Dissecting the assays to assess microbial tolerance to toxic chemicals in bioprocessing.

Science.gov (United States)

Zingaro, Kyle A; Nicolaou, Sergios A; Papoutsakis, Eleftherios T

2013-11-01

Microbial strains are increasingly used for the industrial production of chemicals and biofuels, but the toxicity of components in the feedstock and product streams limits process outputs. Selected or engineered microbes that thrive in the presence of toxic chemicals can be assessed using tolerance assays. Such assays must reasonably represent the conditions the cells will experience during the intended process and measure the appropriate physiological trait for the desired application. We review currently used tolerance assays, and examine the many parameters that affect assay outcomes. We identify and suggest the use of the best-suited assays for each industrial bioreactor operating condition, discuss next-generation assays, and propose a standardized approach for using assays to examine tolerance to toxic chemicals. Copyright © 2013 Elsevier Ltd. All rights reserved.

Assessment of the chemical toxicity of long-lived radionuclides on the basis of Who guidelines for drinking-water quality

International Nuclear Information System (INIS)

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

2003-01-01

The current assessment of health risks related to long lived radionuclides waste management is not complete if accounting only for radiological toxicity aspects. Although such an approach is justified for a large number of radionuclides of concern, it nevertheless cannot be exclusive and generalised: the chemical toxicity should be considered for radionuclides with a radioactive half-life exceeding 10 5 years. When assessing the chemical or radiological toxicity of a radionuclide, a reference dose applied to drinking water consumption (0.1 mSv/year) can be compared to existing toxicological data. Such an approach has been used by the World Health Organization for natural uranium, for which a guideline value in drinking water derived from its chemical toxicity (2 μg/l) is recommended. WHO's approach is used here for illustrating that the potential chemical toxicity of an element is to be considered for assessing health risks related to long-lived radionuclides. (authors)

Radiation-dosimetry and chemical-toxicity considerations for 99Tc

International Nuclear Information System (INIS)

Coffey, J.L.; Hayes, R.L.; Rafter, J.J.; Watson, E.E.; Carlton, J.E.

1982-01-01

Technetium-99 (T/sub 1/2/ = 2.13 x 10 5 y) is produced in the fission of 235 U and 239 Pu. Technitium-99 has been found to contaminate some areas of the uranium re-enrichment process. ICRP-30 Part 2 gives the Annual Limit on Intake (ALI) for 99 Tc as 2 x 10 8 Bq (5.4 mCi) for class D inhaled material (IC80). The ICRP states clearly that ALIs are based on radiation risk only and that chemical toxicity is not considered (IC79). No data were found on the chemical toxicity of 99 Tc, possibly because there are no stable isotopes of technetium with which to study the toxicity, although, because of its long T/sub 1/2/, 99 Tc can, for all practical purposes, be considered stable. The ALI values for 99 Tc are based on data obtained using high specific activity /sup 99m/Tc (T/sub 1/2/ = 6 h) and /sup 95m/Tc (T/sub 1/2/ = 61 days). Since the specific activities of 99 Tc and Na 99 TcO 4 are quite low (17 mCi/g and 9 mCi/g, respectively) and 99 Tc is available in abundant supply, we have attempted to assess the relative radiation and chemical hazards that are associated with this radionuclide. The approach in this study was (1) to study the effect of chemical dose on the whole body retention of 99 Tc sodium pertechnetate in rats and to relate these effects to the radiation dose and the ALI and (2) to compare the chemical toxicity of 99 Tc sodium pertechnetate with the ALI at different chemical dose levels

Aquatic toxicity testing of liquid hydrophobic chemicals – Passive dosing exactly at the saturation limit

DEFF Research Database (Denmark)

Stibany, Felix; Nørgaard Schmidt, Stine; Schäffer, Andreas

2017-01-01

The aims of the present study were (1) to develop a passive dosing approach for aquatic toxicity testing of liquid substances with very high Kow values and (2) to apply this approach to the model substance dodecylbenzene (DDB, Log Kow = 8.65). The first step was to design a new passive dosing...... format for testing DDB exactly at its saturation limit. Silicone O-rings were saturated by direct immersion in pure liquid DDB, which resulted in swelling of >14%. These saturated O-rings were used to establish and maintain DDB exposure exactly at the saturation limit throughout 72-h algal growth...... at chemical activity of unity was higher than expected relative to a reported hydrophobicity cut-off in toxicity, but lower than expected relative to a reported chemical activity range for baseline toxicity. The present study introduces a new effective approach for toxicity testing of an important group...

Toxic Release Inventory Chemicals by Groupings

Data.gov (United States)

U.S. Environmental Protection Agency — The Toxics Release Inventory (TRI) makes available information for more than 600 toxic chemicals that are being used, manufactured, treated, transported, or released...

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.

Toxicity evaluation and prediction of toxic chemicals on activated sludge system.

Science.gov (United States)

Cai, Bijing; Xie, Li; Yang, Dianhai; Arcangeli, Jean-Pierre

2010-05-15

The gaps of data for evaluating toxicity of new or overloaded organic chemicals on activated sludge system resulted in the requirements for methodology of toxicity estimation. In this study, 24 aromatic chemicals typically existed in the industrial wastewater were selected and classified into three groups of benzenes, phenols and anilines. Their toxicity on activated sludge was then investigated. Two indexes of IC(50-M) and IC(50-S) were determined respectively from the respiration rates of activated sludge with different toxicant concentration at mid-term (24h) and short-term (30min) time intervals. Experimental results showed that the group of benzenes was the most toxic, followed by the groups of phenols and anilines. The values of IC(50-M) of the tested chemicals were higher than those of IC(50-S). In addition, quantitative structure-activity relationships (QSARs) models developed from IC(50-M) were more stable and accurate than those of IC(50-S). The multiple linear models based on molecular descriptors and K(ow) presented better reliability than single linear models based on K(ow). Among these molecular descriptors, E(lumo) was the most important impact factor for evaluation of mid-term toxicity. Copyright (c) 2009 Elsevier B.V. All rights reserved.

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.

Yellow phosphorus process to convert toxic chemicals to non-toxic products

Science.gov (United States)

Chang, S.G.

1994-07-26

The present invention relates to a process for generating reactive species for destroying toxic chemicals. This process first contacts air or oxygen with aqueous emulsions of molten yellow phosphorus. This contact results in rapid production of abundant reactive species such as O, O[sub 3], PO, PO[sub 2], etc. A gaseous or liquid aqueous solution organic or inorganic chemicals is next contacted by these reactive species to reduce the concentration of toxic chemical and result in a non-toxic product. The final oxidation product of yellow phosphorus is phosphoric acid of a quality which can be recovered for commercial use. A process is developed such that the byproduct, phosphoric acid, is obtained without contamination of toxic species in liquids treated. A gas stream containing ozone without contamination of phosphorus containing species is also obtained in a simple and cost-effective manner. This process is demonstrated to be effective for destroying many types of toxic organic, or inorganic, compounds, including polychlorinated biphenyls (PCB), aromatic chlorides, amines, alcohols, acids, nitro aromatics, aliphatic chlorides, polynuclear aromatic compounds (PAH), dyes, pesticides, sulfides, hydroxyamines, ureas, dithionates and the like. 20 figs.

Runaway chemical reaction exposes community to highly toxic chemicals

International Nuclear Information System (INIS)

Kaszniak, Mark; Vorderbrueggen, John

2008-01-01

The U.S. Chemical Safety and Hazard Investigation Board (CSB) conducted a comprehensive investigation of a runaway chemical reaction at MFG Chemical (MFG) in Dalton, Georgia on April 12, 2004 that resulted in the uncontrolled release of a large quantity of highly toxic and flammable allyl alcohol and allyl chloride into the community. Five people were hospitalized and 154 people required decontamination and treatment for exposure to the chemicals. This included police officers attempting to evacuate the community and ambulance personnel who responded to 911 calls from residents exposed to the chemicals. This paper presents the findings of the CSB report (U.S. Chemical Safety and Hazard Investigation Board (CSB), Investigation Report: Toxic Chemical Vapor Cloud Release, Report No. 2004-09-I-GA, Washington DC, April 2006) including a discussion on tolling practices; scale-up of batch reaction processes; Process Safety Management (PSM) and Risk Management Plan (RMP) implementation; emergency planning by the company, county and the city; and emergency response and mitigation actions taken during the incident. The reactive chemical testing and atmospheric dispersion modeling conducted by CSB after the incident and recommendations adopted by the Board are also discussed

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

Comparative toxicity of chemicals to earthworms

Energy Technology Data Exchange (ETDEWEB)

Callahan, C.A.; Shirazi, M.A. (Environmental Protection Agency, Corvallis, OR (United States)); Neuhauser, E.F. (Niagara Mohawk Power Corp., Syracuse, NY (United States))

1994-02-01

The concentration-response (mortality) relationships of four species of earthworms, Eisenia fetida (Savigny), Allolobophora tuberculata (Eisen), Eudrilus eugeniae (Kinberg), and Perionyx excavatus (Perrier) are summarized for 62 chemicals and two test protocols. A Weibull function is used to summarize these data for each chemical in terms of sensitivity and toxicity, in addition to the LC50. The estimation of the Weibull parameters a and k summarize the entire concentration-response relationship. This technique should be applicable to a variety of testing protocols with different species whenever the goal is summarizing the shape of the concentration-response curves to fully evaluate chemical impact on organisms. In some cases for these data four orders of magnitude separate LC50s of the soil test and the contact test for the same chemical and species. All four species appear to be similar in range of toxicity and tolerance to these chemicals, suggesting that Eisenia fetida and may be representative of these four species and these chemicals.

Chemical mixtures in untreated water from public-supply wells in the U.S. — Occurrence, composition, and potential toxicity

International Nuclear Information System (INIS)

Toccalino, Patricia L.; Norman, Julia E.; Scott, Jonathon C.

2012-01-01

Chemical mixtures are prevalent in groundwater used for public water supply, but little is known about their potential health effects. As part of a large-scale ambient groundwater study, we evaluated chemical mixtures across multiple chemical classes, and included more chemical contaminants than in previous studies of mixtures in public-supply wells. We (1) assessed the occurrence of chemical mixtures in untreated source-water samples from public-supply wells, (2) determined the composition of the most frequently occurring mixtures, and (3) characterized the potential toxicity of mixtures using a new screening approach. The U.S. Geological Survey collected one untreated water sample from each of 383 public wells distributed across 35 states, and analyzed the samples for as many as 91 chemical contaminants. Concentrations of mixture components were compared to individual human-health benchmarks; the potential toxicity of mixtures was characterized by addition of benchmark-normalized component concentrations. Most samples (84%) contained mixtures of two or more contaminants, each at concentrations greater than one-tenth of individual benchmarks. The chemical mixtures that most frequently occurred and had the greatest potential toxicity primarily were composed of trace elements (including arsenic, strontium, or uranium), radon, or nitrate. Herbicides, disinfection by-products, and solvents were the most common organic contaminants in mixtures. The sum of benchmark-normalized concentrations was greater than 1 for 58% of samples, suggesting that there could be potential for mixtures toxicity in more than half of the public-well samples. Our findings can be used to help set priorities for groundwater monitoring and suggest future research directions for drinking-water treatment studies and for toxicity assessments of chemical mixtures in water resources. - Highlights: ► We assessed mixtures in untreated groundwater samples from public-supply wells. ► A screening

CADDIS Volume 2. Sources, Stressors and Responses: Unspecified Toxic Chemicals - Detailed Conceptual Diagram

Science.gov (United States)

Intro to the unspecified toxic chemicals module, when to list toxic chemicals as a candidate cause, ways to measure toxic chemicals, simple and detailed conceptual diagrams for toxic chemicals, toxic chemicals module references and literature reviews.

CADDIS Volume 2. Sources, Stressors and Responses: Unspecified Toxic Chemicals - Simple Conceptual Diagram

Science.gov (United States)

Intro to the unspecified toxic chemicals module, when to list toxic chemicals as a candidate cause, ways to measure toxic chemicals, simple and detailed conceptual diagrams for toxic chemicals, toxic chemicals module references and literature reviews.

Chemical mixtures in untreated water from public-supply wells in the U.S. - Occurrence, composition, and potential toxicity

Energy Technology Data Exchange (ETDEWEB)

Toccalino, Patricia L., E-mail: ptocca@usgs.gov [U.S. Geological Survey (USGS), 6000 J Street, Placer Hall, Sacramento, California 95819 (United States); Norman, Julia E., E-mail: jnorman@usgs.gov [USGS, 2130 SW 5th Avenue, Portland, Oregon 97201 (United States); Scott, Jonathon C., E-mail: jon@usgs.gov [USGS, 202 NW 66th Street, Oklahoma City, Oklahoma 73116 (United States)

2012-08-01

Chemical mixtures are prevalent in groundwater used for public water supply, but little is known about their potential health effects. As part of a large-scale ambient groundwater study, we evaluated chemical mixtures across multiple chemical classes, and included more chemical contaminants than in previous studies of mixtures in public-supply wells. We (1) assessed the occurrence of chemical mixtures in untreated source-water samples from public-supply wells, (2) determined the composition of the most frequently occurring mixtures, and (3) characterized the potential toxicity of mixtures using a new screening approach. The U.S. Geological Survey collected one untreated water sample from each of 383 public wells distributed across 35 states, and analyzed the samples for as many as 91 chemical contaminants. Concentrations of mixture components were compared to individual human-health benchmarks; the potential toxicity of mixtures was characterized by addition of benchmark-normalized component concentrations. Most samples (84%) contained mixtures of two or more contaminants, each at concentrations greater than one-tenth of individual benchmarks. The chemical mixtures that most frequently occurred and had the greatest potential toxicity primarily were composed of trace elements (including arsenic, strontium, or uranium), radon, or nitrate. Herbicides, disinfection by-products, and solvents were the most common organic contaminants in mixtures. The sum of benchmark-normalized concentrations was greater than 1 for 58% of samples, suggesting that there could be potential for mixtures toxicity in more than half of the public-well samples. Our findings can be used to help set priorities for groundwater monitoring and suggest future research directions for drinking-water treatment studies and for toxicity assessments of chemical mixtures in water resources. - Highlights: Black-Right-Pointing-Pointer We assessed mixtures in untreated groundwater samples from public

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...

Combinatorial QSAR modeling of chemical toxicants tested against Tetrahymena pyriformis.

Science.gov (United States)

Zhu, Hao; Tropsha, Alexander; Fourches, Denis; Varnek, Alexandre; Papa, Ester; Gramatica, Paola; Oberg, Tomas; Dao, Phuong; Cherkasov, Artem; Tetko, Igor V

2008-04-01

Selecting most rigorous quantitative structure-activity relationship (QSAR) approaches is of great importance in the development of robust and predictive models of chemical toxicity. To address this issue in a systematic way, we have formed an international virtual collaboratory consisting of six independent groups with shared interests in computational chemical toxicology. We have compiled an aqueous toxicity data set containing 983 unique compounds tested in the same laboratory over a decade against Tetrahymena pyriformis. A modeling set including 644 compounds was selected randomly from the original set and distributed to all groups that used their own QSAR tools for model development. The remaining 339 compounds in the original set (external set I) as well as 110 additional compounds (external set II) published recently by the same laboratory (after this computational study was already in progress) were used as two independent validation sets to assess the external predictive power of individual models. In total, our virtual collaboratory has developed 15 different types of QSAR models of aquatic toxicity for the training set. The internal prediction accuracy for the modeling set ranged from 0.76 to 0.93 as measured by the leave-one-out cross-validation correlation coefficient ( Q abs2). The prediction accuracy for the external validation sets I and II ranged from 0.71 to 0.85 (linear regression coefficient R absI2) and from 0.38 to 0.83 (linear regression coefficient R absII2), respectively. The use of an applicability domain threshold implemented in most models generally improved the external prediction accuracy but at the same time led to a decrease in chemical space coverage. Finally, several consensus models were developed by averaging the predicted aquatic toxicity for every compound using all 15 models, with or without taking into account their respective applicability domains. We find that consensus models afford higher prediction accuracy for the

Sources of toxicity and exposure information for identifying chemicals of high concern to children

International Nuclear Information System (INIS)

Stone, Alex; Delistraty, Damon

2010-01-01

Due to the large number of chemicals in commerce without adequate toxicity characterization data, coupled with an ineffective federal policy for chemical management in the United States, many states are grappling with the challenge to identify toxic chemicals that may pose a risk to human health and the environment. Specific populations (e.g., children, elderly) are particularly sensitive to these toxic chemicals. In 2008, the Children's Safe Product Act (CSPA) was passed in Washington State. The CSPA included specific requirements to identify High Priority Chemicals (HPCs) and Chemicals of High Concern to Children (CHCCs). To implement this legislation, a methodology was developed to identify HPCs from authoritative scientific and regulatory sources on the basis of toxicity criteria. Another set of chemicals of concern was then identified from authoritative sources, based on their potential exposure to children. Exposure potential was evaluated by identifying chemicals detected in biomonitoring studies (i.e., human tissues), as well as those present in residential exposure media (e.g., indoor air, house dust, drinking water, consumer products). Accordingly, CHCCs were defined as HPCs that also appear in biomonitoring studies or relevant exposure media. For chemicals with unique Chemical Abstracts Service (CAS) numbers, we identified 2044 HPCs and 2219 chemicals with potential exposure to children, resulting in 476 CHCCs. The process of chemical identification is dynamic, so that chemicals may be added or subtracted as new information becomes available. Although beyond the scope of this paper, the 476 CHCCs will be prioritized in a more detailed assessment, based on the strength and weight of evidence of toxicity and exposure data. Our approach was developed to be flexible which allows the addition or removal of specific sources of toxicity or exposure information, as well as transparent to allow clear identification of inputs. Although the methodology was

In silico assessment of the acute toxicity of chemicals: recent advances and new model for multitasking prediction of toxic effect.

Science.gov (United States)

Kleandrova, Valeria V; Luan, Feng; Speck-Planche, Alejandro; Cordeiro, M Natália D S

2015-01-01

The assessment of acute toxicity is one of the most important stages to ensure the safety of chemicals with potential applications in pharmaceutical sciences, biomedical research, or any other industrial branch. A huge and indiscriminate number of toxicity assays have been carried out on laboratory animals. In this sense, computational approaches involving models based on quantitative-structure activity/toxicity relationships (QSAR/QSTR) can help to rationalize time and financial costs. Here, we discuss the most significant advances in the last 6 years focused on the use of QSAR/QSTR models to predict acute toxicity of drugs/chemicals in laboratory animals, employing large and heterogeneous datasets. The advantages and drawbacks of the different QSAR/QSTR models are analyzed. As a contribution to the field, we introduce the first multitasking (mtk) QSTR model for simultaneous prediction of acute toxicity of compounds by considering different routes of administration, diverse breeds of laboratory animals, and the reliability of the experimental conditions. The mtk-QSTR model was based on artificial neural networks (ANN), allowing the classification of compounds as toxic or non-toxic. This model correctly classified more than 94% of the 1646 cases present in the whole dataset, and its applicability was demonstrated by performing predictions of different chemicals such as drugs, dietary supplements, and molecules which could serve as nanocarriers for drug delivery. The predictions given by the mtk-QSTR model are in very good agreement with the experimental results.

2008 Toxic Chemical Release Inventory 2008 Toxic Chemical Release Inventory Community Right-to-Know Act of 1986, Title III, Section 313

Energy Technology Data Exchange (ETDEWEB)

Ecology and Air Quality Group

2009-10-01

For reporting year 2008, Los Alamos National Laboratory (LANL) submitted a Form R report for lead as required under the Emergency Planning and Community Right-to- Know Act (EPCRA) Section 313. No other EPCRA Section 313 chemicals were used in 2008 above the reportable thresholds. This document was prepared to provide a description of the evaluation of EPCRA Section 313 chemical use and threshold determinations for LANL for calendar year 2008, as well as to provide background information about data included on the Form R reports. Section 313 of EPCRA specifically requires facilities to submit a Toxic Chemical Release Inventory Report (Form R) to the U.S. Environmental Protection Agency (EPA) and state agencies if the owners and operators manufacture, process, or otherwise use any of the listed toxic chemicals above listed threshold quantities. EPA compiles this data in the Toxic Release Inventory database. Form R reports for each chemical over threshold quantities must be submitted on or before July 1 each year and must cover activities that occurred at the facility during the previous year. In 1999, EPA promulgated a final rule on persistent bioaccumulative toxics (PBTs). This rule added several chemicals to the EPCRA Section 313 list of toxic chemicals and established lower reporting thresholds for these and other PBT chemicals that were already reportable. These lower thresholds became applicable in reporting year 2000. In 2001, EPA expanded the PBT rule to include a lower reporting threshold for lead and lead compounds. Facilities that manufacture, process, or otherwise use more than 100 lb of lead or lead compounds must submit a Form R.

Comparative toxicity of ten organic chemicals to four earthworm species

Energy Technology Data Exchange (ETDEWEB)

Neuhauser, E.F.; Durkin, P.R.; Malecki, M.R.; Anatra, M.

1986-01-01

Ten organic chemicals were tested for toxicity to four earthworm species: Allolobophora tuberculata, Eisenia fetida, Eudrilus eugeniae and Perionyx excavatus, using the European Economic Community's (EEC) earthworm artificial soil and contact testing procedure. The phenols were the most toxic chemicals tested, followed by the amine, substituted benzenes, halogenated aliphatic hydrocarbon, polycyclic aromatic hydrocarbon and phthalate as the least toxic chemical tested. Correlations among species within each type of test for a given chemical were extremely high, suggesting that the selection of earthworm test species does not markedly affect the assessment of a chemical's toxicity. The correlation between the two tests was low for all test species. The contact test LC50 for a given chemical cannot be directly correlated to an artificial soil test LC50 for the same earthworm species.

DOE contractor's meeting on chemical toxicity

Energy Technology Data Exchange (ETDEWEB)

1987-01-01

The Office of Health and Environmental Research (OHER) is required to determine the potential health and environmental effects associated with energy production and use. To ensure appropriate communication among investigators and scientific disciplines that these research studies represent, OHER has sponsored workshops. This document provides a compilation of activities at the Third Annual DOE/OHER Workshop. This year's workshop was broadened to include all OHER activities identified as within the chemical effects area. The workshop consisted of eight sessions entitled Isolation and Detection of Toxic chemicals; Adduct Formation and Repair; Chemical Toxicity (Posters); Metabolism and Genotoxicity; Inhalation Toxicology; Gene Regulation; Metals Toxicity; and Biological Mechanisms. This document contains abstracts of the information presented by session.

Transformation of highly toxic chemicals factory for Fuqing nuclear power plant

International Nuclear Information System (INIS)

Wang Hongkai; Gao Yuan; Li Hua

2014-01-01

For the iodine adsorption tests of current M310 nuclear power plant, dimethyl sulfate is one of highly toxic chemical of national strict standard management, and the nation make strict control over toxic chemicals procurement, transportation, storage, management requirements. Since the appropriate toxic chemicals storage place was not considered in the design of M310 nuclear power plant, Fuqing nuclear power sites for storage of dimethyl sulfate implement technical transformation to meet and regulate the storage requirements for highly toxic chemical. This will lay the foundation for carrying out smoothly the relevant tests of nuclear power plant, and provide the reference for the use and construction of toxic chemicals reactor in the same type nuclear power plant. (authors)

Children's vulnerability to toxic chemicals: a challenge and opportunity to strengthen health and environmental policy.

Science.gov (United States)

Landrigan, Philip J; Goldman, Lynn R

2011-05-01

A key policy breakthrough occurred nearly twenty years ago with the discovery that children are far more sensitive than adults to toxic chemicals in the environment. This finding led to the recognition that chemical exposures early in life are significant and preventable causes of disease in children and adults. We review this knowledge and recommend a new policy to regulate industrial and consumer chemicals that will protect the health of children and all Americans, prevent disease, and reduce health care costs. The linchpins of a new US chemical policy will be: first, a legally mandated requirement to test the toxicity of chemicals already in commerce, prioritizing chemicals in the widest use, and incorporating new assessment technologies; second, a tiered approach to premarket evaluation of new chemicals; and third, epidemiologic monitoring and focused health studies of exposed populations.

Comparison of the radiological and chemical toxicity of lead

Energy Technology Data Exchange (ETDEWEB)

Beitel, G.A.; Mott, S.

1995-03-01

This report estimates the worst-case radiological dose to an individual from ingested lead containing picocurie levels of radionuclides and then compares the calculated radiological health effects to the chemical toxic effects from that same lead. This comparison provides an estimate of the consequences of inadvertently recycling, in the commercial market, lead containing nominally undetectable concentrations of radionuclides. Quantitative expressions for the radiological and chemical toxicities of lead are based on concentrations of lead in the blood stream. The result shows that the chemical toxicity of lead is a greater health hazard, by orders of magnitude, than any probable companion radiation dose.

Comparison of the radiological and chemical toxicity of lead

International Nuclear Information System (INIS)

Beitel, G.A.; Mott, S.

1995-03-01

This report estimates the worst-case radiological dose to an individual from ingested lead containing picocurie levels of radionuclides and then compares the calculated radiological health effects to the chemical toxic effects from that same lead. This comparison provides an estimate of the consequences of inadvertently recycling, in the commercial market, lead containing nominally undetectable concentrations of radionuclides. Quantitative expressions for the radiological and chemical toxicities of lead are based on concentrations of lead in the blood stream. The result shows that the chemical toxicity of lead is a greater health hazard, by orders of magnitude, than any probable companion radiation dose

In silico toxicology: computational methods for the prediction of chemical toxicity

KAUST Repository

Raies, Arwa B.; Bajic, Vladimir B.

2016-01-01

Determining the toxicity of chemicals is necessary to identify their harmful effects on humans, animals, plants, or the environment. It is also one of the main steps in drug design. Animal models have been used for a long time for toxicity testing. However, in vivo animal tests are constrained by time, ethical considerations, and financial burden. Therefore, computational methods for estimating the toxicity of chemicals are considered useful. In silico toxicology is one type of toxicity assessment that uses computational methods to analyze, simulate, visualize, or predict the toxicity of chemicals. In silico toxicology aims to complement existing toxicity tests to predict toxicity, prioritize chemicals, guide toxicity tests, and minimize late-stage failures in drugs design. There are various methods for generating models to predict toxicity endpoints. We provide a comprehensive overview, explain, and compare the strengths and weaknesses of the existing modeling methods and algorithms for toxicity prediction with a particular (but not exclusive) emphasis on computational tools that can implement these methods and refer to expert systems that deploy the prediction models. Finally, we briefly review a number of new research directions in in silico toxicology and provide recommendations for designing in silico models.

In silico toxicology: computational methods for the prediction of chemical toxicity

KAUST Repository

Raies, Arwa B.

2016-01-06

Determining the toxicity of chemicals is necessary to identify their harmful effects on humans, animals, plants, or the environment. It is also one of the main steps in drug design. Animal models have been used for a long time for toxicity testing. However, in vivo animal tests are constrained by time, ethical considerations, and financial burden. Therefore, computational methods for estimating the toxicity of chemicals are considered useful. In silico toxicology is one type of toxicity assessment that uses computational methods to analyze, simulate, visualize, or predict the toxicity of chemicals. In silico toxicology aims to complement existing toxicity tests to predict toxicity, prioritize chemicals, guide toxicity tests, and minimize late-stage failures in drugs design. There are various methods for generating models to predict toxicity endpoints. We provide a comprehensive overview, explain, and compare the strengths and weaknesses of the existing modeling methods and algorithms for toxicity prediction with a particular (but not exclusive) emphasis on computational tools that can implement these methods and refer to expert systems that deploy the prediction models. Finally, we briefly review a number of new research directions in in silico toxicology and provide recommendations for designing in silico models.

SCREENING FOR TOXIC INDUSTRIAL CHEMICALS USING SEMIPERMEABLE MEMBRANE DEVICES WITH RAPID TOXICITY ASSAYS

Science.gov (United States)

A time-integrated sampling device interfaced with two toxicity-based assays is reported for monitoring volatile toxic industrial chemicals (TICs). Semipermeable membrane devices (SPMDs) using dimethylsulfoxide (DMSO) as the fill solvent accumulated each of 17 TICs from the vapor...

Toxicity studies of drugs and chemicals in animals: An overview

Directory of Open Access Journals (Sweden)

S. Saganuwan

2017-12-01

Full Text Available Toxicity study is the investigation of either short or long-term toxic effects of a drug or chemical on animals. The toxicity is dose-dependent as asserted by Paracelsus over 500 years ago. However, short-term toxic effect is determined using median lethal dose (LD50 first introduced by Trevan in 1927 and revised many times. Presently there is a growing preponderance of rejection of scientific papers on acute toxicity study, simply because of the belief that in the current hazard and safety as-sessment of drugs and chemicals, LD50 values are no longer used. In view of this, literature search was carried out with a view to investigating the relevance of LD50 in development and assessment of drugs and chemicals. The findings revealed that in the past, many animals had been used for LD50 determination. OECD has reduced the number of test animals to 5–15 and presently it is further re-duced to 2–6. Acute toxicity study is being carried out in medicinal plants research and in the study of patent medicine. Although the application of LD50 has been drastically reduced, it is still applied and accepted in some parts of the world. Moreover, animals on which LD50 tests are conducted, should be allowed to die to see the end effect of the test drug or chemical because euthanisia of test animals may mask some toxicity signs of the test agents. Therefore, toxicity study of drugs and chemicals is a sci-entific process necessary for discovery and development of drugs as well as identification of potential toxicants.

In silico toxicology: comprehensive benchmarking of multi-label classification methods applied to chemical toxicity data

KAUST Repository

Raies, Arwa B.

2017-12-05

One goal of toxicity testing, among others, is identifying harmful effects of chemicals. Given the high demand for toxicity tests, it is necessary to conduct these tests for multiple toxicity endpoints for the same compound. Current computational toxicology methods aim at developing models mainly to predict a single toxicity endpoint. When chemicals cause several toxicity effects, one model is generated to predict toxicity for each endpoint, which can be labor and computationally intensive when the number of toxicity endpoints is large. Additionally, this approach does not take into consideration possible correlation between the endpoints. Therefore, there has been a recent shift in computational toxicity studies toward generating predictive models able to predict several toxicity endpoints by utilizing correlations between these endpoints. Applying such correlations jointly with compounds\\' features may improve model\\'s performance and reduce the number of required models. This can be achieved through multi-label classification methods. These methods have not undergone comprehensive benchmarking in the domain of predictive toxicology. Therefore, we performed extensive benchmarking and analysis of over 19,000 multi-label classification models generated using combinations of the state-of-the-art methods. The methods have been evaluated from different perspectives using various metrics to assess their effectiveness. We were able to illustrate variability in the performance of the methods under several conditions. This review will help researchers to select the most suitable method for the problem at hand and provide a baseline for evaluating new approaches. Based on this analysis, we provided recommendations for potential future directions in this area.

In silico toxicology: comprehensive benchmarking of multi-label classification methods applied to chemical toxicity data

KAUST Repository

Raies, Arwa B.; Bajic, Vladimir B.

2017-01-01

One goal of toxicity testing, among others, is identifying harmful effects of chemicals. Given the high demand for toxicity tests, it is necessary to conduct these tests for multiple toxicity endpoints for the same compound. Current computational toxicology methods aim at developing models mainly to predict a single toxicity endpoint. When chemicals cause several toxicity effects, one model is generated to predict toxicity for each endpoint, which can be labor and computationally intensive when the number of toxicity endpoints is large. Additionally, this approach does not take into consideration possible correlation between the endpoints. Therefore, there has been a recent shift in computational toxicity studies toward generating predictive models able to predict several toxicity endpoints by utilizing correlations between these endpoints. Applying such correlations jointly with compounds' features may improve model's performance and reduce the number of required models. This can be achieved through multi-label classification methods. These methods have not undergone comprehensive benchmarking in the domain of predictive toxicology. Therefore, we performed extensive benchmarking and analysis of over 19,000 multi-label classification models generated using combinations of the state-of-the-art methods. The methods have been evaluated from different perspectives using various metrics to assess their effectiveness. We were able to illustrate variability in the performance of the methods under several conditions. This review will help researchers to select the most suitable method for the problem at hand and provide a baseline for evaluating new approaches. Based on this analysis, we provided recommendations for potential future directions in this area.

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

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

Toxicity and chemical analyses of airport runoff waters in Poland.

Science.gov (United States)

Sulej, Anna Maria; Polkowska, Zaneta; Wolska, Lidia; Cieszynska, Monika; Namieśnik, Jacek

2014-05-01

The aim of this study was to assess the ecotoxicological effects of various compounds in complex airport effluents using a chemical and ecotoxicological integrated strategy. The present work deals with the determination of sum of PCBs, PAHs, pesticides, cations, anions, phenols, anionic, cationic, non-ionic detergents, formaldehyde and metals--as well as TOC and conductivity--in runoff water samples collected from 2009 to 2011 at several locations on two Polish international airports. Two microbiotests (Vibrio fischeri bacteria and the crustacean Thamnocephalus platyurus) have been used to determine the ecotoxicity of airport runoff waters. The levels of many compounds exceeded several or even several tens of times the maximum permissible levels. Analysis of the obtained data shows that samples that displayed maximum toxicity towards the bioindicators Vibrio fischeri were not toxic towards Thamnocephalus platyurus. Levels of toxicity towards T. platyurus are strongly correlated with pollutants that originate from the technological operations related to the maintenance of airport infrastructure. The integrated (chemical-ecotoxicological) approach to environmental contamination assessment in and around airports yields extensive information on the quality of the environment. These methodologies can be then used as tools for tracking the environmental fate of these compounds and for assessing the environmental effect of airports. Subsequently, these data will provide a basis for airport infrastructure management.

Metal-organic frameworks for the removal of toxic industrial chemicals and chemical warfare agents.

Science.gov (United States)

Bobbitt, N Scott; Mendonca, Matthew L; Howarth, Ashlee J; Islamoglu, Timur; Hupp, Joseph T; Farha, Omar K; Snurr, Randall Q

2017-06-06

Owing to the vast diversity of linkers, nodes, and topologies, metal-organic frameworks can be tailored for specific tasks, such as chemical separations or catalysis. Accordingly, these materials have attracted significant interest for capture and/or detoxification of toxic industrial chemicals and chemical warfare agents. In this paper, we review recent experimental and computational work pertaining to the capture of several industrially-relevant toxic chemicals, including NH 3 , SO 2 , NO 2 , H 2 S, and some volatile organic compounds, with particular emphasis on the challenging issue of designing materials that selectively adsorb these chemicals in the presence of water. We also examine recent research on the capture and catalytic degradation of chemical warfare agents such as sarin and sulfur mustard using metal-organic frameworks.

Linear solvation energy relationships for toxicity of selected organic chemicals to Daphnia pulex and Daphnia magna

Science.gov (United States)

Passino, Dora R.M.; Hickey, James P.; Frank, Anthony M.

1988-01-01

In the Laurentian Great Lakes, more than 300 contaminants have been identified in fish, other biota, water, and sediment. Current hazard assessment of these chemicals by the National Fisheries Research Center-Great Lakes is based on their toxicity, occurrence in the environment, and source. Although scientists at the Center have tested over 70 chemicals with the crustacean Daphnia pulex, the number of experimental data needed to screen the huge array of chemicals in the Great Lakes exceeds the practical capabilities of conducting bioassays. This limitation can be partly circumvented, however, by using mathematical models based on quantitative structure-activity relationships (QSAR) to provide rapid, inexpensive estimates of toxicity. Many properties of chemicals, including toxicity, bioaccumulation and water solubility are well correlated and can be predicted by equations of the generalized linear solvation energy relationships (LSER). The equation we used to model solute toxicity is Toxicity = constant + mVI/100 + s (π* + dδ) + bβm + aαm where VI = intrinsic (Van der Waals) molar volume; π* = molecular dipolarity/polarizability; δ = polarizability 'correction term'; βm = solute hydrogen bond acceptor basicity; and αm = solute hydrogen bond donor acidity. The subscript m designates solute monomer values for α and β. We applied the LSER model to 48-h acute toxicity data (measured as immobilization) for six classes of chemicals detected in Great Lakes fish. The following regression was obtained for Daphnia pulex (concentration = μM): log EC50 = 4.86 - 4.35 VI/100; N = 38, r2 = 0.867, sd = 0.403 We also used the LSER modeling approach to analyze to a large published data set of 24-h acute toxicity for Daphnia magna; the following regression resulted, for eight classes of compounds (concentration = mM): log EC50 = 3.88 - 4.52 VI/100 - 1.62 π* + 1.66 βm - 0.916 αm; N = 62, r2 = 0.859, sd = 0.375 In addition we developed computer software that identifies

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.

Materials Safety Data Sheets: the basis for control of toxic chemicals

Energy Technology Data Exchange (ETDEWEB)

Ketchen, E.E.; Porter, W.E.

1979-09-01

The Material Safety Data Sheets contained in this volume are the basis for the Toxic Chemical Control Program developed by the Industrial Hygiene Department, Health Division, ORNL. The three volumes are the update and expansion of ORNL/TM-5721 and ORNL/TM-5722 Material Safety Data Sheets: The Basis for Control of Toxic Chemicals, Volume I and Volume II. As such, they are a valuable adjunct to the data cards issued with specific chemicals. The chemicals are identified by name, stores catalog number where appropriate, and sequence numbers from the NIOSH Registry of Toxic Effects of Chemical Substances, 1977 Edition, if available. The data sheets were developed and compiled to aid in apprising the employees of hazards peculiar to the handling and/or use of specific toxic chemicals. Space limitation necessitate the use of descriptive medical terms and toxicological abbreviations. A glossary and an abbreviation list were developed to define some of those sometimes unfamiliar terms and abbreviations. The page numbers are keyed to the catalog number in the chemical stores at ORNL.

Modeling drug- and chemical- induced hepatotoxicity with systems biology approaches

Directory of Open Access Journals (Sweden)

Sudin eBhattacharya

2012-12-01

Full Text Available We provide an overview of computational systems biology approaches as applied to the study of chemical- and drug-induced toxicity. The concept of ‘toxicity pathways’ is described in the context of the 2007 US National Academies of Science report, Toxicity testing in the 21st Century: A Vision and A Strategy. Pathway mapping and modeling based on network biology concepts are a key component of the vision laid out in this report for a more biologically-based analysis of dose-response behavior and the safety of chemicals and drugs. We focus on toxicity of the liver (hepatotoxicity – a complex phenotypic response with contributions from a number of different cell types and biological processes. We describe three case studies of complementary multi-scale computational modeling approaches to understand perturbation of toxicity pathways in the human liver as a result of exposure to environmental contaminants and specific drugs. One approach involves development of a spatial, multicellular virtual tissue model of the liver lobule that combines molecular circuits in individual hepatocytes with cell-cell interactions and blood-mediated transport of toxicants through hepatic sinusoids, to enable quantitative, mechanistic prediction of hepatic dose-response for activation of the AhR toxicity pathway. Simultaneously, methods are being developing to extract quantitative maps of intracellular signaling and transcriptional regulatory networks perturbed by environmental contaminants, using a combination of gene expression and genome-wide protein-DNA interaction data. A predictive physiological model (DILIsymTM to understand drug-induced liver injury (DILI, the most common adverse event leading to termination of clinical development programs and regulatory actions on drugs, is also described. The model initially focuses on reactive metabolite-induced DILI in response to administration of acetaminophen, and spans multiple biological scales.

Meta-analysis of toxicity and teratogenicity of 133 chemicals from zebrafish developmental toxicity studies

Science.gov (United States)

Zebrafish developmental toxicity testing is an emerging field, which faces considerable challenges regarding data meta-analysis and the establishment of standardized test protocols. Here, we present an initial correlation study on toxicity of 133 chemicals based on data in the li...

76 FR 7841 - Agency Information Collection Activities; Proposed Collections; Toxic Chemical Release Reporting...

Science.gov (United States)

2011-02-11

... agencies, and others to promote reductions in toxic chemical releases. Industrial facilities use the TRI... Activities; Proposed Collections; Toxic Chemical Release Reporting; Request for Comments on Proposed Renewal... the individual listed in the preceding FOR FURTHER INFORMATION CONTACT section. Title: Toxic Chemical...

Electron Beam Treatment of Toxic Chemicals

International Nuclear Information System (INIS)

Jung, In Ha; Lee, Myun Joo; Lee, Oh Mi; Kim, Tae Hoon

2011-01-01

Polychlorinated biphenyls (PCBs) were commercially produced from 1920s as complex mixtures containing multiple isomers for a variety of applications. They are very toxic, chemically stable and resist microbial, photochemical, chemical, and thermal degradation. The public, legal, and scientific concerns about PCBs arose from research indicating they were environmental contaminants that had a potential to adversely impact the environment, and, therefore, were undesirable as commercial products. Eventually, most producers reduced or stopped production of PCBs in the 1970s. Stockholm convention on POPs (Persistent Organic Pollutants), which was effective on May 2004 and 151 nations including Korea were joined on June 2005, asked to dispose of PCBs by 2028 with environmental friendly methods. Korean government also has declared to perform by 2015. According to the Environmental law of Korea, over 2 ppm of PCBs has to be decomposed by legal methods of incineration and thermal destruction. But those are inapplicable owing to the environmental groups. KAERI(Korea Atomic Energy Research Institute) has recently developed a remarkable technology for radiation treatment of toxic chemicals including chlorides using an electron beam accelerator

Allium-test as a tool for toxicity testing of environmental radioactive-chemical mixtures

Science.gov (United States)

Oudalova, A. A.; Geras'kin, S. A.; Dikareva, N. S.; Pyatkova, S. V.

2017-01-01

Bioassay-based approaches have been propagated to assess toxicity of unknown mixtures of environmental contaminants, but it was rarely applied in cases of chemicals with radionuclides combinations. Two Allium-test studies were performed to assess environmental impact from potential sources of combined radioactive-chemical pollution. Study sites were located at nuclear waste storage facilities in European and in Far-Eastern parts of Russia. As environmental media under impact, waters from monitor wells and nearby water bodies were tested. Concentrations of some chemicals and radionuclides in the samples collected enhanced the permitted limits. Cytogenetic and cytotoxic effects were used as biological endpoints, namely, frequency and spectrum of chromosome aberrations and mitotic abnormalities in anatelophase cells as well as mitotic activity in Allium root tips. Sample points were revealed where waters have an enhanced mutagenic potential. The findings obtained could be used to optimize monitoring system and advance decision making on management and rehabilitation of industrial sites. The Allium-test could be recommended and applied as an effective tool for toxicity testing in case of combined contamination of environmental compartments with radionuclides and chemical compounds.

Development of a toxicity-based fractionation approach for the identification of phototoxic PAHs in pore water

International Nuclear Information System (INIS)

Kosian, P.A.; Makynen, E.A.; Ankley, G.T.; Monson, P.D.

1995-01-01

Environmental matrices often contain complex mixtures of chemical compounds, however, typically only a few chemicals are responsible for observed toxicity. To determine those chemicals responsible for toxicity, a toxicity-based fractionation technique coupled with gas chromatography/mass spectrometry (GC/MS) has been used for the isolation and identification of nonpolar toxicants in aqueous samples. In this study, this technique was modified to separate and identify polycyclic aromatic hydrocarbons (PAHs) responsible for phototoxicity in pore water. Whole pore water, obtained from sediments collected near an oil refinery discharge site, was found to be toxic to Lumbriculus variegatus in the presence of ultraviolet (UV) light. Solid phase extraction disks and high pressure liquid chromatography were used, in conjunction with toxicity tests with L. variegatus, to extract and fractionate phototoxic chemicals from the pore water. GC/MS analysis was performed on the toxic fractions and a tentative list of compound identifications were made based on interpretation of mass spectra and elution information from the chromatographic separation. The compounds identified include PAHs and substituted PAHs that are known or predicted to be phototoxic in the presence of UV light. The results show that a modified toxicity-based fractionation approach can be successfully applied to identify phototoxic PAHs in sediment pore water and therefore used in the assessment of contaminated sediments

Studies of radiation and chemical toxicity. Progress report

International Nuclear Information System (INIS)

1986-01-01

Annual report for the Studies of Radiation and Chemical Toxicity Program at the University of Rochester is presented. Progress is reported on four projects: Neurobehavorial Toxicity of Organometallic Fuel Additives, Mechanisms of Permanent and Delayed Pathologic Effects of Ionizing Radiation, Solid State Radiation Chemistry of the DNA Backbone, and Pulmonary Biochemistry

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.

Investigation of the potential influence of production treatment chemicals on produced water toxicity

International Nuclear Information System (INIS)

Stine, E.R.; Gala, W.R.; Henry, L.R.

1993-01-01

Production treatment chemicals represent a diverse collection of chemical classes, added at various points from the wellhead to the final flotation cell, to prevent operational upsets and enhance the separation of oil from water. Information in the literature indicates that while many treatment chemicals are thought to partition into oil and not into the produced water, there are cases where a sufficiently water soluble treatment chemical is added at high enough concentrations to suggest that the treatment chemical may add to the aquatic toxicity of the produced water. A study was conducted to evaluate the potential effect of production treatment chemicals on the toxicity of produced waters using the US EPA Seven-day Mysidopsis bahia Survival, Growth and Fecundity Test. Samples of produced water were collected and tested for toxicity from three platforms under normal operating conditions, followed by repeated sampling and testing after a 72-hour period in which treatment chemical usage was discontinued, to the degree possible. Significant reductions in produced water toxicity were observed for two of the three platforms tested following either cessation of treatment chemical usage, or by comparing the toxicity of samples collected upstream and downstream of the point of treatment chemical addition

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...

[Assessment of the relationship of properties of chemical compounds and their toxicity to a unified hygienic standardization for chemicals].

Science.gov (United States)

Trushkov, V F; Perminov, K A; Sapozhnikova, V V; Ignatova, O L

2013-01-01

The connection of thermodynamic properties and parameters of toxicity of chemical substances was determined. Obtained data are used for the evaluation of toxicity and hygienic rate setting of chemical compounds. The relationship between enthalpy and toxicity of chemical compounds has been established. Orthogonal planning of the experiment was carried out in the course of the investigations. Equation of unified hygienic rate setting in combined, complex, conjunct influence on the organism is presented. Prospects of determination of toxicity and methodology of unified hygienic rate setting in combined, complex, conjunct influence on the organism are presented

Allium -test as a tool for toxicity testing of environmental radioactive-chemical mixtures

International Nuclear Information System (INIS)

Oudalova, A A; Pyatkova, S V; Geras’kin, S A; Dikareva, N S

2017-01-01

Bioassay-based approaches have been propagated to assess toxicity of unknown mixtures of environmental contaminants, but it was rarely applied in cases of chemicals with radionuclides combinations. Two Allium -test studies were performed to assess environmental impact from potential sources of combined radioactive-chemical pollution. Study sites were located at nuclear waste storage facilities in European and in Far-Eastern parts of Russia. As environmental media under impact, waters from monitor wells and nearby water bodies were tested. Concentrations of some chemicals and radionuclides in the samples collected enhanced the permitted limits. Cytogenetic and cytotoxic effects were used as biological endpoints, namely, frequency and spectrum of chromosome aberrations and mitotic abnormalities in anatelophase cells as well as mitotic activity in Allium root tips. Sample points were revealed where waters have an enhanced mutagenic potential. The findings obtained could be used to optimize monitoring system and advance decision making on management and rehabilitation of industrial sites. The Allium -test could be recommended and applied as an effective tool for toxicity testing in case of combined contamination of environmental compartments with radionuclides and chemical compounds. (paper)

76 FR 64022 - Hydrogen Sulfide; Community Right-to-Know Toxic Chemical Release Reporting

Science.gov (United States)

2011-10-17

... Hydrogen Sulfide; Community Right-to-Know Toxic Chemical Release Reporting AGENCY: Environmental Protection Agency (EPA). ACTION: Lifting of Administrative Stay for Hydrogen Sulfide. SUMMARY: EPA is announcing... (EPCRA) section 313 toxic chemical release reporting requirements for hydrogen sulfide (Chemical...

COMPUTER SUPPORT SYSTEMS FOR ESTIMATING CHEMICAL TOXICITY: PRESENT CAPABILITIES AND FUTURE TRENDS

Science.gov (United States)

Computer Support Systems for Estimating Chemical Toxicity: Present Capabilities and Future Trends A wide variety of computer-based artificial intelligence (AI) and decision support systems exist currently to aid in the assessment of toxicity for environmental chemicals. T...

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

Chemical mixtures in untreated water from public-supply wells in the U.S.--occurrence, composition, and potential toxicity.

Science.gov (United States)

Toccalino, Patricia L; Norman, Julia E; Scott, Jonathon C

2012-08-01

Chemical mixtures are prevalent in groundwater used for public water supply, but little is known about their potential health effects. As part of a large-scale ambient groundwater study, we evaluated chemical mixtures across multiple chemical classes, and included more chemical contaminants than in previous studies of mixtures in public-supply wells. We (1) assessed the occurrence of chemical mixtures in untreated source-water samples from public-supply wells, (2) determined the composition of the most frequently occurring mixtures, and (3) characterized the potential toxicity of mixtures using a new screening approach. The U.S. Geological Survey collected one untreated water sample from each of 383 public wells distributed across 35 states, and analyzed the samples for as many as 91 chemical contaminants. Concentrations of mixture components were compared to individual human-health benchmarks; the potential toxicity of mixtures was characterized by addition of benchmark-normalized component concentrations. Most samples (84%) contained mixtures of two or more contaminants, each at concentrations greater than one-tenth of individual benchmarks. The chemical mixtures that most frequently occurred and had the greatest potential toxicity primarily were composed of trace elements (including arsenic, strontium, or uranium), radon, or nitrate. Herbicides, disinfection by-products, and solvents were the most common organic contaminants in mixtures. The sum of benchmark-normalized concentrations was greater than 1 for 58% of samples, suggesting that there could be potential for mixtures toxicity in more than half of the public-well samples. Our findings can be used to help set priorities for groundwater monitoring and suggest future research directions for drinking-water treatment studies and for toxicity assessments of chemical mixtures in water resources. Published by Elsevier B.V.

In situ exposures using caged organisms: a multi-compartment approach to detect aquatic toxicity and bioaccumulation

International Nuclear Information System (INIS)

Burton, G. Allen; Greenberg, Marc S.; Rowland, Carolyn D.; Irvine, Cameron A.; Lavoie, Daniel R.; Brooker, John A.; Moore, Laurie; Raymer, Delia F.N.; McWilliam, Ruth A.

2005-01-01

An in situ toxicity and bioaccumulation assessment approach is described to assess stressor exposure and effects in surface waters (low and high flow), the sediment-water interface, surficial sediments and pore waters (including groundwater upwellings). This approach can be used for exposing species, representing major functional and taxonomic groups. Pimephales promelas, Daphnia magna, Ceriodaphnia dubia, Hyalella azteca, Hyalella sp., Chironomus tentans, Lumbriculus variegatus, Hydra attenuatta, Hexagenia sp. and Baetis tibialis were successfully used to measure effects on survival, growth, feeding, and/or uptake. Stressors identified included chemical toxicants, suspended solids, photo-induced toxicity, indigenous predators, and flow. Responses varied between laboratory and in situ exposures in many cases and were attributed to differing exposure dynamics and sample-processing artifacts. These in situ exposure approaches provide unique assessment information that is complementary to traditional laboratory-based toxicity and bioaccumulation testing and reduce the uncertainties of extrapolating from the laboratory to field responses. - In situ exposures provide unique information that is complementary to traditional lab-based toxicity results

Acute toxicity of fire control chemicals to Daphnia magna(Straus) and Selenastrum capricornutum(Printz)

Science.gov (United States)

McDonald, Susan F.; Hamilton, Steven J.; Buhl, Kevin J.; Heisinger, James F.

1996-01-01

Acute toxicity tests were conducted exposingDaphnia magnaStraus (daphnid) in soft and hard reconstituted waters (hardness 42 and 162 mg/liter as CaCO3, respectively), andSelenastrum capricornutumPrintz (algae) in ASTM algal assay medium (hardness 15 mg/liter as CaCO3) to fire retardants Fire-Trol GTS-R, Fire-Trol LCG-R, and Phos-Chek D75-F, and foam suppressants Phos-Chek WD-881 and Silv-Ex. The chemicals were slightly toxic to practically harmless to daphnids and moderately toxic to algae. Water quality did not consistently alter the toxicity of the test chemicals to daphnids. The most toxic chemical to daphnids was Silv-Ex (48-hr EC507 mg/liter in soft and hard waters), whereas the least toxic chemical to daphnids was Fire-Trol LCG-R (48-hr EC50848 mg/liter in soft water, 813 mg/liter in hard water). The most toxic chemical to algae was Fire-Trol LCG-R (96-hr IC5010 mg/liter), and the least toxic chemical was Phos-Chek D75-F (96-hr IC5079 mg/liter). Un-ionized ammonia concentrations near the EC50or IC50value in tests with the Fire-Trol compounds were frequently equal to or above reported LC50un-ionized ammonia concentrations. Un-ionized ammonia concentrations in tests with Phos-Chek D75-F were low, thus other toxic components present in the compounds probably contributed to the toxicity. When compared to the daphnids tested in ASTM soft water, the Fire-Trol compounds were most toxic to algae, whereas Phos-Chek D75-F and the foam suppressants were most toxic to daphnids. The results of these tests are comparable to those obtained from research conducted in other laboratories with the same species and similar chemicals. Accidental entry of fire-fighting chemicals into aquatic environments could adversely affect algae and aquatic invertebrates, thus disrupting ecosystem function.

Temperature influence on chemical toxicity to aquatic organisms

International Nuclear Information System (INIS)

Cairns, J. Jr.; Heath, A.G.; Parker, B.C.

1975-01-01

The literature on the effects of temperature on chemical toxicity to aquatic animals and microorganisms is reviewed. Microbial photosynthesis and respiration is briefly discussed. It is concluded that there is a paucity of information on the inter-relations of temperature and toxicants to algae, bacteria, and protozoa and that standards based on the in situ response of indigenous organisms to specific discharge areas should be developed

Toxicity studies of drugs and chemicals in animals: An overview

OpenAIRE

S. Saganuwan

2017-01-01

Toxicity study is the investigation of either short or long-term toxic effects of a drug or chemical on animals. The toxicity is dose-dependent as asserted by Paracelsus over 500 years ago. However, short-term toxic effect is determined using median lethal dose (LD50) first introduced by Trevan in 1927 and revised many times. Presently there is a growing preponderance of rejection of scientific papers on acute toxicity study, simply because of the belief that in the current hazard and safety ...

Base catalyzed decomposition of toxic and hazardous chemicals

International Nuclear Information System (INIS)

Rogers, C.J.; Kornel, A.; Sparks, H.L.

1991-01-01

There are vast amounts of toxic and hazardous chemicals, which have pervaded our environment during the past fifty years, leaving us with serious, crucial problems of remediation and disposal. The accumulation of polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins (PCDDs), ''dioxins'' and pesticides in soil sediments and living systems is a serious problem that is receiving considerable attention concerning the cancer-causing nature of these synthetic compounds.US EPA scientists developed in 1989 and 1990 two novel chemical Processes to effect the dehalogenation of chlorinated solvents, PCBs, PCDDs, PCDFs, PCP and other pollutants in soil, sludge, sediment and liquids. This improved technology employs hydrogen as a nucleophile to replace halogens on halogenated compounds. Hydrogen as nucleophile is not influenced by steric hinderance as with other nucleophile where complete dehalogenation of organohalogens can be achieved. This report discusses catalyzed decomposition of toxic and hazardous chemicals

Toxic chemical considerations for tank farm releases

Energy Technology Data Exchange (ETDEWEB)

Van Keuren, J.C.; Davis, J.S., Westinghouse Hanford

1996-08-01

This topical report contains technical information used to determine the accident consequences of releases of toxic chemical and gases for the Tank Farm Final Safety Analysis report (FSAR).It does not provide results for specific accident scenarios but does provide information for use in those calculations including chemicals to be considered, chemical concentrations, chemical limits and a method of summing the fractional contributions of each chemical. Tank farm composites evaluated were liquids and solids for double shell tanks, single shell tanks, all solids,all liquids, headspace gases, and 241-C-106 solids. Emergency response planning guidelines (ERPGs) were used as the limits.Where ERPGs were not available for the chemicals of interest, surrogate ERPGs were developed. Revision 2 includes updated sample data, an executive summary, and some editorial revisions.

Oxidative stress in chemical toxicity

Energy Technology Data Exchange (ETDEWEB)

Kappus, H.

1986-05-01

The toxic effect of compounds which undergo redox cycling enzymatic one-electron reduction are reviewed. First of all, the enzymatic reduction of these compounds leads to reactive intermediates, mainly radicals which react with oxygen, whereby superoxide anion radicals are formed. Further oxygen metabolites are hydrogen peroxide, singlet oxygen and hydroxyl radicals. The role of these oxygen metabolites in toxicity is discussed. The occurrence of lipid peroxidation during redox cycling of quinonoide compounds, e.g., adriamycin, and the possible relationship to their toxicity is critically evaluated. It is shown that iron ions play a crucial role in lipid peroxidation induced by redox cycling compounds. DNA damage by metal chelates, e.g., bleomycin, is discussed on the basis of findings that enzymatic redox cycling of a bleomycin-iron complex has been observed. The involvement of hydroxyl radicals in bleomycin-induced DNA damage occurring during redox cycling in cell nuclei is claimed. Redox cycling of other substances, e.g., aromatic amines, is discussed in relation to carcinogenesis. Other chemical groups, e.g., nitroaromatic compounds, hydroxylamines and azo compounds are included. Other targets for oxygen radical attack, e.g., proteins, are also dealt with. It is concluded that oxygen radical formation by redox cycling may be a critical event in toxic effects of several compounds if the protective mechanisms of cells are overwhelmed.

A FLUORESCENCE BASED ASSAY FOR DNA DAMAGE INDUCED BY TOXIC INDUSTRIAL CHEMICALS

Science.gov (United States)

One of the reported effects for exposure to many of the toxic industrial chemicals is DNA damage. The present study describes a simple, rapid and innovative assay to detect DNA damage resulting from exposure of surrogate DNA to toxic industrial chemicals (acrolein, allylamine, ch...

Toxics Release Inventory Chemical Hazard Information Profiles (TRI-CHIP) Dataset

Data.gov (United States)

U.S. Environmental Protection Agency — The Toxics Release Inventory (TRI) Chemical Hazard Information Profiles (TRI-CHIP) dataset contains hazard information about the chemicals reported in TRI. Users can...

An assessment of the long-term impact of chemically toxic contaminants from the disposal of nuclear fuel waste

International Nuclear Information System (INIS)

Goodwin, B.W.; Garisto, N.C.; Barnard, J.W.

1987-01-01

This paper presents a study on the potential for impact on man of chemically toxic contaminants associated with the Canadian concept for the disposal of nuclear fuel waste. The elements of concern are determined through a series of screening criteria such as elemental abundances and solubilities. A systems variability analysis approach is then used to predict the possible concentrations of these elements that may arise in the biosphere. These concentrations are compared with environmental guidelines such as permissible levels in drinking water. Conclusions are made regarding the potential for the chemically toxic contaminants to have an impact on man. 54 refs

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....

The underlying toxicological mechanism of chemical mixtures: A case study on mixture toxicity of cyanogenic toxicants and aldehydes to Photobacterium phosphoreum

International Nuclear Information System (INIS)

Tian, Dayong; Lin, Zhifen; Zhou, Xianghong; Yin, Daqiang

2013-01-01

Intracellular chemical reaction of chemical mixtures is one of the main reasons that cause synergistic or antagonistic effects. However, it still remains unclear what the influencing factors on the intracellular chemical reaction are, and how they influence on the toxicological mechanism of chemical mixtures. To reveal this underlying toxicological mechanism of chemical mixtures, a case study on mixture toxicity of cyanogenic toxicants and aldehydes to Photobacterium phosphoreum was employed, and both their joint effects and mixture toxicity were observed. Then series of two-step linear regressions were performed to describe the relationships between joint effects, the expected additive toxicities and descriptors of individual chemicals (including concentrations, binding affinity to receptors, octanol/water partition coefficients). Based on the quantitative relationships, the underlying joint toxicological mechanisms were revealed. The result shows that, for mixtures with their joint effects resulting from intracellular chemical reaction, their underlying toxicological mechanism depends on not only their interaction with target proteins, but also their transmembrane actions and their concentrations. In addition, two generic points of toxicological mechanism were proposed including the influencing factors on intracellular chemical reaction and the difference of the toxicological mechanism between single reactive chemicals and their mixtures. This study provided an insight into the understanding of the underlying toxicological mechanism for chemical mixtures with intracellular chemical reaction. - Highlights: • Joint effects of nitriles and aldehydes at non-equitoxic ratios were determined. • A novel descriptor, ligand–receptor interaction energy (E binding ), was employed. • Quantitative relationships for mixtures were developed based on a novel descriptor. • The underlying toxic mechanism was revealed based on quantitative relationships. • Two generic

The underlying toxicological mechanism of chemical mixtures: A case study on mixture toxicity of cyanogenic toxicants and aldehydes to Photobacterium phosphoreum

Energy Technology Data Exchange (ETDEWEB)

Tian, Dayong [State Key Laboratory of Pollution Control and Resource Reuse, College of Environmental Science and Engineering, Tongji University, Shanghai 200092 (China); Department of Chemical and Environmental Engineering, Anyang Institute of Technology, Anyang 455000 (China); Lin, Zhifen, E-mail: lzhifen@tongji.edu.cn [State Key Laboratory of Pollution Control and Resource Reuse, College of Environmental Science and Engineering, Tongji University, Shanghai 200092 (China); Zhou, Xianghong [Department of Public Management, Tongji University, Shanghai 200092 (China); Yin, Daqiang [Key Laboratory of Yangtze River Water Environment, Ministry of Education, College of Environmental Science and Engineering, Tongji University, Shanghai 200092 (China)

2013-10-15

Intracellular chemical reaction of chemical mixtures is one of the main reasons that cause synergistic or antagonistic effects. However, it still remains unclear what the influencing factors on the intracellular chemical reaction are, and how they influence on the toxicological mechanism of chemical mixtures. To reveal this underlying toxicological mechanism of chemical mixtures, a case study on mixture toxicity of cyanogenic toxicants and aldehydes to Photobacterium phosphoreum was employed, and both their joint effects and mixture toxicity were observed. Then series of two-step linear regressions were performed to describe the relationships between joint effects, the expected additive toxicities and descriptors of individual chemicals (including concentrations, binding affinity to receptors, octanol/water partition coefficients). Based on the quantitative relationships, the underlying joint toxicological mechanisms were revealed. The result shows that, for mixtures with their joint effects resulting from intracellular chemical reaction, their underlying toxicological mechanism depends on not only their interaction with target proteins, but also their transmembrane actions and their concentrations. In addition, two generic points of toxicological mechanism were proposed including the influencing factors on intracellular chemical reaction and the difference of the toxicological mechanism between single reactive chemicals and their mixtures. This study provided an insight into the understanding of the underlying toxicological mechanism for chemical mixtures with intracellular chemical reaction. - Highlights: • Joint effects of nitriles and aldehydes at non-equitoxic ratios were determined. • A novel descriptor, ligand–receptor interaction energy (E{sub binding}), was employed. • Quantitative relationships for mixtures were developed based on a novel descriptor. • The underlying toxic mechanism was revealed based on quantitative relationships. • Two

Evaluation of Chemical Warfare Agent Percutaneous Vapor Toxicity: Derivation of Toxicity Guidelines for Assessing Chemical Protective Ensembles.

Energy Technology Data Exchange (ETDEWEB)

Watson, A.P.

2003-07-24

Percutaneous vapor toxicity guidelines are provided for assessment and selection of chemical protective ensembles (CPEs) to be used by civilian and military first responders operating in a chemical warfare agent vapor environment. The agents evaluated include the G-series and VX nerve agents, the vesicant sulfur mustard (agent HD) and, to a lesser extent, the vesicant Lewisite (agent L). The focus of this evaluation is percutaneous vapor permeation of CPEs and the resulting skin absorption, as inhalation and ocular exposures are assumed to be largely eliminated through use of SCBA and full-face protective masks. Selection of appropriately protective CPE designs and materials incorporates a variety of test parameters to ensure operability, practicality, and adequacy. One aspect of adequacy assessment should be based on systems tests, which focus on effective protection of the most vulnerable body regions (e.g., the groin area), as identified in this analysis. The toxicity range of agent-specific cumulative exposures (Cts) derived in this analysis can be used as decision guidelines for CPE acceptance, in conjunction with weighting consideration towards more susceptible body regions. This toxicity range is bounded by the percutaneous vapor estimated minimal effect (EME{sub pv}) Ct (as the lower end) and the 1% population threshold effect (ECt{sub 01}) estimate. Assumptions of exposure duration used in CPE certification should consider that each agent-specific percutaneous vapor cumulative exposure Ct for a given endpoint is a constant for exposure durations between 30 min and 2 hours.

Microbial contamination and chemical toxicity of the Rio Grande

Directory of Open Access Journals (Sweden)

Valles Adrian

2004-04-01

Full Text Available Abstract Background The Rio Grande River is the natural boundary between U.S. and Mexico from El Paso, TX to Brownsville, TX. and is one of the major water resources of the area. Agriculture, farming, maquiladora industry, domestic activities, as well as differences in disposal regulations and enforcement increase the contamination potential of water supplies along the border region. Therefore, continuous and accurate assessment of the quality of water supplies is of paramount importance. The objectives of this study were to monitor water quality of the Rio Grande and to determine if any correlations exist between fecal coliforms, E. coli, chemical toxicity as determined by Botsford's assay, H. pylori presence, and environmental parameters. Seven sites along a 112-Km segment of the Rio Grande from Sunland Park, NM to Fort Hancock, TX were sampled on a monthly basis between January 2000 and December 2002. Results The results showed great variability in the number of fecal coliforms, and E. coli on a month-to-month basis. Fecal coliforms ranged between 0–106 CFU/100 ml while E. coli ranged between 6 to > 2419 MPN. H. pylori showed positive detection for all the sites at different times. Toxicity ranged between 0 to 94% of inhibition capacity (IC. Since values above 50% are considered to be toxic, most of the sites displayed significant chemical toxicity at different times of the year. No significant correlations were observed between microbial indicators and chemical toxicity. Conclusion The results of the present study indicate that the 112-Km segment of the Rio Grande river from Sunland Park, NM to Fort Hancock, TX exceeds the standards for contact recreation water on a continuous basis. In addition, the presence of chemical toxicity in most sites along the 112-Km segment indicates that water quality is an area of concern for the bi-national region. The presence of H. pylori adds to the potential health hazards of the Rio Grande. Since no

Radiation treatment of toxic chemicals

International Nuclear Information System (INIS)

Lee, M.J.; Jung, I.H.; Jo, S.K.

2010-01-01

Polychlorinated biphenyls (PCBs) were commercially produced from 1920s as complex mixtures containing multiple isomers for a variety of applications. They are very toxic, chemically stable and resist microbial, photochemical, chemical, and thermal degradation. The public, legal, and scientific concerns about PCBs arose from research indicating they were environmental contaminants that had a potential to adversely impact the environment, and, therefore, were undesirable as commercial products. Eventually, most producers reduced or stopped production of PCBs in the 1970s. Stockholm convention on POPs (Persistent Organic Pollutants), which was effective on May 2004 and 151 nations including Korea were joined on June 2005, asked to dispose of PCBs by 2028 with environmental friendly methods. Korean government also has declared to conduct by 2015. According to the Environmental law of Korea, over 2 ppm of PCBs has to be decomposed by legal methods of incineration and thermal destruction. But those are inapplicable owing to the environmental groups. KAERI(Korea Atomic Energy Research Institute) has recently developed a remarkable technology for radiation treatment of toxic chemicals including chlorides using an electron beam accelerator. Electron beam accelerator of 2.5 MeV energy and 100 kW power capacity was used to decompose of PCBs having been used as a commercial transformer oil for more than 30 years. The oil were irradiated with ∼ 0.1 percent of TEA (Triethyl Amin) to make chloride ion aparted off from the PCBs into precipitate at the conditions of normal temperature and pressure. The concentrations of PCBs were measured by GC (Gas Chromatography) with ECD (Electron Capture Detector) following the KS (Korean Standard) test procedure. Electron beam should be a useful tool for environmental conservation. Residual concentrations of PCBs after irradiation were depended on the absorption dose of electron beam energy. Advantages comparing to other methods such as

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

Toxicity of selected organic chemicals to the earthworm Eisenia fetida

Energy Technology Data Exchange (ETDEWEB)

Neuhauser, E.F.; Loehr, R.C.; Malecki, M.R.; Milligan, D.L.; Durkin, P.R.

A number of methods recently have been developed to biologically evaluate the impact of man's activities on soil ecosystems. Two test methods, the 2-d contact test and the 14-d artificial soil test, were used to evaluate the impact of six major classes of organic chemicals on the earthworm Eisenia fetida (Savigny). Of the organic chemicals tested, phenols and amines were the most toxic to the worms, followed in descending order of toxicity by the substituted aromatics, halogenated aliphatics, polycyclic aromatic hydrocarbons, and phthalates. No relationship was found between earthworm toxicity as determined by the contact test and rat, Rattus norvegicus Berkenhout and mouse, Mus musculus L. LD/sub 50/ values. The physicochemical parameters of water solubility, vapor pressure, and octanol/water partition coefficient for the chemicals tested in the contact test did not show a significant relationship to the E. fetida LC/sub 50/ values. These studies indicate that: (i) earthworms can be a suitable biomonitoring tool to assist in measuring the impact of organic chemicals in wastes added to soils and (ii) contact and artificial soil tests can be useful in measuring biological impacts.

Generally applicable limits on intakes of uranium based on its chemical toxicity and the radiological significance of intakes at those limits

International Nuclear Information System (INIS)

Thorne, M C; Wilson, J

2015-01-01

Uranium is chemically toxic and radioactive, and both considerations have to be taken into account when limiting intakes of the element, in the context of both occupational and public exposures. Herein, the most recent information available on the chemical toxicity and biokinetics of uranium is used to propose new standards for limiting intakes of the element. The approach adopted allows coherent standards to be set for ingestion and inhalation of different chemical forms of the element by various age groups. It also allows coherent standards to be set for occupational and public exposures (including exposures of different age groups) and for various exposure regimes (including short-term and chronic exposures). The proposed standards are more restrictive than those used previously, but are less restrictive than the Minimal Risk Levels proposed recently by the US Agency for Toxic Substances and Disease Registry. Having developed a set of proposed limits based solely on chemical toxicity considerations, the radiological implications of exposure at those proposed limits are investigated for natural, depleted and enriched uranium. (paper)

40 CFR 372.45 - Notification about toxic chemicals.

Science.gov (United States)

2010-07-01

...) If the person considers the specific identity of a toxic chemical in a mixture or trade name product... corporate or business interest (including common ownership or control), as described in § 372.38(f), operate...

Toxic industrial chemicals and chemical weapons: exposure, identification, and management by syndrome.

Science.gov (United States)

Tomassoni, Anthony J; French, Robert N E; Walter, Frank G

2015-02-01

Toxidromes aid emergency care providers in the context of the patient presenting with suspected poisoning, unexplained altered mental status, unknown hazardous materials or chemical weapons exposure, or the unknown overdose. The ability to capture an adequate chemical exposure history and to recognize toxidromes may reduce dependence on laboratory tests, speed time to delivery of specific antidote therapy, and improve selection of supportive care practices tailored to the etiologic agent. This article highlights elements of the exposure history and presents selected toxidromes that may be caused by toxic industrial chemicals and chemical weapons. Specific antidotes for toxidromes and points regarding their use, and special supportive measures, are presented. Copyright © 2015 Elsevier Inc. All rights reserved.

Sampling the stratum corneum for toxic chemicals.

Science.gov (United States)

Coman, Garrett; Blickenstaff, Nicholas R; Blattner, Collin M; Andersen, Rosa; Maibach, Howard I

2014-01-01

Dermal exposure is an important pathway in environmental health. Exposure comes from contaminated water, soil, treated surfaces, textiles, aerosolized chemicals, and agricultural products. It can occur in homes, schools, play areas, and work settings in the form of industrial sources, consumer products, or hazardous wastes. Dermal exposure is most likely to occur through contact with liquids, water, soil, sediment, and contaminated surfaces. The ability to detect and measure exposure to toxic materials on the skin is an important environmental health issue. The stratum corneum is the skin's first and principal barrier layer of protection from the outside world. It has a complex structure that can effectively protect against a wide variety of physical, chemical, and biological contaminants. However, there are a variety of chemical agents that can damage the stratum corneum and the underlying epidermis, dermis and subcutis, and/or enter systemic circulation through the skin. There are numerous ways of sampling the stratum corneum for these toxic materials like abrasion techniques, biopsy, suction blistering, imaging, washing, wipe sampling, tape stripping, and spot testing. Selecting a method likely depends on the particular needs of the situation. Hence, there is a need to review practical considerations for their use in sampling the stratum corneum for toxins.

Fluorescence-based assay as a new screening tool for toxic chemicals

Science.gov (United States)

Moczko, Ewa; Mirkes, Evgeny M.; Cáceres, César; Gorban, Alexander N.; Piletsky, Sergey

2016-09-01

Our study involves development of fluorescent cell-based diagnostic assay as a new approach in high-throughput screening method. This highly sensitive optical assay operates similarly to e-noses and e-tongues which combine semi-specific sensors and multivariate data analysis for monitoring biochemical processes. The optical assay consists of a mixture of environmental-sensitive fluorescent dyes and human skin cells that generate fluorescence spectra patterns distinctive for particular physico-chemical and physiological conditions. Using chemometric techniques the optical signal is processed providing qualitative information about analytical characteristics of the samples. This integrated approach has been successfully applied (with sensitivity of 93% and specificity of 97%) in assessing whether particular chemical agents are irritating or not for human skin. It has several advantages compared with traditional biochemical or biological assays and can impact the new way of high-throughput screening and understanding cell activity. It also can provide reliable and reproducible method for assessing a risk of exposing people to different harmful substances, identification active compounds in toxicity screening and safety assessment of drugs, cosmetic or their specific ingredients.

Comparison of modeling approaches to prioritize chemicals based on estimates of exposure and exposure potential.

Science.gov (United States)

Mitchell, Jade; Arnot, Jon A; Jolliet, Olivier; Georgopoulos, Panos G; Isukapalli, Sastry; Dasgupta, Surajit; Pandian, Muhilan; Wambaugh, John; Egeghy, Peter; Cohen Hubal, Elaine A; Vallero, Daniel A

2013-08-01

While only limited data are available to characterize the potential toxicity of over 8 million commercially available chemical substances, there is even less information available on the exposure and use-scenarios that are required to link potential toxicity to human and ecological health outcomes. Recent improvements and advances such as high throughput data gathering, high performance computational capabilities, and predictive chemical inherency methodology make this an opportune time to develop an exposure-based prioritization approach that can systematically utilize and link the asymmetrical bodies of knowledge for hazard and exposure. In response to the US EPA's need to develop novel approaches and tools for rapidly prioritizing chemicals, a "Challenge" was issued to several exposure model developers to aid the understanding of current systems in a broader sense and to assist the US EPA's effort to develop an approach comparable to other international efforts. A common set of chemicals were prioritized under each current approach. The results are presented herein along with a comparative analysis of the rankings of the chemicals based on metrics of exposure potential or actual exposure estimates. The analysis illustrates the similarities and differences across the domains of information incorporated in each modeling approach. The overall findings indicate a need to reconcile exposures from diffuse, indirect sources (far-field) with exposures from directly, applied chemicals in consumer products or resulting from the presence of a chemical in a microenvironment like a home or vehicle. Additionally, the exposure scenario, including the mode of entry into the environment (i.e. through air, water or sediment) appears to be an important determinant of the level of agreement between modeling approaches. Copyright © 2013 Elsevier B.V. All rights reserved.

Comparison of modeling approaches to prioritize chemicals based on estimates of exposure and exposure potential

Science.gov (United States)

Mitchell, Jade; Arnot, Jon A.; Jolliet, Olivier; Georgopoulos, Panos G.; Isukapalli, Sastry; Dasgupta, Surajit; Pandian, Muhilan; Wambaugh, John; Egeghy, Peter; Cohen Hubal, Elaine A.; Vallero, Daniel A.

2014-01-01

While only limited data are available to characterize the potential toxicity of over 8 million commercially available chemical substances, there is even less information available on the exposure and use-scenarios that are required to link potential toxicity to human and ecological health outcomes. Recent improvements and advances such as high throughput data gathering, high performance computational capabilities, and predictive chemical inherency methodology make this an opportune time to develop an exposure-based prioritization approach that can systematically utilize and link the asymmetrical bodies of knowledge for hazard and exposure. In response to the US EPA’s need to develop novel approaches and tools for rapidly prioritizing chemicals, a “Challenge” was issued to several exposure model developers to aid the understanding of current systems in a broader sense and to assist the US EPA’s effort to develop an approach comparable to other international efforts. A common set of chemicals were prioritized under each current approach. The results are presented herein along with a comparative analysis of the rankings of the chemicals based on metrics of exposure potential or actual exposure estimates. The analysis illustrates the similarities and differences across the domains of information incorporated in each modeling approach. The overall findings indicate a need to reconcile exposures from diffuse, indirect sources (far-field) with exposures from directly, applied chemicals in consumer products or resulting from the presence of a chemical in a microenvironment like a home or vehicle. Additionally, the exposure scenario, including the mode of entry into the environment (i.e. through air, water or sediment) appears to be an important determinant of the level of agreement between modeling approaches. PMID:23707726

Exploring the role of quantum chemical descriptors in modeling acute toxicity of diverse chemicals to Daphnia magna.

Science.gov (United States)

Reenu; Vikas

2015-09-01

Various quantum-mechanically computed molecular and thermodynamic descriptors along with physico-chemical, electrostatic and topological descriptors are compared while developing quantitative structure-activity relationships (QSARs) for the acute toxicity of 252 diverse organic chemicals towards Daphnia magna. QSAR models based on the quantum-chemical descriptors, computed with routinely employed advanced semi-empirical and ab-initio methods, along with the electron-correlation contribution (CORR) of the descriptors, are analyzed for the external predictivity of the acute toxicity. The models with reliable internal stability and external predictivity are found to be based on the HOMO energy along with the physico-chemical, electrostatic and topological descriptors. Besides this, the total energy and electron-correlation energy are also observed as highly reliable descriptors, suggesting that the intra-molecular interactions between the electrons play an important role in the origin of the acute toxicity, which is in fact an unexplored phenomenon. The models based on quantum-chemical descriptors such as chemical hardness, absolute electronegativity, standard Gibbs free energy and enthalpy are also observed to be reliable. A comparison of the robust models based on the quantum-chemical descriptors computed with various quantum-mechanical methods suggests that the advanced semi-empirical methods such as PM7 can be more reliable than the ab-initio methods which are computationally more expensive. Copyright © 2015 Elsevier Inc. All rights reserved.

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.

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.

The chemical toxicity of cesium in Indian mustard (Brassica juncea L.) seedlings

International Nuclear Information System (INIS)

Lai, Jin-long; Tao, Zong-ya; Fu, Qian; Han, Na; Wu, Guo; Zhang, Hong; Lu, Hong; Luo, Xue-gang

2016-01-01

To distinguish between the radiological and chemical effects of radiocesium, we study the chemical toxicity of cesium in the seedlings of Indian mustard (Brassica juncea L.). In this study, the experiment was designed in two factors and five levels random block design to investigate the interaction effects of Cs and K. Results showed that excessive Cs was one of the main factors influence the growth of Brassica juncea seedlings. And the toxicity of Cs in Brassica juncea is likely to be caused by Cs interacts with K-binding sites in essential K-dependent protein, either competes with K for essential biochemical functions, causing intracellular metabolic disturbance. To test the hypothesis that the toxicity of Cs might cause intracellular metabolic disturbance, next-generation sequencing (NGS)-based Illumina paired-end Solexa sequencing platform was employed to analysis the changes in gene expression, and understand the key genes in B. juncea seedlings responding to the toxicity of Cs. Based on the assembled de novo transcriptome, 2032 DEGs that play significant roles in the response to the toxicity of Cs were identified. Further analysis showed that excessive Cs is disturbance the auxin signal transduction pathway, and inhibited the indoleacetic acid-induced protein (AUX/IAA) genes expression eventually lead the seedlings growth and development be inhibited. The results suggest that disturbances to tryptophan metabolism might be linked to changes in growth. - Highlights: • Analyze the chemical toxicity of cesium in seedlings of Indian mustard. • Distinguish between the radiological and chemical effects of radiocesium. • 2032 DEGs that play significant roles in the response to Cs toxicity were identified. • Excessive Cs is disturbance the auxin signal transduction pathway.

Effects of toxic metals and chemicals on biofilm and biocorrosion.

Science.gov (United States)

Fang, Herbert H P; Xu, Li-Chong; Chan, Kwong-Yu

2002-11-01

Microbes in marine biofilms aggregated into clusters and increased the production of extracellular polymeric substances (EPS), by over 100% in some cases, when the seawater media containing toxic metals and chemicals, such as Cd(II), Cu(II), Pb(II), Zn(II), AI(III), Cr(III), glutaraldehyde, and phenol. The formation of microbial cluster and the increased production of EPS, which contained 84-92% proteins and 8-16% polysaccharides, accelerated the corrosion of the mild steel. However, there was no quantitative relationship between the degree of increased corrosion and the toxicity of metals/chemicals towards sulfate-reducing bacteria, or the increased EPS production.

The current status of exposure-driven approaches for chemical safety assessment: A cross-sector perspective.

Science.gov (United States)

Sewell, Fiona; Aggarwal, Manoj; Bachler, Gerald; Broadmeadow, Alan; Gellatly, Nichola; Moore, Emma; Robinson, Sally; Rooseboom, Martijn; Stevens, Alexander; Terry, Claire; Burden, Natalie

2017-08-15

For the purposes of chemical safety assessment, the value of using non-animal (in silico and in vitro) approaches and generating mechanistic information on toxic effects is being increasingly recognised. For sectors where in vivo toxicity tests continue to be a regulatory requirement, there has been a parallel focus on how to refine studies (i.e. reduce suffering and improve animal welfare) and increase the value that in vivo data adds to the safety assessment process, as well as where to reduce animal numbers where possible. A key element necessary to ensure the transition towards successfully utilising both non-animal and refined safety testing is the better understanding of chemical exposure. This includes approaches such as measuring chemical concentrations within cell-based assays and during in vivo studies, understanding how predicted human exposures relate to levels tested, and using existing information on human exposures to aid in toxicity study design. Such approaches promise to increase the human relevance of safety assessment, and shift the focus from hazard-driven to risk-driven strategies similar to those used in the pharmaceutical sectors. Human exposure-based safety assessment offers scientific and 3Rs benefits across all sectors marketing chemical or medicinal products. The UK's National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) convened an expert working group of scientists across the agrochemical, industrial chemical and pharmaceutical industries plus a contract research organisation (CRO) to discuss the current status of the utilisation of exposure-driven approaches, and the challenges and potential next steps for wider uptake and acceptance. This paper summarises these discussions, highlights the challenges - particularly those identified by industry - and proposes initial steps for moving the field forward. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

Acute toxicity of fire-retardant and foam-suppressant chemicals to yalella azteca (Saussure)

Science.gov (United States)

McDonald, Susan F.; Hamilton, Steven J.; Buhl, Kevin J.; Heisinger, James F.

1997-01-01

Acute toxicity tests were conducted with Hyalella azteca Saussure (an amphipod) exposed in soft and hard waters to three fire retardants (Fire-Trol GTS-R, Fire-Trol LCG-R, and Phos-Chek D75-F) and two foam suppressants (Phos-Chek WD-881 and Silv-Ex). The chemicals were slightly to moderately toxic to amphipods. The most toxic chemical to amphipods in soft and hard water was Phos-Chek WD-881 (96-h mean lethal concentration [LC50] equal to 10 mg/L and 22 mg/L, respectively), and the least toxic chemical to amphipods in soft water was Fire-Trol GTS-R (96-h LC50 equal to 127 mg/L) and in hard water was Fire-Trol LCG-R (96-h LC50 equal to 535 mg/L). Concentrations of ammonia in tests with the three fire retardants and both water types were greater than reported LC50 values and probably were the major toxic component. Estimated un-ionized ammonia concentrations near the LC50 were frequently less than the reported LC50 ammonia concentrations for amphipods. The three fire retardants were more toxic in soft water than in hard water even though ammonia and un-ionized ammonia concentrations were higher in hard water tests than in soft water tests. The accidental entry of fire-fighting chemicals into aquatic environments could adversely affect aquatic invertebrates, thereby disrupting ecosystem function.

Fate of chemical warfare agents and toxic indutrial chemicals in landfills

DEFF Research Database (Denmark)

Bartelt-Hunt, D.L.; Barlaz, M.A.; Knappe, D.R.U.

2006-01-01

One component of preparedness for a chemical attack is planning for the disposal of contaminated debris. To assess the feasibility of contaminated debris disposal in municipal solid waste (MSW) landfills, the fate of selected chemical warfare agents (CWAs) and toxic industrial chemicals (TICs......], and two TICs [furan and carbon disulfide] were studied. The effects of both infiltration (climate) and contaminant biodegradability on fate predictions were assessed. Model results showed that hydrolysis and gas-phase advection were the principal fate pathways for CWAs and TICs, respectively. Apart from...... CX and the TICs, none of the investigated compounds was predicted to persist in a landfill for more than 5 years. Climate had little impact on CWA/TIC fate, and biodegradability was only important for compounds with long hydrolysis halflives. Monte Carlo simulations were performed to assess...

Toxicity of organic chemical pollution in groundwater downgradient of a landfill (Grindsted, Denmark)

DEFF Research Database (Denmark)

Baun, Anders; Jensen, S. D.; Bjerg, Poul Løgstrup

2000-01-01

The aim of the present study was to describe the occurrence and distribution of toxicity related to organic chemical contaminants in the leachate plume downgradient of the Grindsted Landfill (Denmark). A total of 27 groundwater samples were preconcentrated by solidphase extraction (SPE) using XAD-2...... bioassays, it was concluded that SPE extracts of groundwater collected close to the landfill were toxic. The toxicity decreased with the distance from the landfill. At distances greater than 80 m from the border of the landfill, the groundwater toxicity was not significantly different from the background...... characterization and hazard ranking of groundwater polluted with complex chemical mixtures, such as landfill leachates....

Use of computer-assisted prediction of toxic effects of chemical substances

International Nuclear Information System (INIS)

Simon-Hettich, Brigitte; Rothfuss, Andreas; Steger-Hartmann, Thomas

2006-01-01

The current revision of the European policy for the evaluation of chemicals (REACH) has lead to a controversy with regard to the need of additional animal safety testing. To avoid increases in animal testing but also to save time and resources, alternative in silico or in vitro tests for the assessment of toxic effects of chemicals are advocated. The draft of the original document issued in 29th October 2003 by the European Commission foresees the use of alternative methods but does not give further specification on which methods should be used. Computer-assisted prediction models, so-called predictive tools, besides in vitro models, will likely play an essential role in the proposed repertoire of 'alternative methods'. The current discussion has urged the Advisory Committee of the German Toxicology Society to present its position on the use of predictive tools in toxicology. Acceptable prediction models already exist for those toxicological endpoints which are based on well-understood mechanism, such as mutagenicity and skin sensitization, whereas mechanistically more complex endpoints such as acute, chronic or organ toxicities currently cannot be satisfactorily predicted. A potential strategy to assess such complex toxicities will lie in their dissection into models for the different steps or pathways leading to the final endpoint. Integration of these models should result in a higher predictivity. Despite these limitations, computer-assisted prediction tools already today play a complementary role for the assessment of chemicals for which no data is available or for which toxicological testing is impractical due to the lack of availability of sufficient compounds for testing. Furthermore, predictive tools offer support in the screening and the subsequent prioritization of compound for further toxicological testing, as expected within the scope of the European REACH program. This program will also lead to the collection of high-quality data which will broaden the

An Acetyltransferase Conferring Tolerance to Toxic Aromatic Amine Chemicals

Science.gov (United States)

Martins, Marta; Rodrigues-Lima, Fernando; Dairou, Julien; Lamouri, Aazdine; Malagnac, Fabienne; Silar, Philippe; Dupret, Jean-Marie

2009-01-01

Aromatic amines (AA) are a major class of environmental pollutants that have been shown to have genotoxic and cytotoxic potentials toward most living organisms. Fungi are able to tolerate a diverse range of chemical compounds including certain AA and have long been used as models to understand general biological processes. Deciphering the mechanisms underlying this tolerance may improve our understanding of the adaptation of organisms to stressful environments and pave the way for novel pharmaceutical and/or biotechnological applications. We have identified and characterized two arylamine N-acetyltransferase (NAT) enzymes (PaNAT1 and PaNAT2) from the model fungus Podospora anserina that acetylate a wide range of AA. Targeted gene disruption experiments revealed that PaNAT2 was required for the growth and survival of the fungus in the presence of toxic AA. Functional studies using the knock-out strains and chemically acetylated AA indicated that tolerance of P. anserina to toxic AA was due to the N-acetylation of these chemicals by PaNAT2. Moreover, we provide proof-of-concept remediation experiments where P. anserina, through its PaNAT2 enzyme, is able to detoxify the highly toxic pesticide residue 3,4-dichloroaniline in experimentally contaminated soil samples. Overall, our data show that a single xenobiotic-metabolizing enzyme can mediate tolerance to a major class of pollutants in a eukaryotic species. These findings expand the understanding of the role of xenobiotic-metabolizing enzyme and in particular of NATs in the adaptation of organisms to their chemical environment and provide a basis for new systems for the bioremediation of contaminated soils. PMID:19416981

78 FR 69414 - Toxic Substances Control Act Chemical Testing; Receipt of Test Data

Science.gov (United States)

2013-11-19

...; Acute emulsion polymerization in Inhalation Toxicity in paper, textile, fiber, and Rats; Bacterial.../ Reproduction Development Toxicity. Note: CAS No. = Chemical Abstracts Service Registry Number. Authority: 15 U...

Plant exposure chambers for study of toxic chemical-plant interactions (journal version)

International Nuclear Information System (INIS)

McFarlane, J.C.; Pfleeger, T.

1987-01-01

Chambers for the study of plant uptake and phytotoxicity of toxic, radio-labeled chemicals are described. The chambers are designed to meet the criteria of continuously stirred tank reactors while providing containment for toxic chemicals. They are computer managed and operated within a controlled-environment room. Besides providing controlled conditions within the contained spaces, continuous measurements are made of various environmental parameters and plant transpiration, net photosynthesis, and dark respiration in up to 18 separate chambers

Metal and proton toxicity to lake zooplankton: A chemical speciation based modelling approach

International Nuclear Information System (INIS)

Stockdale, Anthony; Tipping, Edward; Lofts, Stephen; Fott, Jan; Garmo, Øyvind A.; Hruska, Jakub; Keller, Bill; Löfgren, Stefan; Maberly, Stephen C.; Majer, Vladimir; Nierzwicki-Bauer, Sandra A.; Persson, Gunnar; Schartau, Ann-Kristin; Thackeray, Stephen J.

2014-01-01

The WHAM-F TOX model quantifies the combined toxic effects of protons and metal cations towards aquatic organisms through the toxicity function (F TOX ), a linear combination of the products of organism-bound cation and a toxic potency coefficient for each cation. We describe the application of the model to predict an observable ecological field variable, species richness of pelagic lake crustacean zooplankton, studied with respect to either acidification or the impacts of metals from smelters. The fitted results give toxic potencies increasing in the order H + TOX to relate combined toxic effects of protons and metal cations towards lake crustacean zooplankton. • The fitted results give toxic potencies increasing in the order H + TOX model has been applied to field data for pelagic lake crustacean zooplankton. The fitted results give metal toxic potencies increasing in the order H + < Al < Cu < Zn < Ni

Cobalt toxicity: Chemical and radiological combined effects on HaCaT keratinocyte cell line

International Nuclear Information System (INIS)

Sandre, C.; Moulin, C.; Bresson, C.; Gault, N.; Poncy, J. L.; Lefaix, J. L.

2010-01-01

Cobalt (Co) is an essential trace element well known as a constituent of vitamin B 12 , but different compounds of Co are also described as highly toxic and/or radio-toxic for individuals or the environment. In nuclear power plants, 58 Co and 60 Co are radioactive isotopes of cobalt present as activation products of stable Co and Ni used in alloys. Skin exposure is a current occupational risk in the hard metal and nuclear industries. As biochemical and molecular cobalt-induced toxicological mechanisms are not fully identified, we investigated cobalt toxicity in a model human keratinocyte cell line, HaCaT. In this study, we propose a model to determine the in vitro chemical impact on cell viability of a soluble form of cobalt (CoCl 2 ) with or without gamma-ray doses to mimic contamination by 60 Co, to elucidate the mechanisms of cobalt intracellular chemical and radiological toxicity. Intracellular cobalt concentration was determined after HaCaT cell contamination and chemical toxicity was evaluated in terms of cellular viability and clonogenic survival. We investigated damage to DNA in HaCaT cells by combined treatment with chemical cobalt and a moderate gamma-ray dose. Additive effects of cobalt and irradiation were demonstrated. The underlying mechanism of cobalt toxicity is not clearly established, but our results seem to indicate that the toxicity of Co(II) and of irradiation arises from production of reactive oxygen species. (authors)

Cobalt toxicity: Chemical and radiological combined effects on HaCaT keratinocyte cell line

Energy Technology Data Exchange (ETDEWEB)

Gault, N. [CEA Fontenay aux Roses, DSV/IRCM/SCSR/LRTS, 92265 Fontenay aux Rose (France); Sandre, C.; Moulin, B.; Bresson, C. [CEA, DEN, SECR, Laboratoire de Speciation des Radionucleides et des Molecules, F-91191 Gif-sur-Yvette (France); Poncy, J.L. [CEA Bruyeres Le Chatel, DSV/IRCM/SREIT/LRT, 91680 Bruyeres Le Chatel (France); Lefaix, J.L. [CEA Caen, DSV/IRCM/SRO/LARIA, 14070 Caen (France)

2010-07-01

Cobalt (Co) is an essential trace element well known as a constituent of vitamin B12, but different compounds of Co are also described as highly toxic and/or radio-toxic for individuals or the environment. In nuclear power plants, {sup 58}Co and {sup 60}Co are radioactive isotopes of cobalt present as activation products of stable Co and Ni used in alloys. Skin exposure is a current occupational risk in the hard metal and nuclear industries. As biochemical and molecular cobalt-induced toxicological mechanisms are not fully identified, we investigated cobalt toxicity in a model human keratinocyte cell line, HaCaT. In this study, we propose a model to determine the in vitro chemical impact on cell viability of a soluble form of cobalt (CoCl{sub 2}) with or without {gamma}-ray doses to mimic contamination by {sup 60}Co, to elucidate the mechanisms of cobalt intracellular chemical and radiological toxicity. Intracellular cobalt concentration was determined after HaCaT cell contamination and chemical toxicity was evaluated in terms of cellular viability and clonogenic survival. We investigated damage to DNA in HaCaT cells by combined treatment with chemical cobalt and a moderate {gamma}-ray dose. Additive effects of cobalt and irradiation were demonstrated. The underlying mechanism of cobalt toxicity is not clearly established, but our results seem to indicate that the toxicity of Co(II) and of irradiation arises from production of reactive oxygen species. (authors)

Cobalt toxicity: Chemical and radiological combined effects on HaCaT keratinocyte cell line

Energy Technology Data Exchange (ETDEWEB)

Sandre, C.; Moulin, C.; Bresson, C. [CEA Saclay, DEN, SECR, Lab Speciat Radionucleides and Mol, F-91191 Gif Sur Yvette (France); Gault, N. [CEA Fontenay Roses, DSV IRCM SCSR LRTS, F-92265 Fontenay Aux Roses (France); Poncy, J. L. [CEA Bruyeres Le Chatel, DSV IRCM SREIT LRT, F-91680 Bruyeres Le Chatel (France); Lefaix, J. L. [CEA Caen, DSV IRCM SRO LARIA, F-14070 Caen (France)

2010-07-01

Cobalt (Co) is an essential trace element well known as a constituent of vitamin B{sub 12}, but different compounds of Co are also described as highly toxic and/or radio-toxic for individuals or the environment. In nuclear power plants, {sup 58}Co and {sup 60}Co are radioactive isotopes of cobalt present as activation products of stable Co and Ni used in alloys. Skin exposure is a current occupational risk in the hard metal and nuclear industries. As biochemical and molecular cobalt-induced toxicological mechanisms are not fully identified, we investigated cobalt toxicity in a model human keratinocyte cell line, HaCaT. In this study, we propose a model to determine the in vitro chemical impact on cell viability of a soluble form of cobalt (CoCl{sub 2}) with or without gamma-ray doses to mimic contamination by {sup 60}Co, to elucidate the mechanisms of cobalt intracellular chemical and radiological toxicity. Intracellular cobalt concentration was determined after HaCaT cell contamination and chemical toxicity was evaluated in terms of cellular viability and clonogenic survival. We investigated damage to DNA in HaCaT cells by combined treatment with chemical cobalt and a moderate gamma-ray dose. Additive effects of cobalt and irradiation were demonstrated. The underlying mechanism of cobalt toxicity is not clearly established, but our results seem to indicate that the toxicity of Co(II) and of irradiation arises from production of reactive oxygen species. (authors)

Elucidating mechanisms of toxic action of dissolved organic chemicals in oil sands process-affected water (OSPW).

Science.gov (United States)

Morandi, Garrett D; Wiseman, Steve B; Guan, Miao; Zhang, Xiaowei W; Martin, Jonathan W; Giesy, John P

2017-11-01

Oil sands process-affected water (OSPW) is generated during extraction of bitumen in the surface-mining oil sands industry in Alberta, Canada, and is acutely and chronically toxic to aquatic organisms. It is known that dissolved organic compounds in OSPW are responsible for most toxic effects, but knowledge of the specific mechanism(s) of toxicity, is limited. Using bioassay-based effects-directed analysis, the dissolved organic fraction of OSPW has previously been fractionated, ultimately producing refined samples of dissolved organic chemicals in OSPW, each with distinct chemical profiles. Using the Escherichia coli K-12 strain MG1655 gene reporter live cell array, the present study investigated relationships between toxic potencies of each fraction, expression of genes and characterization of chemicals in each of five acutely toxic and one non-toxic extract of OSPW derived by use of effects-directed analysis. Effects on expressions of genes related to response to oxidative stress, protein stress and DNA damage were indicative of exposure to acutely toxic extracts of OSPW. Additionally, six genes were uniquely responsive to acutely toxic extracts of OSPW. Evidence presented supports a role for sulphur- and nitrogen-containing chemical classes in the toxicity of extracts of OSPW. Copyright © 2017 Elsevier Ltd. All rights reserved.

Chemical toxicity and radiological health detriment associated with the inhalation of various enrichments of uranium

International Nuclear Information System (INIS)

3C Limited, Queen Square House, 18-21 Queen Square, Bristol BS1 4NH (United Kingdom))" data-affiliation=" (SR3C Limited, Queen Square House, 18-21 Queen Square, Bristol BS1 4NH (United Kingdom))" >Bryant, P A

2014-01-01

The occupational risks associated with the chemical toxicity of uranium can be overlooked during the processing, handling and storage of the material, as the radioactivity of the material is often used alone to assess the health consequences of exposure to uranium compounds. This note provides a summary of the current United Kingdom occupational standards for uranium based on radiation dose and/or chemical toxicity with a particular focus on intake via inhalation. A simple model is subsequently presented to allow a comparison to be drawn between the occupational exposure standard for chemical toxicity and radiological dose limit. Using these data a set of suggested limits on occupational exposure to airborne uranium is proposed that indicate where the legal annual radiological dose limit for workers or the Health and Safety Executive occupational exposure standard for chemical toxicity are at risk of being breached. (note)

Acclimation of Chlamydomonas reinhardtii to ultraviolet radiation and its impact on chemical toxicity

Energy Technology Data Exchange (ETDEWEB)

Korkaric, Muris; Xiao, Mao [Eawag, Swiss Federal Institute of Aquatic Science and Technology, Department of Environmental Toxicology, 8600 Duebendorf (Switzerland); ETH Zürich, Institute of Biogeochemistry and Pollutant Dynamics, 8092 Zürich (Switzerland); Behra, Renata [Eawag, Swiss Federal Institute of Aquatic Science and Technology, Department of Environmental Toxicology, 8600 Duebendorf (Switzerland); Eggen, Rik I.L., E-mail: rik.eggen@eawag.ch [Eawag, Swiss Federal Institute of Aquatic Science and Technology, Department of Environmental Toxicology, 8600 Duebendorf (Switzerland); ETH Zürich, Institute of Biogeochemistry and Pollutant Dynamics, 8092 Zürich (Switzerland)

2015-10-15

Highlights: • Systematic study of UVR acclimation and its impact on chemical toxicity in C. reinhardtii. • UVR acclimation is mediated through fast and reversible physiological defense mechanisms. • Pigment analysis suggests a role of lutein in UVR acclimation. • Co-tolerance to rose bengal suggests a role of singlet oxygen defense in UVR acclimation. • Knowledge on the toxic mechanism of chemicals needed to predict co-tolerance. - Abstract: The toxicity of chemical pollutants can be modulated under stressful environmental conditions, such as increased temperature, salinity or ultraviolet radiation (UVR), due to the interaction of effects during simultaneous stressor exposure. However, organisms may acclimate to such conditions by activation of physiological and biochemical defence mechanisms. In sequential exposures, organisms acclimated to environmental stressors may display an increased sensitivity or co-tolerance towards chemical pollutants. It has been suggested that co-tolerance might be expected for similarly acting stressors due to common defence mechanisms. To test this for combinations of UVR and chemical stressors, we first acclimatized the model green alga Chlamydomonas reinhardtii to UVR and subsequently compared the sensitivity of UVR pre-exposed and control algae towards chemicals. Selected chemicals all act on photosynthesis and thus share a common physiological target, but display distinct toxicity mechanisms. Results showed that UVR pre-exposure for four days partially inhibited algal growth and photosynthesis, but also increased algal tolerance to higher UVR levels, confirming UVR acclimation. HPLC analysis of algal pigments indicated that UVR acclimation might in part be explained by the protective function of lutein while the contribution of UVR absorbing compounds was less clear. Challenge exposure to chemicals in the absence of UVR showed that acclimated algae were co-tolerant to the photosensitizer rose bengal, but not to the

Acclimation of Chlamydomonas reinhardtii to ultraviolet radiation and its impact on chemical toxicity

International Nuclear Information System (INIS)

Korkaric, Muris; Xiao, Mao; Behra, Renata; Eggen, Rik I.L.

2015-01-01

Highlights: • Systematic study of UVR acclimation and its impact on chemical toxicity in C. reinhardtii. • UVR acclimation is mediated through fast and reversible physiological defense mechanisms. • Pigment analysis suggests a role of lutein in UVR acclimation. • Co-tolerance to rose bengal suggests a role of singlet oxygen defense in UVR acclimation. • Knowledge on the toxic mechanism of chemicals needed to predict co-tolerance. - Abstract: The toxicity of chemical pollutants can be modulated under stressful environmental conditions, such as increased temperature, salinity or ultraviolet radiation (UVR), due to the interaction of effects during simultaneous stressor exposure. However, organisms may acclimate to such conditions by activation of physiological and biochemical defence mechanisms. In sequential exposures, organisms acclimated to environmental stressors may display an increased sensitivity or co-tolerance towards chemical pollutants. It has been suggested that co-tolerance might be expected for similarly acting stressors due to common defence mechanisms. To test this for combinations of UVR and chemical stressors, we first acclimatized the model green alga Chlamydomonas reinhardtii to UVR and subsequently compared the sensitivity of UVR pre-exposed and control algae towards chemicals. Selected chemicals all act on photosynthesis and thus share a common physiological target, but display distinct toxicity mechanisms. Results showed that UVR pre-exposure for four days partially inhibited algal growth and photosynthesis, but also increased algal tolerance to higher UVR levels, confirming UVR acclimation. HPLC analysis of algal pigments indicated that UVR acclimation might in part be explained by the protective function of lutein while the contribution of UVR absorbing compounds was less clear. Challenge exposure to chemicals in the absence of UVR showed that acclimated algae were co-tolerant to the photosensitizer rose bengal, but not to the

A Decision Analytic Approach to Exposure-Based Chemical ...

Science.gov (United States)

The manufacture of novel synthetic chemicals has increased in volume and variety, but often the environmental and health risks are not fully understood in terms of toxicity and, in particular, exposure. While efforts to assess risks have generally been effective when sufficient data are available, the hazard and exposure data necessary to assess risks adequately are unavailable for the vast majority of chemicals in commerce. The US Environmental Protection Agency has initiated the ExpoCast Program to develop tools for rapid chemical evaluation based on potential for exposure. In this context, a model is presented in which chemicals are evaluated based on inherent chemical properties and behaviorally-based usage characteristics over the chemical’s life cycle. These criteria are assessed and integrated within a decision analytic framework, facilitating rapid assessment and prioritization for future targeted testing and systems modeling. A case study outlines the prioritization process using 51 chemicals. The results show a preliminary relative ranking of chemicals based on exposure potential. The strength of this approach is the ability to integrate relevant statistical and mechanistic data with expert judgment, allowing for an initial tier assessment that can further inform targeted testing and risk management strategies. The National Exposure Research Laboratory′s (NERL′s) Human Exposure and Atmospheric Sciences Division (HEASD) conducts research in suppor

2001 Toxic Chemical Release Inventory Emergency Planning and Community Right to Know Act SEC 313

International Nuclear Information System (INIS)

ZALOUDEK, D.E.

2002-01-01

Pursuant to section 313 of the Emergency Planning and Community Right-To-Know Act of 1986 (EPCRA), and Executive Order 13148, Greening the Government Through Leadership in Environmental Management, the US Department of Energy has prepared and submitted a Toxic Chemical Release Inventory for the Hanford Site covering activities performed during calendar year 2001. EPCRA Section 313 requires facilities that manufacture, process, or otherwise use listed toxic chemicals in quantities exceeding established threshold levels to report total annual releases of those chemicals. During calendar year 2001, Hanford Site activities resulted in one chemical used in amounts exceeding an activity threshold. Accordingly, the Hanford Site 2001 Toxic Chemical Release Inventory, DOE/RL-2002-37, includes total annual amount of lead released to the environment, transferred to offsite locations, and otherwise managed as waste

The ChemScreen project to design a pragmatic alternative approach to predict reproductive toxicity of chemicals

DEFF Research Database (Denmark)

van der Burg, Bart; Wedebye, Eva Bay; Dietrich, Daniel R.

2015-01-01

to validate the test panel using mechanistic approaches. We are actively engaged in promoting regulatory acceptance of the tools developed as an essential step towards practical application, including case studies for read-across purposes. With this approach, a significant saving in animal use and associated......There is a great need for rapid testing strategies for reproductive toxicity testing, avoiding animal use. The EU Framework program 7 project ChemScreen aimed to fill this gap in a pragmatic manner preferably using validated existing tools and place them in an innovative alternative testing...

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

Toxics release inventory: List of toxic chemicals within the polychlorinated alkanes category and guidance for reporting

Energy Technology Data Exchange (ETDEWEB)

NONE

1995-02-01

Section 313 of the Emergency Planning and Community Right-to-Know Act of 1986 (EPCRA) requires certain facilities manufacturing, processing, or otherwise using listed toxic chemicals to report their environmental releases of such chemicals annually. On November 30, 1994 EPA added 286 chemicals and chemical categories. Six chemical categories (nicotine and salts, strychnine and salts, polycyclic aromatic compounds, water dissociable nitrate compounds, diisocyanates, and polychlorinated alkanes) are included in these additions. At the time of the addition, EPA indicated that the Agency would develop, as appropriate, interpretations and guidance that the Agency determines are necessary to facilitate accurate reporting for these categories. This document constitutes such guidance for the polychlorinated alkanes category.

Using combined bio-omics methods to evaluate the complicated toxic effects of mixed chemical wastewater and its treated effluent

International Nuclear Information System (INIS)

Zhang, Yan; Deng, Yongfeng; Zhao, Yanping; Ren, Hongqiang

2014-01-01

Highlights: • Mice exposed to mixed chemical wastewater and its treated effluent for 90 days. • Hepatic transcriptomic alterations were analyzed by digital gene expression. • Serum metabolomic alterations were analyzed by proton nuclear magnetic resonance. • The water samples induced disruption of lipid metabolism and hepatotoxicity. • Omics approaches are valuable to evaluate the complicated toxicity of wastewater. - Abstract: Mixed chemical wastewaters (MCWW) from industrial park contain complex mixtures of trace contaminants, which cannot be effectively removed by wastewater treatment plants (WWTP) and have become an unignored threat to ambient environment. However, limited information is available to evaluate the complicated toxic effects of MCWW and its effluent from wastewater treatment plant (WTPE) from the perspective of bio-omics. In this study, mice were exposed to the MCWW and WTPE for 90 days and distinct differences in the hepatic transcriptome and serum metabolome were analyzed by digital gene expression (DGE) and proton nuclear magnetic resonance ( 1 H-NMR) spectra, respectively. Our results indicated that disruption of lipid metabolism in liver and hepatotoxicity were induced by both MCWW and WTPE exposure. WTPE is still a health risk to the environment, which is in need of more attention. Furthermore, we demonstrated the potential ability of bio-omics approaches for evaluating toxic effects of MCWW and WTPE

Using combined bio-omics methods to evaluate the complicated toxic effects of mixed chemical wastewater and its treated effluent

Energy Technology Data Exchange (ETDEWEB)

Zhang, Yan; Deng, Yongfeng; Zhao, Yanping; Ren, Hongqiang, E-mail: hqren@nju.edu.cn

2014-05-01

Highlights: • Mice exposed to mixed chemical wastewater and its treated effluent for 90 days. • Hepatic transcriptomic alterations were analyzed by digital gene expression. • Serum metabolomic alterations were analyzed by proton nuclear magnetic resonance. • The water samples induced disruption of lipid metabolism and hepatotoxicity. • Omics approaches are valuable to evaluate the complicated toxicity of wastewater. - Abstract: Mixed chemical wastewaters (MCWW) from industrial park contain complex mixtures of trace contaminants, which cannot be effectively removed by wastewater treatment plants (WWTP) and have become an unignored threat to ambient environment. However, limited information is available to evaluate the complicated toxic effects of MCWW and its effluent from wastewater treatment plant (WTPE) from the perspective of bio-omics. In this study, mice were exposed to the MCWW and WTPE for 90 days and distinct differences in the hepatic transcriptome and serum metabolome were analyzed by digital gene expression (DGE) and proton nuclear magnetic resonance ({sup 1}H-NMR) spectra, respectively. Our results indicated that disruption of lipid metabolism in liver and hepatotoxicity were induced by both MCWW and WTPE exposure. WTPE is still a health risk to the environment, which is in need of more attention. Furthermore, we demonstrated the potential ability of bio-omics approaches for evaluating toxic effects of MCWW and WTPE.

The complex interaction between marine debris and toxic chemicals in the ocean.

Science.gov (United States)

Engler, Richard E

2012-11-20

Marine debris, especially plastic debris, is widely recognized as a global environmental problem. There has been substantial research on the impacts of plastic marine debris, such as entanglement and ingestion. These impacts are largely due to the physical presence of plastic debris. In recent years there has been an increasing focus on the impacts of toxic chemicals as they relate to plastic debris. Some plastic debris acts as a source of toxic chemicals: substances that were added to the plastic during manufacturing leach from plastic debris. Plastic debris also acts as a sink for toxic chemicals. Plastic sorbs persistent, bioaccumulative, and toxic substances (PBTs), such as polychlorinated biphenyls (PCBs) and dioxins, from the water or sediment. These PBTs may desorb when the plastic is ingested by any of a variety of marine species. This broad look at the current research suggests that while there is significant uncertainty and complexity in the kinetics and thermodynamics of the interaction, plastic debris appears to act as a vector transferring PBTs from the water to the food web, increasing risk throughout the marine food web, including humans. Because of the extremely long lifetime of plastic and PBTs in the ocean, prevention strategies are vital to minimizing these risks.

MULTIDISCIPLINARY APPROACH TO TOXICOLOGICAL SCREENING: I. SYSTEMIC TOXICITY

Science.gov (United States)

The toxicity of 10 chemicals (carbaryl, carbon tetrachloride, chlordane, ethylhexylphthalate, dichloromethane, heptachlor, phenol, tetrachloroethylene, triadimefon, and trichloroethylene were examined in the liver, kidney, spleen, thymus, and adrenal of female F-344 rats. cute le...

Handbook of acute toxicity of chemicals to fish and aquatic invertebrates : summaries of toxicity tests conducted at Columbia National Fisheries Research Laboratory, 1965-78

Science.gov (United States)

Johnson, W. Waynon; Finley, Mack T.

1980-01-01

Acute toxicity is a major subject of research at Columbia National Fisheries Research Laboratory for evaluating the impact of toxic chemicals on fishery resources. The Laboratory has played a leading role in developing research technology for toxicity testing and data interpretation. In 1965-78, more than 400 chemicals were tested against a variety of invertebrates and fish species representative of both cold- and warm-water climates.The use of acute toxicity tests for assessing the potential hazard of chemical contaminants to aquatic organisms is well documented (Boyd 1957; Henderson et al. 1960; Sanders and Cope 1966; Macek and McAllister 1970). Static acute toxicity tests provide rapid and (within limits) reproducible concentration-response curves for estimating toxic effects of chemicals on aquatic organisms. These tests provide a database for determining relative toxicity of a large number of chemicals to a variety of species and for estimating acute effects of chemical spills on natural aquatic systems; they also assist in determining priority and design of additional toxicity studies.Acute toxicity tests usually provide estimates of the exposure concentration causing 50% mortality (LC50) to test organisms during a specified period of time. For certain invertebrates, the effective concentration is based on immobilization, or some other identifiable endpoint, rather than on lethality. The application of the LC50 has gained acceptance among toxicologists and is generally the most highly rated test for assessing potential adverse effects of chemical contaminants to aquatic life (Brungs and Mount 1978; American Institute for Biological Sciences 1978a).The literature contains numerous papers dealing with the acute toxicity of chemicals to freshwater organisms. However, there is a tremendous need for a concise compendium of toxicity data covering a large variety of chemicals and test species. This Handbook is a compilation of a large volume of acute toxicity data

Comparing rankings of selected TRI organic chemicals for two environments using a level III fugacity model and toxicity

International Nuclear Information System (INIS)

Edwards, F.G.; Egemen, E.; Nirmalakhandan, N.

1998-01-01

The Toxics Release Inventory, TRI (USEPA, 1995) is a comprehensive listing of chemicals, mass released, source of releases, and other related information for chemicals which are released into the environment in the US. These chemicals are then ranked according to the mass released as a indication of their environmental impact. Industries have been encouraged to adopt production methods to decrease the release of chemicals which are ranked highly in the TRI. Clearly, this ranking of the chemicals based upon the mass released fails to take into account very important environmental aspects. The first and most obvious aspect is the wide range of toxicity's of the chemicals released. Numerous researchers have proposed systems to rank chemicals according to their toxicity. The second aspect, which a mass released based ranking does not take into account, is the fate and transport of each chemical within the environment. Cohen and Ryan (1985) and Mackay and Paterson (1991) have proposed models to evaluate the fate and transport of chemicals released into the environment. Some authors have incorporated the mass released and toxicity with some fate and transport aspects to rank the impact of released chemicals. But, due to the complexities of modeling the environment, the lack of published data on properties of chemicals, and the lack of information on the speciation of chemicals in complex systems, modeling the fate and transport of toxic chemicals in the environment remains difficult. To provide an indication of the need to rank chemicals according to their environmental impact instead of the mass released, the authors have utilized a subset of 45 organic chemicals from the TRI, modeled the fate and transport of the chemicals using a Level III fugacity model, and compared those equilibrium concentrations with toxicity data to yield a hazard value for each chemical

An Inverse Analysis Approach to the Characterization of Chemical Transport in Paints

Science.gov (United States)

Willis, Matthew P.; Stevenson, Shawn M.; Pearl, Thomas P.; Mantooth, Brent A.

2014-01-01

The ability to directly characterize chemical transport and interactions that occur within a material (i.e., subsurface dynamics) is a vital component in understanding contaminant mass transport and the ability to decontaminate materials. If a material is contaminated, over time, the transport of highly toxic chemicals (such as chemical warfare agent species) out of the material can result in vapor exposure or transfer to the skin, which can result in percutaneous exposure to personnel who interact with the material. Due to the high toxicity of chemical warfare agents, the release of trace chemical quantities is of significant concern. Mapping subsurface concentration distribution and transport characteristics of absorbed agents enables exposure hazards to be assessed in untested conditions. Furthermore, these tools can be used to characterize subsurface reaction dynamics to ultimately design improved decontaminants or decontamination procedures. To achieve this goal, an inverse analysis mass transport modeling approach was developed that utilizes time-resolved mass spectroscopy measurements of vapor emission from contaminated paint coatings as the input parameter for calculation of subsurface concentration profiles. Details are provided on sample preparation, including contaminant and material handling, the application of mass spectrometry for the measurement of emitted contaminant vapor, and the implementation of inverse analysis using a physics-based diffusion model to determine transport properties of live chemical warfare agents including distilled mustard (HD) and the nerve agent VX. PMID:25226346

Chemical composition and toxicities of essential oil of Illicium ...

African Journals Online (AJOL)

The aim of this research was to determine the chemical composition and toxicities of essential oil derived from Illicium fargesii Finet et Gagnep fruits against the maize weevil (Sitophilus zeamais Motsch). Essential oil of I. fargesii fruits was obtained from hydrodistillation and was investigated by GC (Gas Chromatography) ...

VAPOR SAMPLING DEVICE FOR INTERFACE WITH MICROTOX ASSAY FOR SCREENING TOXIC INDUSTRIAL CHEMICALS

Science.gov (United States)

A time-integrated sampling system interfaced with a toxicity-based assay is reported for monitoring volatile toxic industrial chemicals (TICs). Semipermeable membrane devices (SPMDs) using dimethyl sulfoxide (DMSO) as the fill solvent accumulated each of 17 TICs from the vapor...

TOXIC LEADERSHIP: A SYSTEMIC APPROACH TO SHIFT FROM REACTIVE TO PROACTIVE SOLUTIONS

Science.gov (United States)

2017-03-01

AIR COMMAND AND STAFF COLLEGE AIR UNIVERSITY TOXIC LEADERSHIP: A SYSTEMIC APPROACH TO SHIFT FROM REACTIVE TO PROACTIVE SOLUTIONS...DISTRIBUTION A. Approved for public release: distribution unlimited. Toxic Leadership: A Systemic Approach to Shift From Reactive to Proactive Solutions 1...US military loses valuable personnel when it is too late to implement corrective action and after those toxic Toxic Leadership: A Systemic Approach

Toxicity challenges in environmental chemicals: Prediction of ...

Science.gov (United States)

Physiologically based pharmacokinetic (PBPK) models bridge the gap between in vitro assays and in vivo effects by accounting for the adsorption, distribution, metabolism, and excretion of xenobiotics, which is especially useful in the assessment of human toxicity. Quantitative structure-activity relationships (QSAR) serve as a vital tool for the high-throughput prediction of chemical-specific PBPK parameters, such as the fraction of a chemical unbound by plasma protein (Fub). The presented work explores the merit of utilizing experimental pharmaceutical Fub data for the construction of a universal QSAR model, in order to compensate for the limited range of high-quality experimental Fub data for environmentally relevant chemicals, such as pollutants, pesticides, and consumer products. Independent QSAR models were constructed with three machine-learning algorithms, k nearest neighbors (kNN), random forest (RF), and support vector machine (SVM) regression, from a large pharmaceutical training set (~1000) and assessed with independent test sets of pharmaceuticals (~200) and environmentally relevant chemicals in the ToxCast program (~400). Small descriptor sets yielded the optimal balance of model complexity and performance, providing insight into the biochemical factors of plasma protein binding, while preventing over fitting to the training set. Overlaps in chemical space between pharmaceutical and environmental compounds were considered through applicability of do

The effects on health of radiological and chemical toxicity

International Nuclear Information System (INIS)

Toledano, M.; Flury-Herard, A.

2003-01-01

Future trends in the protection against the effects on health of radiological and/or chemical toxicity will certainly be based on improved knowledge of specific biological mechanisms and individual sensitivity. Progress in these areas will most likely be made at the interfaces between research, health care and biomedical monitoring. (authors)

78 FR 64210 - Extension of Review Periods Under the Toxic Substances Control Act; Certain Chemicals and...

Science.gov (United States)

2013-10-28

... Under the Toxic Substances Control Act; Certain Chemicals and Microorganisms; Premanufacture... 325 and 324110), e.g., chemical manufacturing and petroleum refineries. The North American Industrial... Agency under section 5 of the Toxic Substances Control Act (TSCA), received by EPA on or before October 1...

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.

Antioxidants as potential medical countermeasures for chemical warfare agents and toxic industrial chemicals.

Science.gov (United States)

McElroy, Cameron S; Day, Brian J

2016-01-15

The continuing horrors of military conflicts and terrorism often involve the use of chemical warfare agents (CWAs) and toxic industrial chemicals (TICs). Many CWA and TIC exposures are difficult to treat due to the danger they pose to first responders and their rapid onset that can produce death shortly after exposure. While the specific mechanism(s) of toxicity of these agents are diverse, many are associated either directly or indirectly with increased oxidative stress in affected tissues. This has led to the exploration of various antioxidants as potential medical countermeasures for CWA/TIC exposures. Studies have been performed across a wide array of agents, model organisms, exposure systems, and antioxidants, looking at an almost equally diverse set of endpoints. Attempts at treating CWAs/TICs with antioxidants have met with mixed results, ranging from no effect to nearly complete protection. The aim of this commentary is to summarize the literature in each category for evidence of oxidative stress and antioxidant efficacy against CWAs and TICs. While there is great disparity in the data concerning methods, models, and remedies, the outlook on antioxidants as medical countermeasures for CWA/TIC management appears promising. Copyright © 2015 Elsevier Inc. All rights reserved.

A toxicity reduction evaluation for an oily waste treatment plant exhibiting episodic effluent toxicity.

Science.gov (United States)

Erten-Unal, M; Gelderloos, A B; Hughes, J S

1998-07-30

A Toxicity Reduction Evaluation (TRE) was conducted on the oily wastewater treatment plant (Plant) at a Naval Fuel Depot. The Plant treats ship and ballast wastes, berm water from fuel storage areas and wastes generated in the fuel reclamation plant utilizing physical/chemical treatment processes. In the first period of the project (Period I), the TRE included chemical characterization of the plant wastewaters, monitoring the final effluent for acute toxicity and a thorough evaluation of each treatment process and Plant operating procedures. Toxicity Identification Evaluation (TIE) procedures were performed as part of the overall TRE to characterize and identify possible sources of toxicity. Several difficulties were encountered because the effluent was saline, test organisms were marine species and toxicity was sporadic and unpredictable. The treatability approach utilizing enhancements, improved housekeeping, and operational changes produced substantial reductions in the acute toxicity of the final effluent. In the second period (Period II), additional acute toxicity testing and chemical characterization were performed through the Plant to assess the long-term effects of major unit process improvements for the removal of toxicity. The TIE procedures were also modified for saline wastewaters to focus on suspected class of toxicants such as surfactants. The TRE was successful in reducing acute toxicity of the final effluent through process improvements and operational modifications. The results indicated that the cause of toxicity was most likely due to combination of pollutants (matrix effect) rather than a single pollutant.

A novel approach: chemical relational databases, and the role of the ISSCAN database on assessing chemical carcinogenicity.

Science.gov (United States)

Benigni, Romualdo; Bossa, Cecilia; Richard, Ann M; Yang, Chihae

2008-01-01

Mutagenicity and carcinogenicity databases are crucial resources for toxicologists and regulators involved in chemicals risk assessment. Until recently, existing public toxicity databases have been constructed primarily as "look-up-tables" of existing data, and most often did not contain chemical structures. Concepts and technologies originated from the structure-activity relationships science have provided powerful tools to create new types of databases, where the effective linkage of chemical toxicity with chemical structure can facilitate and greatly enhance data gathering and hypothesis generation, by permitting: a) exploration across both chemical and biological domains; and b) structure-searchability through the data. This paper reviews the main public databases, together with the progress in the field of chemical relational databases, and presents the ISSCAN database on experimental chemical carcinogens.

In silico prediction of toxicity of phenols to Tetrahymena pyriformis by using genetic algorithm and decision tree-based modeling approach.

Science.gov (United States)

Abbasitabar, Fatemeh; Zare-Shahabadi, Vahid

2017-04-01

Risk assessment of chemicals is an important issue in environmental protection; however, there is a huge lack of experimental data for a large number of end-points. The experimental determination of toxicity of chemicals involves high costs and time-consuming process. In silico tools such as quantitative structure-toxicity relationship (QSTR) models, which are constructed on the basis of computational molecular descriptors, can predict missing data for toxic end-points for existing or even not yet synthesized chemicals. Phenol derivatives are known to be aquatic pollutants. With this background, we aimed to develop an accurate and reliable QSTR model for the prediction of toxicity of 206 phenols to Tetrahymena pyriformis. A multiple linear regression (MLR)-based QSTR was obtained using a powerful descriptor selection tool named Memorized_ACO algorithm. Statistical parameters of the model were 0.72 and 0.68 for R training 2 and R test 2 , respectively. To develop a high-quality QSTR model, classification and regression tree (CART) was employed. Two approaches were considered: (1) phenols were classified into different modes of action using CART and (2) the phenols in the training set were partitioned to several subsets by a tree in such a manner that in each subset, a high-quality MLR could be developed. For the first approach, the statistical parameters of the resultant QSTR model were improved to 0.83 and 0.75 for R training 2 and R test 2 , respectively. Genetic algorithm was employed in the second approach to obtain an optimal tree, and it was shown that the final QSTR model provided excellent prediction accuracy for the training and test sets (R training 2 and R test 2 were 0.91 and 0.93, respectively). The mean absolute error for the test set was computed as 0.1615. Copyright © 2016 Elsevier Ltd. All rights reserved.

Toxicity assessment of industrial chemicals and airborne contaminants: transition from in vivo to in vitro test methods: a review.

Science.gov (United States)

Bakand, S; Winder, C; Khalil, C; Hayes, A

2005-12-01

Exposure to occupational and environmental contaminants is a major contributor to human health problems. Inhalation of gases, vapors, aerosols, and mixtures of these can cause a wide range of adverse health effects, ranging from simple irritation to systemic diseases. Despite significant achievements in the risk assessment of chemicals, the toxicological database, particularly for industrial chemicals, remains limited. Considering there are approximately 80,000 chemicals in commerce, and an extremely large number of chemical mixtures, in vivo testing of this large number is unachievable from both economical and practical perspectives. While in vitro methods are capable of rapidly providing toxicity information, regulatory agencies in general are still cautious about the replacement of whole-animal methods with new in vitro techniques. Although studying the toxic effects of inhaled chemicals is a complex subject, recent studies demonstrate that in vitro methods may have significant potential for assessing the toxicity of airborne contaminants. In this review, current toxicity test methods for risk evaluation of industrial chemicals and airborne contaminants are presented. To evaluate the potential applications of in vitro methods for studying respiratory toxicity, more recent models developed for toxicity testing of airborne contaminants are discussed.

Toxic Elements in Food: Occurrence, Binding, and Reduction Approaches

DEFF Research Database (Denmark)

Hajeb, P.; Sloth, Jens Jørgen; Shakibazadeh, Sh

2014-01-01

Toxic elements such as mercury, arsenic, cadmium, and lead, sometimes called heavy metals, can diminish mental and central nervous system function; elicit damage to blood composition as well as the kidneys, lungs, and liver; and reduce energy levels. Food is considered one of the main routes...... of their entry into the human body. Numerous studies have been performed to examine the effects of common food processing procedures on the levels of toxic elements in food. While some studies have reported negative effects of processing, several have shown that processing practices may have a positive effect...... on the reduction of toxic elements in foodstuffs. A number of studies have also introduced protocols and suggested chemical agents that reduce the amount of toxic elements in the final food products. In this review, the reported methods employed for the reduction of toxic elements are discussed with particular...

Host Response to Environmental Hazards: Using Literature, Bioinformatics, and Computation to Derive Candidate Biomarkers of Toxic Industrial Chemical Exposure

Science.gov (United States)

2015-10-01

military threat chemicals with adverse health effects and clinical outcomes to improve diagnostic potential after exposure to toxic industrial...end organ injury following chemical exposures in the field. Markers of end-organ injury and toxicity and other health effects markers, particularly...Biomarkers of Toxic Industrial Chemical Exposure Major Jonathan D. Stallings *1 , Danielle L. Ippolito 1 , Anders Wallqvist 2 , B. Claire McDyre 3 , and

Effects-driven chemical fractionation of heavy fuel oil to isolate compounds toxic to trout embryos.

Science.gov (United States)

Bornstein, Jason M; Adams, Julie; Hollebone, Bruce; King, Thomas; Hodson, Peter V; Brown, R Stephen

2014-04-01

Heavy fuel oil (HFO) spills account for approximately 60% of ship-source oil spills and are up to 50 times more toxic than medium and light crude oils. Heavy fuel oils contain elevated concentrations of polycyclic aromatic hydrocarbons (PAHs) and alkyl-PAHs, known to be toxic to fish; however, little direct characterization of HFO toxicity has been reported. An effects-driven chemical fractionation was conducted on HFO 7102 to separate compounds with similar chemical and physical properties, including toxicity, to isolate the groups of compounds most toxic to trout embryos. After each separation, toxicity tests directed the next phase of fractionation, and gas chromatography-mass spectrometry analysis correlated composition with toxicity, with a focus on PAHs. Low-temperature vacuum distillation permitted the separation of HFO into 3 fractions based on boiling point ranges. The most toxic of these fractions underwent wax precipitation to remove long-chain n-alkanes. The remaining PAH-rich extract was further separated using open column chromatography, which provided distinct fractions that were grouped according to increasing aromatic ring count. The most toxic of these fractions was richest in PAHs and alkyl-PAHs. The results of the present study were consistent with previous crude oil studies that identified PAH-rich fractions as the most toxic. © 2013 SETAC.

Physical and chemical parameters of sediment extraction and fractionation that influence toxicity, as evaluated by microtox (trade name)

International Nuclear Information System (INIS)

Ho, K.T.Y.; Quinn, J.G.

1993-01-01

Several physical and chemical parameters of sediment extraction and fractionation of organic compounds that influence bioassay results were evaluated. Each parameter was evaluated with a photoluminescent bacterial bioassay (Microtox) as an end point. Three solvents (acetonitrile, acetone, and methanol) were studied for their ability to extract toxic organic components from marine sediments. Acetone extracted the most toxicity, with no difference between acetonitrile and methanol. Two methods of fractionating sediment extracts (silica-gel-column chromatography (SGCC) and acid-base fractionation) were compared. SGCC was more useful because it resulted in a wider range of responses and was faster to perform than acid-base fractionation. Microtox was used to rank four marine sediments with respect to toxicity and to determine if one chemical class (or fraction) was consistently more toxic among different sediments. With some caveats, Microtox results agreed with general chemical concentration trends and other bioassay results in distinguishing between contaminated and noncontaminated sediments. Although results indicated there was not a consistently most toxic fraction among sediments, there was a consistently least toxic fraction. The effect of sediment storage time on toxicity was also evaluated. Results indicated that the most stable chemical fraction (containing nonpolar hydrocarbons) did not change toxicologically for 30 weeks, whereas the more chemically active fraction (containing ketones, quinones, and carboxyls) changed as soon as one week

Acute oral toxicity of chemicals in terrestrial life stages of amphibians: Comparisons to birds and mammals.

Science.gov (United States)

Crane, Mark; Finnegan, Meaghean; Weltje, Lennart; Kosmala-Grzechnik, Sylwia; Gross, Melanie; Wheeler, James R

2016-10-01

Amphibians are currently the most threatened and rapidly declining group of vertebrates and this has raised concerns about their potential sensitivity and exposure to plant protection products and other chemicals. Current environmental risk assessment procedures rely on surrogate species (e.g. fish and birds) to cover the risk to aquatic and terrestrial life stages of amphibians, respectively. Whilst a recent meta-analysis has shown that in most cases amphibian aquatic life stages are less sensitive to chemicals than fish, little research has been conducted on the comparative sensitivity of terrestrial amphibian life stages. Therefore, in this paper we address the questions "What is the relative sensitivity of terrestrial amphibian life stages to acute chemical oral exposure when compared with mammals and birds?" and "Are there correlations between oral toxicity data for amphibians and data for mammals or birds?" Identifying a relationship between these data may help to avoid additional vertebrate testing. Acute oral amphibian toxicity data collected from the scientific literature and ecotoxicological databases were compared with toxicity data for mammals and birds. Toxicity data for terrestrial amphibian life stages are generally sparse, as noted in previous reviews. Single-dose oral toxicity data for terrestrial amphibian life stages were available for 26 chemicals and these were positively correlated with LD50 values for mammals, while no correlation was found for birds. Further, the data suggest that oral toxicity to terrestrial amphibian life stages is similar to or lower than that for mammals and birds, with a few exceptions. Thus, mammals or birds are considered adequate toxicity surrogates for use in the assessment of the oral exposure route in amphibians. However, there is a need for further data on a wider range of chemicals to explore the wider applicability of the current analyses and recommendations. Copyright © 2016 Elsevier Inc. All rights reserved.

Machine learning for toxicity characterization of organic chemical emissions using USEtox database: Learning the structure of the input space.

Science.gov (United States)

Marvuglia, Antonino; Kanevski, Mikhail; Benetto, Enrico

2015-10-01

Toxicity characterization of chemical emissions in Life Cycle Assessment (LCA) is a complex task which usually proceeds via multimedia (fate, exposure and effect) models attached to models of dose-response relationships to assess the effects on target. Different models and approaches do exist, but all require a vast amount of data on the properties of the chemical compounds being assessed, which are hard to collect or hardly publicly available (especially for thousands of less common or newly developed chemicals), therefore hampering in practice the assessment in LCA. An example is USEtox, a consensual model for the characterization of human toxicity and freshwater ecotoxicity. This paper places itself in a line of research aiming at providing a methodology to reduce the number of input parameters necessary to run multimedia fate models, focusing in particular to the application of the USEtox toxicity model. By focusing on USEtox, in this paper two main goals are pursued: 1) performing an extensive exploratory analysis (using dimensionality reduction techniques) of the input space constituted by the substance-specific properties at the aim of detecting particular patterns in the data manifold and estimating the dimension of the subspace in which the data manifold actually lies; and 2) exploring the application of a set of linear models, based on partial least squares (PLS) regression, as well as a nonlinear model (general regression neural network--GRNN) in the seek for an automatic selection strategy of the most informative variables according to the modelled output (USEtox factor). After extensive analysis, the intrinsic dimension of the input manifold has been identified between three and four. The variables selected as most informative may vary according to the output modelled and the model used, but for the toxicity factors modelled in this paper the input variables selected as most informative are coherent with prior expectations based on scientific knowledge

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.

Predicting algal growth inhibition toxicity: three-step strategy using structural and physicochemical properties.

Science.gov (United States)

Furuhama, A; Hasunuma, K; Hayashi, T I; Tatarazako, N

2016-05-01

We propose a three-step strategy that uses structural and physicochemical properties of chemicals to predict their 72 h algal growth inhibition toxicities against Pseudokirchneriella subcapitata. In Step 1, using a log D-based criterion and structural alerts, we produced an interspecies QSAR between algal and acute daphnid toxicities for initial screening of chemicals. In Step 2, we categorized chemicals according to the Verhaar scheme for aquatic toxicity, and we developed QSARs for toxicities of Class 1 (non-polar narcotic) and Class 2 (polar narcotic) chemicals by means of simple regression with a hydrophobicity descriptor and multiple regression with a hydrophobicity descriptor and a quantum chemical descriptor. Using the algal toxicities of the Class 1 chemicals, we proposed a baseline QSAR for calculating their excess toxicities. In Step 3, we used structural profiles to predict toxicity either quantitatively or qualitatively and to assign chemicals to the following categories: Pesticide, Reactive, Toxic, Toxic low and Uncategorized. Although this three-step strategy cannot be used to estimate the algal toxicities of all chemicals, it is useful for chemicals within its domain. The strategy is also applicable as a component of Integrated Approaches to Testing and Assessment.

Upper parameters of toxicity (LDsub(50/30)) of some radioactive and chemical substances

International Nuclear Information System (INIS)

Rodionova, L.F.; Kupriyanova, V.M.; Zasedatelev, A.A.

1978-01-01

The toxicities of radioactive ( 90 Sr, 210 Po) and chemical (lead nitrate, mercuric chloride) substances were compared using equivalent procedures. Ninety six doses of toxic substances in various concentrations were tested on mice to which these substances were administered by intragastric intubation. The material was processed and analyzed by conventional methods used in toxicology. The upper limits of toxicity for the tested substances were determined from their LDsub(50/30) values by various methods of calculation

A novel approach for rapidly and cost-effectively assessing toxicity of toxic metals in acidic water using an acidophilic iron-oxidizing biosensor.

Science.gov (United States)

Yang, Shih-Hung; Cheng, Kuo-Chih; Liao, Vivian Hsiu-Chuan

2017-11-01

Contamination by heavy metals and metalloids is a serious environmental and health concern. Acidic wastewaters are often associated with toxic metals which may enter and spread into agricultural soils. Several biological assays have been developed to detect toxic metals; however, most of them can only detect toxic metals in a neutral pH, not in an acidic environment. In this study, an acidophilic iron-oxidizing bacterium (IOB) Strain Y10 was isolated, characterized, and used to detect toxic metals toxicity in acidic water at pH 2.5. The colorimetric acidophilic IOB biosensor was based on the inhibition of the iron oxidizing ability of Strain Y10, an acidophilic iron-oxidizing bacterium, by metals toxicity. Our results showed that Strain Y10 is acidophilic iron-oxidizing bacterium. Thiobacillus caldus medium (TCM) (pH 2.5) supplied with both S 4 O 6 2- and glucose was the optimum growth medium for Strain Y10. The optimum temperature and pH for the growth of Strain Y10 was 45 °C and pH 2.5, respectively. Our study demonstrates that the color-based acidophilic IOB biosensor can be semi-quantitatively observed by eye or quantitatively measured by spectrometer to detect toxicity from multiple toxic metals at pH 2.5 within 45 min. Our study shows that monitoring toxic metals in acidic water is possible by using the acidophilic IOB biosensor. Our study thus provides a novel approach for rapid and cost-effective detection of toxic metals in acidic conditions that can otherwise compromise current methods of chemical analysis. This method also allows for increased efficiency when screening large numbers of environmental samples. Copyright © 2017 Elsevier Ltd. All rights reserved.

Lethal toxicity of industrial chemicals to early life stages of Tilapia guineensis.

Science.gov (United States)

Ezemonye, L I N; Ogeleka, D F; Okieimen, F E

2008-08-30

The toxic effects of industrial chemicals on three early life stages of an economically important fish, Tilapia guineensis were investigated using the Organisation for Economic Cooperation and Development (OECD) # 203 recommended semi-static renewal bioassay. The assessment was necessary for the uncontrollable disposal of Neatex (liquid detergent) and Norust CR 486 (corrosion inhibitor) into the Niger Delta environment of Nigeria. The estimated 96-h LC(50) for 7-, 14- and 28-day-old fish in Norust CR 486 exposure was considered "more toxic" than Neatex in all life stages and was dependent on species age, exposure duration and environment. In the fresh water test, for Neatex and Norust CR 486 exposures for day 7, 14 and 28, the 96-h LC50 were 8.79, 17.10 and 82.42 mg/l and 5.55, 13.58 and 20.21 mg/l, respectively. In the brackish test, 15.42 and 46.52 mg/l, not determined (ND) and 7.35, 13.95 and 24.50mg/l were obtained. Differential toxicity was observed in the fresh and brackish water fish for the two chemicals and controls at pchemicals provides a rationale for regulatory surveillance and monitoring of both chemicals in the fragile Niger Delta environment.

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.

A Chemical Activity Approach to Exposure and Risk Assessment of Chemicals

DEFF Research Database (Denmark)

Gobas, Frank A. P. C.; Mayer, Philipp; Parkerton, Thomas F.

2018-01-01

activity approach, its strengths and limitations, and provides examples of how this concept may be applied to the management of single chemicals and chemical mixtures. The examples demonstrate that the chemical activity approach provides a useful framework for 1) compiling and evaluating exposure......To support the goals articulated in the vision for exposure and risk assessment in the twenty-first century, we highlight the application of a thermodynamic chemical activity approach for the exposure and risk assessment of chemicals in the environment. The present article describes the chemical...... assessment. The article further illustrates that the chemical activity approach can support an adaptive management strategy for environmental stewardship of chemicals where “safe” chemical activities are established based on toxicological studies and presented as guidelines for environmental quality...

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

A comprehensive study of the toxicity of natural multi-contaminated sediments: New insights brought by the use of a combined approach using the medaka embryo-larval assay and physico-chemical analyses.

Science.gov (United States)

Barjhoux, Iris; Clérandeau, Christelle; Menach, Karyn Le; Anschutz, Pierre; Gonzalez, Patrice; Budzinski, Hélène; Morin, Bénédicte; Baudrimont, Magalie; Cachot, Jérôme

2017-08-01

Sediment compartment is a long term sink for pollutants and a secondary source of contamination for aquatic species. The abiotic factors controlling the bioavailability and thus the toxicity of complex mixtures of pollutants accumulated in sediments are poorly documented. To highlight the different factors influencing sediment toxicity, we identified and analyzed the physico-chemical properties, micro-pollutant contents, and toxicity level of six contrasted sediments in the Lot-Garonne continuum. Sediment toxicity was evaluated using the recently described Japanese medaka (Oryzias latipes) embryo-larval assay with direct exposure to whole sediment (MELAc). Multiple toxicity endpoints including embryotoxicity, developmental defects and DNA damage were analyzed in exposed embryos. Chemical analyses revealed significant variations in the nature and contamination profile of sediments, mainly impacted by metallic trace elements and, unexpectedly, polycyclic aromatic hydrocarbons. Exposure to sediments induced different toxic impacts on medaka early life stages when compared with the reference site. Principal component analysis showed that the toxic responses following exposure to sediments from the Lot River and its tributary were associated with micro-pollutant contamination: biometric measurements, hatching success, genotoxicity, craniofacial deformities and yolk sac malabsorption were specifically correlated to metallic and organic contaminants. Conversely, the main biological responses following exposure to the Garonne River sediments were more likely related to their physico-chemical properties than to their contamination level. Time to hatch, cardiovascular injuries and spinal deformities were correlated to organic matter content, fine particles and dissolved oxygen levels. These results emphasize the necessity of combining physico-chemical analysis of sediment with toxicity assessment to accurately evaluate the environmental risks associated with sediment

Toxicity testing of chemical mixtures: some general aspects and need of international guidelines.

Science.gov (United States)

Kappus, H; Yang, R S

1996-01-01

The topics discussed by the Working Group on Toxicity Testing of Chemical Mixtures included the following (1) the study designs and results from two real-life exposure scenarios as additional information to the various investigations reported at the conference; (2) the need to take into consideration low-level, long-term exposure (i.e. mimicking human exposure conditions) as well as the issue of limited resources in experimental toxicology studies; (3) the importance of exploring alternative and predictive toxicology methodologies to minimize animal use and to conserve resources; (4) the realization that interactive toxicity should include the consideration of physical and biological agents in addition to chemicals. Two specific studies reported at the conference were also discussed. A number of recommendations were made concerning the planning and implementation of toxicology studies on chemical mixtures.

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.

Integrated approaches for determination of environmental and human risks of persistent toxic substances

International Nuclear Information System (INIS)

Blaha, L.; Cupr, P.; Dusek, L.; Hilscherova, K.; Holoubek, I.; Klanova, J.

2008-01-01

Substances that are persistent and bioaccumulative often posses toxic characteristics and cause adverse human health or environmental effects. Basic objective of the long-term research project INCHEMBIOL undertaken by the Centre RECETOX are the complex studies of interactions among chemical compounds present in environmental compartments and their biological effects and studies of the fate of mainly persistent chemical compounds in the environment, their effects on the environment and living organisms including human. Destiny in this concept consists of a summary of transport (from their input in the environment, transport within the environmental compartment, where they are discharged, transport among compartments and long-range transport in the environment) and transformation processes (abiotic and biotic transformations). It also includes study of distribution equilibriums, properties conditioning their environmental behaviour, study of the transformation processes and their products. This complex approach is a part of long-term research activities of the centre RECETOX. In the contribution methods used and results obtained in exploration of the causality among chemical (presence of chemical compounds in the environment) and biological (mechanisms of effects on the living organisms) are described.

Toxic effect of chemicals dumped in premises of UCIL, Bhopal leading to environmental pollution: An in silico approach

Directory of Open Access Journals (Sweden)

Manish Kumar Tripathi

2016-04-01

Full Text Available Objective: To investigate the role of dumped residues in the loss of immunity using human immune proteins, which provides protection against Mycobacterium tuberculosis. Methods: In this study, toxic chemicals were docked with immune proteins using AutoDock 4.0, and further, molecular dynamics simulations were performed for refinement of the docked complexes which were obtained from docking to confirm its stable behaviour over the entire simulation period. Results: Results revealed that alpha-naphthol showed the maximum inhibition with glutathione synthetase protein, while butylated hydroxytoluene and carbaryl showed the maximum inhibition with p38 MAPK14 protein with binding free energy ΔG -5.06, -5.1 and -5.36 kcal/ mol, respectively. Molecular dynamics simulation supported the greater stability of carbaryl and alpha-naphthol complexes with p38 MAPK 14 and glutathione synthetase protein as compared to butylated hydroxytoluene. Conclusions: In summary, findings suggested that toxic exposure of carbaryl and alphanaphthol as compared to butylated hydroxytoluene generated immunotoxicity and disrupted the functioning of immune system thus it may have caused an increase in susceptibility to Mycobacterium tuberculosis infection.

Terrestrial ecotoxicity of eight chemicals in a systematic approach

Energy Technology Data Exchange (ETDEWEB)

Hund-Rinke, K.; Simon, M. [Fraunhofer Inst. for Molecular Biology and Applied Ecology, Schmallenberg (Germany)

2005-07-01

Background and objective. Terrestrial ecotoxicity data are required for many research purposes. The data are derived either from the literature or elaborated by own investigations. As the terrestrial toxicity tests are usually time-consuming and labour intensive, the experiments are performed with a limited number of test organisms and soils. In the context of a project sponsored by CEFIC-LRI (European Chemical Industry Council - Long-Range Research Initiative), EC{sub 50}-values were systematically elaborated for eight chemicals with a wide range of logK{sub ow}-values (CdCl{sub 2}, Trinitrotoluene, 3,4-dichloroaniline, 2,4-dichlorophenol, Tributyltinchloride, Pentachlorophenol, Benzo(a)pyrene, p,p-dichloro-2,2-diphenyl-1,1,1-trichloroethane). The substances were selected covering a broad range of physico-chemical and ecotoxicological properties. As toxicity endpoints, microbial activities, plant germination and growth as well as reproduction of earthworms and collembola were determined. As such systematic investigations are rarely performed and for some substances no data existed, the data pool is made available to the scientific community. Methods. All toxicity tests were conducted on three different soil types (sandy soil, silty soil, loamy soil), according to ISO and OECD guidelines Results, discussion, conclusion and outlook. The different toxicities of the chemicals, the influence of soil properties on bioavailability as well as different sensitivities of test organisms and test parameters are reflected by the EC{sub 50}-values. The results showed that the EC{sub 50}-values calculated on the basis of nominal concentrations can significantly vary from EC{sub 50}-values derived from analytical concentrations for some substances. To avoid false conclusions, this has to be considered especially when concentrations determined in the field are compared with toxicity data obtained from the literature or calculated on the basis of nominal concentrations. Moreover

Chemical toxicity and radioactivity of depleted uranium: The evidence from in vivo and in vitro studies.

Science.gov (United States)

Asic, Adna; Kurtovic-Kozaric, Amina; Besic, Larisa; Mehinovic, Lejla; Hasic, Azra; Kozaric, Mirza; Hukic, Mirsada; Marjanovic, Damir

2017-07-01

The main aim of this review is to summarize and discuss the current state of knowledge on chemical toxicity and radioactivity of depleted uranium (DU) and their effect on living systems and cell lines. This was done by presenting a summary of previous investigations conducted on different mammalian body systems and cell cultures in terms of potential changes caused by either chemical toxicity or radioactivity of DU. In addition, the authors aimed to point out the limitations of those studies and possible future directions. The majority of both in vitro and in vivo studies performed using animal models regarding possible effects caused by acute or chronic DU exposure has been reviewed. Furthermore, exposure time and dose, DU particle solubility, and uranium isotopes as factors affecting the extent of DU effects have been discussed. Special attention has been dedicated to chromosomal aberrations, DNA damage and DNA breaks, as well as micronuclei formation and epigenetic changes, as DU has recently been considered a possible causative factor of all these processes. Therefore, this approach might represent a novel area of study of DU-related irradiation effects on health. Since different studies offer contradictory results, the main aim of this review is to summarize and briefly discuss previously obtained results in order to identify the current opinion on DU toxicity and radioactivity effects in relation to exposure type and duration, as well as DU properties. Copyright © 2017 Elsevier Inc. All rights reserved.

Characterization of ZnS thin films synthesized through a non-toxic precursors chemical bath

Energy Technology Data Exchange (ETDEWEB)

Rodríguez, C.A. [Department of Materials Engineering, Faculty of Engineering, University of Concepción, Edmundo Larenas 270, Concepción 4070409 (Chile); Sandoval-Paz, M.G. [Department of Physics, Faculty of Physics and Mathematics, University of Concepción, Concepción (Chile); Cabello, G. [Department of Basic Sciences, Faculty of Sciences, University of Bío-Bío, Campus Fernando May, Chillán (Chile); Flores, M.; Fernández, H. [Department of Physics, Faculty of Physics and Mathematics, University of Chile, Beauchef 850, Santiago (Chile); Carrasco, C., E-mail: ccarrascoc@udec.cl [Department of Materials Engineering, Faculty of Engineering, University of Concepción, Edmundo Larenas 270, Concepción 4070409 (Chile)

2014-12-15

Highlights: • High quality ZnS thin films have been deposited by chemical bath deposition technique from a non-toxic precursor’s solution. • Nanocrystalline ZnS thin films with large band gap energy were synthesized without using ammonia. • Evidence that the growing of the thin films is carried out by means of hydroxide mechanism was found. • The properties of these ZnS thin films are similar and in some cases better than the corresponding ones produced using toxic precursors such as ammonia. - Abstract: In solar cells, ZnS window layer deposited by chemical bath technique can reach the highest conversion efficiency; however, precursors used in the process normally are materials highly volatile, toxic and harmful to the environment and health (typically ammonia and hydrazine). In this work the characterization of ZnS thin films deposited by chemical bath in a non-toxic alkaline solution is reported. The effect of deposition technique (growth in several times) on the properties of the ZnS thin film was studied. The films exhibited a high percentage of optical transmission (greater than 80%); as the deposition time increased a decreasing in the band gap values from 3.83 eV to 3.71 eV was observed. From chemical analysis, the presence of ZnS and Zn(OH){sub 2} was identified and X-ray diffraction patterns exhibited a clear peak corresponding to ZnS hexagonal phase (1 0 3) plane, which was confirmed by electron diffraction patterns. From morphological studies, compact samples with well-defined particles, low roughness, homogeneous and pinhole-free in the surface were observed. From obtained results, it is evident that deposits of ZnS–CBD using a non-toxic solution are suitable as window layer for TFSC.

CHEMICAL CONTAMINATION AND TOXICITY ASSOCIATED WITH A COASTAL GOLF COURSE COMPLEX

Science.gov (United States)

The increasing density of golf courses represents a potential source of contamination to nearby coastal areas, the chemical and biological magnitude of which is almost unknown. The objective of this study was to compare the concentrations of contaminants and toxicities of sedime...

Passive dosing of polycyclic aromatic hydrocarbon (PAH) mixtures to terrestrial springtails: Linking mixture toxicity to chemical activities, equilibrium lipid concentrations, and toxic units

DEFF Research Database (Denmark)

Schmidt, Stine Nørgaard; Holmstrup, Martin; Smith, Kilian E. C.

2013-01-01

treatments, containing the polycyclic aromatic hydrocarbons (PAHs) naphthalene, phenanthrene, and pyrene. Springtail lethality was then linked to sum chemical activities (∑a), sum equilibrium lipid concentrations (∑Clipid eq.), and sum toxic units (∑TU). In each case, the effects of all 12 mixture treatments...... could be fitted to one sigmoidal exposure-response relationship. The effective lethal chemical activity (La50) of 0.027 was well within the expected range for baseline toxicity of 0.01-0.1. Linking the effects to the lipid-based exposure parameter yielded an effective lethal concentration (LClipid eq...

Mobility and Attenuation Dynamics of Potentially Toxic Chemical Species at an Abandoned Copper Mine Tailings Dump

Directory of Open Access Journals (Sweden)

Wilson Mugera Gitari

2018-02-01

Full Text Available Large volumes of disposed mine tailings abound in several regions of South Africa, as a consequence of unregulated, unsustainable long years of mining activities. Tailings dumps occupy a large volume of valuable land, and present a potential risk for aquatic systems, through leaching of potentially toxic chemical species. This paper reports on the evaluation of the geochemical processes controlling the mobility of potentially toxic chemical species within the tailings profile, and their potential risk with regard to surface and groundwater systems. Combination of X-ray fluorescence (XRF, X-ray diffraction (XRD, and scanning electron microscopy-energy dispersive spectroscopy (SEM-EDS techniques, show that the tailing profiles are uniform, weakly altered, and vary slightly with depth in both physical and geochemical properties, as well as mineralogical composition. Mineralogical analysis showed the following order of abundance: quartz > epidote > chlorite > muscovite > calcite > hematite within the tailings profiles. The neutralization of the dominant alumino-silicate minerals and the absence of sulfidic minerals, have produced medium alkaline pH conditions (7.97–8.37 at all depths and low concentrations of dissolved Cu (20.21–47.9 µg/L, Zn (0.88–1.80 µg/L, Pb (0.27–0.34 µg/L, and SO42− (15.71–55.94 mg/L in the tailings profile leachates. The relative percentage leach for the potentially toxic chemical species was low in the aqueous phase (Ni 0.081%, Cu 0.006%, and Zn 0.05%. This indicates that the transport load of potentially toxic chemical species from tailings to the aqueous phase is very low. The precipitation of secondary hematite has an important known ability to trap and attenuate the mobility of potentially toxic chemical species (Cu, Zn, and Pb by adsorption on the surface area. Geochemical modelling MINTEQA2 showed that the tailings leachates were below saturation regarding oxyhydroxide minerals, but oversaturated with Cu

Removal of toxic dichlorophenol from water by sorption with chemically activated carbon of almond shells - a green approach

International Nuclear Information System (INIS)

Jamil, N.; Ahsan, N.; Munwar, M.A.; Anwar, J.; Shafiq, U.

2011-01-01

Chloro phenols (CP) represents a group of organic compounds having substituted chlorines attached to phenol ring. These trace organic pollutants represent a major environmental concern, because of toxicity, non-biodegradability, carcinogenic and stubborn properties. The adsorption of 2, 4-dichlorophenol (DCP) by chemically activated carbon of almond shells (CAC-AS) has been studied in the batch setup. Operational parameters like adsorbent dose, pH, and shaking speed were investigated. Langmuir and Freundlich isotherms were employed to calculate adsorption capacity and other sorption features of CAC-AS. The maximum amount of DCP adsorbed was 24.3 mg per gram of activated carbon derived from almond shells. Optimum conditions for DCP uptake were 2.5 g adsorbent dose, pH 5 and agitation speed of 200 rpm whereas the concentration of DCP solution was 25 mg/L (50 mL). Results corroborated that almond shells pretreated chemically, can be an excellent low cost adsorbents for removal of DCP from contaminated water. (author)

Comparison of toxicity of class-based organic chemicals to algae and fish based on discrimination of excess toxicity from baseline level.

Science.gov (United States)

Li, Jin J; Tai, Hong W; Yu, Yang; Wen, Yang; Wang, Xiao H; Zhao, Yuan H

2015-07-01

Toxicity data to fish and algae were used to investigate excess toxicity between species. Results show that chemicals exhibiting excess toxicity to fish also show excess toxicity to algae for most of the compounds. This indicates that they share the same mode of action between species. Similar relationships between logKOW and toxicities to fish and algae for baseline and less inert compounds suggest that they have similar critical body residues in the two species. Differences in excess toxicity for some compounds suggest that there is a difference of physiological structure and metabolism between fish and algae. Some reactive compounds (e.g. polyamines) exhibit greater toxic effects for algae than those for fish because of relatively low bio-uptake potential of these hydrophilic compounds in fish as compared with that in algae. Esters exhibiting greater toxicity in fish than that in algae indicate that metabolism can affect the discrimination of excess toxicity from baseline level. Algae growth inhibition is a very good surrogate for fish lethality. This is not only because overall toxicity sensitivity to algae is greater than that to fish, but also the excess toxicity calculated from algal toxicity can better reflect reactivity of compounds with target molecules than fish toxicity. Copyright © 2015 Elsevier B.V. All rights reserved.

Passive dosing of polycyclic aromatic hydrocarbon (PAH) mixtures to terrestrial springtails: linking mixture toxicity to chemical activities, equilibrium lipid concentrations, and toxic units.

Science.gov (United States)

Schmidt, Stine N; Holmstrup, Martin; Smith, Kilian E C; Mayer, Philipp

2013-07-02

A 7-day mixture toxicity experiment with the terrestrial springtail Folsomia candida was conducted, and the effects were linked to three different mixture exposure parameters. Passive dosing from silicone was applied to tightly control exposure levels and compositions of 12 mixture treatments, containing the polycyclic aromatic hydrocarbons (PAHs) naphthalene, phenanthrene, and pyrene. Springtail lethality was then linked to sum chemical activities (∑a), sum equilibrium lipid concentrations (∑C(lipid eq.)), and sum toxic units (∑TU). In each case, the effects of all 12 mixture treatments could be fitted to one sigmoidal exposure-response relationship. The effective lethal chemical activity (La50) of 0.027 was well within the expected range for baseline toxicity of 0.01-0.1. Linking the effects to the lipid-based exposure parameter yielded an effective lethal concentration (LC(lipid eq 50)) of 133 mmol kg(-1) lipid in good correspondence with the lethal membrane burden for baseline toxicity (40-160 mmol kg(-1) lipid). Finally, the effective lethal toxic unit (LTU50) of 1.20 was rather close to the expected value of 1. Altogether, passive dosing provided tightly controlled mixture exposure in terms of both level and composition, while ∑a, ∑C(lipid eq.), and ∑TU allowed baseline toxicity to be linked to mixture exposure.

Reactive formulations for a neutralization of toxic industrial chemicals

Science.gov (United States)

Tucker, Mark D [Albuqueruqe, NM; Betty, Rita G [Rio Rancho, NM

2006-10-24

Decontamination formulations for neutralization of toxic industrial chemicals, and methods of making and using same. The formulations are effective for neutralizing malathion, hydrogen cyanide, sodium cyanide, butyl isocyanate, carbon disulfide, phosgene gas, capsaicin in commercial pepper spray, chlorine gas, anhydrous ammonia gas; and may be effective at neutralizing hydrogen sulfide, sulfur dioxide, formaldehyde, ethylene oxide, methyl bromide, boron trichloride, fluorine, tetraethyl pyrophosphate, phosphorous trichloride, arsine, and tungsten hexafluoride.

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

A Novel Approach: Chemical Relational Databases, and the ...

Science.gov (United States)

Mutagenicity and carcinogenicity databases are crucial resources for toxicologists and regulators involved in chemicals risk assessment. Until recently, existing public toxicity databases have been constructed primarily as

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.

Management of diabetic complications: a chemical constituents based approach.

Science.gov (United States)

Singh, Randhir; Kaur, Navpreet; Kishore, Lalit; Gupta, Girish Kumar

2013-10-28

Long term hyperglycemia leads to development of complications associated with diabetes. Diabetic complications are now a global health problem without effective therapeutic approach. Hyperglycemia and oxidative stress are important components for the development of diabetic complications. Over the past few decades, herbal medicines have attracted much attention as potential therapeutic agents in the prevention and treatment of diabetic complications due to their multiple targets and less toxic side effects. This review aims to assess the current available knowledge of medicinal herbs for attenuation and management of diabetic complications and their underlying mechanisms. Bibliographic investigation was carried out by scrutinizing classical text books and peer reviewed papers, consulting worldwide accepted scientific databases (SCOPUS, PUBMED, SCIELO, NISCAIR, Google Scholar) to retrieve available published literature. The inclusion criteria for the selection of plants were based upon all medicinal herbs and their active compounds with attributed potentials in relieving diabetic complications. Moreover, plants which have potential effect in ameliorating oxidative stress in diabetic animals have been included. Overall, 238 articles were reviewed for plant literature and out of the reviewed literature, 127 articles were selected for the study. Various medicinal plants/plant extracts containing flavonoids, alkaloids, phenolic compounds, terpenoids, saponins and phytosterol type chemical constituents were found to be effective in the management of diabetic complications. This effect might be attributed to amelioration of persistent hyperglycemia, oxidative stress and modulation of various metabolic pathways involved in the pathogenesis of diabetic complications. Screening chemical candidate from herbal medicine might be a promising approach for new drug discovery to treat the diabetic complications. There is still a dire need to explore the mechanism of action of

UTMTOX, Toxic Chemical Transport in Atmosphere, Ground Water, Sediments

International Nuclear Information System (INIS)

1988-01-01

A - Description of program or function: UTMTOX is a unified transport model for toxic materials. It combines hydrologic, atmospheric, and sediment transport in one computer code and extends the scope to predict the transport of not only trace metals but also many chemical compounds, including organics. UTMTOX is capable of calculating 1) the atmospheric dispersion of up to 20 chemicals from a maximum of 10 point, 10 line, and 10 area sources; 2) deposition of one chemical at a time in both wet and dry form on foliage or the surface of the earth; 3) surface flow and erosion; 4) percolation through the soil to a stream channel; and 5) flow in the stream channel to the outfall of a watershed. B - Method of solution: UTMTOX calculates rates of flux of chemicals from release to the atmosphere, through deposition on a watershed, infiltration, and runoff from the soil to flow in the stream channel and the associated sediment transport. From these values, mass balances can be established, budgets for the chemical can be made, and concentrations in many environmental compartments can be estimated. Since the coupling is established among three major submodels, they can share data

Protecting children from toxic chemicals: putting it on Australia's public health agenda.

Science.gov (United States)

Lantz, Sarah

2013-11-01

The high volume and widespread use of industrial chemicals, the backlog of internationally untested chemicals, the uptake of synthetic chemicals found in babies in utero, cord blood, and in breast milk, and the lack of a unified and comprehensive regulatory framework all necessitate developing policies that protect the most vulnerable in our society - our children. Australia's failure to do so raises profound intergenerational ethical issues. This article tells a story of international policy, and where Australia is falling down. It demonstrates that we can learn from countries already taking critical steps to reduce the toxic chemical exposure, and that the development of a comprehensive, child-centered chemical regulation framework is central to turning around Australia's failure.

Toxic effects of the interaction of titanium dioxide nanoparticles with chemicals or physical factors

Science.gov (United States)

Liu, Kui; Lin, Xialu; Zhao, Jinshun

2013-01-01

Due to their chemical stability and nonallergic, nonirritant, and ultraviolet protective properties, titanium dioxide (TiO2) nanoparticles (NPs) have been widely used in industries such as electronics, optics, and material sciences, as well as architecture, medicine, and pharmacology. However, increasing concerns have been raised in regards to its ecotoxicity and toxicity on the aquatic environment as well as to humans. Although insights have been gained into the effects of TiO2 NPs on susceptible biological systems, there is still much ground to be covered, particularly in respect of our knowledge of the effects of the interaction of TiO2 NPs with other chemicals or physical factors. Studies suggest that interactions of TiO2 NPs with other chemicals or physical factors may result in an increase in toxicity or adverse effects. This review highlights recent progress in the study of the interactive effects of TiO2 NPs with other chemicals or physical factors. PMID:23901269

1997 toxic chemical release inventory. Emergency Planning and Community Right-To-Know Act, Section 313

International Nuclear Information System (INIS)

Zaloudek, D.E.

1998-01-01

Two listed toxic chemicals were used at the Hanford Site above established activity thresholds: phosphoric acid and chlorine. Because total combined quantities of chlorine released, disposed, treated, recovered through recycle operations, co-combusted for energy recovery, and transferred to off-site locations for the purpose of recycle, energy recovery, treatment, and/or disposal, amounted to less than 500 pounds, the Hanford Site qualified for the alternate one million pound threshold for chlorine. Accordingly, this Toxic Chemical Release Inventory includes a Form A for chlorine, and a Form B for phosphoric acid

Fate of chemical warfare agents and toxic industrial chemicals in landfills.

Science.gov (United States)

Bartelt-Hunt, Shannon L; Barlaz, Morton A; Knappe, Detlef R U; Kjeldsen, Peter

2006-07-01

One component of preparedness for a chemical attack is planning for the disposal of contaminated debris. To assess the feasibility of contaminated debris disposal in municipal solid waste (MSW) landfills, the fate of selected chemical warfare agents (CWAs) and toxic industrial chemicals (TICs) in MSW landfills was predicted with a mathematical model. Five blister agents [sulfur mustard (HD), nitrogen mustard (HN-2), lewisite (L), ethyldichloroarsine (ED), and phosgene oxime (CX)], eight nerve agents [tabun (GA), sarin (GB), soman (GD), GE, GF, VX, VG, and VM], one riot-control agent [CS], and two TICs [furan and carbon disulfide] were studied. The effects of both infiltration (climate) and contaminant biodegradability on fate predictions were assessed. Model results showed that hydrolysis and gas-phase advection were the principal fate pathways for CWAs and TICs, respectively. Apart from CX and the TICs, none of the investigated compounds was predicted to persist in a landfill for more than 5 years. Climate had little impact on CWA/TIC fate, and biodegradability was only important for compounds with long hydrolysis half-lives. Monte Carlo simulations were performed to assess the influence of uncertainty in model input parameters on CWA/TIC fate predictions. Correlation analyses showed that uncertainty in hydrolysis rate constants was the primary contributor to variance of CWA fate predictions, while uncertainty in the Henry's Law constant and landfill gas-production rate accounted for most of the variance of TIC fate predictions. CWA hydrolysates were more persistent than the parent CWAs, but limited information is available on abiotic or biotic transformation rates for these chemicals.

Low-toxic and safe nanomaterials by surface-chemical design, carbon nanotubes, fullerenes, metallofullerenes, and graphenes

Science.gov (United States)

YanEqual Contribution, Liang; Zhao, Feng; Li, Shoujian; Hu, Zhongbo; Zhao, Yuliang

2011-02-01

The toxicity grade for a bulk material can be approximately determined by three factors (chemical composition, dose, and exposure route). However, for a nanomaterial it depends on more than ten factors. Interestingly, some nano-factors (like huge surface adsorbability, small size, etc.) that endow nanomaterials with new biomedical functions are also potential causes leading to toxicity or damage to the living organism. Is it possible to create safe nanomaterials if such a number of complicated factors need to be regulated? We herein try to find answers to this important question. We first discuss chemical processes that are applicable for nanosurface modifications, in order to improve biocompatibility, regulate ADME, and reduce the toxicity of carbon nanomaterials (carbon nanotubes, fullerenes, metallofullerenes, and graphenes). Then the biological/toxicological effects of surface-modified and unmodified carbon nanomaterials are comparatively discussed from two aspects: the lowered toxic responses or the enhanced biomedical functions. We summarize the eight biggest challenges in creating low-toxicity and safer nanomaterials and some significant topics of future research needs: to find out safer nanofactors; to establish controllable surface modifications and simpler chemistries for low-toxic nanomaterials; to explore the nanotoxicity mechanisms; to justify the validity of current toxicological theories in nanotoxicology; to create standardized nanomaterials for toxicity tests; to build theoretical models for cellular and molecular interactions of nanoparticles; and to establish systematical knowledge frameworks for nanotoxicology.

Computational Approaches to Chemical Hazard Assessment

Science.gov (United States)

Luechtefeld, Thomas; Hartung, Thomas

2018-01-01

Summary Computational prediction of toxicity has reached new heights as a result of decades of growth in the magnitude and diversity of biological data. Public packages for statistics and machine learning make model creation faster. New theory in machine learning and cheminformatics enables integration of chemical structure, toxicogenomics, simulated and physical data in the prediction of chemical health hazards, and other toxicological information. Our earlier publications have characterized a toxicological dataset of unprecedented scale resulting from the European REACH legislation (Registration Evaluation Authorisation and Restriction of Chemicals). These publications dove into potential use cases for regulatory data and some models for exploiting this data. This article analyzes the options for the identification and categorization of chemicals, moves on to the derivation of descriptive features for chemicals, discusses different kinds of targets modeled in computational toxicology, and ends with a high-level perspective of the algorithms used to create computational toxicology models. PMID:29101769

1992 Toxic Chemical Release Inventory: Emergency Planning and Community Right-To-Know-Act of 1986 Section 313

International Nuclear Information System (INIS)

1993-07-01

Section 313 of the Emergency Planning and Community Right-To-Know Act of 1986 (EPCRA) requires the annual submittal of toxic chemical release information to the US Environmental Protection Agency (EPA). The following document is the July 1993 submittal of the EPCRA Toxic Chemical Release Inventory Report (Form R). Included is a Form R for chlorine and for lead, the two chemicals used in excess of the established regulatory thresholds at the Hanford Site by the US Department of Energy, Richland Operations Office and its contractors during calendar year 1992

Emergency planning and preparedness for the deliberate release of toxic industrial chemicals.

Science.gov (United States)

Russell, David; Simpson, John

2010-03-01

Society in developed and developing countries is hugely dependent upon chemicals for health, wealth, and economic prosperity, with the chemical industry contributing significantly to the global economy. Many chemicals are synthesized, stored, and transported in vast quantities and classified as high production volume chemicals; some are recognized as being toxic industrial chemicals (TICs). Chemical accidents involving chemical installations and transportation are well recognized. Such chemical accidents occur with relative frequency and may result in large numbers of casualties with acute and chronic health effects as well as fatalities. The large-scale production of TICs, the potential for widespread exposure and significant public health impact, together with their relative ease of acquisition, makes deliberate release an area of potential concern. The large numbers of chemicals, together with the large number of potential release scenarios means that the number of possible forms of chemical incident are almost infinite. Therefore, prior to undertaking emergency planning and preparedness, it is necessary to prioritize risk and subsequently mitigate. This is a multi-faceted process, including implementation of industrial protection layers, substitution of hazardous chemicals, and relocation away from communities. Residual risk provides the basis for subsequent planning. Risk-prioritized emergency planning is a tool for identifying gaps, enhancing communication and collaboration, and for policy development. It also serves to enhance preparedness, a necessary prelude to preventing or mitigating the public health risk to deliberate release. Planning is an iterative and on-going process that requires multi-disciplinary agency input, culminating in the formation of a chemical incident plan complimentary to major incident planning. Preparedness is closely related and reflects a state of readiness. It is comprised of several components, including training and exercising

SEDIMENT CHEMICAL CONTAMINATION AND TOXICITY ASSOCIATED WITH A COASTAL GOLF COURSE COMPLEX.

Science.gov (United States)

The increasing density of golf courses represents a potential source of sediment contamination to nearby coastal areas, the chemical and biological magnitude of which is almost unknown. The objective of this study was to determine the concentrations of contaminants and toxicities...

Enhancement of developmental toxicity effects of chemicals by gestational stress. A review

DEFF Research Database (Denmark)

Hougaard, Karin S; Hansen, Åse Marie

2007-01-01

Risk assessment of developmental toxicants is almost exclusively based on single chemicals studied in animals under controlled experimental conditions, as to reduce stress. Although humans may be exposed simultaneously to numerous hazards, little is known about the interaction of prenatal chemica...

1998 Toxic Chemical Release Inventory Report for the Emergency Planning and Community Right-to-Know Act of 1986, Title III

International Nuclear Information System (INIS)

Stockton, Marjorie B.

1999-01-01

The Emergency Planning and Community Right-to-Know Act (EPCRA) of 1986 [also known as the Superfund Amendment and Reauthorization Act (SARA), Title III], as modified by Executive Order 12856, requires that all federal facilities evaluate the need to submit an annual Toxic Chemical Release Inventory report as prescribed in Title III, Section 313 of this Act. This annual report is due every July for the preceding calendar year. Owners and operators who manufacture, process, or otherwise use certain toxic chemicals above listed threshold quantities are required to report their toxic chemical releases to all environmental mediums (air, water, soil, etc.). At Los Alamos National Laboratory (LANL), no EPCRA Section 313 chemicals were used in 1998 above the reportable threshold limits of 10,000 lb or 25,000 lb. Therefore LANL was not required to submit any Toxic Chemical Release Inventory reports (Form Rs) for 1998. This document was prepared to provide a detailed description of the evaluation on chemical usage and EPCRA Section 313 threshold determinations for LANL for 1998

Chemical Compounds Toxic to Invertebrates Isolated from Marine Cyanobacteria of Potential Relevance to the Agricultural Industry

KAUST Repository

Essack, Magbubah

2014-10-29

In spite of advances in invertebrate pest management, the agricultural industry is suffering from impeded pest control exacerbated by global climate changes that have altered rain patterns to favour opportunistic breeding. Thus, novel naturally derived chemical compounds toxic to both terrestrial and aquatic invertebrates are of interest, as potential pesticides. In this regard, marine cyanobacterium-derived metabolites that are toxic to both terrestrial and aquatic invertebrates continue to be a promising, but neglected, source of potential pesticides. A PubMed query combined with hand-curation of the information from retrieved articles allowed for the identification of 36 cyanobacteria-derived chemical compounds experimentally confirmed as being toxic to invertebrates. These compounds are discussed in this review.

Chemical Compounds Toxic to Invertebrates Isolated from Marine Cyanobacteria of Potential Relevance to the Agricultural Industry

KAUST Repository

Essack, Magbubah; Alzubaidy, Hanin S.; Bajic, Vladimir B.; Archer, John A.C.

2014-01-01

In spite of advances in invertebrate pest management, the agricultural industry is suffering from impeded pest control exacerbated by global climate changes that have altered rain patterns to favour opportunistic breeding. Thus, novel naturally derived chemical compounds toxic to both terrestrial and aquatic invertebrates are of interest, as potential pesticides. In this regard, marine cyanobacterium-derived metabolites that are toxic to both terrestrial and aquatic invertebrates continue to be a promising, but neglected, source of potential pesticides. A PubMed query combined with hand-curation of the information from retrieved articles allowed for the identification of 36 cyanobacteria-derived chemical compounds experimentally confirmed as being toxic to invertebrates. These compounds are discussed in this review.

Chemical Compounds Toxic to Invertebrates Isolated from Marine Cyanobacteria of Potential Relevance to the Agricultural Industry

Science.gov (United States)

Essack, Magbubah; Alzubaidy, Hanin S.; Bajic, Vladimir B.; Archer, John A. C.

2014-01-01

In spite of advances in invertebrate pest management, the agricultural industry is suffering from impeded pest control exacerbated by global climate changes that have altered rain patterns to favour opportunistic breeding. Thus, novel naturally derived chemical compounds toxic to both terrestrial and aquatic invertebrates are of interest, as potential pesticides. In this regard, marine cyanobacterium-derived metabolites that are toxic to both terrestrial and aquatic invertebrates continue to be a promising, but neglected, source of potential pesticides. A PubMed query combined with hand-curation of the information from retrieved articles allowed for the identification of 36 cyanobacteria-derived chemical compounds experimentally confirmed as being toxic to invertebrates. These compounds are discussed in this review. PMID:25356733

Colloid formation as an approach to remediate toxic wastes containing chromium and lead

Energy Technology Data Exchange (ETDEWEB)

Barton, Larry L [Laboratory of Microbial Chemistry, Department of Biology, University of New Mexico, Albuquerque, NM (United States); Lindemann, William C [Department of Agronomy and Horticulture, New Mexico State University, Las Cruces, NM (United States); Bearden, Deborah L [Department of Chemical and Nuclear Engineering, University of New Mexico, Albuquerque, NM (United States)

1992-07-01

We have explored the use of bacteria to remediate soil and aquatic sites containing toxic levels of Pb II or Cr VI. Bacterial isolates from metal-containing sites are capable of detoxifying water containing up to 10 mM Pb II. This activity is a two step process with an initial binding of Pb II to the cells followed by production of a black Pb-containing colloid. Numerous bacteria will reduce Cr VI to Cr III and some isolates have been found to bind Cr III to the bacterial cell. Colloids consisting of Cr III would result from the formation of chromium hydroxide or from binding to bacteria. The bacterial metabolism of Pb II and Cr III converts the biologically toxic and chemically reactive metal to compounds of reduced toxicity and modified chemical activity. We propose a system which can employ bacteria for the bioremediation of toxic sites containing lead or chromium. (author)

A high-throughput method for assessing chemical toxicity using a Caenorhabditis elegans reproduction assay

International Nuclear Information System (INIS)

Boyd, Windy A.; McBride, Sandra J.; Rice, Julie R.; Snyder, Daniel W.; Freedman, Jonathan H.

2010-01-01

The National Research Council has outlined the need for non-mammalian toxicological models to test the potential health effects of a large number of chemicals while also reducing the use of traditional animal models. The nematode Caenorhabditis elegans is an attractive alternative model because of its well-characterized and evolutionarily conserved biology, low cost, and ability to be used in high-throughput screening. A high-throughput method is described for quantifying the reproductive capacity of C. elegans exposed to chemicals for 48 h from the last larval stage (L4) to adulthood using a COPAS Biosort. Initially, the effects of exposure conditions that could influence reproduction were defined. Concentrations of DMSO vehicle ≤ 1% did not affect reproduction. Previous studies indicated that C. elegans may be influenced by exposure to low pH conditions. At pHs greater than 4.5, C. elegans reproduction was not affected; however below this pH there was a significant decrease in the number of offspring. Cadmium chloride was chosen as a model toxicant to verify that automated measurements were comparable to those of traditional observational studies. EC 50 values for cadmium for automated measurements (176-192 μM) were comparable to those previously reported for a 72-h exposure using manual counting (151 μM). The toxicity of seven test toxicants on C. elegans reproduction was highly correlative with rodent lethality suggesting that this assay may be useful in predicting the potential toxicity of chemicals in other organisms.

Impact of bioavailability on the correlation between in vitro cytotoxic and in vivo acute fish toxic concentrations of chemicals

International Nuclear Information System (INIS)

Guelden, Michael; Seibert, Hasso

2005-01-01

The lower sensitivity of in vitro cytotoxicity assays currently restricts their use as alternative to the fish acute toxicity assays for hazard assessment of chemicals in the aquatic environment. In vitro cytotoxic potencies mostly refer to nominal concentrations. The main objective of the present study was to investigate, whether a reduced availability of chemicals in vitro can account for the lower sensitivity of in vitro toxicity test systems. For this purpose, the bioavailable free fractions of the nominal cytotoxic concentrations (EC 50 ) of chemicals determined with a cytotoxicity test system using Balb/c 3T3 cells and the corresponding free cytotoxic concentrations (ECu 50 ) were calculated. The algorithm applied is based on a previously developed simple equilibrium distribution model for chemicals in cell cultures with serum-supplemented culture media. This model considers the distribution of chemicals between water, lipids and serum albumin. The algorithm requires the relative lipid volume of the test system, the octanol-water partition coefficient (K ow ) and the in vitro albumin-bound fraction of the chemicals. The latter was determined from EC 50 -measurements in the presence of different albumin concentrations with the Balb/c 3T3 test system. Organic chemicals covering a wide range of cytotoxic potency (EC 50 : 0.16-527000 μM) and lipophilicity (log K ow : -5.0-6.96) were selected, for which fish acute toxicity data (LC 50 -values) from at least one of the three fish species, medaka, rainbow trout and fathead minnow, respectively, were available. The availability of several chemicals was shown to be extensively reduced either by partitioning into lipids or by serum albumin binding, or due to both mechanisms. Reduction of bioavailability became more important with increasing cytotoxic potency. The sensitivity of the Balb/c 3T3 cytotoxicity assay and the correspondence between in vivo and in vitro toxic potencies were increased when the free cytotoxic

Role of environmental stress in the physiological response to chemical toxicants

International Nuclear Information System (INIS)

Gordon, C.J.

2003-01-01

Environmental physiology is the study of the physiological mechanisms that allow animals to cope with and adapt to changes in temperature, humidity, atmospheric pressure, and other natural factors of their physical environment. Nearly all toxicological and pharmacological studies are performed in resting (i.e., non exercising) experimental animals acclimatized to standard environmental conditions that are usually considered ideal to the animal's physiological well-being. These ideal test conditions are clearly not representative of the fluctuations in the natural environment encountered by humans and other animals on a day-to-day basis. It behooves the toxicologist, especially those interested in extrapolating experimental data from laboratory animals to humans, to consider how variations in the natural environment will alter physiological responses to toxicants. Temperature and exercise are the two most well-studied parameters in the fields of environmental physiology and toxicology. In general, high temperatures exacerbate the toxic effects of many environmental toxicants. Moreover, exercising subjects are generally more vulnerable to airborne toxic agents. The prospect of global warming also warrants a better assessment of how higher environmental temperatures may impact on the response of humans and other species to toxic chemicals. Hence, this paper and accompanying papers from the proceedings of a symposium focus on the salient aspects of the interaction between environmental stress and physiological response to toxic agents with particular emphasis on temperature and exercise

Testing of toxicity based methods to develop site specific clean up objectives - phase 1: Toxicity protocol screening and applicability

International Nuclear Information System (INIS)

Hamilton, H.; Kerr, D.; Thorne, W.; Taylor, B.; Zadnik, M.; Goudey, S.; Birkholz, D.

1994-03-01

A study was conducted to develop a cost-effective and practical protocol for using bio-assay based toxicity assessment methods for remediation of decommissioned oil and gas production, and processing facilities. The objective was to generate site-specific remediation criteria for contaminated sites. Most companies have used the chemical-specific approach which, however, did not meet the ultimate land use goal of agricultural production. The toxicity assessment method described in this study dealt with potential impairment to agricultural crop production and natural ecosystems. Human health concerns were not specifically addressed. It was suggested that chemical-specific methods should be used when human health concerns exist. . Results showed that toxicity tests will more directly identify ecological stress caused by site contamination than chemical-specific remediation criteria, which can be unnecessarily protective. 11 refs., 7 tabs., 6 figs

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

Linkage of genomic biomarkers to whole organism endpoints in a Toxicity Identification Evaluation (TIE).

Science.gov (United States)

Aquatic organisms are exposed to many toxic chemicals and interpreting the cause and effect relationships between occurrence and impairment is difficult. Toxicity Identification Evaluation (TIE) provides a systematic approach for identifying responsible toxicants. TIE relies on ...

Relationship between physico-chemical characteristics and potential toxicity of PM10.

Science.gov (United States)

Megido, Laura; Suárez-Peña, Beatriz; Negral, Luis; Castrillón, Leonor; Suárez, Susana; Fernández-Nava, Yolanda; Marañón, Elena

2016-11-01

PM10 was sampled at a suburban location affected by traffic and industry in the north of Spain. The samples were analysed to determine the chemical components of PM10 (organic and elemental carbon, soluble chemical species and metals). The aim of this study was to assess the toxicity of PM10 in terms of the bulk analysis and the physico-chemical properties of the particles. Total carbon, sulphates, ammonium, chlorides and nitrates were found to be the major constituents of PM10. The contribution of the last of these was found to increase significantly with PM10 concentration (Pearson coefficient correlation of 0.7, p-value major risk to human health. Copyright © 2016 Elsevier Ltd. All rights reserved.

In silico prediction of Tetrahymena pyriformis toxicity for diverse industrial chemicals with substructure pattern recognition and machine learning methods.

Science.gov (United States)

Cheng, Feixiong; Shen, Jie; Yu, Yue; Li, Weihua; Liu, Guixia; Lee, Philip W; Tang, Yun

2011-03-01

There is an increasing need for the rapid safety assessment of chemicals by both industries and regulatory agencies throughout the world. In silico techniques are practical alternatives in the environmental hazard assessment. It is especially true to address the persistence, bioaccumulative and toxicity potentials of organic chemicals. Tetrahymena pyriformis toxicity is often used as a toxic endpoint. In this study, 1571 diverse unique chemicals were collected from the literature and composed of the largest diverse data set for T. pyriformis toxicity. Classification predictive models of T. pyriformis toxicity were developed by substructure pattern recognition and different machine learning methods, including support vector machine (SVM), C4.5 decision tree, k-nearest neighbors and random forest. The results of a 5-fold cross-validation showed that the SVM method performed better than other algorithms. The overall predictive accuracies of the SVM classification model with radial basis functions kernel was 92.2% for the 5-fold cross-validation and 92.6% for the external validation set, respectively. Furthermore, several representative substructure patterns for characterizing T. pyriformis toxicity were also identified via the information gain analysis methods. Copyright © 2010 Elsevier Ltd. All rights reserved.

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.

Effects of toxic chemicals on the reproductive system. Council on Scientific Affairs.

Science.gov (United States)

1985-06-21

In an effort to make physicians more aware of the hazards of the workplace to pregnant workers, the Council on Scientific Affairs' Advisory Panel on Reproductive Hazards in the Workplace prepared this third and final report reviewing the effects of chemical exposure. A total of 120 chemicals were considered for reviews based on an estimation of their imminent hazard, ie, widespread use and/or inherent toxicity. Following a brief introduction, which sets out general principles, clinical applications, and aids to the recognition of a human teratogen, the report presents reviews and opinions for three representative chemicals. Information concerning the remaining 117 compounds is available upon request.

Chemical and Plant-Based Insect Repellents: Efficacy, Safety, and Toxicity.

Science.gov (United States)

Diaz, James H

2016-03-01

Most emerging infectious diseases today are arthropod-borne and cannot be prevented by vaccinations. Because insect repellents offer important topical barriers of personal protection from arthropod-borne infectious diseases, the main objectives of this article were to describe the growing threats to public health from emerging arthropod-borne infectious diseases, to define the differences between insect repellents and insecticides, and to compare the efficacies and toxicities of chemical and plant-derived insect repellents. Internet search engines were queried with key words to identify scientific articles on the efficacy, safety, and toxicity of chemical and plant-derived topical insect repellants and insecticides to meet these objectives. Data sources reviewed included case reports; case series; observational, longitudinal, and surveillance studies; and entomological and toxicological studies. Descriptive analysis of the data sources identified the most effective application of insect repellents as a combination of topical chemical repellents, either N-diethyl-3-methylbenzamide (formerly N, N-diethyl-m-toluamide, or DEET) or picaridin, and permethrin-impregnated or other pyrethroid-impregnated clothing over topically treated skin. The insecticide-treated clothing would provide contact-level insecticidal effects and provide better, longer lasting protection against malaria-transmitting mosquitoes and ticks than topical DEET or picaridin alone. In special cases, where environmental exposures to disease-transmitting ticks, biting midges, sandflies, or blackflies are anticipated, topical insect repellents containing IR3535, picaridin, or oil of lemon eucalyptus (p-menthane-3, 8-diol or PMD) would offer better topical protection than topical DEET alone. Copyright © 2016 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.

Approaches to advancing quantitative human health risk assessment of environmental chemicals in the post-genomic era.

Science.gov (United States)

Chiu, Weihsueh A; Euling, Susan Y; Scott, Cheryl Siegel; Subramaniam, Ravi P

2013-09-15

The contribution of genomics and associated technologies to human health risk assessment for environmental chemicals has focused largely on elucidating mechanisms of toxicity, as discussed in other articles in this issue. However, there is interest in moving beyond hazard characterization to making more direct impacts on quantitative risk assessment (QRA)--i.e., the determination of toxicity values for setting exposure standards and cleanup values. We propose that the evolution of QRA of environmental chemicals in the post-genomic era will involve three, somewhat overlapping phases in which different types of approaches begin to mature. The initial focus (in Phase I) has been and continues to be on "augmentation" of weight of evidence--using genomic and related technologies qualitatively to increase the confidence in and scientific basis of the results of QRA. Efforts aimed towards "integration" of these data with traditional animal-based approaches, in particular quantitative predictors, or surrogates, for the in vivo toxicity data to which they have been anchored are just beginning to be explored now (in Phase II). In parallel, there is a recognized need for "expansion" of the use of established biomarkers of susceptibility or risk of human diseases and disorders for QRA, particularly for addressing the issues of cumulative assessment and population risk. Ultimately (in Phase III), substantial further advances could be realized by the development of novel molecular and pathway-based biomarkers and statistical and in silico models that build on anticipated progress in understanding the pathways of human diseases and disorders. Such efforts would facilitate a gradual "reorientation" of QRA towards approaches that more directly link environmental exposures to human outcomes. Published by Elsevier Inc.

Approaches to advancing quantitative human health risk assessment of environmental chemicals in the post-genomic era

Energy Technology Data Exchange (ETDEWEB)

Chiu, Weihsueh A., E-mail: chiu.weihsueh@epa.gov [National Center for Environmental Assessment, U.S. Environmental Protection Agency, Washington DC, 20460 (United States); Euling, Susan Y.; Scott, Cheryl Siegel; Subramaniam, Ravi P. [National Center for Environmental Assessment, U.S. Environmental Protection Agency, Washington DC, 20460 (United States)

2013-09-15

The contribution of genomics and associated technologies to human health risk assessment for environmental chemicals has focused largely on elucidating mechanisms of toxicity, as discussed in other articles in this issue. However, there is interest in moving beyond hazard characterization to making more direct impacts on quantitative risk assessment (QRA) — i.e., the determination of toxicity values for setting exposure standards and cleanup values. We propose that the evolution of QRA of environmental chemicals in the post-genomic era will involve three, somewhat overlapping phases in which different types of approaches begin to mature. The initial focus (in Phase I) has been and continues to be on “augmentation” of weight of evidence — using genomic and related technologies qualitatively to increase the confidence in and scientific basis of the results of QRA. Efforts aimed towards “integration” of these data with traditional animal-based approaches, in particular quantitative predictors, or surrogates, for the in vivo toxicity data to which they have been anchored are just beginning to be explored now (in Phase II). In parallel, there is a recognized need for “expansion” of the use of established biomarkers of susceptibility or risk of human diseases and disorders for QRA, particularly for addressing the issues of cumulative assessment and population risk. Ultimately (in Phase III), substantial further advances could be realized by the development of novel molecular and pathway-based biomarkers and statistical and in silico models that build on anticipated progress in understanding the pathways of human diseases and disorders. Such efforts would facilitate a gradual “reorientation” of QRA towards approaches that more directly link environmental exposures to human outcomes.

Approaches to advancing quantitative human health risk assessment of environmental chemicals in the post-genomic era

International Nuclear Information System (INIS)

Chiu, Weihsueh A.; Euling, Susan Y.; Scott, Cheryl Siegel; Subramaniam, Ravi P.

2013-01-01

The contribution of genomics and associated technologies to human health risk assessment for environmental chemicals has focused largely on elucidating mechanisms of toxicity, as discussed in other articles in this issue. However, there is interest in moving beyond hazard characterization to making more direct impacts on quantitative risk assessment (QRA) — i.e., the determination of toxicity values for setting exposure standards and cleanup values. We propose that the evolution of QRA of environmental chemicals in the post-genomic era will involve three, somewhat overlapping phases in which different types of approaches begin to mature. The initial focus (in Phase I) has been and continues to be on “augmentation” of weight of evidence — using genomic and related technologies qualitatively to increase the confidence in and scientific basis of the results of QRA. Efforts aimed towards “integration” of these data with traditional animal-based approaches, in particular quantitative predictors, or surrogates, for the in vivo toxicity data to which they have been anchored are just beginning to be explored now (in Phase II). In parallel, there is a recognized need for “expansion” of the use of established biomarkers of susceptibility or risk of human diseases and disorders for QRA, particularly for addressing the issues of cumulative assessment and population risk. Ultimately (in Phase III), substantial further advances could be realized by the development of novel molecular and pathway-based biomarkers and statistical and in silico models that build on anticipated progress in understanding the pathways of human diseases and disorders. Such efforts would facilitate a gradual “reorientation” of QRA towards approaches that more directly link environmental exposures to human outcomes

Introducing Toxics

Directory of Open Access Journals (Sweden)

David C. Bellinger

2013-04-01

Full Text Available With this inaugural issue, Toxics begins its life as a peer-reviewed, open access journal focusing on all aspects of toxic chemicals. We are interested in publishing papers that present a wide range of perspectives on toxicants and naturally occurring toxins, including exposure, biomarkers, kinetics, biological effects, fate and transport, treatment, and remediation. Toxics differs from many other journals in the absence of a page or word limit on contributions, permitting authors to present their work in as much detail as they wish. Toxics will publish original research papers, conventional reviews, meta-analyses, short communications, theoretical papers, case reports, commentaries and policy perspectives, and book reviews (Book reviews will be solicited and should not be submitted without invitation. Toxins and toxicants concern individuals from a wide range of disciplines, and Toxics is interested in receiving papers that represent the full range of approaches applied to their study, including in vitro studies, studies that use experimental animal or non-animal models, studies of humans or other biological populations, and mathematical modeling. We are excited to get underway and look forward to working with authors in the scientific and medical communities and providing them with a novel venue for sharing their work. [...

Identifying developmental toxicity pathways for a subset of ToxCast chemicals using human embryonic stem cells and metabolomics

Energy Technology Data Exchange (ETDEWEB)

Kleinstreuer, N.C., E-mail: kleinstreuer.nicole@epa.gov [NCCT, US EPA, RTP, NC 27711 (United States); Smith, A.M.; West, P.R.; Conard, K.R.; Fontaine, B.R. [Stemina Biomarker Discovery, Inc., Madison, WI 53719 (United States); Weir-Hauptman, A.M. [Covance, Inc., Madison, WI 53704 (United States); Palmer, J.A. [Stemina Biomarker Discovery, Inc., Madison, WI 53719 (United States); Knudsen, T.B.; Dix, D.J. [NCCT, US EPA, RTP, NC 27711 (United States); Donley, E.L.R. [Stemina Biomarker Discovery, Inc., Madison, WI 53719 (United States); Cezar, G.G. [Stemina Biomarker Discovery, Inc., Madison, WI 53719 (United States); University of Wisconsin-Madison, Madison, WI 53706 (United States)

2011-11-15

Metabolomics analysis was performed on the supernatant of human embryonic stem (hES) cell cultures exposed to a blinded subset of 11 chemicals selected from the chemical library of EPA's ToxCast Trade-Mark-Sign chemical screening and prioritization research project. Metabolites from hES cultures were evaluated for known and novel signatures that may be indicative of developmental toxicity. Significant fold changes in endogenous metabolites were detected for 83 putatively annotated mass features in response to the subset of ToxCast chemicals. The annotations were mapped to specific human metabolic pathways. This revealed strong effects on pathways for nicotinate and nicotinamide metabolism, pantothenate and CoA biosynthesis, glutathione metabolism, and arginine and proline metabolism pathways. Predictivity for adverse outcomes in mammalian prenatal developmental toxicity studies used ToxRefDB and other sources of information, including Stemina Biomarker Discovery's predictive DevTox Registered-Sign model trained on 23 pharmaceutical agents of known developmental toxicity and differing potency. The model initially predicted developmental toxicity from the blinded ToxCast compounds in concordance with animal data with 73% accuracy. Retraining the model with data from the unblinded test compounds at one concentration level increased the predictive accuracy for the remaining concentrations to 83%. These preliminary results on a 11-chemical subset of the ToxCast chemical library indicate that metabolomics analysis of the hES secretome provides information valuable for predictive modeling and mechanistic understanding of mammalian developmental toxicity. -- Highlights: Black-Right-Pointing-Pointer We tested 11 environmental compounds in a hESC metabolomics platform. Black-Right-Pointing-Pointer Significant changes in secreted small molecule metabolites were observed. Black-Right-Pointing-Pointer Perturbed mass features map to pathways critical for normal

Identifying developmental toxicity pathways for a subset of ToxCast chemicals using human embryonic stem cells and metabolomics

International Nuclear Information System (INIS)

Kleinstreuer, N.C.; Smith, A.M.; West, P.R.; Conard, K.R.; Fontaine, B.R.; Weir-Hauptman, A.M.; Palmer, J.A.; Knudsen, T.B.; Dix, D.J.; Donley, E.L.R.; Cezar, G.G.

2011-01-01

Metabolomics analysis was performed on the supernatant of human embryonic stem (hES) cell cultures exposed to a blinded subset of 11 chemicals selected from the chemical library of EPA's ToxCast™ chemical screening and prioritization research project. Metabolites from hES cultures were evaluated for known and novel signatures that may be indicative of developmental toxicity. Significant fold changes in endogenous metabolites were detected for 83 putatively annotated mass features in response to the subset of ToxCast chemicals. The annotations were mapped to specific human metabolic pathways. This revealed strong effects on pathways for nicotinate and nicotinamide metabolism, pantothenate and CoA biosynthesis, glutathione metabolism, and arginine and proline metabolism pathways. Predictivity for adverse outcomes in mammalian prenatal developmental toxicity studies used ToxRefDB and other sources of information, including Stemina Biomarker Discovery's predictive DevTox® model trained on 23 pharmaceutical agents of known developmental toxicity and differing potency. The model initially predicted developmental toxicity from the blinded ToxCast compounds in concordance with animal data with 73% accuracy. Retraining the model with data from the unblinded test compounds at one concentration level increased the predictive accuracy for the remaining concentrations to 83%. These preliminary results on a 11-chemical subset of the ToxCast chemical library indicate that metabolomics analysis of the hES secretome provides information valuable for predictive modeling and mechanistic understanding of mammalian developmental toxicity. -- Highlights: ► We tested 11 environmental compounds in a hESC metabolomics platform. ► Significant changes in secreted small molecule metabolites were observed. ► Perturbed mass features map to pathways critical for normal development and pregnancy. ► Arginine, proline, nicotinate, nicotinamide and glutathione pathways were affected.

Comparative analysis of pharmaceuticals versus industrial chemicals acute aquatic toxicity classification according to the United Nations classification system for chemicals. Assessment of the (Q)SAR predictability of pharmaceuticals acute aquatic toxicity and their predominant acute toxic mode-of-action

DEFF Research Database (Denmark)

Sanderson, Hans; Thomsen, Marianne

2009-01-01

data. Pharmaceuticals were found to be more frequent than industrial chemicals in GHS category III. Acute toxicity was predictable (>92%) using a generic (Q)SAR ((Quantitative) Structure Activity Relationship) suggesting a narcotic MOA. Analysis of model prediction error suggests that 68...

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.

1995 Toxic chemical release inventory: Emergency Planning and Community Right-to-Know Act of 1986, Section 313

International Nuclear Information System (INIS)

Mincey, S.L.

1996-08-01

Section 313 of the Emergency Planning and Community Right-To-Know Act (EPCRA) requires the annual submittal of toxic chemical release information to the U.S. Environmental Protection Agency.Executive Order 12856, 'Federal Compliance With Right-to-Know Laws and Pollution Prevention Requirements' extends the requirements of EPCRA to all Federal agencies. The following document is the August 1996 submittal of the Hanford Site Toxic Chemical Release Inventory report. Included is a Form R for ethylene glycol, the sole chemical used in excess of the established regulatory thresholds at the Hanford Site by the U.S. Department of Energy, Richland Operations Office and its contractors during Calendar Year 1995

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

Computational chemistry approach for the early detection of drug-induced idiosyncratic liver toxicity.

Science.gov (United States)

Cruz-Monteagudo, Maykel; Cordeiro, M Natália D S; Borges, Fernanda

2008-03-01

Idiosyncratic drug toxicity (IDT), considered as a toxic host-dependent event, with an apparent lack of dose response relationship, is usually not predictable from early phases of clinical trials, representing a particularly confounding complication in drug development. Albeit a rare event (usually approach proposed in the present study, can play an important role in addressing IDT in early drug discovery. We report for the first time a systematic evaluation of classification models to predict idiosyncratic hepatotoxicity based on linear discriminant analysis (LDA), artificial neural networks (ANN), and machine learning algorithms (OneR) in conjunction with a 3D molecular structure representation and feature selection methods. These modeling techniques (LDA, feature selection to prevent over-fitting and multicollinearity, ANN to capture nonlinear relationships in the data, as well as the simple OneR classifier) were found to produce QSTR models with satisfactory internal cross-validation statistics and predictivity on an external subset of chemicals. More specifically, the models reached values of accuracy/sensitivity/specificity over 84%/78%/90%, respectively in the training series along with predictivity values ranging from ca. 78 to 86% of correctly classified drugs. An LDA-based desirability analysis was carried out in order to select the levels of the predictor variables needed to trigger the more desirable drug, i.e. the drug with lower potential for idiosyncratic hepatotoxicity. Finally, two external test sets were used to evaluate the ability of the models in discriminating toxic from nontoxic structurally and pharmacologically related drugs and the ability of the best model (LDA) in detecting potential idiosyncratic hepatotoxic drugs, respectively. The computational approach proposed here can be considered as a useful tool in early IDT prognosis.

Monitoring and trace detection of hazardous waste and toxic chemicals using resonance Raman spectroscopy

International Nuclear Information System (INIS)

Sedlacek, A.J. III; Dougherty, D.R.; Chen, C.L.

1993-01-01

Raman scattering is a coherent, inelastic, two-photon process, which shifts the frequency of an outgoing photon according to the vibrational structure of the irradiated species, thereby providing a unique fingerprint of the molecule. When involving an allowed electronic transition (resonance Raman), this scattering cross section can be enhanced by 10 4 to 10 6 and provides the basis for a viable technique that can monitor and detect trace quantities of hazardous wastes and toxic chemicals. Resonance Raman spectroscopy (RRS) possesses many of the ideal characteristics for monitoring and detecting of hazardous waste and toxic chemicals. Some of these traits are: (1) very high selectivity (chemical specific fingerprints); (2) independence from the excitation wavelength (ability to monitor in the solar blind region); (3) chemical mixture fingerprints are the sum of its individual components (no spectral cross-talk); (4) near independence of the Raman fingerprint to its physical state (very similar spectra for gas, liquid, solid and solutions -- either bulk or aerosols); and (5) insensitivity of the Raman signature to environmental conditions (no quenching). Data from a few chemicals will be presented which illustrate these features. In cases where background fluorescence accompanies the Raman signals, an effective frequency modulation technique has been developed, which can completely eliminate this interference

76 FR 38169 - Toxic Substances Control Act Chemical Testing; Receipt of Test Data

Science.gov (United States)

2011-06-29

... (7405M), Office of Pollution Prevention and Toxics, Environmental Protection Agency, 1200 Pennsylvania... gold leaf, dyeing mixtures, antifreeze mixtures, extraction of resins and waxes, preservative for...: June 21, 2011. Maria J. Doa, Director, Chemical Control Division, Office of Pollution Prevention and...

76 FR 69136 - Hydrogen Sulfide; Community Right-to-Know Toxic Chemical Release Reporting

Science.gov (United States)

2011-11-08

... Hydrogen Sulfide; Community Right-to-Know Toxic Chemical Release Reporting AGENCY: Environmental Protection Agency (EPA). ACTION: Lifting of Administrative Stay for Hydrogen Sulfide; Correction. SUMMARY: The... Administrative Stay of the reporting requirements for hydrogen sulfide. The Office of the Federal Register...

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

History of EPI Suite™ and future perspectives on chemical property estimation in US Toxic Substances Control Act new chemical risk assessments.

Science.gov (United States)

Card, Marcella L; Gomez-Alvarez, Vicente; Lee, Wen-Hsiung; Lynch, David G; Orentas, Nerija S; Lee, Mari Titcombe; Wong, Edmund M; Boethling, Robert S

2017-03-22

Chemical property estimation is a key component in many industrial, academic, and regulatory activities, including in the risk assessment associated with the approximately 1000 new chemical pre-manufacture notices the United States Environmental Protection Agency (US EPA) receives annually. The US EPA evaluates fate, exposure and toxicity under the 1976 Toxic Substances Control Act (amended by the 2016 Frank R. Lautenberg Chemical Safety for the 21 st Century Act), which does not require test data with new chemical applications. Though the submission of data is not required, the US EPA has, over the past 40 years, occasionally received chemical-specific data with pre-manufacture notices. The US EPA has been actively using this and publicly available data to develop and refine predictive computerized models, most of which are housed in EPI Suite™, to estimate chemical properties used in the risk assessment of new chemicals. The US EPA develops and uses models based on (quantitative) structure-activity relationships ([Q]SARs) to estimate critical parameters. As in any evolving field, (Q)SARs have experienced successes, suffered failures, and responded to emerging trends. Correlations of a chemical structure with its properties or biological activity were first demonstrated in the late 19 th century and today have been encapsulated in a myriad of quantitative and qualitative SARs. The development and proliferation of the personal computer in the late 20 th century gave rise to a quickly increasing number of property estimation models, and continually improved computing power and connectivity among researchers via the internet are enabling the development of increasingly complex models.

Zebrafish Get Connected: Investigating Neurotransmission Targets and Alterations in Chemical Toxicity

Directory of Open Access Journals (Sweden)

Katharine A. Horzmann

2016-08-01

Full Text Available Neurotransmission is the basis of neuronal communication and is critical for normal brain development, behavior, learning, and memory. Exposure to drugs and chemicals can alter neurotransmission, often through unknown pathways and mechanisms. The zebrafish (Danio rerio model system is increasingly being used to study the brain and chemical neurotoxicity. In this review, the major neurotransmitter systems, including glutamate, GABA, dopamine, norepinephrine, serotonin, acetylcholine, histamine, and glutamate are surveyed and pathways of synthesis, transport, metabolism, and action are examined. Differences between human and zebrafish neurochemical pathways are highlighted. We also review techniques for evaluating neurological function, including the measurement of neurotransmitter levels, assessment of gene expression through transcriptomic analysis, and the recording of neurobehavior. Finally examples of chemical toxicity studies evaluating alterations in neurotransmitter systems in the zebrafish model are reviewed.

Investigations with beagles about toxicity and radioprotective effect of the chemical radioprotection substance WR 2721

International Nuclear Information System (INIS)

Wagner, M.; Sedlmeier, H.; Wustrow, T.; Messerschmidt, O.

1980-01-01

The toxicity of the chemical radioprotection substance WR 2721 (S-2-(3-aminopropylamino)ethyl-thiophosphate) was examined in 25 beagles. The study showed that the toxicity of the substance increases as the dose gets higher. Between the doses 200 and 250 mg/kg of body weight, the increase of toxicity was significantly greater than could be expected on the basis of the dose difference. Until a dose of 200 mg/kg, the authors found no side effects which would have disturbed vital functions, but higher doses led to marked symptoms of intoxication. (orig.) [de

Low Level Chemical Toxicity: Relevance to Chemical Agent Defense

Science.gov (United States)

2005-07-01

or confirm a diagnosis of chemical sensitivity and suggest novel approaches in managing this malady. Project 4: Studies of gene expression...Lindberg I, Ugleholdt R, Holst J & Steiner DF 2002b Disruption of PC1/3 expression in mice causes dwarfism and multiple neuroendocrine peptide processing...2004;1:32- 34. [10] Diederich S,Eckmanns,T,Exner,P,Al-Saadi,N,Bahr,V,Oelkers,W. Differential diagnosis of polyuric/polydipsic syndromes with the aid

Guidance on health effects of toxic chemicals. Safety Analysis Report Update Program

Energy Technology Data Exchange (ETDEWEB)

Foust, C.B.; Griffin, G.D.; Munro, N.B.; Socolof, M.L.

1994-02-01

Martin Marietta Energy Systems, Inc. (MMES), and Martin Marietta Utility Services, Inc. (MMUS), are engaged in phased programs to update the safety documentation for the existing US Department of Energy (DOE)-owned facilities. The safety analysis of potential toxic hazards requires a methodology for evaluating human health effects of predicted toxic exposures. This report provides a consistent set of health effects and documents toxicity estimates corresponding to these health effects for some of the more important chemicals found within MMES and MMUS. The estimates are based on published toxicity information and apply to acute exposures for an ``average`` individual. The health effects (toxicological endpoints) used in this report are (1) the detection threshold; (2) the no-observed adverse effect level; (3) the onset of irritation/reversible effects; (4) the onset of irreversible effects; and (5) a lethal exposure, defined to be the 50% lethal level. An irreversible effect is defined as a significant effect on a person`s quality of life, e.g., serious injury. Predicted consequences are evaluated on the basis of concentration and exposure time.

General approaches to the risk assessment of chemicals

Energy Technology Data Exchange (ETDEWEB)

Murphy, Patrick [Commission of the European Communities, Directorate General XI, Environment, Nuclear Safety and Civil Protection (Belgium)

1992-07-01

deciding upon the granting of permits for landfill sites or the discharge of toxic chemicals to water or air and in doing so they must take into account the hydrology, geology and climate of the specific locality. While the basic approach to chemical risk assessment will be the same, irrespective of the specific objective for which the assessment is carried out, the details will vary as a function of: the product type (pharmaceutical, pesticide, industrial chemical, etc.), the target population of interest (patient, environment, consumer, worker, etc.) and the exposure scenario (global, international, national, local)

General approaches to the risk assessment of chemicals

International Nuclear Information System (INIS)

Murphy, Patrick

1992-01-01

deciding upon the granting of permits for landfill sites or the discharge of toxic chemicals to water or air and in doing so they must take into account the hydrology, geology and climate of the specific locality. While the basic approach to chemical risk assessment will be the same, irrespective of the specific objective for which the assessment is carried out, the details will vary as a function of: the product type (pharmaceutical, pesticide, industrial chemical, etc.), the target population of interest (patient, environment, consumer, worker, etc.) and the exposure scenario (global, international, national, local)

75 FR 19319 - Hydrogen Sulfide; Community Right-to-Know Toxic Chemical Release Reporting; Extension of Comment...

Science.gov (United States)

2010-04-14

... Hydrogen Sulfide; Community Right-to-Know Toxic Chemical Release Reporting; Extension of Comment Period... reporting requirements for hydrogen sulfide (Chemical Abstracts Service Number (CAS No.) 7783-06-4) (75 FR... may be potentially affected by this action if you manufacture, process, or otherwise use hydrogen...

DESIGN AND PERFORMANCE OF A XENOBIOTIC METABOLISM DATABASE MANAGER FOR METABOLIC SIMULATOR ENHANCEMENT AND CHEMICAL RISK ANALYSIS

Science.gov (United States)

A major uncertainty that has long been recognized in evaluating chemical toxicity is accounting for metabolic activation of chemicals resulting in increased toxicity. In silico approaches to predict chemical metabolism and to subsequently screen and prioritize chemicals for risk ...

Therapeutic values, chemical constituents and toxicity of Taiwanese Dysosma pleiantha--a review.

Science.gov (United States)

Karuppaiya, Palaniyandi; Tsay, Hsin Sheng

2015-07-16

Dysosma pleiantha (Hance) Woodson also called as Bajiaolian belongs to the family Berberidaceae, is widely used in Taiwan as traditional Chinese herbal medicine for more than thousands of years. It is usually recommended by various traditional Chinese medical doctors and herbal pharmacies for general remedies including postpartum recovery, treatment of weakness, neck mass, acne, hepatoma, lumbago, snakebite, tumor growth and dysmenorrhea. In the textbooks of traditional Chinese medicine, there is limited information about the toxicity of Bajiaolian. Podophyllotoxin, a lignan is the main toxic ingredient of Bajiaolian rhizome. Therefore, Bajiaolian is documented as the fifth highest cause of poisoning among the herbal medicine in Taiwan. Since the therapeutic and toxic doses are very close, Bajiaolian poisoning cases are frequently reported in Taiwan. Moreover, Dysosma poisoning cases are difficult to diagnosis because physicians are unfamiliar with this medicine's multiple clinical presentations in different stages of intoxication. Therefore, the objective of this review is to represent the collective information available in literatures regarding D. pleiantha, a cytotoxic lignan containing medicinal plant. Specifically, the literatures have been reviewed for articles pertaining to chemical constituents, properties, therapeutical benefits, toxicity, poisoning symptoms, toxic as well as therapeutic dose and medical management. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Toxic industrial chemicals (TICs) as asymmetric weapons: the design basis threat

International Nuclear Information System (INIS)

Skinner, L.

2009-01-01

Asymmetric warfare concepts relate well to the use of improvised chemical weapons against urban targets. Sources of information on toxic industrial chemicals (TICs) and lists of high threat chemicals are available that point to likely choices for an attack. Accident investigations can be used as a template for attacks, and to judge the possible effectiveness of an attack using TICs. The results of a chlorine rail car accident in South Carolina, USA and the Russian military assault on a Moscow theater provide many illustrative points for similar incidents that mighty be carried out deliberately. Computer modeling of outdoor releases shows how an attack might take into consideration issues of stand-off distance and dilution. Finally, the preceding may be used to estimate with some accuracy the design basis threat posed by the used of TICs as weapons.(author)

Copper bioavailability and toxicity to Mytilus galloprovincialis in Shelter Island Yacht Basin, San Diego, CA.

Science.gov (United States)

Bosse, Casey; Rosen, Gunther; Colvin, Marienne; Earley, Patrick; Santore, Robert; Rivera-Duarte, Ignacio

2014-08-15

The bioavailability and toxicity of copper (Cu) in Shelter Island Yacht Basin (SIYB), San Diego, CA, USA, was assessed with simultaneous toxicological, chemical, and modeling approaches. Toxicological measurements included laboratory toxicity testing with Mytilus galloprovincialis (Mediterranean mussel) embryos added to both site water (ambient) and site water spiked with multiple Cu concentrations. Chemical assessment of ambient samples included total and dissolved Cu concentrations, and Cu complexation capacity measurements. Modeling was based on chemical speciation and predictions of bioavailability and toxicity using a marine Biotic Ligand Model (BLM). Cumulatively, these methods assessed the natural buffering capacity of Cu in SIYB during singular wet and dry season sampling events. Overall, the three approaches suggested negligible bioavailability, and isolated observed or predicted toxicity, despite an observed gradient of increasing Cu concentration, both horizontally and vertically within the water body, exceeding current water quality criteria for saltwater. Published by Elsevier Ltd.

Biodegradation of toxic chemicals by Pleurotus eryngii in submerged fermentation and solid-state fermentation.

Science.gov (United States)

Chang, Bea-Ven; Chang, Yi-Ming

2016-04-01

The toxic chemicals bisphenol A (BPA), bisphenol F (BPF), nonylphenol (NP), and tetrabromobisphenol A (TBBPA) are endocrine-disrupting chemicals that have consequently drawn much concern regarding their effect on the environment. The objectives of this study were to investigate the degradation of BPA, BPF, NP, and TBBPA by enzymes from Pleurotus eryngii in submerged fermentation (SmF) and solid-state fermentation (SSF), and also to assess the removal of toxic chemicals in spent mushroom compost (SMC). BPA and BPF were analyzed by high-performance liquid chromatography; NP and TBBPA were analyzed by gas chromatography. NP degradation was enhanced by adding CuSO4 (1 mM), MnSO4 (0.5 mM), gallic acid (1 mM), tartaric acid (20 mM), citric acid (20 mM), guaiacol (1 mM), or 2,2'-azino-bis- (3-ethylbenzothiazoline-6-sulfonic acid; 1 mM), with the last yielding a higher NP degradation rate than the other additives from SmF. The optimal conditions for enzyme activity from SSF were a sawdust/wheat bran ratio of 1:4 and a moisture content of 5 mL/g. The enzyme activities were higher with sawdust/wheat bran than with sawdust/rice bran. The optimal conditions for the extraction of enzyme from SMC required using sodium acetate buffer (pH 5.0, solid/solution ratio 1:5), and extraction over 3 hours. The removal rates of toxic chemicals by P. eryngii, in descending order of magnitude, were SSF > SmF > SMC. The removal rates were BPF > BPA > NP > TBBPA. Copyright © 2014. Published by Elsevier B.V.

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...

Insect-gene-activity detection system for chemical and biological warfare agents and toxic industrial chemicals

Science.gov (United States)

Mackie, Ryan S.; Schilling, Amanda S.; Lopez, Arturo M.; Rayms-Keller, Alfredo

2002-02-01

Detection of multiple chemical and biological weapons (CBW) agents and/or complex mixtures of toxic industrial chemicals (TIC) is imperative for both the commercial and military sectors. In a military scenario, a multi-CBW attack would create confusion, thereby delaying decontamination and therapeutic efforts. In the commercial sector, polluted sites invariably contain a mixture of TIC. Novel detection systems capable of detecting CBW and TIC are sorely needed. While it may be impossible to build a detector capable of discriminating all the possible combinations of CBW, a detection system capable of statistically predicting the most likely composition of a given mixture is within the reach of current emerging technologies. Aquatic insect-gene activity may prove to be a sensitive, discriminating, and elegant paradigm for the detection of CBW and TIC. We propose to systematically establish the expression patterns of selected protein markers in insects exposed to specific mixtures of chemical and biological warfare agents to generate a library of biosignatures of exposure. The predicting capabilities of an operational library of biosignatures of exposures will allow the detection of emerging novel or genetically engineered agents, as well as complex mixtures of chemical and biological weapons agents. CBW and TIC are discussed in the context of war, terrorism, and pollution.

Environmental toxicity of Chemical Warfare Agents (CWAs) - MicrotoxTM and Spontaneous Locomotor Changes

DEFF Research Database (Denmark)

Storgaard, Morten Swayne; Sanderson, Hans; Baatrup, Erik

After the 2nd World War the CWAs were prohibited by law and 11,000 tonnes of toxic agents were dumped in the Bornholm Basin east of Bornholm. The dumped chemical munitions have not reached attention from politicians and scientists until recently. During earlier projects, such as MERCW (2005...

Genetic and chemical modifiers of a CUG toxicity model in Drosophila.

Directory of Open Access Journals (Sweden)

Amparo Garcia-Lopez

2008-02-01

Full Text Available Non-coding CUG repeat expansions interfere with the activity of human Muscleblind-like (MBNL proteins contributing to myotonic dystrophy 1 (DM1. To understand this toxic RNA gain-of-function mechanism we developed a Drosophila model expressing 60 pure and 480 interrupted CUG repeats in the context of a non-translatable RNA. These flies reproduced aspects of the DM1 pathology, most notably nuclear accumulation of CUG transcripts, muscle degeneration, splicing misregulation, and diminished Muscleblind function in vivo. Reduced Muscleblind activity was evident from the sensitivity of CUG-induced phenotypes to a decrease in muscleblind genetic dosage and rescue by MBNL1 expression, and further supported by the co-localization of Muscleblind and CUG repeat RNA in ribonuclear foci. Targeted expression of CUG repeats to the developing eye and brain mushroom bodies was toxic leading to rough eyes and semilethality, respectively. These phenotypes were utilized to identify genetic and chemical modifiers of the CUG-induced toxicity. 15 genetic modifiers of the rough eye phenotype were isolated. These genes identify putative cellular processes unknown to be altered by CUG repeat RNA, and they include mRNA export factor Aly, apoptosis inhibitor Thread, chromatin remodelling factor Nurf-38, and extracellular matrix structural component Viking. Ten chemical compounds suppressed the semilethal phenotype. These compounds significantly improved viability of CUG expressing flies and included non-steroidal anti-inflammatory agents (ketoprofen, muscarinic, cholinergic and histamine receptor inhibitors (orphenadrine, and drugs that can affect sodium and calcium metabolism such as clenbuterol and spironolactone. These findings provide new insights into the DM1 phenotype, and suggest novel candidates for DM1 treatments.

Dependence of Nanoparticle Toxicity on Their Physical and Chemical Properties

Science.gov (United States)

Sukhanova, Alyona; Bozrova, Svetlana; Sokolov, Pavel; Berestovoy, Mikhail; Karaulov, Alexander; Nabiev, Igor

2018-02-01

Studies on the methods of nanoparticle (NP) synthesis, analysis of their characteristics, and exploration of new fields of their applications are at the forefront of modern nanotechnology. The possibility of engineering water-soluble NPs has paved the way to their use in various basic and applied biomedical researches. At present, NPs are used in diagnosis for imaging of numerous molecular markers of genetic and autoimmune diseases, malignant tumors, and many other disorders. NPs are also used for targeted delivery of drugs to tissues and organs, with controllable parameters of drug release and accumulation. In addition, there are examples of the use of NPs as active components, e.g., photosensitizers in photodynamic therapy and in hyperthermic tumor destruction through NP incorporation and heating. However, a high toxicity of NPs for living organisms is a strong limiting factor that hinders their use in vivo. Current studies on toxic effects of NPs aimed at identifying the targets and mechanisms of their harmful effects are carried out in cell culture models; studies on the patterns of NP transport, accumulation, degradation, and elimination, in animal models. This review systematizes and summarizes available data on how the mechanisms of NP toxicity for living systems are related to their physical and chemical properties.

Toxicity of fire retardant chemicals and fire suppressant foams to vertebrate and invertebrate wildlife species

Science.gov (United States)

Vyas, Nimish B.; Hill, Elwood F.

1996-01-01

Under laboratory conditions, acute single-dose oral toxicity tests (LD50) were conducted with three fire retardant chemicals (Fire-Trol GTS-R, Phos-Chek D75-F, and Fire-Trol LCG-R) and two fire suppressant foams (Silv-Ex and Phos-Chek WD-881) to determine effects on adult northern bobwhite, American kestrel, red-winged blackbird, and white-footed mouse. In addition, earthworms were exposed (LC50) for 14 days in treated soil.In general, no toxic responses were evident. For northern bobwhite, the LD50 for all five chemicals was >2000 mg a.l./kg of body mass. American kestrels regurgitated all chemicals except Silv-ex; LD50s all exceeded 2000 mg/kg. The LD50 for red-winged blackbird was also >2000 mg/kg for all chemicals except Fire-Trol GTS-R which is currently undergoing further testing. In addition, the LD50 for white-footed mouse was >2000 mg/kg for Phos-Chek D75F. The 14-day LC50 for earthworms was >1000 ppm for all chemicals. Therefore, we concluded that these retardants and foams do not pose an acute hazard to adult birds, mammals, or earthworms. However, ecological studies to evaluate the potential effects of these formulations on vertebrate behavior and population dynamics are in progress.

Exploring Chemical Routes Relevant to the Toxicity of Paracetamol and Its meta-Analogue at a Molecular Level.

Science.gov (United States)

Castañeda-Arriaga, Romina; Galano, Annia

2017-06-19

Several chemical routes related to the toxicity of paracetamol (APAP, also known as acetaminophen), its analogue N-acetyl-m-aminophenol (AMAP), and their deacetylated derivatives, were investigated using the density functional theory. It was found that AMAP is more resilient to chemical oxidation than APAP. The chemical degradation of AMAP into radical intermediates is predicted to be significant only when it is induced by strong oxidants. This might explain the apparent contradictions among experimental evidence regarding AMAP toxicity. All of the investigated species are incapable of oxidizing DNA, but they can damage lipids by H atom transfer (HAT) from the bis-allylic site, with the phenoxyl radical of AMAP being the most threatening to the lipids' chemical integrity. Regarding protein damage, Cys residues were identified as the most likely targets. The damage in this case may involve two different routes: (i) HAT from the thiol site by phenoxyl radicals and (ii) protein arylation by the quinone imine (QI) derivatives. Both are not only thermochemically viable, but also are very fast reactions. According to the mechanism identified here as the most likely one for protein arylation, a rather large concentration of QI would be necessary for this damage to be significant. This might explain why APAP is nontoxic in therapeutic doses, while overdoses can result in hepatic toxicity. In addition, the QI derived from both APAP and AMAP were found to be capable of inflicting this kind of damage. In addition, it is proposed that they might increase • OH production via the Fenton reaction, which would contribute to their toxicity.

ToxiFly: Can Fruit Flies be Used to Identify Toxicity Pathways for Airborne Chemicals?

Science.gov (United States)

Current high-throughput and alternative screening assays for chemical toxicity are unable to test volatile organic compounds (VOCs), thus limiting their scope. Further, the data generated by these assays require mechanistic information to link effects at molecular targets to adve...

[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.

2002 Toxic Chemical Release Inventory Report for the Emergency Planning and Community Right-to-Know Act of 1986, Title III, Section 313

International Nuclear Information System (INIS)

Stockton, M.

2003-01-01

For reporting year 2002, Los Alamos National Laboratory (LANL or the Laboratory) submitted Form R reports for lead compounds and mercury as required under the Emergency Planning and Community Right-to-Know Act (EPCRA), Section 313. No other EPCRA Section 313 chemicals were used in 2002 above the reportable thresholds. This document was prepared to provide a description of the evaluation of EPCRA Section 313 chemical usage and threshold determinations for LANL for calendar year 2002 as well as provide background information about the data included on the Form R reports. Section 313 of EPCRA specifically requires facilities to submit a Toxic Chemical Release Inventory report (Form R) to the U.S. Environmental Protection Agency (EPA) and state agencies if the owners and operators manufacture, process, or otherwise use any of the listed toxic chemicals above listed threshold quantities. EPA compiles this data in the Toxic Release Inventory database. Form R reports for each chemical over threshold quantities must be submitted on or before July 1 each year and must cover activities that occurred at the facility during the previous year. In 1999 EPA promulgated a final rule on Persistent Bioaccumulative Toxics (PBTs). This rule added several chemicals to the EPCRA Section 313 list of toxic chemicals and established lower reporting thresholds for these and other PBT chemicals that were already reportable under EPCRA Section 313. These lower thresholds became applicable in reporting year 2000. In 2001, EPA expanded the PBT rule to include a lower reporting threshold for lead and lead compounds. Facilities that manufacture, process, or otherwise use more than 100 lb of lead or lead compounds must submit a Form R

2006 Toxic Chemical Release Inventory Report for the Emergency Planning and Community Right-to-Know Act of 1986, Title III, Section 313

Energy Technology Data Exchange (ETDEWEB)

Ecology and Air Quality Group (ENV-EAQ)

2007-12-12

For reporting year 2006, Los Alamos National Laboratory (LANL or the Laboratory) submitted Form R reports for lead as required under the Emergency Planning and Community Right-to-Know Act (EPCRA) Section 313. No other EPCRA Section 313 chemicals were used in 2006 above the reportable thresholds. This document was prepared to provide a description of the evaluation of EPCRA Section 313 chemical use and threshold determinations for LANL for calendar year 2006, as well as to provide background information about data included on the Form R reports. Section 313 of EPCRA specifically requires facilities to submit a Toxic Chemical Release Inventory Report (Form R) to the U.S. Environmental Protection Agency (EPA) and state agencies if the owners and operators manufacture, process, or otherwise use any of the listed toxic chemicals above listed threshold quantities. EPA compiles this data in the Toxic Release Inventory database. Form R reports for each chemical over threshold quantities must be submitted on or before July 1 each year and must cover activities that occurred at the facility during the previous year. In 1999, EPA promulgated a final rule on persistent bioaccumulative toxics (PBTs). This rule added several chemicals to the EPCRA Section 313 list of toxic chemicals and established lower reporting thresholds for these and other PBT chemicals that were already reportable. These lower thresholds became applicable in reporting year 2000. In 2001, EPA expanded the PBT rule to include a lower reporting threshold for lead and lead compounds. Facilities that manufacture, process, or otherwise use more than 100 lb of lead or lead compounds must submit a Form R.

Sacrifice zones: the front lines of toxic chemical exposure in the United States

National Research Council Canada - National Science Library

Lerner, Steve

2010-01-01

... States of America. Library of Congress Cataloging-in-Publication Data Lerner, Steve. Sacrifice zones: the front lines of toxic chemical exposure in the United States / Steve Lerner. p. cm. Includes bibliographical references and index. ISBN 978-0-262-01440-3 (hardcover : alk. paper) 1. Environmental toxicology- United States- Case studies. 2. Che...

Probing nanomechanical interaction at the interface between biological membrane and potentially toxic chemical.

Science.gov (United States)

Lim, Chanoong; Park, Sohee; Park, Jinwoo; Ko, Jina; Lee, Dong Woog; Hwang, Dong Soo

2018-04-12

Various xenobiotics interact with biological membranes, and precise evaluations of the molecular interactions between them are essential to foresee the toxicity and bioavailability of existing or newly synthesized molecules. In this study, surface forces apparatus (SFA) measurement and Langmuir trough based tensiometry are performed to reveal nanomechanical interaction mechanisms between potential toxicants and biological membranes for ex vivo toxicity evaluation. As a toxicant, polyhexamethylene guanidine (PHMG) was selected because PHMG containing humidifier disinfectant and Vodka caused lots of victims in both S. Korea and Russia, respectively, due to the lack of holistic toxicity evaluation of PHMG. Here, we measured strong attraction (Wad ∼4.2 mJ/m 2 ) between PHMG and head group of biological membranes while no detectable adhesion force between the head group and control molecules was measured. Moreover, significant changes in π-A isotherm of 1,2-Dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) monolayers were measured upon PHMG adsorption. These results indicate PHMG strongly binds to hydrophilic group of lipid membranes and alters the structural and phase behavior of them. More importantly, complementary utilization of SFA and Langmuir trough techniques are found to be useful to predict the potential toxicity of a chemical by evaluating the molecular interaction with biological membranes, the primary protective barrier for living organisms. Copyright © 2018 Elsevier B.V. All rights reserved.

Toxicity assessments of nonsteroidal anti-inflammatory drugs in isolated mitochondria, rat hepatocytes, and zebrafish show good concordance across chemical classes

Energy Technology Data Exchange (ETDEWEB)

Nadanaciva, Sashi [Compound Safety Prediction, Worldwide Medicinal Chemistry, Pfizer, Inc., Groton, CT 06340 (United States); Aleo, Michael D. [Drug Safety Research and Development, Pfizer Inc., Groton, CT 06340 (United States); Strock, Christopher J. [Cyprotex US, Watertown, MA 02472 (United States); Stedman, Donald B. [Drug Safety Research and Development, Pfizer Inc., Groton, CT 06340 (United States); Wang, Huijun [Computational Sciences, Pfizer Inc., Groton, CT 06340 (United States); Will, Yvonne, E-mail: yvonne.will@pfizer.com [Compound Safety Prediction, Worldwide Medicinal Chemistry, Pfizer, Inc., Groton, CT 06340 (United States)

2013-10-15

To reduce costly late-stage compound attrition, there has been an increased focus on assessing compounds in in vitro assays that predict attributes of human safety liabilities, before preclinical in vivo studies are done. Relevant questions when choosing a panel of assays for predicting toxicity are (a) whether there is general concordance in the data among the assays, and (b) whether, in a retrospective analysis, the rank order of toxicity of compounds in the assays correlates with the known safety profile of the drugs in humans. The aim of our study was to answer these questions using nonsteroidal anti-inflammatory drugs (NSAIDs) as a test set since NSAIDs are generally associated with gastrointestinal injury, hepatotoxicity, and/or cardiovascular risk, with mitochondrial impairment and endoplasmic reticulum stress being possible contributing factors. Eleven NSAIDs, flufenamic acid, tolfenamic acid, mefenamic acid, diclofenac, meloxicam, sudoxicam, piroxicam, diflunisal, acetylsalicylic acid, nimesulide, and sulindac (and its two metabolites, sulindac sulfide and sulindac sulfone), were tested for their effects on (a) the respiration of rat liver mitochondria, (b) a panel of mechanistic endpoints in rat hepatocytes, and (c) the viability and organ morphology of zebrafish. We show good concordance for distinguishing among/between NSAID chemical classes in the observations among the three approaches. Furthermore, the assays were complementary and able to correctly identify “toxic” and “non-toxic” drugs in accordance with their human safety profile, with emphasis on hepatic and gastrointestinal safety. We recommend implementing our multi-assay approach in the drug discovery process to reduce compound attrition. - Highlights: • NSAIDS cause liver and GI toxicity. • Mitochondrial uncoupling contributes to NSAID liver toxicity. • ER stress is a mechanism that contributes to liver toxicity. • Zebrafish and cell based assays are complimentary.

Toxicity assessments of nonsteroidal anti-inflammatory drugs in isolated mitochondria, rat hepatocytes, and zebrafish show good concordance across chemical classes

International Nuclear Information System (INIS)

Nadanaciva, Sashi; Aleo, Michael D.; Strock, Christopher J.; Stedman, Donald B.; Wang, Huijun; Will, Yvonne

2013-01-01

To reduce costly late-stage compound attrition, there has been an increased focus on assessing compounds in in vitro assays that predict attributes of human safety liabilities, before preclinical in vivo studies are done. Relevant questions when choosing a panel of assays for predicting toxicity are (a) whether there is general concordance in the data among the assays, and (b) whether, in a retrospective analysis, the rank order of toxicity of compounds in the assays correlates with the known safety profile of the drugs in humans. The aim of our study was to answer these questions using nonsteroidal anti-inflammatory drugs (NSAIDs) as a test set since NSAIDs are generally associated with gastrointestinal injury, hepatotoxicity, and/or cardiovascular risk, with mitochondrial impairment and endoplasmic reticulum stress being possible contributing factors. Eleven NSAIDs, flufenamic acid, tolfenamic acid, mefenamic acid, diclofenac, meloxicam, sudoxicam, piroxicam, diflunisal, acetylsalicylic acid, nimesulide, and sulindac (and its two metabolites, sulindac sulfide and sulindac sulfone), were tested for their effects on (a) the respiration of rat liver mitochondria, (b) a panel of mechanistic endpoints in rat hepatocytes, and (c) the viability and organ morphology of zebrafish. We show good concordance for distinguishing among/between NSAID chemical classes in the observations among the three approaches. Furthermore, the assays were complementary and able to correctly identify “toxic” and “non-toxic” drugs in accordance with their human safety profile, with emphasis on hepatic and gastrointestinal safety. We recommend implementing our multi-assay approach in the drug discovery process to reduce compound attrition. - Highlights: • NSAIDS cause liver and GI toxicity. • Mitochondrial uncoupling contributes to NSAID liver toxicity. • ER stress is a mechanism that contributes to liver toxicity. • Zebrafish and cell based assays are complimentary

In Vitro Screening of Environmental Chemicals for Targeted Testing Prioritization: The ToxCast Project

OpenAIRE

Judson, Richard S.; Houck, Keith A.; Kavlock, Robert J.; Knudsen, Thomas B.; Martin, Matthew T.; Mortensen, Holly M.; Reif, David M.; Rotroff, Daniel M.; Shah, Imran; Richard, Ann M.; Dix, David J.

2009-01-01

Background Chemical toxicity testing is being transformed by advances in biology and computer modeling, concerns over animal use, and the thousands of environmental chemicals lacking toxicity data. The U.S. Environmental Protection Agency?s ToxCast program aims to address these concerns by screening and prioritizing chemicals for potential human toxicity using in vitro assays and in silico approaches. Objectives This project aims to evaluate the use of in vitro assays for understanding the ty...

Acute and chronic toxicity study of the water accommodated fraction (WAF), chemically enhanced WAF (CEWAF) of crude oil and dispersant in the rock pool copepod Tigriopus japonicus.

Science.gov (United States)

Lee, Kyun-Woo; Shim, Won Joon; Yim, Un Hyuk; Kang, Jung-Hoon

2013-08-01

We determined the toxicity of the water accommodated hydrocarbon fraction (WAF), two chemically enhanced WAFs (CEWAFs; CEWAF-C, Crude oil+Corexit 9500 and CEWAF-H, Crude oil+Hiclean) of crude oil and two dispersants (Corexit 9500 and Hiclean) to the rock pool copepod Tigriopus japonicus. In the acute toxicity test, Corexit 9500 was the most toxic of all the chemicals studied. The nauplius stage of T. japonicus was more susceptible to the toxic chemicals studied than the adult female. The toxicity data using the nauplius stage was then considered as baseline to determine the spiking concentration of chemicals for chronic toxicity tests on the copepod. As the endpoints in the chronic toxicity test, survival, sex ratio, developmental time and fecundity of the copepod were used. All chemicals used in this study resulted in increased toxicity in the F1 generation. The lowest-observed-adverse-effect (LOAE) concentrations of WAF, CEWAF-H, CEWAF-C, Hiclean and Corexit 9500 were observed to be 50%, 10%, 0.1%, 1% and 1%, respectively. The results in present study imply that copepods in marine may be negatively influenced by spilled oil and dispersant. Copyright © 2013 Elsevier Ltd. All rights reserved.

Analysis of Chemical Bioactivity through In Vitro Profiling ...

Science.gov (United States)

Safety assessment of drugs and environmental chemicals relies extensively on animal testing. However, the quantity of chemicals needing assessment and challenges of species extrapolation drive the development of alternative approaches. The EPA’s ToxCast and the multiagency Tox21 programs address this through use of an extensive in vitro screening program to generate data on a large library of important environmental chemicals. These in vitro assays encompass both cell-free, biochemical assays targeting proteins that may be potential molecular initiating events and cellular assays that provide coverage of critical signaling pathways and toxicity phenotypes. Effects on model organisms such as the developing zebrafish, are also part of the testing strategy. A variety of computational approaches are used to analyze the resulting complex data sets to gain insight in to inherent biological activity of chemicals and possible mechanisms of toxicity. Several case studies including identification of modulators of estrogen receptor and aromatic hydrocarbon receptor pathways with effects in primary human cell systems will be described. In addition, existing in vivo data from a subset of the chemicals was used to anchor predictive models using in vitro data for a number of adverse endpoints including reproductive and developmental toxicities. The strengths and weaknesses of this approach will be described. This work does not necessarily reflect official Agency policy. Pres

Amazing variational approach to chemical reactions

OpenAIRE

Fernández, Francisco M.

2009-01-01

In this letter we analyse an amazing variational approach to chemical reactions. Our results clearly show that the variational expressions are unsuitable for the analysis of empirical data obtained from chemical reactions.

Comparative analysis of pharmaceuticals versus industrial chemicals acute aquatic toxicity classification according to the United Nations classification system for chemicals. Assessment of the (Q)SAR predictability of pharmaceuticals acute aquatic toxicity and their predominant acute toxic mode-of-action

DEFF Research Database (Denmark)

Sanderson, Hans; Thomsen, Marianne

2009-01-01

data. Pharmaceuticals were found to be more frequent than industrial chemicals in GHS category III. Acute toxicity was predictable (>92%) using a generic (Q)SAR ((Quantitative) Structure Activity Relationship) suggesting a narcotic MOA. Analysis of model prediction error suggests that 68...... a comprehensive database based on OECD's standardized measured ecotoxicological data and to evaluate if there is generally cause of greater concern with regards to pharmaceutical aquatic toxicological profiles relative to industrial chemicals. Comparisons were based upon aquatic ecotoxicity classification under...... the United Nations Global Harmonized System for classification and labeling of chemicals (GHS). Moreover, we statistically explored whether the predominant mode-of-action (MOA) for pharmaceuticals is narcosis. We found 275 pharmaceuticals with 569 acute aquatic effect data; 23 pharmaceuticals had chronic...

Evaluation of an adherent mouse embryonic stem cell in vitro assay to predict developmental toxicity of ToxCast chemicals.

Science.gov (United States)

The potential for most environmental chemicals to produce developmental toxicity is unknown. Mouse embryonic stem cell (mESC) assays are an alternative in vitro model to assess chemicals. The chemical space evaluated using mESC and compared to in vivo is limited. We used an adher...

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

Assessing joint toxicity of chemicals in Enchytraeus albidus (Enchytraeidae) and Porcellionides pruinosus (Isopoda) using avoidance behaviour as an endpoint

International Nuclear Information System (INIS)

Loureiro, Susana; Amorim, Monica J.B.; Campos, Bruno; Rodrigues, Sandra M.G.; Soares, Amadeu M.V.M.

2009-01-01

Contamination problems are often characterized by complex mixtures of chemicals. There are two conceptual models usually used to evaluate patterns of mixture toxicity: Concentration Addition (CA) and Independent Action (IA). Deviations from these models as synergism, antagonism and dose dependency also occur. In the present study, single and mixture toxicity of atrazine, dimethoate, lindane, zinc and cadmium were tested in Porcellionides pruinosus and Enchytraeus albidus, using avoidance as test parameter. For both species patterns of antagonism were found when exposed to dimethoate and atrazine, synergism for lindane and dimethoate exposures (with the exception of lower doses in the isopod case study) and concentration addition for cadmium and zinc occurred, while the exposure to cadmium and dimethoate showed dissimilar patterns. This study highlights the importance of dose dependencies when testing chemical mixtures and that avoidance tests can also be used to asses the effects of mixture toxicity. - Avoidance behaviour to binary mixtures of chemicals in two edaphic species

Passive dosing of pyrethroid insecticides to Daphnia magna: Expressing excess toxicity by chemical activity

DEFF Research Database (Denmark)

Nørgaard Schmidt, Stine; Gan, Jay; Kretschmann, A. C.

2015-01-01

) Effective chemical activities resulting in 50% immobilisation (Ea50) will be estimated from pyrethroid EC50 values via the correlation of sub-cooled liquid solubility (S L, [mmol/L], representing a=1) and octanol to water partitioning ratios (Kow), (3) The excess toxicity observed for pyrethroids...

Toxic chemical considerations for tank farm releases. Revision 1

Energy Technology Data Exchange (ETDEWEB)

Van Keuren, J.C.

1995-11-01

This document provides a method of determining the toxicological consequences of accidental releases from Hanford Tank Farms. A determination was made of the most restrictive toxic chemicals that are expected to be present in the tanks. Concentrations were estimated based on the maximum sample data for each analyte in all the tanks in the composite. Composite evaluated were liquids and solids from single shell tanks, double shell tanks, flammable gas watch list tanks, as well as all solids, all liquids, head space gases, and 241-C-106 solids. A sum of fractions of the health effects was computed for each composite for unit releases based emergency response planning guidelines (ERPGs). Where ERPGs were not available for chemical compounds of interest, surrogate guidelines were established. The calculation method in this report can be applied to actual release scenarios by multiplying the sum of fractions by the release rate for continuous releases, or the release amount for puff releases. Risk guidelines are met if the product is less than for equal to one.

Toxic chemical considerations for tank farm releases. Revision 1

International Nuclear Information System (INIS)

Van Keuren, J.C.

1995-11-01

This document provides a method of determining the toxicological consequences of accidental releases from Hanford Tank Farms. A determination was made of the most restrictive toxic chemicals that are expected to be present in the tanks. Concentrations were estimated based on the maximum sample data for each analyte in all the tanks in the composite. Composite evaluated were liquids and solids from single shell tanks, double shell tanks, flammable gas watch list tanks, as well as all solids, all liquids, head space gases, and 241-C-106 solids. A sum of fractions of the health effects was computed for each composite for unit releases based emergency response planning guidelines (ERPGs). Where ERPGs were not available for chemical compounds of interest, surrogate guidelines were established. The calculation method in this report can be applied to actual release scenarios by multiplying the sum of fractions by the release rate for continuous releases, or the release amount for puff releases. Risk guidelines are met if the product is less than for equal to one

Predicting Chemical Toxicity from Proteomics and Computational Chemistry

Science.gov (United States)

2008-07-30

perfluorooctanoic acid , perfluorodecanoic acid , clofibrate , and diethylhexyl phthalate) show that the leading eigenvalue of the D/D matrix derived from embedded... clofibrate , and DEHP, show that this approach clusters the first three highly-fluorinated and mechanistically similar chemicals together, while

Taking Multiple Exposure Into Account Can Improve Assessment of Chemical Risks.

Science.gov (United States)

Clerc, Frédéric; Bertrand, Nicolas Jean Hyacinthe; La Rocca, Bénédicte

2017-12-15

During work, operators may be exposed to several chemicals simultaneously. Most exposure assessment approaches only determine exposure levels for each substance individually. However, such individual-substance approaches may not correctly estimate the toxicity of 'cocktails' of chemicals, as the toxicity of a cocktail may differ from the toxicity of substances on their own. This study presents an approach that can better take into account multiple exposure when assessing chemical risks. Almost 30000 work situations, monitored between 2005 and 2014 and recorded in two French databases, were analysed using MiXie software. The algorithms employed in MiXie can identify toxicological classes associated with several substances, based on the additivity of the selected effects of each substance. The results of our retrospective analysis show that MiXie was able to identify almost 20% more potentially hazardous situations than identified using a single-substance approach. It therefore appears essential to review the ways in which multiple exposure is taken into account during risk assessment. © The Author(s) 2017. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.

Physical and toxic properties of hazardous chemicals regularly stored and transported in the vicinity of nuclear installations

International Nuclear Information System (INIS)

1976-03-01

This report gives a compilation of data based on information assembled by the US Nuclear Regulatory Commission and completed by the Safety and Reliability Directorate of the UK AEA, the Dutch Reactor Safety Commission, the French Atomic Energy Commission, and the CSNI Secretariat. Data sheets for a large number of hazardous chemicals are presented (from acetaldehyde to xylene), giving details of their physical and toxic properties such as: molecular weight, boiling point, vapor density, heat of vaporization, toxic concentration in air, flammability limits, toxic effects, vapor pressure data, etc.

QSAR modeling of toxicity of diverse organic chemicals to Daphnia magna using 2D and 3D descriptors

International Nuclear Information System (INIS)

Kar, Supratik; Roy, Kunal

2010-01-01

One of the major economic alternatives to experimental toxicity testing is the use of quantitative structure-activity relationships (QSARs) which are used in formulating regulatory decisions of environmental protection agencies. In this background, we have modeled a large diverse group of 297 chemicals for their toxicity to Daphnia magna using mechanistically interpretable descriptors. Three-dimensional (3D) (electronic and spatial) and two-dimensional (2D) (topological and information content indices) descriptors along with physicochemical parameter log K o/w (n-octanol/water partition coefficient) and structural descriptors were used as predictor variables. The QSAR models were developed by stepwise multiple linear regression (MLR), partial least squares (PLS), genetic function approximation (GFA), and genetic PLS (G/PLS). All the models were validated internally and externally. Among several models developed using different chemometric tools, the best model based on both internal and external validation characteristics was a PLS equation with 7 descriptors and three latent variables explaining 67.8% leave-one-out predicted variance and 74.1% external predicted variance. The PLS model suggests that higher lipophilicity and electrophilicity, less negative charge surface area and presence of ether linkage, hydrogen bond donor groups and acetylenic carbons are responsible for greater toxicity of chemicals. The developed model may be used for prediction of toxicity, safety and risk assessment of chemicals to achieve better ecotoxicological management and prevent adverse health consequences.

QSAR modeling of toxicity of diverse organic chemicals to Daphnia magna using 2D and 3D descriptors

Energy Technology Data Exchange (ETDEWEB)

Kar, Supratik [Drug Theoretics and Cheminformatics Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Raja S C Mullick Road, Kolkata 700032 (India); Roy, Kunal, E-mail: kunalroy_in@yahoo.com [Drug Theoretics and Cheminformatics Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Raja S C Mullick Road, Kolkata 700032 (India)

2010-05-15

One of the major economic alternatives to experimental toxicity testing is the use of quantitative structure-activity relationships (QSARs) which are used in formulating regulatory decisions of environmental protection agencies. In this background, we have modeled a large diverse group of 297 chemicals for their toxicity to Daphnia magna using mechanistically interpretable descriptors. Three-dimensional (3D) (electronic and spatial) and two-dimensional (2D) (topological and information content indices) descriptors along with physicochemical parameter log K{sub o/w} (n-octanol/water partition coefficient) and structural descriptors were used as predictor variables. The QSAR models were developed by stepwise multiple linear regression (MLR), partial least squares (PLS), genetic function approximation (GFA), and genetic PLS (G/PLS). All the models were validated internally and externally. Among several models developed using different chemometric tools, the best model based on both internal and external validation characteristics was a PLS equation with 7 descriptors and three latent variables explaining 67.8% leave-one-out predicted variance and 74.1% external predicted variance. The PLS model suggests that higher lipophilicity and electrophilicity, less negative charge surface area and presence of ether linkage, hydrogen bond donor groups and acetylenic carbons are responsible for greater toxicity of chemicals. The developed model may be used for prediction of toxicity, safety and risk assessment of chemicals to achieve better ecotoxicological management and prevent adverse health consequences.

Chronic uranium exposure and growth toxicity for phytoplankton. Dose-effect relationship: first comparison of chemical and radiological toxicity

International Nuclear Information System (INIS)

Gilbin, R.; Pradines, C.; Garnier-Laplace, J.

2004-01-01

The bioavailability of uranium for freshwater organisms, as for other dissolved metals, is closely linked to chemical speciation in solution (U aqueous speciation undergoes tremendous changes in the presence of ligands commonly found in natural waters e.g. carbonate, phosphate, hydroxide and natural organic matter). For the studied chemical domain, short-term uranium uptake experiments have already shown that the free uranyl ion concentration [UO 2 2+ ] is a good predictor of uranium uptake by the green algae Chlamydomonas reinhardtii, as predicted by the Free Ion Activity Model. In agreement with these results, acidic pH and low ligands concentrations in water enhance uranium bioavailability and consequently its potential chronic effects on phytoplankton. Moreover, uranium is known to be both radio-toxic and chemo-toxic. The use of different isotopes of uranium allows to expose organisms to different radiological doses for the same molar concentration: e.g. for a given element concentration (chemical dose), replacing depleted U by U-233 obviously leads to an enhanced radiological delivered dose to organisms (x10 4 ). In this work we established relationships between uranium doses (depleted uranium and 233-U ) and effect on the growth rate of the green algae Chlamydomonas reinhardtii. Uranium bioaccumulation was also monitored. Growth rate was measured both in classical batch (0-72 hrs) and continuous (turbidostat) cultures, the latter protocol allowing medium renewal to diminish exudates accumulation and speciation changes in the medium. The differences in effects will be, if possible, related to the development of defence mechanisms against the formation of reactive oxygen species (forms of glutathione) and the production of phyto-chelatins (small peptides rich in cystein that play an important role in the homeostasis and the detoxication of metals in cells). (author)

Fourier-transform infrared spectroscopy as a novel approach to providing effect-based endpoints in duckweed toxicity testing.

Science.gov (United States)

Hu, Li-Xin; Ying, Guang-Guo; Chen, Xiao-Wen; Huang, Guo-Yong; Liu, You-Sheng; Jiang, Yu-Xia; Pan, Chang-Gui; Tian, Fei; Martin, Francis L

2017-02-01

Traditional duckweed toxicity tests only measure plant growth inhibition as an endpoint, with limited effects-based data. The present study aimed to investigate whether Fourier-transform infrared (FTIR) spectroscopy could enhance the duckweed (Lemna minor L.) toxicity test. Four chemicals (Cu, Cd, atrazine, and acetochlor) and 4 metal-containing industrial wastewater samples were tested. After exposure of duckweed to the chemicals, standard toxicity endpoints (frond number and chlorophyll content) were determined; the fronds were also interrogated using FTIR spectroscopy under optimized test conditions. Biochemical alterations associated with each treatment were assessed and further analyzed by multivariate analysis. The results showed that comparable x% of effective concentration (ECx) values could be achieved based on FTIR spectroscopy in comparison with those based on traditional toxicity endpoints. Biochemical alterations associated with different doses of toxicant were mainly attributed to lipid, protein, nucleic acid, and carbohydrate structural changes, which helped to explain toxic mechanisms. With the help of multivariate analysis, separation of clusters related to different exposure doses could be achieved. The present study is the first to show successful application of FTIR spectroscopy in standard duckweed toxicity tests with biochemical alterations as new endpoints. Environ Toxicol Chem 2017;36:346-353. © 2016 SETAC. © 2016 SETAC.

A New Statistical Approach to Characterize Chemical-Elicited Behavioral Effects in High-Throughput Studies Using Zebrafish.

Directory of Open Access Journals (Sweden)

Guozhu Zhang

Full Text Available Zebrafish have become an important alternative model for characterizing chemical bioactivity, partly due to the efficiency at which systematic, high-dimensional data can be generated. However, these new data present analytical challenges associated with scale and diversity. We developed a novel, robust statistical approach to characterize chemical-elicited effects in behavioral data from high-throughput screening (HTS of all 1,060 Toxicity Forecaster (ToxCast™ chemicals across 5 concentrations at 120 hours post-fertilization (hpf. Taking advantage of the immense scale of data for a global view, we show that this new approach reduces bias introduced by extreme values yet allows for diverse response patterns that confound the application of traditional statistics. We have also shown that, as a summary measure of response for local tests of chemical-associated behavioral effects, it achieves a significant reduction in coefficient of variation compared to many traditional statistical modeling methods. This effective increase in signal-to-noise ratio augments statistical power and is observed across experimental periods (light/dark conditions that display varied distributional response patterns. Finally, we integrated results with data from concomitant developmental endpoint measurements to show that appropriate statistical handling of HTS behavioral data can add important biological context that informs mechanistic hypotheses.

Nature and prevalence of non-additive toxic effects in industrially relevant mixtures of organic chemicals.

Science.gov (United States)

Parvez, Shahid; Venkataraman, Chandra; Mukherji, Suparna

2009-06-01

The concentration addition (CA) and the independent action (IA) models are widely used for predicting mixture toxicity based on its composition and individual component dose-response profiles. However, the prediction based on these models may be inaccurate due to interaction among mixture components. In this work, the nature and prevalence of non-additive effects were explored for binary, ternary and quaternary mixtures composed of hydrophobic organic compounds (HOCs). The toxicity of each individual component and mixture was determined using the Vibrio fischeri bioluminescence inhibition assay. For each combination of chemicals specified by the 2(n) factorial design, the percent deviation of the predicted toxic effect from the measured value was used to characterize mixtures as synergistic (positive deviation) and antagonistic (negative deviation). An arbitrary classification scheme was proposed based on the magnitude of deviation (d) as: additive (50%, class-IV) antagonistic/synergistic. Naphthalene, n-butanol, o-xylene, catechol and p-cresol led to synergism in mixtures while 1, 2, 4-trimethylbenzene and 1, 3-dimethylnaphthalene contributed to antagonism. Most of the mixtures depicted additive or antagonistic effect. Synergism was prominent in some of the mixtures, such as, pulp and paper, textile dyes, and a mixture composed of polynuclear aromatic hydrocarbons. The organic chemical industry mixture depicted the highest abundance of antagonism and least synergism. Mixture toxicity was found to depend on partition coefficient, molecular connectivity index and relative concentration of the components.

A Novel Approach: Chemical Relational Databases, and the Role of the ISSCAN Database on Assessing Chemical Carcinogenity

Science.gov (United States)

Mutagenicity and carcinogenicity databases are crucial resources for toxicologists and regulators involved in chemicals risk assessment. Until recently, existing public toxicity databases have been constructed primarily as "look-up-tables" of existing data, and most often did no...

Natural and active chemical remediation of toxic metals and radionuclides in the aquatic environment

International Nuclear Information System (INIS)

McPherson, G.; Pintauro, P.; O'Connor, S.; Zhang, J.; Gonzales, R.; Flowers, G.

1993-01-01

The focus of this research is the non-biological, chemical remediation of toxic heavy metals and radionuclides in aquatic environments. This Tulane/Xavier group includes researchers from Chemistry, Chemical Engineering, and Geology. Active methods using novel zeolites and ion exchange membranes are currently being evaluated for use in removing heavy metals from natural waters. In addition, field and laboratory studies of metal ion exchange reactions and competitive, heavy metal adsorption on clay substrates are underway to determine sediment metal sequestering capacity. A summary of progress to date and future work is presented

NODC Standard Format Marine Toxic Substances and Pollutants (F144) chemical identification codes (NODC Accession 9200273)

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — This archival information package contains a listing of codes and chemical names that were used in NODC Standard Format Marine Toxic Substances and Pollutants (F144)...

[Prospects in getting accordance between chemical analytic control means and medical technical requirements to safety system concerning chemical weapons destruction].

Science.gov (United States)

Rembovskiĭ, V R; Mogilenkova, L A; Savel'eva, E I

2005-01-01

The major unit monitoring chemical weapons destruction objects is a system of chemical analyticcontrol over the technologic process procedures and possibility of environment and workplace pollution withtoxicchemicals and their destruction products. At the same time, physical and chemical control means meet sanitary and hygienic requirements incompletely. To provide efficient control, internationally recognized approaches should be adapted to features of Russian system monitoring pollution of chemical weapons destruction objects with toxic chemicals.

Novel approaches to mitigating parathion toxicity: targeting cytochrome P450-mediated metabolism with menadione.

Science.gov (United States)

Jan, Yi-Hua; Richardson, Jason R; Baker, Angela A; Mishin, Vladimir; Heck, Diane E; Laskin, Debra L; Laskin, Jeffrey D

2016-08-01

Accidental or intentional exposures to parathion, an organophosphorus (OP) pesticide, can cause severe poisoning in humans. Parathion toxicity is dependent on its metabolism by the cytochrome P450 (CYP) system to paraoxon (diethyl 4-nitrophenyl phosphate), a highly poisonous nerve agent and potent inhibitor of acetylcholinesterase. We have been investigating inhibitors of CYP-mediated bioactivation of OPs as a method of preventing or reversing progressive parathion toxicity. It is well recognized that NADPH-cytochrome P450 reductase, an enzyme required for the transfer of electrons to CYPs, mediates chemical redox cycling. In this process, the enzyme diverts electrons from CYPs to support chemical redox cycling, which results in inhibition of CYP-mediated biotransformation. Using menadione as the redox-cycling chemical, we discovered that this enzymatic reaction blocks metabolic activation of parathion in rat and human liver microsomes and in recombinant CYPs important to parathion metabolism, including CYP1A2, CYP2B6, and CYP3A4. Administration of menadione to rats reduces metabolism of parathion, as well as parathion-induced inhibition of brain cholinesterase activity. This resulted in inhibition of parathion neurotoxicity. Menadione has relatively low toxicity and is approved by the Food and Drug Administration for other indications. Its ability to block parathion metabolism makes it an attractive therapeutic candidate to mitigate parathion-induced neurotoxicity. © 2016 New York Academy of Sciences.

Extensive review of fish embryo acute toxicities for the prediction of GHS acute systemic toxicity categories.

Science.gov (United States)

Scholz, Stefan; Ortmann, Julia; Klüver, Nils; Léonard, Marc

2014-08-01

Distribution and marketing of chemicals require appropriate labelling of health, physical and environmental hazards according to the United Nations global harmonisation system (GHS). Labelling for (human) acute toxicity categories is based on experimental findings usually obtained by oral, dermal or inhalative exposure of rodents. There is a strong societal demand for replacing animal experiments conducted for safety assessment of chemicals. Fish embryos are considered as alternative to animal testing and are proposed as predictive model both for environmental and human health effects. Therefore, we tested whether LC50s of the fish embryo acute toxicity test would allow effectively predicting of acute mammalian toxicity categories. A database of published fish embryo LC50 containing 641 compounds was established. For these compounds corresponding rat oral LD50 were identified resulting in 364 compounds for which both fish embryo LC50 and rat LD50 was available. Only a weak correlation of fish embryo LC50 and rat oral LD50 was obtained. Fish embryos were also not able to effectively predict GHS oral acute toxicity categories. We concluded that due to fundamental exposure protocol differences (single oral dose versus water-borne exposure) a reverse dosimetry approach is needed to explore the predictive capacity of fish embryos. Copyright © 2014 Elsevier Inc. All rights reserved.

Colorimetric sensor array for determination and identification of toxic industrial chemicals.

Science.gov (United States)

Feng, Liang; Musto, Christopher J; Kemling, Jonathan W; Lim, Sung H; Zhong, Wenxuan; Suslick, Kenneth S

2010-11-15

A low-cost yet highly sensitive colorimetric sensor array for the detection and identification of toxic industrial chemicals (TICs) has been developed. The sensor consists of a disposable array of cross-responsive nanoporous pigments whose colors are changed by diverse chemical interactions with analytes. Clear differentiation among 20 different TICs has been easily achieved at both their IDLH (immediately dangerous to life or health) concentration within 2 min of exposure and PEL (permissible exposure limit) concentration within 5 min of exposure with no errors or misclassifications. Detection limits are generally well below the PEL (in most cases below 5% of PEL) and are typically in the low ppb range. The colorimetric sensor array is not responsive to changes in humidity or temperature over a substantial range. The printed arrays show excellent batch to batch reproducibility and long shelf life (greater than 3 months).

Reducing aquatic hazards of industrial chemicals: probabilistic assessment of sustainable molecular design guidelines.

Science.gov (United States)

Connors, Kristin A; Voutchkova-Kostal, Adelina M; Kostal, Jakub; Anastas, Paul; Zimmerman, Julie B; Brooks, Bryan W

2014-08-01

Basic toxicological information is lacking for the majority of industrial chemicals. In addition to increasing empirical toxicity data through additional testing, prospective computational approaches to drug development aim to serve as a rational basis for the design of chemicals with reduced toxicity. Recent work has resulted in the derivation of a "rule of 2," wherein chemicals with an octanol-water partition coefficient (log P) less than 2 and a difference between the lowest unoccupied molecular orbital and the highest occupied molecular orbital (ΔE) greater than 9 (log P9 eV) are predicted to be 4 to 5 times less likely to elicit acute or chronic toxicity to model aquatic organisms. The present study examines potential reduction of aquatic toxicity hazards from industrial chemicals if these 2 molecular design guidelines were employed. Probabilistic hazard assessment approaches were used to model the likelihood of encountering industrial chemicals exceeding toxicological categories of concern both with and without the rule of 2. Modeling predicted that utilization of these molecular design guidelines for log P and ΔE would appreciably decrease the number of chemicals that would be designated to be of "high" and "very high" concern for acute and chronic toxicity to standard model aquatic organisms and end points as defined by the US Environmental Protection Agency. For example, 14.5% of chemicals were categorized as having high and very high acute toxicity to the fathead minnow model, whereas only 3.3% of chemicals conforming to the design guidelines were predicted to be in these categories. Considerations of specific chemical classes (e.g., aldehydes), chemical attributes (e.g., ionization), and adverse outcome pathways in representative species (e.g., receptor-mediated responses) could be used to derive future property guidelines for broader classes of contaminants. © 2014 SETAC.

2004 Toxic Chemical Release Inventory Report for the Emergency Planning and Community Right-to-Know Act of 1986, Title III, Section 313

Energy Technology Data Exchange (ETDEWEB)

M. Stockton

2006-01-15

Section 313 of Emergency Planning and Community Right-to-Know Act (EPCRA) specifically requires facilities to submit a Toxic Chemical Release Inventory Report (Form R) to the U.S. Environmental Protection Agency (EPA) and state agencies if the owners and operators manufacture, process, or otherwise use any of the listed toxic chemicals above listed threshold quantities. EPA compiles this data in the Toxic Release Inventory database. Form R reports for each chemical over threshold quantities must be submitted on or before July 1 each year and must cover activities that occurred at the facility during the previous year. For reporting year 2004, Los Alamos National Laboratory (LANL or the Laboratory) submitted Form R reports for lead compounds, nitric acid, and nitrate compounds as required under the EPCRA Section 313. No other EPCRA Section 313 chemicals were used in 2004 above the reportable thresholds. This document provides a description of the evaluation of EPCRA Section 313 chemical use and threshold determinations for LANL for calendar year 2004, as well as background information about data included on the Form R reports.

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.

Prediction of Chemical Carcinogenicity in Rodents from in vitro Genetic Toxicity Assays

Science.gov (United States)

Tennant, Raymond W.; Margolin, Barry H.; Shelby, Michael D.; Zeiger, Errol; Haseman, Joseph K.; Spalding, Judson; Caspary, William; Resnick, Michael; Stasiewicz, Stanley; Anderson, Beth; Minor, Robert

1987-05-01

Four widely used in vitro assays for genetic toxicity were evaluated for their ability to predict the carcinogenicity of selected chemicals in rodents. These assays were mutagenesis in Salmonella and mouse lymphoma cells and chromosome aberrations and sister chromatid exchanges in Chinese hamster ovary cells. Seventy-three chemicals recently tested in 2-year carcinogenicity studies conducted by the National Cancer Institute and the National Toxicology Program were used in this evaluation. Test results from the four in vitro assays did not show significant differences in individual concordance with the rodent carcinogenicity results; the concordance of each assay was approximately 60 percent. Within the limits of this study there was no evidence of complementarity among the four assays, and no battery of tests constructed from these assays improved substantially on the overall performance of the Salmonella assay. The in vitro assays which represented a range of three cell types and four end points did show substantial agreement among themselves, indicating that chemicals positive in one in vitro assay tended to be positive in the other in vitro assays. To help put this project into its proper context, we emphasize certain features of the study: 1) Standard protocols were used to mimic the major use of STTs worldwide--screening for mutagens and carcinogens; no attempt was made to optimize protocols for specific chemicals. 2) The 73 NTP chemicals and their 60% incidence of carcinogenicity are probably not representative of the universe of chemicals but rather reflect the recent chemical selection process for the NTP carcinogenicity assay. 3) The small, diverse group of chemicals precludes a meaningful evaluation of the predictive utility of chemical structure information. 4) The NTP is currently testing these same 73 chemicals in two in vivo STTs for chromosomal effects. 5) Complete data for an additional group of 30 to 40 NTP chemicals will be gathered on

Development of a Combined In Vitro Physiologically Based Kinetic (PBK) and Monte Carlo Modelling Approach to Predict Interindividual Human Variation in Phenol-Induced Developmental Toxicity.

Science.gov (United States)

Strikwold, Marije; Spenkelink, Bert; Woutersen, Ruud A; Rietjens, Ivonne M C M; Punt, Ans

2017-06-01

With our recently developed in vitro physiologically based kinetic (PBK) modelling approach, we could extrapolate in vitro toxicity data to human toxicity values applying PBK-based reverse dosimetry. Ideally information on kinetic differences among human individuals within a population should be considered. In the present study, we demonstrated a modelling approach that integrated in vitro toxicity data, PBK modelling and Monte Carlo simulations to obtain insight in interindividual human kinetic variation and derive chemical specific adjustment factors (CSAFs) for phenol-induced developmental toxicity. The present study revealed that UGT1A6 is the primary enzyme responsible for the glucuronidation of phenol in humans followed by UGT1A9. Monte Carlo simulations were performed taking into account interindividual variation in glucuronidation by these specific UGTs and in the oral absorption coefficient. Linking Monte Carlo simulations with PBK modelling, population variability in the maximum plasma concentration of phenol for the human population could be predicted. This approach provided a CSAF for interindividual variation of 2.0 which covers the 99th percentile of the population, which is lower than the default safety factor of 3.16 for interindividual human kinetic differences. Dividing the dose-response curve data obtained with in vitro PBK-based reverse dosimetry, with the CSAF provided a dose-response curve that reflects the consequences of the interindividual variability in phenol kinetics for the developmental toxicity of phenol. The strength of the presented approach is that it provides insight in the effect of interindividual variation in kinetics for phenol-induced developmental toxicity, based on only in vitro and in silico testing. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Probing the ToxCastTM Chemical Library for Predictive Signatures of Developmental Toxicity - Poster at Teratology Society Annual Meeting

Science.gov (United States)

EPA’s ToxCast™ project is profiling the in vitro bioactivity of chemical compounds to assess pathway-level and cell-based signatures that correlate with observed in vivo toxicity. We hypothesize that cell signaling pathways are primary targets for diverse environmental chemicals ...

RELATIONSHIP BETWEEN COMPOSITION AND TOXICITY OF ENGINE EMISSION SAMPLES

Energy Technology Data Exchange (ETDEWEB)

(1)Mauderly, J; Seagrave, J; McDonald; J (2)Eide,I (3)Zielinska, B (4)Lawson, D

2003-08-24

Differences in the lung toxicity and bacterial mutagenicity of seven samples from gasoline and diesel vehicle emissions were reported previously [1]. Filter and vapor-phase semivolatile organic samples were collected from normal and high-emitter gasoline and diesel vehicles operated on chassis dynamometers on the Unified Driving Cycle, and the compositions of the samples were measured in detail. The two fractions of each sample were combined in their original mass collection ratios, and the toxicity of the seven samples was compared by measuring inflammation and tissue damage in rat lungs and mutagenicity in bacteria. There was good agreement among the toxicity response variables in ranking the samples and demonstrating a five-fold range of toxicity. The relationship between chemical composition and toxicity was analyzed by a combination of principal component analysis (PCA) and partial least squares regression (PLS, also known as projection to latent surfaces). The PCA /PLS analysis revealed the chemical constituents co-varying most strongly with toxicity and produced models predicting the relative toxicity of the samples with good accuracy. The results demonstrated the utility of the PCA/PLS approach, which is now being applied to additional samples, and it also provided a starting point for confirming the compounds that actually cause the effects.

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

In vitro screening of environmental chemicals for targeted testing prioritization: the ToxCast project.

Science.gov (United States)

Judson, Richard S; Houck, Keith A; Kavlock, Robert J; Knudsen, Thomas B; Martin, Matthew T; Mortensen, Holly M; Reif, David M; Rotroff, Daniel M; Shah, Imran; Richard, Ann M; Dix, David J

2010-04-01

Chemical toxicity testing is being transformed by advances in biology and computer modeling, concerns over animal use, and the thousands of environmental chemicals lacking toxicity data. The U.S. Environmental Protection Agency's ToxCast program aims to address these concerns by screening and prioritizing chemicals for potential human toxicity using in vitro assays and in silico approaches. This project aims to evaluate the use of in vitro assays for understanding the types of molecular and pathway perturbations caused by environmental chemicals and to build initial prioritization models of in vivo toxicity. We tested 309 mostly pesticide active chemicals in 467 assays across nine technologies, including high-throughput cell-free assays and cell-based assays, in multiple human primary cells and cell lines plus rat primary hepatocytes. Both individual and composite scores for effects on genes and pathways were analyzed. Chemicals displayed a broad spectrum of activity at the molecular and pathway levels. We saw many expected interactions, including endocrine and xenobiotic metabolism enzyme activity. Chemicals ranged in promiscuity across pathways, from no activity to affecting dozens of pathways. We found a statistically significant inverse association between the number of pathways perturbed by a chemical at low in vitro concentrations and the lowest in vivo dose at which a chemical causes toxicity. We also found associations between a small set of in vitro assays and rodent liver lesion formation. This approach promises to provide meaningful data on the thousands of untested environmental chemicals and to guide targeted testing of environmental contaminants.

The aquatic toxicity and chemical forms of coke plant effluent cyanide -- Implications for discharge limits

International Nuclear Information System (INIS)

Garibay, R.; Rupnow, M.; Godwin-Saad, E.; Hall, S.

1995-01-01

Cyanide is present in treated cokemaking process waters at concentrations as high as 8.0 mg/L. In assessing options for managing the discharge of a treated effluent, the development and implementation of discharge limits for cyanide became a critical issue. A study was initiated to evaluate possible alternatives to cyanide permit limits at the US Steel Gary Works Facility. The objectives of the study were to: (1) evaluation the forms of cyanide present in coke plant effluent; (2) determine whether these forms of cyanide are toxic to selected aquatic organisms; (3) compare the aquatic toxicity of various chemical forms of cyanide; (4) identify if the receiving water modifies cyanide bioavailability; and (5) confirm, with respect to water quality-based effluent limits, an appropriate analytical method for monitoring cyanide in a coke plant effluent. The results of aquatic toxicity tests and corresponding analytical data are presented. Toxicity tests were conducted with various pure chemical forms of cyanide as well as whole coke plant effluent (generated from a pilot-scale treatment system). Test species included the fathead minnow (Pimephales promelas), rainbow trout (Oncorhynchus mykiss), Ceriodaphnia dubia (C. dubia) and Daphnia magna (D. magna). Analytical measurements for cyanide included total, weak acid dissociable, diffusible cyanide and selected metal species of cyanide. The findings presented by the paper are relevant with respect to the application of cyanide water quality criteria for a coke plant effluent discharge, the translation of these water quality-based effluent limits to permit limits, and methods for compliance monitoring for cyanide

In vitro toxicities of experimental jet fuel system ice-inhibiting agents.

Science.gov (United States)

Geiss, K T; Frazier, J M

2001-07-02

One research emphasis within the Department of Defense has been to seek the replacement of operational compounds with alternatives that pose less potential risk to human and ecological systems. Alternatives to glycol ethers, such as diethylene glycol monomethyl ether (M-DE), were investigated for use as jet fuel system ice-inhibiting agents (FSIIs). This group of chemicals includes three derivatives of 1,3-dioxolane-4-methanol (M-1, M-2, and M-3) and a 1,3-dioxane (M-27). In addition, M-DE was evaluated as a reference compound. Our approach was to implement an in vitro test battery based on primary rat hepatocyte cultures to perform initial toxicity evaluations. Hepatocytes were exposed to experimental chemicals (0, 0.001, 0.01, 0.1, 1, 10 mM dosages) for periods up to 24 h. Samples were assayed for lactate dehydrogenase (LDH) release, MTT dye reduction activity, glutathione level, and rate of protein synthesis as indicators of toxicity. Of the compounds tested, M-1, especially at the 10-mM dose, appeared to be more potent than the other chemicals, as measured by these toxicity assays. M-DE, the current FSII, elicited little response in the toxicity assays. Although some variations in toxicity were observed at the 10-mM dose, the in vitro toxicities of the chemicals tested (except for M-1) were not considerably greater than that of M-DE.

Investigations of chemical warfare agents and toxic industrial compounds with proton-transfer-reaction mass spectrometry for a real-time threat monitoring scenario.

Science.gov (United States)

Kassebacher, Thomas; Sulzer, Philipp; Jürschik, Simone; Hartungen, Eugen; Jordan, Alfons; Edtbauer, Achim; Feil, Stefan; Hanel, Gernot; Jaksch, Stefan; Märk, Lukas; Mayhew, Chris A; Märk, Tilmann D

2013-01-30

Security and protection against terrorist attacks are major issues in modern society. One especially challenging task is the monitoring and protection of air conditioning and heating systems of buildings against terrorist attacks with toxic chemicals. As existing technologies have low selectivity, long response times or insufficient sensitivity, there is a need for a novel approach such as we present here. We have analyzed various chemical warfare agents (CWAs) and/or toxic industrial compounds (TICs) and related compounds, namely phosgene, diphosgene, chloroacetone, chloroacetophenone, diisopropylaminoethanol, and triethyl phosphate, utilizing a high-resolution proton-transfer-reaction time-of-flight mass spectrometry (PTR-TOFMS) instrument with the objective of finding key product ions and their intensities, which will allow a low-resolution quadrupole mass spectrometry based PTR-MS system to be used with high confidence in the assignment of threat agents in the atmosphere. We obtained high accuracy PTR-TOFMS mass spectra of the six compounds under study at two different values for the reduced electric field in the drift tube (E/N). From these data we have compiled a table containing product ions, and isotopic and E/N ratios for highly selective threat compound detection with a compact and cost-effective quadrupole-based PTR-MS instrument. Furthermore, using chloroacetophenone (tear gas), we demonstrated that this instrument's response is highly linear in the concentration range of typical Acute Exposure Guideline Levels (AEGLs). On the basis of the presented results it is possible to develop a compact and cost-effective PTR-QMS instrument that monitors air supply systems and triggers an alarm as soon as the presence of a threat agent is detected. We hope that this real-time surveillance device will help to seriously improve safety and security in environments vulnerable to terrorist attacks with toxic chemicals. Copyright © 2012 John Wiley & Sons, Ltd.

In Vitro Rat Hepatocyte Toxicity and Bacteria Genotoxicity Evaluation of High Energy Chemicals for Replacement of Hydrazine

National Research Council Canada - National Science Library

Husain, S

2002-01-01

In an effort to develop methods to predict the toxicological response of newly synthesized chemicals that are of interest to the US Air Force, in vitro rat hepatocyte toxicity and bacteria (Salmonella...

Introducing Toxics

OpenAIRE

David C. Bellinger

2013-01-01

With this inaugural issue, Toxics begins its life as a peer-reviewed, open access journal focusing on all aspects of toxic chemicals. We are interested in publishing papers that present a wide range of perspectives on toxicants and naturally occurring toxins, including exposure, biomarkers, kinetics, biological effects, fate and transport, treatment, and remediation. Toxics differs from many other journals in the absence of a page or word limit on contributions, permitting authors to present ...

An integrative risk assessment approach for persistent chemicals: a case study on dioxins, furans and dioxin-like PCBs in France.

Science.gov (United States)

Béchaux, Camille; Zeilmaker, Marco; Merlo, Mathilde; Bokkers, Bas; Crépet, Amélie

2014-10-01

For persistent chemicals slowly eliminated from the body, the accumulated concentration (body burden), rather than the daily exposure, is considered the proper starting point for the risk assessment. This work introduces an integrative approach for persistent chemical risk assessment by means of a dynamic body burden approach. To reach this goal a Kinetic Dietary Exposure Model (KDEM) was extended with the long term time trend in the exposure (historic exposure) and the comparison of bioaccumulation with body burden references for toxicity. The usefulness of the model was illustrated on the dietary exposure to PolyChlorinatedDibenzo-p-Dioxins (PCDDs), PolyChlorinatedDibenzoFurans (PCDFs) and PolyChlorinated Biphenyls (PCBs) in France. Firstly the dietary exposure to these compounds was determined in 2009 and combined with its long term time trend. In order to take differences between the kinetics of PCDD/F and dl-PCBs into account, three groups of congeners were considered i.e. PCDD/Fs, PCB 126 and remaining dl-PCBs. The body burden was compared with reference body burdens corresponding to reproductive, hepatic and thyroid toxicity. In the case of thyroid toxicity this comparison indicated that in 2009 the probability of the body burden to exceed its reference ranged from 2.8% (95% CI: 1.5-4.9%) up to 3.9% (95% CI: 2.7-7.1%) (18-29 vs. 60-79year olds). Notwithstanding the decreasing long-term time trend of the dietary dioxin exposure in France, this probability still is expected to be 1.5% (95% CI: 0.3-2.5%) in 2030 in 60-79 olds. In the case of reproductive toxicity the probability of the 2009 body burden to exceed its reference ranged from 3.1% (95% CI: 1.4-5.0%) (18-29year olds) to 3.5% (95% CI: 2.2-5.2%) (30-44year olds). In 2030 this probability is negligible in 18-29year olds, however small though significant in 30-44year olds (0.7%, 95% CI: 0-1.6%). In the case of hepatic toxicity the probability in 2009 even in 60-79year olds already was negligible. In

Developing predictions of in vivo developmental toxicity of ToxCast chemicals using mouse embryonic stem cells.

Science.gov (United States)

Developing predictions of in vivo developmental toxicity of ToxCast chemicals using mouse embryonic stem cells S. Hunter, M. Rosen, M. Hoopes, H. Nichols, S. Jeffay, K. Chandler1, Integrated Systems Toxicology Division, National Health and Environmental Effects Research Labor...

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

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.

Orion Emergency Mask Approach

Science.gov (United States)

Tuan, George C.; Graf, John C.

2009-01-01

Emergency mask approach on Orion poses a challenge to the traditional Shuttle or Station approaches. Currently, in the case of a fire or toxic spill event, the crew utilizes open loop oxygen masks that provide the crew with oxygen to breath, but also dumps the exhaled oxygen into the cabin. For Orion, with a small cabin volume, the extra oxygen will exceed the flammability limit within a short period of time, unless a nitrogen purge is also provided. Another approach to a fire or toxic spill event is the use of a filtering emergency masks. These masks utilize some form of chemical beds to scrub the air clean of toxic providing the crew safe breathing air for a period without elevating the oxygen level in the cabin. Using the masks and a form of smoke-eater filter, it may be possible to clean the cabin completely or to a level for safe transition to a space suit to perform a cabin purge. Issues with filters in the past have been the reaction time, breakthroughs, and high breathing resistance. Development in a new form of chemical filters has shown promise to make the filtering approach feasible.

PAH toxicity at aqueous solubility in the fish embryo test with Danio rerio using passive dosing

DEFF Research Database (Denmark)

Seiler, Thomas-Benjamin; Best, Nina; Fernqvist, Margit Møller

2014-01-01

to animal testing in (eco)toxicology. However, for hydrophobic organic chemicals it remains a technical challenge to ensure constant freely dissolved concentration at the maximum exposure level during such biotests. Passive dosing with PDMS silicone was thus applied to control the freely dissolved...... further data to support the close relationship between the chemical activity and the toxicity of hydrophobic organic compounds. Passive dosing from PDMS silicone enabled reliable toxicity testing of (highly) hydrophobic substances at aqueous solubility, providing a practical way to control toxicity...... exactly at the maximum exposure level. This approach is therefore expected to be useful as a cost-effective initial screening of hydrophobic chemicals for potential adverse effects to freshwater vertebrates....

Impacts of chemical modification on the toxicity of diverse nanocellulose materials to developing zebrafish.

Science.gov (United States)

Harper, Bryan J; Clendaniel, Alicea; Sinche, Federico; Way, Daniel; Hughes, Michael; Schardt, Jenna; Simonsen, John; Stefaniak, Aleksandr B; Harper, Stacey L

2016-06-01

Cellulose is an abundant and renewable resource currently being investigated for utility in nanomaterial form for various promising applications ranging from medical and pharmaceutical uses to mechanical reinforcement and biofuels. The utility of nanocellulose and wide implementation ensures increasing exposure to humans and the environment as nanocellulose-based technologies advance. Here, we investigate how differences in aspect ratio and changes to surface chemistry, as well as synthesis methods, influence the biocompatibility of nanocellulose materials using the embryonic zebrafish. Investigations into the toxicity of neutral, cationic and anionic surface functionalities revealed that surface chemistry had a minimal influence on the overall toxicity of nanocellulose materials. Higher aspect ratio cellulose nanofibers produced by mechanical homogenization were, in some cases, more toxic than other cellulose-based nanofibers or nanocrystals produced by chemical synthesis methods. Using fluorescently labeled nanocellulose we were able to show that nanocellulose uptake did occur in embryonic zebrafish during development. We conclude that the benign nature of nanocellulose materials makes them an ideal platform to systematically investigate the inherent surface features driving nanomaterial toxicity in order to create safer design principles for engineered nanoparticles.

Toxic chemical release inventory reporting form R and instructions. Revised 1992 version. Section 313 of the Emergency Planning and Community Right-to-Know Act

International Nuclear Information System (INIS)

1993-01-01

Reporting is required to provide the public with information on the releases of listed toxic chemicals in their communities and to provide EPA with release information to assist the Agency in determining the need for future regulations. Facilities must report the quantities of both routine and accidental releases of listed toxic chemicals, as well as the maximum amount of the listed toxic chemical on-site during the calendar year and the amount contained in wastes transferred off-site. These instructions supplement and elaborate on the requirements in the reporting rule (40 CFR Part 372). Together with the reporting rule, they constitute the reporting requirements. All references in these instructions are to sections in the reporting rule unless otherwise indicated

Source apportionment of toxic chemical pollutants at Trombay region

International Nuclear Information System (INIS)

Sahu, S.K.; Pandit, G.G.; Puranik, V.D.

2007-05-01

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 find their way into various environmental compartments. One of the main issues of environmental pollution is the chemical composition of aerosols and their sources. In spite of all the efforts a considerable part of the atmospheric aerosol mass is still not accounted for. 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 an attempt has been made to collect different size fractionated ambient aerosols and to quantify the percentage contribution of each size fraction to the total aerosol mass. Subsequently, an effort has been made for chemical characterization (inorganic, organic and carbon content) of these particulate matter using different analytical techniques. The comprehensive data set on chemical characterization of particulate matter thus generated is being used with receptor modeling techniques to identify the possible sources contributing to the observed concentrations of the measured pollutants. The use of this comprehensive data set in receptor modeling has been helpful in distinguishing the source types in a better way. Receptor modeling techniques are powerful tools that can be used to locate sources of pollutants to the atmosphere. The major advantage of the receptor models is that actual ambient data are used to apportion source contributions, negating the need for dispersion calculations. Pollution sources affecting the sampling site were statistically identified using varimax rotated factor analysis of

Estimating chemical footprint: Contamination with mercury and its compounds

DEFF Research Database (Denmark)

Tarasova, Natalia; Makarova, Anna; Fantke, Peter

2018-01-01

-SETAC scientific consensus model USEtox, which is recommended for and widely applied in life cycle impact assessment. Our approach was tested using the example of mercury, which has been shown to be a hazardous pollutant at regional and global scales. Results show that the main contribution to the overall chemical......Chemical pollution is a problem of global importance. However, there are currently no agreed approaches for integrated environmental impact assessment (EIA) of chemical effects at global scale. We present a new systems-based approach to EIA of chemicals. Our methodology considers propagation...... of chemical pollutants in the environment, in conjunction with the approach followed in the Russian regulatory system. To estimate chemical footprints related to environmental contamination by potentially toxic substances, measured environmental concentrations were combined with results from the UNEP...

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).

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.

Exploring the Q-marker of "sweat soaking method" processed radix Wikstroemia indica: Based on the "effect-toxicity-chemicals" study.

Science.gov (United States)

Feng, Guo; Chen, Yun-Long; Li, Wei; Li, Lai-Lai; Wu, Zeng-Guang; Wu, Zi-Jun; Hai, Yue; Zhang, Si-Chao; Zheng, Chuan-Qi; Liu, Chang-Xiao; He, Xin

2018-06-01

Radix Wikstroemia indica (RWI), named "Liao Ge Wang" in Chinese, is a kind of toxic Chinese herbal medicine (CHM) commonly used in Miao nationality of South China. "Sweat soaking method" processed RWI could effectively decrease its toxicity and preserve therapeutic effect. However, the underlying mechanism of processing is still not clear, and the Q-markers database for processed RWI has not been established. Our study is to investigate and establish the quality evaluation system and potential Q-markers based on "effect-toxicity-chemicals" relationship of RWI for quality/safety assessment of "sweat soaking method" processing. The variation of RWI in efficacy and toxicity before and after processing was investigated by pharmacological and toxicological studies. Cytotoxicity test was used to screen the cytotoxicity of components in RWI. The material basis in ethanol extract of raw and processed RWI was studied by UPLC-Q-TOF/MS. And the potential Q-markers were analyzed and predicted according to "effect-toxicity-chemical" relationship. RWI was processed by "sweat soaking method", which could preserve efficacy and reduce toxicity. Raw RWI and processed RWI did not show significant difference on the antinociceptive and anti-inflammatory effect, however, the injury of liver and kidney by processed RWI was much weaker than that by raw RWI. The 20 compounds were identified from the ethanol extract of raw product and processed product of RWI using UPLC-Q-TOF/MS, including daphnoretin, emodin, triumbelletin, dibutyl phthalate, Methyl Paraben, YH-10 + OH and matairesinol, arctigenin, kaempferol and physcion. Furthermore, 3 diterpenoids (YH-10, YH-12 and YH-15) were proved to possess the high toxicity and decreased by 48%, 44% and 65%, respectively, which could be regarded as the potential Q-markers for quality/safety assessment of "sweat soaking method" processed RWI. A Q-marker database of processed RWI by "sweat soaking method" was established according to the results

Toxic Effects of Peracetic Acid Used as a Chemical Weapon During Workers Riots

International Nuclear Information System (INIS)

Jovic-Stosic, J.; Todorovic, V.; Segrt, Z.

2007-01-01

Peracetic acid (PAA) is a mixture of acetic acid and hydrogen peroxide, often used as antimicrobial agent on food processing equipment. It may explosively decompose on shock, friction or concussion. PAA is a strong oxidant, corrosive to the eyes, skin, respiratory and digestive tract. Depending on concentration, contact may cause severe burns of the skin or the eyes, and inhalation may cause lung edema. We report toxic effects of PAA used as a chemical weapon in workers riots. Group of workers attacked the security guards in beverage plant, throwing out beer bottles filled with PAA. Bottles exploded, producing irritant mists and fumes, and splashing some of the guards with acid. After about 20 minutes of exposure in the closed space, 30 persons were transported to the emergency room; 22 of them were transferred to the hospital. After the initial treatment, 10 patients were admitted for further treatment. The symptoms of exposure included burning sensation and pain of the eyes, throat and skin, cough and shortness of breath. Effects on the eyes included redness and corneal erosions. Pulmonary disturbances were prolonged expirium and wheezing by auscultation, and hypoxemia. Skin burns were ranged as grade I-III. Treatment included rinse of eyes and skin, systemic therapy with corticosteroids, beta adrenergic drugs and theophylline. Surgical treatment was necessary in grade III skin burns. A variety of common industrial chemicals may be misused as a chemical weapon. We point out the hazards of serious toxic effects of PAA if used in riots or terrorists attacks. (author)

An overview of data mining algorithms in drug induced toxicity prediction.

Science.gov (United States)

Omer, Ankur; Singh, Poonam; Yadav, N K; Singh, R K

2014-04-01

The growth in chemical diversity has increased the need to adjudicate the toxicity of different chemical compounds raising the burden on the demand of animal testing. The toxicity evaluation requires time consuming and expensive undertaking, leading to the deprivation of the methods employed for screening chemicals pointing towards the need to develop more efficient toxicity assessment systems. Computational approaches have reduced the time as well as the cost for evaluating the toxicity and kinetic behavior of any chemical. The accessibility of a large amount of data and the intense need of turning this data into useful information have attracted the attention towards data mining. Machine Learning, one of the powerful data mining techniques has evolved as the most effective and potent tool for exploring new insights on combinatorial relationships among various experimental data generated. The article accounts on some sophisticated machine learning algorithms like Artificial Neural Networks (ANN), Support Vector Machine (SVM), k-mean clustering and Self Organizing Maps (SOM) with some of the available tools used for classification, sorting and toxicological evaluation of data, clarifying, how data mining and machine learning interact cooperatively to facilitate knowledge discovery. Addressing the association of some commonly used expert systems, we briefly outline some real world applications to consider the crucial role of data set partitioning.

ToxCast Chemical Landscape: Paving the Road to 21st Century Toxicology.

Science.gov (United States)

Richard, Ann M; Judson, Richard S; Houck, Keith A; Grulke, Christopher M; Volarath, Patra; Thillainadarajah, Inthirany; Yang, Chihae; Rathman, James; Martin, Matthew T; Wambaugh, John F; Knudsen, Thomas B; Kancherla, Jayaram; Mansouri, Kamel; Patlewicz, Grace; Williams, Antony J; Little, Stephen B; Crofton, Kevin M; Thomas, Russell S

2016-08-15

The U.S. Environmental Protection Agency's (EPA) ToxCast program is testing a large library of Agency-relevant chemicals using in vitro high-throughput screening (HTS) approaches to support the development of improved toxicity prediction models. Launched in 2007, Phase I of the program screened 310 chemicals, mostly pesticides, across hundreds of ToxCast assay end points. In Phase II, the ToxCast library was expanded to 1878 chemicals, culminating in the public release of screening data at the end of 2013. Subsequent expansion in Phase III has resulted in more than 3800 chemicals actively undergoing ToxCast screening, 96% of which are also being screened in the multi-Agency Tox21 project. The chemical library unpinning these efforts plays a central role in defining the scope and potential application of ToxCast HTS results. The history of the phased construction of EPA's ToxCast library is reviewed, followed by a survey of the library contents from several different vantage points. CAS Registry Numbers are used to assess ToxCast library coverage of important toxicity, regulatory, and exposure inventories. Structure-based representations of ToxCast chemicals are then used to compute physicochemical properties, substructural features, and structural alerts for toxicity and biotransformation. Cheminformatics approaches using these varied representations are applied to defining the boundaries of HTS testability, evaluating chemical diversity, and comparing the ToxCast library to potential target application inventories, such as used in EPA's Endocrine Disruption Screening Program (EDSP). Through several examples, the ToxCast chemical library is demonstrated to provide comprehensive coverage of the knowledge domains and target inventories of potential interest to EPA. Furthermore, the varied representations and approaches presented here define local chemistry domains potentially worthy of further investigation (e.g., not currently covered in the testing library or

A practical approach to determine dose metrics for nanomaterials.

Science.gov (United States)

Delmaar, Christiaan J E; Peijnenburg, Willie J G M; Oomen, Agnes G; Chen, Jingwen; de Jong, Wim H; Sips, Adriënne J A M; Wang, Zhuang; Park, Margriet V D Z

2015-05-01

Traditionally, administered mass is used to describe doses of conventional chemical substances in toxicity studies. For deriving toxic doses of nanomaterials, mass and chemical composition alone may not adequately describe the dose, because particles with the same chemical composition can have completely different toxic mass doses depending on properties such as particle size. Other dose metrics such as particle number, volume, or surface area have been suggested, but consensus is lacking. The discussion regarding the most adequate dose metric for nanomaterials clearly needs a systematic, unbiased approach to determine the most appropriate dose metric for nanomaterials. In the present study, the authors propose such an approach and apply it to results from in vitro and in vivo experiments with silver and silica nanomaterials. The proposed approach is shown to provide a convenient tool to systematically investigate and interpret dose metrics of nanomaterials. Recommendations for study designs aimed at investigating dose metrics are provided. © 2015 SETAC.

Novel approaches to mitigating parathion toxicity: targeting cytochrome P450–mediated metabolism with menadione

Science.gov (United States)

Jan, Yi-Hua; Richardson, Jason R.; Baker, Angela A.; Mishin, Vladimir; Heck, Diane E.; Laskin, Debra L.; Laskin, Jeffrey D.

2016-01-01

Accidental or intentional exposures to parathion, an organophosphorus (OP) pesticide, can cause severe poisoning in humans. Parathion toxicity is dependent on its metabolism by the cytochrome P450 (CYP) system to paraoxon (diethyl 4-nitrophenyl phosphate), a highly poisonous nerve agent and potent inhibitor of acetylcholinesterase (AChE). We have been investigating inhibitors of CYP-mediated bioactivation of OPs as a method of preventing or reversing progressive parathion toxicity. It is well recognized that NADPH–cytochrome P450 reductase, an enzyme required for the transfer of electrons to CYPs, mediates chemical redox cycling. In this process, the enzyme diverts electrons from CYPs to support chemical redox cycling, which results in inhibition of CYP-mediated biotransformation. Using menadione as the redox-cycling chemical, we discovered that this enzymatic reaction blocks metabolic activation of parathion in rat and human liver microsomes and in recombinant CYPs important to parathion metabolism, including CYP1A2, CYP2B6, and CYP3A4. Administration of menadione to rats reduces metabolism of parathion, as well as parathion-induced inhibition of brain cholinesterase activity. This resulted in inhibition of parathion neurotoxicity. Menadione has relatively low toxicity and is approved by the FDA for other indications. Its ability to block parathion metabolism makes it an attractive therapeutic candidate to mitigate parathion-induced neurotoxicity. PMID:27441453

Toxic substances handbook

Science.gov (United States)

Junod, T. L.

1979-01-01

Handbook, published in conjunction with Toxic Substances Alert Program at NASA Lewis Research Center, profiles 187 toxic chemicals in their relatively pure states and include 27 known or suspected carcinogens.

Assessment of multi-chemical pollution in aquatic ecosystems using toxic units: compound prioritization, mixture characterization and relationships with biological descriptors.

Science.gov (United States)

Ginebreda, Antoni; Kuzmanovic, Maja; Guasch, Helena; de Alda, Miren López; López-Doval, Julio C; Muñoz, Isabel; Ricart, Marta; Romaní, Anna M; Sabater, Sergi; Barceló, Damià

2014-01-15

Chemical pollution is typically characterized by exposure to multiple rather than to single or a limited number of compounds. Parent compounds, transformation products and other non-targeted compounds yield mixtures whose composition can only be partially identified by monitoring, while a substantial proportion remains unknown. In this context, risk assessment based on the application of additive ecotoxicity models, such as concentration addition (CA), is rendered somewhat misleading. Here, we show that ecotoxicity risk information can be better understood upon consideration of the probabilistic distribution of risk among the different compounds. Toxic units of the compounds identified in a sample fit a lognormal probability distribution. The parameters characterizing this distribution (mean and standard deviation) provide information which can be tentatively interpreted as a measure of the toxic load and its apportionment among the constituents in the mixture (here interpreted as mixture complexity). Furthermore, they provide information for compound prioritization tailored to each site and enable prediction of some of the functional and structural biological variables associated with the receiving ecosystem. The proposed approach was tested in the Llobregat River basin (NE Spain) using exposure and toxicity data (algae and Daphnia) corresponding to 29 pharmaceuticals and 22 pesticides, and 5 structural and functional biological descriptors related to benthic macroinvertebrates (diversity, biomass) and biofilm metrics (diatom quality, chlorophyll-a content and photosynthetic capacity). Aggregated toxic units based on Daphnia and algae bioassays provided a good indication of the pollution pattern of the Llobregat River basin. Relative contribution of pesticides and pharmaceuticals to total toxic load was variable and highly site dependent, the latter group tending to increase its contribution in urban areas. Contaminated sites' toxic load was typically dominated by

Approaches to chemical synthetic biology.

Science.gov (United States)

Chiarabelli, Cristiano; Stano, Pasquale; Anella, Fabrizio; Carrara, Paolo; Luisi, Pier Luigi

2012-07-16

Synthetic biology is first represented in terms of two complementary aspects, the bio-engineering one, based on the genetic manipulation of extant microbial forms in order to obtain forms of life which do not exist in nature; and the chemical synthetic biology, an approach mostly based on chemical manipulation for the laboratory synthesis of biological structures that do not exist in nature. The paper is mostly devoted to shortly review chemical synthetic biology projects currently carried out in our laboratory. In particular, we describe: the minimal cell project, then the "Never Born Proteins" and lastly the Never Born RNAs. We describe and critically analyze the main results, emphasizing the possible relevance of chemical synthetic biology for the progress in basic science and biotechnology. Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

CHEMICAL COMPOSITION AND TOXICITY OF CITRUS ESSENTIAL OILS ON Dysmicoccus brevipes (HEMIPTERA: PSEUDOCOCCIDAE)

OpenAIRE

MARTINS, GISELE DOS SANTOS OLIVEIRA; ZAGO, HUGO BOLSONI; COSTA, ADILSON VIDAL; ARAUJO JUNIOR, LUIS MOREIRA DE; CARVALHO, JOSÉ ROMÁRIO DE

2017-01-01

ABSTRACT The insect Dysmicoccus brevipes (Hemiptera: Pseudococcidae) has been reported as an important pest for several crops, especially coffee. The citrus essential oils can be obtained as by-products of the citrus-processing industry and have been tested as an alternative to control different insect groups. Therefore, the objective of this work was to determine the chemical composition and evaluate the toxicity of commercial sweet orange (Citrus sinensis), bitter orange (Citrus aurantium) ...

Toxicity of Depleted Uranium Dust Particles: Results of a New Model

International Nuclear Information System (INIS)

Zucchetti, M.

2013-01-01

Depleted uranium (DU) is mostly composed of U-238, a naturally radioactive isotope. Concerning chemical toxicity, uranium, being a heavy metal, is known to have toxic effects on specific organs in the body, the kidneys in particular. Its effects are similar to those of other heavy metals, such as lead and cadmium. Scientific evidence resulting both from in vitro and in vivo analyses shows that current models of the mechanisms of toxicity of uranium dust are not fully satisfactory. They should be refined in order to obtain more effective responses and predictions regarding health effects. In particular, radiotoxicity potential of Depleted Uranium dust originated by military use of this material for ammunition must be re-evaluated taking into account the bystander effect, the dose enhancing effect and other minor phenomena. Uranium dust has both chemical and radiological toxicity: the synergistic aspect of the two effects has to be accounted for, in order to arrive to a complete description of the phenomenon. The combination of the two different toxicities (chemical and radiological) of depleted uranium is attempted here for the first time, approaching the long-term effects of Depleted Uranium, and in particular the carcinogenetic effects. A case study (Balkan war, 1999) is discussed. (Author)

Predicting Developmental Toxicity of ToxCast Phase I Chemicals Using Human Embryonic Stem Cells and Metabolomics

Science.gov (United States)

EPA’s ToxRefDB contains prenatal guideline study data from rats and rabbits for over 240 chemicals that overlap with the ToxCast in vitro high throughput screening project. A subset of these compounds were tested in Stemina Biomarker Discovery's developmental toxicity platform, a...

Overview of Chronic Oral Toxicity Values for Chemicals Present in Hydraulic Fracturing Fluids, Flowback and Produced Waters

Science.gov (United States)

as part of EPA's Hydraulic Fracturing Drinking Water Assessment, EPA is summarizing existing toxicity data for chemicals reported to be used in hydraulic fracturing fluids and/or found in flowback or produced waters from hydraulically fractured wells

Proteomic Signatures of the Zebrafish (Danio rerio) Embryo: Sensitivity and Specificity in Toxicity Assessment of Chemicals.

Science.gov (United States)

Hanisch, Karen; Küster, Eberhard; Altenburger, Rolf; Gündel, Ulrike

2010-01-01

Studies using embryos of the zebrafish Danio rerio (DarT) instead of adult fish for characterising the (eco-) toxic potential of chemicals have been proposed as animal replacing methods. Effect analysis at the molecular level might enhance sensitivity, specificity, and predictive value of the embryonal studies. The present paper aimed to test the potential of toxicoproteomics with zebrafish eleutheroembryos for sensitive and specific toxicity assessment. 2-DE-based toxicoproteomics was performed applying low-dose (EC(10)) exposure for 48 h with three-model substances Rotenone, 4,6-dinitro-o-cresol (DNOC) and Diclofenac. By multivariate "pattern-only" PCA and univariate statistical analyses, alterations in the embryonal proteome were detectable in nonetheless visibly intact organisms and treatment with the three substances was distinguishable at the molecular level. Toxicoproteomics enabled the enhancement of sensitivity and specificity of the embryonal toxicity assay and bear the potency to identify protein markers serving as general stress markers and early diagnosis of toxic stress.

Toxicity Identification and Evaluation for the Effluent from Wastewater Treatment Plant in Industrial Complex using D.magna

Science.gov (United States)

Lee, S.; Keum, H.; Chun Sang, H.

2015-12-01

In recent years, the interests on the impacts of industrial wastewater on aquatic ecosystem have increased with concern about ecosystem protection and human health. Whole effluent toxicity tests are used to monitor toxicity by unknown toxic chemicals as well as conventional pollutants from industrial effluent discharges. This study describes the application of TIE (toxicity identification evaluation) procedures to an acutely toxic effluent from a wastewater treatment plant in industrial complex which was toxic to Daphnia magna. In TIE phase I (characterization step), the toxic effects by heavy metals, organic compounds, oxidants, volatile organic compounds, suspended solids and ammonia were screened and revealed that the source of toxicity is far from these toxicants group. Chemical analysis (TIE phase II) on TDS showed that the concentration of chloride ion (6,900 mg/L) was substantially higher than that predicted from EC50 for D. magna. In confirmation step (TIE phase III), chloride ion was demonstrated to be main toxicant in this effluent by the spiking approach, species sensitivity approach and deletion approach. Calcium, potassium, magnesium, sodium, fluorine, sulfate ion concentration (450, 100, 80, 5,300, 0.66, 2,200mg/L) was not shown toxicity from D. magna. Finally, we concluded that chloride was the most contributing toxicant in the waste water treatment plant. Further research activities are needed for technical support of toxicity identification and evaluation on the various types of wastewater treatment plant discharge in Korea. Keywords : TIE, D. magna, Industrial waste water Acknowledgement This research was supported by a grant (15IFIP-B089908-02) from Plant Research Program funded by Ministry of Land, Infrastructure and Transport of Korean government

An Optoelectronic Nose for Detection of Toxic Gases

Science.gov (United States)

Lim, Sung H.; Feng, Liang; Kemling, Jonathan W.; Musto, Christopher J.; Suslick, Kenneth S.

2009-01-01

We have developed a simple colorimetric sensor array (CSA) for the detection of a wide range of volatile analytes and applied it to the detection of toxic gases. The sensor consists of a disposable array of cross-responsive nanoporous pigments whose colors are changed by diverse chemical interactions with analytes. Although no single chemically responsive pigment is specific for any one analyte, the pattern of color change for the array is a unique molecular fingerprint. Clear differentiation among 19 different toxic industrial chemicals (TICs) within two minutes of exposure at IDLH (immediately dangerous to life or health) concentration has been demonstrated. Quantification of each analyte is easily accomplished based on the color change of the array, and excellent detection limits have been demonstrated, generally below the PELs (permissible exposure limits). Identification of the TICs was readily achieved using a standard chemometric approach, i.e., hierarchical clustering analysis (HCA), with no misclassifications over 140 trials. PMID:20160982

Toxicity of nickel to soil microbial community with and without the presence of its mineral collectors-a calorimetric approach.

Science.gov (United States)

Bararunyeretse, Prudence; Ji, Hongbing; Yao, Jun

2017-06-01

The toxicity of nickel and three of its main collectors, sodium isopropyl xanthate (SIPX), sodium ethyl xanthate (SEX), and potassium ethyl xanthate (PEX) to soil microbial activity, was analyzed, individually and as a binary combination of nickel and each of the collectors. The investigation was performed through the microcalorimetric analysis method. For the single chemicals, all power-time curves exhibited lag, exponential, stationary, and death phases of microbial growth. Different parameters exhibited a significant adverse effect of the analyzed chemicals on soil microbial activity, with a positive relationship between the inhibitory ratio and the chemical dose (p soil in the case of Ni while for the mineral collectors, only 5 μg g -1 soil and 50 μg g -1 soil induced a peak power reduction level of over 35 and 50%, respectively, in general. The inhibitory ratio ranged in the following order: PEX > SEX > SIPX > Ni. Similar behavior was observed with the mixture toxicity whose inhibitory ratio substantially decreased (maximum decrease of 38.35%) and slightly increased (maximum increase of 15.34%), in comparison with the single toxicity of mineral collectors and nickel, respectively. The inhibitory ratio of the mixture toxicity was positively correlated (p toxic effects are those of mixtures containing SIPX and PEX, respectively.

Assessment of acrylamide toxicity using a battery of standardised bioassays.

Science.gov (United States)

Zovko, Mira; Vidaković-Cifrek, Željka; Cvetković, Želimira; Bošnir, Jasna; Šikić, Sandra

2015-12-01

Acrylamide is a monomer widely used as an intermediate in the production of organic chemicals, e.g. polyacrylamides (PAMs). Since PAMs are low cost chemicals with applications in various industries and waste- and drinking water treatment, a certain amount of non-polymerised acrylamide is expected to end up in waterways. PAMs are non-toxic but acrylamide induces neurotoxic effects in humans and genotoxic, reproductive, and carcinogenic effects in laboratory animals. In order to evaluate the effect of acrylamide on freshwater organisms, bioassays were conducted on four species: algae Desmodesmus subspicatus and Pseudokirchneriella subcapitata, duckweed Lemna minor and water flea Daphnia magna according to ISO (International Organization for Standardisation) standardised methods. This approach ensures the evaluation of acrylamide toxicity on organisms with different levels of organisation and the comparability of results, and it examines the value of using a battery of low-cost standardised bioassays in the monitoring of pollution and contamination of aquatic ecosystems. These results showed that EC50 values were lower for Desmodesmus subspicatus and Pseudokirchneriella subcapitata than for Daphnia magna and Lemna minor, which suggests an increased sensitivity of algae to acrylamide. According to the toxic unit approach, the values estimated by the Lemna minor and Daphnia magna bioassays, classify acrylamide as slightly toxic (TU=0-1; Class 1). The results obtained from algal bioassays (Desmodesmus subspicatus and Pseudokirchneriella subcapitata) revealed the toxic effect of acrylamide (TU=1-10; Class 2) on these organisms.

Destruction of highly toxic chemical materials by using the energy of underground thermonuclear explosion

International Nuclear Information System (INIS)

Trutnev, Y.

1991-01-01

One of the main problems of modern technogenic civilisation is the evergrowing ecological crisis caused by the growth of industrial wastes harmful for biosphere. Among them the radioactive wastes of atomic energetics, worked out nuclear energy facilities and toxic wastes from various chemical plants begin to play a specific role. Traditional technologies of destruction and disposal of these wastes demand great investments up to many billions of dollars, enormous maintenance expenditures, occupation of substantial territories by new productions and security zones as well as many qualified specialists. On the other hand potential accidents during the conventional processes of waste reprocessing are fraught with the possibility of large ecological disasters, that are the reason of strong oppositions of population and 'green movement' to the foundation of such installations. So, rather progressive seem to be the technologies based on the utilisation of underground nuclear explosion energy for annihilations and disposal of high-level wastes of atomic energetics and nuclear facilities as well as for thermal decomposition of chemically toxic substances at extremely high temperatures. These technologies will be rather cheap, they will allow to process big amounts of materials in ecologically safe form far from the populated regions and will need a commercially beneficial if used for international purposes. The application of these technologies may be of great significance for realisation of disarmament process- destruction of chemical weapons and in future the nuclear warheads and some production components. (au)

Data gaps in toxicity testing of chemicals allowed in food in the United States.

Science.gov (United States)

Neltner, Thomas G; Alger, Heather M; Leonard, Jack E; Maffini, Maricel V

2013-12-01

In the United States, chemical additives cannot be used in food without an affirmative determination that their use is safe by FDA or additive manufacturer. Feeding toxicology studies designed to estimate the amount of a chemical additive that can be eaten safely provide the most relevant information. We analyze how many chemical additives allowed in human food have feeding toxicology studies in three toxicological information sources including the U.S. Food and Drug Administration's (FDA) database. Less than 38% of FDA-regulated additives have a published feeding study. For chemicals directly added to food, 21.6% have feeding studies necessary to estimate a safe level of exposure and 6.7% have reproductive or developmental toxicity data in FDA's database. A program is needed to fill these significant knowledge gaps by using in vitro and in silico methods complemented with targeted in vivo studies to ensure public health is protected. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Human Pluripotent Stem Cell-Based Assay Predicts Developmental Toxicity Potential of ToxCast Chemicals (ACT meeting)

Science.gov (United States)

Worldwide initiatives to screen for toxicity potential among the thousands of chemicals currently in use require inexpensive and high-throughput in vitro models to meet their goals. The devTOX quickPredict platform is an in vitro human pluripotent stem cell-based assay used to as...

Estimation of toxicity using the Toxicity Estimation Software Tool (TEST)

Science.gov (United States)

Tens of thousands of chemicals are currently in commerce, and hundreds more are introduced every year. Since experimental measurements of toxicity are extremely time consuming and expensive, it is imperative that alternative methods to estimate toxicity are developed.

An optoelectronic nose for the detection of toxic gases.

Science.gov (United States)

Lim, Sung H; Feng, Liang; Kemling, Jonathan W; Musto, Christopher J; Suslick, Kenneth S

2009-10-01

We have developed a simple colorimetric sensor array that detects a wide range of volatile analytes and then applied it to the detection of toxic gases. The sensor consists of a disposable array of cross-responsive nanoporous pigments with colours that are changed by diverse chemical interactions with analytes. Although no single chemically responsive pigment is specific for any one analyte, the pattern of colour change for the array is a unique molecular fingerprint. Clear differentiation among 19 different toxic industrial chemicals (TICs) within two minutes of exposure at concentrations immediately dangerous to life or health were demonstrated. Based on the colour change of the array, quantification of each analyte was accomplished easily, and excellent detection limits were achieved, generally below the permissible exposure limits. Different TICs were identified readily using a standard chemometric approach (hierarchical clustering analysis), with no misclassifications over 140 trials.

Applicability of the fish embryo acute toxicity (FET) test (OECD 236) in the regulatory context of Registration, Evaluation, Authorisation, and Restriction of Chemicals (REACH).

NARCIS (Netherlands)

Sobanska, Marta; Scholz, Stefan; Nyman, Anna-Maija; Cesnaitis, Romanas; Gutierrez Alonso, Simon; Klüver, Nils; Kühne, Ralph; Tyle, Henrik; de Knecht, Joop; Dang, Zhichao; Lundbergh, Ivar; Carlon, Claudio; De Coen, Wim

In 2013 the Organisation for Economic Co-operation and Development (OECD) test guideline (236) for fish embryo acute toxicity (FET) was adopted. It determines the acute toxicity of chemicals to embryonic fish. Previous studies show a good correlation of FET with the standard acute fish toxicity

From basic physics to mechanisms of toxicity: the ``liquid drop'' approach applied to develop predictive classification models for toxicity of metal oxide nanoparticles

Science.gov (United States)

Sizochenko, Natalia; Rasulev, Bakhtiyor; Gajewicz, Agnieszka; Kuz'min, Victor; Puzyn, Tomasz; Leszczynski, Jerzy

2014-10-01

Many metal oxide nanoparticles are able to cause persistent stress to live organisms, including humans, when discharged to the environment. To understand the mechanism of metal oxide nanoparticles' toxicity and reduce the number of experiments, the development of predictive toxicity models is important. In this study, performed on a series of nanoparticles, the comparative quantitative-structure activity relationship (nano-QSAR) analyses of their toxicity towards E. coli and HaCaT cells were established. A new approach for representation of nanoparticles' structure is presented. For description of the supramolecular structure of nanoparticles the ``liquid drop'' model was applied. It is expected that a novel, proposed approach could be of general use for predictions related to nanomaterials. In addition, in our study fragmental simplex descriptors and several ligand-metal binding characteristics were calculated. The developed nano-QSAR models were validated and reliably predict the toxicity of all studied metal oxide nanoparticles. Based on the comparative analysis of contributed properties in both models the LDM-based descriptors were revealed to have an almost similar level of contribution to toxicity in both cases, while other parameters (van der Waals interactions, electronegativity and metal-ligand binding characteristics) have unequal contribution levels. In addition, the models developed here suggest different mechanisms of nanotoxicity for these two types of cells.Many metal oxide nanoparticles are able to cause persistent stress to live organisms, including humans, when discharged to the environment. To understand the mechanism of metal oxide nanoparticles' toxicity and reduce the number of experiments, the development of predictive toxicity models is important. In this study, performed on a series of nanoparticles, the comparative quantitative-structure activity relationship (nano-QSAR) analyses of their toxicity towards E. coli and HaCaT cells were

Chemical and biological properties of toxic metals and use of chelating agents for the pharmacological treatment of metal poisoning

Energy Technology Data Exchange (ETDEWEB)

Sinicropi, Maria Stefania; Caruso, Anna [University of Calabria, Department of Pharmaceutical Sciences, Rende (Italy); Amantea, Diana [University of Calabria, Department of Pharmacobiology, Rende (Italy); Saturnino, Carmela [University of Salerno, Department of Pharmaceutical Sciences, Fisciano (Italy)

2010-07-15

Exposure to toxic metals is a well-known problem in industrialized countries. Metals interfere with a number of physiological processes, including central nervous system (CNS), haematopoietic, hepatic and renal functions. In the evaluation of the toxicity of a particular metal it is crucial to consider many parameters: chemical forms (elemental, organic or inorganic), binding capability, presence of specific proteins that selectively bind metals, etc. Medical treatment of acute and chronic metal toxicity is provided by chelating agents, namely organic compounds capable of interacting with metal ions to form structures called chelates. The present review attempts to provide updated information about the mechanisms, the cellular targets and the effects of toxic metals. (orig.)

Toxic effects exerted on methanogenic, nitrifying and denitrifying bacteria by chemicals used in a milk analysis laboratory

NARCIS (Netherlands)

Lopez-Fiuza, J.; Buys, B.; Mosquera-Corral, A.; Omil, F.; Mendez, R.

2002-01-01

The toxic effects caused by the chemicals contained in wastewaters generated by laboratories involved in raw milk analyses were assessed using batch assays. These assays were carried out separately with methanogenic, ammonium-oxidizing, nitrite-oxidizing and denitrifying bacteria. Since sodium azide

Windows of sensitivity to toxic chemicals in the motor effects development.

Science.gov (United States)

Ingber, Susan Z; Pohl, Hana R

2016-02-01

Many chemicals currently used are known to elicit nervous system effects. In addition, approximately 2000 new chemicals introduced annually have not yet undergone neurotoxicity testing. This review concentrated on motor development effects associated with exposure to environmental neurotoxicants to help identify critical windows of exposure and begin to assess data needs based on a subset of chemicals thoroughly reviewed by the Agency for Toxic Substances and Disease Registry (ATSDR) in Toxicological Profiles and Addenda. Multiple windows of sensitivity were identified that differed based on the maturity level of the neurological system at the time of exposure, as well as dose and exposure duration. Similar but distinct windows were found for both motor activity (GD 8-17 [rats], GD 12-14 and PND 3-10 [mice]) and motor function performance (insufficient data for rats, GD 12-17 [mice]). Identifying specific windows of sensitivity in animal studies was hampered by study designs oriented towards detection of neurotoxicity that occurred at any time throughout the developmental process. In conclusion, while this investigation identified some critical exposure windows for motor development effects, it demonstrates a need for more acute duration exposure studies based on neurodevelopmental windows, particularly during the exposure periods identified in this review. Published by Elsevier Inc.

Distributed Structure Searchable Toxicity

Data.gov (United States)

U.S. Environmental Protection Agency — The Distributed Structure Searchable Toxicity (DSSTox) online resource provides high quality chemical structures and annotations in association with toxicity data....

Toxicity testing and chemical analyses of recycled fibre-based paper for food contact

DEFF Research Database (Denmark)

Binderup, Mona-Lise; Pedersen, Gitte Alsing; Vinggaard, Anne

2002-01-01

of different qualities as food-contact materials and to Perform a preliminary evaluation of their suitability from a safety point of view, and, second, to evaluate the use of different in vitro toxicity tests for screening of paper and board. Paper produced from three different categories of recycled fibres (B...... of the paper products were extracted with either 99% ethanol or water. Potential migrants in the extracts were identified and semiquantified by GC-1R-MS or GC-HRMS. In parallel to the chemical analyses, a battery of four different in vitro toxicity tests with different endpoints were applied to the same...... was less cytotoxic than the extracts prepared from paper made from recycled fibres, and extracts prepared from C was the most cytotoxic. None of the extracts showed mutagenic activity No conclusion about the oestrogenic activity could be made, because all extracts were cytotoxic to the test organism (yeast...

In Silico Prediction of Chemical Toxicity for Drug Design Using Machine Learning Methods and Structural Alerts

Science.gov (United States)

Yang, Hongbin; Sun, Lixia; Li, Weihua; Liu, Guixia; Tang, Yun

2018-02-01

For a drug, safety is always the most important issue, including a variety of toxicities and adverse drug effects, which should be evaluated in preclinical and clinical trial phases. This review article at first simply introduced the computational methods used in prediction of chemical toxicity for drug design, including machine learning methods and structural alerts. Machine learning methods have been widely applied in qualitative classification and quantitative regression studies, while structural alerts can be regarded as a complementary tool for lead optimization. The emphasis of this article was put on the recent progress of predictive models built for various toxicities. Available databases and web servers were also provided. Though the methods and models are very helpful for drug design, there are still some challenges and limitations to be improved for drug safety assessment in the future.

In Silico Prediction of Chemical Toxicity for Drug Design Using Machine Learning Methods and Structural Alerts

Directory of Open Access Journals (Sweden)

Hongbin Yang

2018-02-01

Full Text Available During drug development, safety is always the most important issue, including a variety of toxicities and adverse drug effects, which should be evaluated in preclinical and clinical trial phases. This review article at first simply introduced the computational methods used in prediction of chemical toxicity for drug design, including machine learning methods and structural alerts. Machine learning methods have been widely applied in qualitative classification and quantitative regression studies, while structural alerts can be regarded as a complementary tool for lead optimization. The emphasis of this article was put on the recent progress of predictive models built for various toxicities. Available databases and web servers were also provided. Though the methods and models are very helpful for drug design, there are still some challenges and limitations to be improved for drug safety assessment in the future.

In Silico Prediction of Chemical Toxicity for Drug Design Using Machine Learning Methods and Structural Alerts.

Science.gov (United States)

Yang, Hongbin; Sun, Lixia; Li, Weihua; Liu, Guixia; Tang, Yun

2018-01-01

During drug development, safety is always the most important issue, including a variety of toxicities and adverse drug effects, which should be evaluated in preclinical and clinical trial phases. This review article at first simply introduced the computational methods used in prediction of chemical toxicity for drug design, including machine learning methods and structural alerts. Machine learning methods have been widely applied in qualitative classification and quantitative regression studies, while structural alerts can be regarded as a complementary tool for lead optimization. The emphasis of this article was put on the recent progress of predictive models built for various toxicities. Available databases and web servers were also provided. Though the methods and models are very helpful for drug design, there are still some challenges and limitations to be improved for drug safety assessment in the future.

A new index to assess chemicals increasing the greenhouse effect based on their toxicity to algae.

Science.gov (United States)

Wang, Ting; Zhang, Xiaoxian; Tian, Dayong; Gao, Ya; Lin, Zhifen; Liu, Ying; Kong, Lingyun

2015-11-01

CO2, as the typical greenhouse gas causing the greenhouse effect, is a major global environmental problem and has attracted increasing attention from governments. Using algae to eliminate CO2, which has been proposed as an effective way to reduce the greenhouse effect in the past decades, can be disturbed by a growing number of artificial chemicals. Thus, seven types of chemicals and Selenastrum capricornutum (algae) were examined in this study, and the good consistency between the toxicity of artificial chemicals to algae and the disturbance of carbon fixation by the chemicals was revealed. This consistency showed that the disturbance of an increasing number of artificial chemicals to the carbon fixation of algae might be a "malware" worsening the global greenhouse effect. Therefore, this study proposes an original, promising index to assess the risk of deepening the greenhouse effect by artificial chemicals before they are produced and marketed. Copyright © 2015 Elsevier B.V. All rights reserved.

Toxicity alarm: Case history

International Nuclear Information System (INIS)

Hogan, D.; Retallack, J.

1993-01-01

In late fall 1991, the Novacor petrochemical plant near Joffre, Alberta experienced a toxicity alarm, the first since its startup 14 years ago. Fish exposed to a normal toxicity test were stressed within 2 h and showed 100% mortality after 24 h. A history of the events leading up to, during, and after the toxicity alarm is presented. The major effluent sources were three cooling water systems. Although these sources are well characterized, the event causes were not immediately clear. Initial toxic screening indicated that one was very toxic, another moderately toxic, and the third not toxic at all. All three systems utilized the same chemical treatment program to avoid fouling: stabilized phosphates with minor variants. The most toxic of the cooling systems operated at 10-12 cycles, had three chemicals for biocide control, and had three makeup streams. Toxic and nontoxic system characteristics were compared. An in-depth modified toxicity identification and evaluation program was then performed to identify and evaluate the cause of the toxicity alarm for future prevention. The most probable causes of toxicity were identified by elimination. The combination of high numbers of cycles, hydrocarbons in the makeup water, and bromine added as an antifoulant resulted in formation of aromatic bromamines which are capable of causing the toxic condition experienced. 2 tabs

Toxicity tests with crustaceans for detecting sublethal effects of potential endocrine disrupting chemicals

DEFF Research Database (Denmark)

Wollenberger, Leah

/antagonistic activity with the ecdysteroid-responsive Drosophila melanogaster BII cell line 6) to draft an OECD guideline proposal for testing of chemicals based on the experimental work performed within this study In preliminary investigations with A. tonsa were studied various parameters related to processes......New and updated test methods to detect and characterise endocrine disrupting chemicals are urgently needed for the purpose of environmental risk assessment. Although endocrine disruption in invertebrates has not been studied as extensive as in vertebrates, in particular in fish, numerous reports...... of the present Ph.D. project were: 1) to develop a fully synthetic saltwater medium suitable for laboratory culturing of marine copepods including their feeding organism as well as for toxicity testing 2) to identify sensitive endpoints related to growth, development and reproduction of the pelagic calanoid...

A Tox21 Approach to Altered Epigenetic Landscapes: Assessing Epigenetic Toxicity Pathways Leading to Altered Gene Expression and Oncogenic Transformation In Vitro

Directory of Open Access Journals (Sweden)

Craig L. Parfett

2017-06-01

Full Text Available An emerging vision for toxicity testing in the 21st century foresees in vitro assays assuming the leading role in testing for chemical hazards, including testing for carcinogenicity. Toxicity will be determined by monitoring key steps in functionally validated molecular pathways, using tests designed to reveal chemically-induced perturbations that lead to adverse phenotypic endpoints in cultured human cells. Risk assessments would subsequently be derived from the causal in vitro endpoints and concentration vs. effect data extrapolated to human in vivo concentrations. Much direct experimental evidence now shows that disruption of epigenetic processes by chemicals is a carcinogenic mode of action that leads to altered gene functions playing causal roles in cancer initiation and progression. In assessing chemical safety, it would therefore be advantageous to consider an emerging class of carcinogens, the epigenotoxicants, with the ability to change chromatin and/or DNA marks by direct or indirect effects on the activities of enzymes (writers, erasers/editors, remodelers and readers that convey the epigenetic information. Evidence is reviewed supporting a strategy for in vitro hazard identification of carcinogens that induce toxicity through disturbance of functional epigenetic pathways in human somatic cells, leading to inactivated tumour suppressor genes and carcinogenesis. In the context of human cell transformation models, these in vitro pathway measurements ensure high biological relevance to the apical endpoint of cancer. Four causal mechanisms participating in pathways to persistent epigenetic gene silencing were considered: covalent histone modification, nucleosome remodeling, non-coding RNA interaction and DNA methylation. Within these four interacting mechanisms, 25 epigenetic toxicity pathway components (SET1, MLL1, KDM5, G9A, SUV39H1, SETDB1, EZH2, JMJD3, CBX7, CBX8, BMI, SUZ12, HP1, MPP8, DNMT1, DNMT3A, DNMT3B, TET1, MeCP2, SETDB2, BAZ2

Assessing the toxic effects of ethylene glycol ethers using Quantitative Structure Toxicity Relationship models

International Nuclear Information System (INIS)

Ruiz, Patricia; Mumtaz, Moiz; Gombar, Vijay

2011-01-01

Experimental determination of toxicity profiles consumes a great deal of time, money, and other resources. Consequently, businesses, societies, and regulators strive for reliable alternatives such as Quantitative Structure Toxicity Relationship (QSTR) models to fill gaps in toxicity profiles of compounds of concern to human health. The use of glycol ethers and their health effects have recently attracted the attention of international organizations such as the World Health Organization (WHO). The board members of Concise International Chemical Assessment Documents (CICAD) recently identified inadequate testing as well as gaps in toxicity profiles of ethylene glycol mono-n-alkyl ethers (EGEs). The CICAD board requested the ATSDR Computational Toxicology and Methods Development Laboratory to conduct QSTR assessments of certain specific toxicity endpoints for these chemicals. In order to evaluate the potential health effects of EGEs, CICAD proposed a critical QSTR analysis of the mutagenicity, carcinogenicity, and developmental effects of EGEs and other selected chemicals. We report here results of the application of QSTRs to assess rodent carcinogenicity, mutagenicity, and developmental toxicity of four EGEs: 2-methoxyethanol, 2-ethoxyethanol, 2-propoxyethanol, and 2-butoxyethanol and their metabolites. Neither mutagenicity nor carcinogenicity is indicated for the parent compounds, but these compounds are predicted to be developmental toxicants. The predicted toxicity effects were subjected to reverse QSTR (rQSTR) analysis to identify structural attributes that may be the main drivers of the developmental toxicity potential of these compounds.

Bioassay of Lake Onego bottom sediments toxicity based on their chemical composition and deepwater macrozoobenthos state

Directory of Open Access Journals (Sweden)

Kalinkina Nataliya Michailovna

2017-03-01

Full Text Available The bioassay of the toxicity of bottom sediments sampled in different areas of Lake Onega was carried out by crustaceans biotesting (Ceriodaphnia affinis Lillijeborg. It was shown that in the most areas of Lake Onega there are non-toxic bottom sediments. Toxic bottom sediments were found in Kondopogskaya Bay, intensively polluted with pulp-and-paper mill wastewaters. For the first time in the deep central part of Lake Onega the area was revealed where the toxic bottom sediments contain a high content of iron, manganese and other trace elements typical for the central areas of the lake. The mapping of the bottom of Lake Onega was accomplished, and three zones were identified based on the analysis of the data concerning the chemical composition of bottom sediments, bioassay toxicity data and the results of the deepwater macrozoobenthos assessment. For each zone the parameters of the main groups of benthos (Amphipoda, Oligochaeta, Chironomidae were defined. The first zone is located in the area of intensive anthropogenic influence (Kondopogskaya Bay, Petrozavodskaya Bay, Povenets Bay, Kizhi Skerries. The second zone is located mostly in the deep part of Petrozavodskaya Bay, where the most intensive development of amphipods is observed. The third area is identified for the first time: it is located in the central deep part of Lake Onega, where the communities of macrozoobenthos are limited by a natural toxic factor.

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...

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.

Test systems to identify reproductive toxicants.

Science.gov (United States)

Riecke, K; Stahlmann, R

2000-09-01

Experience with drugs and other xenobiotics indicates that both animal testing and epidemiological studies are necessary to provide adequate data for an estimation of risks that might be associated with exposure to a chemical substance. In this review, the pros and cons of test systems for reproductive toxicity are discussed. Usually, several studies are performed to cover the different phases of the reproductive cycle. In the preclinical development of drugs, the three so-called 'segment testing protocols' have been used for several decades now. More recently, new testing concepts have been accepted internationally which include more flexibility in implementation. Several examples of compounds with the potential for reproductive toxicity are presented in more detail in a discussion of some pitfalls of the tests for fertility (phthalates and fluoroquinolones), teratogenicity (acyclovir and protease inhibitors) and postnatal developmental toxicity (fluoroquinolones). In addition, important aspects of kinetics and metabolism as a prerequisite for a rational interpretation of results from toxicological studies are briefly discussed. In vitro assays are useful for supplementing the routinely used in vivo approaches or for studying an expected or defined effect, but they are not suitable for revealing an unknown effect of a chemical on the complex reproductive process.

Full-thickness human skin explants for testing the toxicity of topically applied chemicals

International Nuclear Information System (INIS)

Nakamura, M.; Rikimaru, T.; Yano, T.; Moore, K.G.; Pula, P.J.; Schofield, B.H.; Dannenberg, A.M. Jr.

1990-01-01

This report describes a model organ-culture system for testing the toxicity of chemical substances that are topically applied to human skin. In this system, the viable keratinocytes in the full-thickness skin explants are protected by the same keratinized layer as skin remaining on the donor, and toxicity can be assessed microscopically and/or biochemically. The human skin specimens were discards from a variety of surgical procedures. They were cut into full-thickness 1.0-cm2 explants, and briefly exposed to the military vesicant sulfur mustard (SM), which was used as a model toxicant. The explants were then organ cultured in small Petri dishes for 24 h at 36 degrees C. In the 0.03-1.0% dosage range, a straight-line dose-response relationship occurred between the concentration of SM applied and the number of paranuclear vacuoles seen histologically in the epidermis. Within the same SM dosage range, there was also a proportional decrease in 14C-leucine incorporation by the explants. Thus, the number of paranuclear vacuoles reflected decreases in protein synthesis by the injured epidermal cells. The epidermis of full-thickness untreated (control) human skin explants usually remained viable for 7 d when stored at 4 degrees C in culture medium. During storage, a relatively small number of paranuclear vacuoles developed within the epidermis, but the explants were still quite satisfactory for testing SM toxicity. Incubation (for 4 or 24 h at 36 degrees C) of such control skin explants reduced (often by 50%) the small number of paranuclear vacuoles produced during 4-7 d of storage. This reduction was probably caused by autolysis of many of the vacuolated cells. Two types of paranuclear vacuoles could be identified by both light and electron microscopy: a storage type and a toxicant type. The storage type seemed to be caused by autolysis of cell components

Full-thickness human skin explants for testing the toxicity of topically applied chemicals

Energy Technology Data Exchange (ETDEWEB)

Nakamura, M.; Rikimaru, T.; Yano, T.; Moore, K.G.; Pula, P.J.; Schofield, B.H.; Dannenberg, A.M. Jr. (Johns Hopkins Univ., Baltimore, MD (USA))

1990-09-01

This report describes a model organ-culture system for testing the toxicity of chemical substances that are topically applied to human skin. In this system, the viable keratinocytes in the full-thickness skin explants are protected by the same keratinized layer as skin remaining on the donor, and toxicity can be assessed microscopically and/or biochemically. The human skin specimens were discards from a variety of surgical procedures. They were cut into full-thickness 1.0-cm2 explants, and briefly exposed to the military vesicant sulfur mustard (SM), which was used as a model toxicant. The explants were then organ cultured in small Petri dishes for 24 h at 36 degrees C. In the 0.03-1.0% dosage range, a straight-line dose-response relationship occurred between the concentration of SM applied and the number of paranuclear vacuoles seen histologically in the epidermis. Within the same SM dosage range, there was also a proportional decrease in 14C-leucine incorporation by the explants. Thus, the number of paranuclear vacuoles reflected decreases in protein synthesis by the injured epidermal cells. The epidermis of full-thickness untreated (control) human skin explants usually remained viable for 7 d when stored at 4 degrees C in culture medium. During storage, a relatively small number of paranuclear vacuoles developed within the epidermis, but the explants were still quite satisfactory for testing SM toxicity. Incubation (for 4 or 24 h at 36{degrees}C) of such control skin explants reduced (often by 50%) the small number of paranuclear vacuoles produced during 4-7 d of storage. This reduction was probably caused by autolysis of many of the vacuolated cells. Two types of paranuclear vacuoles could be identified by both light and electron microscopy: a storage type and a toxicant type. The storage type seemed to be caused by autolysis of cell components.

ToxiM: A Toxicity Prediction Tool for Small Molecules Developed Using Machine Learning and Chemoinformatics Approaches

Directory of Open Access Journals (Sweden)

Ashok K. Sharma

2017-11-01

Full Text Available The experimental methods for the prediction of molecular toxicity are tedious and time-consuming tasks. Thus, the computational approaches could be used to develop alternative methods for toxicity prediction. We have developed a tool for the prediction of molecular toxicity along with the aqueous solubility and permeability of any molecule/metabolite. Using a comprehensive and curated set of toxin molecules as a training set, the different chemical and structural based features such as descriptors and fingerprints were exploited for feature selection, optimization and development of machine learning based classification and regression models. The compositional differences in the distribution of atoms were apparent between toxins and non-toxins, and hence, the molecular features were used for the classification and regression. On 10-fold cross-validation, the descriptor-based, fingerprint-based and hybrid-based classification models showed similar accuracy (93% and Matthews's correlation coefficient (0.84. The performances of all the three models were comparable (Matthews's correlation coefficient = 0.84–0.87 on the blind dataset. In addition, the regression-based models using descriptors as input features were also compared and evaluated on the blind dataset. Random forest based regression model for the prediction of solubility performed better (R2 = 0.84 than the multi-linear regression (MLR and partial least square regression (PLSR models, whereas, the partial least squares based regression model for the prediction of permeability (caco-2 performed better (R2 = 0.68 in comparison to the random forest and MLR based regression models. The performance of final classification and regression models was evaluated using the two validation datasets including the known toxins and commonly used constituents of health products, which attests to its accuracy. The ToxiM web server would be a highly useful and reliable tool for the prediction of toxicity

Enhanced toxic cloud knockdown spray system for decontamination applications

Science.gov (United States)

Betty, Rita G [Rio Rancho, NM; Tucker, Mark D [Albuquerque, NM; Brockmann, John E [Albuquerque, NM; Lucero, Daniel A [Albuquerque, NM; Levin, Bruce L [Tijeras, NM; Leonard, Jonathan [Albuquerque, NM

2011-09-06

Methods and systems for knockdown and neutralization of toxic clouds of aerosolized chemical or biological warfare (CBW) agents and toxic industrial chemicals using a non-toxic, non-corrosive aqueous decontamination formulation.

Oocyte toxicity: female germ-cell loss from radiation and chemical exposures

International Nuclear Information System (INIS)

Dobson, R.L.

1984-01-01

In some mammals, female germ cells are extraordinarily sensitive to killing by exposure to ionizing radiation, especially during development. Immature oocytes, which constitute the lifetime germ-cell pool of the female, have an LD 50 in juvenile mice of only 6 rad (compared with typical LD 50 s of 100-300 rad for most other cell types studied). Essentially, the entire germ-cell supply in female squirrel monkeys is destroyed prenatally by exposure of only 0.7 rad/day. Severe but lesser destruction has been found in other species. However, evidence suggests (though not ruled out for all developmental stages) that unusually high sensitivity probably does not occur in the human female. Germ cells can also be killed by certain chemicals, and similarities exist between chemical and radiation effects. More than 75 compounds have been quantitatively studied in mice, with determination of OTI values (OTI = oocyte toxicity index = mouse LD 50 /oocyte LD 50 ) to measure the degree of preferential oocyte killing. High sensitivity in mice does not mean necessarily high sensitivity in women. Of special interest is the recent discovery that the lethal target in the extremely sensitive mouse immature oocyte is probably the plasma membrane, not DNA. Since mouse data form the main basis from which human genetic hazard (for both radiation and chemicals) is estimated, this has important implications for the determination of genetic risk in women

Acute sensitivity of freshwater mollusks and commonly tested invertebrates to select chemicals with different toxic models of action

Science.gov (United States)

Previous studies indicate that freshwater mollusks are more sensitive than commonly tested organisms to some chemicals, such as copper and ammonia. Nevertheless, mollusks are generally under-represented in toxicity databases. Studies are needed to generate data with which to comp...

Evaluation of e-liquid toxicity using an open-source high-throughput screening assay

Science.gov (United States)

Keating, James E.; Zorn, Bryan T.; Kochar, Tavleen K.; Wolfgang, Matthew C.; Glish, Gary L.; Tarran, Robert

2018-01-01

The e-liquids used in electronic cigarettes (E-cigs) consist of propylene glycol (PG), vegetable glycerin (VG), nicotine, and chemical additives for flavoring. There are currently over 7,700 e-liquid flavors available, and while some have been tested for toxicity in the laboratory, most have not. Here, we developed a 3-phase, 384-well, plate-based, high-throughput screening (HTS) assay to rapidly triage and validate the toxicity of multiple e-liquids. Our data demonstrated that the PG/VG vehicle adversely affected cell viability and that a large number of e-liquids were more toxic than PG/VG. We also performed gas chromatography–mass spectrometry (GC-MS) analysis on all tested e-liquids. Subsequent nonmetric multidimensional scaling (NMDS) analysis revealed that e-liquids are an extremely heterogeneous group. Furthermore, these data indicated that (i) the more chemicals contained in an e-liquid, the more toxic it was likely to be and (ii) the presence of vanillin was associated with higher toxicity values. Further analysis of common constituents by electron ionization revealed that the concentration of cinnamaldehyde and vanillin, but not triacetin, correlated with toxicity. We have also developed a publicly available searchable website (www.eliquidinfo.org). Given the large numbers of available e-liquids, this website will serve as a resource to facilitate dissemination of this information. Our data suggest that an HTS approach to evaluate the toxicity of multiple e-liquids is feasible. Such an approach may serve as a roadmap to enable bodies such as the Food and Drug Administration (FDA) to better regulate e-liquid composition. PMID:29584716

Removal of toxic chemicals from water with activated carbon

Science.gov (United States)

Dawson, V.K.; Marking, L.L.; Bills, T.D.

1976-01-01

Activated carbon was effective in removing fish toxicants and anesthetics from water solutions. Its capacity to adsorb 3-trifluoromethyl-4-nitrophenol (TFM), antimycin, NoxfishA? (5% rotenone), Dibrorms, juglone, MSa??222, and benzocaine ranged from 0.1 to 64 mg per gram of carbon. The adsorptive capacity (end point considered as a significant discharge) of activated carbon for removal of TFM was determined at column depths of 15, 30, and 60 cm; temperatures of 7, 12, 17, and 22 C; pH's of 6.5, 7.5, 8.5, and 9.5; and flow rates of 50, 78, 100, 200, and 940 ml/min. Adsorptive capacity increased when the contact time was increased by reducing the flow rate or increasing the column depth. The adsorptive capacity was not significantly influenced by temperature but was substantially higher at pH 6.5 than at the other pH's tested. A practical and efficient filter for purifying chemically treated water was developed.

Predicting degradability of organic chemicals

Energy Technology Data Exchange (ETDEWEB)

Finizio, A; Vighi, M [Milan Univ. (Italy). Ist. di Entomologia Agraria

1992-05-01

Degradability, particularly biodegradability, is one of the most important factors governing the persistence of pollutants in the environment and consequently influencing their behavior and toxicity in aquatic and terrestrial ecosystems. The need for reliable persistence data in order to assess the environmental fate and hazard of chemicals by means of predictive approaches, is evident. Biodegradability tests are requested by the EEC directive on new chemicals. Neverthless, degradation tests are not easy to carry out and data on existing chemicals are very scarce. Therefore, assessing the fate of chemicals in the environment from the simple study of their structure would be a useful tool. Rates of degradation are a function of the rates of a series of processes. Correlation between degradation rates and structural parameters are will be facilitated if one of the processes is rate determining. This review is a survey of studies dealing with relationships between structure and biodegradation of organic chemicals, to identify the value and limitations of this approach.

Toxicity Estimation Software Tool (TEST)

Science.gov (United States)

The Toxicity Estimation Software Tool (TEST) was developed to allow users to easily estimate the toxicity of chemicals using Quantitative Structure Activity Relationships (QSARs) methodologies. QSARs are mathematical models used to predict measures of toxicity from the physical c...

Membrane alterations following toxic chemical insult. Research progress report No. 3 (Final), 15 July 1984-31 January 1988

Energy Technology Data Exchange (ETDEWEB)

Liss, A.

1988-03-10

A procaryotic cell system was developed that can be used to determine the toxic action of chemicals acting at the level of the eucaryotic or procaryotic cytoplasmic membrane. Cell wall-less microbes known as mycoplasmas were used. In this current study, two perfluorinated fatty acids (CB and C10) were found to inhibit the growth of the test mycoplasmas. Two apparent activities, cytotoxicity and cytolysis, were observed. At high concentrations (>10 mM), a detergent-like action was noted. At low concentrations (<10 mM), cell death was observed without detectable cell lysis. Altering the cell membrane (the presumed target of the toxic compounds) resulted in altered levels to toxicity. Similar results were obtained when human or murine B-cells were used as the target organism. The toxic action of the perfluorinated fatty acids apparently involves some interaction with the membrane of the cells being treated.

Genomic interrogation of mechanism(s) underlying cellular responses to toxicants

International Nuclear Information System (INIS)

Amin, Rupesh P.; Hamadeh, Hisham K.; Bushel, Pierre R.; Bennett, Lee; Afshari, Cynthia A.; Paules, Richard S.

2002-01-01

Assessment of the impact of xenobiotic exposure on human health and disease progression is complex. Knowledge of mode(s) of action, including mechanism(s) contributing to toxicity and disease progression, is valuable for evaluating compounds. Toxicogenomics, the subdiscipline which merges genomics with toxicology, holds the promise to contributing significantly toward the goal of elucidating mechanism(s) by studying genome-wide effects of xenobiotics. Global gene expression profiling, revolutionized by microarray technology and a crucial aspect of a toxicogenomic study, allows measuring transcriptional modulation of thousands of genes following exposure to a xenobiotic. We use our results from previous studies on compounds representing two different classes of xenobiotics (barbiturate and peroxisome proliferator) to discuss the application of computational approaches for analyzing microarray data to elucidate mechanism(s) underlying cellular responses to toxicants. In particular, our laboratory demonstrated that chemical-specific patterns of gene expression can be revealed using cDNA microarrays. Transcript profiling provides discrimination between classes of toxicants, as well as, genome-wide insight into mechanism(s) of toxicity and disease progression. Ultimately, the expectation is that novel approaches for predicting xenobiotic toxicity in humans will emerge from such information

A category approach for reproductive effects of phthalates.

NARCIS (Netherlands)

Fabjan, Evelin; Hulzebos, Etje; Mennes, W; Piersma, Aldert H

2006-01-01

In regulatory toxicology, the experimental assessment of reproductive toxicity is one of the most costly endpoints to perform. Categorizing chemicals is an approach that can be used to reduce animal tests in risk assessments of chemicals, for example, via REACH (Registration, Evaluation, and

Mitochondrial Toxicity in Human Pregnancy: An Update on Clinical and Experimental Approaches in the Last 10 Years

Directory of Open Access Journals (Sweden)

Constanza Morén

2014-09-01

Full Text Available Mitochondrial toxicity can be one of the most dreadful consequences of exposure to a wide range of external agents including pathogens, therapeutic agents, abuse drugs, toxic gases and other harmful chemical substances. However, little is known about the effects of mitochondrial toxicity on pregnant women exposed to these agents that may exert transplacental activity and condition fetal remodeling. It has been hypothesized that mitochondrial toxicity may be involved in some adverse obstetric outcomes. In the present study, we investigated the association between exposure to mitochondrial toxic agents and pathologic conditions ranging from fertility defects, detrimental fetal development and impaired newborn health due to intra-uterine exposure. We have reviewed data from studies in human subjects to propose mechanisms of mitochondrial toxicity that could be associated with the symptoms present in both exposed pregnant and fetal patients. Since some therapeutic interventions or accidental exposure cannot be avoided, further research is needed to gain insight into the molecular pathways leading to mitochondrial toxicity during pregnancy. The ultimate objective of these studies should be to reduce the mitochondrial toxicity of these agents and establish biomarkers for gestational monitoring of harmful effects.

A stochastic approach to chemical evolution

International Nuclear Information System (INIS)

Copi, C.J.

1997-01-01

Observations of elemental abundances in the Galaxy have repeatedly shown an intrinsic scatter as a function of time and metallicity. The standard approach to chemical evolution does not attempt to address this scatter in abundances since only the mean evolution is followed. In this work, the scatter is addressed via a stochastic approach to solving chemical evolution models. Three simple chemical evolution scenarios are studied using this stochastic approach: a closed box model, an infall model, and an outflow model. These models are solved for the solar neighborhood in a Monte Carlo fashion. The evolutionary history of one particular region is determined randomly based on the star formation rate and the initial mass function. Following the evolution in an ensemble of such regions leads to the predicted spread in abundances expected, based solely on different evolutionary histories of otherwise identical regions. In this work, 13 isotopes are followed, including the light elements, the CNO elements, a few α-elements, and iron. It is found that the predicted spread in abundances for a 10 5 M circle-dot region is in good agreement with observations for the α-elements. For CN, the agreement is not as good, perhaps indicating the need for more physics input for low-mass stellar evolution. Similarly for the light elements, the predicted scatter is quite small, which is in contradiction to the observations of 3 He in HII regions. The models are tuned for the solar neighborhood so that good agreement with HII regions is not expected. This has important implications for low-mass stellar evolution and on using chemical evolution to determine the primordial light-element abundances in order to test big bang nucleosynthesis. copyright 1997 The American Astronomical Society

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.

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

E-SovTox: An online database of the main publicly-available sources of toxicity data concerning REACH-relevant chemicals published in the Russian language.

Science.gov (United States)

Sihtmäe, Mariliis; Blinova, Irina; Aruoja, Villem; Dubourguier, Henri-Charles; Legrand, Nicolas; Kahru, Anne

2010-08-01

A new open-access online database, E-SovTox, is presented. E-SovTox provides toxicological data for substances relevant to the EU Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) system, from publicly-available Russian language data sources. The database contains information selected mainly from scientific journals published during the Soviet Union era. The main information source for this database - the journal, Gigiena Truda i Professional'nye Zabolevania [Industrial Hygiene and Occupational Diseases], published between 1957 and 1992 - features acute, but also chronic, toxicity data for numerous industrial chemicals, e.g. for rats, mice, guinea-pigs and rabbits. The main goal of the abovementioned toxicity studies was to derive the maximum allowable concentration limits for industrial chemicals in the occupational health settings of the former Soviet Union. Thus, articles featured in the database include mostly data on LD50 values, skin and eye irritation, skin sensitisation and cumulative properties. Currently, the E-SovTox database contains toxicity data selected from more than 500 papers covering more than 600 chemicals. The user is provided with the main toxicity information, as well as abstracts of these papers in Russian and in English (given as provided in the original publication). The search engine allows cross-searching of the database by the name or CAS number of the compound, and the author of the paper. The E-SovTox database can be used as a decision-support tool by researchers and regulators for the hazard assessment of chemical substances. 2010 FRAME.

Specific Chemical and Genetic Markers Revealed a Thousands-Year Presence of Toxic Nodularia spumigena in the Baltic Sea.

Science.gov (United States)

Cegłowska, Marta; Toruńska-Sitarz, Anna; Kowalewska, Grażyna; Mazur-Marzec, Hanna

2018-04-04

In the Baltic Sea, diazotrophic cyanobacteria have been present for thousands of years, over the whole brackish water phase of the ecosystem. However, our knowledge about the species composition of the cyanobacterial community is limited to the last several decades. In the current study, the presence of species-specific chemical and genetic markers in deep sediments were analyzed to increase the existing knowledge on the history of toxic Nodularia spumigena blooms in the Baltic Sea. As chemical markers, three cyclic nonribosomal peptides were applied: the hepatotoxic nodularin, which in the sea was detected solely in N. spumigena , and two anabaenopeptins (AP827 and AP883a) characteristic of two different chemotypes of this species. From the same sediment samples, DNA was isolated and the gene involved in biosynthesis of nodularin, as well as the phycocyanin intergenic spacer region (PC-IGS), were amplified. The results of chemical and genetic analyses proved for the first time the thousands-year presence of toxic N. spumigena in the Baltic Sea. They also indicated that through all this time, the same two sub-populations of the species co-existed.

QSAR Models for Reproductive Toxicity and Endocrine Disruption Activity

Directory of Open Access Journals (Sweden)

Marjan Vračko

2010-03-01

Full Text Available Reproductive toxicity is an important regulatory endpoint, which is required in registration procedures of chemicals used for different purposes (for example pesticides. The in vivo tests are expensive, time consuming and require large numbers of animals, which must be sacrificed. Therefore an effort is ongoing to develop alternative In vitro and in silico methods to evaluate reproductive toxicity. In this review we describe some modeling approaches. In the first example we describe the CAESAR model for prediction of reproductive toxicity; the second example shows a classification model for endocrine disruption potential based on counter propagation artificial neural networks; the third example shows a modeling of relative binding affinity to rat estrogen receptor, and the fourth one shows a receptor dependent modeling experiment.

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.

Evaluation of single and joint toxic effects of diuron and its main metabolites on natural phototrophic biofilms using a pollution-induced community tolerance (PICT) approach.

Science.gov (United States)

Pesce, Stéphane; Lissalde, Sophie; Lavieille, Delphine; Margoum, Christelle; Mazzella, Nicolas; Roubeix, Vincent; Montuelle, Bernard

2010-09-15

This study assessed the single and joint acute toxicity of diuron and two of its metabolites (DCPMU and 3,4-DCA) on natural phototrophic biofilms using a PICT approach with photosynthesis bioassays. River biofilm communities were collected at three sampling stations exhibiting increasing concentrations of diuron, DCPMU and 3,4-DCA from upstream to downstream. Applied individually, the parent compound was more toxic than its metabolites, with DCPMU being more toxic than 3,4-DCA which only inhibited photosynthesis at very high concentrations (EC25 at about 5 mg/l). Sensitivity of biofilm communities to diuron and DCPMU decreased from upstream to downstream, revealing tolerance induction in contaminated sections of the river, as expected from the PICT concept. Nevertheless, PICT was not applicable for 3,4-DCA, which similarly affected upstream, intermediate and downstream biofilm communities. Chemical mixtures of diuron and DCPMU demonstrated additive effects whereas combinations with 3,4-DCA enhanced the observed effects. Our results reveal that the individual and combined presence of diuron and DCPMU in lotic ecosystems can have both short-term effects (as shown with bioassays) and long-term effects (as shown through the PICT approach) on phototrophic biofilms, whereas environmental concentrations of 3,4-DCA may not affect biofilm photosynthetic activity. 2010 Elsevier B.V. All rights reserved.

Bioalerts: a python library for the derivation of structural alerts from bioactivity and toxicity data sets.

Science.gov (United States)

Cortes-Ciriano, Isidro

2016-01-01

Assessing compound toxicity at early stages of the drug discovery process is a crucial task to dismiss drug candidates likely to fail in clinical trials. Screening drug candidates against structural alerts, i.e. chemical fragments associated to a toxicological response prior or after being metabolized (bioactivation), has proved a valuable approach for this task. During the last decades, diverse algorithms have been proposed for the automatic derivation of structural alerts from categorical toxicity data sets. Here, the python library bioalerts is presented, which comprises functionalities for the automatic derivation of structural alerts from categorical (dichotomous), e.g. toxic/non-toxic, and continuous bioactivity data sets, e.g. [Formula: see text] or [Formula: see text] values. The library bioalerts relies on the RDKit implementation of the circular Morgan fingerprint algorithm to compute chemical substructures, which are derived by considering radial atom neighbourhoods of increasing bond radius. In addition to the derivation of structural alerts, bioalerts provides functionalities for the calculation of unhashed (keyed) Morgan fingerprints, which can be used in predictive bioactivity modelling with the advantage of allowing for a chemically meaningful deconvolution of the chemical space. Finally, bioalerts provides functionalities for the easy visualization of the derived structural alerts.

Chemical toxicity of uranium hexafluoride compared to acute effects of radiation

International Nuclear Information System (INIS)

McGuire, S.A.

1991-02-01

The chemical effects from acute exposures to uranium hexafluoride are compared to the nonstochastic effects from acute radiation doses of 25 rems to the whole body and 300 rems to the thyroid. The analysis concludes that an intake of about 10 mg of uranium in soluble form is roughly comparable, in terms of early effects, to an acute whole body dose of 25 rems because both are just below the threshold for significant nonstochastic effects. Similarly, an exposure to hydrogen fluoride at a concentration of 25 mg/m 3 for 30 minutes is roughly comparable because there would be no significant nonstochastic effects. For times t other than 30 minutes, the concentration C of hydrogen fluoride considered to have the same effect can be calculated using a quadratic equation: C = 25 mg/m 3 (30 min/t). The purpose of these analyses is to provide information for developing design and siting guideline based on chemical toxicity for enrichment plants using uranium hexafluoride. These guidelines are to be similar, in terms of stochastic health effects, to criteria in NRC regulations of nuclear power plants, which are based on radiation doses. 26 refs., 1 fig., 5 tabs

Chemical toxicity of uranium hexafluoride compared to acute effects of radiation

Energy Technology Data Exchange (ETDEWEB)

McGuire, S.A.

1991-02-01

The chemical effects from acute exposures to uranium hexafluoride are compared to the nonstochastic effects from acute radiation doses of 25 rems to the whole body and 300 rems to the thyroid. The analysis concludes that an intake of about 10 mg of uranium in soluble form is roughly comparable, in terms of early effects, to an acute whole body dose of 25 rems because both are just below the threshold for significant nonstochastic effects. Similarly, an exposure to hydrogen fluoride at a concentration of 25 mg/m{sup 3} for 30 minutes is roughly comparable because there would be no significant nonstochastic effects. For times t other than 30 minutes, the concentration C of hydrogen fluoride considered to have the same effect can be calculated using a quadratic equation: C = 25 mg/m{sup 3} (30 min/t). The purpose of these analyses is to provide information for developing design and siting guideline based on chemical toxicity for enrichment plants using uranium hexafluoride. These guidelines are to be similar, in terms of stochastic health effects, to criteria in NRC regulations of nuclear power plants, which are based on radiation doses. 26 refs., 1 fig., 5 tabs.

Evidence of Coal-Fly-Ash Toxic Chemical Geoengineering in the Troposphere: Consequences for Public Health.

Science.gov (United States)

Herndon, J Marvin

2015-08-11

The widespread, intentional and increasingly frequent chemical emplacement in the troposphere has gone unidentified and unremarked in the scientific literature for years. The author presents evidence that toxic coal combustion fly ash is the most likely aerosolized particulate sprayed by tanker-jets for geoengineering, weather-modification and climate-modification purposes and describes some of the multifold consequences on public health. Two methods are employed: (1) Comparison of 8 elements analyzed in rainwater, leached from aerosolized particulates, with corresponding elements leached into water from coal fly ash in published laboratory experiments, and (2) Comparison of 14 elements analyzed in dust collected outdoors on a high-efficiency particulate air (HEPA) filter with corresponding elements analyzed in un-leached coal fly ash material. The results show: (1) the assemblage of elements in rainwater and in the corresponding experimental leachate are essentially identical. At a 99% confidence interval, they have identical means (T-test) and identical variances (F-test); and (2) the assemblage of elements in the HEPA dust and in the corresponding average un-leached coal fly ash are likewise essentially identical. The consequences on public health are profound, including exposure to a variety of toxic heavy metals, radioactive elements, and neurologically-implicated chemically mobile aluminum released by body moisture in situ after inhalation or through transdermal induction.

Endocrine disrupting chemicals in fish: developing exposure indicators and predictive models of effects based on mechanism of action.

Science.gov (United States)

Ankley, Gerald T; Bencic, David C; Breen, Michael S; Collette, Timothy W; Conolly, Rory B; Denslow, Nancy D; Edwards, Stephen W; Ekman, Drew R; Garcia-Reyero, Natalia; Jensen, Kathleen M; Lazorchak, James M; Martinović, Dalma; Miller, David H; Perkins, Edward J; Orlando, Edward F; Villeneuve, Daniel L; Wang, Rong-Lin; Watanabe, Karen H

2009-05-05

Knowledge of possible toxic mechanisms (or modes) of action (MOA) of chemicals can provide valuable insights as to appropriate methods for assessing exposure and effects, thereby reducing uncertainties related to extrapolation across species, endpoints and chemical structure. However, MOA-based testing seldom has been used for assessing the ecological risk of chemicals. This is in part because past regulatory mandates have focused more on adverse effects of chemicals (reductions in survival, growth or reproduction) than the pathways through which these effects are elicited. A recent departure from this involves endocrine-disrupting chemicals (EDCs), where there is a need to understand both MOA and adverse outcomes. To achieve this understanding, advances in predictive approaches are required whereby mechanistic changes caused by chemicals at the molecular level can be translated into apical responses meaningful to ecological risk assessment. In this paper we provide an overview and illustrative results from a large, integrated project that assesses the effects of EDCs on two small fish models, the fathead minnow (Pimephales promelas) and zebrafish (Danio rerio). For this work a systems-based approach is being used to delineate toxicity pathways for 12 model EDCs with different known or hypothesized toxic MOA. The studies employ a combination of state-of-the-art genomic (transcriptomic, proteomic, metabolomic), bioinformatic and modeling approaches, in conjunction with whole animal testing, to develop response linkages across biological levels of organization. This understanding forms the basis for predictive approaches for species, endpoint and chemical extrapolation. Although our project is focused specifically on EDCs in fish, we believe that the basic conceptual approach has utility for systematically assessing exposure and effects of chemicals with other MOA across a variety of biological systems.

Innovative Strategies to Develop Chemical Categories Using a Combination of Structural and Toxicological Properties

Directory of Open Access Journals (Sweden)

Monika Batke

2016-09-01

Full Text Available 1.AbstractInterest is increasing in the development of non-animal methods for toxicological evaluations. These methods are however, particularly challenging for complex toxicological endpoints such as repeated dose toxicity. European Legislation, e.g. the European Union´s Cosmetic Directive and REACH, demands the use of alternative methods. Frameworks, such as the Read-across Assessment Framework or the Adverse Outcome Pathway Knowledge Base, support the development of these methods. The aim of the project presented in this publication was to develop substance categories for a read-across with complex endpoints of toxicity based on existing databases. The basic conceptual approach was to combine structural similarity with shared mechanisms of action. Substances with similar chemical structure and toxicological profile form candidate categories suitable for read-across. We combined two databases on repeated dose toxicity, RepDose database and ELINCS database to form a common database for the identification of categories. The resulting database contained physicochemical, structural and toxicological data, which were refined and curated for cluster analyses. We applied the Predictive Clustering Tree (PCT approach for clustering chemicals based on structural and on toxicological information to detect groups of chemicals with similar toxic profiles and pathways/mechanisms of toxicity. As many of the experimental toxicity values were not available, this data was imputed by predicting them with a multi-label classification method, prior to clustering. The clustering results were evaluated by assessing chemical and toxicological similarities with the aim of identifying clusters with a concordance between structural information and toxicity profiles/mechanisms. From these chosen clusters, seven were selected for a quantitative read-across, based on a small ratio of NOAEL of the members with the highest and the lowest NOAEL in the cluster (<5. We discuss

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

Engineering electrical properties of graphene: chemical approaches

International Nuclear Information System (INIS)

Kim, Yong-Jin; Kim, Yuna; Hong, Byung Hee; Novoselov, Konstantin

2015-01-01

To ensure the high performance of graphene-based devices, it is necessary to engineer the electrical properties of graphene with enhanced conductivity, controlled work function, opened or closed bandgaps, etc. This can be performed by various non-covalent chemical approaches, including molecular adsorption, substrate-induced doping, polymerization on graphene, deposition of metallic thin films or nanoparticles, etc. In addition, covalent approaches such as the substitution of carbon atoms with boron or nitrogen and the functionalization with hydrogen or fluorine are useful to tune the bandgaps more efficiently, with better uniformity and stability. In this review, representative examples of chemically engineered graphene and its device applications will be reviewed, and remaining challenges will be discussed. (topical review)

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

Gas chromatography-mass spectrometry based metabolomic approach for optimization and toxicity evaluation of earthworm sub-lethal responses to carbofuran.

Directory of Open Access Journals (Sweden)

Mohana Krishna Reddy Mudiam

Full Text Available Despite recent advances in understanding mechanism of toxicity, the development of biomarkers (biochemicals that vary significantly with exposure to chemicals for pesticides and environmental contaminants exposure is still a challenging task. Carbofuran is one of the most commonly used pesticides in agriculture and said to be most toxic carbamate pesticide. It is necessary to identify the biochemicals that can vary significantly after carbofuran exposure on earthworms which will help to assess the soil ecotoxicity. Initially, we have optimized the extraction conditions which are suitable for high-throughput gas chromatography mass spectrometry (GC-MS based metabolomics for the tissue of earthworm, Metaphire posthuma. Upon evaluation of five different extraction solvent systems, 80% methanol was found to have good extraction efficiency based on the yields of metabolites, multivariate analysis, total number of peaks and reproducibility of metabolites. Later the toxicity evaluation was performed to characterize the tissue specific metabolomic perturbation of earthworm, Metaphire posthuma after exposure to carbofuran at three different concentration levels (0.15, 0.3 and 0.6 mg/kg of soil. Seventeen metabolites, contributing to the best classification performance of highest dose dependent carbofuran exposed earthworms from healthy controls were identified. This study suggests that GC-MS based metabolomic approach was precise and sensitive to measure the earthworm responses to carbofuran exposure in soil, and can be used as a promising tool for environmental eco-toxicological studies.

Toxicity induced by chemical warfare agents: insights on the protective role of melatonin.

Science.gov (United States)

Pita, René; Marco-Contelles, José; Ramos, Eva; Del Pino, Javier; Romero, Alejandro

2013-11-25

Chemical Warfare Agents (CWAs) are substances that can be used to kill, injure or incapacitate an enemy in warfare, but also against civilian population in terrorist attacks. Many chemical agents are able to generate free radicals and derived reactants, excitotoxicity process, or inflammation, and as consequence they can cause neurological symptoms and damage in different organs. Nowadays, taking into account that total immediate decontamination after exposure is difficult to achieve and there are not completely effective antidotes and treatments against all CWAs, we advance and propose that medical countermeasures against CWAs poisoning would benefit from a broad-spectrum multipotent molecule. Melatonin, a versatile and ubiquitous antioxidant molecule, originally discovered as a hormone synthesized mainly in the pineal gland, has low toxicity and high efficacy in reducing oxidative damage, anti-inflammatory effects by regulation of multiple cellular pathways and properties to prevent excitotoxicity, among others. The purpose of this review is to show the multiple and diverse properties of melatonin, as a pleiotropic indole derivative, and its marked potential for improving human health against the most widely used chemical weapons. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Accelerating cocaine metabolism as an approach to the treatment of cocaine abuse and toxicity

Science.gov (United States)

Schindler, Charles W; Goldberg, Steven R

2012-01-01

One pharmacokinetic approach to the treatment of cocaine abuse and toxicity involves the development of compounds that can be safely administered to humans and that accelerate the metabolism of cocaine to inactive components. Catalytic antibodies have been developed and shown to accelerate cocaine metabolism, but their catalytic efficiency for cocaine is relatively low. Mutations of human butyrylcholinesterase and a bacterial cocaine esterase found in the soil of coca plants have also been developed. These compounds accelerate cocaine metabolism and antagonize the behavioral and toxic effects of cocaine in animal models. Of these two approaches, the human butyrylcholinesterase mutants show the most immediate promise as they would not be expected to evoke an immune response in humans. PMID:22300096

Advancing environmental toxicology through chemical dosimetry: External exposures versus tissue residues

Science.gov (United States)

McCarty, L.S.; Landrum, P.F.; Luoma, S.N.; Meador, J.P.; Merten, A.A.; Shephard, B.K.; van Wezelzz, A.P.

2011-01-01

The tissue residue dose concept has been used, although in a limited manner, in environmental toxicology for more than 100 y. This review outlines the history of this approach and the technical background for organic chemicals and metals. Although the toxicity of both can be explained in tissue residue terms, the relationship between external exposure concentration, body and/or tissues dose surrogates, and the effective internal dose at the sites of toxic action tends to be more complex for metals. Various issues and current limitations related to research and regulatory applications are also examined. It is clear that the tissue residue approach (TRA) should be an integral component in future efforts to enhance the generation, understanding, and utility of toxicity testing data, both in the laboratory and in the field. To accomplish these goals, several key areas need to be addressed: 1) development of a risk-based interpretive framework linking toxicology and ecology at multiple levels of biological organization and incorporating organism-based dose metrics; 2) a broadly applicable, generally accepted classification scheme for modes/mechanisms of toxic action with explicit consideration of residue information to improve both single chemical and mixture toxicity data interpretation and regulatory risk assessment; 3) toxicity testing protocols updated to ensure collection of adequate residue information, along with toxicokinetics and toxicodynamics information, based on explicitly defined toxicological models accompanied by toxicological model validation; 4) continued development of residueeffect databases is needed ensure their ongoing utility; and 5) regulatory guidance incorporating residue-based testing and interpretation approaches, essential in various jurisdictions. ??:2010 SETAC.

Metabolic Toxicity Screening Using Electrochemiluminescence Arrays Coupled with Enzyme-DNA Biocolloid Reactors and Liquid Chromatography–Mass Spectrometry

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Hvastkovs, Eli G.; Schenkman, John B.; Rusling, James F.

2012-01-01

New chemicals or drugs must be guaranteed safe before they can be marketed. Despite widespread use of bioassay panels for toxicity prediction, products that are toxic to a subset of the population often are not identified until clinical trials. This article reviews new array methodologies based on enzyme/DNA films that form and identify DNA-reactive metabolites that are indicators of potentially genotoxic species. This molecularly based methodology is designed in a rapid screening array that utilizes electrochemiluminescence (ECL) to detect metabolite-DNA reactions, as well as biocolloid reactors that provide the DNA adducts and metabolites for liquid chromatography–mass spectrometry (LC-MS) analysis. ECL arrays provide rapid toxicity screening, and the biocolloid reactor LC-MS approach provides a valuable follow-up on structure, identification, and formation rates of DNA adducts for toxicity hits from the ECL array screening. Specific examples using this strategy are discussed. Integration of high-throughput versions of these toxicity-screening methods with existing drug toxicity bioassays should allow for better human toxicity prediction as well as more informed decision making regarding new chemical and drug candidates. PMID:22482786

Case Study Approaches for Implementing the 2007 NRC Report “Toxicity Testing in the 21st Century: A Vision and A Strategy”

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Andersen, Melvin E.; Clewell, Harvey J.; Carmichael, Paul L.; Boekelheide, Kim

2013-01-01

The 2007 report “Toxicity Testing in the 21st Century: A Vision and A Strategy” argued for a change in toxicity testing for environmental agents and discussed federal funding mechanisms that could be used to support this transformation within the USA. The new approach would test for in vitro perturbations of toxicity pathways using human cells with high throughput testing platforms. The NRC report proposed a deliberate timeline, spanning about 20 years, to implement a wholesale replacement of current in-life toxicity test approaches focused on apical responses with in vitro assays. One approach to accelerating implementation is to focus on well-studied prototype compounds with known toxicity pathway targets. Through a series of carefully executed case studies with four or five pathway prototypes, the various steps required for implementation of an in vitro toxicity pathway approach to risk assessment could be developed and refined. In this article, we discuss alternative approaches for implementation and also outline advantages of a case study approach and the manner in which the cases studies could be pursued using current methodologies. A case study approach would be complementary to recently proposed efforts to map the human toxome, while representing a significant extension toward more formal risk assessment compared to the profiling and prioritization approaches offered by programs such as the EPA’s ToxCast effort. PMID:21993955

Advances on a Decision Analytic Approach to Exposure-Based Chemical Prioritization.

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Wood, Matthew D; Plourde, Kenton; Larkin, Sabrina; Egeghy, Peter P; Williams, Antony J; Zemba, Valerie; Linkov, Igor; Vallero, Daniel A

2018-05-11

The volume and variety of manufactured chemicals is increasing, although little is known about the risks associated with the frequency and extent of human exposure to most chemicals. The EPA and the recent signing of the Lautenberg Act have both signaled the need for high-throughput methods to characterize and screen chemicals based on exposure potential, such that more comprehensive toxicity research can be informed. Prior work of Mitchell et al. using multicriteria decision analysis tools to prioritize chemicals for further research is enhanced here, resulting in a high-level chemical prioritization tool for risk-based screening. Reliable exposure information is a key gap in currently available engineering analytics to support predictive environmental and health risk assessments. An elicitation with 32 experts informed relative prioritization of risks from chemical properties and human use factors, and the values for each chemical associated with each metric were approximated with data from EPA's CP_CAT database. Three different versions of the model were evaluated using distinct weight profiles, resulting in three different ranked chemical prioritizations with only a small degree of variation across weight profiles. Future work will aim to include greater input from human factors experts and better define qualitative metrics. © 2018 Society for Risk Analysis.

A Novel Two-Step Hierarchial Quantitative Structure-Activity Relationship Modeling Workflow for Predicting Acute Toxicity of Chemicals in Rodents

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Background: Accurate prediction of in vivo toxicity from in vitro testing is a challenging problem. Large public–private consortia have been formed with the goal of improving chemical safety assessment by the means of high-throughput screening. Methods and results: A database co...

Investigation of Acute Toxicity of a Chemical Warfare Agent in Kidneys

Directory of Open Access Journals (Sweden)

Turgut Topal

2007-08-01

Full Text Available One of the most important chemical warfare agents, sulfur mustard (SM causes crucial acute and chronic toxic effects. Lung, skin, eye and kidneys are the most affected organs. In this work, it was investigated if increased nitric oxide (NO and peroxynitrite are involved in nitrogen mustard (NM induced kidney damage. In this experimen, aminoguanidine (AG as inducible nitric oxide synthase (iNOS inhibitor and ebselen as peroxynitrite scavenger were used. NM administration resulted in important oxidant and antioxidant changes as well as tissue damage in kidneys. Therapeutic agents showed significant protection and reduced oxidant parameteres leading to tissue healing was observed. Results of this study suggest that drugs with similar properties can be used to protect kidney damage caused by NM. [TAF Prev Med Bull. 2007; 6(4: 227-232

Investigation of Acute Toxicity of a Chemical Warfare Agent in Kidneys

Directory of Open Access Journals (Sweden)

Turgut Topal

2007-08-01

Full Text Available One of the most important chemical warfare agents, sulfur mustard (SM causes crucial acute and chronic toxic effects. Lung, skin, eye and kidneys are the most affected organs. In this work, it was investigated if increased nitric oxide (NO and peroxynitrite are involved in nitrogen mustard (NM induced kidney damage. In this experimen, aminoguanidine (AG as inducible nitric oxide synthase (iNOS inhibitor and ebselen as peroxynitrite scavenger were used. NM administration resulted in important oxidant and antioxidant changes as well as tissue damage in kidneys. Therapeutic agents showed significant protection and reduced oxidant parameteres leading to tissue healing was observed. Results of this study suggest that drugs with similar properties can be used to protect kidney damage caused by NM. [TAF Prev Med Bull 2007; 6(4.000: 227-232

New facility for processing and storage of radioactive and toxic chemical waste

International Nuclear Information System (INIS)

Gallagher, F.E. III

1976-01-01

A new facility for the processing and storage of radioactive and toxic chemical waste is described. The facility is located in the science and engineering complex of the Santa Barbara campus of the University of California, near the Pacific Ocean. It is designed to provide a safe and secure processing and storage area for hazardous wastes, while meeting the high aesthetic standards and ecological requirements of campus and community regulatory boards. The ventilation system and fire prevention features will be described in detail. During the design phase, a small laboratory was added to provide an area for the radiation protection and industrial hygiene programs. Operational experience with this new facility is discussed

Characterization of toxic waste produced in PYMES manufacturing detergents

International Nuclear Information System (INIS)

Campuzano, Silvia; Camacho, Judith Elena; Alvarez, Alicia

2006-01-01

From the protection of the environment, the problem of the residuals squatter a main place in the environmental administration; presently study a test pilot was standardized, to characterize the toxic waste generated in the production of detergents, to standardize methods of chemical valuation and microbiological of polluted waters that allow later on to apply methods of biological purification and processes of bio-treatment of residuals, the project macro of handling of toxic waste it was addressed this way in small and medium companies producers of detergents. The presence settled down of toxic in the studied waste, represented in surfactants significant amounts, phenols, hydrocarbons, fat and phosphates and the decrease of its quantity in front of the action of bacteria, situation that allowed concluding that the approach to the biotransformation process could be carried out

VirtualToxLab — A platform for estimating the toxic potential of drugs, chemicals and natural products

International Nuclear Information System (INIS)

Vedani, Angelo; Dobler, Max; Smieško, Martin

2012-01-01

The VirtualToxLab is an in silico technology for estimating the toxic potential (endocrine and metabolic disruption, some aspects of carcinogenicity and cardiotoxicity) of drugs, chemicals and natural products. The technology is based on an automated protocol that simulates and quantifies the binding of small molecules towards a series of proteins, known or suspected to trigger adverse effects. The toxic potential, a non-linear function ranging from 0.0 (none) to 1.0 (extreme), is derived from the individual binding affinities of a compound towards currently 16 target proteins: 10 nuclear receptors (androgen, estrogen α, estrogen β, glucocorticoid, liver X, mineralocorticoid, peroxisome proliferator-activated receptor γ, progesterone, thyroid α, and thyroid β), four members of the cytochrome P450 enzyme family (1A2, 2C9, 2D6, and 3A4), a cytosolic transcription factor (aryl hydrocarbon receptor) and a potassium ion channel (hERG). The interface to the technology allows building and uploading molecular structures, viewing and downloading results and, most importantly, rationalizing any prediction at the atomic level by interactively analyzing the binding mode of a compound with its target protein(s) in real-time 3D. The VirtualToxLab has been used to predict the toxic potential for over 2500 compounds: the results are posted on (http://www.virtualtoxlab.org). The free platform — the OpenVirtualToxLab — is accessible (in client–server mode) over the Internet. It is free of charge for universities, governmental agencies, regulatory bodies and non-profit organizations. -- Highlights: ► In silico technology for estimating the toxic potential of drugs and chemicals. ► Simulation of binding towards 16 proteins suspected to trigger adverse effects. ► Mechanistic interpretation and real-time 3D visualization. ► Accessible over the Internet. ► Free of charge for universities, governmental agencies, regulatory bodies and NPOs.

VirtualToxLab — A platform for estimating the toxic potential of drugs, chemicals and natural products

Energy Technology Data Exchange (ETDEWEB)

Vedani, Angelo, E-mail: angelo.vedani@unibas.ch [Biographics Laboratory 3R, Klingelbergstrasse 50, 4056 Basel (Switzerland); Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, 4056 Basel (Switzerland); Dobler, Max [Biographics Laboratory 3R, Klingelbergstrasse 50, 4056 Basel (Switzerland); Smieško, Martin [Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, 4056 Basel (Switzerland)

2012-06-01

The VirtualToxLab is an in silico technology for estimating the toxic potential (endocrine and metabolic disruption, some aspects of carcinogenicity and cardiotoxicity) of drugs, chemicals and natural products. The technology is based on an automated protocol that simulates and quantifies the binding of small molecules towards a series of proteins, known or suspected to trigger adverse effects. The toxic potential, a non-linear function ranging from 0.0 (none) to 1.0 (extreme), is derived from the individual binding affinities of a compound towards currently 16 target proteins: 10 nuclear receptors (androgen, estrogen α, estrogen β, glucocorticoid, liver X, mineralocorticoid, peroxisome proliferator-activated receptor γ, progesterone, thyroid α, and thyroid β), four members of the cytochrome P450 enzyme family (1A2, 2C9, 2D6, and 3A4), a cytosolic transcription factor (aryl hydrocarbon receptor) and a potassium ion channel (hERG). The interface to the technology allows building and uploading molecular structures, viewing and downloading results and, most importantly, rationalizing any prediction at the atomic level by interactively analyzing the binding mode of a compound with its target protein(s) in real-time 3D. The VirtualToxLab has been used to predict the toxic potential for over 2500 compounds: the results are posted on (http://www.virtualtoxlab.org). The free platform — the OpenVirtualToxLab — is accessible (in client–server mode) over the Internet. It is free of charge for universities, governmental agencies, regulatory bodies and non-profit organizations. -- Highlights: ► In silico technology for estimating the toxic potential of drugs and chemicals. ► Simulation of binding towards 16 proteins suspected to trigger adverse effects. ► Mechanistic interpretation and real-time 3D visualization. ► Accessible over the Internet. ► Free of charge for universities, governmental agencies, regulatory bodies and NPOs.

OECD validation study to assess intra- and inter-laboratory reproducibility of the zebrafish embryo toxicity test for acute aquatic toxicity testing.

Science.gov (United States)

Busquet, François; Strecker, Ruben; Rawlings, Jane M; Belanger, Scott E; Braunbeck, Thomas; Carr, Gregory J; Cenijn, Peter; Fochtman, Przemyslaw; Gourmelon, Anne; Hübler, Nicole; Kleensang, André; Knöbel, Melanie; Kussatz, Carola; Legler, Juliette; Lillicrap, Adam; Martínez-Jerónimo, Fernando; Polleichtner, Christian; Rzodeczko, Helena; Salinas, Edward; Schneider, Katharina E; Scholz, Stefan; van den Brandhof, Evert-Jan; van der Ven, Leo T M; Walter-Rohde, Susanne; Weigt, Stefan; Witters, Hilda; Halder, Marlies

2014-08-01

The OECD validation study of the zebrafish embryo acute toxicity test (ZFET) for acute aquatic toxicity testing evaluated the ZFET reproducibility by testing 20 chemicals at 5 different concentrations in 3 independent runs in at least 3 laboratories. Stock solutions and test concentrations were analytically confirmed for 11 chemicals. Newly fertilised zebrafish eggs (20/concentration and control) were exposed for 96h to chemicals. Four apical endpoints were recorded daily as indicators of acute lethality: coagulation of the embryo, lack of somite formation, non-detachment of the tail bud from the yolk sac and lack of heartbeat. Results (LC50 values for 48/96h exposure) show that the ZFET is a robust method with a good intra- and inter-laboratory reproducibility (CV30%) for some very toxic or volatile chemicals, and chemicals tested close to their limit of solubility. The ZFET is now available as OECD Test Guideline 236. Considering the high predictive capacity of the ZFET demonstrated by Belanger et al. (2013) in their retrospective analysis of acute fish toxicity and fish embryo acute toxicity data, the ZFET is ready to be considered for acute fish toxicity for regulatory purposes. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Toxic fables: the advertising and marketing of agricultural chemicals in the great plains, 1945-1985.

Science.gov (United States)