying; Liu, Yuanyuan; Niu, Zhiguang; Jin, Shaopei

    2017-05-01

    To estimate the ecological risk of toxic organic pollutant (formaldehyde) and heavy metals (mercury (Hg), arsenic (As), cadmium (Cd), and chromium (Cr)) in water and sediment from a landscape Lake in Tianjin City, an ecological risk assessment was performed. The risk quotient (RQ) method and the AQUATOX model were used to assess the ecological risk of formaldehyde in landscape water. Meanwhile, the RQ method and the potential ecological risk index method were used to assess the ecological risk of four heavy metals in water and sediment from the studied landscape lake, respectively. The results revealed that the maximum concentration of formaldehyde in landscape water was lower than the environmental quality standards of surface water in China. The maximum simulated concentrations of formaldehyde in phytoplankton and invertebrates were 3.15 and 22.91 μg/L, respectively, which were far less than its toxicity data values (1000 and 510 μg/L, respectively), suggesting that formaldehyde in landscape water was at a safe level for aquatic organisms. The RQ model indicated that the risks of phytoplankton and invertebrates were higher than that of fish posed by Hg and Cd in landscape water, and the risks from As and Cr were acceptable for all test organisms. Cd is the most important pollution factor among all heavy metals in sediment from studied landscape lake, and the pollution factor sequence of heavy metals was Hg > As > Cr > Cd. The values of risk index (RI) for four heavy metals in samples a and b were 43.48 and 72.66, which were much lower than the threshold value (150), suggesting that the ecological risk posed by heavy metals in sediment was negligible.

  9. Toxicity of Pb-contaminated soil to Japanese quail (Coturnix japonica) and the use of the blood-dietary Pb slope in risk assessment

    Science.gov (United States)

    Beyer, W. Nelson; Chen, Yu; Henry, Paula; May, Thomas; Mosby, David; Rattner, Barnett A.; Shearn-Bochsler, Valerie I.; Sprague, Daniel; Weber, John

    2014-01-01

    This study relates tissue concentrations and toxic effects of Pb in Japanese quail (Coturnix japonica) to the dietary exposure of soil-borne Pb associated with mining and smelting. From 0% to 12% contaminated soil, by weight, was added to 5 experimental diets (0.12 to 382 mg Pb/kg, dry wt) and fed to the quail for 6 weeks. Benchmark doses associated with a 50% reduction in delta-aminolevulinic acid dehydratase activity were 0.62 mg Pb/kg in the blood, dry wt, and 27 mg Pb/kg in the diet. Benchmark doses associated with a 20% increase in the concentration of erythrocyte protoporphyrin were 2.7 mg Pb/kg in the blood and 152 mg Pb/kg in the diet. The quail showed no other signs of toxicity (histopathological lesions, alterations in plasma–testosterone concentration, and body and organ weights). The relation of the blood Pb concentration to the soil Pb concentration was linear, with a slope of 0.013 mg Pb/kg of blood (dry wt) divided by mg Pb/kg of diet. We suggest that this slope is potentially useful in ecological risk assessments on birds in the same way that the intake slope factor is an important parameter in risk assessments of children exposed to Pb. The slope may also be used in a tissue-residue approach as an additional line of evidence in ecological risk assessment, supplementary to an estimate of hazard based on dietary toxicity reference values.

  10. Persistent Environmental Toxicants in Breast Milk and Rapid Infant Growth

    NARCIS (Netherlands)

    Criswell, Rachel; Lenters, Virissa; Mandal, Siddhartha; Stigum, Hein; Iszatt, Nina; Eggesbø, Merete

    2017-01-01

    BACKGROUND/AIMS: Many environmental toxicants are passed to infants in utero and through breast milk. Exposure to toxicants during the perinatal period can alter growth patterns, impairing growth or increasing obesity risk. Previous studies have focused on only a few toxicants at a time, which may

  11. Risk assessment of potentially toxic element pollution in soils and rice (Oryza sativa) in a typical area of the Yangtze River Delta

    International Nuclear Information System (INIS)

    Hang Xiaoshuai; Wang Huoyan; Zhou Jianmin; Ma Chengling; Du Changwen; Chen Xiaoqin

    2009-01-01

    Soil pollution with potentially toxic elements (PTEs) resulting from rapid industrial development has caused major concerns. Selected PTEs and their accumulation and distribution in soils and rice (Oryza sativa) collected from Changshu, east China, were analyzed to evaluate the potential health risk to the local population. The soils were primarily contaminated with Hg, followed by Cu, Cd, Pb, and Zn. The concentrations of Pb, Hg, and Cd of 46, 32, and 1 rice samples exceeded their national maximum allowable levels in foods, respectively. Spatial distributions of total Cr, Cu, Pb, Zn, and Cd in soils shared similar geographical trends. The risk assessment of PTEs through rice consumption suggests that the concentrations of Cu, Pb, and Cd in some rice samples exceed their reference oral dose for adults and children. In general, there was no target hazard quotient value of any individual element that was greater than 1, but hazard index values for adults and children were 1.726 and 1.523, respectively. - Industrial development has led to increased risk from potentially toxic elements in soils and rice.

  12. Toxic combustion products from pesticide fires. Executive summary

    NARCIS (Netherlands)

    Molag, M.; Bartelds, H.; Weger, D. de

    1992-01-01

    In order to obtain reliable data on the generation of toxic combustion products and to get more insight into the risks of fires in pesticide warehouses TNO performed the research project 'Toxic combustion products from pesticide fires'. The following research activities have been performed during

  13. Modeling Aquatic Toxicity through Chromatographic Systems.

    Science.gov (United States)

    Fernández-Pumarega, Alejandro; Amézqueta, Susana; Farré, Sandra; Muñoz-Pascual, Laura; Abraham, Michael H; Fuguet, Elisabet; Rosés, Martí

    2017-08-01

    Environmental risk assessment requires information about the toxicity of the growing number of chemical products coming from different origins that can contaminate water and become toxicants to aquatic species or other living beings via the trophic chain. Direct toxicity measurements using sensitive aquatic species can be carried out but they may become expensive and ethically questionable. Literature refers to the use of chromatographic measurements that correlate to the toxic effect of a compound over a specific aquatic species as an alternative to get toxicity information. In this work, we have studied the similarity in the response of the toxicity to different species and we have selected eight representative aquatic species (including tadpoles, fish, water fleas, protozoan, and bacteria) with known nonspecific toxicity to chemical substances. Next, we have selected four chromatographic systems offering good perspectives for surrogation of the eight selected aquatic systems, and thus prediction of toxicity from the chromatographic measurement. Then toxicity has been correlated to the chromatographic retention factor. Satisfactory correlation results have been obtained to emulate toxicity in five of the selected aquatic species through some of the chromatographic systems. Other aquatic species with similar characteristics to these five representative ones could also be emulated by using the same chromatographic systems. The final aim of this study is to model chemical products toxicity to aquatic species by means of chromatographic systems to reduce in vivo testing.

  14. Assessing the impact of waterborne and dietborne cadmium toxicity on susceptibility risk for rainbow trout

    International Nuclear Information System (INIS)

    Liao, Chung-Min; Ju, Yun-Ru; Chen, Wei-Yu; Chen, Bo-Ching

    2011-01-01

    The purpose of this study was to use a risk-based integrated-scale toxicological model to examine the impact of waterborne and dietborne cadmium (Cd) toxicity on rainbow trout (Oncorhynchus mykiss) susceptibility appraised with recent published data. A probabilistic assessment model was performed to estimate Cd susceptibility risk. The dose-response models were constructed based on two endpoints of % Cd in metabolically active pool (MAP) and susceptibility time that causes 50% effect (ST50). We further constructed an elimination-detoxification-recovery scheme to enhance the model predictive ability. We found a 95% probability of % Cd in gill and liver MAP exceeding 47-49% and it was likely (70% probability) to have exceeded 52-55%, but it was unlikely (30% probability) to have exceeded 56-60%. In contrast to gill and liver, gut had a relative lower Cd susceptibility risk (15-17% Cd in MAP) with a longer ST50. We suggested that the proposed probabilistic risk assessment framework can incorporate the elimination-detoxification-recovery scheme to help government based biomonitoring and bioassessment programs to prevent potential aquatic ecosystems and human health consequences. - Research Highlights: → An integrated-scale toxicological model was used to examine the impact of Cd on rainbow trout. → A probabilistic assessment model was performed to estimate Cd susceptibility risk. → An elimination-detoxification-recovery scheme was constructed to enhance the model predictive ability. → Gut had a relative lower Cd susceptibility risk than that in gill and liver.

  15. Assessing the impact of waterborne and dietborne cadmium toxicity on susceptibility risk for rainbow trout

    Energy Technology Data Exchange (ETDEWEB)

    Liao, Chung-Min, E-mail: cmliao@ntu.edu.tw [Department of Bioenvironmental Systems Engineering, National Taiwan University, Taipei, 10617, Taiwan (China); Ju, Yun-Ru; Chen, Wei-Yu [Department of Bioenvironmental Systems Engineering, National Taiwan University, Taipei, 10617, Taiwan (China); Chen, Bo-Ching [Department of Post-Modern Agriculture, Mingdao University, Changhua, 52345, Taiwan (China)

    2011-01-01

    The purpose of this study was to use a risk-based integrated-scale toxicological model to examine the impact of waterborne and dietborne cadmium (Cd) toxicity on rainbow trout (Oncorhynchus mykiss) susceptibility appraised with recent published data. A probabilistic assessment model was performed to estimate Cd susceptibility risk. The dose-response models were constructed based on two endpoints of % Cd in metabolically active pool (MAP) and susceptibility time that causes 50% effect (ST50). We further constructed an elimination-detoxification-recovery scheme to enhance the model predictive ability. We found a 95% probability of % Cd in gill and liver MAP exceeding 47-49% and it was likely (70% probability) to have exceeded 52-55%, but it was unlikely (30% probability) to have exceeded 56-60%. In contrast to gill and liver, gut had a relative lower Cd susceptibility risk (15-17% Cd in MAP) with a longer ST50. We suggested that the proposed probabilistic risk assessment framework can incorporate the elimination-detoxification-recovery scheme to help government based biomonitoring and bioassessment programs to prevent potential aquatic ecosystems and human health consequences. - Research Highlights: {yields} An integrated-scale toxicological model was used to examine the impact of Cd on rainbow trout. {yields} A probabilistic assessment model was performed to estimate Cd susceptibility risk. {yields} An elimination-detoxification-recovery scheme was constructed to enhance the model predictive ability. {yields} Gut had a relative lower Cd susceptibility risk than that in gill and liver.

  16. The Effects of Temperature and Hydrostatic Pressure on Metal Toxicity: Insights into Toxicity in the Deep Sea.

    Science.gov (United States)

    Brown, Alastair; Thatje, Sven; Hauton, Chris

    2017-09-05

    Mineral prospecting in the deep sea is increasing, promoting concern regarding potential ecotoxicological impacts on deep-sea fauna. Technological difficulties in assessing toxicity in deep-sea species has promoted interest in developing shallow-water ecotoxicological proxy species. However, it is unclear how the low temperature and high hydrostatic pressure prevalent in the deep sea affect toxicity, and whether adaptation to deep-sea environmental conditions moderates any effects of these factors. To address these uncertainties we assessed the effects of temperature and hydrostatic pressure on lethal and sublethal (respiration rate, antioxidant enzyme activity) toxicity in acute (96 h) copper and cadmium exposures, using the shallow-water ecophysiological model organism Palaemon varians. Low temperature reduced toxicity in both metals, but reduced cadmium toxicity significantly more. In contrast, elevated hydrostatic pressure increased copper toxicity, but did not affect cadmium toxicity. The synergistic interaction between copper and cadmium was not affected by low temperature, but high hydrostatic pressure significantly enhanced the synergism. Differential environmental effects on toxicity suggest different mechanisms of action for copper and cadmium, and highlight that mechanistic understanding of toxicity is fundamental to predicting environmental effects on toxicity. Although results infer that sensitivity to toxicants differs across biogeographic ranges, shallow-water species may be suitable ecotoxicological proxies for deep-sea species, dependent on adaptation to habitats with similar environmental variability.

  17. Which risk understandings can be derived from the current disharmonized regulation of complementary and alternative medicine in Europe?

    Science.gov (United States)

    Wiesener, Solveig; Salamonsen, Anita; Fønnebø, Vinjar

    2018-01-10

    Many European citizens are seeking complementary and alternative medicine (CAM). These treatments are regulated very differently in the EU/EFTA countries. This may demonstrate differences in how risk associated with the use of CAM is perceived. Since most CAM treatments are practiced fairly similarly across Europe, differing risk understandings may influence patient safety for European CAM users. The overall aim of this article is thus to contribute to an overview and awareness of possible differing risk understandings in the field of CAM at a policymaking/structural level in Europe. The study is a re-analysis of data collected in the CAMbrella EU FP7 document and interview study on the regulation of CAM in 39 European countries. The 12 CAM modalities included in the CAMbrella study were ranked with regard to assumed risk potential depending on the number of countries limiting its practice to regulated professions. The 39 countries were ranked according to how many of the included CAM modalities they limit to be practiced by regulated professions. Twelve of 39 countries generally understand the included CAM treatments to represent "high risk", 20 countries "low risk", while the remaining 7 countries understand CAM treatments as carrying "very little or no risk". The CAM modalities seen as carrying a risk high enough to warrant professional regulation in the highest number of countries are chiropractic, acupuncture, massage, homeopathy and osteopathy. The countries understanding most of the CAM modalities in the study as potentially high-risk treatments are with two exceptions (Portugal and Belgium) all concentrated in the southeastern region of Europe. The variation in regulation of CAM may represent a substantial lack of common risk understandings between health policymakers in Europe. We think the discrepancies in regulation are to a considerable degree also based on factors unrelated to patient risk. We argue that it is important for patient safety that policy

  18. Sodium monofluoroacetate (1080) risk assessment and risk communication

    International Nuclear Information System (INIS)

    Eason, Charles

    2002-01-01

    Sodium monofluoroacetate (1080) is a vertebrate pesticide widely used for possum control in New Zealand. Fluoroacetate is also a toxic component of poisonous plants found in Australia, South Africa, South America, and India. Because of its importance and effectiveness in pest control and the highly toxic nature of this compound, its acute sub-lethal and target organ toxicity have been extensively studied. In relation to its use as a pesticide its environmental fate, persistence, non-target impacts and general toxicology have been and continue to be extensively studied. Toxic baits must be prepared and used with extreme care, otherwise humans, livestock, and non-target wildlife will be put at risk. The high risk of secondary poisoning of dogs is a cause for concern. 1080 acts by interfering with cellular energy production. Possums die from heart failure, usually within 6-18 h of eating baits. Long-term exposure to sub-lethal doses can have harmful effects and strict safety precautions are enforced to protect contractors and workers in the bait manufacturing industry. Considerable care is taken when using 1080 to ensure that the risks of using it are outweighed by the ecological benefits achieved from its use. When its use is controversial, risk communicators must take care not to trivialise the toxicity of the compound. The benefits of 1080 use in conservation, pest control, and disease control should be weighed up alongside the risks of using 1080 and other techniques for pest control

  19. Human health risk assessment methodology for the UMTRA Ground Water Project

    International Nuclear Information System (INIS)

    1994-11-01

    This document presents the method used to evaluate human risks associated with ground water contamination at inactive uranium processing sites. The intent of these evaluations is to provide the public and remedial action decision-makers with information about the health risks that might be expected at each site in a manner that is easily understood. The method (1) develops probabilistic distributions for exposure variables where sufficient data exist, (2) simulates predicted exposure distributions using Monte Carlo techniques, and (3) develops toxicity ranges that reflect human data when available, animal data if human data are insufficient, regulatory levels, and uncertainties. Risk interpretation is based on comparison of the potential exposure distributions with the derived toxicity ranges. Graphic presentations are an essential element of the semiquantitative interpretation and are expected to increase understanding by the public and decision-makers

  20. Potential fluoride toxicity from oral medicaments: A review

    Directory of Open Access Journals (Sweden)

    Rizwan Ullah

    2017-08-01

    Full Text Available The beneficial effects of fluoride on human oral health are well studied. There are numerous studies demonstrating that a small amount of fluoride delivered to the oral cavity decreases the prevalence of dental decay and results in stronger teeth and bones. However, ingestion of fluoride more than the recommended limit leads to toxicity and adverse effects. In order to update our understanding of fluoride and its potential toxicity, we have described the mechanisms of fluoride metabolism, toxic effects, and management of fluoride toxicity. The main aim of this review is to highlight the potential adverse effects of fluoride overdose and poorly understood toxicity. In addition, the related clinical significance of fluoride overdose and toxicity has been discussed.

  1. Uranium: biokinetics and toxicity

    International Nuclear Information System (INIS)

    Menetrier, F.; Renaud-Salis, V.; Flury-Herard, A.

    2000-01-01

    This report was achieved as a part of a collaboration with the Fuel Cycle Direction. Its aim was to give the state of the art about: the behaviour of uranium in the human organism (biokinetics) after ingestion, its toxicity (mainly renal) and the current regulation about its incorporation. Both in the upstream and in the downstream of the fuel cycle, uranium remains, quantitatively, the first element in the cycle which is, at the present time, temporarily disposed or recycled. Such a considerable quantity of uranium sets the problem of its risk on the health. In the long term, the biosphere may be affected and consequently the public may ingest water or food contaminated with uranium. In this way, radiological and chemical toxicity risk may be activated. This report emphasizes: the necessity of confirming some experimental and epidemiological biokinetic data used or not in the ICRP models. Unsolved questions remain about the gastrointestinal absorption according to chemical form (valency state, mixtures...), mass and individual variations (age, disease) further a chronic ingestion of uranium. It is well established that uranium is mainly deposited in the skeleton and the kidney. But the skeleton kinetics following a chronic ingestion and especially in some diseases has to be more elucidated; the necessity of taking into account uranium at first as a chemical toxic, essentially in the kidney and determining the threshold of functional lesion. In this way, it is important to look for some specific markers; the problem of not considering chemical toxicity of uranium in the texts regulating its incorporation

  2. Brand switching and toxic chemicals in cigarette smoke: A national study.

    Directory of Open Access Journals (Sweden)

    Jennifer R Mendel

    Full Text Available US law requires disclosure of quantities of toxic chemicals (constituents in cigarette smoke by brand and sub-brand. This information may drive smokers to switch to cigarettes with lower chemical quantities, under the misperception that doing so can reduce health risk. We sought to understand past brand-switching behavior and whether learning about specific chemicals in cigarette smoke increases susceptibility to brand switching.Participants were US adult smokers surveyed by phone (n = 1,151, probability sample and online (n = 1,561, convenience sample. Surveys assessed whether smokers had ever switched cigarette brands or styles to reduce health risk and about likelihood of switching if the smoker learned their brand had more of a specific chemical than other cigarettes. Chemicals presented were nicotine, carbon monoxide, lead, formaldehyde, arsenic, and ammonia.Past brand switching to reduce health risk was common among smokers (43% in phone survey, 28% in online survey. Smokers who were female, over 25, and current "light" cigarette users were more likely to have switched brands to reduce health risks (all p < .05. Overall, 61-92% of smokers were susceptible to brand switching based on information about particular chemicals. In both samples, lead, formaldehyde, arsenic, and ammonia led to more susceptibility to switch than nicotine (all p < .05.Many US smokers have switched brands or styles to reduce health risks. The majority said they might or would definitely switch brands if they learned their cigarettes had more of a toxic chemical than other brands. Brand switching is a probable unintended consequence of communications that show differences in smoke chemicals between brands.

  3. The Industrial Toxics Project: Targeting chemicals for environmental results

    International Nuclear Information System (INIS)

    Burch, W.M.

    1991-01-01

    In September, 1990, the Administrator of the US Environmental Protection Agency committed the Agency to a program of targeting chemicals for multi-media risk reduction activities through pollution prevention. The Industrial Toxics Project will place emphasis on obtaining voluntary commitments from industry to reduce releases of toxic chemicals to the air, water, and land with a goal of reducing releases nationwide by 33% by 1992 and 50% by 1995. An initial list of 18 chemicals have been selected based on recommendations from each Agency program. The chemicals selected are subject to reporting under the Toxic Chemical Release Inventory Program which will provide the basis for tracking progress. The chemicals are characterized by high production volume, toxicity and releases and present the potential for significant risk reduction through pollution prevention. This presentation will discuss the focus and direction of this new initiative

  4. Physico-chemical evaluation and toxicity risk assessment of the urban rivers of Metro Cebu, Philippines

    International Nuclear Information System (INIS)

    Ramal, Allan; Santos, Alfredo; Florentino, Nathaniel; Castanares, Josephine; Suico, Ma. Ligaya; Koyama, Jiro

    2013-01-01

    Three prominent urban rivers in Metro Cebu were samples and analysed for their physico-chemical properties and their toxicity as to surfactant levels was evaluated using tilapia (Oreochromis niloticus L.). Surfactants in rivers, particularly the linear alkylbenzene sulfonates (LAS), ammonia (NH 3 ), nitrate, nitrite and phosphate were determined colorimetrically using UV-Vis spectrophotometer. Physical parameters such as conductivity, salinity, temperature, pH and Dissolved Oxygen (DO) were determined in situ using a Multi-probe digital meter. Winkler Method was carried out to confirm the levels of DO in water samples. Results revealed that Guadalupe, Mahiga and Butuanon Downstream contain DO levels lower than 5 ppm, which is level needed to support aquatic life. This result further correlates the levels of NH 3 in the samples with Guadalupe containing the highest NH 3 level of 13.09 ppm, followed by, Butuanon Dowstream (8.20 ppm), Mahiga (5.95ppm) and Butuanon Upstream (1.22 ppm) which are all beyond the DENR standard limit of 0.5 ppm. The LAS levels were found high in Butuanon Downstream (3.35 ppm), Guadalupe River (1.51 ppm), followed by Mahiga (1.02 ppm), and Butuanon Upstream (0.42 ppm). All of the river water samples except for Butuanon Upstream were beyond the tolerable limit for surfactants as prescribed by the DENR for surface water which is 0.5 ppm. Nitrate and nitrite levels for all river samples were below the DEBR standard limit of 10.0 ppm. Only Guadalupe (0.91 ppm) and Mahiga (0.52 ppm) failed to meet the DENR standard of 0.4 ppm for phosphate. Definitive Test for toxicity of LAS to Tilapia juveniles after 96 h showed an LC 5 0 of 7.6 ppm. This result was used for risk assessment of the three river systems for LAS. Toxicity Test of river samples showed 100% mortality for Guadalupe, Mahiga and Butuanon Downstream. Predicted Environment Concentrations (PEC) to Predicted No Effect Concentration (PNEC) ratio revealed that all river systems were at

  5. Increased risk for congenital heart defects in children carrying the ABCB1 Gene C3435T polymorphism and maternal periconceptional toxicants exposure.

    Directory of Open Access Journals (Sweden)

    Chuan Wang

    Full Text Available BACKGROUNDS: The etiology of congenital heart defect (CHD is commonly believed to involve the interaction of multiple environmental and genetic factors. This study aimed to explore the joint effects of the ABCB1 gene C3435T polymorphism and maternal periconceptional toxicants exposure on the CHD risk in a Han Chinese population. METHODS: An age and gender matched case-control study with standardized data collection involving 201 pairs was conducted. Periconceptional toxicants exposure was obtained through a structured questionnaire. A job exposure matrix (JEM was used for toxicants exposure assessment. Genotyping of the ABCB1 C3435T polymorphism was performed by sequencing. Logistic regression analysis was performed to assess the joint effects of the ABCB1 gene C3435T polymorphism and toxicants exposure on the risk of CHD. Placenta tissues and umbilical cords were collected to investigate the impact of C3435T polymorphism on the transcription and translation activities of ABCB1 gene. RESULTS: MATERNAL PERICONCEPTIONAL EXPOSURES TO PHTHALATES (ADJUSTED OR: 1.6; 95%CI: 1.0-2.6 and alkylphenolic compounds (adjusted OR:1.8; 95%CI:1.1-3.0 were associated with a higher incidence of CHDs in general. More cases were carriers of the ABCB1 CC/CT genotypes (OR: 2.0, 95%CI: 1.1-3.5, P-value: 0.021. Children carrying the CC/CT genotype and periconceptionally exposed to phthalates and alkylphenolic compounds suffered almost 3.5-fold increased risk of having CHD than non-exposed children with TT genotype (adjusted OR: 3.5, 95%CI: 1.5-7.9, P-value: 0.003, and the OR changed to 4.4 for septal defects (adjusted OR: 4.4,95%CI:1.8-10.9,P-value:0.001. The ABCB1 mRNA expression of the TT genotype was significantly higher than that of the CC genotype (P = 0.03. Compared with TT genotype, lower P-glycoprotein expression was observed for the CC/CT genotypes. CONCLUSION: The C3435T polymorphism in the ABCB1 gene of fetus increases the risks of CHD in a Han Chinese

  6. Neurological manifestation of phenytoin toxicity, resulting from drug ...

    African Journals Online (AJOL)

    Phenytoin toxicity masquerading as deterioration of neurological symptoms caused by interaction with chloramphenicol is a very rare but real risk. To the authors' knowledge only one such case occurring in humans has been reported in the English literature. No case of clinical phenytoin toxicity occurring at less than ...

  7. Towards a more complete understanding of the occurrence and toxicities of the cylindrospermopsins

    Directory of Open Access Journals (Sweden)

    Ross Sadler

    2015-08-01

    Full Text Available The existence of a number of cylindrospermopsin analogs has been confirmed by several authors. These cylindrospermopsin analogs were formerly seen as minor constituents, with normal cylindrospermopsin always being the dominant form. However, it is now clear that the cylindrospermopsin analogs are the major species produced by certain organisms, the production being enhanced, at least in some cases, under specific physiological conditions. Presently, relatively little information is available concerning the properties, physiology of occurrence and toxicity of these molecules. The existing literature pertaining to these aspects is reviewed with respect to known cylindrospermopsin analogs.The biosynthesis of the cylindrospermopsins is discussed and the previously established pathway has been modified to take account of the production of the known cylindrospermopsin forms. The anomalies in terms of in-vivo toxicity of 7-deoxy-cylindrospermopsin are reported, along with further attempts to rationalize the situation. We also discuss reasons for the apparently similar toxicity of 7-deoxy-cylindrospermopsin and cylindrospermopsin to cell cultures in vitro. It is hypothesized that the similarity of cylindrospermopsin intoxication to nonalcoholic fatty liver disease may argue for these cyanotoxins to exert their effects via a lysosomal pathway.

  8. Assessing the toxicity and risk of salt-impacted winter road runoff to the early life stages of freshwater mussels in the Canadian province of Ontario.

    Science.gov (United States)

    Prosser, R S; Rochfort, Q; McInnis, R; Exall, K; Gillis, P L

    2017-11-01

    In temperate urbanized areas where road salting is used for winter road maintenance, the level of chloride in surface waters has been increasing. While a number of studies have shown that the early-life stages of freshwater mussels are particularly sensitive to salt; few studies have examined the toxicity of salt-impacted winter road runoff to the early-life stages of freshwater mussels to confirm that chloride is the driver of toxicity in this mixture. This study examines the acute toxicity of field-collected winter road runoff to the glochidia of wavy-rayed lampmussels (Lampsilis fasciola) (48 h exposure) and newly released juvenile fatmucket mussels (Lampsilis siliquoidea) (road run-off created with moderately hard synthetic water (∼80 mg CaCO 3 /L) were 1177 (95% confidence interval (CI): 1011-1344 mg Cl - /L) and 2276 mg Cl - /L (95% CI: 1698-2854 mg Cl - /L), respectively. These effect concentrations correspond with the toxicity of chloride reported in other studies, indicating that chloride is likely the driver of toxicity in salt-impacted road-runoff, with other contaminants (e.g., metals, polycyclic aromatic hydrocarbons) playing a de minimis role. Toxicity data from the current study and literature and concentrations of chloride in the surface waters of Ontario were used to conduct a probabilistic risk assessment of chloride to early-life stage freshwater mussels. The assessment indicated that chronic exposure to elevated chloride levels could pose a risk to freshwater mussels; further investigation is warranted to ensure that the most sensitive organisms are protected. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

  9. What Makes Youth Harass Their Immigrant Peers? Understanding the Risk Factors

    Science.gov (United States)

    Bayram Özdemir, Sevgi; Özdemir, Metin; Stattin, Håkan

    2016-01-01

    Immigrant youth are at risk of experiencing harassment in school; however, we have only limited understanding of what makes youth harass their peers on ground of their ethnic origin. To address this major limitation, we examined (a) whether youth's negative attitudes toward immigrants impact their engagement in ethnic harassment over time and (b)…

  10. [Specific iatrogenic risks to patients with HIV infection].

    Science.gov (United States)

    De Tournemire, R; Yeni, P

    1994-01-01

    Human immunodeficiency virus-infected patients are exposed to more or less specific iatrogenic diseases. The main characteristics of the risks encountered in this field are described: drug intolerance, mostly to sulfamethoxazole-trimethoprim, is extremely frequent; nucleoside analogue antiviral toxicity is reminiscent of that of chemotherapy; nosocomial infections, in general, are more prominent than in HIV-non infected patients. Intravenous line infections are particularly frequent, but these devices are necessary for prolonged intravenous therapies such as anti-CMV treatment of parenteral nutrition. An improved understanding of different etiopathogenic mechanisms and a better approach of the toxicity/efficacy ratio for each treatment would allow to reduce the excessive morbidity due to iatrogenicity.

  11. Comparative hazard analysis and toxicological modeling of diverse nanomaterials using the embryonic zebrafish (EZ) metric of toxicity

    International Nuclear Information System (INIS)

    Harper, Bryan; Thomas, Dennis; Chikkagoudar, Satish; Baker, Nathan; Tang, Kaizhi; Heredia-Langner, Alejandro; Lins, Roberto; Harper, Stacey

    2015-01-01

    The integration of rapid assays, large datasets, informatics, and modeling can overcome current barriers in understanding nanomaterial structure–toxicity relationships by providing a weight-of-the-evidence mechanism to generate hazard rankings for nanomaterials. Here, we present the use of a rapid, low-cost assay to perform screening-level toxicity evaluations of nanomaterials in vivo. Calculated EZ Metric scores, a combined measure of morbidity and mortality in developing embryonic zebrafish, were established at realistic exposure levels and used to develop a hazard ranking of diverse nanomaterial toxicity. Hazard ranking and clustering analysis of 68 diverse nanomaterials revealed distinct patterns of toxicity related to both the core composition and outermost surface chemistry of nanomaterials. The resulting clusters guided the development of a surface chemistry-based model of gold nanoparticle toxicity. Our findings suggest that risk assessments based on the size and core composition of nanomaterials alone may be wholly inappropriate, especially when considering complex engineered nanomaterials. Research should continue to focus on methodologies for determining nanomaterial hazard based on multiple sub-lethal responses following realistic, low-dose exposures, thus increasing the availability of quantitative measures of nanomaterial hazard to support the development of nanoparticle structure–activity relationships

  12. Comparative hazard analysis and toxicological modeling of diverse nanomaterials using the embryonic zebrafish (EZ) metric of toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Harper, Bryan [Oregon State University (United States); Thomas, Dennis; Chikkagoudar, Satish; Baker, Nathan [Pacific Northwest National Laboratory (United States); Tang, Kaizhi [Intelligent Automation, Inc. (United States); Heredia-Langner, Alejandro [Pacific Northwest National Laboratory (United States); Lins, Roberto [CPqAM, Oswaldo Cruz Foundation, FIOCRUZ-PE (Brazil); Harper, Stacey, E-mail: stacey.harper@oregonstate.edu [Oregon State University (United States)

    2015-06-15

    The integration of rapid assays, large datasets, informatics, and modeling can overcome current barriers in understanding nanomaterial structure–toxicity relationships by providing a weight-of-the-evidence mechanism to generate hazard rankings for nanomaterials. Here, we present the use of a rapid, low-cost assay to perform screening-level toxicity evaluations of nanomaterials in vivo. Calculated EZ Metric scores, a combined measure of morbidity and mortality in developing embryonic zebrafish, were established at realistic exposure levels and used to develop a hazard ranking of diverse nanomaterial toxicity. Hazard ranking and clustering analysis of 68 diverse nanomaterials revealed distinct patterns of toxicity related to both the core composition and outermost surface chemistry of nanomaterials. The resulting clusters guided the development of a surface chemistry-based model of gold nanoparticle toxicity. Our findings suggest that risk assessments based on the size and core composition of nanomaterials alone may be wholly inappropriate, especially when considering complex engineered nanomaterials. Research should continue to focus on methodologies for determining nanomaterial hazard based on multiple sub-lethal responses following realistic, low-dose exposures, thus increasing the availability of quantitative measures of nanomaterial hazard to support the development of nanoparticle structure–activity relationships.

  13. Addendum to ‘Understanding risks in the light of uncertainty: low-probability, high-impact coastal events in cities’

    Science.gov (United States)

    Galarraga, Ibon; Sainz de Murieta, Elisa; Markandya, Anil; María Abadie, Luis

    2018-02-01

    This addendum adds to the analysis presented in ‘Understanding risks in the light of uncertainty: low-probability, high-impact coastal events in cities’ Abadie et al (2017 Environ. Res. Lett. 12 014017). We propose to use the framework developed earlier to enhance communication and understanding of risks, with the aim of bridging the gap between highly technical risk management discussion to the public risk aversion debate. We also propose that the framework could be used for stress-testing resilience.

  14. A Risk Assessment Methodology for Toxic Chemicals Evaporation ...

    African Journals Online (AJOL)

    This study presents a method for determining the mass transfer coefficient for the toxic chemicals evaporation from circular pools formed due to the failure of plant integrity or escape from valves. The approach used in this present research work is to develop a correlation by a robust optimization technique known as Genetic ...

  15. Probabilistic risk assessment of gold nanoparticles after intravenous administration by integrating in vitro and in vivo toxicity with physiologically based pharmacokinetic modeling.

    Science.gov (United States)

    Cheng, Yi-Hsien; Riviere, Jim E; Monteiro-Riviere, Nancy A; Lin, Zhoumeng

    2018-04-14

    This study aimed to conduct an integrated and probabilistic risk assessment of gold nanoparticles (AuNPs) based on recently published in vitro and in vivo toxicity studies coupled to a physiologically based pharmacokinetic (PBPK) model. Dose-response relationships were characterized based on cell viability assays in various human cell types. A previously well-validated human PBPK model for AuNPs was applied to quantify internal concentrations in liver, kidney, skin, and venous plasma. By applying a Bayesian-based probabilistic risk assessment approach incorporating Monte Carlo simulation, probable human cell death fractions were characterized. Additionally, we implemented in vitro to in vivo and animal-to-human extrapolation approaches to independently estimate external exposure levels of AuNPs that cause minimal toxicity. Our results suggest that under the highest dosing level employed in existing animal studies (worst-case scenario), AuNPs coated with branched polyethylenimine (BPEI) would likely induce ∼90-100% cellular death, implying high cytotoxicity compared to risk prediction, and point of departure estimation of AuNP exposure for humans and illustrate an approach that could be applied to other NPs when sufficient data are available.

  16. A Systematic Review on Exposure to Toxic and Essential Elements through Black Tea Consumption in Iran: Could It be a Major Risk for Human Health?

    Directory of Open Access Journals (Sweden)

    Elahe Rezaee

    2014-01-01

    Conclusions: The hazard of excessive element intake through black tea consumption should be considered as negligible in Iran. However, related risk for manganese appeared to be more than toxic metals.

  17. Consent for blood transfusion: do patients understand the risks and benefits?

    Science.gov (United States)

    Cheung, D; Lieberman, L; Lin, Y; Callum, J

    2014-10-01

    Blood transfusion is a frequent medical intervention in hospitals. The benefits of, risks of and alternatives to blood transfusions are not consistently understood by patients. The objective of this study was to assess gaps in knowledge and comfort with the current process of consenting patients for blood transfusions. A standardised video regarding the risk and benefits of blood transfusions was developed and feedback regarding this tool was assessed. After informed consent had been obtained, 25 patients receiving their first transfusion at a single academic centre were asked to complete a survey, watch a standardised educational video and complete a follow-up survey. The patient survey revealed that the information recollected from informed consent discussions was variable and incomplete. After the informed consent discussion, the majority of patients were comfortable with having a blood transfusion, although one-third did express concerns or worry about having a blood transfusion. After viewing the video, patients felt that the video improved their understanding of the risks (7·3 of 10), benefits (6·9 of 10) and alternatives (7·1 of 10) to transfusion, but it did not change their comfort with blood transfusion consent. Patients experienced a variable informed consent process prior to blood transfusion. Although the video improved their understanding of risks, it did not improve patient comfort towards giving consent for transfusion as the level of comfort was already high. The video is available online (http://www.youtube.com/watch?v=RxaPnLkgh-0) as an optional resource for patients (and physicians) who wish to receive standardised and accurate information about blood transfusions. © 2014 British Blood Transfusion Society.

  18. Understanding household preferences for hurricane risk mitigation information: evidence from survey responses.

    Science.gov (United States)

    Chatterjee, Chiradip; Mozumder, Pallab

    2014-06-01

    Risk information is critical to adopting mitigation measures, and seeking risk information is influenced by a variety of factors. An essential component of the recently adopted My Safe Florida Home (MSFH) program by the State of Florida is to provide homeowners with pertinent risk information to facilitate hurricane risk mitigation activities. We develop an analytical framework to understand household preferences for hurricane risk mitigation information through allowing an intensive home inspection. An empirical analysis is used to identify major drivers of household preferences to receive personalized information regarding recommended hurricane risk mitigation measures. A variety of empirical specifications show that households with home insurance, prior experience with damages, and with a higher sense of vulnerability to be affected by hurricanes are more likely to allow inspection to seek information. However, households with more members living in the home and households who live in manufactured/mobile homes are less likely to allow inspection. While findings imply MSFH program's ability to link incentives offered by private and public agencies in promoting mitigation, households that face a disproportionately higher level of risk can get priority to make the program more effective. © 2014 Society for Risk Analysis.

  19. Acute toxicity of anionic and non-ionic surfactants to aquatic organisms.

    Science.gov (United States)

    Lechuga, M; Fernández-Serrano, M; Jurado, E; Núñez-Olea, J; Ríos, F

    2016-03-01

    The environmental risk of surfactants requires toxicity measurements. As different test organisms have different sensitivity to the toxics, it is necessary to establish the most appropriate organism to classify the surfactant as very toxic, toxic, harmful or safe, in order to establish the maximum permissible concentrations in aquatic ecosystems. We have determined the toxicity values of various anionic surfactants ether carboxylic derivatives using four test organisms: the freshwater crustacean Daphnia magna, the luminescent bacterium Vibrio fischeri, the microalgae Selenastrum capricornutum (freshwater algae) and Phaeodactylum tricornutum (seawater algae). In addition, in order to compare and classify the different families of surfactants, we have included a compilation of toxicity data of surfactants collected from literature. The results indicated that V. fischeri was more sensitive to the toxic effects of the surfactants than was D. magna or the microalgae, which was the least sensitive. This result shows that the most suitable toxicity assay for surfactants may be the one using V. fischeri. The toxicity data revealed considerable variation in toxicity responses with the structure of the surfactants regardless of the species tested. The toxicity data have been related to the structure of the surfactants, giving a mathematical relationship that helps to predict the toxic potential of a surfactant from its structure. Model-predicted toxicity agreed well with toxicity values reported in the literature for several surfactants previously studied. Predictive models of toxicity is a handy tool for providing a risk assessment that can be useful to establish the toxicity range for each surfactant and the different test organisms in order to select efficient surfactants with a lower impact on the aquatic environment. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Long-term toxicity assessment of soils in a recovered area affected by a mining spill

    International Nuclear Information System (INIS)

    Romero-Freire, A.; García Fernández, I.; Simón Torres, M.; Martínez Garzón, F.J.; Martín Peinado, F.J.

    2016-01-01

    Residual pollution in the Guadiamar Green Corridor still remains after Aználcollar mine spill in 1998. The polluted areas are identified by the absence of vegetation, soil acidic pH and high concentrations of As, Pb, Zn and Cu. Soil toxicity was assessed by lettuce root elongation and induced soil respiration bioassays. In bare soils, total As and Pb concentrations and water-extractable levels for As, Zn and Cu exceeded the toxicity guidelines. Pollutants responsible for toxicity were different depending on the tested organism, with arsenic being most toxic for lettuce and the metal mixture to soil respiration. Soil properties, such as pH or organic carbon content, are key factors to control metal availability and toxicity in the area. According to our results, there is a risk of pollution to living organisms and the soil quality criteria established in the area should be revised to reduce the risk of toxicity. - Highlights: • 15 years after the Aznalcóllar mine spill residual pollution remains in some areas. • Toxic levels were exceeded for total As and Pb and for soluble As, Zn and Cu. • Metals responsible for soil toxicity are different depending on the tested organism. • pH and organic carbon content reduce metal availability and therefore soil toxicity. • Regulatory guidelines in the area should be revised to reduce the risk of toxicity. - Residual pollution in the Guadiamar Green Corridor remains in some areas after long-term stabilization, with some risk of pollution according to toxicity bioassays.

  1. What do men understand about lifetime risk following genetic testing? The effect of context and numeracy.

    Science.gov (United States)

    Rolison, Jonathan J; Hanoch, Yaniv; Miron-Shatz, Talya

    2012-07-01

    Genetic testing for gene mutations associated with specific cancers provides an opportunity for early detection, surveillance, and intervention (Smith, Cokkinides, & Brawley, 2008). Lifetime risk estimates provided by genetic testing refer to the risk of developing a specific disease within one's lifetime, and evidence suggests that this is important for the medical choices people make, as well as their future family and financial plans. The present studies tested whether adult men understand the lifetime risks of prostate cancer informed by genetic testing. In 2 experiments, adult men were asked to interpret the lifetime risk information provided in statements about risks of prostate cancer. Statement format was manipulated such that the most appropriate interpretation of risk statements referred to an absolute risk of cancer in experiment 1 and a relative risk in experiment 2. Experiment 1 revealed that few men correctly interpreted the lifetime risks of cancer when these refer to an absolute risk of cancer, and numeracy levels positively predicted correct responding. The proportion of correct responses was greatly improved in experiment 2 when the most appropriate interpretation of risk statements referred instead to a relative rather than an absolute risk, and numeracy levels were less involved. Understanding of lifetime risk information is often poor because individuals incorrectly believe that these refer to relative rather than absolute risks of cancer.

  2. The fish embryo toxicity test as an animal alternative method in hazard and risk assessment and scientific research

    International Nuclear Information System (INIS)

    Embry, Michelle R.; Belanger, Scott E.; Braunbeck, Thomas A.; Galay-Burgos, Malyka; Halder, Marlies; Hinton, David E.; Leonard, Marc A.; Lillicrap, Adam; Norberg-King, Teresa; Whale, Graham

    2010-01-01

    Animal alternatives research has historically focused on human safety assessments and has only recently been extended to environmental testing. This is particularly for those assays that involve the use of fish. A number of alternatives are being pursued by the scientific community including the fish embryo toxicity (FET) test, a proposed replacement alternative to the acute fish test. Discussion of the FET methodology and its application in environmental assessments on a global level was needed. With this emerging issue in mind, the ILSI Health and Environmental Sciences Institute (HESI) and the European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC) held an International Workshop on the Application of the Fish Embryo Test as an Animal Alternative Method in Hazard and Risk Assessment and Scientific Research in March, 2008. The workshop included approximately 40 scientists and regulators representing government, industry, academia, and non-governmental organizations from North America, Europe, and Asia. The goal was to review the state of the science regarding the investigation of fish embryonic tests, pain and distress in fish, emerging approaches utilizing fish embryos, and the use of fish embryo toxicity test data in various types of environmental assessments (e.g., hazard, risk, effluent, and classification and labeling of chemicals). Some specific key outcomes included agreement that risk assessors need fish data for decision-making, that extending the FET to include eluethereombryos was desirable, that relevant endpoints are being used, and that additional endpoints could facilitate additional uses beyond acute toxicity testing. The FET was, however, not yet considered validated sensu OECD. An important action step will be to provide guidance on how all fish tests can be used to assess chemical hazard and to harmonize the diverse terminology used in test guidelines adopted over the past decades. Use of the FET in context of effluent assessments

  3. The fish embryo toxicity test as an animal alternative method in hazard and risk assessment and scientific research

    Energy Technology Data Exchange (ETDEWEB)

    Embry, Michelle R., E-mail: membry@ilsi.org [ILSI Health and Environmental Sciences Institute, 1156 15th Street, NW, Suite 200, Washington, DC 20005 (United States); Belanger, Scott E., E-mail: belanger.se@pg.com [Procter and Gamble, Central Product Safety, PO Box 538707, Miami Valley Innovation Center, Cincinnati, OH 45253-8707 (United States); Braunbeck, Thomas A., E-mail: braunbeck@zoo.uni-heidelberg.de [University of Heidelberg, Im Neuenheimer Feld 230, Heidelberg D -69120 (Germany); Galay-Burgos, Malyka, E-mail: malyka.galay-burgos@ecetoc.org [European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC), 4 Avenue E. Van Nieuwenhuyse B-1160, Brussels (Belgium); Halder, Marlies, E-mail: marlies.halder@jrc.ec.europa.eu [European Commission, Joint Research Centre, Institute for Health and Consumer Protection, In-Vitro Methods Unit TP-580 Ispra 21027 (Italy); Hinton, David E., E-mail: dhinton@duke.edu [Duke University, Nicholas School of the Environment, PO Box 90328, Durham, NC 27708, Unites States (United States); Leonard, Marc A., E-mail: mleonard@rd.loreal.com [L' Oreal Recherche Avancee, Unite d' Ecotoxicologie, 1 av. E. Schueller, 93601 Aulnay sous bois (France); Lillicrap, Adam, E-mail: Adam.lillicrap@niva.no [AstraZeneca, Freshwater Quarry, Brixham TQ5 8BA (United Kingdom); Norberg-King, Teresa, E-mail: norberg-king.teresa@epa.gov [U.S. EPA, Mid-Continent Ecology Division, 6201 Congdon Boulevard, Duluth, MN 55804-1636 (United States); Whale, Graham, E-mail: graham.whale@shell.com [Shell Global Solutions, Analytical Technology, P.O. Box 1, Chester CH1 3SH (United Kingdom)

    2010-04-15

    Animal alternatives research has historically focused on human safety assessments and has only recently been extended to environmental testing. This is particularly for those assays that involve the use of fish. A number of alternatives are being pursued by the scientific community including the fish embryo toxicity (FET) test, a proposed replacement alternative to the acute fish test. Discussion of the FET methodology and its application in environmental assessments on a global level was needed. With this emerging issue in mind, the ILSI Health and Environmental Sciences Institute (HESI) and the European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC) held an International Workshop on the Application of the Fish Embryo Test as an Animal Alternative Method in Hazard and Risk Assessment and Scientific Research in March, 2008. The workshop included approximately 40 scientists and regulators representing government, industry, academia, and non-governmental organizations from North America, Europe, and Asia. The goal was to review the state of the science regarding the investigation of fish embryonic tests, pain and distress in fish, emerging approaches utilizing fish embryos, and the use of fish embryo toxicity test data in various types of environmental assessments (e.g., hazard, risk, effluent, and classification and labeling of chemicals). Some specific key outcomes included agreement that risk assessors need fish data for decision-making, that extending the FET to include eluethereombryos was desirable, that relevant endpoints are being used, and that additional endpoints could facilitate additional uses beyond acute toxicity testing. The FET was, however, not yet considered validated sensu OECD. An important action step will be to provide guidance on how all fish tests can be used to assess chemical hazard and to harmonize the diverse terminology used in test guidelines adopted over the past decades. Use of the FET in context of effluent assessments

  4. Understanding and managing risk attitude

    National Research Council Canada - National Science Library

    Hillson, David; Murray-Webster, Ruth

    2007-01-01

    ... This book highlights how risk attitude factors influence the human psyche, and carefully explains the impacts. Organisations seeking to dramatically improve the effectiveness of their risk management process will want to use this book's insights. Craig Peterson, President, PMI Risk Management SIG This book has prompted me to think more deeply as a change d...

  5. Hazard and risk of herbicides for marine microalgae.

    Science.gov (United States)

    Sjollema, Sascha B; Martínezgarcía, Gema; van der Geest, Harm G; Kraak, Michiel H S; Booij, Petra; Vethaak, A Dick; Admiraal, Wim

    2014-04-01

    Due to their specific effect on photosynthesis, herbicides pose a potential threat to coastal and estuarine microalgae. However, comprehensive understanding of the hazard and risk of these contaminants is currently lacking. Therefore the aim of the present study was to investigate the toxic effects of four ubiquitous herbicides (atrazine, diuron, Irgarol(®)1051 and isoproturon) and herbicide mixtures on marine microalgae. Using a Pulse Amplitude Modulation (PAM) fluorometry based bioassay we demonstrated a clear species and herbicide specific toxicity and showed that the current environmental legislation does not protect algae sufficiently against diuron and isoproturon. Although a low actual risk of herbicides in the field was demonstrated, monitoring data revealed that concentrations occasionally reach potential effect levels. Hence it cannot be excluded that herbicides contribute to observed changes in phytoplankton species composition in coastal waters, but this is likely to occur only occasionally. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. The Early Result of Whole Pelvic Radiotherapy and Stereotactic Body Radiotherapy Boost for High Risk Localized Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Yu-Wei eLin

    2014-10-01

    Full Text Available PurposeThe rationale for hypofractionated radiotherapy in the treatment of prostate cancer is based on the modern understanding of radiobiology and advances in stereotactic body radiotherapy (SBRT techniques. Whole-pelvis irradiation combined with SBRT boost for high-risk prostate cancer might escalate biologically effective dose without increasing toxicity. Here, we report our 4-year results of SBRT boost for high-risk localized prostate cancer.Methods and MaterialsFrom October 2009 to August 2012, 41 patients of newly diagnosed, high-risk or very high-risk (NCCN definition localized prostate cancer patients were treated with whole-pelvis irradiation and SBRT boost. The whole pelvis dose was 45Gy (25 fractions of 1.8Gy. The SBRT boost dose was 21 Gy (three fractions of 7 Gy. Ninety percent of these patients received hormone therapy. The toxicities of gastrointestinal (GI and genitourinary (GU tracts were scored by Common Toxicity Criteria Adverse Effect (CTCAE v3.0. Biochemical failure was defined by Phoenix definition.ResultsMedian follow-up was 42 months. Mean PSA before treatment was 44.18 ng/ml. Mean PSA level at 3, 6, 12, 18, and 24 months was 0.94, 0.44, 0.13, 0.12, and 0.05 ng/ml, respectively. The estimated 4-year biochemical failure-free survival was 91.9%. Three biochemical failures were observed. GI and GU tract toxicities were minimal. No grade 3 acute GU or GI toxicity was noted. During radiation therapy, 27% of the patient had grade 2 acute GU toxicity and 12% had grade 2 acute GI toxicity. At 3 months, most toxicity scores had returned to baseline. At the last follow up, there was no grade 3 late GU or GI toxicity.ConclusionsWhole-pelvis irradiation combined with SBRT boost for high-risk localized prostate cancer is feasible with minimal toxicity and encouraging biochemical failure-free survival. Continued accrual and follow-up would be necessary to confirm the biochemical control rate and the toxicity profiles.

  7. Radiological and chemical toxicity risks of uranium in groundwater based-drinking at Immigration Headquarters Gosa and Federal Housing Lugbe area of Abuja, North Central Nigeria

    International Nuclear Information System (INIS)

    Omeje Maxwell; Universiti Teknologi Malaysia, Johor; Husin Wagiran; Olusegun Adewoyin; Joel, E.S.; Ngozi Adeleye; Zaidi Embong; Tenebe, I.T.

    2017-01-01

    Inadequate public water supply by the Water Board in Abuja has forced the public to source for groundwater as the only alternative for consumption without consideration for radiological risk. The radiological risk for cancer mortality of uranium in Immigration Headquarters Gosa and Federal-Housing Lugbe groundwater water samples were measured and compared with Water Board and hand-dug well water samples from the same area using inductively coupled plasma mass spectrometry. The highest radiological risks for cancer mortality and morbidity were found to be low, with highest values of 1.24 × 10"-"7 and 1.64 × 10"-"7 obtained from Federal-Housing Lugbe borehole. The chemical toxicity risk of "2"3"8U in drinking water over life time consumption has a mean value of 4.0 × 10"-"4 μg kg"-"1 day"-"1 with highest value of 6.0 × 10"-"3 μg kg"-"1 day"-"1 obtained from Federal-Housing Lugbe. Significantly, this study inferred that the "2"3"8U concentrations reported in groundwater based-drinking originated from sheared zone of magmatic metamorphosed basaltic dyke intrusion. Due to the low risk values found in the water samples when compared with the International Reference Standard, radiological and chemical toxicity risks values may not pose any health risk to the public that rely on groundwater in the area. (author)

  8. Bioinformatics analysis to assess potential risks of allergenicity and toxicity of HRAP and PFLP proteins in genetically modified bananas resistant to Xanthomonas wilt disease.

    Science.gov (United States)

    Jin, Yuan; Goodman, Richard E; Tetteh, Afua O; Lu, Mei; Tripathi, Leena

    2017-11-01

    Banana Xanthomonas wilt (BXW) disease threatens banana production and food security throughout East Africa. Natural resistance is lacking among common cultivars. Genetically modified (GM) bananas resistant to BXW disease were developed by inserting the hypersensitive response-assisting protein (Hrap) or/and the plant ferredoxin-like protein (Pflp) gene(s) from sweet pepper (Capsicum annuum). Several of these GM banana events showed 100% resistance to BXW disease under field conditions in Uganda. The current study evaluated the potential allergenicity and toxicity of the expressed proteins HRAP and PFLP based on evaluation of published information on the history of safe use of the natural source of the proteins as well as established bioinformatics sequence comparison methods to known allergens (www.AllergenOnline.org and NCBI Protein) and toxins (NCBI Protein). The results did not identify potential risks of allergy and toxicity to either HRAP or PFLP proteins expressed in the GM bananas that might suggest potential health risks to humans. We recognize that additional tests including stability of these proteins in pepsin assay, nutrient analysis and possibly an acute rodent toxicity assay may be required by national regulatory authorities. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  9. Toxicity of compounds with endocrine activity in the OECD 421 reproductive toxicity screening test

    NARCIS (Netherlands)

    Piersma AH; Verhoef A; Elvers LH; Wester PW; LEO; LPI

    1998-01-01

    The issue of endocrine disruption has, in view of human risk assessment, raised the question on whether more sensitive test methods are needed to detect the reproductive toxic properties of xenobiotic compounds with endocrine properties. We studied six known and alleged endocrine disruptors in an

  10. Evaluation of the Potential Risk of Drugs to Induce Hepatotoxicity in Human—Relationships between Hepatic Steatosis Observed in Non-Clinical Toxicity Study and Hepatotoxicity in Humans-

    Science.gov (United States)

    Goda, Keisuke; Kobayashi, Akio; Takahashi, Akemi; Takahashi, Tadakazu; Saito, Kosuke; Maekawa, Keiko; Saito, Yoshiro; Sugai, Shoichiro

    2017-01-01

    In the development of drugs, we sometimes encounter fatty change of the hepatocytes (steatosis) which is not accompanied by degenerative change in the liver in non-clinical toxicity studies. In this study, we investigated the relationships between fatty change of the hepatocytes noted in non-clinical toxicity studies of compound X, a candidate compound in drug development, and mitochondrial dysfunction in order to estimate the potential risk of the compound to induce drug-induced liver injury (DILI) in humans. We conducted in vivo and in vitro exploratory studies for this purpose. In vivo lipidomics analysis was conducted to investigate the relationships between alteration of the hepatic lipids and mitochondrial dysfunction. In the liver of rats treated with compound X, triglycerides containing long-chain fatty acids, which are the main energy source of the mitochondria, accumulated. Accumulation of these triglycerides was considered to be related to the inhibition of mitochondrial respiration based on the results of in vitro mitochondria toxicity studies. In conclusion, fatty change of the hepatocytes (steatosis) in non-clinical toxicity studies of drug candidates can be regarded as a critical finding for the estimation of their potential risk to induce DILI in humans when the fatty change is induced by mitochondrial dysfunction. PMID:28417920

  11. Understanding socioeconomic aspects of risk perception: Progress report, FY-1987: Working draft

    International Nuclear Information System (INIS)

    Liebow, E.B.; Fawcett-Long, J.A.; Terrill, E.S.

    1987-11-01

    This report summarizes progress to date in understanding the issue of risk perception and its implications for the suitability of the Hanford Site in eastern Washington as a location for an underground radioactive waste repository. It presents some observations about the causes, consequences and processes of risk perception gained from a review of the professional literature. It also contains an extensive working bibliography of useful reference materials, and a compilation of abstracts from selected articles that are felt to be of particular relevance to the BWIP licensing and institutional support efforts. 293 refs

  12. Treatment of unresectable hepatocellular carcinoma with intrahepatic yttrium 90 microspheres: factors associated with liver toxicities.

    Science.gov (United States)

    Goin, James E; Salem, Riad; Carr, Brian I; Dancey, Janet E; Soulen, Michael C; Geschwind, Jean Francois H; Goin, Kathleen; Van Buskirk, Mark; Thurston, Kenneth

    2005-02-01

    Intraarterial injection of yttrium 90 microspheres (TheraSpheres) is used in the treatment of hepatocellular carcinoma (HCC). This article presents an analysis of the incidence of liver toxicities (liver-related events) and pretreatment factors associated with liver toxicities after TheraSphere treatment. Eighty-eight TheraSphere-treated patients with low 90-day mortality risk were selected for analysis, with liver toxicities coded with use of standard oncology criteria. Descriptive and inferential statistical methods were applied to estimate the incidence of liver toxicities and to evaluate the influence of liver radiation dose and various pretreatment factors on the risk of their occurrence. Sixty-eight liver toxicities occurred in 37 of the 88 patients (42%). Thirty-two patients (36%) experienced 50 liver toxicities after the first treatment and nine of 23 patients (39%) who received a second treatment experienced 18 liver toxicities. Pretreatment total bilirubin and liver radiation dose were found to be associated with the risk of at least one liver toxicity and with the time to first occurrence of a liver toxicity after first treatment. Pretreatment total bilirubin also was associated with liver toxicities after the second treatment. Most of the toxicities resolved; however, those that did not resolve were attributed to tumor progression or advancing cirrhosis. The risk of liver toxicities in patients with unresectable HCC treated with TheraSpheres increases with increasing pretreatment total bilirubin level and liver radiation dose to a maximum of 150 Gy for a single administration. The toxicities attributed to treatment resolved over time, and none of the patients studied had confirmed radiation-induced liver disease. Consequently, doses as high as 150 Gy on a single administration and as high as 268 Gy on repeated administrations were well tolerated.

  13. Nanotechnology and health safety--toxicity and risk assessments of nanostructured materials on human health.

    Science.gov (United States)

    Singh, Surya; Nalwa, Hari Singh

    2007-09-01

    The field of nanotechnology has recently emerged as the most commercially viable technology of this century because of its wide-ranging applications in our daily lives. Man-made nanostructured materials such as fullerenes, nanoparticles, nanopowders, nanotubes, nanowires, nanorods, nanofibers, quantum dots, dendrimers, nanoclusters, nanocrystals, and nanocomposites are globally produced in large quantities due to their wide potential applications, e.g., in skincare and consumer products, healthcare, electronics, photonics, biotechnology, engineering products, pharmaceuticals, drug delivery, and agriculture. Human exposure to these nanostructured materials is inevitable, as they can enter the body through the lungs or other organs via food, drink, and medicine and affect different organs and tissues such as the brain, liver, kidney, heart, colon, spleen, bone, blood, etc., and may cause cytotoxic effects, e.g., deformation and inhibition of cell growth leading to various diseases in humans and animals. Since a very wide variety of nanostructured materials exits, their interactions with biological systems and toxicity largely depend upon their properties, such as size, concentration, solubility, chemical and biological properties, and stability. The toxicity of nanostructured materials could be reduced by chemical approaches such by surface treatment, functionalization, and composite formation. This review summarizes the sources of various nanostructured materials and their human exposure, biocompatibility in relation to potential toxicological effects, risk assessment, and safety evaluation on human and animal health as well as on the environment.

  14. Degradation of roxarsone in a silt loam soil and its toxicity assessment.

    Science.gov (United States)

    Liang, Tengfang; Ke, Zhengchen; Chen, Qing; Liu, Li; Chen, Guowei

    2014-10-01

    The land application of poultry or swine litter, containing large amounts of roxarsone, causes serious arsenic pollution in soil. Understanding biotransformation process of roxarsone and its potential risks favors proper disposal of roxarsone-contaminated animal litter, yet remains not achieved. We report an experimental study of biotransformation process of roxarsone in a silt loam soil under various soil moisture and temperature conditions, and the toxicity of roxarsone and its products from degradation. Results showed that soil moisture and higher temperature promoted roxarsone degradation, associating with emergent pentavalent arsenic. Analysis of fluorescein diacetate (FDA) hydrolysis activity revealed that roxarsone does not exert acute toxic on soil microbes. With the release of inorganic arsenic, FDA hydrolysis activity was inhibited gradually, as evidenced by ecotoxicological assessment using Photobacterium leiognathi. The results shade new lights on the dynamic roxarsone biotransformation processes in soil, which is important for guiding appropriate disposal of poultry or swine litter in the environment. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Where Lies the Risk? An Ecological Approach to Understanding Child Mental Health Risk and Vulnerabilities in Sub-Saharan Africa

    OpenAIRE

    Atilola, Olayinka

    2014-01-01

    Efforts at improving child-health and development initiatives in sub-Saharan Africa had focused on the physical health of children due to the neglect of child and adolescent mental health (CAMH) policy initiatives. A thorough and broad-based understanding of the prevalent child mental-health risk and vulnerability factors is needed to successfully articulate CAMH policies. In this discourse, we present a narrative on the child mental-health risk and vulnerability factors in sub-Saharan Africa...

  16. Evaluation of levels of select toxic metals in commonly used herbal ...

    African Journals Online (AJOL)

    Even at low concentrations or levels of exposure, toxic metals have also been reported to pose health risks to man. Aim: To ... Materials/Methods :Herbal medicines (n=8) were purchased from on-the-street vendors and evaluated for levels of five toxic metals (Lead, Nickel, Mercury, Cadmium and Arsenic).Analysis of toxic ...

  17. Air toxics: A new concern for the utility industry

    International Nuclear Information System (INIS)

    Torrens, I.; Chow, W.

    1992-01-01

    The 1990 Clean Air Acts Amendments call for EPA studies on utility emissions of potentially hazardous air pollutants and their impact, prior to any decision on regulation of these emissions. The Electric Power Research Institute is carrying out a comprehensive assessment of air toxics risk assessment, consisting of data compilation and analysis, field measurements of priority air toxics at power plants and test facilities, atmospheric transport and deposition, and health/ecological risk assessment. The paper reports on progress to data and objectives of the EPRI assessment

  18. Understanding the toxic potencies of xenobiotics inducing TCDD/TCDF-like effects.

    Science.gov (United States)

    Şahin, A D; Saçan, M T

    2018-02-01

    Toxic potencies of xenobiotics such as halogenated aromatic hydrocarbons inducing 2,3,7,8-tetrachlorodibenzo-p-dioxin/2,3,7,8-tetrachlorodibenzofuran (TCDD/TCDF)-like effects were investigated by quantitative structure-toxicity relationships (QSTR) using their aryl hydrocarbon receptor (AhR) binding affinity data. A descriptor pool was created using the SPARTAN 10, DRAGON 6.0 and ADMET 8.0 software packages, and the descriptors were selected using QSARINS (v.2.2.1) software. The QSTR models generated for AhR binding affinities of chemicals with TCDD/TCDF-like effects were internally and externally validated in line with the Organization of Economic Co-operation and Development (OECD) principles. The TCDD-based model had six descriptors from DRAGON 6.0 and ADMET 8.0, whereas the TCDF-based model had seven descriptors from DRAGON 6.0. The predictive ability of the generated models was tested on a diverse group of chemicals including polychlorinated/brominated biphenyls, dioxins/furans, ethers, polyaromatic hydrocarbons with fused heterocyclic rings (i.e. phenoxathiins, thianthrenes and dibenzothiophenes) and polyaromatic hydrocarbons (i.e. halogenated naphthalenes and phenanthrenes) with no AhR binding data. For the external set chemicals, the structural coverage of the generated models was 90% and 89% for TCDD and TCDF-like effects, respectively.

  19. Sediment nickel bioavailability and toxicity to estuarine crustaceans of contrasting bioturbative behaviors--an evaluation of the SEM-AVS paradigm.

    Science.gov (United States)

    Chandler, G Thomas; Schlekat, Christian E; Garman, Emily R; He, Lijian; Washburn, Katherine M; Stewart, Emily R; Ferry, John L

    2014-11-04

    Robust sediment quality criteria require chemistry and toxicity data predictive of concentrations where population/community response should occur under known geochemical conditions. Understanding kinetic and geochemical effects on toxicant bioavailability is key, and these are influenced by infaunal sediment bioturbation. This study used fine-scale sediment and porewater measurement of contrasting infaunal effects on carbon-normalized SEM-AVS to evaluate safe or potentially toxic nickel concentrations in a high-binding Spartina saltmarsh sediment (4%TOC; 35-45 μmol-S2-·g(-1)). Two crustaceans producing sharply contrasting bioturbation--the copepod Amphiascus tenuiremis and amphipod Leptocheirus plumulosus--were cultured in oxic to anoxic sediments with SEM[Ni]-AVS, TOC, porewater [Ni], and porewater DOC measured weekly. From 180 to 750 μg-Ni·g(-1) sediment, amphipod bioturbation reduced [AVS] and enhanced porewater [Ni]. Significant amphipod uptake, mortality, and growth-depression occurred at the higher sediment [Ni] even when [SEM-AVS]/foc suggested acceptable risk. Less bioturbative copepods produced higher AVS and porewater DOC but exhibited net population growth despite porewater [Ni] 1.3-1.7× their aqueous [Ni] LOEC. Copepod aqueous tests with/without dissolved organic matter showed significant aqueous DOC protection, which suggests porewater DOC attenuates sediment Ni toxicity. The SEM[Ni]-AVS relationship was predictive of acceptable risk for copepods at the important population-growth level.

  20. Toxicity of clay flocculation of the toxic dinoflagellate, Karenia brevis, to estuarine invertebrates and fish

    Science.gov (United States)

    The benthic environmental effects of proposed control procedures for red tide events are relatively unknown but important to understand. The objective of this study was to determine the laboratory-derived toxicities of a clay flocculation technique proposed for the Florida red ti...

  1. Pollution and health risk of potentially toxic metals in urban road dust in Nanjing, a mega-city of China

    International Nuclear Information System (INIS)

    Liu, Enfeng; Yan, Ting; Birch, Gavin; Zhu, Yuxin

    2014-01-01

    Spatial variations in concentrations of a suite of potentially toxic metals (Ba, Cr, Cu, Fe, Mn, Ni, Pb and Zn) and Ca in road dusts (n = 99) from urban trunk roads (TR) in Nanjing, a mega-city in China, were established. Metal pollution levels, sources and human health risk (non-carcinogenic) were studied. In contrast to previous studies, we labeled the indicative metals relating to non-exhaust traffic emissions by comparing metal pollution between crossroad and park road dusts, and then anthropogenic sources of metals in TR dusts were assessed combining their spatial pollution patterns, principal component analysis and Pb isotopic compositions. Results showed that the metals were enriched in TR dusts compared to background soil concentrations with mean enrichment factors (EFs) of 2.2–23, indicating considerable anthropogenic influence. The degrees of metal pollution ranged from minimal to extremely high and ranked by Ca > Cu > Pb ≈ Zn > Cr ≈ Fe > Ni ≈ Ba > Mn on average. Pollution of Cr, Cu, Fe, Mn, Ni, Pb and Zn in TR dusts resulted primarily from industrial emissions (e.g., coal combustion and smelting) and high pollution levels were found close to suburb industrial complexes, whereas pollution of Ba and Ca was mainly related to construction/demolition sources and was generally distributed homogeneously. The relatively minor contribution of non-exhaust traffic emissions to metal pollution in TR dusts was considered to be due to overwhelming industrial and construction/demolition contributions, as well as to the dilution effect of natural soil particles. Ingestion appears to be the major route of exposure for road dust for both adults and children, followed by dermal contact. The non-carcinogenic health risk resulting from exposure to the potentially toxic metals in TR dusts was within the safe level based on the Hazard Index (HI), except in pollution hotspots where exposure to Pb, Cr, and Cu may be hazardous to children. - Highlights: • Pollution and

  2. Pollution and health risk of potentially toxic metals in urban road dust in Nanjing, a mega-city of China

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Enfeng, E-mail: efliu@niglas.ac.cn [State Key Laboratory of Lake Science and Environment, Nanjing Institute of Geography and Limnology, Chinese Academy of Sciences, Nanjing 210008 (China); Yan, Ting [State Key Laboratory of Lake Science and Environment, Nanjing Institute of Geography and Limnology, Chinese Academy of Sciences, Nanjing 210008 (China); Graduate University of Chinese Academy of Sciences, Beijing 100049 (China); Birch, Gavin [School of Geosciences, University of Sydney, Sydney, NSW 2006 (Australia); Zhu, Yuxin [State Key Laboratory of Lake Science and Environment, Nanjing Institute of Geography and Limnology, Chinese Academy of Sciences, Nanjing 210008 (China)

    2014-04-01

    Spatial variations in concentrations of a suite of potentially toxic metals (Ba, Cr, Cu, Fe, Mn, Ni, Pb and Zn) and Ca in road dusts (n = 99) from urban trunk roads (TR) in Nanjing, a mega-city in China, were established. Metal pollution levels, sources and human health risk (non-carcinogenic) were studied. In contrast to previous studies, we labeled the indicative metals relating to non-exhaust traffic emissions by comparing metal pollution between crossroad and park road dusts, and then anthropogenic sources of metals in TR dusts were assessed combining their spatial pollution patterns, principal component analysis and Pb isotopic compositions. Results showed that the metals were enriched in TR dusts compared to background soil concentrations with mean enrichment factors (EFs) of 2.2–23, indicating considerable anthropogenic influence. The degrees of metal pollution ranged from minimal to extremely high and ranked by Ca > Cu > Pb ≈ Zn > Cr ≈ Fe > Ni ≈ Ba > Mn on average. Pollution of Cr, Cu, Fe, Mn, Ni, Pb and Zn in TR dusts resulted primarily from industrial emissions (e.g., coal combustion and smelting) and high pollution levels were found close to suburb industrial complexes, whereas pollution of Ba and Ca was mainly related to construction/demolition sources and was generally distributed homogeneously. The relatively minor contribution of non-exhaust traffic emissions to metal pollution in TR dusts was considered to be due to overwhelming industrial and construction/demolition contributions, as well as to the dilution effect of natural soil particles. Ingestion appears to be the major route of exposure for road dust for both adults and children, followed by dermal contact. The non-carcinogenic health risk resulting from exposure to the potentially toxic metals in TR dusts was within the safe level based on the Hazard Index (HI), except in pollution hotspots where exposure to Pb, Cr, and Cu may be hazardous to children. - Highlights: • Pollution and

  3. Comparison of Toxicities to Vibrio fischeri and Fish Based on Discrimination of Excess Toxicity from Baseline Level

    Science.gov (United States)

    Wang, Xiao H.; Yu, Yang; Huang, Tao; Qin, Wei C.; Su, Li M.; Zhao, Yuan H.

    2016-01-01

    Investigations on the relationship of toxicities between species play an important role in the understanding of toxic mechanisms to environmental organisms. In this paper, the toxicity data of 949 chemicals to fish and 1470 chemicals to V. fischeri were used to investigate the modes of action (MOAs) between species. The results show that although there is a positive interspecies correlation, the relationship is poor. Analysis on the excess toxicity calculated from toxic ratios (TR) shows that many chemicals have close toxicities and share the same MOAs between the two species. Linear relationships between the toxicities and octanol/water partition coefficient (log KOW) for baseline and less inert compounds indicate that the internal critical concentrations (CBRs) approach a constant both to fish and V. fischeri for neutral hydrophobic compounds. These compounds share the same toxic mechanisms and bio-uptake processes between species. On the other hand, some hydrophilic compounds exhibit different toxic effects with greatly different log TR values between V. fischeri and fish species. These hydrophilic compounds were identified as reactive MOAs to V. fischeri, but not to fish. The interspecies correlation is improved by adding a hydrophobic descriptor into the correlation equation. This indicates that the differences in the toxic ratios between fish and V. fischeri for these hydrophilic compounds can be partly attributed to the differences of bioconcentration between the two species, rather than the differences of reactivity with the target macromolecules. These hydrophilic compounds may more easily pass through the cell membrane of V. fischeri than the gill and skin of fish, react with the target macromolecules and exhibit excess toxicity. The compounds with log KOW > 7 exhibiting very low toxicity (log TR toxicity and MOAs. PMID:26901437

  4. A review of current knowledge on toxic benthic freshwater cyanobacteria--ecology, toxin production and risk management.

    Science.gov (United States)

    Catherine, Quiblier; Susanna, Wood; Isidora, Echenique-Subiabre; Mark, Heath; Aurélie, Villeneuve; Jean-François, Humbert

    2013-10-01

    Benthic cyanobacteria are found globally in plethora of environments. Although they have received less attention than their planktonic freshwater counterparts, it is now well established that they produce toxins and reports of their involvement in animal poisonings have increased markedly during the last decade. Most of the known cyanotoxins have been identified from benthic cyanobacteria including: the hepatotoxic microcystins, nodularins and cylindrospermopsins, the neurotoxic saxitoxins, anatoxin-a and homoanatoxin-a and dermatotoxins, such as lyngbyatoxin. In most countries, observations of toxic benthic cyanobacteria are fragmented, descriptive and in response to animal toxicosis events. Only a limited number of long-term studies have aimed to understand why benthic proliferations occur, and/or how toxin production is regulated. These studies have shown that benthic cyanobacterial blooms are commonly a mixture of toxic and non-toxic genotypes and that toxin concentrations can be highly variable spatially and temporally. Physiochemical parameters responsible for benthic proliferation vary among habitat type with physical disturbance (e.g., flow regimes, wave action) and nutrients commonly identified as important. As climatic conditions change and anthropogenic pressures on waterways increase, it seems likely that the prevalence of blooms of benthic cyanobacteria will increase. In this article we review current knowledge on benthic cyanobacteria: ecology, toxin-producing species, variables that regulate toxin production and bloom formation, their impact on aquatic and terrestrial organisms and current monitoring and management strategies. We suggest research needs that will assist in filling knowledge gaps and ultimately allow more robust monitoring and management protocols to be developed. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Maternal and developmental toxicity of ayahuasca in Wistar rats.

    Science.gov (United States)

    Oliveira, Carolina Dizioli Rodrigues; Moreira, Camila Queiroz; de Sá, Lilian Rose Marques; Spinosa, Helenice de Souza; Yonamine, Mauricio

    2010-06-01

    Ayahuasca is a psychotropic plant beverage initially used by shamans throughout the Amazon region during traditional religious cult. In recent years, ayahuasca has also been used in ceremonies of a number of modern syncretic religious groups, including pregnant women. However, no documented study has been performed to evaluate the risk of developmental toxicity of ayahuasca. In the present work, maternal and developmental toxicity was evaluated in Wistar rats. Ayahuasca was administered to pregnant rats in three different doses [the equivalent typical dose (TD) administered to humans, five-fold TD and 10-fold TD] during the gestational period (6-20 days). Dams treated with the highest ayahuasca dose showed maternal toxicity with decrease of weight gain and food intake. Visceral fetal findings were observed in all treatment groups. Skeletal findings were observed in the intermediate- and high-dose groups. The fetuses deriving from the highest dose group also presented a decrease in body weight. From these results, it is possible to conclude that there is a risk of maternal and developmental toxicity following ayahuasca exposure and that the level of toxicity appears to be dose-dependent.

  6. Risk of Severe Toxicity According to Site of Recurrence in Patients Treated With Stereotactic Body Radiation Therapy for Recurrent Head and Neck Cancer

    International Nuclear Information System (INIS)

    Ling, Diane C.; Vargo, John A.; Ferris, Robert L.; Ohr, James; Clump, David A.; Yau, Wai-Ying Wendy; Duvvuri, Umamaheswar; Kim, Seungwon; Johnson, Jonas T.; Bauman, Julie E.; Branstetter, Barton F.; Heron, Dwight E.

    2016-01-01

    Purpose: To report a 10-year update of our institutional experience with stereotactic body radiation therapy (SBRT) for reirradiation of locally recurrent head and neck cancer, focusing on predictors of toxicity. Methods and Materials: A retrospective review was performed on 291 patients treated with SBRT for recurrent, previously irradiated head and neck cancer between April 2002 and March 2013. Logistic regression analysis was performed to identify predictors of severe acute and late toxicity. Patients with <3 months of follow-up (n=43) or who died within 3 months of treatment (n=21) were excluded from late toxicity analysis. Results: Median time to death or last clinical follow-up was 9.8 months among the entire cohort and 53.1 months among surviving patients. Overall, 33 patients (11.3%) experienced grade ≥3 acute toxicity and 43 (18.9%) experienced grade ≥3 late toxicity. Compared with larynx/hypopharynx, treatment of nodal recurrence was associated with a lower risk of severe acute toxicity (P=.03), with no significant differences in severe acute toxicity among other sites. Patients treated for a recurrence in the larynx/hypopharynx experienced significantly more severe late toxicity compared with those with oropharyngeal, oral cavity, base of skull/paranasal sinus, salivary gland, or nodal site of recurrence (P<.05 for all). Sixteen patients (50%) with laryngeal/hypopharyngeal recurrence experienced severe late toxicity, compared with 6-20% for other sites. Conclusions: Salvage SBRT is a safe and effective option for most patients with previously irradiated head and neck cancer. However, patients treated to the larynx or hypopharynx experience significantly more late toxicity compared with others and should be carefully selected for treatment, with consideration given to patient performance status, pre-existing organ dysfunction, and goals of care. Treatment toxicity in these patients may be mitigated with more conformal plans to allow for increased

  7. Risk of Severe Toxicity According to Site of Recurrence in Patients Treated With Stereotactic Body Radiation Therapy for Recurrent Head and Neck Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Ling, Diane C.; Vargo, John A. [Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania (United States); Ferris, Robert L. [Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania (United States); Department of Otolaryngology, Head and Neck Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Ohr, James [Division of Medical Oncology, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Clump, David A.; Yau, Wai-Ying Wendy [Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania (United States); Duvvuri, Umamaheswar; Kim, Seungwon; Johnson, Jonas T. [Department of Otolaryngology, Head and Neck Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Bauman, Julie E. [Division of Medical Oncology, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Branstetter, Barton F. [Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania (United States); Heron, Dwight E., E-mail: herond2@umpc.edu [Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania (United States); Department of Otolaryngology, Head and Neck Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania (United States)

    2016-07-01

    Purpose: To report a 10-year update of our institutional experience with stereotactic body radiation therapy (SBRT) for reirradiation of locally recurrent head and neck cancer, focusing on predictors of toxicity. Methods and Materials: A retrospective review was performed on 291 patients treated with SBRT for recurrent, previously irradiated head and neck cancer between April 2002 and March 2013. Logistic regression analysis was performed to identify predictors of severe acute and late toxicity. Patients with <3 months of follow-up (n=43) or who died within 3 months of treatment (n=21) were excluded from late toxicity analysis. Results: Median time to death or last clinical follow-up was 9.8 months among the entire cohort and 53.1 months among surviving patients. Overall, 33 patients (11.3%) experienced grade ≥3 acute toxicity and 43 (18.9%) experienced grade ≥3 late toxicity. Compared with larynx/hypopharynx, treatment of nodal recurrence was associated with a lower risk of severe acute toxicity (P=.03), with no significant differences in severe acute toxicity among other sites. Patients treated for a recurrence in the larynx/hypopharynx experienced significantly more severe late toxicity compared with those with oropharyngeal, oral cavity, base of skull/paranasal sinus, salivary gland, or nodal site of recurrence (P<.05 for all). Sixteen patients (50%) with laryngeal/hypopharyngeal recurrence experienced severe late toxicity, compared with 6-20% for other sites. Conclusions: Salvage SBRT is a safe and effective option for most patients with previously irradiated head and neck cancer. However, patients treated to the larynx or hypopharynx experience significantly more late toxicity compared with others and should be carefully selected for treatment, with consideration given to patient performance status, pre-existing organ dysfunction, and goals of care. Treatment toxicity in these patients may be mitigated with more conformal plans to allow for increased

  8. Methotrexate-induced toxicity pharmacogenetics: an umbrella review of systematic reviews and meta-analyses.

    Science.gov (United States)

    Campbell, Jared M; Bateman, Emma; Stephenson, Matthew D; Bowen, Joanne M; Keefe, Dorothy M; Peters, Micah D J

    2016-07-01

    Methotrexate chemotherapy is associated with various toxicities which can result in the interruption or discontinuation of treatment and a subsequently raised risk of relapse. This umbrella systematic review was conducted to synthesize the results of all existing systematic reviews that investigate the pharmacogenetics of methotrexate-induced toxicity, with the aim of developing a comprehensive reference for personalized medicine. Databases searched were PubMed, Embase, JBI Database of Systematic Reviews and Implementation Reports, DARE, and ProQuest. Papers were critically appraised by two reviewers, and data were extracted using a standardized tool. Three systematic reviews on methotrexate-induced toxicity were included in the review. Meta-analyses were reported across Asian, Caucasian, pediatric and adult patients for the MTHFR C677T and A1298C polymorphisms. Toxicity outcomes included different forms of hematologic, ectodermal and hepatic toxicities. Results varied considerably depending on the patient groups and subgroups investigated in the different systematic reviews, as well as the genetic models utilized. However, significant associations were found between the MTHFR C677T allele and; hepatic toxicity, myelosuppression, oral mucositis, gastrointestinal toxicity, and skin toxicity. Additionally, limited evidence suggests that the MTHFR A1298C polymorphism may be associated with decreased risk of skin toxicity and leukopenia. This umbrella systematic review has synthesized the best available evidence on the pharmacogenetics of methotrexate toxicity. The next step in making personalized medicine for methotrexate therapy a clinical reality is research on the effectiveness and cost-effectiveness of MTHFR genotype testing to enable the close monitoring of at-risk patients for the timely initiation of rescue therapies.

  9. A neurogenetics approach to understanding individual differences in brain, behavior, and risk for psychopathology.

    Science.gov (United States)

    Bogdan, R; Hyde, L W; Hariri, A R

    2013-03-01

    Neurogenetics research has begun to advance our understanding of how genetic variation gives rise to individual differences in brain function, which, in turn, shapes behavior and risk for psychopathology. Despite these advancements, neurogenetics research is currently confronted by three major challenges: (1) conducting research on individual variables with small effects, (2) absence of detailed mechanisms, and (3) a need to translate findings toward greater clinical relevance. In this review, we showcase techniques and developments that address these challenges and highlight the benefits of a neurogenetics approach to understanding brain, behavior and psychopathology. To address the challenge of small effects, we explore approaches including incorporating the environment, modeling epistatic relationships and using multilocus profiles. To address the challenge of mechanism, we explore how non-human animal research, epigenetics research and genome-wide association studies can inform our mechanistic understanding of behaviorally relevant brain function. Finally, to address the challenge of clinical relevance, we examine how neurogenetics research can identify novel therapeutic targets and for whom treatments work best. By addressing these challenges, neurogenetics research is poised to exponentially increase our understanding of how genetic variation interacts with the environment to shape the brain, behavior and risk for psychopathology.

  10. Gastrointestinal toxicity, systemic inflammation, and liver biochemistry in allogeneic hematopoietic stem cell transplantation

    DEFF Research Database (Denmark)

    Jordan, Karina; Pontoppidan, Peter; Uhlving, Hilde Hylland

    2017-01-01

    Liver toxicity is frequently seen in relation to allogeneic hematopoietic stem cell transplantation (HSCT), but pathogenesis and the risk factors are poorly understood. The purpose of this study was to investigate associations between liver toxicity, gastrointestinal toxicity, and levels of immun...

  11. The distinction between risk and hazard: understanding and use in stakeholder communication.

    Science.gov (United States)

    Scheer, Dirk; Benighaus, Christina; Benighaus, Ludger; Renn, Ortwin; Gold, Stefan; Röder, Bettina; Böl, Gaby-Fleur

    2014-07-01

    A major issue in all risk communication efforts is the distinction between the terms "risk" and "hazard." The potential to harm a target such as human health or the environment is normally defined as a hazard, whereas risk also encompasses the probability of exposure and the extent of damage. What can be observed again and again in risk communication processes are misunderstandings and communication gaps related to these crucial terms. We asked a sample of 53 experts from public authorities, business and industry, and environmental and consumer organizations in Germany to outline their understanding and use of these terms using both the methods of expert interviews and focus groups. The empirical study made clear that the terms risk and hazard are perceived and used very differently in risk communication depending on the perspective of the stakeholders. Several factors can be identified, such as responsibility for hazard avoidance, economic interest, or a watchdog role. Thus, communication gaps can be reduced to a four-fold problem matrix comprising a semantic, conceptual, strategic, and control problem. The empirical study made clear that risks and hazards are perceived very differently depending on the stakeholders' perspective. Their own worldviews played a major role in their specific use of the two terms hazards and risks in communication. © 2014 Society for Risk Analysis.

  12. TGFβ1 SNPs and radio-induced toxicity in prostate cancer patients

    International Nuclear Information System (INIS)

    Fachal, Laura; Gómez-Caamaño, Antonio; Sánchez-García, Manuel; Carballo, Ana; Peleteiro, Paula; Lobato-Busto, Ramón; Carracedo, Ángel; Vega, Ana

    2012-01-01

    Background and purpose: We have performed a case-control study in 413 prostate cancer patients to test for association between TGFβ1 and the development of late normal-tissue toxicity among prostate cancer patients treated with three-dimensional conformational radiotherapy (3D-CRT) Materials and methods: Late gastrointestinal and genitourinary toxicities were assessed for at least two years after radiotherapy in 413 patients according to CTCAEvs3 scores. Codominant genotypic tests and haplotypic analyses were undertaken to evaluate the correlation between TGFβ1 SNPs rs1800469, rs1800470 and rs1800472 and radio-induced toxicity. Results: Neither the SNPs nor the haplotypes were found to be associated with the risk of late toxicity. Conclusions: We were able to exclude up to a 2-fold increase in the risk of developing late gastrointestinal and genitourinary radio-induced toxicity due to the TGFβ1 SNPs rs1800469 and rs1800470, as well as the two most frequent TGFβ1 haplotypes.

  13. Systems Toxicology: The Future of Risk Assessment.

    Science.gov (United States)

    Sauer, John Michael; Hartung, Thomas; Leist, Marcel; Knudsen, Thomas B; Hoeng, Julia; Hayes, A Wallace

    2015-01-01

    Risk assessment, in the context of public health, is the process of quantifying the probability of a harmful effect to individuals or populations from human activities. With increasing public health concern regarding the potential risks associated with chemical exposure, there is a need for more predictive and accurate approaches to risk assessment. Developing such an approach requires a mechanistic understanding of the process by which xenobiotic substances perturb biological systems and lead to toxicity. Supplementing the shortfalls of traditional risk assessment with mechanistic biological data has been widely discussed but not routinely implemented in the evaluation of chemical exposure. These mechanistic approaches to risk assessment have been generally referred to as systems toxicology. This Symposium Overview article summarizes 4 talks presented at the 35th Annual Meeting of the American College of Toxicology. © The Author(s) 2015.

  14. Pollution, toxicity, and ecological risk of heavy metals in surface river sediments of a large basin undergoing rapid economic development.

    Science.gov (United States)

    Tang, Wenzhong; Zhang, Chao; Zhao, Yu; Shan, Baoqing; Song, Zhixin

    2017-05-01

    A comprehensive and detailed investigation of heavy metal pollution, toxicity, and ecological risk assessment was conducted for the surface river sediments of the Haihe Basin in China based on 220 sampling sites selected in 2013. The average concentrations of Cr, Cu, Ni, Pb, and Zn in the sediments were 129 mg/kg, 63.4 mg/kg, 36.6 mg/kg, 50.0 mg/kg, and 202 mg/kg, respectively. As indicated by the geoaccumulation and pollution load indices, most surface river sediments of the Haihe Basin were contaminated with the investigated metals, especially in the junction region of the Zi Ya He and Hei Long Gang watersheds. The 5 heavy metals in the sediments all had anthropogenic sources, and the enrichment degrees followed the order Cu > Pb > Zn > Cr > Ni, with mean enrichment factors of 3.27, 2.77, 2.58, 1.81, and 1.44, respectively. According to the mean index of comprehensive potential ecological risk (38.9), the studied sediments of the Haihe Basin showed low potential ecological risk, but the sediments were potentially biologically toxic based on the mean probable effect concentration quotient (0.547), which may be the result of speciation of the 5 metals in the sediments. The results indicate that heavy metal pollution should be considered during the development of ecological restoration strategies in the Haihe Basin. Environ Toxicol Chem 2017;36:1149-1155. © 2016 SETAC. © 2016 SETAC.

  15. Evaluation of the Potential Risk of Drugs to Induce Hepatotoxicity in Human?Relationships between Hepatic Steatosis Observed in Non-Clinical Toxicity Study and Hepatotoxicity in Humans-

    OpenAIRE

    Goda, Keisuke; Kobayashi, Akio; Takahashi, Akemi; Takahashi, Tadakazu; Saito, Kosuke; Maekawa, Keiko; Saito, Yoshiro; Sugai, Shoichiro

    2017-01-01

    In the development of drugs, we sometimes encounter fatty change of the hepatocytes (steatosis) which is not accompanied by degenerative change in the liver in non-clinical toxicity studies. In this study, we investigated the relationships between fatty change of the hepatocytes noted in non-clinical toxicity studies of compound X, a candidate compound in drug development, and mitochondrial dysfunction in order to estimate the potential risk of the compound to induce drug-induced liver injury...

  16. Understanding radiation and risk: the importance of primary and secondary education

    International Nuclear Information System (INIS)

    Tada, Junichiro

    1999-01-01

    In Japan's primary and secondary schools, radiation and radioactivity are taught as part of the curriculum dealing with social science subjects. Students learn much about the hazardous features of radiation, but lack the scientific understanding necessary to build a more balanced picture. Although the same point applies to education covering the harmful effects of volcanic eruptions, earthquakes, electrical storms and so on, public understanding of these events is relatively high and students are generally able to make informed judgments about the risks involved. By contrast, their limited understanding of radiation often contributes to fears that it is evil or even supernatural. To correct this distortion, it is important that primary and secondary education includes a scientific explanation of radiation. Like heat and light, radiation is fundamental to the history of the universe; and scientific education programs should give appropriate emphasis to this important subject. Students would then be able to make more objective judgments about the useful and hazardous aspects of radiation. (author)

  17. Understanding radiation and risk: the importance of primary and secondary education

    Energy Technology Data Exchange (ETDEWEB)

    Tada, Junichiro [Japan Synchrotron Radiation Research Institute (SPring-8), Mikaduki, Hyogo (Japan)

    1999-09-01

    In Japan's primary and secondary schools, radiation and radioactivity are taught as part of the curriculum dealing with social science subjects. Students learn much about the hazardous features of radiation, but lack the scientific understanding necessary to build a more balanced picture. Although the same point applies to education covering the harmful effects of volcanic eruptions, earthquakes, electrical storms and so on, public understanding of these events is relatively high and students are generally able to make informed judgments about the risks involved. By contrast, their limited understanding of radiation often contributes to fears that it is evil or even supernatural. To correct this distortion, it is important that primary and secondary education includes a scientific explanation of radiation. Like heat and light, radiation is fundamental to the history of the universe; and scientific education programs should give appropriate emphasis to this important subject. Students would then be able to make more objective judgments about the useful and hazardous aspects of radiation. (author)

  18. [Tetany secondary to phosphate enema toxicity, case report].

    Science.gov (United States)

    Núñez Sánchez, María José; Leighton Swaneck, Sofía; Díaz, Franco

    2017-06-01

    Phosphate enemas are frequently used in the treatment of constipation. Errors in dosage and administration can lead to severe complications. To report a case of severe toxicity of phosphate enemas in a child with no risk factors. 2 years old female, with functional constipation, was brought to emergency department because abdominal pain. She was diagnosed with fecal impaction and received half a bottle of Fleet Adult® (Laboratorio Synthon, Chile) two times, with no clinical resolution, deciding to start proctoclisis in pediatric ward. Soon after admission, she presented painful tetany, but alert and oriented. Patient was transferred to PICU where severe hyperphosphatemia and secondary hypocalcemia were confirmed. Her treatment included electrolyte correction; removal of residual phosphate enema and hyperhydration. Tetany resolved over 2 hours after admission and no other complications. Proctoclisis was performed and patient was discharged three days after admission with pharmacological management of constipation. Phosphate enemas may cause serious complications in children with no risk factors. Errors in dosage, administration and removal of the enema are causes of toxicity in this group. Pediatricians and health personnel must be aware of risks and signs of toxicity of phosphate enema.

  19. Risk Assessment for Toxic Air Pollutants: A Citizen's Guide

    Science.gov (United States)

    ... poisonous substances in the air that come from natural sources (for example, radon gas coming up from the ground) or from manmade sources (for example, chemical compounds given off by factory smokestacks) and can harm the environment or your health. Inhaling (or breathing) toxic air ...

  20. Major Late Toxicities After Conformal Radiotherapy for Nasopharyngeal Carcinoma-Patient- and Treatment-Related Risk Factors

    International Nuclear Information System (INIS)

    Lee, Anne W.M.; Ng, W.T.; Hung, W.M.; Choi, C.W.; Tung, Raymond; Ling, Y.H.; Cheng, Peter T.C.; Yau, T.K.; Chang, Amy T.Y.; Leung, Samuel K.C.; Lee, Michael C.H.; Bentzen, Soren M.

    2009-01-01

    Purpose: To retrospectively analyze the factors affecting late toxicity for nasopharyngeal carcinoma. Methods and Materials: Between 1998 and 2003, 422 patients were treated with a conformal technique with 2-Gy daily fractions to a total dose of 70 Gy. Conventional fractionation (5 fractions weekly) was used in 232 patients and accelerated fractionation (6 fractions weekly) in 190 patients. One hundred seventy-one patients were treated with the basic radiotherapy course alone (Group 1), 55 patients had an additional boost of 5 Gy in 2 fractions (Group 2), and 196 patients underwent concurrent cisplatin-based chemotherapy (Group 3). Results: The 5-year overall toxicity rate was significantly greater in Group 3 than in Group 1 (37% vs. 27%, p = 0.009). Although the overall rate in Group 2 was not elevated (28% vs. 27%, p = 0.697), a significant increase in temporal lobe necrosis was observed (4.8% vs. 0%, p = 0.015). Multivariate analyses showed that age and concurrent chemotherapy were significant factors. The hazard ratio of overall toxicity attributed to chemotherapy was 1.99 (95% confidence interval, 1.32-2.99, p = 0.001). The mean radiation dose to the cochlea was another significant factor affecting deafness, with a hazard ratio of 1.03 (95% confidence interval, 1.01-1.05, p = 0.005) per 1-Gy increase. The cochlea that received >50 Gy had a significantly greater deaf rate (Group 1, 18% vs. 7%; and Group 3, 22% vs. 14%). Conclusion: The therapeutic margin for nasopharyngeal carcinoma is extremely narrow, and a significant increase in brain necrosis could result from dose escalation. The significant factors affecting the risk of deafness included age, concurrent chemoradiotherapy, and greater radiation dose to the cochlea

  1. Gastrointestinal toxicity, systemic inflammation, and liver biochemistry in allogeneic hematopoietic stem cell transplantation

    Science.gov (United States)

    Liver toxicity is frequently seen in relation to allogeneic hematopoietic stem cell transplantation (HSCT), but pathogenesis and the risk factors are poorly understood. The purpose of this study was to investigate associations between liver toxicity, gastrointestinal toxicity, and levels of immune-r...

  2. Microplastics: addressing ecological risk through lessons learned.

    Science.gov (United States)

    Syberg, Kristian; Khan, Farhan R; Selck, Henriette; Palmqvist, Annemette; Banta, Gary T; Daley, Jennifer; Sano, Larissa; Duhaime, Melissa B

    2015-05-01

    Plastic litter is an environmental problem of great concern. Despite the magnitude of the plastic pollution in our water bodies, only limited scientific understanding is available about the risk to the environment, particularly for microplastics. The apparent magnitude of the problem calls for quickly developing sound scientific guidance on the ecological risks of microplastics. The authors suggest that future research into microplastics risks should be guided by lessons learned from the more advanced and better understood areas of (eco) toxicology of engineered nanoparticles and mixture toxicity. Relevant examples of advances in these two fields are provided to help accelerate the scientific learning curve within the relatively unexplored area of microplastics risk assessment. Finally, the authors advocate an expansion of the "vector effect" hypothesis with regard to microplastics risk to help focus research of microplastics environmental risk at different levels of biological and environmental organization. © 2015 SETAC.

  3. Haloacetonitriles: metabolism and toxicity.

    Science.gov (United States)

    Lipscomb, John C; El-Demerdash, Ebtehal; Ahmed, Ahmed E

    2009-01-01

    bioactivation process, depending on the particular HAN and the enzyme involved. HANs can inhibit CYP2E1-mediated metabolism, an effect which may be dependent on a covalent interaction with the enzyme. In addition, HAN compounds inhibit GST-mediated conjugation, but this effect is reversible upon dialysis, indicating that the interaction does not represent covalent binding. No subchronic studies of HAN toxicity are available in the literature. However, studies show that HANs produce developmental toxicity in experimental animals. The nature of developmental toxicity is affected by the type of administration vehicle, which renders interpretation of results more difficult. Skin tumors have been found following dermal application of HANs, but oral studies for carcinogenicity are negative. Pulmonary adenomas were increased following oral administration of HANs, but the A/J strain of mice employed has a characteristically high background rate of such tumors. HANs interact with DNA to produce unscheduled DNA repair, SCE and reverse mutations in Salmonella. HANs did not induce micronuclei or cause alterations in sperm head morphology in mice, but did induce micronuclei in newts. Thus, there is concern for the potential carcinogenicity of HANs. It would be valuable to delineate any relationship between the apparent threshold for micronuclei formation in newts and the potential mechanism of toxicity involving HAN-induced oxidative stress. Dose-response studies in rodents may provide useful information on toxicity mechanisms and dose selection for longer term toxicity studies. Additional studies are warranted before drawing firm conclusions on the hazards of HAN exposure. Moreover, additional studies on HAN-DNA and HAN-protein interaction mechanisms, are needed. Such studies can better characterize the role of metabolism in toxicity of individual HANs, and delineate the role of oxidative stress, both of which enhance the capacity to predict risk. Most needed, now, are new subchronic (and

  4. Predicting the risk of developmental toxicity from in vitro assays

    International Nuclear Information System (INIS)

    Spielmann, Horst

    2005-01-01

    Reproductive toxicity refers to the adverse effects of a substance on any aspect of the reproductive cycle, including the impairment of reproductive function, the induction of adverse effects in the embryo, such as growth retardation, malformations, and death. Due to the complexity of the mammalian reproductive cycle, it is impossible to model the whole cycle in a single in vitro system in order to detect chemical effects on mammalian reproduction. However, the cycle can be broken down in its biological components which may be studied individually or in combination. This approach has the advantage that the target tissue/organ of a developmental toxicant can be identified. In specific areas of developmental toxicity, a number of useful and promising in vitro models are already available. The individual tests may be used as building blocks of a tiered testing strategy. So far, research has focused on developing and validating tests covering only a few components of the reproductive cycle, in particular organogenesis of the embryo, reflecting important concerns for teratogenic chemicals. During the last three decades, a number of established models and promising new developments have emerged that will be discussed, e.g. culture of mammalian embryos and embryonic cells and tissues and the use of embryonic stem cells

  5. [Does nodal irradiation (clavicular and internal mammary chains) increase the toxicity of adjuvant breast radiotherapy?].

    Science.gov (United States)

    Riou, O; Bourgier, C; Fenoglietto, P; Azria, D

    2015-06-01

    Treatment volume is a major risk factor of radiation-induced toxicity. As nodal irradiation increases treatment volume, radiation toxicity should be greater. Nevertheless, scientific randomised data do not support this fact. However, a radiation-induced toxicity is possible outside tangential fields in the nodal volumes not related to breast-only treatment. Treatment should not be adapted only to the disease but personalized to the individual risk of toxicity for each patient. Copyright © 2015 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

  6. Precarity in late life: Understanding new forms of risk and insecurity.

    Science.gov (United States)

    Grenier, Amanda; Phillipson, Chris; Laliberte Rudman, Debbie; Hatzifilalithis, Stephanie; Kobayashi, Karen; Marier, Patrik

    2017-12-01

    Population aging and longevity in the context of declining social commitments, raises concerns about disadvantage and widening inequality in late life. This paper explores the concept of precarity as a means to understand new and sustained forms of risk and insecurity that affect late life. The article begins with a review of the definition and uses of precarity in a range of scholarly fields including social gerontology. It then draws on illustrations from three locations of experience including older women, aging with a disability, and the foreign-born, to outline how precarity renders visible the disadvantages carried into late life, and new insecurities that emerge at the moment of needing care in the context of austerity. The argument being put forward is that precarity can be used to illustrate how risks and insecurities, experienced over time, in longevity, and the context of austerity, can deepen disadvantage. This lens thus holds the potential to challenge individual interpretations of risk, and situate experiences of disadvantage in the economic and political context. We conclude that contemporary conditions of austerity and longevity intersect to produce and sustain risk and disadvantage into late life. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Genome-wide association study identifies chromosome 10q24.32 variants associated with arsenic metabolism and toxicity phenotypes in Bangladesh.

    Directory of Open Access Journals (Sweden)

    Brandon L Pierce

    Full Text Available Arsenic contamination of drinking water is a major public health issue in many countries, increasing risk for a wide array of diseases, including cancer. There is inter-individual variation in arsenic metabolism efficiency and susceptibility to arsenic toxicity; however, the basis of this variation is not well understood. Here, we have performed the first genome-wide association study (GWAS of arsenic-related metabolism and toxicity phenotypes to improve our understanding of the mechanisms by which arsenic affects health. Using data on urinary arsenic metabolite concentrations and approximately 300,000 genome-wide single nucleotide polymorphisms (SNPs for 1,313 arsenic-exposed Bangladeshi individuals, we identified genome-wide significant association signals (P<5×10(-8 for percentages of both monomethylarsonic acid (MMA and dimethylarsinic acid (DMA near the AS3MT gene (arsenite methyltransferase; 10q24.32, with five genetic variants showing independent associations. In a follow-up analysis of 1,085 individuals with arsenic-induced premalignant skin lesions (the classical sign of arsenic toxicity and 1,794 controls, we show that one of these five variants (rs9527 is also associated with skin lesion risk (P = 0.0005. Using a subset of individuals with prospectively measured arsenic (n = 769, we show that rs9527 interacts with arsenic to influence incident skin lesion risk (P = 0.01. Expression quantitative trait locus (eQTL analyses of genome-wide expression data from 950 individual's lymphocyte RNA suggest that several of our lead SNPs represent cis-eQTLs for AS3MT (P = 10(-12 and neighboring gene C10orf32 (P = 10(-44, which are involved in C10orf32-AS3MT read-through transcription. This is the largest and most comprehensive genomic investigation of arsenic metabolism and toxicity to date, the only GWAS of any arsenic-related trait, and the first study to implicate 10q24.32 variants in both arsenic metabolism and arsenical

  8. The effects of infographics and several quantitative versus qualitative formats for cardiovascular disease risk, including heart age, on people's risk understanding.

    Science.gov (United States)

    Damman, Olga C; Vonk, Suzanne I; van den Haak, Maaike J; van Hooijdonk, Charlotte M J; Timmermans, Danielle R M

    2018-03-11

    To study how comprehension of cardiovascular disease (CVD) risk is influenced by: (1) infographics about qualitative risk information, with/without risk numbers; (2) which qualitative risk dimension is emphasized; (3) heart age vs. traditional risk format. For aim 1, a 2 (infographics versus text) x 2 (risk number versus no risk number) between-subjects design was used. For aim 2, three pieces of information were tested within-subjects. Aim 3 used a simple comparison group. Participants (45-65 yrs old) were recruited through an online access panel; low educated people were oversampled. They received hypothetical risk information (20%/61yrs). Primary outcomes: recall, risk appraisals, subjective/objective risk comprehension. behavioral intentions, information evaluations. Infographics of qualitative risk dimensions negatively affected recall, subjective risk comprehension and information evaluations. No effect of type of risk dimension was found on risk perception. Heart age influenced recall, comprehension, evaluations and affective risk appraisals. Infographics of hypothetical CVD risk information had detrimental effects on measures related to risk perception/comprehension, but effects were mainly seen in undereducated participants. Heart age influenced perceptions/comprehension of hypothetical risk in a way that seemed to support understanding. Heart age seems a fruitful risk communication approach in disease risk calculators. Copyright © 2018 Elsevier B.V. All rights reserved.

  9. Group Waterpipe Tobacco Smoking Increases Smoke Toxicant Concentration.

    Science.gov (United States)

    Ramôa, Carolina P; Shihadeh, Alan; Salman, Rola; Eissenberg, Thomas

    2016-05-01

    Waterpipe tobacco smoking is a global health concern. Laboratory research has focused on individual waterpipe users while group use is common. This study examined user toxicant exposure and smoke toxicant yield associated with individual and group waterpipe smoking. Twenty-two pairs of waterpipe smokers used a waterpipe individually and as a dyad. Before and after smoking, blood was sampled and expired carbon monoxide (CO) measured; puff topography was recorded throughout. One participant from each pair was selected randomly and their plasma nicotine and expired air CO concentrations were compared when smoking alone to when smoking as part of a dyad. Recorded puff topography was used to machine-produce smoke that was analyzed for toxicant content. There was no difference in mean plasma nicotine concentration when an individual smoked as part of a dyad (mean = 14.9 ng/ml; standard error of the mean [SEM] = 3.0) compared to when smoking alone (mean = 10.0 ng/ml; SEM = 1.5). An individual smoking as part of as a dyad had, on average, lower CO (mean = 15.8 ppm; SEM = 2.0) compared to when smoking alone (mean= 21.3 ppm; SEM = 2.7). When two participants smoked as a dyad they took, on average, more puffs (mean = 109.8; SEM = 7.6) than a singleton smoker (mean = 77.7; SEM = 8.1) and a shorter interpuff interval (IPI; dyad mean = 23.8 seconds; SEM = 1.9; singleton mean = 40.8 seconds; SEM = 4.8). Higher concentrations of several toxicants were observed in dyad-produced smoke. Dyad smoking may increase smoke toxicant content, likely due to the dyad's shorter IPIs and greater puff number. More work is needed to understand if group waterpipe smoking alters the health risks of waterpipe tobacco smoking. This study is the first to measure toxicants in smoke generated from a waterpipe when used by a dyad. Relative to smoke generated by a singleton, dyad smoke had higher concentration of some toxicants. These differences may be attributed to differences in puffing behavior

  10. Dehydropyrrolizidine alkaloid toxicity, cytotoxicity, and carcinogenicity

    Science.gov (United States)

    Dehyro-pyrrolizidine alkaloid (PA)-containing plants compose about 5% of the world’s flowering plants and they commonly poison livestock, wildlife and humans. Previous work has produced considerable understanding of PA toxicity, species susceptibility, conditions and routes of exposure, toxin metab...

  11. Current understanding of the toxicological risk posed to the fetus following maternal exposure to nanoparticles.

    Science.gov (United States)

    Zhang, Yanli; Wu, Junrong; Feng, Xiaoli; Wang, Ruolan; Chen, Aijie; Shao, Longquan

    2017-12-01

    With the broad use of nanotechnology, the number and variety of nanoparticles that humans can be exposed to has further increased. Consequently, there is growing concern about the potential effect of maternal exposure to various nanoparticles during pregnancy on a fetus. However, the nature of this risk is not fully known. Areas covered: In this review, materno-fetal transfer of nanoparticles through the placenta is described. Both prenatal and postnatal adverse effects, such as fetal resorption, malformation and injury to various organs in mice exposed to nanoparticles are reviewed. The potential mechanisms of toxicity are also discussed. Expert opinion: The toxicology and safe application of recently developed nanoparticles has attracted much attention in the past few years. Although many studies have demonstrated the toxicology of nanoparticles in various species, only a small number of studies have examined the effect on a fetus after maternal exposure to nanoparticles. This is particularly important, because the developing fetus is especially vulnerable to the toxic effects of nanoparticles during fetal development due to the unique physical stage of the fetus. Nanoparticles may directly or indirectly impair fetal development and growth after maternal exposure to nanoparticles.

  12. Assessment of diurnal systemic dose of agrochemicals in regulatory toxicity testing--an integrated approach without additional animal use.

    Science.gov (United States)

    Saghir, Shakil A; Bartels, Michael J; Rick, David L; McCoy, Alene T; Rasoulpour, Reza J; Ellis-Hutchings, Robert G; Sue Marty, M; Terry, Claire; Bailey, Jason P; Billington, Richard; Bus, James S

    2012-07-01

    Integrated toxicokinetics (TK) data provide information on the rate, extent and duration of systemic exposure across doses, species, strains, gender, and life stages within a toxicology program. While routine for pharmaceuticals, TK assessments of non-pharmaceuticals are still relatively rare, and have never before been included in a full range of guideline studies for a new agrochemical. In order to better understand the relationship between diurnal systemic dose (AUC(24h)) and toxicity of agrochemicals, TK analyses in the study animals is now included in all short- (excluding acute), medium- and long-term guideline mammalian toxicity studies including reproduction/developmental tests. This paper describes a detailed procedure for the implementation of TK in short-, medium- and long-term regulatory toxicity studies, without the use of satellite animals, conducted on three agrochemicals (X11422208, 2,4-D and X574175). In these studies, kinetically-derived maximum doses (KMD) from short-term studies instead of, or along with, maximum tolerated doses (MTD) were used for the selection of the high dose in subsequent longer-term studies. In addition to leveraging TK data to guide dose level selection, the integrated program was also used to select the most appropriate method of oral administration (i.e., gavage versus dietary) of test materials for rat and rabbit developmental toxicity studies. The integrated TK data obtained across toxicity studies (without the use of additional/satellite animals) provided data critical to understanding differences in response across doses, species, strains, sexes, and life stages. Such data should also be useful in mode of action studies and to improve human risk assessments. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. Air toxics from heavy oil production and consumption

    International Nuclear Information System (INIS)

    Lipfert, F.W.; DePhillips, M.P.; Moskowitz, P.D.

    1992-01-01

    This report assesses the potential impact of recent Federal and state regulations for airborne toxic substances on the production and consumption of heavy fuel oils. Emissions of nickel from heavy oil production in California are considered in some detail, in conjunction with California state regulations for toxic emissions. Although the use of thermal energy from heavy crude oils could in theory be impacted by toxic air pollution regulations, recent trends towards the use of natural gas for the required extraction energy appear to provide substantial relief, in addition to reducing emissions of criteria air pollutants. However, the consumption of residual fuel oils containing toxic metals could result in higher population exposures to these substances and their attendant risks may be worthy of more detailed analysis

  14. The toxic effects of chlorophenols and associated mechanisms in fish

    International Nuclear Information System (INIS)

    Ge, Tingting; Han, Jiangyuan; Qi, Yongmei; Gu, Xueyan; Ma, Lin; Zhang, Chen; Naeem, Sajid; Huang, Dejun

    2017-01-01

    Highlights: • We review the toxic effects of chlorophenols (CPs) and underlying mechanisms in fish. • CPs induce lethal effects, oxidative stress, endocrine disruption, reproductive toxicity and apoptosis in fish. • CPs exhibit toxicity through multiple signaling pathways in fish and different pathways co-exist under the same conditions. • Studies on DNA methylation provide new insights into our understanding of epigenetic mechanisms of CPs-induced toxicity. • Mechanisms studies on CPs toxicity performed under environmental concentrations need more attentions. - Abstract: Chlorophenols (CPs) are ubiquitous contaminants in the environment primarily released from agricultural and industrial wastewater. These compounds are not readily degraded naturally, and easily accumulate in organs, tissues and cells via food chains, further leading to acute and chronic toxic effects on aquatic organisms. Herein, we review the available literature regarding CP toxicity in fish, with special emphasis on the potential toxic mechanisms. CPs cause oxidative stress via generation of reactive oxygen species, induction of lipid peroxidation and/or oxidative DNA damage along with inhibition of antioxidant systems. CPs affect immune system by altering the number of mature B cells and macrophages, while suppressing phagocytosis and down-regulating the expression of immune factors. CPs also disrupt endocrine function by affecting hormone levels, or inducing abnormal gene expression and interference with hormone receptors. CPs at relatively higher concentrations induce apoptosis via mitochondria-mediated pathway, cell death receptor-mediated pathway, and/or DNA damage-mediated pathway. CPs at relatively lower concentrations promote cell proliferation, and foster cancers-prone environment by increasing the rate of point mutations and oxidative DNA lesions. These toxic effects in fish are induced directly by CPs per se or indirectly by their metabolic products. In addition, recent

  15. The toxic effects of chlorophenols and associated mechanisms in fish

    Energy Technology Data Exchange (ETDEWEB)

    Ge, Tingting; Han, Jiangyuan; Qi, Yongmei; Gu, Xueyan; Ma, Lin; Zhang, Chen; Naeem, Sajid; Huang, Dejun, E-mail: huangdj@lzu.edu.cn

    2017-03-15

    Highlights: • We review the toxic effects of chlorophenols (CPs) and underlying mechanisms in fish. • CPs induce lethal effects, oxidative stress, endocrine disruption, reproductive toxicity and apoptosis in fish. • CPs exhibit toxicity through multiple signaling pathways in fish and different pathways co-exist under the same conditions. • Studies on DNA methylation provide new insights into our understanding of epigenetic mechanisms of CPs-induced toxicity. • Mechanisms studies on CPs toxicity performed under environmental concentrations need more attentions. - Abstract: Chlorophenols (CPs) are ubiquitous contaminants in the environment primarily released from agricultural and industrial wastewater. These compounds are not readily degraded naturally, and easily accumulate in organs, tissues and cells via food chains, further leading to acute and chronic toxic effects on aquatic organisms. Herein, we review the available literature regarding CP toxicity in fish, with special emphasis on the potential toxic mechanisms. CPs cause oxidative stress via generation of reactive oxygen species, induction of lipid peroxidation and/or oxidative DNA damage along with inhibition of antioxidant systems. CPs affect immune system by altering the number of mature B cells and macrophages, while suppressing phagocytosis and down-regulating the expression of immune factors. CPs also disrupt endocrine function by affecting hormone levels, or inducing abnormal gene expression and interference with hormone receptors. CPs at relatively higher concentrations induce apoptosis via mitochondria-mediated pathway, cell death receptor-mediated pathway, and/or DNA damage-mediated pathway. CPs at relatively lower concentrations promote cell proliferation, and foster cancers-prone environment by increasing the rate of point mutations and oxidative DNA lesions. These toxic effects in fish are induced directly by CPs per se or indirectly by their metabolic products. In addition, recent

  16. Toxic aluminium and heavy metals in groundwater of middle Russia: health risk assessment.

    Science.gov (United States)

    Momot, Olga; Synzynys, Boris

    2005-08-01

    Two approaches are distinguished in modern ecological monitoring. The first one is physicochemical analysis of environmental objects with respect to maximum allowable concentrations (MACs) of chemical substances, which is performed by standards methods in accordance with state regulations. The second approach (biological monitoring) is based on the methodology of biotesting and bio indication. The task of this work is to create biotests for estimation of Al and other metals toxicity in ground water and to compare these results with physicochemical analysis dates. Risk assessment for heavy metals contaminated groundwater was also performed. Risk assessment was performed accordingly EPA US recommendation and gave results about 90 per 100000 citizens for Al and 402 per 100000 for mixture of different heavy metals. For comparison: risk for earth background radiation for Middle Russia is (Individual dose 1 millisivert per year) consist 5 per 100000 people. It was shown that groundwater consist HCO3- ions (360 mg/l), sometimes Al compounds 0.21-0.65 mg/l (MAC for Al is 0.5 mg/l for Russia). Other groundwater contain Hg - 0.004 mg/l (MAC - 0.0005 mg/l); Cr - 0.072 mg/l (MAC - 0.05 mg/l); As - less than 0.03 mg/l (MAC - 0.05 mg/l). We developed plant biotest for estimation of groundwater quality with barley roots, tradescatia and others. Some biotests parameters correlate with HCO3-, Cl-, SO(4)2- and metal ions content positively, for another biotest this correlation is strongly negative. The quality of groundwater near Obninsk and in Kaluga Region is very different but hasnit been changed since the year 1998.

  17. Hazard and risk of herbicides for marine microalgae

    International Nuclear Information System (INIS)

    Sjollema, Sascha B.; MartínezGarcía, Gema; Geest, Harm G. van der; Kraak, Michiel H.S.; Booij, Petra; Vethaak, A. Dick; Admiraal, Wim

    2014-01-01

    Due to their specific effect on photosynthesis, herbicides pose a potential threat to coastal and estuarine microalgae. However, comprehensive understanding of the hazard and risk of these contaminants is currently lacking. Therefore the aim of the present study was to investigate the toxic effects of four ubiquitous herbicides (atrazine, diuron, Irgarol ® 1051 and isoproturon) and herbicide mixtures on marine microalgae. Using a Pulse Amplitude Modulation (PAM) fluorometry based bioassay we demonstrated a clear species and herbicide specific toxicity and showed that the current environmental legislation does not protect algae sufficiently against diuron and isoproturon. Although a low actual risk of herbicides in the field was demonstrated, monitoring data revealed that concentrations occasionally reach potential effect levels. Hence it cannot be excluded that herbicides contribute to observed changes in phytoplankton species composition in coastal waters, but this is likely to occur only occasionally. - Highlights: • The hazard of herbicides for microalgae is compound and species specific. • In general a low risk although occasional potential effect levels are reached. • Current legislation does not protect marine microalgae sufficiently. - The hazard of herbicides in the coastal waters is compound and species specific and although the general risk in the field is low, occasionally potential effect levels are reached

  18. Is the phototransformation of pharmaceuticals a natural purification process that decreases ecological and human health risks?

    International Nuclear Information System (INIS)

    Wang, Xiao-Huan; Lin, Angela Yu-Chen

    2014-01-01

    Sunlight photodegradation has long been considered a significant process in lowering the concentrations of pharmaceuticals in surface waters and thus decreasing the ecological risk. For the first time, this study identified the significance of investigating the environmental photodegradation of a pharmaceutical residue mixture (rather than a single compound) and the associated toxicity of transformation byproducts in environmental waters, including rivers, hospital wastewaters, and effluents from wastewater treatment plants and pharmaceutical production facilities. Pharmaceuticals undergo phototransformation rather than mineralization (11–23% in 34 h). Pharmaceutical mixtures could possibly act as dissolved organic matter for each individual compound and subsequently affect the photolysis rates. The increased toxicity of irradiated pharmaceutical mixtures challenges the validity of the current understanding of sunlight photolysis. The implications of this work suggest that current knowledge concerning the occurrence, natural attenuation, ecotoxicity, and human health risks of pharmaceuticals is far from complete; photolysis is not necessarily a purification process. -- Highlights: • Pharmaceutical mixtures could possibly act as DOMs for each other. • Pharmaceuticals underwent merely phototransformation rather than mineralization. • Increased toxicity from photo byproducts associated with the pharmaceutical mixture. • Phototransformation does not necessary mitigate the risk to human and the ecosystem. -- Transformation byproducts associated with a pharmaceutical mixture could be more toxic, and phototransformation does not necessary mitigate the risk to humans and the ecosystem

  19. Toxic chemical hazard classification and risk acceptance guidelines for use in DOE facilities. Revision 2

    International Nuclear Information System (INIS)

    Craig, D.K.; Davis, J.S.; Prowse, J.; Hoffman, P.W.

    1995-01-01

    The concentration-limit guidelines presented in this document apply to airborne releases of chemicals evaluated with respect to human health effects for the purposes of hazard classification and categorization, risk assessment and safety analysis. They apply to all DOE facilities and operations involving the use of potentially hazardous chemicals. The guidelines do not address other nonradiological hazards such as fire, pressure releases (including explosions), and chemical reactivity, but the guidelines are applicable to hazardous chemical releases resulting from these events. This report presents the subcommittee's evaluation and recommendations regarding analyses of accidentally released toxic chemicals. The premise upon which these recommendations are based is that the mechanism of action of toxic chemicals is fundamentally different from that associated with radionuclides, with the exception of carcinogens. The recommendations reported herein are restricted to the airborne pathway because in an accident scenario this typically represents the most immediately significant route of public exposure. However, the subcommittee recognizes that exposure to chemicals through other pathways, in particular waterborne, can have significant impacts on human health and the environment. Although there are a number of chemicals for which absorption through the skin can contribute measurably to the total dose in chronic (e.g., occupational) exposure situations, this pathway has not been considered for the acute exposure scenarios considered in this report. Later studies. will address these issues if it appears desirable

  20. Non-animal approaches for consumer safety risk assessments: Unilever's scientific research programme.

    Science.gov (United States)

    Carmichael, Paul; Davies, Michael; Dent, Matt; Fentem, Julia; Fletcher, Samantha; Gilmour, Nicola; MacKay, Cameron; Maxwell, Gavin; Merolla, Leona; Pease, Camilla; Reynolds, Fiona; Westmoreland, Carl

    2009-12-01

    Non-animal based approaches to risk assessment are now routinely used for assuring consumer safety for some endpoints (such as skin irritation) following considerable investment in developing and applying new methods over the past 20 years. Unilever's research programme into non-animal approaches for safety assessment is currently focused on the application of new technologies to risk assessments in the areas of skin allergy, cancer and general toxicity (including inhalation toxicity). In all of these areas, a long-term investment is essential to increase the scientific understanding of the underlying biological and chemical processes that we believe will ultimately form a sound basis for novel risk assessment approaches. Our research programme in these priority areas consists of in-house research as well as Unilever-sponsored academic research, involvement with EU-funded projects (e.g. Sens-it-iv, carcinoGENOMICS), participation in cross-industry collaborative research (e.g. COLIPA, EPAA) and ongoing involvement with other scientific initiatives on non-animal approaches to risk assessment (e.g. UK NC3Rs, US 'Human Toxicology Project' consortium). 2009 FRAME.

  1. Contamination and ecological risk assessment of toxic trace elements in the Xi River, an urban river of Shenyang city, China.

    Science.gov (United States)

    Lin, Chunye; He, Mengchang; Liu, Xitao; Guo, Wei; Liu, Shaoqing

    2013-05-01

    The objectives of this study were to assess the enrichment, contamination, and ecological risk posed by toxic trace elements in the sediments of the Xi River in the industrialized city of Shenyang, China. Surface sediment and sediment core were collected; analyzed for toxic trace elements; and assessed with an index of geoaccumulation (Igeo), enrichment factor (EF) value, potential ecological risk factor (Er), ecological risk index (RI), and probable effect concentration quotient (PECQ). Elemental concentrations (milligram per kilogram) were 8.5-637.9 for As, 6.5-103.9 for Cd, 12.2-21.9 for Co, 90.6-516.0 for Cr, 258.1-1,791.5 for Cu, 2.6-19.0 for Hg, 70.5-174.5 for Ni, 126.9-1,405.8 for Pb, 3.7-260.0 for Sb, 38.4-100.4 for V, and 503-4,929 for Zn. The Igeo, EF, Er, and PECQ indices showed that the contamination of Cd and Hg was more serious than that of As, Cr, Cu, Ni, Pb, Sb, and Zn, whereas the presence of Co and V might be primarily from natural sources. The Igeo index for Cr and Ni might underestimate the degree of contamination, potentially as a result of high concentrations of these elements in the shale. The RI index was higher than 600, indicating a notably high ecological risk of sediment for the river. The average PECQ for As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn ranged from 1.4 to 4.1 for surface sediment and from 5.2 to 9.6 in the sediment cores, indicating a high potential for an adverse biological effect. It was concluded that the sediment in the Xi River was severely contaminated and should be remediated as a hazardous material.

  2. A theory-based approach to understanding suicide risk in shelter-seeking women.

    Science.gov (United States)

    Wolford-Clevenger, Caitlin; Smith, Phillip N

    2015-04-01

    Women seeking shelter from intimate partner violence are at an increased risk for suicide ideation and attempts compared to women in the general population. Control-based violence, which is common among shelter-seeking women, may play a pivotal role in the development of suicide ideation and attempts. Current risk assessment and management practices for shelter-seeking women are limited by the lack of an empirically grounded understanding of increased risk in this population. We argue that in order to more effectively promote risk assessment and management, an empirically supported theory that is sensitive to the experiences of shelter-seeking women is needed. Such a theory-driven approach has the benefits of identifying and prioritizing targetable areas for intervention. Here, we review the evidence for the link between coercive control and suicide ideation and attempts from the perspective of Baumeister's escape theory of suicide. This theory has the potential to explain the role of coercive control in the development of suicide ideation and eventual attempts in shelter-seeking women. Implications for suicide risk assessment and prevention in domestic violence shelters are discussed. © The Author(s) 2014.

  3. Impact of Toxicity Grade and Scoring System on the Relationship Between Mean Lung Dose and Risk of Radiation Pneumonitis in a Large Cohort of Patients With Non-Small Cell Lung Cancer

    International Nuclear Information System (INIS)

    Tucker, Susan L.; Jin Hekun; Wei Xiong

    2010-01-01

    Purpose: To compute the risk of radiation pneumonitis (RP) as a function of mean lung dose (MLD), with RP scored using three grading systems and analyzed at four threshold levels of toxicity in a large cohort of patients with non-small cell lung cancer (NSCLC) treated with definitive radiotherapy (RT). Methods and Materials: On the basis of medical records and radiographic images, RP was scored retrospectively in 442 patients with NSCLC who had ≥6 months of follow-up after the end of RT. The severity of RP was scored for each patient using the National Cancer Institute (NCI) Common Toxicity Criteria, version 2.0 (CTC2.0); the NCI Common Terminology Criteria for Adverse Events, version 3.0 (CTCAE3.0); and the grading system of the Radiation Therapy Oncology Group (RTOG). For each grading system and for each of four levels of toxicity (Grade ≥1, ≥2, ≥3, ≥4), the Lyman, logistic, and log-logistic normal tissue complication probability (NTCP) models were fitted to the data as functions of MLD. The parameter estimates from the model fits are listed in table form, and the RP risk estimates are presented graphically for the Lyman and log-logistic NTCP models. Results: The results presented here illustrate the impact of scoring system and level of toxicity on the relationship between MLD and RP risk. Conclusions: These results facilitate quantitative comparisons between our data and studies of RP risk reported by others, and several examples of such comparisons are provided.

  4. Benthic invertebrate exposure and chronic toxicity risk analysis for cyclic volatile methylsiloxanes: Comparison of hazard quotient and probabilistic risk assessment approaches.

    Science.gov (United States)

    Woodburn, Kent B; Seston, Rita M; Kim, Jaeshin; Powell, David E

    2018-02-01

    This study utilized probabilistic risk assessment techniques to compare field sediment concentrations of the cyclic volatile methylsiloxane (cVMS) materials octamethylcyclotetrasiloxane (D4, CAS # 556-67-2), decamethylcyclopentasiloxane (D5, CAS # 541-02-6), and dodecamethylcyclohexasiloxane (D6, CAS # 540-97-6) to effect levels for these compounds determined in laboratory chronic toxicity tests with benthic organisms. The concentration data for D4/D5/D6 in sediment were individually sorted and the 95th centile concentrations determined in sediment on an organic carbon (OC) fugacity basis. These concentrations were then compared to interpolated 5th centile benthic sediment no-observed effect concentration (NOEC) fugacity levels, calculated from a distribution of chronic D4/D5/D6 toxicologic assays per OECD guidelines using a variety of standard benthic species. The benthic invertebrate fugacity biota NOEC values were then compared to field-measured invertebrate biota fugacity levels to see if risk assessment evaluations were similar on a field sediment and field biota basis. No overlap was noted for D4 and D5 95th centile sediment and biota fugacity levels and their respective 5th centile benthic organism NOEC values. For D6, there was a small level of overlap at the exposure 95th centile sediment fugacity and the 5th centile benthic organism NOEC fugacity value; the sediment fugacities indicate that a negligible risk (1%) exists for benthic species exposed to D6. In contrast, there was no indication of risk when the field invertebrate exposure 95th centile biota fugacity and the 5th centile benthic organism NOEC fugacity values were compared. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  5. High-dose-rate brachytherapy as monotherapy delivered in two fractions within one day for favorable/intermediate-risk prostate cancer: preliminary toxicity data.

    Science.gov (United States)

    Ghilezan, Michel; Martinez, Alvaro; Gustason, Gary; Krauss, Daniel; Antonucci, J Vito; Chen, Peter; Fontanesi, James; Wallace, Michelle; Ye, Hong; Casey, Alyse; Sebastian, Evelyn; Kim, Leonard; Limbacher, Amy

    2012-07-01

    To report the toxicity profile of high-dose-rate (HDR)-brachytherapy (BT) as monotherapy in a Human Investigation Committee-approved study consisting of a single implant and two fractions (12 Gy × 2) for a total dose of 24 Gy, delivered within 1 day. The dose was subsequently increased to 27 Gy (13.5 Gy × 2) delivered in 1 day. We report the acute and early chronic genitourinary and gastrointestinal toxicity. A total of 173 patients were treated between December 2005 and July 2010. However, only the first 100 were part of the IRB-approved study and out of these, only 94 had a minimal follow-up of 6 months, representing the study population for this preliminary report. All patients had clinical Stage T2b or less (American Joint Committee on Cancer, 5th edition), Gleason score 6-7 (3+4), and prostate-specific antigen level of ≤12 ng/mL. Ultrasound-guided HDR-BT with real-time dosimetry was used. The prescription dose was 24 Gy for the first 50 patients and 27 Gy thereafter. The dosimetric goals and constraints were the same for the two dose groups. Toxicity was scored using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3. The highest toxicity scores encountered at any point during follow-up are reported. The median follow-up was 17 months (range, 6-40.5). Most patients had Grade 0-1 acute toxicity. The Grade 2 acute genitourinary toxicity was mainly frequency/urgency (13%), dysuria (5%), hematuria, and dribbling/hesitancy (2%). None of the patients required a Foley catheter at any time; however, 8% of the patients experienced transient Grade 1 diarrhea. No other acute gastrointestinal toxicities were found. The most common chronic toxicity was Grade 2 urinary frequency/urgency in 16% of patients followed by dysuria in 4% of patients; 2 patients had Grade 2 rectal bleeding and 1 had Grade 4, requiring laser treatment. Favorable-risk prostate cancer patients treated with a single implant HDR-BT to 24-27 Gy in two fractions

  6. High-Dose-Rate Brachytherapy as Monotherapy Delivered in Two Fractions Within One Day for Favorable/Intermediate-Risk Prostate Cancer: Preliminary Toxicity Data

    Energy Technology Data Exchange (ETDEWEB)

    Ghilezan, Michel, E-mail: mghilezan@beaumont.edu [Department of Radiation Oncology, William Beaumont Hospital and Rose Cancer Institute, Royal Oak, Michigan (United States); Martinez, Alvaro; Gustason, Gary; Krauss, Daniel; Antonucci, J. Vito; Chen, Peter; Fontanesi, James; Wallace, Michelle; Ye Hong; Casey, Alyse; Sebastian, Evelyn; Kim, Leonard; Limbacher, Amy [Department of Radiation Oncology, William Beaumont Hospital and Rose Cancer Institute, Royal Oak, Michigan (United States)

    2012-07-01

    Purpose: To report the toxicity profile of high-dose-rate (HDR)-brachytherapy (BT) as monotherapy in a Human Investigation Committee-approved study consisting of a single implant and two fractions (12 Gy Multiplication-Sign 2) for a total dose of 24 Gy, delivered within 1 day. The dose was subsequently increased to 27 Gy (13.5 Gy Multiplication-Sign 2) delivered in 1 day. We report the acute and early chronic genitourinary and gastrointestinal toxicity. Methods and Materials: A total of 173 patients were treated between December 2005 and July 2010. However, only the first 100 were part of the IRB-approved study and out of these, only 94 had a minimal follow-up of 6 months, representing the study population for this preliminary report. All patients had clinical Stage T2b or less (American Joint Committee on Cancer, 5th edition), Gleason score 6-7 (3+4), and prostate-specific antigen level of {<=}12 ng/mL. Ultrasound-guided HDR-BT with real-time dosimetry was used. The prescription dose was 24 Gy for the first 50 patients and 27 Gy thereafter. The dosimetric goals and constraints were the same for the two dose groups. Toxicity was scored using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3. The highest toxicity scores encountered at any point during follow-up are reported. Results: The median follow-up was 17 months (range, 6-40.5). Most patients had Grade 0-1 acute toxicity. The Grade 2 acute genitourinary toxicity was mainly frequency/urgency (13%), dysuria (5%), hematuria, and dribbling/hesitancy (2%). None of the patients required a Foley catheter at any time; however, 8% of the patients experienced transient Grade 1 diarrhea. No other acute gastrointestinal toxicities were found. The most common chronic toxicity was Grade 2 urinary frequency/urgency in 16% of patients followed by dysuria in 4% of patients; 2 patients had Grade 2 rectal bleeding and 1 had Grade 4, requiring laser treatment. Conclusions: Favorable-risk

  7. High-Dose-Rate Brachytherapy as Monotherapy Delivered in Two Fractions Within One Day for Favorable/Intermediate-Risk Prostate Cancer: Preliminary Toxicity Data

    International Nuclear Information System (INIS)

    Ghilezan, Michel; Martinez, Alvaro; Gustason, Gary; Krauss, Daniel; Antonucci, J. Vito; Chen, Peter; Fontanesi, James; Wallace, Michelle; Ye Hong; Casey, Alyse; Sebastian, Evelyn; Kim, Leonard; Limbacher, Amy

    2012-01-01

    Purpose: To report the toxicity profile of high-dose-rate (HDR)-brachytherapy (BT) as monotherapy in a Human Investigation Committee-approved study consisting of a single implant and two fractions (12 Gy × 2) for a total dose of 24 Gy, delivered within 1 day. The dose was subsequently increased to 27 Gy (13.5 Gy × 2) delivered in 1 day. We report the acute and early chronic genitourinary and gastrointestinal toxicity. Methods and Materials: A total of 173 patients were treated between December 2005 and July 2010. However, only the first 100 were part of the IRB-approved study and out of these, only 94 had a minimal follow-up of 6 months, representing the study population for this preliminary report. All patients had clinical Stage T2b or less (American Joint Committee on Cancer, 5th edition), Gleason score 6-7 (3+4), and prostate-specific antigen level of ≤12 ng/mL. Ultrasound-guided HDR-BT with real-time dosimetry was used. The prescription dose was 24 Gy for the first 50 patients and 27 Gy thereafter. The dosimetric goals and constraints were the same for the two dose groups. Toxicity was scored using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3. The highest toxicity scores encountered at any point during follow-up are reported. Results: The median follow-up was 17 months (range, 6–40.5). Most patients had Grade 0-1 acute toxicity. The Grade 2 acute genitourinary toxicity was mainly frequency/urgency (13%), dysuria (5%), hematuria, and dribbling/hesitancy (2%). None of the patients required a Foley catheter at any time; however, 8% of the patients experienced transient Grade 1 diarrhea. No other acute gastrointestinal toxicities were found. The most common chronic toxicity was Grade 2 urinary frequency/urgency in 16% of patients followed by dysuria in 4% of patients; 2 patients had Grade 2 rectal bleeding and 1 had Grade 4, requiring laser treatment. Conclusions: Favorable-risk prostate cancer patients treated with

  8. Late Toxicities after Conventional Radiotherapy for Nasopharyngeal Carcinoma: Incidence and Risk Factors

    International Nuclear Information System (INIS)

    Siala, W.; Mnejja, W.; Elloumi, F.; Daoud, J.; Ghorbel, A.; Mnif, J.; Frikha, M.

    2014-01-01

    Background. To determine the incidence and analyze the factors affecting late toxicity for nasopharyngeal carcinoma patients treated with conventional radiotherapy. Patients and Methods. Retrospective analysis was performed on 239 NPC patients treated between 1993 and 2004 in our institution. One hundred and fifty-seven patients were treated with conventional fractionation (2 Gy per fraction, 5 fractions per week) and eighty-two patients with hyperfractionated radiotherapy (1.6 Gy per fraction twice a day, 5 days per week). One hundred fifty nine patients underwent neoadjuvant cisplatin based chemotherapy. Late toxicity was evaluated according to the RTOG/EORTC score. Results. Xerostomia was the most common related complication (98.7%). Neoadjuvant chemotherapy and hyperfractionated radiotherapy did not increase late toxicities. Multivariate analyses showed that radiation dose was a significant factor for hearing impairment, younger age for trismus, initial node status for neck fibrosis, and initial dental hygiene for dental complications. Female gender was associated with significantly higher incidence of trismus and hearing impairment. Conclusion. Conventional radiotherapy was associated with a high rate of late toxicities which affect patients’ quality of life. With the development of three-dimensional conformal radiotherapy and intensity modulated radiotherapy, a reduced incidence of radiation related complications could be expected.

  9. Monitoring of essential and toxic metals in imported herbal teas ...

    African Journals Online (AJOL)

    ADOWIE PERE

    ABSTRACT: Teas are the most consumed beverage worldwide after water, and its consumption among. Nigerians has ... toxic metals in food and beverages with regards to the permissible ...... Risk assessment and risk management, in: D.R. ...

  10. Rapid screening of aquatic toxicity of several metal-based nanoparticles using the MetPLATE Trade-Mark-Sign bioassay

    Energy Technology Data Exchange (ETDEWEB)

    Pokhrel, Lok R.; Silva, Thilini [Department of Environmental Health, College of Public Health, East Tennessee State University, Johnson City, TN 37614 (United States); Dubey, Brajesh, E-mail: bdubey@uoguelph.ca [Environmental Engineering, School of Engineering, University of Guelph, 50 Stone Road East, Guelph, Ontario (Canada); El Badawy, Amro M. [Department of Civil and Environmental Engineering, University of Cincinnati, Cincinnati, OH (United States); Tolaymat, Thabet M. [USEPA, Office of Research and Development, National Risk Management Laboratory, 26 West Martin Luther King Drive, Cincinnati, OH 45224 (United States); Scheuerman, Phillip R. [Department of Environmental Health, College of Public Health, East Tennessee State University, Johnson City, TN 37614 (United States)

    2012-06-01

    Current understanding of potential toxicity of engineered nanomaterials to aquatic microorganisms is limited for risk assessment and management. Here we evaluate if the MetPLATE Trade-Mark-Sign test can be used as an effective and rapid screening tool to test for potential aquatic toxicity of various metal-based nanoparticles (NPs). The MetPLATE bioassay is a heavy metal sensitive test based on {beta}-galactosidase activity in Escherichia coli. Five different types of metal-based NPs were screened for toxicity: (1) citrate coated nAg (Citrate-nanosilver), (2) polyvinylpyrrolidone coated nAg (PVP-nAg), (3) uncoated nZnO, (4) uncoated nTiO{sub 2} and (5) 1-Octadecylamine coated CdSe Quantum Dots (CdSe QDs); and compared with their corresponding ionic salt toxicity. Citrate-nAg was further fractionated into clean Citrate-nAg, unclean Citrate-nAg and permeate using a tangential flow filtration (TFF) system to eliminate residual ions and impurities from the stock Citrate-nAg suspension and also to differentiate between ionic- versus nano-specific toxicity. Our results showed that nAg, nZnO and CdSe QDs were less toxic than their corresponding ionic salts tested, while nano- or ionic form of TiO{sub 2} was not toxic as high as 2.5 g L{sup -1} to the MetPLATE Trade-Mark-Sign bacteria. Although coating-dependent toxicity was noticeable between two types of Ag NPs evaluated, particle size and surface charge were not adequate to explain the observed toxicity; hence, the toxicity appeared to be material-specific. Overall, the toxicity followed the trend: CdCl{sub 2} > AgNO{sub 3} > PVP-nAg > unclean Citrate-nAg > clean Citrate-nAg > ZnSO{sub 4} > nZnO > CdSe QDs > nTiO{sub 2}/TiO{sub 2}. These results indicate that an evaluation of {beta}-galactosidase inhibition in MetPLATE Trade-Mark-Sign E. coli can be an important consideration for rapid screening of metal-based NP toxicity, and should facilitate ecological risk assessment of these emerging contaminants. - Highlights

  11. QSAR models for reproductive toxicity and endocrine disruption in regulatory use – a preliminary investigation

    DEFF Research Database (Denmark)

    Jensen, Gunde Egeskov; Niemelä, Jay Russell; Wedebye, Eva Bay

    2008-01-01

    the new legislation. This article focuses on a screening exercise by use of our own and commercial QSAR models for identification of possible reproductive toxicants. Three QSAR models were used for reproductive toxicity for the endpoints teratogenic risk to humans (based on animal tests, clinical data...... for humans owing to possible developmental toxic effects: Xn (Harmful) and R63 (Possible risk of harm to the unborn child). The chemicals were also screened in three models for endocrine disruption....

  12. Comparative analysis of the toxic effects of natural toxins and harmful substances produced by conventional processing methods or by irradiation and of toxicity tests

    International Nuclear Information System (INIS)

    Dahlhelm, H.; Arndt, K.; Groeger, G.; Schreiber, G.A.; Boegl, K.W.

    1994-01-01

    In this review, tasks and methods of food toxicology as well as the application of the different toxicity tests for the risk assessment of food ingredients are described. Particular reference is made to short-term genotoxicity tests. Enzymatic digestion and extraction methods for complex foodstuffs which are used in the toxicological testing of foods in in vitro systems are described. Radiolytic products which result from irradiation of foods or components of foodstuffs and corresponding results of toxicity testing are reviewed. Foodstuffs irradiated with doses of up to 10 kGy are regarded as toxicologically safe. A survey of the toxicologically tested irradiated foodstuffs as well as the applied maximum doses are given in tables at the end of chapter 8. Among the great number of toxicological studies of irradiated foods those are especially mentioned which have given rise to discussions on the health risks involved. In addition, the difficulties associated with the testing of toxicity of irradiated foodstuffs in feeding experiments are discussed. Short-term tests used to establish the benotoxicity of irradiated foods and essential results of toxicological testing are also presented in tables. An overview is given of the occurrence, frequency and health risks of natural toxins in foods and harmful substances produced by conventional methods of cooking and preservation, in order to enable a comparison with the health risks of irradiated foods. The relevance of animal experiments and in vitro investigations for the prediction of toxic effects of harmful substances of foodstuffs in man is discussed in the final chapter. (VHE) [de

  13. Geant4 simulation of the Elekta XVI kV CBCT unit for accurate description of potential late toxicity effects of image-guided radiotherapy

    International Nuclear Information System (INIS)

    Brochu, F M; Burnet, N G; Jena, R; Plaistow, R; Thomas, S J; Parker, M A

    2014-01-01

    This paper describes the modelisation of the Elekta XVI Cone Beam Computed Tomography (CBCT) machine components with Geant4 and its validation against calibration data taken for two commonly used machine setups. Preliminary dose maps of simulated CBCTs coming from this modelisation work are presented. This study is the first step of a research project, GHOST, aiming to improve the understanding of late toxicity risk in external beam radiotherapy patients by simulating dose depositions integrated from different sources (imaging, treatment beam) over the entire treatment plan. The second cancer risk will then be derived from different models relating irradiation dose and second cancer risk. (paper)

  14. Radiation Therapy, Cardiac Risk Factors, and Cardiac Toxicity in Early-Stage Breast Cancer Patients

    International Nuclear Information System (INIS)

    Doyle, John J.; Neugut, Alfred I.; Jacobson, Judith S.; Wang Jian; McBride, Russell; Grann, Alison; Grann, Victor R.; Hershman, Dawn

    2007-01-01

    Purpose: The benefits of adjuvant radiation therapy (RT) for breast cancer may be counterbalanced by the risk of cardiac toxicity. We studied the cardiac effects of RT and the impact of pre-existing cardiac risk factors (CRFs) in a population-based sample of older patients with breast cancer. Methods and Materials: In the Surveillance, Epidemiology and End-Results (SEER)-Medicare database of women ≥65 years diagnosed with Stages I to III breast cancer from January 1, 1992 to December 31, 2000, we used multivariable logistic regression to model the associations of demographic and clinical variables with postmastectomy and postlumpectomy RT. Using Cox proportional hazards regression, we then modeled the association between treatment and myocardial infarction (MI) and ischemia in the 10 or more years after diagnosis, taking the predictors of treatment into account. Results: Among 48,353 women with breast cancer; 19,897 (42%) were treated with lumpectomy and 26,534 (55%) with mastectomy; the remainder had unknown surgery type (3%). Receipt of RT was associated with later year of diagnosis, younger age, fewer comorbidities, nonrural residence, and chemotherapy. Postlumpectomy RT was also associated with white ethnicity and no prior history of heart disease (HD). The RT did not increase the risk of MI. Presence of MI was associated with age, African American ethnicity, advanced stage, nonrural residence, more than one comorbid condition, a hormone receptor-negative tumor, CRFs and HD. Among patients who received RT, tumor laterality was not associated with MI outcome. The effect of RT on the heart was not influenced by HD or CRFs. Conclusion: It appears unlikely that RT would increase the risk of MI in elderly women with breast cancer, regardless of type of surgery, tumor laterality, or history of CRFs or HD, for at least 10 years

  15. Discriminating modes of toxic action in mice using toxicity in BALB/c mouse fibroblast (3T3) cells.

    Science.gov (United States)

    Huang, Tao; Yan, Lichen; Zheng, Shanshan; Wang, Yue; Wang, Xiaohong; Fan, Lingyun; Li, Chao; Zhao, Yuanhui; Martyniuk, Christopher J

    2017-12-01

    The objective of this study was to determine whether toxicity in mouse fibroblast cells (3T3 cells) could predict toxicity in mice. Synthesized data on toxicity was subjected to regression analysis and it was observed that relationship of toxicities between mice and 3T3 cells was not strong (R 2  = 0.41). Inclusion of molecular descriptors (e.g. ionization, pKa) improved the regression to R 2  = 0.56, indicating that this relationship is influenced by kinetic processes of chemicals or specific toxic mechanisms associated to the compounds. However, to determine if we were able to discriminate modes of action (MOAs) in mice using the toxicities generated from 3T3 cells, compounds were first classified into "baseline" and "reactive" guided by the toxic ratio (TR) for each compound in mice. Sequence, binomial and recursive partitioning analyses provided strong predictions of MOAs in mice based upon toxicities in 3T3 cells. The correct classification of MOAs based on these methods was 86%. Nearly all the baseline compounds predicted from toxicities in 3T3 cells were identified as baseline compounds from the TR in mice. The incorrect assignment of MOAs for some compounds is hypothesized to be due to experimental uncertainty that exists in toxicity assays for both mice and 3T3 cells. Conversely, lack of assignment can also arise because some reactive compounds have MOAs that are different in mice compared to 3T3 cells. The methods developed here are novel and contribute to efforts to reduce animal numbers in toxicity tests that are used to evaluate risks associated with organic pollutants in the environment. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Toxicity assessment strategies, data requirements, and risk assessment approaches to derive health based guidance values for non-relevant metabolites of plant protection products.

    Science.gov (United States)

    Dekant, Wolfgang; Melching-Kollmuss, Stephanie; Kalberlah, Fritz

    2010-03-01

    In Europe, limits for tolerable concentrations of "non-relevant metabolites" for active ingredients (AI) of plant protection products in drinking water between 0.1 and 10 microg/L are discussed depending on the toxicological information available. "Non-relevant metabolites" are degradation products of AIs, which do not or only partially retain the targeted toxicities of AIs. For "non-relevant metabolites" without genotoxicity (to be confirmed by testing in vitro), the application of the concept of "thresholds of toxicological concern" results in a health-based drinking water limit of 4.5 microg/L even for Cramer class III compounds, using the TTC threshold of 90 microg/person/day (divided by 10 and 2). Taking into account the thresholds derived from two reproduction toxicity data bases a drinking water limit of 3.0 microg/L is proposed. Therefore, for "non-relevant metabolites" whose drinking water concentration is below 3.0 microg/L, no toxicity testing is necessary. This work develops a toxicity assessment strategy as a basis to delineate health-based limits for "non-relevant metabolites" in ground and drinking water. Toxicological testing is recommended to investigate, whether the metabolites are relevant or not, based on the hazard properties of the parent AIs, as outlined in the SANCO Guidance document. Also, genotoxicity testing of the water metabolites is clearly recommended. In this publication, tiered testing strategies are proposed for non-relevant metabolites, when drinking water concentrations >3.0 microg/L will occur. Conclusions based on structure-activity relationships and the detailed toxicity database on the parent AI should be included. When testing in animals is required for risk assessment, key aspects are studies along OECD-testing guidelines with "enhanced" study designs addressing additional endpoints such as reproductive toxicity and a developmental screening test to derive health-based tolerable drinking water limits with a limited number

  17. Toxicological risk at workplace and toxicity as Life Cycle Assessment impact category: Substitution of solvents as an example.

    Science.gov (United States)

    Schupp, Thomas; Georg, Philipp Alexander; Kirstein, Guenter

    2017-01-01

    Substitution of hazardous substances against less hazardous ones is a central requirement of the European Chemical Regulation REACH (European Regulation 1907/2006/EC). Hazardous substances emitted from products may not only affect the worker; drift off and distribution in the environment may finally result in exposure of the general population. This potential threat to health is covered by the impact category "toxicity" in Life Cycle Assessments. In this paper, we present a case of a substitution of volatile organic compounds in a reactive varnish, and compare the "old" formulation with the "new" formulation against health risk to the worker, and concerning the Life Cycle Assessment impact category "toxicity". The "old" formulation contained Naphtha (petroleum), hydrodesulfurized, heavy and Solvent naphtha (petroleum), light, aromatic. In the new formulation, both naphthas were replaced by n-Butylacetate, 1-Ethoxy-2-propyl acetate and Ethyl-3-ethoxy propionate. In the European Union, the naphthas are classified as mutagens and carcinogens category 1, officially. However, if benzene is below 0.1 %, registrants in the EU proposed to omit this classification, and todays naptha products on the market obviously have benzene contents below 0.1 %. On a first glance, the improvement for workplace safety introduced by the substitution, therefore, is comparatively small, as it is for toxicity in Life Cycle Assessment. However, when background knowledge concerning chemical production processes of naphtha is included, benzene below a content of 0.1 % needs to be taken into consideration, and the benefit of substitution is more obvious.

  18. The interrelation between organophosphate toxicity and the epidemiology of depression and suicide.

    Science.gov (United States)

    Jaga, Kushik; Dharmani, Chandrabhan

    2007-01-01

    The literature on an association between organophosphate (OP) toxicity and depression or suicide is scarce. An interrelation exists among populations exposed to OPs, acute OP toxicity, neurobehavioral effects, depression, suicide, and fatality. Acute OP toxicity is characterized by the cholinergic syndrome with systemic and central nervous system effects. Organophosphate-induced neurobehavioral effects result in depression. A potential risk of depression and suicide exists in farm workers exposed to OPs. The sociodemographics of depression include age, gender, race, geographic region, social factors, economics, psychiatric disorders, medical conditions, and hereditary factors. Suicide is a major consequence of depression, with multiple sociodemographic risk factors. Developing countries have a higher incidence of OP toxicity, with limited information on the prevalence of depression. In these countries, the incidence of suicide is high, affecting more females. Suicide is more prevalent in rural areas, and in farming communities, commonly with ingestion of OPs. In industrialized countries, the incidence of OP toxicity is lower, but the prevalence of depression is higher. Suicide rates are lower in industrialized countries, affecting more males, the urban population, and farming communities. Other lethal methods of suicide, such as hanging, firearms, electrocution, and drug overdose are more common in industrialized countries. A potential risk of depression or suicide certainly exists from OP toxicity, largely depending on the epidemiology or sociodemographics of these disorders. Scientific evidence shows that the association between environmental toxicology and psychiatry has important public health implications.

  19. Application of Toxic Chinese Medicine in Chinese Pharmacopoeia

    Science.gov (United States)

    Zhao, Hui; Feng, Yu; Mao, Mingsan

    2018-01-01

    Objective: Explore the application characteristics of proprietary Chinese medicine prescriptions containing toxic herbs in pharmacopoeia. Methods: In this paper, according to the clinical application of pharmacopoeia proprietary Chinese medicine is divided into table agent, Qushu agent, diarrhea agent, heat agent, Wen Li agent, cough and asthma agents, resuscitation agent, Gutian agent, Fuzheng agent, Anshen agent, hemostatic agent, The traditional Chinese medicine prescription and the clinical application of the Chinese herbal medicine containing the toxic Chinese medicine were analyzed and sorted out., Summed up the compatibility of toxic herbs and application characteristics. Results: Toxic Chinese herbal medicine in the cure of traditional Chinese medicine to play a long-standing role, through the overall thinking, dialectical thinking, and thinking of toxic Chinese medicine in the analysis of Chinese medicine that [2], toxic Chinese medicine in the application of proprietary Chinese medicine can not lack. Conclusion: Pharmacopoeia included proprietary Chinese medicine not only in the clinical treatment of good, but also the application of its toxic traditional Chinese medicine and its understanding of the enrichment of the toxic characteristics of traditional Chinese medicine and treatment-related disease pathology between the points of contact for patients with clinical applications Based on and theoretical guidance of Chinese medicine [3].

  20. Reproductive and developmental toxicity of hydrofluorocarbons used as refrigerants.

    Science.gov (United States)

    Ema, Makoto; Naya, Masato; Yoshida, Kikuo; Nagaosa, Ryuichi

    2010-04-01

    The present paper summarizes data on the reproductive and developmental toxicity of hydrofluorocarbons (HFCs), including pentafluoroethane (HFC-125), 1,1,1,2-tetrafluoroethane (HFC-134a), 1,1,1-trifluoroethane (HFC-143a), 1,1-difluoroethane (HFC-152a), difluoromethane (HFC-32) and 1,1,1,3,3-pentafluoropropane (HFC-245fa), used as refrigerants, published in openly available scientific literature. No developmental toxicity of HFC-125 was found even at 50,000 ppm in rats or rabbits. Although HFC-134a exhibited no dominant lethal effect or reproductive toxicity in rats, it caused low body weight in pre- and postnatal offspring and slightly retarded skeletal ossification in fetuses at 50,000 ppm in rats. No maternal or developmental toxicity was noted after exposure to HFC-143a even at 40,000 ppm in rats or rabbits or HFC-152a even at 50,000 ppm in rats. HFC-32 is slightly maternally and developmentally toxic at 50,000 ppm in rats, but not in rabbits. HFC-245fa caused decreases in maternal body weight and food consumption at 10,000 and 50,000 ppm and fetal weight at 50 000ppm. No evidence of teratogenicity for these HFCs was noted in rats or rabbits. There is limited information about the reproductive toxicity of these HFCs. Animal studies remain necessary for risk assessments of chemicals because it is difficult to find alternative methods to determine the toxic effects of chemicals. It is required to reduce emissions of organic vapors containing HFCs to reduce the risk of exposure. Copyright 2009 Elsevier Inc. All rights reserved.

  1. Understanding interannual, decadal level variability in paralytic shellfish poisoning toxicity in the Gulf of Maine: The HAB Index

    Science.gov (United States)

    Anderson, Donald M.; Couture, Darcie A.; Kleindinst, Judith L.; Keafer, Bruce A.; McGillicuddy, Dennis J., Jr.; Martin, Jennifer L.; Richlen, Mindy L.; Hickey, J. Michael; Solow, Andrew R.

    2014-05-01

    A major goal in harmful algal bloom (HAB) research has been to identify mechanisms underlying interannual variability in bloom magnitude and impact. Here the focus is on variability in Alexandrium fundyense blooms and paralytic shellfish poisoning (PSP) toxicity in Maine, USA, over 34 years (1978-2011). The Maine coastline was divided into two regions - eastern and western Maine, and within those two regions, three measures of PSP toxicity (the percent of stations showing detectable toxicity over the year, the cumulative amount of toxicity per station measured in all shellfish (mussel) samples during that year, and the duration of measurable toxicity) were examined for each year in the time series. These metrics were combined into a simple HAB Index that provides a single measure of annual toxin severity across each region. The three toxin metrics, as well as the HAB Index that integrates them, reveal significant variability in overall toxicity between individual years as well as long-term, decadal patterns or regimes. Based on different conceptual models of the system, we considered three trend formulations to characterize the long-term patterns in the Index - a three-phase (mean-shift) model, a linear two-phase model, and a pulse-decline model. The first represents a “regime shift” or multiple equilibria formulation as might occur with alternating periods of sustained high and low cyst abundance or favorable and unfavorable growth conditions, the second depicts a scenario of more gradual transitions in cyst abundance or growth conditions of vegetative cells, and the third characterizes a ”sawtooth” pattern in which upward shifts in toxicity are associated with major cyst recruitment events, followed by a gradual but continuous decline until the next pulse. The fitted models were compared using both residual sum of squares and Akaike's Information Criterion. There were some differences between model fits, but none consistently gave a better fit than the

  2. Autophagy as a Possible Underlying Mechanism of Nanomaterial Toxicity

    Directory of Open Access Journals (Sweden)

    Vanessa Cohignac

    2014-07-01

    Full Text Available The rapid development of nanotechnologies is raising safety concerns because of the potential effects of engineered nanomaterials on human health, particularly at the respiratory level. Since the last decades, many in vivo studies have been interested in the pulmonary effects of different classes of nanomaterials. It has been shown that some of them can induce toxic effects, essentially depending on their physico-chemical characteristics, but other studies did not identify such effects. Inflammation and oxidative stress are currently the two main mechanisms described to explain the observed toxicity. However, the exact underlying mechanism(s still remain(s unknown and autophagy could represent an interesting candidate. Autophagy is a physiological process in which cytoplasmic components are digested via a lysosomal pathway. It has been shown that autophagy is involved in the pathogenesis and the progression of human diseases, and is able to modulate the oxidative stress and pro-inflammatory responses. A growing amount of literature suggests that a link between nanomaterial toxicity and autophagy impairment could exist. In this review, we will first summarize what is known about the respiratory effects of nanomaterials and we will then discuss the possible involvement of autophagy in this toxicity. This review should help understand why autophagy impairment could be taken as a promising candidate to fully understand nanomaterials toxicity.

  3. Toxicity of 56 substances to trees

    DEFF Research Database (Denmark)

    Clausen, Lauge Peter Westergaard; Trapp, Stefan

    2017-01-01

    Toxicity data of substances to higher plants is needed for the purpose of risk assessment, site evaluation, phytoremediation, and plant protection. However, the results from the most common phytotoxicity tests, like the OECD algae and Lemna test, are not necessarily valid for higher terrestrial...

  4. Toxicity of Silver Nanoparticles to Green Algae – Towards a Biotic Ligand Understanding

    DEFF Research Database (Denmark)

    Laruelle, Sacha; Sørensen, Sara Nørgaard; Cupi, Denisa

    with the freshwater green algae Pseudokirschneriella subcapitata were carried out to falsify the hypothesis: “The toxicity of silver nanoparticles towards algae is solely caused by the monovalent silver ion”. These experiments were based on PHREEQC modeling of silver ion behavior (added as AgNO3) in 72h OECD algal...

  5. DNA Repair Alterations in Children With Pediatric Malignancies: Novel Opportunities to Identify Patients at Risk for High-Grade Toxicities

    International Nuclear Information System (INIS)

    Ruebe, Claudia E.; Fricke, Andreas; Schneider, Ruth; Simon, Karin; Kuehne, Martin; Fleckenstein, Jochen; Graeber, Stefan; Graf, Norbert; Ruebe, Christian

    2010-01-01

    Purpose: To evaluate, in a pilot study, the phosphorylated H2AX (γH2AX) foci approach for identifying patients with double-strand break (DSB) repair deficiencies, who may overreact to DNA-damaging cancer therapy. Methods and Materials: The DSB repair capacity of children with solid cancers was analyzed compared with that of age-matched control children and correlated with treatment-related normal-tissue responses (n = 47). Double-strand break repair was investigated by counting γH2AX foci in blood lymphocytes at defined time points after irradiation of blood samples. Results: Whereas all healthy control children exhibited proficient DSB repair, 3 children with tumors revealed clearly impaired DSB repair capacities, and 2 of these repair-deficient children developed life-threatening or even lethal normal-tissue toxicities. The underlying mutations affecting regulatory factors involved in DNA repair pathways were identified. Moreover, significant differences in mean DSB repair capacity were observed between children with tumors and control children, suggesting that childhood cancer is based on genetic alterations affecting DSB repair function. Conclusions: Double-strand break repair alteration in children may predispose to cancer formation and may affect children's susceptibility to normal-tissue toxicities. Phosphorylated H2AX analysis of blood samples allows one to detect DSB repair deficiencies and thus enables identification of children at risk for high-grade toxicities.

  6. A Review of the Toxicity of Compounds Found in Herbal Dietary Supplements.

    Science.gov (United States)

    Hudson, Amy; Lopez, Elizabeth; Almalki, Ahmad J; Roe, Amy L; Calderón, Angela I

    2018-04-19

    Use of herbal dietary supplements by the public is common and has been happening for centuries. In the United States, the Food and Drug Administration has a limited scope of regulation over marketed herbal dietary supplements, which may contain toxic botanical compounds that pose a public health risk. While the Food and Drug Administration has made efforts to prohibit the sale of unsafe herbal dietary supplements, numerous reports have proliferated of adverse events due to these supplements. This literature review investigates bioactive plant compounds commonly used in herbal dietary supplements and their relative toxicities. Using primarily the National Library of Medicine journal database and SciFinder for current reports, 47 toxic compounds in 55 species from 46 plant families were found to demonstrate harmful effects due to hepatic, cardiovascular, central nervous system, and digestive system toxicity. This review further contributes a novel and comprehensive view of toxicity across the botanical dietary market, and investigates the toxicity of the top ten botanical dietary supplements purchased in the United States of America to gauge the exposure risk of toxicity to the public. The criteria of measuring toxicity in this review (plant compound, family, quantity, and toxicity effects) across the entire market in the United States, with special attention to those supplements whose exposure to the consumer is maximal, provides a unique contribution to the investigation of botanical supplements. Georg Thieme Verlag KG Stuttgart · New York.

  7. Biological toxicity evaluation of Hanford Site waste grouts

    International Nuclear Information System (INIS)

    Rebagay, T.V. Dodd, D.A.; Voogd, J.A.

    1992-10-01

    Liquid wastes containing radioactive, hazardous, and regulated chemicals have been generated throughout the 50 years of operation of the Hanford Site of the US Department of Energy near Richland, Washington. These wastes are currently stored onsite in single- and double-shell carbon steel tanks. To effectively handle and treat these wastes, their degree of toxicity must be determined. The disposal of the low-level radioactive liquid portion of the wastes involves mixing the wastes with pozzolanic blends to form grout. Potential environmental hazards posed by grouts are largely unknown. Biological evaluation of grout toxicity is needed to provide information on the potential risks of animal and plant exposure to the grouts. The fish, rat, and Microtox toxicity tests described herein indicate that the grouts formed from Formulations I and 2 are nonhazardous and nondangerous. Using the Microtox solid-phase protocol, both soluble and insoluble organic and inorganic toxicants in the grouts can be detected. This protocol may be used for rapid screening of environmental pollutants and toxicants

  8. Sanitary Assessment of Hazardous Materials Exposed To Highly Toxic Chemical Compounds

    International Nuclear Information System (INIS)

    Rembovskiy, V.; Ermolaeva, E.

    2007-01-01

    Industrial or terroristic accidents in which toxic chemicals (TC) are the main or attendant damaging factors should be regarded as a new challenge for experts, because of little knowledge on the methodology to estimating the long-term risk for humans due to contamination of the building materials and environment. In the Russian Federation, there appeared to be a kind of model systems for developing an algorithm for solving these or similar problems. Under dismantling and liquidation of the former facilities for chemical weapon production (FCWP) the building materials are regarded as potential waste products the fate of which (processing, warehousing, utilization, and destruction) is dependent on their possible hazard for human population and environment. The standard approaches for hazard assessment of waste products of the FCWP turned out to be insufficient. When conducting the present work, the following problems have been solved: 1. Selection of representative samples taking into consideration a diversity of construction materials, great quantities of potentially toxic waste materials, information on the production conditions, breakdowns in the process of production, accidents, composition of the decontaminators used, decontamination frequency, etc. 2. Analysis of TC in composite matrixes complicated by the following problems: extraction, masking effects of concomitant components during indirect analysis, lack of certified methods of direct analysis of TC, discrepancy of results of GC and direct GCMS analysis, low sensitivity of GCMS analysis, big volume of samples (more than 0.5 kg), heterogeneity of physical-chemical properties of different matrixes influencing the process of degradation of TC. 3. Hazard assessment of the wastes in toxic-and-sanitary experiment relying on non-specific signs of intoxication due to relatively low percentage of TC and masking effects of various matrix components. Application of the integral toxicity tests with soil

  9. Probabilistic human health risk assessment of degradation-related chemical mixtures in heterogeneous aquifers: Risk statistics, hot spots, and preferential channels

    Science.gov (United States)

    Henri, Christopher V.; Fernàndez-Garcia, Daniel; de Barros, Felipe P. J.

    2015-06-01

    The increasing presence of toxic chemicals released in the subsurface has led to a rapid growth of social concerns and the need to develop and employ models that can predict the impact of groundwater contamination on human health risk under uncertainty. Monitored natural attenuation is a common remediation action in many contamination cases. However, natural attenuation can lead to the production of daughter species of distinct toxicity that may pose challenges in pollution management strategies. The actual threat that these contaminants pose to human health depends on the interplay between the complex structure of the geological media and the toxicity of each pollutant byproduct. This work addresses human health risk for chemical mixtures resulting from the sequential degradation of a contaminant (such as a chlorinated solvent) under uncertainty through high-resolution three-dimensional numerical simulations. We systematically investigate the interaction between aquifer heterogeneity, flow connectivity, contaminant injection model, and chemical toxicity in the probabilistic characterization of health risk. We illustrate how chemical-specific travel times control the regime of the expected risk and its corresponding uncertainties. Results indicate conditions where preferential flow paths can favor the reduction of the overall risk of the chemical mixture. The overall human risk response to aquifer connectivity is shown to be nontrivial for multispecies transport. This nontriviality is a result of the interaction between aquifer heterogeneity and chemical toxicity. To quantify the joint effect of connectivity and toxicity in health risk, we propose a toxicity-based Damköhler number. Furthermore, we provide a statistical characterization in terms of low-order moments and the probability density function of the individual and total risks.

  10. Safety Evaluation of Potential Toxic Metals Exposure from Street Foods Consumed in Mid-West Nigeria

    Directory of Open Access Journals (Sweden)

    O. C. Ekhator

    2017-01-01

    Full Text Available Objective. Street-vended foods offer numerous advantages to food security; nevertheless, the safety of street food should be considered. This study has investigated the level of potential toxic metal (Pb, Cd, Hg, Sb, Mn, and Al contamination among street-vended foods in Benin City and Umunede. Methods. Twenty street food samples were purchased from vendors at bus stops. Metals were analyzed with atomic absorption spectrophotometry. The methods developed by the US EPA were employed to evaluate the potential health risk of toxic metals. Results. The concentrations of the toxic metals in mg/kg were in the range of Pb (0.014–1.37, Cd (0.00–0.00017, Hg (0.00–0.00014, Sb (0.00–0.021, Mn (0.00–0.012, and Al (0.00–0.22. All the toxic metals except Pb were below permissible limit set by WHO, EU, and USEPA. The daily intake, hazard quotient, and hazard index of all toxic metals except for Pb in some street foods were below the tolerable daily intake and threshold value of 1, indicating an insignificant health risk. Total cancer risk was within the priority risk level of 1.0E-04 but higher than the acceptable risk level of 1E-06. Conclusion. Consumption of some of these street foods is of public health concern.

  11. The Simplest Flowchart Stating the Mechanisms for Organic Xenobiotics-induced Toxicity: Can it Possibly be Accepted as a "Central Dogma" for Toxic Mechanisms?

    Science.gov (United States)

    Park, Yeong-Chul; Lee, Sundong; Cho, Myung-Haing

    2014-09-01

    Xenobiotics causing a variety of toxicity in biological systems could be classified as two types, inorganic and organic chemicals. It is estimated that the organic xenobiotics are responsible for approximately 80~90% of chemical-induced toxicity in human population. In the class for toxicology, we have encountered some difficulties in explaining the mechanisms of toxicity caused especially by organic chemicals. Here, a simple flowchart was introduced for explaining the mechanism of toxicity caused by organic xenobiotics, as the central dogma of molecular biology. This flowchart, referred to as a central dogma, was described based on a view of various aspects as follows: direct-acting chemicals vs. indirect-acting chemicals, cytochrome P450-dependent vs. cytochrome P450-independent biotransformation, reactive intermediates, reactivation, toxicokinetics vs. toxicodynamics, and reversibility vs. irreversibility. Thus, the primary objective of this flowchart is to help better understanding of the organic xenobiotics-induced toxic mechanisms, providing a major pathway for toxicity occurring in biological systems.

  12. Distribution, exposure pathways, sources and toxicity of nonylphenol ...

    African Journals Online (AJOL)

    Water SA. Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue ... of their toxicity, oestrogenic properties and widespread contamination. ... to provide better understanding of these emerging environmental contaminants.

  13. Attenuating the toxicity of cisplatin by using selenosulfate with reduced risk of selenium toxicity as compared with selenite

    International Nuclear Information System (INIS)

    Zhang Jinsong; Peng Dungeng; Lu Hongjuan; Liu Qingliang

    2008-01-01

    It has been reported that high doses of sodium selenite can reduce side effects of cisplatin (CDDP) without compromising its antitumor activity, thus substantially enhancing the cure rate in tumor-bearing mice. However, the toxicity of selenite at high doses should be a concern. The present study revealed that selenosulfate had much lower toxicity, but possessed equal efficacy in selenium (Se) utilization, as compared with selenite at similar doses when used for the intervention of CDDP. In addition, Se accumulation in whole blood and kidney of mice treated with selenosulfate was highly correlated with the survival rate of mice treated with CDDP (both r > 0.96 and both p < 0.05), suggesting that whole blood Se is a potential clinical biomarker to predict host tolerance to CDDP. In either Se-deficient or -sufficient mice bearing solid tumors of hepatoma 22 (H22), selenosulfate did not disturb the therapeutic effect of CDDP on tumors but effectively attenuated the toxicity of CDDP. Furthermore, in a highly malignant cancer model, with Se-sufficient mice bearing ascitic H22 cells, 8 or 10 mg/kg CDDP alone only achieved a null or 25% cure rate, whereas coadministration of selenosulfate with the above two doses of CDDP achieved cure rates of 87.5% or 75%. These results together argue for consideration of selenosulfate as an agent to enhance the therapeutic efficacy of CDDP

  14. Toxic stress and child refugees.

    Science.gov (United States)

    Murray, John S

    2018-01-01

    The purpose of this article was to describe the phenomenon of toxic stress and its impact on the physical and mental health of child refugees. Almost two decades ago, researchers found that recurring adverse childhood events (ACEs; e.g., physical, psychological, and sexual abuse, neglect, and household dysfunction such as substance abuse, mental illness, and criminal behavior) were associated with a significant increase in serious illnesses during adulthood. Illnesses include heart, lung, and liver disease, cancer, and bone fractures. The scientists reported that experiencing four or more ACEs during childhood significantly increases the risk for toxic stress. Toxic stress is defined as the exposure to extreme, frequent, and persistent adverse events without the presence of a supportive caretaker. There is a paucity of literature related to toxic stress and child refugees. However, it has been clearly established that the prolonged brutal and traumatizing war in Syria is having a profound impact on the physical and mental health of child refugees at a distressing rate. Prevention of toxic stress should be a primary goal of all pediatric healthcare professionals working with child refugees. While this seems daunting given the population, and the seemingly insurmountable stressors they experience, some basic interventions should be considered. Providing basic anticipatory guidance to parents and caregivers of child refugees, to encourage positive parenting and strengthening support networks, will be highly effective in developing the requisite buffers that mitigate the effects of stress and avoid toxic stress. Efforts should also be focused on addressing caregiver stress and improving their ability to provide safe, reliable, and nurturing care that will help to mitigate any stress response experienced by a child. It is critical that greater awareness be placed on the effects of toxic stress on child refugees who are exposed to significant adverse events early in life

  15. Potential fluoride toxicity from oral medicaments: A review

    OpenAIRE

    Rizwan Ullah; Muhammad Sohail Zafar; Nazish Shahani

    2017-01-01

    The beneficial effects of fluoride on human oral health are well studied. There are numerous studies demonstrating that a small amount of fluoride delivered to the oral cavity decreases the prevalence of dental decay and results in stronger teeth and bones. However, ingestion of fluoride more than the recommended limit leads to toxicity and adverse effects. In order to update our understanding of fluoride and its potential toxicity, we have described the mechanisms of fluoride metabolism, tox...

  16. Understanding your supply chain to reduce the risk of supply chain disruption.

    Science.gov (United States)

    Wildgoose, Nick; Brennan, Patrick; Thompson, Simon

    2012-01-01

    Supply chains are at the heart of the way in which organisations operate and compete today; they also play a critical role in overall organisation performance. In the context of increasingly complex and global supply chains, the actions taken to drive down costs are likely to drive risk into the supply chain. The frequency of supply chain disruptions is high and this paper offers practical advice to help reduce the frequency and cost associated with these. There is advice to help with the understanding of how to identify critical suppliers. The reader is guided through comprehensive risk assessment and mitigation approaches and a selection of practical risk solutions and tools that you can use is described. There is a section on the 'dos and don'ts' relating to supplier due diligence. For those organisations facing the challenge of drawing up a business case relating to investment in improving supply chain resiliency, there is also a section outlining some of the business benefits of improving supply chain resiliency.

  17. Understanding Sociocultural Factors Contributing to HIV Risk Among Ayoreo Bolivian Sex Workers.

    Science.gov (United States)

    López Entrambasaguas, Olga María; Granero-Molina, José; Hernández-Padilla, Jose; Fernández-Sola, Cayetano

    2015-01-01

    The Bolivian indigenous Ayoreo ethnic people are vulnerable to sexually transmitted infections and HIV. Ayoreo women who also work in sex trades belong to an extremely high-risk group, and prevention programs are not delivering effective outcomes for them. The aim of our study was to explore, describe, and understand behavioral and cultural patterns related to sexual and reproductive health in Ayoreo sex workers. A qualitative-ethnographic study was designed; data were collected through participant observation and in-depth interviews with sex workers and key informants. Two fundamental themes contributing to HIV risk for female Ayoreo sex workers in Bolivia emerged: reproductive/sexual freedom and sociocultural risk determinants. We concluded that the in-depth examination of the sexual-reproductive culture amongst the Ayoreo has provided useful information, which might contribute to the cultural adaptation and design of future policies and prevention programs for sexually transmitted infections and HIV in this group. Copyright © 2015 Association of Nurses in AIDS Care. Published by Elsevier Inc. All rights reserved.

  18. Evaluating the Spatial Distribution of Toxic Air Contaminants in Multiple Ecosystem Indicators in the Sierra Nevada-Southern Cascades

    Science.gov (United States)

    Nanus, L.; Simonich, S. L.; Rocchio, J.; Flanagan, C.

    2013-12-01

    Toxic air contaminants originating from agricultural areas of the Central Valley in California threaten vulnerable sensitive receptors including surface water, vegetation, snow, sediments, fish, and amphibians in the Sierra Nevada-Southern Cascades region. The spatial distribution of toxic air contaminants in different ecosystem indicators depends on variation in atmospheric concentrations and deposition, and variation in air toxics accumulation in ecosystems. The spatial distribution of organic air toxics and mercury at over 330 unique sampling locations and sample types over two decades (1990-2009) in the Sierra Nevada-Southern Cascades region were compiled and maps were developed to further understand spatial patterns and linkages between air toxics deposition and ecological effects. Potential ecosystem impacts in the Sierra Nevada-Southern Cascades region include bioaccumulation of air toxics in both aquatic and terrestrial ecosystems, reproductive disruption, and immune suppression. The most sensitive ecological end points in the region that are affected by bioaccumulation of toxic air contaminants are fish. Mercury was detected in all fish and approximately 6% exceeded human consumption thresholds. Organic air toxics were also detected in fish yielding variable spatial patterns. For amphibians, which are sensitive to pesticide exposure and potential immune suppression, increasing trends in current and historic use pesticides are observed from north to south across the region. In other indicators, such as vegetation, pesticide concentrations in lichen increase with increasing elevation. Current and historic use pesticides and mercury were also observed in snowpack at high elevations in the study area. This study shows spatial patterns in toxic air contaminants, evaluates associated risks to sensitive receptors, and identifies data gaps. Future research on atmospheric modeling and information on sources is needed in order to predict which ecosystems are the

  19. A method for measuring sulfide toxicity in the nematode Caenorhabditis elegans.

    Science.gov (United States)

    Livshits, Leonid; Gross, Einav

    2017-01-01

    Cysteine catabolism by gut microbiota produces high levels of sulfide. Excessive sulfide can interfere with colon function, and therefore may be involved in the etiology and risk of relapse of ulcerative colitis, an inflammatory bowel disease affecting millions of people worldwide. Therefore, it is crucial to understand how cells/animals regulate the detoxification of sulfide generated by bacterial cysteine catabolism in the gut. Here we describe a simple and cost-effective way to explore the mechanism of sulfide toxicity in the nematode Caenorhabditis elegans ( C. elegans ). •A rapid cost-effective method to quantify and study sulfide tolerance in C. elegans and other free-living nematodes.•A cost effective method to measure the concentration of sulfide in the inverted plate assay.

  20. Oxidative stress-induced autophagy: Role in pulmonary toxicity

    International Nuclear Information System (INIS)

    Malaviya, Rama; Laskin, Jeffrey D.; Laskin, Debra L.

    2014-01-01

    Autophagy is an evolutionarily conserved catabolic process important in regulating the turnover of essential proteins and in elimination of damaged organelles and protein aggregates. Autophagy is observed in the lung in response to oxidative stress generated as a consequence of exposure to environmental toxicants. Whether autophagy plays role in promoting cell survival or cytotoxicity is unclear. In this article recent findings on oxidative stress-induced autophagy in the lung are reviewed; potential mechanisms initiating autophagy are also discussed. A better understanding of autophagy and its role in pulmonary toxicity may lead to the development of new strategies to treat lung injury associated with oxidative stress. - Highlights: • Exposure to pulmonary toxicants is associated with oxidative stress. • Oxidative stress is known to induce autophagy. • Autophagy is upregulated in the lung following exposure to pulmonary toxicants. • Autophagy may be protective or pathogenic

  1. Oxidative stress-induced autophagy: Role in pulmonary toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Malaviya, Rama [Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854 (United States); Laskin, Jeffrey D. [Department of Environmental and Occupational Medicine, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ 08854 (United States); Laskin, Debra L., E-mail: laskin@eohsi.rutgers.edu [Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854 (United States)

    2014-03-01

    Autophagy is an evolutionarily conserved catabolic process important in regulating the turnover of essential proteins and in elimination of damaged organelles and protein aggregates. Autophagy is observed in the lung in response to oxidative stress generated as a consequence of exposure to environmental toxicants. Whether autophagy plays role in promoting cell survival or cytotoxicity is unclear. In this article recent findings on oxidative stress-induced autophagy in the lung are reviewed; potential mechanisms initiating autophagy are also discussed. A better understanding of autophagy and its role in pulmonary toxicity may lead to the development of new strategies to treat lung injury associated with oxidative stress. - Highlights: • Exposure to pulmonary toxicants is associated with oxidative stress. • Oxidative stress is known to induce autophagy. • Autophagy is upregulated in the lung following exposure to pulmonary toxicants. • Autophagy may be protective or pathogenic.

  2. {sup 131}I treatment of nodular non-toxic goitre

    Energy Technology Data Exchange (ETDEWEB)

    Nygaard, B.; Faber, J.; Hegdeues, L.; Hansen, J.M. [Herlev Hospital (Denmark)

    1996-01-01

    The traditional treatment of a growing nodular non-toxic goitre has for many years been surgical resection or levothyroxine suppressive treatment. During recent years, several studies have reported promising results of {sup 131}I treatment in terms of thyroid size reduction. This review outlines the different treatment modalities on non-toxic nodular goitre with special emphasis on {sup 131}I treatment. By the term nodular goitre the authors include glands with solitary or multiple thyroid nodules with uptake on a scintiscan. At what point of the natural history of non-toxic multinodular goitre {sup 131}I therapy should be used is not clear. In principle, the best result is obtained in smaller goitres and it is possible that the best effect of {sup 131}I is seen if treatment is given to patients with diffuse goitre before these become nodular. However, then there is a potential risk to swing in the direction to where {sup 131}I is used in an indiscriminate way, since the prevalence of non-toxic multinodular goitre is much higher than that of hyperthyroidism. Although we have data on the long-term hazards of {sup 131}I treatment in hyperthyroidism in terms of risk of cancer, we have only follow-up periods of 5 to 10 years for non-toxic goitres in small groups of patients and no data regarding the long-term risk of high-dose {sup 131}I treatment (>600 MBq) for this condition. Ideally, long term randomized studies comparing the effect, side effect and cost-benefit of surgery as opposed to {sup 131}I treatment should be performed. Awaiting this, it is at present mandatory that each individual patient be given a choice of treatment after proper information. 44 refs.

  3. Distinct toxic interactions of TiO2 nanoparticles with four coexisting organochlorine contaminants on algae.

    Science.gov (United States)

    Zhang, Shuai; Deng, Rui; Lin, Daohui; Wu, Fengchang

    Engineered nanoparticles are increasingly discharged into the environment. After discharge, these nanoparticles can interact with co-existing organic contaminants, resulting in a phenomena referred to as 'joint toxicity'. This study evaluated joint toxicities of TiO 2 nanoparticles (TiO 2 NPs) with four different (atrazine, hexachlorobenzene, pentachlorobenzene, and 3,3',4,4'-tetrachlorobiphenyl) organochlorine contaminants (OCs) toward algae (Chlorella pyrenoidosa). The potential mechanisms underlying the joint toxicity were discussed, including TiO 2 NPs-OC interactions, effects of TiO 2 NPs and OCs on biophysicochemical properties of algae and effects of TiO 2 NPs and OCs on each other's bioaccumulation in algae. The results indicate that coexposure led to a synergistic effect on the joint toxicity for TiO 2 NPs-atrazine, antagonistic effect for TiO 2 NPs-hexachlorobenzene and TiO 2 NPs-3,3',4,4'-tetrachlorobiphenyl, and an additive effect for TiO 2 NPs-pentachlorobenzene. There was nearly no adsorption of OCs by TiO 2 NPs, and the physicochemical properties of TiO 2 NPs were largely unaltered by the presence of OCs. However, both OCs and NPs affected the biophysicochemical properties of algal cells and thereby influenced the cell surface binding and/or internalization. TiO 2 NPs significantly increased the bioaccumulation of each OC. However, with the exception of atrazine, the bioaccumulation of TiO 2 NPs decreased when used with each OC. The distinct joint toxicity outcomes were a result of the balance between the increased toxicities of OCs (increased bioaccumulations) and the altered toxicity of TiO 2 NPs (bioaccumulation can either increase or decrease). These results can significantly improve our understanding of the potential environmental risks associated with NPs.

  4. Fundamentals of risk management understanding, evaluating and implementing effective risk management

    CERN Document Server

    Hopkin, Paul

    2012-01-01

    Now more than ever, organizations must plan, response and recognize all forms of risks that they face. "Fundamentals of Risk Management", now in its second edition, provides a comprehensive introduction to the subject of commercial and business risk for anyone studying for a career in risk as well as a broad range of risk professionals. It examines the key components of risk management and its application with examples to demonstrate its benefit to organisations in the public and private sector. The second edition has been completely updated to take into account the greater influence of ISO 3100, the emergence of Governance Risk and Compliance (GRC) and the wide use of the bowtie method to illustrate risk management. In addition, there is now a chapter on the skills and competencies required by an effective risk manager.

  5. Low-level toxicity of chemicals: No acceptable levels?

    Directory of Open Access Journals (Sweden)

    Bruce P Lanphear

    2017-12-01

    Full Text Available Over the past 3 decades, in a series of studies on some of the most extensively studied toxic chemicals and pollutants, scientists have found that the amount of toxic chemical linked with the development of a disease or death-which is central to determining "safe" or "hazardous" levels-is proportionately greater at the lowest dose or levels of exposure. These results, which are contrary to the way the United States Environmental Protection Agency (EPA and other regulatory agencies assess the risk of chemicals, indicate that we have underestimated the impact of toxic chemicals on death and disease. If widely disseminated chemicals and pollutants-like radon, lead, airborne particles, asbestos, tobacco, and benzene-do not exhibit a threshold and are proportionately more toxic at the lowest levels of exposure, we will need to achieve near-zero exposures to protect public health.

  6. An in vitro cytotoxic approach to assess the toxicity of heavy metals and their binary mixtures on hippocampal HT-22 cell line.

    Science.gov (United States)

    Karri, Venkatanaidu; Kumar, Vikas; Ramos, David; Oliveira, Eliandre; Schuhmacher, Marta

    2018-01-05

    Humans are exposed to a cocktail of heavy metal toxicants in the environment. Though heavy metals are deleterious, there is a paucity of information on the toxicity of mixtures. In this study, four common neurotoxicity heavy metals lead (Pb) cadmium (Cd), arsenic (As), and methylmercury (MeHg) were exposed individually and as mixtures to HT-22 cell line for 8days. The study established that low dose exposures induced toxicity to the HT-22 cell line during 8days. The results indicates potency dependent response, the toxicity of single metals on the HT-22 cells; MeHg > As > Cd > Pb. The cytotoxicity data of single metals were used to determine the mixtures interaction profile by using the dose additivity and effect additivity method. Metal mixtures showed higher toxicities compared to individual metals. Synergistic, antagonistic or additive effects of the toxicity were observed in different mixtures in low dose exposure. The interactive responses of mixtures depend on the co-exposure metal and their respective concentration. We concluded that the combined effects should be considered in the risk assessment of heavy metal co-exposure and potency. In future, comprehensive mechanistic based investigations needed for understanding the real interactive mixtures effects at molecular level. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Molecular toxicity of triclosan and carbamazepine to green algae Chlorococcum sp.: A single cell view using synchrotron-based Fourier transform infrared spectromicroscopy.

    Science.gov (United States)

    Xin, Xiaying; Huang, Guohe; Liu, Xia; An, Chunjiang; Yao, Yao; Weger, Harold; Zhang, Peng; Chen, Xiujuan

    2017-07-01

    Although pharmaceuticals and personal care products have been used and introduced into the environment in large quantities, little information on potential ecological risks is currently available considering their effects on living organisms. We verified the feasibility of using synchrotron-based Fourier Transform Infrared (SR-FTIR) spectromicroscopy to explore in vivo toxic effects on single living Chlorococcum sp. cells. The study provided important information to achieve a better understanding of the toxic mechanism of triclosan and carbamazepine on living algae Chlorococcum sp.. Triclosan and carbamazepine had distinctive toxic effects on unicellular living algae. Most strikingly, triclosan had more dramatic toxic effects on biochemical components than carbamazepine. Triclosan can affect algae primarily by inhibiting fatty acid synthesis and causing protein aggregation. The toxicity response was irreversible at higher concentration (100.000 μM), but attenuated at lower concentration (0.391 μM) as time extended. Carbamazepine can produce hydrophobic interactions to affect the phospholipid bilayer and work on specific proteins to disfunction the cell membrane. Carbamazepine-exposed cells developed a resistance while extending exposure time. This is the first demonstration from an ecological standpoint that SR-FTIR can provide an innovative approach to reveal the toxicity of emerging pollutants in aquatic environments. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Estimating the gasoline components and formulations toxicity to microalgae (Tetraselmis chuii) and oyster (Crassostrea rhizophorae) embryos: An approach to minimize environmental pollution risk

    International Nuclear Information System (INIS)

    Paixao, J.F.; Nascimento, I.A.; Pereira, S.A.; Leite, M.B.L.; Carvalho, G.C.; Silveira, J.S.C.; Reboucas, M.; Matias, G.R.A.; Rodrigues, I.L.P.

    2007-01-01

    Even though petrochemical contamination frequently occurs in the form of oil spills, it is thought that a greater danger to coastal habitats is posed by chronic petrochemical toxicity associated with urban run-off, in which gasoline water-soluble-fraction (WSF) plays an important role. The hypothesis of the entrepreneurs, who were associated to the scientists uncharged of this research, was that recycled petrochemical waste may provide different gasoline formulations, having different toxic properties; the correlation between the gasoline formulations and their components' toxicological effects might contribute to the reformulation of the products, in such a way that the gasoline generated could be less toxic and less harmful to the environment. The aim of this research was to determine the toxic effects of 14 different types of gasoline (formulated, in accordance with National Petroleum Agency standards, from petrochemical waste), on Tetraselmis chuii (microalgae culture) and Crassostrea rhizophorae (embryos). Microalgae and oyster embryos were exposed to different gasoline formulations water-soluble fractions (WSF) at a range of concentrations (0%, 4.6%, 10.0%, 22.0%, 46.0%, and 100%), for 96 and 24 h, respectively. The tests were carried out under controlled conditions. End-points have been CI50-96h (concentration causing 50% growth inhibition in microalgae cultures) and EC50-24h (concentration causing abnormalities on 50% of the exposed embryos). Through these procedures, gasoline formulations, which represent the lowest environmental risk, were selected. Bioassays carried out on the 8 different gasoline components aimed to correlate gasoline toxicity with the toxic potential of its components. The analysis of principal components showed that the C9DI, a mixture of aromatic hydrocarbons of 9 carbon atoms, had the highest level of toxic potential, followed by C9S (a mixture of aromatics with 9-11 carbon atoms) and heavy naphtha. The results showed gasoline

  9. Haloacetic acids in the aquatic environment. Part I: macrophyte toxicity

    International Nuclear Information System (INIS)

    Hanson, Mark L.; Solomon, Keith R.

    2004-01-01

    Haloacetic acids (HAAs) are contaminants of aquatic ecosystems with numerous sources, both anthropogenic and natural. The toxicity of HAAs to aquatic plants is generally uncharacterized. Laboratory tests were conducted with three macrophytes (Lemna gibba, Myriophyllum sibiricum and Myriophyllum spicatum) to assess the toxicity of five HAAs. Myriophyllum spp. has been proposed as required test species for pesticide registration in North America, but few studies have been conducted under standard test conditions. The HAAs in the present experiments were monochloroacetic acid (MCA), dichloroacetic acid (DCA), trichloroacetic acid (TCA), trifluoroacetic acid (TFA) and chlorodifluoroacetic acid (CDFA). MCA was the most toxic to Myriophyllum spp. with EC 50 values ranging from 8 to 12.4 mg/l depending on the endpoint, followed by DCA (EC 50 range 62-722.5 mg/l), TCA (EC 50 range 49.5-1702.6 mg/l), CDFA (EC 50 range 105.3 to >10,000 mg/l) and with TFA (EC 50 range 222.1 to 10,000 mg/l) the least toxic. Generally, L. gibba was less sensitive to HAA toxicity than Myriophyllum spp., with the difference in toxicity between them approximately threefold. The range of toxicity within Myriophyllum spp. was normally less than twofold. Statistically, plant length and node number were the most sensitive endpoints as they had the lowest observed coefficients of variation, but they were not the most sensitive to HAA toxicity. Toxicological sensitivity of endpoints varied depending on the measure of effect chosen and the HAA, with morphological endpoints usually an order of magnitude more sensitive than pigments for all plant species. Overall, mass and root measures tended to be the most sensitive indicators of HAA toxicity. The data from this paper were subsequently used in an ecological risk assessment for HAAs and aquatic plants. The assessment found HAAs to be of low risk to aquatic macrophytes and the results are described in the second manuscript of this series

  10. Increased Suicide Risk among Workers following Toxic Metal Exposure at the Paducah Gaseous Diffusion Plant From 1952 to 2003: A Cohort Study

    Directory of Open Access Journals (Sweden)

    LW Figgs

    2011-09-01

    Full Text Available Background: Suicide is a problem worldwide and occupation is an important risk factor. In the last decade, 55 200 deaths in the US were attributed to occupational risk factors. Objective: To determine if toxic metal exposure was associated with suicide risk among Paducah gaseous diffusion plant (PGDP workers. Methods: We assembled a cohort of 6820 nuclear industry workers employed from 1952 to 2003. A job-specific exposure matrix (JEM was used to determine metal exposure likelihood. Uranium exposure was also assessed by urinalysis. All suicide/self-injury International Classification for Disease (ICD codes were used to identify suicides. Standardized mortality ratios (SMR, odds ratios (OR, and hazard ratios (HR were used to estimate suicide risk. Results: PGDP suicide victims typically were younger white men. Within exposure likelihood categories, several suicide SMRs were typically elevated for several metals. Only beryllium exposure likelihood was associated with an increased HR. Uranium urine concentration was associated with an elevated suicide risk after stratification by urinalysis frequency. Conclusion: Suicide risk is associated with uranium exposure.

  11. DOPA Decarboxylase Modulates Tau Toxicity.

    Science.gov (United States)

    Kow, Rebecca L; Sikkema, Carl; Wheeler, Jeanna M; Wilkinson, Charles W; Kraemer, Brian C

    2018-03-01

    The microtubule-associated protein tau accumulates into toxic aggregates in multiple neurodegenerative diseases. We found previously that loss of D 2 -family dopamine receptors ameliorated tauopathy in multiple models including a Caenorhabditis elegans model of tauopathy. To better understand how loss of D 2 -family dopamine receptors can ameliorate tau toxicity, we screened a collection of C. elegans mutations in dopamine-related genes (n = 45) for changes in tau transgene-induced behavioral defects. These included many genes responsible for dopamine synthesis, metabolism, and signaling downstream of the D 2 receptors. We identified one dopamine synthesis gene, DOPA decarboxylase (DDC), as a suppressor of tau toxicity in tau transgenic worms. Loss of the C. elegans DDC gene, bas-1, ameliorated the behavioral deficits of tau transgenic worms, reduced phosphorylated and detergent-insoluble tau accumulation, and reduced tau-mediated neuron loss. Loss of function in other genes in the dopamine and serotonin synthesis pathways did not alter tau-induced toxicity; however, their function is required for the suppression of tau toxicity by bas-1. Additional loss of D 2 -family dopamine receptors did not synergize with bas-1 suppression of tauopathy phenotypes. Loss of the DDC bas-1 reduced tau-induced toxicity in a C. elegans model of tauopathy, while loss of no other dopamine or serotonin synthesis genes tested had this effect. Because loss of activity upstream of DDC could reduce suppression of tau by DDC, this suggests the possibility that loss of DDC suppresses tau via the combined accumulation of dopamine precursor levodopa and serotonin precursor 5-hydroxytryptophan. Published by Elsevier Inc.

  12. Consensus report on the future of animal-free systemic toxicity testing.

    Science.gov (United States)

    Leist, Marcel; Hasiwa, Nina; Rovida, Costanza; Daneshian, Mardas; Basketter, David; Kimber, Ian; Clewell, Harvey; Gocht, Tilman; Goldberg, Alan; Busquet, Francois; Rossi, Anna-Maria; Schwarz, Michael; Stephens, Martin; Taalman, Rob; Knudsen, Thomas B; McKim, James; Harris, Georgina; Pamies, David; Hartung, Thomas

    2014-01-01

    Since March 2013, animal use for cosmetics testing for the European market has been banned. This requires a renewed view on risk assessment in this field. However, in other fields as well, traditional animal experimentation does not always satisfy requirements in safety testing, as the need for human-relevant information is ever increasing. A general strategy for animal-free test approaches was outlined by the US National Research Council`s vision document for Toxicity Testing in the 21st Century in 2007. It is now possible to provide a more defined roadmap on how to implement this vision for the four principal areas of systemic toxicity evaluation: repeat dose organ toxicity, carcinogenicity, reproductive toxicity and allergy induction (skin sensitization), as well as for the evaluation of toxicant metabolism (toxicokinetics) (Fig. 1). CAAT-Europe assembled experts from Europe, America and Asia to design a scientific roadmap for future risk assessment approaches and the outcome was then further discussed and refined in two consensus meetings with over 200 stakeholders. The key recommendations include: focusing on improving existing methods rather than favoring de novo design; combining hazard testing with toxicokinetics predictions; developing integrated test strategies; incorporating new high content endpoints to classical assays; evolving test validation procedures; promoting collaboration and data-sharing of different industrial sectors; integrating new disciplines, such as systems biology and high throughput screening; and involving regulators early on in the test development process. A focus on data quality, combined with increased attention to the scientific background of a test method, will be important drivers. Information from each test system should be mapped along adverse outcome pathways. Finally, quantitative information on all factors and key events will be fed into systems biology models that allow a probabilistic risk assessment with flexible

  13. Male-mediated developmental toxicity

    Directory of Open Access Journals (Sweden)

    Diana Anderson

    2014-02-01

    Full Text Available Male-mediated developmental toxicity has been of concern for many years. The public became aware of male-mediated developmental toxicity in the early 1990s when it was reported that men working at Sellafield might be causing leukemia in their children. Human and animal studies have contributed to our current understanding of male-mediated effects. Animal studies in the 1980s and 1990s suggested that genetic damage after radiation and chemical exposure might be transmitted to offspring. With the increasing understanding that there is histone retention and modification, protamine incorporation into the chromatin and DNA methylation in mature sperm and that spermatozoal RNA transcripts can play important roles in the epigenetic state of sperm, heritable studies began to be viewed differently. Recent reports using molecular approaches have demonstrated that DNA damage can be transmitted to babies from smoking fathers, and expanded simple tandem repeats minisatellite mutations were found in the germline of fathers who were exposed to radiation from the Chernobyl nuclear power plant disaster. In epidemiological studies, it is possible to clarify whether damage is transmitted to the sons after exposure of the fathers. Paternally transmitted damage to the offspring is now recognized as a complex issue with genetic as well as epigenetic components.

  14. The Simplest Flowchart Stating the Mechanisms for Organic Xenobiotics-induced Toxicity: Can it Possibly be Accepted as a “Central Dogma” for Toxic Mechanisms?

    Science.gov (United States)

    Lee, Sundong; Cho, Myung-Haing

    2014-01-01

    Xenobiotics causing a variety of toxicity in biological systems could be classified as two types, inorganic and organic chemicals. It is estimated that the organic xenobiotics are responsible for approximately 80~90% of chemical-induced toxicity in human population. In the class for toxicology, we have encountered some difficulties in explaining the mechanisms of toxicity caused especially by organic chemicals. Here, a simple flowchart was introduced for explaining the mechanism of toxicity caused by organic xenobiotics, as the central dogma of molecular biology. This flowchart, referred to as a central dogma, was described based on a view of various aspects as follows: direct-acting chemicals vs. indirect-acting chemicals, cytochrome P450-dependent vs. cytochrome P450-independent biotransformation, reactive intermediates, reactivation, toxicokinetics vs. toxicodynamics, and reversibility vs. irreversibility. Thus, the primary objective of this flowchart is to help better understanding of the organic xenobiotics-induced toxic mechanisms, providing a major pathway for toxicity occurring in biological systems. PMID:25343011

  15. Quantal health effects for a combination of several toxic agents

    Energy Technology Data Exchange (ETDEWEB)

    Seiler, F A

    1988-12-01

    Quantal health effects caused by the combined action of a number of toxic agents are modeled using the information available for each toxicant acting in isolation. Two basic models are used; one assumes no interaction, the other postulates a separable kind of interaction in which each agent contributes an enhancement factor independent of all other agents. These two models provide yardsticks by which to measure synergisms and antagonisms in the interaction between the effects of toxic agents. Equations are given in approximations for small and large values of the risk. (author)

  16. Quantal health effects for a combination of several toxic agents

    International Nuclear Information System (INIS)

    Seiler, F.A.

    1988-01-01

    Quantal health effects caused by the combined action of a number of toxic agents are modeled using the information available for each toxicant acting in isolation. Two basic models are used; one assumes no interaction, the other postulates a separable kind of interaction in which each agent contributes an enhancement factor independent of all other agents. These two models provide yardsticks by which to measure synergisms and antagonisms in the interaction between the effects of toxic agents. Equations are given in approximations for small and large values of the risk. (author)

  17. Comparative metal oxide nanoparticle toxicity using embryonic zebrafish

    Directory of Open Access Journals (Sweden)

    Leah C. Wehmas

    2015-01-01

    Full Text Available Engineered metal oxide nanoparticles (MO NPs are finding increasing utility in the medical field as anticancer agents. Before validation of in vivo anticancer efficacy can occur, a better understanding of whole-animal toxicity is required. We compared the toxicity of seven widely used semiconductor MO NPs made from zinc oxide (ZnO, titanium dioxide, cerium dioxide and tin dioxide prepared in pure water and in synthetic seawater using a five-day embryonic zebrafish assay. We hypothesized that the toxicity of these engineered MO NPs would depend on physicochemical properties. Significant agglomeration of MO NPs in aqueous solutions is common making it challenging to associate NP characteristics such as size and charge with toxicity. However, data from our agglomerated MO NPs suggests that the elemental composition and dissolution potential are major drivers of toxicity. Only ZnO caused significant adverse effects of all MO particles tested, and only when prepared in pure water (point estimate median lethal concentration = 3.5–9.1 mg/L. This toxicity was life stage dependent. The 24 h toxicity increased greatly (∼22.7 fold when zebrafish exposures started at the larval life stage compared to the 24 h toxicity following embryonic exposure. Investigation into whether dissolution could account for ZnO toxicity revealed high levels of zinc ion (40–89% of total sample were generated. Exposure to zinc ion equivalents revealed dissolved Zn2+ may be a major contributor to ZnO toxicity.

  18. Evaluating the Zebrafish Embryo Toxicity Test for Pesticide ...

    Science.gov (United States)

    Given the numerous chemicals used in society, it is critical to develop tools for accurate and efficient evaluation of potential risks to human and ecological receptors. Fish embryo acute toxicity tests are 1 tool that has been shown to be highly predictive of standard, more resource-intensive, juvenile fish acute toxicity tests. However, there is also evidence that fish embryos are less sensitive than juvenile fish for certain types of chemicals, including neurotoxicants. The utility of fish embryos for pesticide hazard assessment was investigated by comparing published zebrafish embryo toxicity data from pesticides with median lethal concentration 50% (LC50) data for juveniles of 3 commonly tested fish species: rainbow trout, bluegill sunfish, and sheepshead minnow. A poor, albeit significant, relationship (r2 = 0.28; p embryo and juvenile fish toxicity when pesticides were considered as a single group, but a much better relationship (r2 = 0.64; p embryo toxicity test endpoints are particularly insensitive to neurotoxicants. These results indicate that it is still premature to replace juvenile fish toxicity tests with embryo-based tests such as the Organisation for Economic Co-op

  19. Emerging Fusarium and Alternaria Mycotoxins: Occurrence, Toxicity and Toxicokinetics

    Directory of Open Access Journals (Sweden)

    Sophie Fraeyman

    2017-07-01

    Full Text Available Emerging Fusarium and Alternaria mycotoxins gain more and more interest due to their frequent contamination of food and feed, although in vivo toxicity and toxicokinetic data are limited. Whereas the Fusarium mycotoxins beauvericin, moniliformin and enniatins particularly contaminate grain and grain-based products, Alternaria mycotoxins are also detected in fruits, vegetables and wines. Although contamination levels are usually low (µg/kg range, higher contamination levels of enniatins and tenuazonic acid may occasionally occur. In vitro studies suggest genotoxic effects of enniatins A, A1 and B1, beauvericin, moniliformin, alternariol, alternariol monomethyl ether, altertoxins and stemphyltoxin-III. Furthermore, in vitro studies suggest immunomodulating effects of most emerging toxins and a reproductive health hazard of alternariol, beauvericin and enniatin B. More in vivo toxicity data on the individual and combined effects of these contaminants on reproductive and immune system in both humans and animals is needed to update the risk evaluation by the European Food Safety Authority. Taking into account new occurrence data for tenuazonic acid, the complete oral bioavailability, the low total body clearance in pigs and broiler chickens and the limited toxicity data, a health risk cannot be completely excluded. Besides, some less known Alternaria toxins, especially the genotoxic altertoxins and stemphyltoxin III, should be incorporated in risk evaluation as well.

  20. Lead toxicity: current concerns.

    OpenAIRE

    Goyer, R A

    1993-01-01

    Over the 20-year period since the first issue of Environmental Health Perspectives was published, there has been considerable progress in the understanding of the potential toxicity of exposure to lead. Many of these advances have been reviewed in published symposia, conferences, and review papers in EHP. This brief review identifies major advances as well as a number of current concerns that present opportunities for prevention and intervention strategies. The major scientific advance has be...

  1. Toxicity of common ions to marine organisms

    International Nuclear Information System (INIS)

    Pillard, D.A.; DuFresne, D.L.; Evans, J.

    1995-01-01

    Produced waters from oil and gas drilling operations are typically very saline, and these may cause acute toxicity to marine organisms due to osmotic imbalances as well as to an excess or deficiency of specific common ions. In order to better understand the relationship between toxicity and ion concentration, laboratory toxicity tests were conducted using mysid shrimp (Mysidopsis bahia), sheepshead minnow (Cyprinodon variegatus), and inland silverside (Menidia beryllina). For each species the ionic concentration of standard laboratory water was proportionally increased or decreased to produce test solutions with a range of salinities. Organisms were exposed for 48 hours. Individual ions (sodium, potassium, calcium, magnetsium, strontium, chloride, bromide, sulfate, bicarbonate, and borate) were also manipulated to examine individual ion toxicity. The three test species differ in their tolerance of salinity. Mysid shrimp show a marked decrease in survival at salinities less than approximately 5 ppt. Both fish species tolerated low salinity water, however, silversides were less tolerant of saline waters (salinity greater than 40 ppt). There were also significant differences in the responses of the organisms to different ions. The results show that the salinity of the test solution may play an important role in the responses of the organisms to the produced water effluent. Predictable toxicity/ion relationships developed in this study can be used to estimate whether toxicity in a produced water is a result of common ions, salinity, or some other unknown toxicant

  2. Interaction of engineered nanoparticles with toxic and essential elements

    International Nuclear Information System (INIS)

    Shumakova, A A; Gmoshinski, I V; Khotimchenko, S A; Trushina, E N

    2015-01-01

    Interaction of engineered nanoparticles with toxic and essential trace elements must be taken into consideration when estimating risks of NPs presented in the natural environment. The purpose of this work was to study the possible influence of silica, titanium dioxide (rutile) and fullerenol NPs on the toxicity of cadmium and to research the status of some trace elements and related indices of immune function in experiments on laboratory animals. Young male Wistar rats received cadmium salt (1 mg/kg b.w. Cd) orally for 28 days separately or in conjunction with the said kinds of NPs in different doses. A number of effects was observed as a result of combined action of Cd together with NPs, increase in bioaccumulation of this toxic trace element in the liver was most evident. The observed effects didn't show simple dose- dependence in respect to nanomaterials that should be taken into consideration when assessing the possible risks of joint action of nanoparticles and toxic elements existing in the environment in extremely low doses. Violation of microelement homeostasis caused by the combined action of Cd and NPs can have various adverse effects, such as inhibition of T-cell immunity induced by co-administration of Cd with rutile NPs. (paper)

  3. Interaction of engineered nanoparticles with toxic and essential elements

    Science.gov (United States)

    Shumakova, A. A.; Gmoshinski, I. V.; Khotimchenko, S. A.; Trushina, E. N.

    2015-11-01

    Interaction of engineered nanoparticles with toxic and essential trace elements must be taken into consideration when estimating risks of NPs presented in the natural environment. The purpose of this work was to study the possible influence of silica, titanium dioxide (rutile) and fullerenol NPs on the toxicity of cadmium and to research the status of some trace elements and related indices of immune function in experiments on laboratory animals. Young male Wistar rats received cadmium salt (1 mg/kg b.w. Cd) orally for 28 days separately or in conjunction with the said kinds of NPs in different doses. A number of effects was observed as a result of combined action of Cd together with NPs, increase in bioaccumulation of this toxic trace element in the liver was most evident. The observed effects didn't show simple dose- dependence in respect to nanomaterials that should be taken into consideration when assessing the possible risks of joint action of nanoparticles and toxic elements existing in the environment in extremely low doses. Violation of microelement homeostasis caused by the combined action of Cd and NPs can have various adverse effects, such as inhibition of T-cell immunity induced by co-administration of Cd with rutile NPs.

  4. Bioavailability of potentially toxic elements in soil-grapevine (leaf, skin, pulp and seed) system and environmental and health risk assessment.

    Science.gov (United States)

    Milićević, Tijana; Urošević, Mira Aničić; Relić, Dubravka; Vuković, Gordana; Škrivanj, Sandra; Popović, Aleksandar

    2018-06-01

    Monitoring of potentially toxic elements in agricultural soil represents the first measure of caution regarding food safety, while research into element bioavailability should be a step forward in understanding the element transportation chain. This study was conducted in the grapevine growing area ("Oplenac Wine Route") for investigating element bioavailability in the soil-grapevine system accompanied by an assessment of the ecological implications and human health risk. Single extraction procedures (CH 3 COOH, Na 2 EDTA, CaCl 2 , NH 4 NO 3 and deionised H 2 O) and digestion were performed to estimate the bioavailability of 22 elements (Al, As, B, Ba, Be, Ca, Cd, Co, Cr, Cu, Fe, K, Li, Mg, Mn, Na, Ni, Pb, Sb, Sr, V and Zn) from the topsoil (0-30 cm) and subsoil (30-60 cm) to the grapevine parts (leaf, skin, pulp and seed) and wine. The extractants were effective comparing to the pseudo-total concentrations in following order Na 2 EDTA ˃ CH 3 COOH ˃ NH 4 NO 3  ˃ CaCl 2 , H 2 O 2 h and 16 h. The most suitable extractants for assessing the bioavailability of the elements from the soil to the grapevine parts were CaCl 2 , NH 4 NO 3 and Na 2 EDTA, but deionised H 2 O could be suitable, as well. The results showed that Ba was the most bioavailable element in the soil-grapevine system. Contamination factor implied a moderate contamination (1  1), the influence of atmospheric deposition on the aerial grapevine parts (leaves and grape skin) was observed. Nevertheless, low adverse health risk effects (HI wine consumers. Copyright © 2018 Elsevier B.V. All rights reserved.

  5. Applying the reasoned action approach to understanding health protection and health risk behaviors.

    Science.gov (United States)

    Conner, Mark; McEachan, Rosemary; Lawton, Rebecca; Gardner, Peter

    2017-12-01

    The Reasoned Action Approach (RAA) developed out of the Theory of Reasoned Action and Theory of Planned Behavior but has not yet been widely applied to understanding health behaviors. The present research employed the RAA in a prospective design to test predictions of intention and action for groups of protection and risk behaviors separately in the same sample. To test the RAA for health protection and risk behaviors. Measures of RAA components plus past behavior were taken in relation to eight protection and six risk behaviors in 385 adults. Self-reported behavior was assessed one month later. Multi-level modelling showed instrumental attitude, experiential attitude, descriptive norms, capacity and past behavior were significant positive predictors of intentions to engage in protection or risk behaviors. Injunctive norms were only significant predictors of intention in protection behaviors. Autonomy was a significant positive predictor of intentions in protection behaviors and a negative predictor in risk behaviors (the latter relationship became non-significant when controlling for past behavior). Multi-level modelling showed that intention, capacity, and past behavior were significant positive predictors of action for both protection and risk behaviors. Experiential attitude and descriptive norm were additional significant positive predictors of risk behaviors. The RAA has utility in predicting both protection and risk health behaviors although the power of predictors may vary across these types of health behavior. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Do 16 Polycyclic Aromatic Hydrocarbons Represent PAH Air Toxicity?

    Science.gov (United States)

    Samburova, Vera; Zielinska, Barbara; Khlystov, Andrey

    2017-08-15

    Estimation of carcinogenic potency based on analysis of 16 polycyclic aromatic hydrocarbons (PAHs) ranked by U.S. Environmental Protection Agency (EPA) is the most popular approach within scientific and environmental air quality management communities. The majority of PAH monitoring projects have been focused on particle-bound PAHs, ignoring the contribution of gas-phase PAHs to the toxicity of PAH mixtures in air samples. In this study, we analyzed the results of 13 projects in which 88 PAHs in both gas and particle phases were collected from different sources (biomass burning, mining operation, and vehicle emissions), as well as in urban air. The aim was to investigate whether 16 particle-bound U.S. EPA priority PAHs adequately represented health risks of inhalation exposure to atmospheric PAH mixtures. PAH concentrations were converted to benzo(a)pyrene-equivalent (BaPeq) toxicity using the toxic equivalency factor (TEF) approach. TEFs of PAH compounds for which such data is not available were estimated using TEFs of close isomers. Total BaPeq toxicities (∑ 88 BaPeq) of gas- and particle-phase PAHs were compared with BaPeq toxicities calculated for the 16 particle-phase EPA PAH (∑ 16EPA BaPeq). The results showed that 16 EPA particle-bound PAHs underrepresented the carcinogenic potency on average by 85.6% relative to the total (gas and particle) BaPeq toxicity of 88 PAHs. Gas-phase PAHs, like methylnaphthalenes, may contribute up to 30% of ∑ 88 BaPeq. Accounting for other individual non-EPA PAHs (i.e., benzo(e)pyrene) and gas-phase PAHs (i.e., naphthalene, 1- and 2-methylnaphthalene) will make the risk assessment of PAH-containing air samples significantly more accurate.

  7. Nanotoxicity: the toxicity research progress of metal and metal-containing nanoparticles.

    Science.gov (United States)

    Ding, Lingling; Liu, Zhidong; Aggrey, Mike Okweesi; Li, Chunhua; Chen, Jing; Tong, Ling

    2015-01-01

    Along with the exuberant development of nanotechnology, a large number of nanoformulations or non materials are successfully applied in the clinics, biomedicine, cosmetics and industry. Despite some unique advantages of nanoformulations, there exist potentially worrying toxic effects, particularly those related to metal and metal-containing nanoparticles (NPs). Although various researches have been conducted to assess the metallic and metal-containing nanoparticles toxic effects, only little is known about the toxicity expressive types and evaluation, reasons and mechanisms, influencing factors and research methods of metal and metal-containing nanotoxicity. Therefore, it is of importance to acquire a better understanding of metal and metal-containing nanoparticles toxicity for medical application. This review presents a summary on the metal and metal-containing nanoparticles toxicity research progress consulting relevant literature.

  8. Alterations of mitochondrial DNA in CEM cells selected for resistance toward ddC toxicity.

    Science.gov (United States)

    Bjerke, M; Franco, M; Johansson, M; Balzarini, J; Karlsson, A

    2006-01-01

    2 ',3 '-dideoxycytidine (ddC) is a nucleoside analog that has been shown to produce a delayed toxicity which may be due to the depletion of mitochondrial DNA (mtDNA). In order to gain further understanding of the events involved in mitochondrial toxicity, two different CEM cell lines were selected for resistance to the delayed ddC toxicity.

  9. Retrospective analysis of associations between water quality and toxic blooms of golden alga (Prymnesium parvum) in Texas reservoirs: Implications for understanding dispersal mechanisms and impacts of climate change

    Science.gov (United States)

    Patino, Reynaldo; Dawson, D.; VanLandeghem, Matthew M.

    2014-01-01

    Toxic blooms of golden alga (GA, Prymnesium parvum) in Texas typically occur in winter or early spring. In North America, they were first reported in Texas in the 1980s, and a marked range expansion occurred in 2001. Although there is concern about the influence of climate change on the future distribution of GA, factors responsible for past dispersals remain uncertain. To better understand the factors that influence toxic bloom dispersal in reservoirs, this study characterized reservoir water quality associated with toxic GA blooms since 2001, and examined trends in water quality during a 20-year period bracketing the 2001 expansion. Archived data were analyzed for six impacted and six nonimpacted reservoirs from two major Texas basins: Brazos River and Colorado River. Data were simplified for analysis by pooling spatially (across sampling stations) and temporally (winter, December-February) within reservoirs and generating depth-corrected (1 m) monthly values. Classification tree analysis [period of record (POR), 2001-2010] using salinity-associated variables (specific conductance, chloride, sulfate), dissolved oxygen (DO), pH, temperature, total hardness, potassium, nitrate+nitrite, and total phosphorus indicated that salinity best predicts the toxic bloom occurrence. Minimum estimated salinities for toxic bloom formation were 0.59 and 1.02 psu in Brazos and Colorado River reservoirs, respectively. Principal component analysis (POR, 2001-2010) indicated that GA habitat is best defined by higher salinity relative to nonimpacted reservoirs, with winter DO and pH also being slightly higher and winter temperature slightly lower in impacted reservoirs. Trend analysis, however, did not reveal monotonic changes in winter water quality of GA-impacted reservoirs during the 20-year period (1991-2010) bracketing the 2001 dispersal. Therefore, whereas minimum levels of salinity are required for GA establishment and toxic blooms in Texas reservoirs, the lack of trends in

  10. Association of a XRCC3 polymorphism and rectum mean dose with the risk of acute radio-induced gastrointestinal toxicity in prostate cancer patients

    International Nuclear Information System (INIS)

    Fachal, Laura; Gómez-Caamaño, Antonio; Peleteiro, Paula; Carballo, Ana; Calvo-Crespo, Patricia; Sánchez-García, Manuel; Lobato-Busto, Ramón; Carracedo, Ángel; Vega, Ana

    2012-01-01

    Background and purpose: We have performed a case–control study among prostate cancer patients treated with three-dimensional conformational radiotherapy (3D-CRT) in order to investigate the association between single nucleotide polymorphisms (SNPs), treatment and patient features with gastrointestinal and genitourinary acute toxicity. Material and methods: A total of 698 patients were screened for 14 SNPs located in the ATM, ERCC2, LIG4, MLH1 and XRCC3 genes. Gastrointestinal and genitourinary toxicities were recorded prospectively using the Common Terminology Criteria for Adverse Events v3.0. Results: The XRCC3 SNP rs1799794 (G/G OR = 5.65; 95% CI: 1.95–16.38; G/A OR = 2.75; 95% CI: 1.25–6.05; uncorrected p-value = 2.8 × 10 −03 ; corrected p-value = 0.03; FDR q-value = 0.06) as well as the mean dose received by the rectum (OR = 1.06; 95% CI: 1.02–1.1; uncorrected p-value = 2.49 × 10 −03 ; corrected p-value = 0.03; FDR q-value = 0.06) were significantly associated with gastrointestinal toxicity after correction for multiple testing. Those patients who undergone previous prostatectomy were less prone to develop genitourinary toxicity (OR = 0.38; 95% CI: 0.18–0.71; uncorrected p-value = 4.95 × 10 −03 ; corrected p-value = 0.03; FDR q-value = 0.08). Our study excludes the possibility of a >2-fold risk increase in genitourinary acute toxicity being due to rs1801516 ATM SNP, the rs1805386 and rs1805388 LIG4 markers, as well as all the SNPs evaluated in the ERCC2, MLH1 and XRCC3 genes. Conclusions: The XRCC3 rs1799794 SNP and the mean dose received by the rectum are associated with the development of gastrointestinal toxicity after 3D-CRT.

  11. Temporal assessment of copper speciation, bioavailability and toxicity in UK freshwaters using chemical equilibrium and biotic ligand models: Implications for compliance with copper environmental quality standards.

    Science.gov (United States)

    Lathouri, Maria; Korre, Anna

    2015-12-15

    Although significant progress has been made in understanding how environmental factors modify the speciation, bioavailability and toxicity of metals such as copper in aquatic environments, the current methods used to establish water quality standards do not necessarily consider the different geological and geochemical characteristics of a given site and the factors that affect copper fate, bioavailability potential and toxicity. In addition, the temporal variation in the concentration and bioavailable metal fraction is also important in freshwater systems. The work presented in this paper illustrates the temporal and seasonal variability of a range of water quality parameters, and Cu speciation, bioavailability and toxicity at four freshwaters sites in the UK. Rivers Coquet, Cree, Lower Clyde and Eden (Kent) were selected to cover a broad range of different geochemical environments and site characteristics. The monitoring data used covered a period of around six years at almost monthly intervals. Chemical equilibrium modelling was used to study temporal variations in Cu speciation and was combined with acute toxicity modelling to assess Cu bioavailability for two aquatic species, Daphnia magna and Daphnia pulex. The estimated copper bioavailability, toxicity levels and the corresponding ecosystem risks were analysed in relation to key water quality parameters (alkalinity, pH and DOC). Although copper concentrations did not vary much during the sampling period or between the seasons at the different sites; copper bioavailability varied markedly. In addition, through the chronic-Cu BLM-based on the voluntary risk assessment approach, the potential environmental risk in terms of the chronic toxicity was assessed. A much higher likelihood of toxicity effects was found during the cold period at all sites. It is suggested that besides the metal (copper) concentration in the surface water environment, the variability and seasonality of other important water quality

  12. A general mechanism for intracellular toxicity of metal-containing nanoparticles

    Science.gov (United States)

    Sabella, Stefania; Carney, Randy P.; Brunetti, Virgilio; Malvindi, Maria Ada; Al-Juffali, Noura; Vecchio, Giuseppe; Janes, Sam M.; Bakr, Osman M.; Cingolani, Roberto; Stellacci, Francesco; Pompa, Pier Paolo

    2014-05-01

    The assessment of the risks exerted by nanoparticles is a key challenge for academic, industrial, and regulatory communities worldwide. Experimental evidence points towards significant toxicity for a range of nanoparticles both in vitro and in vivo. Worldwide efforts aim at uncovering the underlying mechanisms for this toxicity. Here, we show that the intracellular ion release elicited by the acidic conditions of the lysosomal cellular compartment - where particles are abundantly internalized - is responsible for the cascading events associated with nanoparticles-induced intracellular toxicity. We call this mechanism a ``lysosome-enhanced Trojan horse effect'' since, in the case of nanoparticles, the protective cellular machinery designed to degrade foreign objects is actually responsible for their toxicity. To test our hypothesis, we compare the toxicity of similar gold particles whose main difference is in the internalization pathways. We show that particles known to pass directly through cell membranes become more toxic when modified so as to be mostly internalized by endocytosis. Furthermore, using experiments with chelating and lysosomotropic agents, we found that the toxicity mechanism for different metal containing NPs (such as metallic, metal oxide, and semiconductor NPs) is mainly associated with the release of the corresponding toxic ions. Finally, we show that particles unable to release toxic ions (such as stably coated NPs, or diamond and silica NPs) are not harmful to intracellular environments.The assessment of the risks exerted by nanoparticles is a key challenge for academic, industrial, and regulatory communities worldwide. Experimental evidence points towards significant toxicity for a range of nanoparticles both in vitro and in vivo. Worldwide efforts aim at uncovering the underlying mechanisms for this toxicity. Here, we show that the intracellular ion release elicited by the acidic conditions of the lysosomal cellular compartment - where

  13. A randomized hypofractionation dose escalation trial for high risk prostate cancer patients: interim analysis of acute toxicity and quality of life in 124 patients

    International Nuclear Information System (INIS)

    Norkus, Darius; Valuckas, Konstantinas Povilas; Karklelyte, Agata; Engels, Benedikt; Versmessen, Harijati; Griskevicius, Romas; De Ridder, Mark; Storme, Guy; Aleknavicius, Eduardas; Janulionis, Ernestas

    2013-01-01

    The α/β ratio for prostate cancer is postulated being in the range of 0.8 to 2.2 Gy, giving rise to the hypothesis that there may be a therapeutic advantage to hypofractionation. To do so, we carried out a randomized trial comparing hypofractionated and conventionally fractionated image-guided intensity modulated radiotherapy (IG-IMRT) in high-risk prostate cancer. Here, we report on acute toxicity and quality of life (QOL) for the first 124 randomized patients. The trial compares 76 Gy in 38 fractions (5 fractions/week) (Arm 1) to 63 Gy in 20 fractions (4 fractions/week) (Arm 2) (IG-IMRT). Prophylactic pelvic lymph node irradiation with 46 Gy in 23 fractions sequentially (Arm 1) and 44 Gy in 20 fractions simultaneously (Arm 2) was applied. All patients had long term androgen deprivation therapy (ADT) started before RT. Both physician-rated acute toxicity and patient-reported QOL using EPIC questionnaire are described. There were no differences in overall maximum acute gastrointestinal (GI) or genitourinary (GU) toxicity. Compared to conventional fractionation (Arm 1), GI and GU toxicity both developed significantly earlier but also disappeared earlier in the Arm 2, reaching significant differences from Arm 1 at week 8 and 9. In multivariate analyses, only parameter shown to be related to increased acute Grade ≥1 GU toxicity was the study Arm 2 (p = 0.049). There were no statistically significant differences of mean EPIC scores in any domain and sub-scales. The clinically relevant decrease (CRD) in EPIC urinary domain was significantly higher in Arm 2 at month 1 with a faster recovery at month 3 as compared to Arm 1. Hypofractionation at 3.15 Gy per fraction to 63 Gy within 5 weeks was well tolerated. The GI and GU physician-rated acute toxicity both developed earlier but recovered faster using hypofractionation. There was a correlation between acute toxicity and bowel and urinary QOL outcomes. Longer follow-up is needed to determine the significance of these

  14. Exploring the potential role of tungsten carbide cobalt (WC-Co) nanoparticle internalization in observed toxicity toward lung epithelial cells in vitro.

    Science.gov (United States)

    Armstead, Andrea L; Arena, Christopher B; Li, Bingyun

    2014-07-01

    Tungsten carbide cobalt (WC-Co) has been recognized as a workplace inhalation hazard in the manufacturing, mining and drilling industries by the National Institute of Occupational Safety and Health. Exposure to WC-Co is known to cause "hard metal lung disease" but the relationship between exposure, toxicity and development of disease remain poorly understood. To better understand this relationship, the present study examined the role of WC-Co particle size and internalization on toxicity using lung epithelial cells. We demonstrated that nano- and micro-WC-Co particles exerted toxicity in a dose- and time-dependent manner and that nano-WC-Co particles caused significantly greater toxicity at lower concentrations and shorter exposure times compared to micro-WC-Co particles. WC-Co particles in the nano-size range (not micron-sized) were internalized by lung epithelial cells, which suggested that internalization may play a key role in the enhanced toxicity of nano-WC-Co particles over micro-WC-Co particles. Further exploration of the internalization process indicated that there may be multiple mechanisms involved in WC-Co internalization such as actin and microtubule based cytoskeletal rearrangements. These findings support our hypothesis that WC-Co particle internalization contributes to cellular toxicity and suggest that therapeutic treatments inhibiting particle internalization may serve as prophylactic approaches for those at risk of WC-Co particle exposure. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. On how to understand and acknowledge risk

    International Nuclear Information System (INIS)

    Amundrud, Øystein; Aven, Terje

    2015-01-01

    In Norway two concepts in risk assessment and management – risikoforståelse and risikoerkjennelse – have recently been given much attention, particularly in the oil and gas industry and in societal safety and security contexts. The former concept corresponds quite well to ‘risk understanding’ but the latter does not have an exact counterpart in English – the best term seems to be ‘risk acknowledgement’. The discourse related to these two concepts has given us new general insights concerning the risk concept and its practical use, and the purpose of the present paper is to point to and discuss the main observations made. A main conclusion of the paper is that justified beliefs – what we refer to as knowledge – and the processes of generating these beliefs is an essential feature of both these concepts. - Highlights: • We examine two concepts – ‘risk understanding’ and ‘risk acknowledgement’. • Justified beliefs (knowledge) is an essential feature of both concepts. • Risk assessment is to a large extent about gaining ‘risk understanding’. • ‘Risk acknowledgement’ is of special importance in cases with deep uncertainties

  16. Gaining acceptance for the use of in vitro toxicity assays and QIVIVE in regulatory risk assessment.

    Science.gov (United States)

    Meek, M E Bette; Lipscomb, John C

    2015-06-05

    Testing strategies are anticipated to increasingly rely on in vitro data as a basis to characterize early steps or key events in toxicity at relevant dose levels in human tissues. Such strategies require quantitative in vitro to in vivo extrapolation to characterize dose-response as a basis for comparison with exposure to estimate risk. Current experience in the incorporation of mechanistic and in vitro data in risk assessment is considered here in the context of identified principles to increase the potential for timely acceptance of more progressive and tailored testing strategies by the regulatory community. These principles are outlined as transitioning in a familiar context, tiering to acquire experience and increase confidence, contextual knowledge transfer to facilitate interpretation and communication, coordination and development of expertise and continuing challenge. A proposed pragmatic tiered data driven framework which includes increasing reliance on in vitro data and quantitative in vitro to in vivo extrapolation is considered in the context of these principles. Based on this analysis, possible additional steps that might facilitate timely evolution and potentially, uptake are identified. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  17. Proteomic Assessment of Biochemical Pathways That Are Critical to Nickel-Induced Toxicity Responses in Human Epithelial Cells

    Science.gov (United States)

    Ge, Yue; Bruno, Maribel; Haykal-Coates, Najwa; Wallace, Kathleen; Andrews, Debora; Swank, Adam; Winnik, Witold; Ross, Jeffrey A.

    2016-01-01

    Understanding the mechanisms underlying toxicity initiated by nickel, a ubiquitous environmental contaminant and known human carcinogen is necessary for proper assessment of its risks to human and environment. Among a variety of toxic mechanisms, disruption of protein responses and protein response-based biochemical pathways represents a key mechanism through which nickel induces cytotoxicity and carcinogenesis. To identify protein responses and biochemical pathways that are critical to nickel-induced toxicity responses, we measured cytotoxicity and changes in expression and phosphorylation status of 14 critical biochemical pathway regulators in human BEAS-2B cells exposed to four concentrations of nickel using an integrated proteomic approach. A subset of the pathway regulators, including interleukin-6, and JNK, were found to be linearly correlated with cell viability, and may function as molecular determinants of cytotoxic responses of BEAS-2B cells to nickel exposures. In addition, 128 differentially expressed proteins were identified by two dimensional electrophoresis (2-DE) and mass spectrometry. Principal component analysis, hierarchical cluster analyses, and ingenuity signaling pathway analysis (IPA) identified putative nickel toxicity pathways. Some of the proteins and pathways identified have not previously been linked to nickel toxicity. Based on the consistent results obtained from both ELISA and 2-DE proteomic analysis, we propose a core signaling pathway regulating cytotoxic responses of human BEAS-2B cells to nickel exposures, which integrates a small set of proteins involved in glycolysis and gluconeogenesis pathways, apoptosis, protein degradation, and stress responses including inflammation and oxidative stress. PMID:27626938

  18. The effect of different cardiovascular risk presentation formats on intentions, understanding and emotional affect: a randomised controlled trial using a web-based risk formatter (protocol

    Directory of Open Access Journals (Sweden)

    Newcombe Robert

    2010-07-01

    Full Text Available Abstract Background The future risk of heart disease can be predicted with increasing precision. However, more research is needed into how this risk is conveyed and presented. The aim of this study is to compare the effects of presenting cardiovascular risk in different formats on individuals' intention to change behaviour to reduce risk, understanding of risk information and emotional affect. Methods/design A randomised controlled trial comprising four arms, with a between subjects design will be performed. There will be two intervention groups and two control groups. The first control comprises a pre-intervention questionnaire and presents risk in a bar graph format. The second control presents risk in a bar graph format without pre-intervention questionnaire. These two control groups are to account for the potential Hawthorne effect of thinking about cardiovascular risk before viewing actual risk. The two intervention groups comprise presenting risk in either a pictogram or metonym format (image depicting seriousness of having a myocardial infarction. 800 individuals' aged between 45 and 64 years, who have not been previously diagnosed with heart disease and have access to a computer with internet, will be given a link to a website comprising a risk calculator and electronic questionnaires. 10-year risk of having a coronary heart disease event will be assessed and presented in one of the three formats. A post-intervention questionnaire will be completed after viewing the risk format. Main outcome measures are (i intention to change behaviour, (ii understanding of risk information, (iii emotional affect and (iv worry about future heart disease. Secondary outcomes are the sub-components of the theory of planned behaviour: attitudes, perceived behavioural control and subjective norms. Discussion Having reviewed the literature, we are not aware of any other studies which have used the assessment of actual risk, in a trial to compare different

  19. Interactions between toxic chemicals and natural environmental factors--a meta-analysis and case studies.

    Science.gov (United States)

    Laskowski, Ryszard; Bednarska, Agnieszka J; Kramarz, Paulina E; Loureiro, Susana; Scheil, Volker; Kudłek, Joanna; Holmstrup, Martin

    2010-08-15

    The paper addresses problems arising from effects of natural environmental factors on toxicity of pollutants to organisms. Most studies on interactions between toxicants and natural factors, including those completed in the EU project NoMiracle (Novel Methods for Integrated Risk Assessment of Cumulative Stressors in Europe) described herein, showed that effects of toxic chemicals on organisms can differ vastly depending purely on external conditions. We compiled data from 61 studies on effects of temperature, moisture and dissolved oxygen on toxicity of a range of chemicals representing pesticides, polycyclic aromatic hydrocarbons, plant protection products of bacterial origin and trace metals. In 62.3% cases significant interactions (pnatural factors and chemicals were found, reaching 100% for the effect of dissolved oxygen on toxicity of waterborne chemicals. The meta-analysis of the 61 studies showed that the null hypothesis assuming no interactions between toxic chemicals and natural environmental factors should be rejected at p=2.7 x 10(-82) (truncated product method probability). In a few cases of more complex experimental designs, also second-order interactions were found, indicating that natural factors can modify interactions among chemicals. Such data emphasize the necessity of including information on natural factors and their variation in time and across geographic regions in ecological risk assessment. This can be done only if appropriate ecotoxicological test designs are used, in which test organisms are exposed to toxicants at a range of environmental conditions. We advocate designing such tests for the second-tier ecological risk assessment procedures. Copyright 2010 Elsevier B.V. All rights reserved.

  20. Application of TIE's in assessing toxicity associated with oil sands process waters

    International Nuclear Information System (INIS)

    MacKinnon, M.

    1998-01-01

    The hot water digestion process which separates bitumen from oil sands produces large volumes of process-affected waters which are extremely toxic to aquatic organisms. At Syncrude Canada's northeastern Alberta plant, the toxic waters are contained on the site and none are discharged. Organic acids, hydrocarbons and salts are leached into the tailings waters. A toxicity identification evaluation (TIE) test was used to confirm the main contributors to the acute toxicity in these waters. A battery bioassay approach as well as field and laboratory testing was used to understand the source, pathway and duration of the toxicity. Bioassays helped in developing ways in which to mitigate toxicity issues in both reclamation and operational waters. It was demonstrated that natural bioremediation of process-affected waters can reduce acute and chronic toxicity. The long term reclamation impacts of these waters has yet to be determined

  1. Metal toxicity affects predatory stream invertebrates less than other functional feeding groups

    International Nuclear Information System (INIS)

    Liess, Matthias; Gerner, Nadine V.; Kefford, Ben J.

    2017-01-01

    Ecosystem effects of heavy metals need to be identified for a retrospective risk assessment, and potential impacts need to be predicted for a prospective risk assessment. In this study, we established a strong correlation between the toxic pressure of dissolved metals and invertebrate species. We compiled available data from a wide geographical range of Australian streams that were contaminated with heavy metals [mainly copper (Cu) and zinc (Zn)] and the corresponding invertebrate communities. Heavy metal toxicity is positively related to the proportion of predators within the invertebrate community, represented by the predator ratio , with an effect threshold range of 2.6 μg/L - 26 μg/L for Cu and 62 μg/L - 617 μg/L for Zn. These effect concentrations are in the ranges of the concentrations identified in model ecosystems and other field investigations and are just above the existing guideline limits. Heavy metals also affects the taxa richness negatively. Other community measures, such as the evenness, number of EPT (Ephemeroptera, Plecoptera, and Trichoptera) taxa, SPEcies At Risk (SPEAR) pesticides or SPEAR salinity were relatively poorly correlated with heavy metal toxicity in the streams. Therefore, we suggest applying the predator ratio within the community as a starting point for an indicator of the dissolved metal toxicity, the SPEAR metals . - Highlights: • Data on dissolved metals and invertebrates were compiled for a wide geographical range. • Heavy metal toxicity was strongly related to the predator ratio. • Ecologically relevant thresholds identified for Cu and Zn were above the guideline limits. - Increasing metal toxicity for Cu and Zn in streams could be related to an increasing predator ratio within the invertebrate community.

  2. Carcinogenic Air Toxics Exposure and Their Cancer-Related Health Impacts in the United States.

    Science.gov (United States)

    Zhou, Ying; Li, Chaoyang; Huijbregts, Mark A J; Mumtaz, M Moiz

    2015-01-01

    Public health protection from air pollution can be achieved more effectively by shifting from a single-pollutant approach to a multi-pollutant approach. To develop such multi-pollutant approaches, identifying which air pollutants are present most frequently is essential. This study aims to determine the frequently found carcinogenic air toxics or hazardous air pollutants (HAPs) combinations across the United States as well as to analyze the health impacts of developing cancer due to exposure to these HAPs. To identify the most commonly found carcinogenic air toxics combinations, we first identified HAPs with cancer risk greater than one in a million in more than 5% of the census tracts across the United States, based on the National-Scale Air Toxics Assessment (NATA) by the U.S. EPA for year 2005. We then calculated the frequencies of their two-component (binary), and three-component (ternary) combinations. To quantify the cancer-related health impacts, we focused on the 10 most frequently found HAPs with national average cancer risk greater than one in a million. Their cancer-related health impacts were calculated by converting lifetime cancer risk reported in NATA 2005 to years of healthy life lost or Disability-Adjusted Life Years (DALYs). We found that the most frequently found air toxics with cancer risk greater than one in a million are formaldehyde, carbon tetrachloride, acetaldehyde, and benzene. The most frequently occurring binary pairs and ternary mixtures are the various combinations of these four air toxics. Analysis of urban and rural HAPs did not reveal significant differences in the top combinations of these chemicals. The cumulative annual cancer-related health impacts of inhaling the top 10 carcinogenic air toxics included was about 1,600 DALYs in the United States or 0.6 DALYs per 100,000 people. Formaldehyde and benzene together contribute nearly 60 percent of the total cancer-related health impacts. Our study shows that although there are many

  3. Carcinogenic Air Toxics Exposure and Their Cancer-Related Health Impacts in the United States.

    Directory of Open Access Journals (Sweden)

    Ying Zhou

    Full Text Available Public health protection from air pollution can be achieved more effectively by shifting from a single-pollutant approach to a multi-pollutant approach. To develop such multi-pollutant approaches, identifying which air pollutants are present most frequently is essential. This study aims to determine the frequently found carcinogenic air toxics or hazardous air pollutants (HAPs combinations across the United States as well as to analyze the health impacts of developing cancer due to exposure to these HAPs. To identify the most commonly found carcinogenic air toxics combinations, we first identified HAPs with cancer risk greater than one in a million in more than 5% of the census tracts across the United States, based on the National-Scale Air Toxics Assessment (NATA by the U.S. EPA for year 2005. We then calculated the frequencies of their two-component (binary, and three-component (ternary combinations. To quantify the cancer-related health impacts, we focused on the 10 most frequently found HAPs with national average cancer risk greater than one in a million. Their cancer-related health impacts were calculated by converting lifetime cancer risk reported in NATA 2005 to years of healthy life lost or Disability-Adjusted Life Years (DALYs. We found that the most frequently found air toxics with cancer risk greater than one in a million are formaldehyde, carbon tetrachloride, acetaldehyde, and benzene. The most frequently occurring binary pairs and ternary mixtures are the various combinations of these four air toxics. Analysis of urban and rural HAPs did not reveal significant differences in the top combinations of these chemicals. The cumulative annual cancer-related health impacts of inhaling the top 10 carcinogenic air toxics included was about 1,600 DALYs in the United States or 0.6 DALYs per 100,000 people. Formaldehyde and benzene together contribute nearly 60 percent of the total cancer-related health impacts. Our study shows that although

  4. Acute Toxicity and Ecological Risk Assessment of Benzophenone-3 (BP-3 and Benzophenone-4 (BP-4 in Ultraviolet (UV-Filters

    Directory of Open Access Journals (Sweden)

    Yang Du

    2017-11-01

    Full Text Available Ultraviolet (UV-absorbing chemicals (UV filters are used in personal care products for the protection of human skin and hair from damage by UV radiation. Although these substances are released into the environment in the production and consumption processes, little is known about their ecotoxicology effects. The acute toxicity and potential ecological risk of UV filters benzophenone-3 (BP-3 and benzophenone-4 (BP-4 on Chlorella vulgaris, Daphnia magna, and Brachydanio rerio were analyzed in the present study. The EC50 values (96 h of BP-3 and BP-4 on C. vulgaris were 2.98 and 201.00 mg/L, respectively. The 48 h-LC50 of BP-3 and BP-4 on D. magna were 1.09 and 47.47 mg/L, respectively. The 96 h-LC50 of BP-3 and BP-4 on B. rerio were 3.89 and 633.00 mg/L, respectively. The toxicity of a mixture of BP-3 and BP-4 on C. vulgaris, D. magna, and B. rerio all showed antagonistic effects. The induced predicted no-effect concentrations of BP-3 and BP-4 by the assessment factor method were 1.80 × 10−3 and 0.47 mg/L, respectively, by assessment factor (AF method, which were both lower than the concentrations detected in the environment at present, verifying that BP-3 and BP-4 remain low-risk chemicals to the aquatic ecosystem.

  5. Toxicity of nine insecticides on four natural enemies of Spodoptera exigua

    Science.gov (United States)

    Liu, Yongqiang; Li, Xiangying; Zhou, Chao; Liu, Feng; Mu, Wei

    2016-01-01

    Spodoptera exigua, which feeds on various crops worldwide, has natural enemies that are susceptible to the insecticides used against S. exigua. We investigate the toxicity and residue risk of 9 insecticides on the development of H. axyridis, C. sinica, S. manilae and T. remus. S. manilae and T. remus adults were sensitive to all 9 insecticides (LC50 less than 2.75 mg a.i. liter−1), while H. axyridis and C. sinica adults were less sensitive (LC50 between 6 × 10−5 mg a.i. liter−1 and 78.95 mg a.i. liter−1). Emamectin benzoate, spinosad, indoxacarb, alpha-cypermethrin, chlorfenapyr and chlorantraniliprole showed no toxicity on H. axyridis, C. sinica, S. manilae and T. remus pupae with the recommended field concentrations. The risk analysis indicated that chlorantraniliprole is harmless to larvae of four natural enemies and adult of H. axyridis, C. sinica and S. manilae. Emamectin benzoate and spinosad had higher safety to the development of H. axyridis, C. sinica, S. manilae and T. remus with the risk duration less than 4d. Indoxacarb, tebufenozide, chlorfenapyr, methomyl, alpha-cypermethrin and chlorpyrifos showed dangerously toxic and long risk duration on S. manilae and T. remus adults. PMID:27958333

  6. Toxicity of nine insecticides on four natural enemies of Spodoptera exigua.

    Science.gov (United States)

    Liu, Yongqiang; Li, Xiangying; Zhou, Chao; Liu, Feng; Mu, Wei

    2016-12-13

    Spodoptera exigua, which feeds on various crops worldwide, has natural enemies that are susceptible to the insecticides used against S. exigua. We investigate the toxicity and residue risk of 9 insecticides on the development of H. axyridis, C. sinica, S. manilae and T. remus. S. manilae and T. remus adults were sensitive to all 9 insecticides (LC 50 less than 2.75 mg a.i. liter -1 ), while H. axyridis and C. sinica adults were less sensitive (LC 50 between 6 × 10 -5  mg a.i. liter -1 and 78.95 mg a.i. liter -1 ). Emamectin benzoate, spinosad, indoxacarb, alpha-cypermethrin, chlorfenapyr and chlorantraniliprole showed no toxicity on H. axyridis, C. sinica, S. manilae and T. remus pupae with the recommended field concentrations. The risk analysis indicated that chlorantraniliprole is harmless to larvae of four natural enemies and adult of H. axyridis, C. sinica and S. manilae. Emamectin benzoate and spinosad had higher safety to the development of H. axyridis, C. sinica, S. manilae and T. remus with the risk duration less than 4d. Indoxacarb, tebufenozide, chlorfenapyr, methomyl, alpha-cypermethrin and chlorpyrifos showed dangerously toxic and long risk duration on S. manilae and T. remus adults.

  7. Evaluating the toxicity of selected types of nanochemicals.

    Science.gov (United States)

    Kumar, Vineet; Kumari, Avnesh; Guleria, Praveen; Yadav, Sudesh Kumar

    2012-01-01

    . NPs have produced an array of different toxic effects in many different types of in vivo and in vitro studies. The types of effects that NPs have produced are those on the pulmonary, cardiac, reproductive, renal and cutaneous systems, as well as on various cell lines. After exposures, significant accumulations of NPs have been found in the lungs, brain, liver, spleen, and bones of test species. It has been well established that the degree of toxicity produced by NPs is linked to their surface properties. Soluble NPs are rendered toxic because of their constituents; however, the situation is entirely different for insoluble NPs. Stable metal oxides do not show any toxicity, whereas metallic NPs that have redox potential may be cytotoxic and genotoxic. The available data on NP toxicity is unfortunately limited, and hence, does not allow scientists to yet make a significant quantitative risk assessment of the safety of synthesized NPs. In this review, we have endeavored to illustrate the importance of having and using results from existing nanotoxicological studies and for developing new and more useful future risk assessment systems. Increased efforts of both an individual and collective nature are required to explore the future pros and cons of nanotechnology.

  8. Silver nanoparticle toxicity in sea urchin Paracentrotus lividus

    International Nuclear Information System (INIS)

    Šiller, Lidija; Lemloh, Marie-Louise; Piticharoenphun, Sunthon; Mendis, Budhika G.; Horrocks, Benjamin R.; Brümmer, Franz; Medaković, Davorin

    2013-01-01

    Silver nanoparticles (AgNPS) are an important model system for studying potential environmental risks posed by the use of nanomaterials. So far there is no consensus as to whether toxicity is due to AgNPs themselves or Ag + ions leaching from their surfaces. In sea urchin Paracentrotus lividus, AgNPs cause dose dependent developmental defects such as delayed development, bodily asymmetry and shortened or irregular arms, as well as behavioural changes, particularly in swimming patterns, at concentration ∼0.3 mg/L AgNPs. It has been observed that AgNPs are more toxic than their equivalent Ag + ion dose. -- Silver nanoparticles cause dose dependent developmental defects in sea urchin and they are more toxic than their equivalent Ag + ion dose

  9. Developmental and reproductive toxicity of inorganic arsenic: animal studies and human concerns.

    Science.gov (United States)

    Golub, M S; Macintosh, M S; Baumrind, N

    1998-01-01

    Information on the reproductive and developmental toxicity of inorganic arsenic is available primarily from studies in animals using arsenite and arsenate salts and arsenic trioxide. Inorganic arsenic has been extensively studied as a teratogen in animals. Data from animal studies demonstrate that arsenic can produce developmental toxicity, including malformation, death, and growth retardation, in four species (hamsters, mice, rats, rabbits). A characteristic pattern of malformations is produced, and the developmental toxicity effects are dependent on dose, route, and the day of gestation when exposure occurs. Studies with gavage and diet administration indicate that death and growth retardation are produced by oral arsenic exposure. Arsenic is readily transferred to the fetus and produces developmental toxicity in embryo culture. Animal studies have not identified an effect of arsenic on fertility in males or females. When females were dosed chronically for periods that included pregnancy, the primary effect of arsenic on reproduction was a dose-dependent increase in conceptus mortality and in postnatal growth retardation. Human data are limited to a few studies of populations exposed to arsenic from drinking water or from working at or living near smelters. Associations with spontaneous abortion and stillbirth have been reported in more than one of these studies, but interpretation of these studies is complicated because study populations were exposed to multiple chemicals. Thus, animal studies suggest that environmental arsenic exposures are primarily a risk to the developing fetus. In order to understand the implications for humans, attention must be given to comparative pharmacokinetics and metabolism, likely exposure scenarios, possible mechanisms of action, and the potential role of arsenic as an essential nutrient.

  10. High concentrations of protein test substances may have non-toxic effects on Daphnia magna: implications for regulatory study designs and ecological risk assessments for GM crops.

    Science.gov (United States)

    Raybould, Alan; Burns, Andrea; Hamer, Mick

    2014-01-01

    Laboratory testing for possible adverse effects of insecticidal proteins on non-target organisms (NTOs) is an important part of many ecological risk assessments for regulatory decision-making about the cultivation of insect-resistant genetically modified (IRGM) crops. To increase confidence in the risk assessments, regulatory guidelines for effects testing specify that representative surrogate species for NTOs are exposed to concentrations of insecticidal proteins that are in excess of worst-case predicted exposures in the field. High concentrations in effects tests are achieved by using protein test substances produced in microbes, such as Escherichia coli. In a study that exposed Daphnia magna to a single high concentration of a microbial test substance containing Vip3Aa20, the insecticidal protein in MIR162 maize, small reductions in growth were observed. These effects were surprising as many other studies strongly suggest that the activity of Vip3Aa20 is limited to Lepidoptera. A plausible explanation for the effect on growth is that high concentrations of test substance have a non-toxic effect on Daphnia, perhaps by reducing its feeding rate. A follow-up study tested that hypothesis by exposing D. magna to several concentrations of Vip3Aa20, and a high concentration of a non-toxic protein, bovine serum albumin (BSA). Vip3Aa20 and BSA had sporadic effects on the reproduction and growth of D. magna. The pattern of the effects suggests that they result from non-toxic effects of high concentrations of protein, and not from toxicity. The implications of these results for regulatory NTO effects testing and ERA of IRGM crops are discussed.

  11. Risk, Rationality and Nudging in Late Modern Society: Understanding the dynamics of the climate crisis

    OpenAIRE

    Jakobsen, Terne Sasha Thorn

    2016-01-01

    This study seeks to explore and explain how nudge theory may contribute to the understanding of thedynamics of the climate crisis in a ‘world risk society’. It is based on Ulrich Beck’s theory of a worldrisk society and unfolds through the combination of theories about risk, rationality and behaviour thatare ultimately brought together in relation to the climate crisis. A critical realistic perspective andmethod is taken to explore three hypothetical premises: 1) That the climate crisis is a ...

  12. The water-soluble fraction of potentially toxic elements in contaminated soils: relationships between ecotoxicity, solubility and geochemical reactivity.

    Science.gov (United States)

    Rocha, L; Rodrigues, S M; Lopes, I; Soares, A M V M; Duarte, A C; Pereira, E

    2011-09-01

    To better understand the impacts posed by soil contamination to aquatic ecosystems it is crucial to characterise the links between ecotoxicity, chemical availability and geochemical reactivity of potentially toxic elements (PTE's) in soils. We evaluated the adverse effects of water extracts obtained from soils contaminated by chemical industry and mining, using a test battery including organisms from different trophic levels (bacteria, algae and daphnids). These tests provided a quick assessment of the ecotoxicity of soils with respect to possible adverse effects on aquatic organisms although the ecotoxicological responses could be related to the solubility of PTE's only to a limited extent. The analysis of results of bioassays together with the chemical characterisation of water extracts provided additional relevant insight into the role of conductivity, pH, Al, Fe, and Mn of soil extracts on toxicity to organisms. Furthermore, an important conclusion of this study was that the toxicity of extracts to the aquatic organisms could also be related to the soil properties (pH, Org C and Fe(ox)) and to the reactivity of PTE's in soils which in fact control the soluble fraction of the contaminants. The combined assessment of ecotoxicity in water fractions, solubility and geochemical reactivity of PTE's in soils provided a more comprehensive understanding of the bioavailability of inorganic contaminants than ecotoxicological or chemical studies alone and can therefore be most useful for environmental risks assessment of contaminated soils. Copyright © 2011 Elsevier Ltd. All rights reserved.

  13. Laypersons' understanding of relative risk reductions: Randomised cross-sectional study

    Directory of Open Access Journals (Sweden)

    Kristiansen Ivar S

    2008-07-01

    Full Text Available Abstract Background Despite increasing recognition of the importance of involving patients in decisions on preventive healthcare interventions, little is known about how well patients understand and utilise information provided on the relative benefits from these interventions. The aim of this study was to explore whether lay people can discriminate between preventive interventions when effectiveness is presented in terms of relative risk reduction (RRR, and whether such discrimination is influenced by presentation of baseline risk. Methods The study was a randomised cross-sectional interview survey of a representative sample (n = 1,519 of lay people with mean age 59 (range 40–98 years in Denmark. In addition to demographic information, respondents were asked to consider a hypothetical drug treatment to prevent heart attack. Its effectiveness was randomly presented as RRR of 10, 20, 30, 40, 50 or 60 percent, and half of the respondents were presented with quantitative information on the baseline risk of heart attack. The respondents had also been asked whether they were diagnosed with hypercholesterolemia or had experienced a heart attack. Results In total, 873 (58% of the respondents consented to the hypothetical treatment. While 49% accepted the treatment when RRR = 10%, the acceptance rate was 58–60% for RRR>10. There was no significant difference in acceptance rates across respondents irrespective of whether they had been presented with quantitative information on baseline risk or not. Conclusion In this study, lay people's decisions about therapy were only slightly influenced by the magnitude of the effect when it was presented in terms of RRR. The results may indicate that lay people have difficulties in discriminating between levels of effectiveness when they are presented in terms of RRR.

  14. Essentially deadly: living with toxic elements: Humans and plants have evolved various mechanisms to deal with and even adopt toxic heavy metals

    OpenAIRE

    Hunter, Philip

    2015-01-01

    Organisms have evolved to deal with or make use of toxic metals. Understanding these mechanisms could help to protect the health of mine workers, tackle malnourishment, or improve ways to clean up polluted environments.

  15. Why are Functional Amyloids Non-Toxic in Humans?

    Directory of Open Access Journals (Sweden)

    Matthew P. Jackson

    2017-09-01

    Full Text Available Amyloids were first identified in association with amyloidoses, human diseases in which proteins and peptides misfold into amyloid fibrils. Subsequent studies have identified an array of functional amyloid fibrils that perform physiological roles in humans. Given the potential for the production of toxic species in amyloid assembly reactions, it is remarkable that cells can produce these functional amyloids without suffering any obvious ill effect. Although the precise mechanisms are unclear, there are a number of ways in which amyloid toxicity may be prevented. These include regulating the level of the amyloidogenic peptides and proteins, minimising the production of prefibrillar oligomers in amyloid assembly reactions, sequestrating amyloids within membrane bound organelles, controlling amyloid assembly by other molecules, and disassembling the fibrils under physiological conditions. Crucially, a better understanding of how toxicity is avoided in the production of functional amyloids may provide insights into the prevention of amyloid toxicity in amyloidoses.

  16. Review of toxic episodes and management strategies in the Danish mussel production

    DEFF Research Database (Denmark)

    Jørgensen, Kevin; Andersen, Per; Thorbjørnsen, Bjarne Ring

    Denmark has in many years been one of the world’s main producers of blue mussels caught from natural banks. The Danish mussel aquaculture sector is now growing. The Danish production areas have been regarded as “low risk” areas with respect to toxic algae and occurrence of marine biotoxins....... The change to more production of cultured mussel results in higher risk for occurrence of marine biotoxins because of the closer interaction between toxic algae and mussels. Results showing the difference between content of marine biotoxins in bottom mussel and cultured mussel from the same production areas...... cell toxicity of potential toxic algae in combination with algae cell number and mussel toxicity for opening or closing of production areas....

  17. Plant-associated bacterial degradation of toxic organic compounds in soil.

    LENUS (Irish Health Repository)

    McGuinness, Martina

    2009-08-01

    A number of toxic synthetic organic compounds can contaminate environmental soil through either local (e.g., industrial) or diffuse (e.g., agricultural) contamination. Increased levels of these toxic organic compounds in the environment have been associated with human health risks including cancer. Plant-associated bacteria, such as endophytic bacteria (non-pathogenic bacteria that occur naturally in plants) and rhizospheric bacteria (bacteria that live on and near the roots of plants), have been shown to contribute to biodegradation of toxic organic compounds in contaminated soil and could have potential for improving phytoremediation. Endophytic and rhizospheric bacterial degradation of toxic organic compounds (either naturally occurring or genetically enhanced) in contaminated soil in the environment could have positive implications for human health worldwide and is the subject of this review.

  18. Hydrogen and Gaseous Fuel Safety and Toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Lee C. Cadwallader; J. Sephen Herring

    2007-06-01

    Non-traditional motor fuels are receiving increased attention and use. This paper examines the safety of three alternative gaseous fuels plus gasoline and the advantages and disadvantages of each. The gaseous fuels are hydrogen, methane (natural gas), and propane. Qualitatively, the overall risks of the four fuels should be close. Gasoline is the most toxic. For small leaks, hydrogen has the highest ignition probability and the gaseous fuels have the highest risk of a burning jet or cloud.

  19. Diagnosis of toxic alcohols: limitations of present methods.

    Science.gov (United States)

    Kraut, Jeffrey A

    2015-01-01

    Methanol, ethylene glycol, diethylene glycol, and propylene glycol intoxications are associated with cellular dysfunction and an increased risk of death. Adverse effects can develop quickly; thus, there is a need for methods for rapidly detecting their presence. To examine the value and limitations of present methods to diagnose patients with possible toxic alcohol exposure. I searched MEDLINE for articles published between 1969 and 2014 using the terms: toxic alcohols, serum osmolality, serum osmol gap, serum anion gap, metabolic acidosis, methanol, ethylene glycol, diethylene glycol, propylene glycol, and fomepizole. Each article was reviewed for additional references. The diagnosis of toxic alcohol exposure is often made on the basis of this history and physical findings along with an increase in the serum osmol and anion gaps. However, an increase in the osmol and/or anion gaps is not always present. Definitive detection in blood requires gas or liquid chromatography, laborious and expensive procedures which are not always available. Newer methods including a qualitative colorimetric test for detection of all alcohols or enzymatic tests for a specific alcohol might allow for more rapid diagnosis. Exposure to toxic alcohols is associated with cellular dysfunction and increased risk of death. Treatment, if initiated early, can markedly improve outcome, but present methods of diagnosis including changes in serum osmol and anion gap, and use of gas or liquid chromatography have important limitations. Development of more rapid and effective tests for detection of these intoxications is essential for optimal care of patients.

  20. Integrated fate and toxicity assessment for site contaminants

    International Nuclear Information System (INIS)

    MacDonell, Margaret; Peterson, John; Finster, Molly; Douglas, R.

    2007-01-01

    Understanding the fate and toxicity of environmental contaminants is essential to framing practical management decisions. Forms and bioavailable concentrations often change over time due to natural physical, chemical, and biological processes. For some sites, hundreds of contaminants may be of initial interest, and even small projects can involve a substantial number of contaminants. With multiple assessments common, attention to effectiveness and efficiency is important, and integrating fate and toxicity information provides a valuable way to focus the analyses. Fate assessments help identify what forms may be present where and when, while toxicity information indicates what health effects could result if people were exposed. The integration process is illustrated by an application for the Hanford site, to support long-term management decisions for the cesium and strontium capsules. Fate data, health-based benchmarks, and related toxicity information were effectively combined to indicate performance targets for chemicals and radionuclides identified for capsule leachate that could migrate to groundwater. More than 50 relevant benchmarks and toxicity context were identified for 15 of the 17 study contaminants; values for chronic drinking water exposure provided the common basis for selected indicators. For two chemicals, toxicity information was identified from the scientific literature to guide the performance targets. (authors)

  1. Thyroid cancer in toxic and non-toxic multinodular goiter

    Directory of Open Access Journals (Sweden)

    Cerci C

    2007-01-01

    Full Text Available Background : Many authors have claimed that hyperthyroidism protects against thyroid cancer and believed that the incidence of malignancy is lower in patients with toxic multinodular goiter (TMG than in those with non-toxic multinodular goiter. But in recent studies, it was reported that the incidence of malignancy with TMG is not as low as previously thought. Aim : To compare the thyroid cancer incidence in patients with toxic and non-toxic multinodular goiter. Settings and Design : Histology reports of patients treated surgically with a preoperative diagnosis of toxic and non-toxic multinodular goiter were reviewed to identify the thyroid cancer incidence. Patients having a history of neck irradiation or radioactive iodine therapy were excluded from the study. Materials and Methods : We reviewed 294 patients operated between 2001-2005 from toxic and non-toxic multinodular goiter. One hundred and twenty-four of them were toxic and 170 were non-toxic. Hyperthyroidism was diagnosed by elevated tri-iodothyroinine / thyroxine ratios and low thyroid-stimulating hormone with clinical signs and symptoms. All patients were evaluated with ultrasonography and scintigraphy and fine needle aspiration biopsy. Statistical Analysis Used : Significance of the various parameters was calculated by using ANOVA test. Results : The incidence of malignancy was 9% in the toxic and 10.58% in the non-toxic multinodular goiter group. Any significant difference in the incidence of cancer and tumor size between the two groups could not be detected. Conclusions : The incidence of malignancy in toxic multinodular goiter is not very low as thought earlier and is nearly the same in non-toxic multinodular goiter.

  2. Toxic Aluminium and Heavy Metals in Groundwater of Middle Russia: Health Risk Assessment

    Directory of Open Access Journals (Sweden)

    Boris Synzynys

    2005-08-01

    Full Text Available Two approaches are distinguished in modern ecological monitoring. The first one is physicochemical analysis of environmental objects with respect to maximum allowable concentrations (MACs of chemical substances, which is performed by standards methods in accordance with state regulations. The second approach (biological monitoring is based on the methodology of biotesting and bio indication. The task of this work is to create biotests for estimation of Al and other metals toxicity in ground water and to compare these results with physicochemical analysis dates. Risk assessment for heavy metals contaminated groundwater was also performed. Risk assessment was performed accordingly EPA US recommendation and gave results about 90 per 100000 citizens for Al and 402 per 100000 for mixture of different heavy metals. For comparison: risk for earth background radiation for Middle Russia is (Individual dose 1 millisivert per year consist 5 per 100000 people. It was shown that groundwater consist HCO3- ions (360 mg/l, sometimes Al compounds 0.21-0.65 mg/l (MAC for Al is 0.5 mg/l for Russia. Other groundwater contain Hg – 0.004 mg/l (MAC – 0.0005 mg/l; Cr – 0.072 mg/l (MAC – 0.05 mg/l; As – less than 0.03 mg/l (MAC – 0.05 mg/l. We developed plant biotest for estimation of groundwater quality with barley roots, tradescatia and others. Some biotests parameters correlate with HCO3-, Cl-, SO42- and metal ions content positively, for another biotest this correlation is strongly negative. The quality of groundwater near Obninsk and in Kaluga Region is very different but hasn’t been changed since the year 1998.

  3. Where Lies the Risk? An Ecological Approach to Understanding Child Mental Health Risk and Vulnerabilities in Sub-Saharan Africa

    Directory of Open Access Journals (Sweden)

    Olayinka Atilola

    2014-01-01

    Full Text Available Efforts at improving child-health and development initiatives in sub-Saharan Africa had focused on the physical health of children due to the neglect of child and adolescent mental health (CAMH policy initiatives. A thorough and broad-based understanding of the prevalent child mental-health risk and vulnerability factors is needed to successfully articulate CAMH policies. In this discourse, we present a narrative on the child mental-health risk and vulnerability factors in sub-Saharan Africa. Through an ecological point of view, we identified widespread family poverty, poor availability and uptake of childcare resources, inadequate community and institutional childcare systems, and inadequate framework for social protection for vulnerable children as among the risk and vulnerability factors for CAMH in the region. Others are poor workplace policy/practice that does not support work-family life balance, poor legislative framework for child protection, and some harmful traditional practices. We conclude that an ecological approach shows that child mental-health risks are diverse and cut across different layers of the care environment. The approach also provides a broad and holistic template from which appropriate CAMH policy direction in sub-Saharan Africa can be understood.

  4. Where lies the risk? An ecological approach to understanding child mental health risk and vulnerabilities in sub-saharan Africa.

    Science.gov (United States)

    Atilola, Olayinka

    2014-01-01

    Efforts at improving child-health and development initiatives in sub-Saharan Africa had focused on the physical health of children due to the neglect of child and adolescent mental health (CAMH) policy initiatives. A thorough and broad-based understanding of the prevalent child mental-health risk and vulnerability factors is needed to successfully articulate CAMH policies. In this discourse, we present a narrative on the child mental-health risk and vulnerability factors in sub-Saharan Africa. Through an ecological point of view, we identified widespread family poverty, poor availability and uptake of childcare resources, inadequate community and institutional childcare systems, and inadequate framework for social protection for vulnerable children as among the risk and vulnerability factors for CAMH in the region. Others are poor workplace policy/practice that does not support work-family life balance, poor legislative framework for child protection, and some harmful traditional practices. We conclude that an ecological approach shows that child mental-health risks are diverse and cut across different layers of the care environment. The approach also provides a broad and holistic template from which appropriate CAMH policy direction in sub-Saharan Africa can be understood.

  5. Where Lies the Risk? An Ecological Approach to Understanding Child Mental Health Risk and Vulnerabilities in Sub-Saharan Africa

    Science.gov (United States)

    Atilola, Olayinka

    2014-01-01

    Efforts at improving child-health and development initiatives in sub-Saharan Africa had focused on the physical health of children due to the neglect of child and adolescent mental health (CAMH) policy initiatives. A thorough and broad-based understanding of the prevalent child mental-health risk and vulnerability factors is needed to successfully articulate CAMH policies. In this discourse, we present a narrative on the child mental-health risk and vulnerability factors in sub-Saharan Africa. Through an ecological point of view, we identified widespread family poverty, poor availability and uptake of childcare resources, inadequate community and institutional childcare systems, and inadequate framework for social protection for vulnerable children as among the risk and vulnerability factors for CAMH in the region. Others are poor workplace policy/practice that does not support work-family life balance, poor legislative framework for child protection, and some harmful traditional practices. We conclude that an ecological approach shows that child mental-health risks are diverse and cut across different layers of the care environment. The approach also provides a broad and holistic template from which appropriate CAMH policy direction in sub-Saharan Africa can be understood. PMID:24834431

  6. Critical dose and toxicity index of organs at risk in radiotherapy: Analyzing the calculated effects of modified dose fractionation in non–small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Pedicini, Piernicola, E-mail: ppiern@libero.it [Service of Medical Physics, I.R.C.C.S. Regional Cancer Hospital C.R.O.B, Rionero in Vulture (Italy); Strigari, Lidia [Laboratory of Medical Physics and Expert Systems, Regina Elena National Cancer Institute, Rome (Italy); Benassi, Marcello [Service of Medical Physics, Scientific Institute of Tumours of Romagna I.R.S.T., Meldola (Italy); Caivano, Rocchina [Service of Medical Physics, I.R.C.C.S. Regional Cancer Hospital C.R.O.B, Rionero in Vulture (Italy); Fiorentino, Alba [U.O. of Radiotherapy, I.R.C.C.S. Regional Cancer Hospital C.R.O.B., Rionero in Vulture (Italy); Nappi, Antonio [U.O. of Nuclear Medicine, I.R.C.C.S. Regional Cancer Hospital C.R.O.B., Rionero in Vulture (Italy); Salvatore, Marco [U.O. of Nuclear Medicine, I.R.C.C.S. SDN Foundation, Naples (Italy); Storto, Giovanni [U.O. of Nuclear Medicine, I.R.C.C.S. Regional Cancer Hospital C.R.O.B., Rionero in Vulture (Italy)

    2014-04-01

    To increase the efficacy of radiotherapy for non–small cell lung cancer (NSCLC), many schemes of dose fractionation were assessed by a new “toxicity index” (I), which allows one to choose the fractionation schedules that produce less toxic treatments. Thirty-two patients affected by non resectable NSCLC were treated by standard 3-dimensional conformal radiotherapy (3DCRT) with a strategy of limited treated volume. Computed tomography datasets were employed to re plan by simultaneous integrated boost intensity-modulated radiotherapy (IMRT). The dose distributions from plans were used to test various schemes of dose fractionation, in 3DCRT as well as in IMRT, by transforming the dose-volume histogram (DVH) into a biological equivalent DVH (BDVH) and by varying the overall treatment time. The BDVHs were obtained through the toxicity index, which was defined for each of the organs at risk (OAR) by a linear quadratic model keeping an equivalent radiobiological effect on the target volume. The less toxic fractionation consisted in a severe/moderate hyper fractionation for the volume including the primary tumor and lymph nodes, followed by a hypofractionation for the reduced volume of the primary tumor. The 3DCRT and IMRT resulted, respectively, in 4.7% and 4.3% of dose sparing for the spinal cord, without significant changes for the combined-lungs toxicity (p < 0.001). Schedules with reduced overall treatment time (accelerated fractionations) led to a 12.5% dose sparing for the spinal cord (7.5% in IMRT), 8.3% dose sparing for V{sub 20} in the combined lungs (5.5% in IMRT), and also significant dose sparing for all the other OARs (p < 0.001). The toxicity index allows to choose fractionation schedules with reduced toxicity for all the OARs and equivalent radiobiological effect for the tumor in 3DCRT, as well as in IMRT, treatments of NSCLC.

  7. Safety assessment of VHTR hydrogen production system against fire, explosion and acute toxicity

    International Nuclear Information System (INIS)

    Murakami, Tomoyuki; Nishihara, Tetsuo; Kunitomi, Kazuhiko

    2008-01-01

    The Japan Atomic Energy Agency has been developing a nuclear hydrogen production system by using heat from the Very High Temperature Reactor (VHTR). This system will handle a large amount of combustible gas and toxic gas. The risk from fire, explosion and acute toxic exposure caused by an accident involving chemical material release in a hydrogen production system is assessed. It is important to ensure the safety of the nuclear plant, and the risks for public health should be sufficiently small. This report provides the basic policy for the safety evaluation in cases of accident involving fire, explosion and toxic material release in a hydrogen production system. Preliminary safety analysis of a commercial-sized VHTR hydrogen production system, GTHTR300C, is performed. This analysis provides us with useful information on the separation distance between a nuclear plant and a hydrogen production system and a prospect that an accident in a hydrogen production system does not significantly increase the risks of the public. (author)

  8. Polish Toxic Currency Options

    Directory of Open Access Journals (Sweden)

    Waldemar Gontarski

    2009-06-01

    Full Text Available Toxic currency options are defined on the basis of the opposition to the nature (essence of an option contract, which is justified in terms of norms founded on the general law clause of characteristics (nature of a relation (which represents an independent premise for imposing restrictions on the freedom of contracts. So-understood toxic currency options are unlawful. Indeed they contravene iuris cogentis regulations. These include for instance option contracts, which are concluded with a bank, if the bank has not informed about option risk before concluding the contract; or the barrier options, which focus only on the protection of bank’s interests. Therefore, such options may appear to be invalid. Therefore, performing contracts for toxic currency options may be qualified as a criminal mismanagement. For the sake of security, the manager should then take into consideration filing a claim for stating invalidity (which can be made in a court verdict. At the same time, if the supervisory board member in a commercial company, who can also be a subject to mismanagement offences, commits an omission involving lack of reaction (for example, if he/she fails to notify of the suspected offence committed by the management board members acting to the company’s detriment when the management board makes the company conclude option contracts which are charged with absolute invalidity the supervisory board member so acting may be considered to act to the company’s detriment. In the most recent Polish jurisprudence and judicature the standard of a “good host” is treated to be the last resort for determining whether the manager’s powers resulting from criminal regulations were performed. The manager of the exporter should not, as a rule, issue any options. Issuing options always means assuming an obligation. In the case of currency put options it is an absolute obligation to purchase a given amount in euro at exchange rate set in advance. On the

  9. Use of mass and toxicity balances in risk-based corrective action decisions at contaminated sites

    International Nuclear Information System (INIS)

    Sevigny, J.H.; Lintott, D.; Wrubleski, R.M.; Drury, C.R.

    1997-01-01

    The contaminated groundwater at a sour gas plant facility was studied to identify the chemicals of environmental concern. Simple mass balance principles were used to determine the proportion of organic carbon, organic nitrogen and Microtox R toxicity that can be attributed to two process chemicals that have contaminated several sour gas plants in western Canada. The two process chemicals are sulfolane and diisopropanolamine (DIPA). The organic carbon balance was calculated by determining the molar contribution of sulfolane and DIPA relative to the mass of carboxylic acid-corrected dissolved organic carbon. Organic carbon balances ranged from 44 to 96 per cent. The organic nitrogen balance was calculated by determining the molar contribution of DIPA relative to the mass of ammonium ion-corrected dissolved Kjeldahl nitrogen. The nitrogen balances were highly variable between 8 to 48 per cent for samples with organic nitrogen concentrations between 10 and 32 mg/L. The Microtox R toxicity balance was calculated by determining the proportions of toxicity that could be accounted for by pure phase sulfolane and DIPA. The Microtox R toxicity balance for samples that showed significant toxicity ranged from 71 to 122 per cent

  10. Use of mass and toxicity balances in risk-based corrective action decisions at contaminated sites

    Energy Technology Data Exchange (ETDEWEB)

    Sevigny, J.H. [Komex Consultants Ltd., Calgary, AB (Canada); Lintott, D. [HydroQual Consultants, Inc., Calgary, AB (Canada); Wrubleski, R.M.; Drury, C.R. [Shell Canada Ltd., Calgary, AB (Canada). Calgary Research Centre

    1997-12-31

    The contaminated groundwater at a sour gas plant facility was studied to identify the chemicals of environmental concern. Simple mass balance principles were used to determine the proportion of organic carbon, organic nitrogen and Microtox{sup R} toxicity that can be attributed to two process chemicals that have contaminated several sour gas plants in western Canada. The two process chemicals are sulfolane and diisopropanolamine (DIPA). The organic carbon balance was calculated by determining the molar contribution of sulfolane and DIPA relative to the mass of carboxylic acid-corrected dissolved organic carbon. Organic carbon balances ranged from 44 to 96 per cent. The organic nitrogen balance was calculated by determining the molar contribution of DIPA relative to the mass of ammonium ion-corrected dissolved Kjeldahl nitrogen. The nitrogen balances were highly variable between 8 to 48 per cent for samples with organic nitrogen concentrations between 10 and 32 mg/L. The Microtox{sup R} toxicity balance was calculated by determining the proportions of toxicity that could be accounted for by pure phase sulfolane and DIPA. The Microtox{sup R} toxicity balance for samples that showed significant toxicity ranged from 71 to 122 per cent.

  11. Prostate hypofractionated radiation therapy with injection of hyaluronic acid: acute toxicities in a phase 2 study.

    Science.gov (United States)

    Chapet, Olivier; Decullier, Evelyne; Bin, Sylvie; Faix, Antoine; Ruffion, Alain; Jalade, Patrice; Fenoglietto, Pascal; Udrescu, Corina; Enachescu, Ciprian; Azria, David

    2015-03-15

    Hypofractionated radiation therapy (RT) in prostate cancer can be developed only if the risk of rectal toxicity is controlled. In a multicenter phase 2 trial, hypofractionated irradiation was combined with an injection of hyaluronic acid (HA) to preserve the rectal wall. Tolerance of the injection and acute toxicity rates are reported. The study was designed to assess late grade 2 toxicity rates. The results described here correspond to the secondary objectives. Acute toxicity was defined as occurring during RT or within 3 months after RT and graded according to the Common Terminology Criteria for Adverse Events version 4.0. HA tolerance was evaluated with a visual analog scale during the injection and 30 minutes after injection and then by use of the Common Terminology Criteria at each visit. From 2010 to 2012, 36 patients with low-risk to intermediate-risk prostate cancer were included. The HA injection induced a mean pain score of 4.6/10 ± 2.3. Thirty minutes after the injection, 2 patients still reported pain (2/10 and 3/10), which persisted after the intervention. Thirty-three patients experienced at least 1 acute genitourinary toxicity and 20 patients at least 1 acute gastrointestinal toxicity. Grade 2 toxicities were reported for 19 patients with urinary obstruction, frequency, or both and for 1 patient with proctitis. No grade 3 or 4 toxicities were reported. At the 3-month visit, 4 patients described grade 2 obstruction or frequency, and no patients had any grade 2 gastrointestinal toxicities. The injection of HA makes it possible to deliver hypofractionated irradiation over 4 weeks with a dose per fraction of > 3 Gy, with limited acute rectal toxicity. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Prostate Hypofractionated Radiation Therapy With Injection of Hyaluronic Acid: Acute Toxicities in a Phase 2 Study

    International Nuclear Information System (INIS)

    Chapet, Olivier; Decullier, Evelyne; Bin, Sylvie; Faix, Antoine; Ruffion, Alain; Jalade, Patrice; Fenoglietto, Pascal; Udrescu, Corina; Enachescu, Ciprian; Azria, David

    2015-01-01

    Purpose: Hypofractionated radiation therapy (RT) in prostate cancer can be developed only if the risk of rectal toxicity is controlled. In a multicenter phase 2 trial, hypofractionated irradiation was combined with an injection of hyaluronic acid (HA) to preserve the rectal wall. Tolerance of the injection and acute toxicity rates are reported. Methods and Materials: The study was designed to assess late grade 2 toxicity rates. The results described here correspond to the secondary objectives. Acute toxicity was defined as occurring during RT or within 3 months after RT and graded according to the Common Terminology Criteria for Adverse Events version 4.0. HA tolerance was evaluated with a visual analog scale during the injection and 30 minutes after injection and then by use of the Common Terminology Criteria at each visit. Results: From 2010 to 2012, 36 patients with low-risk to intermediate-risk prostate cancer were included. The HA injection induced a mean pain score of 4.6/10 ± 2.3. Thirty minutes after the injection, 2 patients still reported pain (2/10 and 3/10), which persisted after the intervention. Thirty-three patients experienced at least 1 acute genitourinary toxicity and 20 patients at least 1 acute gastrointestinal toxicity. Grade 2 toxicities were reported for 19 patients with urinary obstruction, frequency, or both and for 1 patient with proctitis. No grade 3 or 4 toxicities were reported. At the 3-month visit, 4 patients described grade 2 obstruction or frequency, and no patients had any grade 2 gastrointestinal toxicities. Conclusions: The injection of HA makes it possible to deliver hypofractionated irradiation over 4 weeks with a dose per fraction of > 3 Gy, with limited acute rectal toxicity

  13. Prostate Hypofractionated Radiation Therapy With Injection of Hyaluronic Acid: Acute Toxicities in a Phase 2 Study

    Energy Technology Data Exchange (ETDEWEB)

    Chapet, Olivier, E-mail: olivier.chapet@chu-lyon.fr [Department of Radiation Oncology, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre Benite (France); EMR3738, Université Lyon 1, Lyon (France); Decullier, Evelyne; Bin, Sylvie [Pole Information Médicale Evaluation Recherche, Hospices Civils de Lyon, Lyon (France); Université Lyon 1, Lyon (France); EA SIS, Université de Lyon, Lyon (France); Faix, Antoine [Department of Urology, Clinique Beausoleil, Montpellier (France); Ruffion, Alain [Université Lyon 1, Lyon (France); Department of Urology, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre Benite (France); Jalade, Patrice [Department of Medical Physics, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre Benite (France); Fenoglietto, Pascal [Department of Radiation Oncology and Physics, Institut du Cancer de Montpellier, Montpellier (France); Udrescu, Corina; Enachescu, Ciprian [Department of Radiation Oncology, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre Benite (France); Azria, David [Department of Radiation Oncology and Physics, Institut du Cancer de Montpellier, Montpellier (France)

    2015-03-15

    Purpose: Hypofractionated radiation therapy (RT) in prostate cancer can be developed only if the risk of rectal toxicity is controlled. In a multicenter phase 2 trial, hypofractionated irradiation was combined with an injection of hyaluronic acid (HA) to preserve the rectal wall. Tolerance of the injection and acute toxicity rates are reported. Methods and Materials: The study was designed to assess late grade 2 toxicity rates. The results described here correspond to the secondary objectives. Acute toxicity was defined as occurring during RT or within 3 months after RT and graded according to the Common Terminology Criteria for Adverse Events version 4.0. HA tolerance was evaluated with a visual analog scale during the injection and 30 minutes after injection and then by use of the Common Terminology Criteria at each visit. Results: From 2010 to 2012, 36 patients with low-risk to intermediate-risk prostate cancer were included. The HA injection induced a mean pain score of 4.6/10 ± 2.3. Thirty minutes after the injection, 2 patients still reported pain (2/10 and 3/10), which persisted after the intervention. Thirty-three patients experienced at least 1 acute genitourinary toxicity and 20 patients at least 1 acute gastrointestinal toxicity. Grade 2 toxicities were reported for 19 patients with urinary obstruction, frequency, or both and for 1 patient with proctitis. No grade 3 or 4 toxicities were reported. At the 3-month visit, 4 patients described grade 2 obstruction or frequency, and no patients had any grade 2 gastrointestinal toxicities. Conclusions: The injection of HA makes it possible to deliver hypofractionated irradiation over 4 weeks with a dose per fraction of > 3 Gy, with limited acute rectal toxicity.

  14. Ecological models and pesticide risk assessment: current modeling practice.

    Science.gov (United States)

    Schmolke, Amelie; Thorbek, Pernille; Chapman, Peter; Grimm, Volker

    2010-04-01

    Ecological risk assessments of pesticides usually focus on risk at the level of individuals, and are carried out by comparing exposure and toxicological endpoints. However, in most cases the protection goal is populations rather than individuals. On the population level, effects of pesticides depend not only on exposure and toxicity, but also on factors such as life history characteristics, population structure, timing of application, presence of refuges in time and space, and landscape structure. Ecological models can integrate such factors and have the potential to become important tools for the prediction of population-level effects of exposure to pesticides, thus allowing extrapolations, for example, from laboratory to field. Indeed, a broad range of ecological models have been applied to chemical risk assessment in the scientific literature, but so far such models have only rarely been used to support regulatory risk assessments of pesticides. To better understand the reasons for this situation, the current modeling practice in this field was assessed in the present study. The scientific literature was searched for relevant models and assessed according to nine characteristics: model type, model complexity, toxicity measure, exposure pattern, other factors, taxonomic group, risk assessment endpoint, parameterization, and model evaluation. The present study found that, although most models were of a high scientific standard, many of them would need modification before they are suitable for regulatory risk assessments. The main shortcomings of currently available models in the context of regulatory pesticide risk assessments were identified. When ecological models are applied to regulatory risk assessments, we recommend reviewing these models according to the nine characteristics evaluated here. (c) 2010 SETAC.

  15. Race, deprivation, and immigrant isolation: The spatial demography of air-toxic clusters in the continental United States.

    Science.gov (United States)

    Liévanos, Raoul S

    2015-11-01

    This article contributes to environmental inequality outcomes research on the spatial and demographic factors associated with cumulative air-toxic health risks at multiple geographic scales across the United States. It employs a rigorous spatial cluster analysis of census tract-level 2005 estimated lifetime cancer risk (LCR) of ambient air-toxic emissions from stationary (e.g., facility) and mobile (e.g., vehicular) sources to locate spatial clusters of air-toxic LCR risk in the continental United States. It then tests intersectional environmental inequality hypotheses on the predictors of tract presence in air-toxic LCR clusters with tract-level principal component factor measures of economic deprivation by race and immigrant status. Logistic regression analyses show that net of controls, isolated Latino immigrant-economic deprivation is the strongest positive demographic predictor of tract presence in air-toxic LCR clusters, followed by black-economic deprivation and isolated Asian/Pacific Islander immigrant-economic deprivation. Findings suggest scholarly and practical implications for future research, advocacy, and policy. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Temperature-dependent toxicity of artemisinin toward the macrophyte Lemna minor and the algae Pseudokirchneriella subcapitata

    DEFF Research Database (Denmark)

    Jessing, Karina Knudsmark; Andresen, Marianne; Cedergreen, Nina

    2014-01-01

    - and groundwater. To make better risk assessments of A. annua which is cultivated under varying climatic conditions, the temperature-dependent toxicity of artemisinin toward the green algae Pseudokirchneriella subcapitata and the macrophyte Lemna minor was evaluated at temperatures ranging from 10 to 30°C....... To include a possible effect of temperature on the degradation rate of artemisinin, artemisinin concentrations were measured during the experiment and toxicity was related to the time-weighted averages of exposure concentrations. The toxicity of artemisinin toward the macrophyte L. minor and the algae P....... subcapitata increased with increasing growth rates, and we conclude that bioavailability plays a minor role in the observed relation between temperature and toxicity of artemisinin. The obtained results are important for possible future risk assessment of A. annua cultivation....

  17. Using biodynamic models to reconcile differences between laboratory toxicity tests and field biomonitoring with aquatic insects

    Science.gov (United States)

    Buchwalter, D.B.; Cain, D.J.; Clements, W.H.; Luoma, S.N.

    2007-01-01

    Aquatic insects often dominate lotic ecosystems, yet these organisms are under-represented in trace metal toxicity databases. Furthermore, toxicity data for aquatic insects do not appear to reflect their actual sensitivities to metals in nature, because the concentrations required to elicit toxicity in the laboratory are considerably higher than those found to impact insect communities in the field. New approaches are therefore needed to better understand how and why insects are differentially susceptible to metal exposures. Biodynamic modeling is a powerful tool for understanding interspecific differences in trace metal bioaccumulation. Because bioaccumulation alone does not necessarily correlate with toxicity, we combined biokinetic parameters associated with dissolved cadmium exposures with studies of the subcellular compartmentalization of accumulated Cd. This combination of physiological traits allowed us to make predictions of susceptibility differences to dissolved Cd in three aquatic insect taxa: Ephemerella excrucians, Rhithrogena morrisoni, and Rhyacophila sp. We compared these predictions with long-term field monitoring data and toxicity tests with closely related taxa: Ephemerella infrequens, Rhithrogena hageni, and Rhyacophila brunea. Kinetic parameters allowed us to estimate steady-state concentrations, the time required to reach steady state, and the concentrations of Cd projected to be in potentially toxic compartments for different species. Species-specific physiological traits identified using biodynamic models provided a means for better understanding why toxicity assays with insects have failed to provide meaningful estimates for metal concentrations that would be expected to be protective in nature. ?? 2007 American Chemical Society.

  18. [Problems of cardiovascular toxicity of coxibs and non-selective NSA].

    Science.gov (United States)

    Forejtová, S

    2006-01-01

    Non-steroidal antirheumatics (NSA) belong to the most often prescribed drugs. Certain observation studies indicate that they are used by 20 to 30% of population of developed countries. The most common NSA's adverse effects are gastrointestinal complications. Coxibs have been developed as an alternative to conventional non-selective NSA; with similar efficacy, they should reduce the risk of development of gastrointestinal complications. In the few last years, possible toxicity of coxibs and other non-steroidal antirheumatics has been widely discussed. The VIGOR study, which was performed 6 years ago, showed five times higher incidence of nonfatal myocardial infarction in patients with rofecoxib therapy as compared with naproxen. Afterwards, there was much debate about rofecoxib, and coxibs in general, whose cardiotoxicity was supported and confuted at the same time. Possible cardioprotective effect of naproxen was discussed too. Later on, results of the APPROVE study (Adenoma Polyp Prevention on Vioxx) made Merck & Co., Inc. withdraw rofecoxib from all markets voluntarily. In the end of 2004, three controversial studies on celecoxib were published. Although the first study (Adenoma Prevention with Celecoxib study, APC) showed higher cardiovascular risk of celecoxib, the second study (Prevention of Adenomatosus Polyps, PreSAP) did not verify these results. Surprisingly, the third study (Alzheimer Disease and Prevention Trial, ADAPT) proved 50% increase of the risk of cardiovascular (CV) toxicity of naproxen. In the last year, researchers have tried to decide whether CV toxicity is a class effect of coxib group or a class effect of all NSA. Many observation studies proved higher CV risk both of coxibs (particularly rofecoxib) and non-selective NSA including naproxen. These new findings moved the American FDA (Food and Drug Administration) to publish guidance concerning higher CV risk of all coxibs and NSA. For the time being, the EMEA (European Agency for Evaluation

  19. Proteome Profiling Reveals Potential Toxicity and Detoxification Pathways Following Exposure of BEAS-2B Cells to Engineered Nanoparticle Titanium Dioxide

    Science.gov (United States)

    Identification of toxicity pathways linked to chemical -exposure is critical for a better understanding of biological effects of the exposure, toxic mechanisms, and for enhancement of the prediction of chemical toxicity and adverse health outcomes. To identify toxicity pathways a...

  20. The acute toxicity of the metaldehyde on the climbing perch

    Science.gov (United States)

    Wahida Mohamad Ismail, Syamimi; Aini Dahalan, Farrah; Zakaria, Ammar; Mad Shakaff, Ali Yeon; Aqlima Ahmad, Siti; Shukor, Mohd Yunus Abd; Khalizan Sabullah, Mohd; Khalil, Khalilah Abdul; Jalil, Mohd Faizal Ab

    2018-03-01

    In Asia, Climbing perch (Anabas testudineus) is commonly found in paddy fields and irrigation systems. Due to its habitat, Climbing perch is exposed to toxic pesticides used in paddy fields such as metaldehyde which is one of the most widely used molluscicide. This study aims to determine the acute toxicity Lethal Concentration50 (LC50) of metaldehyde and its effect on the behaviour and physical changes of the Climbing perch. The fish mortality responses to six different metaldehyde concentrations ranging from 180 to 330 mg/L were investigated. The 96-h LC50 values were determined and analysed using three different analysis methods which is arithmetic, logarithmic and probit graphic. The LC50 values obtained in this study were 239, 234 and 232 mg/L, respectively. After 96-h of exposure to metaldehyde, the fish showed a series of abnormal behavioural response in all cases: imbalance position, and restlessness of movement. The LC50 values show that metaldehyde is moderately toxic to the Climbing perch indicating that metaldehyde is not destructive to Climbing perch. However, long term exposure of aquatic organisms to the metaldehyde means a continuous health risk for the fish population as they are more vulnerable and it is on high risk for human to consume this toxicated fishes.

  1. Influence of carbon nanotube length on toxicity to zebrafish embryos

    Directory of Open Access Journals (Sweden)

    Cheng J

    2012-07-01

    Full Text Available Jinping Cheng,1,2 Shuk Han Cheng11Department of Biology and Chemistry, City University of Hong Kong, Hong Kong; 2State Key Laboratory of Estuarine and Coastal Research, East China Normal University, Shanghai, ChinaAbstract: There is currently a large difference of opinion in nanotoxicology studies of nanomaterials. There is concern about why some studies have indicated that there is strong toxicity, while others have not. In this study, the length of carbon nanotubes greatly affected their toxicity in zebrafish embryos. Multiwalled carbon nanotubes (MWCNTs were sonicated in a nitric acid solution for 24 hours and 48 hours. The modified MWCNTs were tested in early developing zebrafish embryo. MWCNTs prepared with the longer sonication time resulted in severe developmental toxicity; however, the shorter sonication time did not induce any obvious toxicity in the tested developing zebrafish embryos. The cellular and molecular changes of the affected zebrafish embryos were studied and the observed phenotypes scored. This study suggests that length plays an important role in the in vivo toxicity of functionalized CNTs. This study will help in furthering the understanding on current differences in toxicity studies of nanomaterials.Keywords: length, carbon nanotubes, sonication, developmental toxicity, zebrafish

  2. UNDERSTANDING AND ACCOUNTING FOR METHOD VARIABILITY IN WHOLE EFFLUENT TOXICITY APPLICATIONS UNDER THE NPDES PROGRAM

    Science.gov (United States)

    This chapter provides a brief introduction to whole effluent toxicity (WET) testing and describes the regulatory background and context of WET testing. This chapter also describes the purpose of this document and outlines the issues addressed in each chapter.

  3. Standardized toxicity testing may underestimate ecotoxicity: Environmentally relevant food rations increase the toxicity of silver nanoparticles to Daphnia.

    Science.gov (United States)

    Stevenson, Louise M; Krattenmaker, Katherine E; Johnson, Erica; Bowers, Alexandra J; Adeleye, Adeyemi S; McCauley, Edward; Nisbet, Roger M

    2017-11-01

    Daphnia in the natural environment experience fluctuations in algal food supply, with periods when algal populations bloom and seasons when Daphnia have very little algal food. Standardized chronic toxicity tests, used for ecological risk assessment, dictate that Daphnia must be fed up to 400 times more food than they would experience in the natural environment (outside of algal blooms) for a toxicity test to be valid. This disconnect can lead to underestimating the toxicity of a contaminant. We followed the growth, reproduction, and survival of Daphnia exposed to 75 and 200 µg/L silver nanoparticles (AgNPs) at 4 food rations for up to 99 d and found that AgNP exposure at low, environmentally relevant food rations increased the toxicity of AgNPs. Exposure to AgNP at low food rations decreased the survival and/or reproduction of individuals, with potential consequences for Daphnia populations (based on calculated specific population growth rates). We also found tentative evidence that a sublethal concentration of AgNPs (75 µg/L) caused Daphnia to alter energy allocation away from reproduction and toward survival and growth. The present findings emphasize the need to consider resource availability, and not just exposure, in the environment when estimating the effect of a toxicant. Environ Toxicol Chem 2017;36:3008-3018. © 2017 SETAC. © 2017 SETAC.

  4. Late rectal toxicity: dose-volume effects of conformal radiotherapy for prostate cancer

    International Nuclear Information System (INIS)

    Huang, Eugene H.; Pollack, Alan; Levy, Larry; Starkschall, George; Lei Dong; Rosen, Isaac; Kuban, Deborah A.

    2002-01-01

    Purpose: To identify dosimetric, anatomic, and clinical factors that correlate with late rectal toxicity after three-dimensional conformal radiotherapy (3D-CRT) for prostate cancer. Methods and Materials: We retrospectively analyzed the dose-volume histograms and clinical records of 163 Stage T1b-T3c prostate cancer patients treated between 1992 and 1999 with 3D-CRT, to a total isocenter dose of 74-78 Gy at The University of Texas M. D. Anderson Cancer Center. The median follow-up was 62 months (range 24-102). All late rectal complications were scored using modified Radiation Therapy Oncology Group and Late Effects Normal Tissue Task Force criteria. The 6-year toxicity rate was assessed using Kaplan-Meier analysis and the log-rank test. A univariate proportional hazards regression model was used to test the correlation between Grade 2 or higher toxicity and the dosimetric, anatomic, and clinical factors. In a multivariate regression model, clinical factors were added to the dosimetric and anatomic variables to determine whether they significantly altered the risk of developing late toxicity. Results: At 6 years, the rate of developing Grade 2 or higher late rectal toxicity was 25%. A significant volume effect was observed at rectal doses of 60, 70, 75.6, and 78 Gy, and the risk of developing rectal complications increased exponentially as greater volumes were irradiated. Although the percentage of rectal volume treated correlated significantly with the incidence of rectal complications at all dose levels (p 3 of the rectum. Of the clinical variables tested, only a history of hemorrhoids correlated with rectal toxicity (p=0.003). Multivariate analysis showed that the addition of hemorrhoids increased the risk of toxicity for each dosimetric variable found to be significant on univariate analysis (p<0.05 for all comparisons). Conclusion: Dose-volume histogram analyses clearly indicated a volume effect on the probability of developing late rectal complications

  5. Bioavailability as an issue in risk assessment and management of food cadmium: A review

    Energy Technology Data Exchange (ETDEWEB)

    Reeves, Philip G. [U.S. Department of Agriculture, Agricultural Research Service, Grand Forks Human Nutrition Research Center, Grand Forks, ND 58203 (United States)], E-mail: philip.reeves@ars.usda.gov; Chaney, Rufus L. [U.S. Department of Agriculture, Agricultural Research Service, Environmental Management and Byproduct Utilization Lab, Animal and Natural Resources Institute, Henry A. Wallace Beltsville Agricultural Research Center, Beltsville, MD 20705 (United States)

    2008-07-15

    The bioavailability of cadmium (Cd) from food is an important determinant of the potential risk of this toxic element. This review summarizes the effects of marginal deficiencies of the essential nutrients zinc (Zn), iron (Fe), and calcium (Ca) on the enhancement of absorption and organ accumulation and retention of dietary Cd in laboratory animals. These marginal deficiencies enhanced Cd absorption as much as ten-fold from diets containing low Cd concentrations similar to that consumed by some human populations, indicating that people who are nutritionally marginal with respect to Zn, Fe, and Ca are at higher risk of Cd disease than those who are nutritionally adequate. Results from these studies also suggest that the bioavailability of Cd is different for different food sources. This has implications for the design of food safety rules for Cd in that if the dietary source plays such a significant role in the risk of Cd, then different foods would require different Cd limits. Lastly, the importance of food-level exposures of Cd and other potentially toxic elements in the study of risk assessment are emphasized. Most foods contain low concentrations of Cd that are poorly absorbed, and it is neither relevant nor practical to use toxic doses of Cd in experimental diets to study food Cd risks. A more comprehensive understanding of the biochemistry involved in the bioavailability of Cd from foods would help resolve food safety questions and provide the support for a badly needed advance in international policies regarding Cd in crops and foods.

  6. Leucaena toxicity: a new perspective on the most widely used forage tree legume

    Directory of Open Access Journals (Sweden)

    Michael J. Halliday

    2013-09-01

    Full Text Available The tree legume Leucaena leucocephala (leucaena is a high quality ruminant feed, vitally important for livestock production in the tropics, despite the presence of mimosine in the leaves. This toxic non-protein amino acid has the potential to limit productivity and adversely affect the health of animals. In the 1980s, the ruminal bacterium Synergistes jonesii was discovered and subsequently distributed in Australia as an oral inoculum to overcome these toxic effects. However, in recent times, a number of factors, including: surveys of the status of toxicity worldwide; improved understanding of the chemistry and mode of action of the toxins; new techniques for molecular sequencing; and concerns about the efficacy of the in vitro inoculum; have cast doubt on some past understanding of leucaena toxicity and provide new insights into the geographical spread of S. jonesii. There is also confusion and ignorance regarding the occurrence and significance of toxicity in many countries worldwide. Ongoing research into the taxonomy and ecology of the Synergistetes phylum, improved methods of inoculation, and improved management solutions, along with aware-ness-raising extension activities, are vital for the future success of leucaena feeding systems.

  7. Image-Guided Hypofractionated Radiotherapy in Low-Risk Prostate Cancer Patients

    Directory of Open Access Journals (Sweden)

    Maurizio Valeriani

    2014-01-01

    Full Text Available Aim. To evaluate efficacy and toxicity of image-guided hypofractionated radiotherapy (HFRT in the treatment of low-risk prostate cancer. Outcomes and toxicities of this series of patients were compared to another group of 32 low-risk patients treated with conventional fractionation (CFRT. Methods. Fifty-nine patients with low-risk prostate cancer were analysed. Total dose for the prostate and proximal seminal vesicles was 60 Gy delivered in 20 fractions. Results. The median follow-up was 30 months. The actuarial 4-year overall survival, biochemical free survival, and disease specific survival were 100%, 97.4%, and 97.4%, respectively. Acute grade 1-2 gastrointestinal (GI and genitourinary (GU toxicity rates were 11.9% and 40.7%, respectively. Grade 1 GI and GU late toxicity rates were 8.5% and 13.6%, respectively. No grade ≥2 late toxicities were recorded. Acute grade 2-3 GU toxicity resulted significantly lower (P=0.04 in HFRT group compared to the CFRT group. The cumulative 4-year incidence of grade 1-2 GU toxicity was significantly higher (P<0.001 for HFRT patients. Conclusions. Our study demonstrated that hypofractionated regimen provided excellent biochemical control in favorable risk prostate cancer patients. The incidence of GI and GU toxicity was low. However, HFRT presented higher cumulative incidence of low-grade late GU toxicity than CFRT.

  8. Functional toxicology: tools to advance the future of toxicity testing

    Science.gov (United States)

    Gaytán, Brandon D.; Vulpe, Chris D.

    2014-01-01

    The increased presence of chemical contaminants in the environment is an undeniable concern to human health and ecosystems. Historically, by relying heavily upon costly and laborious animal-based toxicity assays, the field of toxicology has often neglected examinations of the cellular and molecular mechanisms of toxicity for the majority of compounds—information that, if available, would strengthen risk assessment analyses. Functional toxicology, where cells or organisms with gene deletions or depleted proteins are used to assess genetic requirements for chemical tolerance, can advance the field of toxicity testing by contributing data regarding chemical mechanisms of toxicity. Functional toxicology can be accomplished using available genetic tools in yeasts, other fungi and bacteria, and eukaryotes of increased complexity, including zebrafish, fruit flies, rodents, and human cell lines. Underscored is the value of using less complex systems such as yeasts to direct further studies in more complex systems such as human cell lines. Functional techniques can yield (1) novel insights into chemical toxicity; (2) pathways and mechanisms deserving of further study; and (3) candidate human toxicant susceptibility or resistance genes. PMID:24847352

  9. Understand Your Risk for Arrhythmia

    Science.gov (United States)

    ... is likely monitoring your heart rhythm with regular EKGs ( electrocardiograms ). But arrhythmias that occur infrequently may not ... patient sheets Popular Articles 1 Understanding Blood Pressure Readings 2 Sodium and Salt 3 Heart Attack Symptoms ...

  10. Toxicity assessment of chemical contaminants;transition from in vitromethods to novel in vitro methods

    Directory of Open Access Journals (Sweden)

    A.A. Farshad

    2007-04-01

    Full Text Available Exposure to occupational and environmental contaminants is a major contributor to human health problems. Despite significant achievements in the risk assessment of chemicals, the toxicological database, particularly for industrial chemicals, remains limited. Considering there areapproximately 80, 000 chemicals in commerce, and an extremely large number of chemical mixtures, in vivo testing of this large number is unachievable from ethical, economical and scientific perspectives. Therefore, increasing the number of available industrial chemicals andnew products has created a demand for alternatives to animal methods for better safety evaluation. Recent toxicity studies have demonstrated that in vitro methods are capable of rapidly providing toxicity information. In this review, current toxicity test methods for risk evaluation of industrial chemical contaminants are presented. To evaluate the potential applications of  more recent test methods developed for toxicity testing of chemical contaminants are discussed. Although  to be considered more broadly for risk assessment of human chemical exposures. In vitro methods,in vitro toxicology methods cannot exactly mimic the biodynamics of the whole body, in vitro  relationships (QSARs and physiologically based toxicokinetic (PBTK models have a potentialtest systems in combination with the knowledge of quantitative structure activity.

  11. Specific toxicity after stereotactic body radiation therapy to the central chest. A comprehensive review

    Energy Technology Data Exchange (ETDEWEB)

    Oskan, Feras; Becker, Gerd; Bleif, Martin [Alb-Fils Kliniken GmbH, Department of Radiation Oncology, Goeppingen (Germany); CyberKnife Suedwest Centre, Radiochirurgicum, Goeppingen (Germany)

    2017-03-15

    The toxicity of stereotactic body radiation therapy in the central chest remains an unsettled issue. The collected data concerning the observed complications are poorly understood and are limited in their quantity and quality, thus hampering a precise delineation of treatment-specific toxicity. The majority of complications scored as toxicity grade 5, namely respiratory failure and fatal hemoptysis, are most likely related to multiple competing risks and occurred at different dose fractionation schemas, e. g., 10-12 fractions of 4-5 Gy, 5 fractions of 10 Gy, 3 fractions of 20-22 Gy, and 1 fraction of 15-30 Gy. Further investigations with longer follow-up and more details of patients' pretreatment and tumor characteristics are required. Furthermore, satisfactory documentation of complications and details of dosimetric parameters, as well as limitation of the wide range of possible fractionation schemes is also warranted for a better understanding of the risk factors relevant for macroscopic damage to the serially organized anatomic structure within the central chest. (orig.) [German] Das Risiko fuer schwere Nebenwirkungen der stereotaktischen Strahlentherapie bei zentralen Lungentumoren ist bisher schlecht definiert. Nicht nur die begrenzte Zahl der dokumentierten Ereignisse, sondern auch die Vielzahl der verwendeten Fraktionierungsschemata erschwert das Herausarbeiten valider prognostischer Faktoren. Auf Basis dieser Datenlage laesst sich das Risiko fuer Grad-5-Toxizitaeten, insbesondere Atemversagen und toedliche Blutungen, kaum einem bestimmten Dosis- oder Fraktionierungsschema, wie z. B. 10-12 Fraktionen mit 4-5 Gy, 5 Fraktionen mit 10 Gy, 3 Fraktionen mit 20-22 Gy und 1 Fraktion mit 15-30 Gy zuordnen, da multiple patientenspezifische, konkurrierende Risiken dabei einen wesentlichen Einfluss zu haben scheinen. Es wird zukuenftig erforderlich sein, praetherapeutische Patienten- und Tumorcharakteristika genauer zu erfassen, dosimetrische Parameter besser zu

  12. Adolescent Exposure to Toxic Volatile Organic Chemicals From E-Cigarettes.

    Science.gov (United States)

    Rubinstein, Mark L; Delucchi, Kevin; Benowitz, Neal L; Ramo, Danielle E

    2018-04-01

    There is an urgent need to understand the safety of e-cigarettes with adolescents. We sought to identify the presence of chemical toxicants associated with e-cigarette use among adolescents. Adolescent e-cigarette users (≥1 use within the past 30 days, ≥10 lifetime e-cigarette use episodes) were divided into e-cigarette-only users (no cigarettes in the past 30 days, urine 4-[methylnitrosamino]-1-[3-pyridyl]-1-butanol [NNAL] level 30 pg/mL; n = 16), and never-using controls ( N = 20). Saliva was collected within 24 hours of the last e-cigarette use for analysis of cotinine and urine for analysis of NNAL and levels of 8 volatile organic chemical compounds. Bivariate analyses compared e-cigarette-only users with dual users, and regression analyses compared e-cigarette-only users with dual users and controls on levels of toxicants. The participants were 16.4 years old on average. Urine excretion of metabolites of benzene, ethylene oxide, acrylonitrile, acrolein, and acrylamide was significantly higher in dual users versus e-cigarette-only users (all P < .05). Excretion of metabolites of acrylonitrile, acrolein, propylene oxide, acrylamide, and crotonaldehyde were significantly higher in e-cigarette-only users compared with controls (all P < .05). Although e-cigarette vapor may be less hazardous than tobacco smoke, our findings can be used to challenge the idea that e-cigarette vapor is safe, because many of the volatile organic compounds we identified are carcinogenic. Messaging to teenagers should include warnings about the potential risk from toxic exposure to carcinogenic compounds generated by these products. Copyright © 2018 by the American Academy of Pediatrics.

  13. Toxicity of 239Pu and 226Ra in young adult beagles: risk estimate in man

    International Nuclear Information System (INIS)

    Miller, S.C.

    1985-01-01

    The overall objective of this research program is to predict the risk to humans following exposure to 239 Pu. The beagle was originally selected for this program because it is relatively long-lived and has skeletal functions and structure analogous to young adults humans, simulating that of a young adult radium dial painter or occupationally exposed person. Young adult (17 month-old) beagles from the moderately inbred colony at the University of Utah were administered one intravenous injection of 239 Pu (0.0007-2.88 μCi/kg in 238 dogs) or 226 Ra (0.007-10.4 μCi/kg in 119 dogs), and compared to appropriate age-matched control beagles. All beagles have been and are being observed clinically throughout their expected 12 to 15 year post-injection lifespan. A thorough clinical and post-mortem survey is conducted to determine causes of death or lesions at death. The clinical findings are being encoded using SNOMED terminology and entered into a computerized database. All beagles in the 226 Ra study are dead and the data are being analyzed and published. The shape of the curve for dose vs. bone tumor incidence is highly linear up to average skeletal doses of 2200 rads. In higher dose groups, the time to tumor appearance is decreased and skeletal tumors occur in almost all animals. The 226 Ra response is being compared with the 239 Pu response in beagles. This toxicity ratio will allow use of the bone tumor response in the radium dial painters to predict the toxicity of plutonium for bone tumor induction in man

  14. Low-dose total skin electron beam therapy for cutaneous lymphoma : Minimal risk of acute toxicities.

    Science.gov (United States)

    Kroeger, Kai; Elsayad, Khaled; Moustakis, Christos; Haverkamp, Uwe; Eich, Hans Theodor

    2017-12-01

    Low-dose total skin electron beam therapy (TSEBT) is attracting increased interest for the effective palliative treatment of primary cutaneous T‑cell lymphoma (pCTCL). In this study, we compared toxicity profiles following various radiation doses. We reviewed the records of 60 patients who underwent TSEBT for pCTCL between 2000 and 2016 at the University Hospital of Munster. The treatment characteristics of the radiotherapy (RT) regimens and adverse events (AEs) were then analyzed and compared. In total, 67 courses of TSEBT were administered to 60 patients. Of these patients, 34 (51%) received a standard dose with a median surface dose of 30 Gy and 33 patients (49%) received a low dose with the median surface dose of 12 Gy (7 salvage low-dose TSEBT courses were administered to 5 patients). After a median follow-up of 15 months, the overall AE rate was 100%, including 38 patients (57%) with grade 2 and 7 (10%) with grade 3 AEs. Patients treated with low-dose TSEBT had significantly fewer grade 2 AEs than those with conventional dose regimens (33 vs. 79%, P dose regimen compared to those with the conventional dose regimens (6 vs. 15%, P = 0.78). Multiple/salvage low-dose TSEBT courses were not associated with an increased risk of acute AEs. Low-dose TSEBT regimens are associated with significantly fewer grade 2 acute toxicities compared with conventional doses of TSEBT. Repeated/Salvage low-dose TSEBT, however, appears to be tolerable and can even be applied safely in patients with cutaneous relapses.

  15. Non-infectious chemotherapy-associated acute toxicities during childhood acute lymphoblastic leukemia therapy

    DEFF Research Database (Denmark)

    Schmiegelow, Kjeld; Müller, Klaus Gottlob; Mogensen, Signe Sloth

    2017-01-01

    During chemotherapy for childhood acute lymphoblastic leukemia, all organs can be affected by severe acute side effects, the most common being opportunistic infections, mucositis, central or peripheral neuropathy (or both), bone toxicities (including osteonecrosis), thromboembolism, sinusoidal...... useful risk factors, and across study groups there has been wide diversity in toxicity definitions, capture strategies, and reporting, thus hampering meaningful comparisons of toxicity incidences for different leukemia protocols. Since treatment of acute lymphoblastic leukemia now yields 5-year overall...... obstruction syndrome, endocrinopathies (especially steroid-induced adrenal insufficiency and hyperglycemia), high-dose methotrexate-induced nephrotoxicity, asparaginase-associated hypersensitivity, pancreatitis, and hyperlipidemia. Few of the non-infectious acute toxicities are associated with clinically...

  16. Acylcarnitine Profiles in Acetaminophen Toxicity in the Mouse: Comparison to Toxicity, Metabolism and Hepatocyte Regeneration

    Directory of Open Access Journals (Sweden)

    Jack Hinson

    2013-08-01

    Full Text Available High doses of acetaminophen (APAP result in hepatotoxicity that involves metabolic activation of the parent compound, covalent binding of the reactive intermediate N-acetyl-p-benzoquinone imine (NAPQI to liver proteins, and depletion of hepatic glutathione. Impaired fatty acid β-oxidation has been implicated in previous studies of APAP-induced hepatotoxicity. To better understand relationships between toxicity and fatty acid β-oxidation in the liver in APAP toxicity, metabolomic assays for long chain acylcarnitines were examined in relationship to established markers of liver toxicity, oxidative metabolism, and liver regeneration in a time course study in mice. Male B6C3F1 mice were treated with APAP (200 mg/kg IP or saline and sacrificed at 1, 2, 4, 8, 24 or 48 h after APAP. At 1 h, hepatic glutathione was depleted and APAP protein adducts were markedly increased. Alanine aminotransferase (ALT levels were elevated at 4 and 8 h, while proliferating cell nuclear antigen (PCNA expression, indicative of hepatocyte regeneration, was apparent at 24 h and 48 h. Elevations of palmitoyl, oleoyl and myristoyl carnitine were apparent by 2–4 h, concurrent with the onset of Oil Red O staining in liver sections. By 8 h, acylcarnitine levels were below baseline levels and remained low at 24 and 48 h. A partial least squares (PLS model suggested a direct association of acylcarnitine accumulation in serum to APAP protein adduct and hepatic glutathione levels in mice. Overall, the kinetics of serum acylcarnitines in APAP toxicity in mice followed a biphasic pattern involving early elevation after the metabolism phases of toxicity and later depletion of acylcarnitines.

  17. Chronic Toxic Metal Exposure and Cardiovascular Disease: Mechanisms of Risk and Emerging Role of Chelation Therapy.

    Science.gov (United States)

    Aneni, Ehimen C; Escolar, Esteban; Lamas, Gervasio A

    2016-12-01

    Over the last few decades, there has been a growing body of epidemiologic evidence linking chronic toxic metal exposure to cardiovascular disease-related morbidity and mortality. The recent and unexpectedly positive findings from a randomized, double-blind, multicenter trial of metal chelation for the secondary prevention of atherosclerotic cardiovascular disease (Trial to Assess Chelation Therapy (TACT)) have focused the discussion on the role of chronic exposure to toxic metals in the development and propagation of cardiovascular disease and the role of toxic metal chelation therapy in the secondary prevention of cardiovascular disease. This review summarizes the most recent evidence linking chronic toxic metal exposure to cardiovascular disease and examines the findings of TACT.

  18. A MultiFactorial Risk Score to weigh toxicities and co-morbidities relative to costs of antiretrovirals in a cohort of HIV-infected patients

    OpenAIRE

    M Tontodonati; F Sozio; F Vadini; E Polilli; T Ursini; G Calella; P Di Stefano; E Mazzotta; A Costantini; C D'Amario; G Parruti

    2012-01-01

    Purpose of the study: Considering costs of antiretrovirals (ARVs) for HIV patients is increasingly needed. A simple and comprehensive tool weighing comorbidities and ARV-related toxicities could be useful to judge the appropriateness of use of more expensive drugs. We conceived a MultiFactorial Risk Score (MFRS) to evaluate the appropriateness of ARVs prescription relative to their costs. Methods: HIV patients were consecutively enrolled in 2010-2011. We considered socio-demographic character...

  19. Oxygen Toxicity and Special Operations Forces Diving: Hidden and Dangerous

    Directory of Open Access Journals (Sweden)

    Thijs T. Wingelaar

    2017-07-01

    Full Text Available In Special Operations Forces (SOF closed-circuit rebreathers with 100% oxygen are commonly utilized for covert diving operations. Exposure to high partial pressures of oxygen (PO2 could cause damage to the central nervous system (CNS and pulmonary system. Longer exposure time and higher PO2 leads to faster development of more serious pathology. Exposure to a PO2 above 1.4 ATA can cause CNS toxicity, leading to a wide range of neurologic complaints including convulsions. Pulmonary oxygen toxicity develops over time when exposed to a PO2 above 0.5 ATA and can lead to inflammation and fibrosis of lung tissue. Oxygen can also be toxic for the ocular system and may have systemic effects on the inflammatory system. Moreover, some of the effects of oxygen toxicity are irreversible. This paper describes the pathophysiology, epidemiology, signs and symptoms, risk factors and prediction models of oxygen toxicity, and their limitations on SOF diving.

  20. A general mechanism for intracellular toxicity of metal-containing nanoparticles

    KAUST Repository

    Sabella, Stefania

    2014-04-09

    The assessment of the risks exerted by nanoparticles is a key challenge for academic, industrial, and regulatory communities worldwide. Experimental evidence points towards significant toxicity for a range of nanoparticles both in vitro and in vivo. Worldwide efforts aim at uncovering the underlying mechanisms for this toxicity. Here, we show that the intracellular ion release elicited by the acidic conditions of the lysosomal cellular compartment-where particles are abundantly internalized-is responsible for the cascading events associated with nanoparticles-induced intracellular toxicity. We call this mechanism a "lysosome-enhanced Trojan horse effect" since, in the case of nanoparticles, the protective cellular machinery designed to degrade foreign objects is actually responsible for their toxicity. To test our hypothesis, we compare the toxicity of similar gold particles whose main difference is in the internalization pathways. We show that particles known to pass directly through cell membranes become more toxic when modified so as to be mostly internalized by endocytosis. Furthermore, using experiments with chelating and lysosomotropic agents, we found that the toxicity mechanism for different metal containing NPs (such as metallic, metal oxide, and semiconductor NPs) is mainly associated with the release of the corresponding toxic ions. Finally, we show that particles unable to release toxic ions (such as stably coated NPs, or diamond and silica NPs) are not harmful to intracellular environments. The Royal Society of Chemistry 2014.