Highlight report: Launch of a large integrated European in vitro toxicology project: EU-ToxRisk.

Science.gov (United States)

Daneshian, Mardas; Kamp, Hennicke; Hengstler, Jan; Leist, Marcel; van de Water, Bob

2016-05-01

The integrated European project, EU-ToxRisk, proudly sees itself as "flagship" exploring new alternative-to-animal approaches to chemical safety evaluation. It promotes mechanism-based toxicity testing and risk assessment according to the principles laid down for toxicology for the twenty-first century. The project was officially launched in January 2016 with a kickoff meeting in Egmond aan Zee, the Netherlands. Over 100 scientists representing academia and industry as well as regulatory authorities attended the inaugural meeting. The project will integrate advances in in vitro and in silico toxicology, read-across methods, and adverse outcome pathways. EU-ToxRisk will continue to make use of the case study strategy deployed in SEURAT-1, a FP7 initiative ended in December 2015. Even though the development of new non-animal methods is one target of EU-ToxRisk, the project puts special emphasis on their acceptance and implementation in regulatory contexts. This €30 million Horizon 2020 project involves 38 European partners and one from the USA. EU-ToxRisk aims at the "development of a new way of risk assessment."

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.

Using Pareto points for model identification in predictive toxicology

Science.gov (United States)

2013-01-01

Predictive toxicology is concerned with the development of models that are able to predict the toxicity of chemicals. A reliable prediction of toxic effects of chemicals in living systems is highly desirable in cosmetics, drug design or food protection to speed up the process of chemical compound discovery while reducing the need for lab tests. There is an extensive literature associated with the best practice of model generation and data integration but management and automated identification of relevant models from available collections of models is still an open problem. Currently, the decision on which model should be used for a new chemical compound is left to users. This paper intends to initiate the discussion on automated model identification. We present an algorithm, based on Pareto optimality, which mines model collections and identifies a model that offers a reliable prediction for a new chemical compound. The performance of this new approach is verified for two endpoints: IGC50 and LogP. The results show a great potential for automated model identification methods in predictive toxicology. PMID:23517649

FORUM - FutureTox II: In vitro Data and In Silico Models for Predictive Toxicology

Science.gov (United States)

FutureTox II, a Society of Toxicology Contemporary Concepts in Toxicology workshop, was held in January, 2014. The meeting goals were to review and discuss the state of the science in toxicology in the context of implementing the NRC 21st century vision of predicting in vivo resp...

Advances in Predictive Toxicology for Discovery Safety through High Content Screening.

Science.gov (United States)

Persson, Mikael; Hornberg, Jorrit J

2016-12-19

High content screening enables parallel acquisition of multiple molecular and cellular readouts. In particular the predictive toxicology field has progressed from the advances in high content screening, as more refined end points that report on cellular health can be studied in combination, at the single cell level, and in relatively high throughput. Here, we discuss how high content screening has become an essential tool for Discovery Safety, the discipline that integrates safety and toxicology in the drug discovery process to identify and mitigate safety concerns with the aim to design drug candidates with a superior safety profile. In addition to customized mechanistic assays to evaluate target safety, routine screening assays can be applied to identify risk factors for frequently occurring organ toxicities. We discuss the current state of high content screening assays for hepatotoxicity, cardiotoxicity, neurotoxicity, nephrotoxicity, and genotoxicity, including recent developments and current advances.

FutureTox II: in vitro data and in silico models for predictive toxicology.

Science.gov (United States)

Knudsen, Thomas B; Keller, Douglas A; Sander, Miriam; Carney, Edward W; Doerrer, Nancy G; Eaton, David L; Fitzpatrick, Suzanne Compton; Hastings, Kenneth L; Mendrick, Donna L; Tice, Raymond R; Watkins, Paul B; Whelan, Maurice

2015-02-01

FutureTox II, a Society of Toxicology Contemporary Concepts in Toxicology workshop, was held in January, 2014. The meeting goals were to review and discuss the state of the science in toxicology in the context of implementing the NRC 21st century vision of predicting in vivo responses from in vitro and in silico data, and to define the goals for the future. Presentations and discussions were held on priority concerns such as predicting and modeling of metabolism, cell growth and differentiation, effects on sensitive subpopulations, and integrating data into risk assessment. Emerging trends in technologies such as stem cell-derived human cells, 3D organotypic culture models, mathematical modeling of cellular processes and morphogenesis, adverse outcome pathway development, and high-content imaging of in vivo systems were discussed. Although advances in moving towards an in vitro/in silico based risk assessment paradigm were apparent, knowledge gaps in these areas and limitations of technologies were identified. Specific recommendations were made for future directions and research needs in the areas of hepatotoxicity, cancer prediction, developmental toxicity, and regulatory toxicology. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Precision toxicology based on single cell sequencing: an evolving trend in toxicological evaluations and mechanism exploration.

Science.gov (United States)

Zhang, Boyang; Huang, Kunlun; Zhu, Liye; Luo, Yunbo; Xu, Wentao

2017-07-01

In this review, we introduce a new concept, precision toxicology: the mode of action of chemical- or drug-induced toxicity can be sensitively and specifically investigated by isolating a small group of cells or even a single cell with typical phenotype of interest followed by a single cell sequencing-based analysis. Precision toxicology can contribute to the better detection of subtle intracellular changes in response to exogenous substrates, and thus help researchers find solutions to control or relieve the toxicological effects that are serious threats to human health. We give examples for single cell isolation and recommend laser capture microdissection for in vivo studies and flow cytometric sorting for in vitro studies. In addition, we introduce the procedures for single cell sequencing and describe the expected application of these techniques to toxicological evaluations and mechanism exploration, which we believe will become a trend in toxicology.

ACToR-AGGREGATED COMPUTATIONAL TOXICOLOGY ...

Science.gov (United States)

One goal of the field of computational toxicology is to predict chemical toxicity by combining computer models with biological and toxicological data. predict chemical toxicity by combining computer models with biological and toxicological data

Risk assessment and toxicology databases for health effects assessment

Energy Technology Data Exchange (ETDEWEB)

Lu, P.Y.; Wassom, J.S. [Oak Ridge National Laboratory, TN (United States)

1990-12-31

Scientific and technological developments bring unprecedented stress to our environment. Society has to predict the results of potential health risks from technologically based actions that may have serious, far-reaching consequences. The potential for error in making such predictions or assessment is great and multiplies with the increasing size and complexity of the problem being studied. Because of this, the availability and use of reliable data is the key to any successful forecasting effort. Scientific research and development generate new data and information. Much of the scientific data being produced daily is stored in computers for subsequent analysis. This situation provides both an invaluable resource and an enormous challenge. With large amounts of government funds being devoted to health and environmental research programs and with maintenance of our living environment at stake, we must make maximum use of the resulting data to forecast and avert catastrophic effects. Along with the readily available. The most efficient means of obtaining the data necessary for assessing the health effects of chemicals is to utilize applications include the toxicology databases and information files developed at ORNL. To make most efficient use of the data/information that has already been prepared, attention and resources should be directed toward projects that meticulously evaluate the available data/information and create specialized peer-reviewed value-added databases. Such projects include the National Library of Medicine`s Hazardous Substances Data Bank, and the U.S. Air Force Installation Restoration Toxicology Guide. These and similar value-added toxicology databases were developed at ORNL and are being maintained and updated. These databases and supporting information files, as well as some data evaluation techniques are discussed in this paper with special focus on how they are used to assess potential health effects of environmental agents. 19 refs., 5 tabs.

SEURAT: Safety Evaluation Ultimately Replacing Animal Testing--recommendations for future research in the field of predictive toxicology.

Science.gov (United States)

Daston, George; Knight, Derek J; Schwarz, Michael; Gocht, Tilman; Thomas, Russell S; Mahony, Catherine; Whelan, Maurice

2015-01-01

The development of non-animal methodology to evaluate the potential for a chemical to cause systemic toxicity is one of the grand challenges of modern science. The European research programme SEURAT is active in this field and will conclude its first phase, SEURAT-1, in December 2015. Drawing on the experience gained in SEURAT-1 and appreciating international advancement in both basic and regulatory science, we reflect here on how SEURAT should evolve and propose that further research and development should be directed along two complementary and interconnecting work streams. The first work stream would focus on developing new 'paradigm' approaches for regulatory science. The goal here is the identification of 'critical biological targets' relevant for toxicity and to test their suitability to be used as anchors for predicting toxicity. The second work stream would focus on integration and application of new approach methods for hazard (and risk) assessment within the current regulatory 'paradigm', aiming for acceptance of animal-free testing strategies by regulatory authorities (i.e. translating scientific achievements into regulation). Components for both work streams are discussed and may provide a structure for a future research programme in the field of predictive toxicology.

Toxicology: a discipline in need of academic anchoring--the point of view of the German Society of Toxicology.

Science.gov (United States)

Gundert-Remy, U; Barth, H; Bürkle, A; Degen, G H; Landsiedel, R

2015-10-01

The paper describes the importance of toxicology as a discipline, its past achievements, current scientific challenges, and future development. Toxicological expertise is instrumental in the reduction of human health risks arising from chemicals and drugs. Toxicological assessment is needed to evaluate evidence and arguments, whether or not there is a scientific base for concern. The immense success already achieved by toxicological work is exemplified by reduced pollution of air, soil, water, and safer working places. Predominantly predictive toxicological testing is derived from the findings to assess risks to humans and the environment. Assessment of the adversity of molecular effects (including epigenetic effects), the effects of mixtures, and integration of exposure and biokinetics into in vitro testing are emerging challenges for toxicology. Toxicology is a translational science with its base in fundamental science. Academic institutions play an essential part by providing scientific innovation and education of young scientists.

Web tools for predictive toxicology model building.

Science.gov (United States)

Jeliazkova, Nina

2012-07-01

The development and use of web tools in chemistry has accumulated more than 15 years of history already. Powered by the advances in the Internet technologies, the current generation of web systems are starting to expand into areas, traditional for desktop applications. The web platforms integrate data storage, cheminformatics and data analysis tools. The ease of use and the collaborative potential of the web is compelling, despite the challenges. The topic of this review is a set of recently published web tools that facilitate predictive toxicology model building. The focus is on software platforms, offering web access to chemical structure-based methods, although some of the frameworks could also provide bioinformatics or hybrid data analysis functionalities. A number of historical and current developments are cited. In order to provide comparable assessment, the following characteristics are considered: support for workflows, descriptor calculations, visualization, modeling algorithms, data management and data sharing capabilities, availability of GUI or programmatic access and implementation details. The success of the Web is largely due to its highly decentralized, yet sufficiently interoperable model for information access. The expected future convergence between cheminformatics and bioinformatics databases provides new challenges toward management and analysis of large data sets. The web tools in predictive toxicology will likely continue to evolve toward the right mix of flexibility, performance, scalability, interoperability, sets of unique features offered, friendly user interfaces, programmatic access for advanced users, platform independence, results reproducibility, curation and crowdsourcing utilities, collaborative sharing and secure access.

Toxicology ontology perspectives.

Science.gov (United States)

Hardy, Barry; Apic, Gordana; Carthew, Philip; Clark, Dominic; Cook, David; Dix, Ian; Escher, Sylvia; Hastings, Janna; Heard, David J; Jeliazkova, Nina; Judson, Philip; Matis-Mitchell, Sherri; Mitic, Dragana; Myatt, Glenn; Shah, Imran; Spjuth, Ola; Tcheremenskaia, Olga; Toldo, Luca; Watson, David; White, Andrew; Yang, Chihae

2012-01-01

The field of predictive toxicology requires the development of open, public, computable, standardized toxicology vocabularies and ontologies to support the applications required by in silico, in vitro, and in vivo toxicology methods and related analysis and reporting activities. In this article we review ontology developments based on a set of perspectives showing how ontologies are being used in predictive toxicology initiatives and applications. Perspectives on resources and initiatives reviewed include OpenTox, eTOX, Pistoia Alliance, ToxWiz, Virtual Liver, EU-ADR, BEL, ToxML, and Bioclipse. We also review existing ontology developments in neighboring fields that can contribute to establishing an ontological framework for predictive toxicology. A significant set of resources is already available to provide a foundation for an ontological framework for 21st century mechanistic-based toxicology research. Ontologies such as ToxWiz provide a basis for application to toxicology investigations, whereas other ontologies under development in the biological, chemical, and biomedical communities could be incorporated in an extended future framework. OpenTox has provided a semantic web framework for the implementation of such ontologies into software applications and linked data resources. Bioclipse developers have shown the benefit of interoperability obtained through ontology by being able to link their workbench application with remote OpenTox web services. Although these developments are promising, an increased international coordination of efforts is greatly needed to develop a more unified, standardized, and open toxicology ontology framework.

Toxicological evaluation of liquids proposed for use in direct contact liquid--liquid heat exchangers for solar heated and cooled buildings

Energy Technology Data Exchange (ETDEWEB)

Buchan, R.M.; Majestic, J.R.; Billau, R.

1976-09-01

This report contains the results of the toxicological evaluation part of the project entitled, ''Direct Contact Liquid-Liquid Heat Exchangers for Solar Heated and Cooled Buildings.'' Obviously any liquid otherwise suitable for use in such a device should be subjected to a toxicological evaluation. 34 liquids (24 denser than water, 10 less dense) have physical and chemical properties that would make them suitable for use in such a device. In addition to the complexity involved in selecting the most promising liquids from the standpoint of their chemical and physical properties is added the additional difficulty of also considering their toxicological properties. Some of the physical and chemical properties of these liquids are listed. The liquids are listed in alphabetical order within groups, the denser than water liquids are listed first followed by those liquids less dense than water.

Toxicological Evaluation of Lactase Derived from Recombinant Pichia pastoris

Science.gov (United States)

Liu, Yifei; Chen, Delong; Luo, Yunbo; Huang, Kunlun; Zhang, Wei; Xu, Wentao

2014-01-01

A recombinant lactase was expressed in Pichia pastoris, resulting in enzymatic activity of 3600 U/mL in a 5 L fermenter. The lactase product was subjected to a series of toxicological tests to determine its safety for use as an enzyme preparation in the dairy industry. This recombinant lactase had the highest activity of all recombinant strains reported thus far. Acute oral toxicity, mutagenicity, genotoxic, and subchronic toxicity tests performed in rats and mice showed no death in any groups. The lethal dose 50% (LD50) based on the acute oral toxicity study is greater than 30 mL/kg body weight, which is in accordance with the 1500 L milk consumption of a 50 kg human daily. The lactase showed no mutagenic activity in the Ames test or a mouse sperm abnormality test at levels of up to 5 mg/plate and 1250 mg/kg body weight, respectively. It also showed no genetic toxicology in a bone marrow cell micronucleus test at levels of up to 1250 mg/kg body weight. A 90-day subchronic repeated toxicity study via the diet with lactase levels up to 1646 mg/kg (1000-fold greater than the mean human exposure) did not show any treatment-related significant toxicological effects on body weight, food consumption, organ weights, hematological and clinical chemistry, or histopathology compared to the control groups. This toxicological evaluation system is comprehensive and can be used in the safety evaluation of other enzyme preparations. The lactase showed no acute, mutagenic, genetic, or subchronic toxicity under our evaluation system. PMID:25184300

Toxicological evaluation of lactase derived from recombinant Pichia pastoris.

Directory of Open Access Journals (Sweden)

Shiying Zou

Full Text Available A recombinant lactase was expressed in Pichia pastoris, resulting in enzymatic activity of 3600 U/mL in a 5 L fermenter. The lactase product was subjected to a series of toxicological tests to determine its safety for use as an enzyme preparation in the dairy industry. This recombinant lactase had the highest activity of all recombinant strains reported thus far. Acute oral toxicity, mutagenicity, genotoxic, and subchronic toxicity tests performed in rats and mice showed no death in any groups. The lethal dose 50% (LD50 based on the acute oral toxicity study is greater than 30 mL/kg body weight, which is in accordance with the 1500 L milk consumption of a 50 kg human daily. The lactase showed no mutagenic activity in the Ames test or a mouse sperm abnormality test at levels of up to 5 mg/plate and 1250 mg/kg body weight, respectively. It also showed no genetic toxicology in a bone marrow cell micronucleus test at levels of up to 1250 mg/kg body weight. A 90-day subchronic repeated toxicity study via the diet with lactase levels up to 1646 mg/kg (1000-fold greater than the mean human exposure did not show any treatment-related significant toxicological effects on body weight, food consumption, organ weights, hematological and clinical chemistry, or histopathology compared to the control groups. This toxicological evaluation system is comprehensive and can be used in the safety evaluation of other enzyme preparations. The lactase showed no acute, mutagenic, genetic, or subchronic toxicity under our evaluation system.

75 FR 25867 - National Toxicology Program (NTP) Interagency Center for the Evaluation of Alternative...

Science.gov (United States)

2010-05-10

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Toxicology Program (NTP) Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM.... Bucher, Associate Director, National Toxicology Program. [FR Doc. 2010-10958 Filed 5-7-10; 8:45 am...

Toxicological relationships between proteins obtained from protein target predictions of large toxicity databases

International Nuclear Information System (INIS)

Nigsch, Florian; Mitchell, John B.O.

2008-01-01

The combination of models for protein target prediction with large databases containing toxicological information for individual molecules allows the derivation of 'toxiclogical' profiles, i.e., to what extent are molecules of known toxicity predicted to interact with a set of protein targets. To predict protein targets of drug-like and toxic molecules, we built a computational multiclass model using the Winnow algorithm based on a dataset of protein targets derived from the MDL Drug Data Report. A 15-fold Monte Carlo cross-validation using 50% of each class for training, and the remaining 50% for testing, provided an assessment of the accuracy of that model. We retained the 3 top-ranking predictions and found that in 82% of all cases the correct target was predicted within these three predictions. The first prediction was the correct one in almost 70% of cases. A model built on the whole protein target dataset was then used to predict the protein targets for 150 000 molecules from the MDL Toxicity Database. We analysed the frequency of the predictions across the panel of protein targets for experimentally determined toxicity classes of all molecules. This allowed us to identify clusters of proteins related by their toxicological profiles, as well as toxicities that are related. Literature-based evidence is provided for some specific clusters to show the relevance of the relationships identified

Animal toxicology

Energy Technology Data Exchange (ETDEWEB)

Amdur, M.

1996-12-31

The chapter evaluates results of toxicological studies on experimental animals to investigate health effects of air pollutants and examines the animal data have predicted the response to human subject. Data are presented on the comparative toxicity of sulfur dioxide and sulfuric acid. The animal data obtained by measurement of airway resistance in guinea pigs and of bronchial clearance of particles in donkeys predicted clearly that sulfuric acid was more irritant than sulfur dioxide. Data obtained on human subjects confirmed this prediction. These acute studies also correctly predicted the comparative toxicity of the two compounds in two year studies of monkeys. Such chronic studies are not possible in human subjects but it is a reasonable to assume that sulfuric acid would be more toxic than sulfur dioxide. Current findings in epidemiological studies certainly support this assumption.

Predictive toxicology in drug safety

National Research Council Canada - National Science Library

Xu, Jinghai J; Urban, Laszlo

2011-01-01

.... It provides information on the present knowledge of drug side effects and their mitigation strategy during drug discovery, gives guidance for risk assessment, and promotes evidence-based toxicology...

Multiscale modeling and simulation of embryogenesis for in silico predictive toxicology (WC9)

Science.gov (United States)

Translating big data from alternative and HTS platforms into hazard identification and risk assessment is an important need for predictive toxicology and for elucidating adverse outcome pathways (AOPs) in developmental toxicity. Understanding how chemical disruption of molecular ...

Antidiabetic And Toxicological Evaluation Of Aqueous Ethanol Leaf ...

African Journals Online (AJOL)

Secamone afzelii Rhoem is used in ethnomedicine for hepatic diseases, diabetes, venereal diseases, amenorrhoea and toothaches. This present study was aimed at evaluating the antidiabetic activity and to establish the toxicological profile of the plant to confirm its traditional application and justify continuous usage.

75 FR 57027 - National Toxicology Program (NTP); NTP Interagency Center for the Evaluation of Alternative...

Science.gov (United States)

2010-09-17

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Toxicology Program (NTP); NTP Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM); Availability of Interagency..., Associate Director, National Toxicology Program. [FR Doc. 2010-23262 Filed 9-16-10; 8:45 am] BILLING CODE...

75 FR 32942 - National Toxicology Program (NTP); NTP Interagency Center for the Evaluation of Alternative...

Science.gov (United States)

2010-06-10

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Toxicology Program (NTP); NTP Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM): Availability of the Biennial... Toxicology Program. [FR Doc. 2010-13952 Filed 6-9-10; 8:45 am] BILLING CODE 4140-01-P ...

Toxicologic evaluation of analytes from Tank 241-C-103

International Nuclear Information System (INIS)

Mahlum, D.D.; Young, J.Y.; Weller, R.E.

1994-11-01

Westinghouse Hanford Company requested PNL to assemble a toxicology review panel (TRP) to evaluate analytical data compiled by WHC, and provide advice concerning potential health effects associated with exposure to tank-vapor constituents. The team's objectives would be to (1) review procedures used for sampling vapors from tanks, (2) identify constituents in tank-vapor samples that could be related to symptoms reported by workers, (3) evaluate the toxicological implications of those constituents by comparison to establish toxicological databases, (4) provide advice for additional analytical efforts, and (5) support other activities as requested by WHC. The TRP represents a wide range of expertise, including toxicology, industrial hygiene, and occupational medicine. The TRP prepared a list of target analytes that chemists at the Oregon Graduate Institute/Sandia (OGI), Oak Ridge National Laboratory (ORNL), and PNL used to establish validated methods for quantitative analysis of head-space vapors from Tank 241-C-103. this list was used by the analytical laboratories to develop appropriate analytical methods for samples from Tank 241-C-103. Target compounds on the list included acetone, acetonitrile, ammonia, benzene, 1, 3-butadiene, butanal, n-butanol, hexane, 2-hexanone, methylene chloride, nitric oxide, nitrogen dioxide, nitrous oxide, dodecane, tridecane, propane nitrile, sulfur oxide, tributyl phosphate, and vinylidene chloride. The TRP considered constituent concentrations, current exposure limits, reliability of data relative to toxicity, consistency of the analytical data, and whether the material was carcinogenic or teratogenic. A final consideration in the analyte selection process was to include representative chemicals for each class of compounds found

Toxicology and Epidemiology: Improving the Science with a Framework for Combining Toxicological and Epidemiological Evidence to Establish Causal Inference

Science.gov (United States)

Adami, Hans-Olov; Berry, Sir Colin L.; Breckenridge, Charles B.; Smith, Lewis L.; Swenberg, James A.; Trichopoulos, Dimitrios; Weiss, Noel S.; Pastoor, Timothy P.

2011-01-01

Historically, toxicology has played a significant role in verifying conclusions drawn on the basis of epidemiological findings. Agents that were suggested to have a role in human diseases have been tested in animals to firmly establish a causative link. Bacterial pathogens are perhaps the oldest examples, and tobacco smoke and lung cancer and asbestos and mesothelioma provide two more recent examples. With the advent of toxicity testing guidelines and protocols, toxicology took on a role that was intended to anticipate or predict potential adverse effects in humans, and epidemiology, in many cases, served a role in verifying or negating these toxicological predictions. The coupled role of epidemiology and toxicology in discerning human health effects by environmental agents is obvious, but there is currently no systematic and transparent way to bring the data and analysis of the two disciplines together in a way that provides a unified view on an adverse causal relationship between an agent and a disease. In working to advance the interaction between the fields of toxicology and epidemiology, we propose here a five-step “Epid-Tox” process that would focus on: (1) collection of all relevant studies, (2) assessment of their quality, (3) evaluation of the weight of evidence, (4) assignment of a scalable conclusion, and (5) placement on a causal relationship grid. The causal relationship grid provides a clear view of how epidemiological and toxicological data intersect, permits straightforward conclusions with regard to a causal relationship between agent and effect, and can show how additional data can influence conclusions of causality. PMID:21561883

In silico toxicology for the pharmaceutical sciences

International Nuclear Information System (INIS)

Valerio, Luis G.

2009-01-01

The applied use of in silico technologies (a.k.a. computational toxicology, in silico toxicology, computer-assisted tox, e-tox, i-drug discovery, predictive ADME, etc.) for predicting preclinical toxicological endpoints, clinical adverse effects, and metabolism of pharmaceutical substances has become of high interest to the scientific community and the public. The increased accessibility of these technologies for scientists and recent regulations permitting their use for chemical risk assessment supports this notion. The scientific community is interested in the appropriate use of such technologies as a tool to enhance product development and safety of pharmaceuticals and other xenobiotics, while ensuring the reliability and accuracy of in silico approaches for the toxicological and pharmacological sciences. For pharmaceutical substances, this means active and impurity chemicals in the drug product may be screened using specialized software and databases designed to cover these substances through a chemical structure-based screening process and algorithm specific to a given software program. A major goal for use of these software programs is to enable industry scientists not only to enhance the discovery process but also to ensure the judicious use of in silico tools to support risk assessments of drug-induced toxicities and in safety evaluations. However, a great amount of applied research is still needed, and there are many limitations with these approaches which are described in this review. Currently, there is a wide range of endpoints available from predictive quantitative structure-activity relationship models driven by many different computational software programs and data sources, and this is only expected to grow. For example, there are models based on non-proprietary and/or proprietary information specific to assessing potential rodent carcinogenicity, in silico screens for ICH genetic toxicity assays, reproductive and developmental toxicity, theoretical

Metabonomics and toxicology.

Science.gov (United States)

Zhao, Liang; Hartung, Thomas

2015-01-01

Being an emerging field of "omics" research, metabonomics has been increasingly used in toxicological studies mostly because this technology has the ability to provide more detailed information to elucidate mechanism of toxicity. As an interdisciplinary field of science, metabonomics combines analytical chemistry, bioinformatics, statistics, and biochemistry. When applied to toxicology, metabonomics also includes aspects of patho-biochemistry, systems biology, and molecular diagnostics. During a toxicological study, the metabolic changes over time and dose after chemical treatment can be monitored. Therefore, the most important use of this emerging technology is the identification of signatures of toxicity-patterns of metabolic changes predictive of a hazard manifestation. This chapter summarizes the current state of metabonomics technology and its applications in various areas of toxicological studies.

Evidence-Based Toxicology.

Science.gov (United States)

Hoffmann, Sebastian; Hartung, Thomas; Stephens, Martin

Evidence-based toxicology (EBT) was introduced independently by two groups in 2005, in the context of toxicological risk assessment and causation as well as based on parallels between the evaluation of test methods in toxicology and evidence-based assessment of diagnostics tests in medicine. The role model of evidence-based medicine (EBM) motivated both proposals and guided the evolution of EBT, whereas especially systematic reviews and evidence quality assessment attract considerable attention in toxicology.Regarding test assessment, in the search of solutions for various problems related to validation, such as the imperfectness of the reference standard or the challenge to comprehensively evaluate tests, the field of Diagnostic Test Assessment (DTA) was identified as a potential resource. DTA being an EBM discipline, test method assessment/validation therefore became one of the main drivers spurring the development of EBT.In the context of pathway-based toxicology, EBT approaches, given their objectivity, transparency and consistency, have been proposed to be used for carrying out a (retrospective) mechanistic validation.In summary, implementation of more evidence-based approaches may provide the tools necessary to adapt the assessment/validation of toxicological test methods and testing strategies to face the challenges of toxicology in the twenty first century.

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

Data-intensive drug development in the information age: applications of Systems Biology/Pharmacology/Toxicology.

Science.gov (United States)

Kiyosawa, Naoki; Manabe, Sunao

2016-01-01

Pharmaceutical companies continuously face challenges to deliver new drugs with true medical value. R&D productivity of drug development projects depends on 1) the value of the drug concept and 2) data and in-depth knowledge that are used rationally to evaluate the drug concept's validity. A model-based data-intensive drug development approach is a key competitive factor used by innovative pharmaceutical companies to reduce information bias and rationally demonstrate the value of drug concepts. Owing to the accumulation of publicly available biomedical information, our understanding of the pathophysiological mechanisms of diseases has developed considerably; it is the basis for identifying the right drug target and creating a drug concept with true medical value. Our understanding of the pathophysiological mechanisms of disease animal models can also be improved; it can thus support rational extrapolation of animal experiment results to clinical settings. The Systems Biology approach, which leverages publicly available transcriptome data, is useful for these purposes. Furthermore, applying Systems Pharmacology enables dynamic simulation of drug responses, from which key research questions to be addressed in the subsequent studies can be adequately informed. Application of Systems Biology/Pharmacology to toxicology research, namely Systems Toxicology, should considerably improve the predictability of drug-induced toxicities in clinical situations that are difficult to predict from conventional preclinical toxicology studies. Systems Biology/Pharmacology/Toxicology models can be continuously improved using iterative learn-confirm processes throughout preclinical and clinical drug discovery and development processes. Successful implementation of data-intensive drug development approaches requires cultivation of an adequate R&D culture to appreciate this approach.

Toxicological evaluation of fracturing fluids; Toxikologische Bewertung von Fracking-Fluiden

Energy Technology Data Exchange (ETDEWEB)

Frimmel, Fritz H.; Gordalla, Birgit [Karlsruher Institut fuer Technologie (KIT), Karlsruhe (Germany). Lehrstuhl fuer Wasserchemie und Wassertechnologie und DVGW-Forschungsstelle Engler-Bunte-Inst.; Ewers, Ulrich [Hygiene-Institut des Ruhrgebiets, Gelsenkirchen (Germany). Abt. fuer Umweltmedizin und Toxikologie; Schmitt-Jansen, Mechthild; Altenburger, Rolf [Helmholtz-Zentrum fuer Umweltforschung - UFZ, Leipzig (Germany). Dept. Bioanalytische Oekotoxikologie

2012-11-01

The fracturing technology utilizes chemicals which have to be evaluated according to the safety and environmental compatibility. Under this aspect, the authors of the contribution under consideration present an integrated evaluation in terms of human toxicology, ecotoxicology as well as in terms of protection of drinking water on the basis of selected examples.

78 FR 45253 - National Toxicology Program Scientific Advisory Committee on Alternative Toxicological Methods...

Science.gov (United States)

2013-07-26

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Toxicology Program... Alternative Methods (ICCVAM), the National Toxicology Program (NTP) Interagency Center for the Evaluation of... Director, National Toxicology Program. [FR Doc. 2013-17919 Filed 7-25-13; 8:45 am] BILLING CODE 4140-01-P ...

In Silico Toxicology – Non-Testing Methods

Science.gov (United States)

Raunio, Hannu

2011-01-01

In silico toxicology in its broadest sense means “anything that we can do with a computer in toxicology.” Many different types of in silico methods have been developed to characterize and predict toxic outcomes in humans and environment. The term non-testing methods denote grouping approaches, structure–activity relationship, and expert systems. These methods are already used for regulatory purposes and it is anticipated that their role will be much more prominent in the near future. This Perspective will delineate the basic principles of non-testing methods and evaluate their role in current and future risk assessment of chemical compounds. PMID:21772821

Real-time prediction of Physicochemical and Toxicological Endpoints Using the Web-based CompTox Chemistry Dashboard (ACS Fall meeting) 10 of 12

Science.gov (United States)

The EPA CompTox Chemistry Dashboard developed by the National Center for Computational Toxicology (NCCT) provides access to data for ~750,000 chemical substances. The data include experimental and predicted data for physicochemical, environmental fate and transport and toxicologi...

Antimicrobial and toxicological evaluation of ethanol leaf extract of Salacia lehmbachii

Directory of Open Access Journals (Sweden)

Essien Augustine Dick

2017-12-01

Full Text Available The leaves of Salacia lehmbachii are used ethnomedically across Africa for the treatment of different diseases its antimicrobial activity as well as toxicological profile were evaluated. Antimicrobial activity against clinical strains of Pseudomonas aeruginosa, Salmonella typhi, Staphylococus aureus, Shigella species, Eschericha coli and Proteus mirabilis were compared with Gentamycin. Toxicological investigation was determined by administering 100 mg/kg, 200 mg/kg and 400 mg/kg of the ethanol leaf extract to male Wistar rats for 21 days with distilled water as control. Hematological and biochemical parameters as well as the vital organs were examined. The ethanol extract inhibited the growth of P. aeruginosa, S. typhi, S. aureus, Shigella species, E. coli and P. mirabilis to varying extents. The LD50 in rats was greater than 5000 mg/kg. Toxicological evaluation of the extract did not produce any significant effect on hematological and biochemical parameters and vital organs in rats. S. lehmbachii ethanol leaf extract did not demonstrate antimicrobial activity against selected microorganisms. Neither did it show any non-toxic effect on the parameters investigated in rats. Thus the extract can be considered safe when administered orally.

Predictive Toxicology: Modeling Chemical Induced Toxicological Response Combining Circular Fingerprints with Random Forest and Support Vector Machine

Directory of Open Access Journals (Sweden)

Alexios eKoutsoukas

2016-03-01

Full Text Available Modern drug discovery and toxicological research are under pressure, as the cost of developing and testing new chemicals for potential toxicological risk is rising. Extensive evaluation of chemical products for potential adverse effects is a challenging task, due to the large number of chemicals and the possible hazardous effects on human health. Safety regulatory agencies around the world are dealing with two major challenges. First, the growth of chemicals introduced every year in household products and medicines that need to be tested, and second the need to protect public welfare. Hence, alternative and more efficient toxicological risk assessment methods are in high demand. The Toxicology in the 21st Century (Tox21 consortium a collaborative effort was formed to develop and investigate alternative assessment methods. A collection of 10,000 compounds composed of environmental chemicals and approved drugs were screened for interference in biochemical pathways and released for crowdsourcing data analysis. The physicochemical space covered by Tox21 library was explored, measured by Molecular Weight (MW and the octanol/water partition coefficient (cLogP. It was found that on average chemical structures had MW of 272.6 Daltons. In case of cLogP the average value was 2.476. Next relationships between assays were examined based on compounds activity profiles across the assays utilizing the Pearson correlation coefficient r. A cluster was observed between the Androgen and Estrogen Receptors and their ligand bind domains accordingly indicating presence of cross talks among the receptors. The highest correlations observed were between NR.AR and NR.AR_LBD, where it was r=0.66 and between NR.ER and NR.ER_LBD, where it was r=0.5.Our approach to model the Tox21 data consisted of utilizing circular molecular fingerprints combined with Random Forest and Support Vector Machine by modeling each assay independently. In all of the 12 sub-challenges our modeling

Integrative Systems Biology Applied to Toxicology

DEFF Research Database (Denmark)

Kongsbak, Kristine Grønning

associated with combined exposure to multiple chemicals. Testing all possible combinations of the tens of thousands environmental chemicals is impractical. This PhD project was launched to apply existing computational systems biology methods to toxicological research. In this thesis, I present in three...... of a system thereby suggesting new ways of thinking specific toxicological endpoints. Furthermore, computational methods can serve as valuable input for the hypothesis generating phase of the preparations of a research project....

Green toxicology.

Science.gov (United States)

Maertens, Alexandra; Anastas, Nicholas; Spencer, Pamela J; Stephens, Martin; Goldberg, Alan; Hartung, Thomas

2014-01-01

Historically, early identification and characterization of adverse effects of industrial chemicals was difficult because conventional toxicological test methods did not meet R&D needs for rapid, relatively inexpensive methods amenable to small amounts of test material. The pharmaceutical industry now front-loads toxicity testing, using in silico, in vitro, and less demanding animal tests at earlier stages of product development to identify and anticipate undesirable toxicological effects and optimize product development. The Green Chemistry movement embraces similar ideas for development of less toxic products, safer processes, and less waste and exposure. Further, the concept of benign design suggests ways to consider possible toxicities before the actual synthesis and to apply some structure/activity rules (SAR) and in silico methods. This requires not only scientific development but also a change in corporate culture in which synthetic chemists work with toxicologists. An emerging discipline called Green Toxicology (Anastas, 2012) provides a framework for integrating the principles of toxicology into the enterprise of designing safer chemicals, thereby minimizing potential toxicity as early in production as possible. Green Toxicology`s novel utility lies in driving innovation by moving safety considerations to the earliest stage in a chemical`s lifecycle, i.e., to molecular design. In principle, this field is no different than other subdisciplines of toxicology that endeavor to focus on a specific area - for example, clinical, environmental or forensic toxicology. We use the same principles and tools to evaluate an existing substance or to design a new one. The unique emphasis is in using 21st century toxicology tools as a preventative strategy to "design out" undesired human health and environmental effects, thereby increasing the likelihood of launching a successful, sustainable product. Starting with the formation of a steering group and a series of workshops

Toxicological Evaluations of Rare Earths and Their Health Impacts to Workers: A Literature Review

Directory of Open Access Journals (Sweden)

Kyung Taek Rim

2013-03-01

Full Text Available In concert with the development of new materials in the last decade, the need for toxicological studies of these materials has been increasing. These new materials include a group of rare earths (RE. The use of RE nanotechnology is being considered in some green applications, to increase their efficiency by using nano-sized RE compounds, and therefore hazard evaluation and risk assessment are highly recommended. This review was conducted through an extensive contemplation of the literatures in toxicology with in vitro and in vivo studies. Major aspects reviewed were the toxicological evaluations of these elements and metallic compounds at the molecular and cellular level, animal and human epidemiological studies and environmental and occupational health impacts on workers. We also discuss the future prospect of industries with appliances using RE together with the significance of preventive efforts for workers’ health. To establish a safe and healthy working environment for RE industries, the use of biomarkers is increasing to provide sustainable measure, due to demand for information about the health risks from unfavorable exposures. Given the recent toxicological results on the exposure of cells, animals and workers to RE compounds, it is important to review the toxicological studies to improve the current understanding of the RE compounds in the field of occupational health. This will help to establish a sustainable, safe and healthy working environment for RE industries.

How Adverse Outcome Pathways Can Aid the Development and Use of Computational Prediction Models for Regulatory Toxicology.

Science.gov (United States)

Wittwehr, Clemens; Aladjov, Hristo; Ankley, Gerald; Byrne, Hugh J; de Knecht, Joop; Heinzle, Elmar; Klambauer, Günter; Landesmann, Brigitte; Luijten, Mirjam; MacKay, Cameron; Maxwell, Gavin; Meek, M E Bette; Paini, Alicia; Perkins, Edward; Sobanski, Tomasz; Villeneuve, Dan; Waters, Katrina M; Whelan, Maurice

2017-02-01

Efforts are underway to transform regulatory toxicology and chemical safety assessment from a largely empirical science based on direct observation of apical toxicity outcomes in whole organism toxicity tests to a predictive one in which outcomes and risk are inferred from accumulated mechanistic understanding. The adverse outcome pathway (AOP) framework provides a systematic approach for organizing knowledge that may support such inference. Likewise, computational models of biological systems at various scales provide another means and platform to integrate current biological understanding to facilitate inference and extrapolation. We argue that the systematic organization of knowledge into AOP frameworks can inform and help direct the design and development of computational prediction models that can further enhance the utility of mechanistic and in silico data for chemical safety assessment. This concept was explored as part of a workshop on AOP-Informed Predictive Modeling Approaches for Regulatory Toxicology held September 24-25, 2015. Examples of AOP-informed model development and its application to the assessment of chemicals for skin sensitization and multiple modes of endocrine disruption are provided. The role of problem formulation, not only as a critical phase of risk assessment, but also as guide for both AOP and complementary model development is described. Finally, a proposal for actively engaging the modeling community in AOP-informed computational model development is made. The contents serve as a vision for how AOPs can be leveraged to facilitate development of computational prediction models needed to support the next generation of chemical safety assessment. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology.

Progress in computational toxicology.

Science.gov (United States)

Ekins, Sean

2014-01-01

Computational methods have been widely applied to toxicology across pharmaceutical, consumer product and environmental fields over the past decade. Progress in computational toxicology is now reviewed. A literature review was performed on computational models for hepatotoxicity (e.g. for drug-induced liver injury (DILI)), cardiotoxicity, renal toxicity and genotoxicity. In addition various publications have been highlighted that use machine learning methods. Several computational toxicology model datasets from past publications were used to compare Bayesian and Support Vector Machine (SVM) learning methods. The increasing amounts of data for defined toxicology endpoints have enabled machine learning models that have been increasingly used for predictions. It is shown that across many different models Bayesian and SVM perform similarly based on cross validation data. Considerable progress has been made in computational toxicology in a decade in both model development and availability of larger scale or 'big data' models. The future efforts in toxicology data generation will likely provide us with hundreds of thousands of compounds that are readily accessible for machine learning models. These models will cover relevant chemistry space for pharmaceutical, consumer product and environmental applications. Copyright © 2013 Elsevier Inc. All rights reserved.

Fossil fuel toxicology

International Nuclear Information System (INIS)

Anon.

1976-01-01

A program is described for the investigation of the toxicology of coal-derived effluents that will utilize a battery of cellular and mammalian test systems and end points to evaluate the toxicological effects of acute, sub-acute, and long-term, low-level exposure to gaseous and particulate effluents from combustion of coal, with special emphasis on fluidized bed combustion

Computational toxicology: Its essential role in reducing drug attrition.

Science.gov (United States)

Naven, R T; Louise-May, S

2015-12-01

Predictive toxicology plays a critical role in reducing the failure rate of new drugs in pharmaceutical research and development. Despite recent gains in our understanding of drug-induced toxicity, however, it is urgent that the utility and limitations of our current predictive tools be determined in order to identify gaps in our understanding of mechanistic and chemical toxicology. Using recently published computational regression analyses of in vitro and in vivo toxicology data, it will be demonstrated that significant gaps remain in early safety screening paradigms. More strategic analyses of these data sets will allow for a better understanding of their domain of applicability and help identify those compounds that cause significant in vivo toxicity but which are currently mis-predicted by in silico and in vitro models. These 'outliers' and falsely predicted compounds are metaphorical lighthouses that shine light on existing toxicological knowledge gaps, and it is essential that these compounds are investigated if attrition is to be reduced significantly in the future. As such, the modern computational toxicologist is more productively engaged in understanding these gaps and driving investigative toxicology towards addressing them. © The Author(s) 2015.

The Predictive Validity of Projective Measures.

Science.gov (United States)

Suinn, Richard M.; Oskamp, Stuart

Written for use by clinical practitioners as well as psychological researchers, this book surveys recent literature (1950-1965) on projective test validity by reviewing and critically evaluating studies which shed light on what may reliably be predicted from projective test results. Two major instruments are covered: the Rorschach and the Thematic…

How adverse outcome pathways can aid the development and use of computational prediction models for regulatory toxicology

Science.gov (United States)

Efforts are underway to transform regulatory toxicology and chemical safety assessment from a largely empirical science based on direct observation of apical toxicity outcomes in whole organism toxicity tests to a predictive one in which outcomes and risk are inferred from accumu...

CERAPP: Collaborative estrogen receptor activity prediction project

DEFF Research Database (Denmark)

Mansouri, Kamel; Abdelaziz, Ahmed; Rybacka, Aleksandra

2016-01-01

). Risk assessors need tools to prioritize chemicals for evaluation in costly in vivo tests, for instance, within the U.S. EPA Endocrine Disruptor Screening Program. oBjectives: We describe a large-scale modeling project called CERAPP (Collaborative Estrogen Receptor Activity Prediction Project...... States and Europe to predict ER activity of a common set of 32,464 chemical structures. Quantitative structure-activity relationship models and docking approaches were employed, mostly using a common training set of 1,677 chemical structures provided by the U.S. EPA, to build a total of 40 categorical......: Individual model scores ranged from 0.69 to 0.85, showing high prediction reliabilities. Out of the 32,464 chemicals, the consensus model predicted 4,001 chemicals (12.3%) as high priority actives and 6,742 potential actives (20.8%) to be considered for further testing. conclusion: This project demonstrated...

Predictive Systems Toxicology

KAUST Repository

Kiani, Narsis A.; Shang, Ming-Mei; Zenil, Hector; Tegner, Jesper

2018-01-01

In this review we address to what extent computational techniques can augment our ability to predict toxicity. The first section provides a brief history of empirical observations on toxicity dating back to the dawn of Sumerian civilization. Interestingly, the concept of dose emerged very early on, leading up to the modern emphasis on kinetic properties, which in turn encodes the insight that toxicity is not solely a property of a compound but instead depends on the interaction with the host organism. The next logical step is the current conception of evaluating drugs from a personalized medicine point-of-view. We review recent work on integrating what could be referred to as classical pharmacokinetic analysis with emerging systems biology approaches incorporating multiple omics data. These systems approaches employ advanced statistical analytical data processing complemented with machine learning techniques and use both pharmacokinetic and omics data. We find that such integrated approaches not only provide improved predictions of toxicity but also enable mechanistic interpretations of the molecular mechanisms underpinning toxicity and drug resistance. We conclude the chapter by discussing some of the main challenges, such as how to balance the inherent tension between the predictive capacity of models, which in practice amounts to constraining the number of features in the models versus allowing for rich mechanistic interpretability, i.e. equipping models with numerous molecular features. This challenge also requires patient-specific predictions on toxicity, which in turn requires proper stratification of patients as regards how they respond, with or without adverse toxic effects. In summary, the transformation of the ancient concept of dose is currently successfully operationalized using rich integrative data encoded in patient-specific models.

Predictive Systems Toxicology

KAUST Repository

Kiani, Narsis A.

2018-01-15

In this review we address to what extent computational techniques can augment our ability to predict toxicity. The first section provides a brief history of empirical observations on toxicity dating back to the dawn of Sumerian civilization. Interestingly, the concept of dose emerged very early on, leading up to the modern emphasis on kinetic properties, which in turn encodes the insight that toxicity is not solely a property of a compound but instead depends on the interaction with the host organism. The next logical step is the current conception of evaluating drugs from a personalized medicine point-of-view. We review recent work on integrating what could be referred to as classical pharmacokinetic analysis with emerging systems biology approaches incorporating multiple omics data. These systems approaches employ advanced statistical analytical data processing complemented with machine learning techniques and use both pharmacokinetic and omics data. We find that such integrated approaches not only provide improved predictions of toxicity but also enable mechanistic interpretations of the molecular mechanisms underpinning toxicity and drug resistance. We conclude the chapter by discussing some of the main challenges, such as how to balance the inherent tension between the predictive capacity of models, which in practice amounts to constraining the number of features in the models versus allowing for rich mechanistic interpretability, i.e. equipping models with numerous molecular features. This challenge also requires patient-specific predictions on toxicity, which in turn requires proper stratification of patients as regards how they respond, with or without adverse toxic effects. In summary, the transformation of the ancient concept of dose is currently successfully operationalized using rich integrative data encoded in patient-specific models.

Chemicals in marine and coastal environments: the need for toxicological information

Energy Technology Data Exchange (ETDEWEB)

Johnson, A.R.

1982-04-01

The tremendous increase in the number and amount of chemicals produced and transported in past years has resulted in increasing problems with accidental spills and uncontrolled waste sites involving these chemicals. The United States government has accordingly developed a mechanism for responding to such incidents. As part of that mechanism, the Hazardous Materials Response Project serves to coordinate scientific activities and facilitate in the gathering of scientific information needed for response to chemical spill or waste site emergencies involving coastal waters. Inevitably, much information of a toxicological nature is required to adequately evaluate potential hazards and appropriate responses. The Hazardous Materials Response Project is also able to provide a framework for significant progress in scientific understanding because it can bring together and encourage collaboration among experts in the various disciplines which are relevant to the environmental toxicological problems encountered.

Toxicological evaluation of Cd-based fluorescent nanoprobes by means of in vivo studies

Science.gov (United States)

Farias, Patricia M. A.; Ma-Hock, Lan; Landsiedel, Robert; van Ravenzwaay, Bennard

2018-02-01

Cadmium still represents a stigma for many research- and/or industrial applications. Some deleterious effects are attributed to Cadmium. In the present work, highly fluorescent Cadmium sulfide quantum dots are investigated by e.g. physical-chemical characterization. Most important however is their application as fluorescent probes for bio-imaging in living cells and tissues. This work presents their toxicological evaluation by means of in vivo studies. Bio-imaging experiments are performed without any pre-treatment. The toxicological studies performed, strongly indicate that the use of Cadmium based nanoparticles as fluorescent probes may be nonhazardous and not induce side effects for cells/tissues.

Postmortem aviation forensic toxicology: an overview.

Science.gov (United States)

Chaturvedi, Arvind K

2010-05-01

An overview of the subtopic aviation combustion toxicology of the field of aerospace toxicology has been published. In a continuation of the overview, the findings associated with postmortem aviation forensic toxicology are being summarized in the present overview. A literature search for the period of 1960-2007 was performed. The important findings related to postmortem toxicology were evaluated. In addition to a brief introduction, this overview is divided into the sections of analytical methods; carboxyhemoglobin and blood cyanide ion; ethanol; drugs; result interpretation; glucose and hemoglobin A(1c); and references. Specific details of the subject matter were discussed. It is anticipated that this overview will be an outline source for aviation forensic toxicology within the field of aerospace toxicology.

Advancing the use of noncoding RNA in regulatory toxicology: Report of an ECETOC workshop.

Science.gov (United States)

Aigner, Achim; Buesen, Roland; Gant, Tim; Gooderham, Nigel; Greim, Helmut; Hackermüller, Jörg; Hubesch, Bruno; Laffont, Madeleine; Marczylo, Emma; Meister, Gunter; Petrick, Jay S; Rasoulpour, Reza J; Sauer, Ursula G; Schmidt, Kerstin; Seitz, Hervé; Slack, Frank; Sukata, Tokuo; van der Vies, Saskia M; Verhaert, Jan; Witwer, Kenneth W; Poole, Alan

2016-12-01

The European Centre for the Ecotoxicology and Toxicology of Chemicals (ECETOC) organised a workshop to discuss the state-of-the-art research on noncoding RNAs (ncRNAs) as biomarkers in regulatory toxicology and as analytical and therapeutic agents. There was agreement that ncRNA expression profiling data requires careful evaluation to determine the utility of specific ncRNAs as biomarkers. To advance the use of ncRNA in regulatory toxicology, the following research priorities were identified: (1) Conduct comprehensive literature reviews to identify possibly suitable ncRNAs and areas of toxicology where ncRNA expression profiling could address prevailing scientific deficiencies. (2) Develop consensus on how to conduct ncRNA expression profiling in a toxicological context. (3) Conduct experimental projects, including, e.g., rat (90-day) oral toxicity studies, to evaluate the toxicological relevance of the expression profiles of selected ncRNAs. Thereby, physiological ncRNA expression profiles should be established, including the biological variability of healthy individuals. To substantiate the relevance of key ncRNAs for cell homeostasis or pathogenesis, molecular events should be dose-dependently linked with substance-induced apical effects. Applying a holistic approach, knowledge on ncRNAs, 'omics and epigenetics technologies should be integrated into adverse outcome pathways to improve the understanding of the functional roles of ncRNAs within a regulatory context. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

Systems Toxicology: From Basic Research to Risk Assessment

Science.gov (United States)

2014-01-01

Systems Toxicology is the integration of classical toxicology with quantitative analysis of large networks of molecular and functional changes occurring across multiple levels of biological organization. Society demands increasingly close scrutiny of the potential health risks associated with exposure to chemicals present in our everyday life, leading to an increasing need for more predictive and accurate risk-assessment approaches. Developing such approaches requires a detailed mechanistic understanding of the ways in which xenobiotic substances perturb biological systems and lead to adverse outcomes. Thus, Systems Toxicology approaches offer modern strategies for gaining such mechanistic knowledge by combining advanced analytical and computational tools. Furthermore, Systems Toxicology is a means for the identification and application of biomarkers for improved safety assessments. In Systems Toxicology, quantitative systems-wide molecular changes in the context of an exposure are measured, and a causal chain of molecular events linking exposures with adverse outcomes (i.e., functional and apical end points) is deciphered. Mathematical models are then built to describe these processes in a quantitative manner. The integrated data analysis leads to the identification of how biological networks are perturbed by the exposure and enables the development of predictive mathematical models of toxicological processes. This perspective integrates current knowledge regarding bioanalytical approaches, computational analysis, and the potential for improved risk assessment. PMID:24446777

Systems Toxicology: The Future of Risk Assessment.

Science.gov (United States)

Sauer, John Michael; Hartung, Thomas; Leist, Marcel; Knudsen, Thomas B; Hoeng, Julia; Hayes, A Wallace

2015-01-01

Risk assessment, in the context of public health, is the process of quantifying the probability of a harmful effect to individuals or populations from human activities. With increasing public health concern regarding the potential risks associated with chemical exposure, there is a need for more predictive and accurate approaches to risk assessment. Developing such an approach requires a mechanistic understanding of the process by which xenobiotic substances perturb biological systems and lead to toxicity. Supplementing the shortfalls of traditional risk assessment with mechanistic biological data has been widely discussed but not routinely implemented in the evaluation of chemical exposure. These mechanistic approaches to risk assessment have been generally referred to as systems toxicology. This Symposium Overview article summarizes 4 talks presented at the 35th Annual Meeting of the American College of Toxicology. © The Author(s) 2015.

Predictive Models and Computational Toxicology (II IBAMTOX)

Science.gov (United States)

EPA’s ‘virtual embryo’ project is building an integrative systems biology framework for predictive models of developmental toxicity. One schema involves a knowledge-driven adverse outcome pathway (AOP) framework utilizing information from public databases, standardized ontologies...

Antisickling and toxicological evaluation of the leaves of Scoparia dulcis Linn (Scrophulariaceae).

Science.gov (United States)

Abere, Tavs A; Okoye, Chiagozie J; Agoreyo, Freddy O; Eze, Gerald I; Jesuorobo, Rose I; Egharevba, Clement O; Aimator, Pauline O

2015-11-23

Scoparia dulcis Linn (Scrophulariaceae) together with other medicinal plants serve as antisickling remedies in Africa. This study was aimed at investigating the antisickling activity of the leaves of the plant as well as establishing the toxicological profile. Chemical tests were employed in phytochemical investigations. Evaluation of the antisickling activity involved the inhibition of sodium metabisulphite-induced sickling of the HbSS red blood cells obtained from confirmed sickle cell patients who were not in crises. Concentrations of the crude extract and its fractions were tested with normal saline and p-hydroxybenzoic acid serving as controls. Acute toxicological evaluation was carried out in mice while 30-day assessment was done in rats. Phytochemical screening revealed the presence of alkaloids, tannins, flavonoids and saponins. Percentage sickling inhibitions of the aqueous methanol extracts of S. dulcis were significant all through the period of assay p Scoparia dulcis in the management of Sickle cell disorders and a candidate for further investigations.

A primer on systematic reviews in toxicology.

Science.gov (United States)

Hoffmann, Sebastian; de Vries, Rob B M; Stephens, Martin L; Beck, Nancy B; Dirven, Hubert A A M; Fowle, John R; Goodman, Julie E; Hartung, Thomas; Kimber, Ian; Lalu, Manoj M; Thayer, Kristina; Whaley, Paul; Wikoff, Daniele; Tsaioun, Katya

2017-07-01

Systematic reviews, pioneered in the clinical field, provide a transparent, methodologically rigorous and reproducible means of summarizing the available evidence on a precisely framed research question. Having matured to a well-established approach in many research fields, systematic reviews are receiving increasing attention as a potential tool for answering toxicological questions. In the larger framework of evidence-based toxicology, the advantages and obstacles of, as well as the approaches for, adapting and adopting systematic reviews to toxicology are still being explored. To provide the toxicology community with a starting point for conducting or understanding systematic reviews, we herein summarized available guidance documents from various fields of application. We have elaborated on the systematic review process by breaking it down into ten steps, starting with planning the project, framing the question, and writing and publishing the protocol, and concluding with interpretation and reporting. In addition, we have identified the specific methodological challenges of toxicological questions and have summarized how these can be addressed. Ultimately, this primer is intended to stimulate scientific discussions of the identified issues to fuel the development of toxicology-specific methodology and to encourage the application of systematic review methodology to toxicological issues.

Waste tank safety program annual status report for FY 1993, Task 5: Toxicology and epidemiology

International Nuclear Information System (INIS)

Mahlum, D.D.; Young, J.Y.

1993-09-01

A toxicology team independently reviewed analytical data and provided advice concerning potential health effects associated with exposure to tank-vapor constituents at the Hanford site. Most of the emphasis was directed toward Tank 241-C-103, but a preliminary assessment was also made of the toxicologic implication of the cyanide levels in the headspace of Tank 241-C-108. The objectives of this program are to (1) review procedures used for sampling vapors from various tanks, (2) identify constituents in tank-vapor samples that could be related to symptoms reported by waste-tank workers, (3) evaluate the toxicologic implications of those constituents by comparison to established toxicologic data bases, (4) provide advice for additional analytical efforts, and (5) support other activities as requested by the project manager and the cognizant Westinghouse Hanford Company Tank Vapor Issues Safety Resolution Manager

Genetic toxicology at the crossroads-from qualitative hazard evaluation to quantitative risk assessment.

Science.gov (United States)

White, Paul A; Johnson, George E

2016-05-01

Applied genetic toxicology is undergoing a transition from qualitative hazard identification to quantitative dose-response analysis and risk assessment. To facilitate this change, the Health and Environmental Sciences Institute (HESI) Genetic Toxicology Technical Committee (GTTC) sponsored a workshop held in Lancaster, UK on July 10-11, 2014. The event included invited speakers from several institutions and the contents was divided into three themes-1: Point-of-departure Metrics for Quantitative Dose-Response Analysis in Genetic Toxicology; 2: Measurement and Estimation of Exposures for Better Extrapolation to Humans and 3: The Use of Quantitative Approaches in Genetic Toxicology for human health risk assessment (HHRA). A host of pertinent issues were discussed relating to the use of in vitro and in vivo dose-response data, the development of methods for in vitro to in vivo extrapolation and approaches to use in vivo dose-response data to determine human exposure limits for regulatory evaluations and decision-making. This Special Issue, which was inspired by the workshop, contains a series of papers that collectively address topics related to the aforementioned themes. The Issue includes contributions that collectively evaluate, describe and discuss in silico, in vitro, in vivo and statistical approaches that are facilitating the shift from qualitative hazard evaluation to quantitative risk assessment. The use and application of the benchmark dose approach was a central theme in many of the workshop presentations and discussions, and the Special Issue includes several contributions that outline novel applications for the analysis and interpretation of genetic toxicity data. Although the contents of the Special Issue constitutes an important step towards the adoption of quantitative methods for regulatory assessment of genetic toxicity, formal acceptance of quantitative methods for HHRA and regulatory decision-making will require consensus regarding the

Watershed-scale evaluation of the Water Erosion Prediction Project (WEPP) model in the Lake Tahoe basin

Science.gov (United States)

Erin S. Brooks; Mariana Dobre; William J. Elliot; Joan Q. Wu; Jan Boll

2016-01-01

Forest managers need methods to evaluate the impacts of management at the watershed scale. The Water Erosion Prediction Project (WEPP) has the ability to model disturbed forested hillslopes, but has difficulty addressing some of the critical processes that are important at a watershed scale, including baseflow and water yield. In order to apply WEPP to...

The FAA's postmortem forensic toxicology self-evaluated proficiency test program: the second seven years.

Science.gov (United States)

Chaturvedi, Arvind K; Craft, Kristi J; Cardona, Patrick S; Rogers, Paul B; Canfield, Dennis V

2009-05-01

During toxicological evaluations of samples from fatally injured pilots involved in civil aviation accidents, a high degree of quality control/quality assurance (QC/QA) is maintained. Under this philosophy, the Federal Aviation Administration (FAA) started a forensic toxicology proficiency-testing (PT) program in July 1991. In continuation of the first seven years of the PT findings reported earlier, PT findings of the next seven years are summarized herein. Twenty-eight survey samples (12 urine, 9 blood, and 7 tissue homogenate) with/without alcohols/volatiles, drugs, and/or putrefactive amine(s) were submitted to an average of 31 laboratories, of which an average of 25 participants returned their results. Analytes in survey samples were correctly identified and quantitated by a large number of participants, but some false positives of concern were reported. It is anticipated that the FAA's PT program will continue to serve the forensic toxicology community through this important part of the QC/QA for laboratory accreditations.

An Object-Based Approach to Evaluation of Climate Variability Projections and Predictions

Science.gov (United States)

Ammann, C. M.; Brown, B.; Kalb, C. P.; Bullock, R.

2017-12-01

Evaluations of the performance of earth system model predictions and projections are of critical importance to enhance usefulness of these products. Such evaluations need to address specific concerns depending on the system and decisions of interest; hence, evaluation tools must be tailored to inform about specific issues. Traditional approaches that summarize grid-based comparisons of analyses and models, or between current and future climate, often do not reveal important information about the models' performance (e.g., spatial or temporal displacements; the reason behind a poor score) and are unable to accommodate these specific information needs. For example, summary statistics such as the correlation coefficient or the mean-squared error provide minimal information to developers, users, and decision makers regarding what is "right" and "wrong" with a model. New spatial and temporal-spatial object-based tools from the field of weather forecast verification (where comparisons typically focus on much finer temporal and spatial scales) have been adapted to more completely answer some of the important earth system model evaluation questions. In particular, the Method for Object-based Diagnostic Evaluation (MODE) tool and its temporal (three-dimensional) extension (MODE-TD) have been adapted for these evaluations. More specifically, these tools can be used to address spatial and temporal displacements in projections of El Nino-related precipitation and/or temperature anomalies, ITCZ-associated precipitation areas, atmospheric rivers, seasonal sea-ice extent, and other features of interest. Examples of several applications of these tools in a climate context will be presented, using output of the CESM large ensemble. In general, these tools provide diagnostic information about model performance - accounting for spatial, temporal, and intensity differences - that cannot be achieved using traditional (scalar) model comparison approaches. Thus, they can provide more

A practice analysis of toxicology.

Science.gov (United States)

Wood, Carol S; Weis, Christopher P; Caro, Carla M; Roe, Amy

2016-12-01

In 2015, the American Board of Toxicology (ABT), with collaboration from the Society of Toxicology (SOT), in consultation with Professional Examination Service, performed a practice analysis study of the knowledge required for general toxicology. The purpose of this study is to help assure that the examination and requirements for attainment of Diplomate status are relevant to modern toxicology and based upon an empirical foundation of knowledge. A profile of the domains and tasks used in toxicology practice was developed by subject-matter experts representing a broad range of experiences and perspectives. An on-line survey of toxicologists, including Diplomates of the ABT and SOT members, confirmed the delineation. Results of the study can be used to improve understanding of toxicology practice, to better serve all toxicologists, and to present the role of toxicologists to those outside the profession. Survey results may also be used by the ABT Board of Directors to develop test specifications for the certifying examination and will be useful for evaluating and updating the content of professional preparation, development, and continuing education programs. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Toxicological and safety evaluation of Nigella sativa lipid and volatile fractions in streptozotocin induced diabetes mellitus

Directory of Open Access Journals (Sweden)

Muhammad Tauseef Sultan

2014-09-01

Full Text Available Objective: To evaluate the toxicological aspects of Nigella sativa (N. sativa lipid and volatile fractions in streptozotocin induced diabetes mellitus. Methods: National Institute of Health (NIH, Islamabad provided us thirty Sprague Dawley rats that were further divided into three groups, i.e. control, N. sativa lipid fraction (4% and N. sativa volatile fraction (0.3%, respectively. The serological and haematological indices were evaluated at 4-week intervals during 56 d study. Results: The results indicated that the diabetes mellitus imparted negative effects on various serological and haematological attributes. However, supplementation of the N. sativa lipid fraction and N. sativa volatile fraction ameliorated the adverse consequences of diabetes mellitus. The diabetes induced renal toxicity and imbalanced serum chemistry were slightly modulated by experimental diets. However, the impact of essential oil was more significant as compared to the fixed oil. Conclusions: In a nutshell, experimental diets containing N. sativa lipid fraction and N. sativa volatile fraction are effective without having any toxicological effects, and experimental diets reduced toxicological and adverse consequences of diabetes mellitus.

Toxicological evaluation of clay minerals and derived nanocomposites: a review.

Science.gov (United States)

Maisanaba, Sara; Pichardo, Silvia; Puerto, María; Gutiérrez-Praena, Daniel; Cameán, Ana M; Jos, Angeles

2015-04-01

wildlife, with laboratory trials showing contradictory outcomes. Clay minerals have different applications in the environment, thus with a strict control of the concentrations used, they can provide beneficial uses. Despite the extensive number of reports available, there is also a need of systematic in vitro-in vivo extrapolation studies, with still scarce information on toxicity biomarkers such as inmunomodulatory effects or alteration of the genetic expression. In conclusion, a case by case toxicological evaluation is required taking into account that different clays have their own toxicological profiles, their modification can change this profile, and the potential increase of the human/environmental exposure to clay minerals due to their novel applications. Copyright © 2014 Elsevier Inc. All rights reserved.

Comparison of toxicological and radiological aspects of K basins sludge

International Nuclear Information System (INIS)

RITTMANN, P.D.

1999-01-01

The composition of various K Basins sludge is evaluated for its toxicological and radiological impacts downwind from accidents. It is shown that the radiological risk evaluation guidelines are always more limiting than the toxicological risk evaluation guidelines

Evaluating the Predictive Value of Growth Prediction Models

Science.gov (United States)

Murphy, Daniel L.; Gaertner, Matthew N.

2014-01-01

This study evaluates four growth prediction models--projection, student growth percentile, trajectory, and transition table--commonly used to forecast (and give schools credit for) middle school students' future proficiency. Analyses focused on vertically scaled summative mathematics assessments, and two performance standards conditions (high…

TOXICOLOGICAL EVALUATION OF REALISTIC EMISSIONS OF SOURCE AEROSOLS (TERESA): APPLICATION TO POWER PLANT-DERIVED PM2.5

Energy Technology Data Exchange (ETDEWEB)

Annette Rohr

2004-12-02

tended to be slightly higher. Exposure concentrations were about 249 {micro}g/m{sup 3} PM, of which 87 {micro}g/m{sup 3} was sulfate and approximately 110 {micro}g/m{sup 3} was secondary organic material ({approx}44%). Results indicated subtle differences in breathing pattern between exposed and control (sham) animals, but no differences in other endpoints (in vivo chemiluminescence, blood cytology, bronchoalveolar lavage fluid analysis). It was suspected that primary particle losses may have been occurring in the venturi aspirator/orifice sampler; therefore, the stack sampling system was redesigned. The modified system resulted in no substantial increase in particle concentration in the emissions, leading us to conclude that the electrostatic precipitator at the power plant has high efficiency, and that the sampled emissions are representative of those exiting the stack into the atmosphere. This is important, since the objective of the Project is to carry out exposures to realistic coal combustion-derived secondary PM arising from power plants. During the next reporting period, we will document and describe the remainder of the fieldwork at Plant 0, which we expect to be complete by mid-November 2004. This report will include detailed Phase I toxicological findings for all scenarios run, and Phase II toxicological findings for one selected scenario. Depending upon the outcome of the ongoing fieldwork at Plant 0 (i.e. the biological effects observed), not all the proposed scenarios may be evaluated. The next report is also expected to include preliminary field data for Plant 1, located in the Southeast.

Behavioral assays in environmental toxicology

Energy Technology Data Exchange (ETDEWEB)

Weiss, B.

1979-01-01

Environmental toxicology is too permeated by questions about how the whole organism functions to abandon intact animals as test systems. Behavior does not participate as a single entity or discipline. It ranges across the total spectrum of functional toxicity, from tenuous subjective complaints to subtle sensory and motor disturbances demanding advanced instrumentation for their evaluation. Three facets of behavioral toxicology that illustrate its breadth of interests and potential contributions are discussed.

Phytochemical analysis and toxicological evaluation of the ...

African Journals Online (AJOL)

Phytochemical analysis revealed the presence of tannins, Flavonoid, Alkaloids, Anthraquinone, Saponin and Cardiac glycosides. This work thus justifies the ethnomedicinal use of the plant in the treatment of anaemia and its safety profile. Keywords: Toxicological, Ethno toxicity, Hematological and phytochemical ...

Toxicology of organic-inorganic hybrid molecules: bio-organometallics and its toxicology.

Science.gov (United States)

Fujie, Tomoya; Hara, Takato; Kaji, Toshiyuki

2016-01-01

Bio-organometallics is a research strategy of biology that uses organic-inorganic hybrid molecules. The molecules are expected to exhibit useful bioactivities based on the unique structure formed by interaction between the organic structure and intramolecular metal(s). However, studies on both biology and toxicology of organic-inorganic hybrid molecules have been incompletely performed. There can be two types of toxicological studies of bio-organometallics; one is evaluation of organic-inorganic hybrid molecules and the other is analysis of biological systems from the viewpoint of toxicology using organic-inorganic hybrid molecules. Our recent studies indicate that cytotoxicity of hybrid molecules containing a metal that is nontoxic in inorganic forms can be more toxic than that of hybrid molecules containing a metal that is toxic in inorganic forms when the structure of the ligand is the same. Additionally, it was revealed that organic-inorganic hybrid molecules are useful for analysis of biological systems important for understanding the toxicity of chemical compounds including heavy metals.

Using Toxicological Evidence from QSAR Models in Practice

Science.gov (United States)

The new generation of QSAR models provides supporting documentation in addition to the predicted toxicological value. Such information enables the toxicologist to explore the properties of chemical substances and to review and increase the reliability of toxicity predictions. Thi...

Toxicology elements

International Nuclear Information System (INIS)

Viala, A.

1998-01-01

This work studies the different aspects of the modern toxicology: toxico-kinetic, biological, medico legal, food, professional, pharmaceuticals, environmental, social and regulatory. It is divided in three parts that consider the principle problems of general toxicology and analytical toxicology. (N.C.)

Multiscale Toxicology - Building the Next Generation Tools for Toxicology

Energy Technology Data Exchange (ETDEWEB)

Thrall, Brian D.; Minard, Kevin R.; Teeguarden, Justin G.; Waters, Katrina M.

2012-09-01

A Cooperative Research and Development Agreement (CRADA) was sponsored by Battelle Memorial Institute (Battelle, Columbus), to initiate a collaborative research program across multiple Department of Energy (DOE) National Laboratories aimed at developing a suite of new capabilities for predictive toxicology. Predicting the potential toxicity of emerging classes of engineered nanomaterials was chosen as one of two focusing problems for this program. PNNL’s focus toward this broader goal was to refine and apply experimental and computational tools needed to provide quantitative understanding of nanoparticle dosimetry for in vitro cell culture systems, which is necessary for comparative risk estimates for different nanomaterials or biological systems. Research conducted using lung epithelial and macrophage cell models successfully adapted magnetic particle detection and fluorescent microscopy technologies to quantify uptake of various forms of engineered nanoparticles, and provided experimental constraints and test datasets for benchmark comparison against results obtained using an in vitro computational dosimetry model, termed the ISSD model. The experimental and computational approaches developed were used to demonstrate how cell dosimetry is applied to aid in interpretation of genomic studies of nanoparticle-mediated biological responses in model cell culture systems. The combined experimental and theoretical approach provides a highly quantitative framework for evaluating relationships between biocompatibility of nanoparticles and their physical form in a controlled manner.

Pharmacological and toxicological evaluation of Urtica dioica.

Science.gov (United States)

Dar, Sabzar Ahmad; Ganai, Farooq Ahmad; Yousuf, Abdul Rehman; Balkhi, Masood-Ul-Hassan; Bhat, Towseef Mohsin; Sharma, Poonam

2013-02-01

Medicinal plants are a largely unexplored source of drug repository. Urtica dioica L. (Urticaceae) is used in traditional medicine to treat diverse conditions. The present study describes the antidiabetic, antiinflammatory, antibacterial activity, and toxicological studies of Urtica dioica. U. dioica leaves were subjected to solvent extraction with hexane, chloroform, ethyl acetate, methanol, and aqueous, respectively, and screened for antidiabetic (300 mg/kg bw by glucose tolerance test; GTT), antiinflammatory (200 mg/kg bw by rat paw edema assay) and antibacterial activities [by disc-diffusion and minimum inhibitory concentration (MIC) assays]. Toxicological studies were carried on Artemia salina and Wistar rats; phytochemical analyses were carried out, using chromatographic and spectroscopic techniques. The aqueous extract of U. dioica (AEUD) significantly (p 1000 μg/mL each on A. salina. Our results showed that the U. dioica leaves are an interesting source of bioactive compounds, justifying their use in folk medicine, to treat various diseases.

Forensic toxicology.

Science.gov (United States)

Davis, Gregory G

2012-01-01

Toxicologic analysis is an integral part of death investigation, and the use or abuse of an unsuspected substance belongs in the differential diagnosis of patients who have a sudden, unexpected change in their condition. History and physical findings may alter suspicion that intoxication played a role in a patient's decline or death, but suspicions cannot be confirmed and is performed, analysis unless toxicologic no toxicologic analysis is possible unless someone collects the proper specimens necessary for analysis. In a hospital autopsy the only specimens that can rightfully be collected are those within the restrictions stated in the autopsy permit. Autopsies performed by the medical examiner do not have these restrictions. Sometimes the importance of toxicologic testing in a case is not evident until days or weeks after the change in the patient's status, thus retaining the appropriate specimens until investigation of that case has ended is important. Proper interpretation of toxicologic findings requires integrating the clinical setting and findings with the toxicologic results in a way that makes medical sense. If called upon to testify concerning findings, answer the questions truthfully, politely, and in a way that is understandable to someone who has no special training in toxicology.

A comprehensive toxicological evaluation of three adhesives using experimental cigarettes.

Science.gov (United States)

Coggins, Christopher R E; Jerome, Ann M; Lilly, Patrick D; McKinney, Willie J; Oldham, Michael J

2013-01-01

Adhesives are used in several different manufacturing operations in the production of cigarettes. The use of new, "high-speed-manufacture" adhesives (e.g. vinyl acetate based) could affect the smoke chemistry and toxicology of cigarettes, compared with older "low-speed-manufacture" adhesives (e.g. starch based). This study was conducted to determine whether the inclusion of different levels of three adhesives (ethylene vinyl acetate, polyvinyl acetate and starch) in experimental cigarettes results in different smoke chemistry and toxicological responses in in vitro and in vivo assays. A battery of tests (analytical chemistry, in vitro and in vivo assays) was used to compare the chemistry and toxicology of smoke from experimental cigarettes made with different combinations of the three adhesives. Varying levels of the different side-seam adhesives, as well as the transfer of adhesives from packaging materials, were tested. There were differences in some mainstream cigarette smoke constituents as a function of the level of adhesive added to experimental cigarettes and between the tested adhesives. None of these differences translated into statistically significant differences in the in vitro or in vivo assays. The use of newer "high-speed-manufacture" vinyl acetate-based adhesives in cigarettes does not produce toxicological profiles that prevent the adhesives from replacing the older "low-speed-manufacture" adhesives (such as starch).

Cornerstones of Toxicology.

Science.gov (United States)

Hayes, A Wallace; Dixon, Darlene

2017-01-01

The 35th Annual Society of Toxicologic Pathology Symposium, held in June 2016 in San Diego, California, focused on "The Basis and Relevance of Variation in Toxicologic Responses." In order to review the basic tenants of toxicology, a "broad brush" interactive talk that gave an overview of the Cornerstones of Toxicology was presented. The presentation focused on the historical milestones and perspectives of toxicology and through many scientific graphs, data, and real-life examples covered the three basic principles of toxicology that can be summarized, as dose matters (as does timing), people differ, and things change (related to metabolism and biotransformation).

Pre implanted mouse embryos as model for uranium toxicology studies

International Nuclear Information System (INIS)

Kundt, Miriam S.

2001-01-01

Full text: The search of 'in vitro' toxicology model that can predict toxicology effects 'in vivo' is a permanent challenge. A toxicology experimental model must to fill to certain requirements: to have a predictive character, an appropriate control to facilitate the interpretation of the data among the experimental groups, and to be able to control the independent variables that can interfere or modify the results that we are analyzing. The preimplantation embryos posses many advantages in this respect: they are a simple model that begins with the development of only one cell. The 'in vitro' model reproduces successfully the 'in vivo' situation. Due to the similarity that exists among the embryos of mammals during this period the model is practically valid for other species. The embryo is itself a stem cell, the toxicology effects are early observed in his clonal development and the physical-chemical parameters are easily controllable. The purpose of the exhibition is to explain the properties of the pre implanted embryo model for toxicology studies of uranium and to show our experimental results. The cultivation 'in vitro' of mouse embryos with uranylo nitrate demonstrated that the uranium causes from the 13 μgU/ml delay of development, decrease the number of cells per embryo and hipoploidy in the embryonic blastomere. (author)

The Toxicology Education Summit: building the future of toxicology through education.

Science.gov (United States)

Barchowsky, Aaron; Buckley, Lorrene A; Carlson, Gary P; Fitsanakis, Vanessa A; Ford, Sue M; Genter, Mary Beth; Germolec, Dori R; Leavens, Teresa L; Lehman-McKeeman, Lois D; Safe, Stephen H; Sulentic, Courtney E W; Eidemiller, Betty J

2012-06-01

Toxicology and careers in toxicology, as well as many other scientific disciplines, are undergoing rapid and dramatic changes as new discoveries, technologies, and hazards advance at a blinding rate. There are new and ever increasing demands on toxicologists to keep pace with expanding global economies, highly fluid policy debates, and increasingly complex global threats to public health. These demands must be met with new paradigms for multidisciplinary, technologically complex, and collaborative approaches that require advanced and continuing education in toxicology and associated disciplines. This requires paradigm shifts in educational programs that support recruitment, development, and training of the modern toxicologist, as well as continued education and retraining of the midcareer professional to keep pace and sustain careers in industry, government, and academia. The Society of Toxicology convened the Toxicology Educational Summit to discuss the state of toxicology education and to strategically address educational needs and the sustained advancement of toxicology as a profession. The Summit focused on core issues of: building for the future of toxicology through educational programs; defining education and training needs; developing the "Total Toxicologist"; continued training and retraining toxicologists to sustain their careers; and, finally, supporting toxicology education and professional development. This report summarizes the outcomes of the Summit, presents examples of successful programs that advance toxicology education, and concludes with strategies that will insure the future of toxicology through advanced educational initiatives.

Toxicological evaluation in silico and in vivo of secondary metabolites of Cissampelos sympodialis in Mus musculus mice following inhalation.

Science.gov (United States)

Alves, Mateus Feitosa; Ferreira, Larissa Adilis Maria Paiva; Gadelha, Francisco Allysson Assis Ferreira; Ferreira, Laércia Karla Diega Paiva; Felix, Mayara Barbalho; Scotti, Marcus Tullius; Scotti, Luciana; de Oliveira, Kardilândia Mendes; Dos Santos, Sócrates Golzio; Diniz, Margareth de Fátima Formiga Melo

2017-12-04

The ethanolic extract of the leaves of Cissampelos sympodialis showed great pharmacological potential, with inflammatory and immunomodulatory activities, however, it showed some toxicological effects. Therefore, this study aims to verify the toxicological potential of alkaloids of the genus Cissampelos through in silico methodologies, to develop a method in LC-MS/MS verifying the presence of alkaloids in the infusion and to evaluate the toxicity of the infusion of the leaves of C. sympodialis when inhaled by Swiss mice. Results in silico showed that alkaloid 93 presented high toxicological potential along with the products of its metabolism. LC-MS/MS results showed that the infusion of the leaves of this plant contained the alkaloids warifteine and methylwarifteine. Finally, the in vivo toxicological analysis of the C. sympodialis infusion showed results, both in biochemistry, organ weights and histological analysis, that the infusion of C. sympodialis leaves presents a low toxicity.

TOXICOLOGICAL EVALUATION OF REALISTIC EMISSIONS OF SOURCE AEROSOLS (TERESA): APPLICATION TO POWER PLANT-DERIVED PM2.5

Energy Technology Data Exchange (ETDEWEB)

Annette Rohr

2006-03-01

TERESA (Toxicological Evaluation of Realistic Emissions of Source Aerosols) involves exposing laboratory rats to realistic coal-fired power plant and mobile source emissions to help determine the relative toxicity of these PM sources. There are three coal-fired power plants in the TERESA program; this report describes the results of fieldwork conducted at the first plant, located in the Upper Midwest. The project was technically challenging by virtue of its novel design and requirement for the development of new techniques. By examining aged, atmospherically transformed aerosol derived from power plant stack emissions, we were able to evaluate the toxicity of PM derived from coal combustion in a manner that more accurately reflects the exposure of concern than existing methodologies. TERESA also involves assessment of actual plant emissions in a field setting--an important strength since it reduces the question of representativeness of emissions. A sampling system was developed and assembled to draw emissions from the stack; stack sampling conducted according to standard EPA protocol suggested that the sampled emissions are representative of those exiting the stack into the atmosphere. Two mobile laboratories were then outfitted for the study: (1) a chemical laboratory in which the atmospheric aging was conducted and which housed the bulk of the analytical equipment; and (2) a toxicological laboratory, which contained animal caging and the exposure apparatus. Animal exposures were carried out from May-November 2004 to a number of simulated atmospheric scenarios. Toxicological endpoints included (1) pulmonary function and breathing pattern; (2) bronchoalveolar lavage fluid cytological and biochemical analyses; (3) blood cytological analyses; (4) in vivo oxidative stress in heart and lung tissue; and (5) heart and lung histopathology. Results indicated no differences between exposed and control animals in any of the endpoints examined. Exposure concentrations for the

A comprehensive evaluation of the toxicology of experimental cigarettes manufactured with banded papers.

Science.gov (United States)

Werley, Michael S; Jerome, Ann M; DeSoi, Darren J; Coggins, Christopher R E; Oldham, Michael J; McKinney, Willie J

2013-01-01

To comply with state requirements, cigarette manufacturers have added low-permeability bands to the cigarette paper. These bands can extinguish the cigarette when it is no longer being puffed by a smoker. This study was conducted to evaluate the toxicology resulting from the addition of different types of bands to experimental cigarettes. A battery of assays that are typically used in toxicology studies with cigarette smoke, namely smoke chemistry, in vitro mutagenicity and cytotoxicity, and inhalation studies with rats, were used to evaluate different band characteristics added to cigarette paper. Although differences in the amount of band material was associated with an increase in some metals measured in mainstream tobacco smoke, it was not dose responsive to any band design parameter (base paper permeability, band width, band spacing, band chalk amount, or citrate). Occasional, minor differences were produced by the different types of bands; overall, there was no increased toxicity. Although there were increases and decreases in some mainstream smoke constituents, the in vitro and in vivo testing performed demonstrated that low-permeability bands on cigarettes do not modify the toxicity of smoke inhaled by smokers.

Prospects for applying synthetic biology to toxicology

DEFF Research Database (Denmark)

Behrendorff, James Bruce Yarnton H; Gillam, Elizabeth M.J.

2017-01-01

The 30 years since the inception of Chemical Research in Toxicology, game-changing advances in chemical and molecular biology, the fundamental disciplines underpinning molecular toxicology, have been made. While these have led to important advances in the study of mechanisms by which chemicals...... damage cells and systems, there has been less focus on applying these advances to prediction, detection, and mitigation of toxicity. Over the last ∼15 years, synthetic biology, the repurposing of biological "parts" in systems engineered for useful ends, has been explored in other areas of the biomedical...... and life sciences, for such applications as detecting metabolites, drug discovery and delivery, investigating disease mechanisms, improving medical treatment, and producing useful chemicals. These examples provide models for the application of synthetic biology to toxicology, which, for the most part, has...

77 FR 22321 - National Toxicology Program (NTP) Interagency Center for the Evaluation of Alternative...

Science.gov (United States)

2012-04-13

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Toxicology Program (NTP) Interagency Center for... (HTS) Assays for the Tox21 Initiative AGENCY: Division of the National Toxicology Program (DNTP...: April 5, 2012. John R. Bucher, Associate Director, National Toxicology Program. [FR Doc. 2012-8942 Filed...

Revisiting EOR Projects in Indonesia through Integrated Study: EOR Screening, Predictive Model, and Optimisation

KAUST Repository

Hartono, A. D.; Hakiki, Farizal; Syihab, Z.; Ambia, F.; Yasutra, A.; Sutopo, S.; Efendi, M.; Sitompul, V.; Primasari, I.; Apriandi, R.

2017-01-01

EOR preliminary analysis is pivotal to be performed at early stage of assessment in order to elucidate EOR feasibility. This study proposes an in-depth analysis toolkit for EOR preliminary evaluation. The toolkit incorporates EOR screening, predictive, economic, risk analysis and optimisation modules. The screening module introduces algorithms which assimilates statistical and engineering notions into consideration. The United States Department of Energy (U.S. DOE) predictive models were implemented in the predictive module. The economic module is available to assess project attractiveness, while Monte Carlo Simulation is applied to quantify risk and uncertainty of the evaluated project. Optimization scenario of EOR practice can be evaluated using the optimisation module, in which stochastic methods of Genetic Algorithms (GA), Particle Swarm Optimization (PSO) and Evolutionary Strategy (ES) were applied in the algorithms. The modules were combined into an integrated package of EOR preliminary assessment. Finally, we utilised the toolkit to evaluate several Indonesian oil fields for EOR evaluation (past projects) and feasibility (future projects). The attempt was able to update the previous consideration regarding EOR attractiveness and open new opportunity for EOR implementation in Indonesia.

Revisiting EOR Projects in Indonesia through Integrated Study: EOR Screening, Predictive Model, and Optimisation

KAUST Repository

Hartono, A. D.

2017-10-17

EOR preliminary analysis is pivotal to be performed at early stage of assessment in order to elucidate EOR feasibility. This study proposes an in-depth analysis toolkit for EOR preliminary evaluation. The toolkit incorporates EOR screening, predictive, economic, risk analysis and optimisation modules. The screening module introduces algorithms which assimilates statistical and engineering notions into consideration. The United States Department of Energy (U.S. DOE) predictive models were implemented in the predictive module. The economic module is available to assess project attractiveness, while Monte Carlo Simulation is applied to quantify risk and uncertainty of the evaluated project. Optimization scenario of EOR practice can be evaluated using the optimisation module, in which stochastic methods of Genetic Algorithms (GA), Particle Swarm Optimization (PSO) and Evolutionary Strategy (ES) were applied in the algorithms. The modules were combined into an integrated package of EOR preliminary assessment. Finally, we utilised the toolkit to evaluate several Indonesian oil fields for EOR evaluation (past projects) and feasibility (future projects). The attempt was able to update the previous consideration regarding EOR attractiveness and open new opportunity for EOR implementation in Indonesia.

Evaluación toxicológica de residuos orgánicos Toxicological evaluation of organic residues

Directory of Open Access Journals (Sweden)

Eduardo de la Peña de Torres

2005-12-01

the use of its results for the human and environmental risk assessment. This evaluation consists, in short, of the identification of dangers, evaluation of dose-response ratio, evaluation of exposure and risk characterization, resulting in the analysis, use and communication of this risk. It is emphasized the high predictive value for carcinogenicity of some of these bioassays.It is shown the utility of short term assays for the evaluation of substances, products and complex mixtures, which would contribute to improve the toxicological knowledge of a greater number substances. This is a vital need in the EU, due to the lack of complete toxicological information of about the 70% of the 106.000 existing and used substances.It is emphasized the great value that mutagenicity assays represent inside the toxicological tests in the basic level, which are used in the evaluation of new and existing substances. It also helps to improve the knowledge about substances with incomplete toxicological data. Another aspect to consider about these methods is that they represent an alternative to animal experimentation, carrying out one of the basic requirements that the EU establishes in the new policy about substances, which is known as REACH, the acronym of record, evaluation and authorization of chemical substances. This policy is a basic part of the European strategy on environment and health (SCALE.

ICPP radiological and toxicological sabotage analysis

International Nuclear Information System (INIS)

Kubiak, V.R.; Mortensen, F.G.

1995-01-01

In June of 1993, the Department of Energy (DOE) issued Notice 5630.3A, open-quotes Protection of Departmental Facilities Against Radiological and Toxicological Sabotage,close quotes which states that all significant radiological and toxicological hazards at Department facilities must be examined for potential sabotage. This analysis has been completed at the Idaho Chemical Processing Plant (ICPP). The ICPP radiological and toxicological hazards include spent government and commercial fuels, Special Nuclear Materials (SNM), high-level liquid wastes, high-level solid wastes, and process and decontamination chemicals. The analysis effort included identification and assessment of quantities of hazardous materials present at the facility; identification and ranking of hazardous material targets; development of worst case scenarios detailing possible sabotage actions and hazard releases; performance of vulnerability assessments using table top and computer methodologies on credible threat targets; evaluation of potential risks to the public, workers, and the environment; evaluation of sabotage risk reduction options; and selection of cost effective prevention and mitigation options

A Standardized Evaluation System for Decadal Climate Prediction

Science.gov (United States)

Kadow, C.; Cubasch, U.

2012-12-01

The evaluation of decadal prediction systems is a scientific challenge as well as a technical challenge in the climate research. The major project MiKlip (www.fona-miklip.de) for medium-term climate prediction funded by the Federal Ministry of Education and Research in Germany (BMBF) has the aim to create a model system that can provide reliable decadal forecasts on climate and weather. The model system to be developed will be novel in several aspects, with great challenges for the methodology development. This concerns especially the determination of the initial conditions, the inclusion into the model of processes relevant to decadal predictions, the increase of the spatial resolution through regionalisation, the improvement or adjustment of statistical post-processing, and finally the synthesis and validation of the entire model system. Therefore, a standardized evaluation system will be part of the MiKlip system to validate it - developed by the project 'Integrated data and evaluation system for decadal scale prediction' (INTEGRATION). The presentation gives an overview of the different linkages of such a project, shows the different development stages and gives an outlook for users and possible end users in climate service. The technical interface combines all projects inside of MiKlip and invites them to participate in a common evaluation system. The system design and the validation strategy from a standalone tool in the beginning to a user friendly web based system using GRID technologies to an integrated part of the operational MiKlip system for industry and society will give the opportunity to enhance the MiKlip strategy. First results of different possibilities of such a system will be shown to present the scientific background through Taylor diagrams, ensemble skill scores and e.g. climatological means to show the usability and possibilities of MiKlip and the INTEGRATION project.

Translational toxicology: a developmental focus for integrated research strategies.

Science.gov (United States)

Hughes, Claude; Waters, Michael; Allen, David; Obasanjo, Iyabo

2013-09-30

Given that toxicology studies the potential adverse effects of environmental exposures on various forms of life and that clinical toxicology typically focuses on human health effects, what can and should the relatively new term of "translational toxicology" be taken to mean? Our assertion is that the core concept of translational toxicology must incorporate existing principles of toxicology and epidemiology, but be driven by the aim of developing safe and effective interventions beyond simple reduction or avoidance of exposure to prevent, mitigate or reverse adverse human health effects of exposures.The field of toxicology has now reached a point where advances in multiple areas of biomedical research and information technologies empower us to make fundamental transitions in directly impacting human health. Translational toxicology must encompass four action elements as follows: 1) Assessing human exposures in critical windows across the lifespan; 2) Defining modes of action and relevance of data from animal models; 3) Use of mathematical models to develop plausible predictions as the basis for: 4) Protective and restorative human health interventions. The discussion focuses on the critical window of in-utero development. Exposure assessment, basic toxicology and development of certain categories of mathematical models are not new areas of research; however overtly integrating these in order to conceive, assess and validate effective interventions to mitigate or reverse adverse effects of environmental exposures is our novel opportunity. This is what we should do in translational toxicology so that we have a portfolio of interventional options to improve human health that include both minimizing exposures and specific preventative/restorative/mitigative therapeutics.

Genetic toxicology in the 21st century: Reflections and future ...

Science.gov (United States)

A symposium at the 40th anniversary of the Environmental Mutagen Society, held from October 24–28, 2009 in St. Louis, MO, surveyed the current status and future directions of genetic toxicology. This article summarizes the presentations and provides a perspective on the future. An abbreviated history is presented, highlighting the current standard battery of genotoxicity assays and persistent challenges. Application of computational toxicology to safety testing within a regulatory setting is discussed as a means for reducing the need for animal testing and human clinical trials, and current approaches and applications of in silico genotoxicity screening approaches across the pharmaceutical industry were surveyed and are reported here. The expanded use of toxicogenomics to illuminate mechanisms and bridge genotoxicity and carcinogenicity, and new public efforts to use high-throughput screening technologies to address lack of toxicity evaluation for the backlog of thousands of industrial chemicals in the environment are detailed. The Tox21 project involves coordinated efforts of four U.S. Government regulatory/research entities to use new and innovative assays to characterize key steps in toxicity pathways, including genotoxic and nongenotoxic mechanisms for carcinogenesis. Progress to date, highlighting preliminary test results from the National Toxicology Program is summarized. Finally, an overview is presented of ToxCast™, a related research program of the

Post-mortem toxicology in young sudden cardiac death victims

DEFF Research Database (Denmark)

Bjune, Thea; Risgaard, Bjarke; Kruckow, Line

2017-01-01

Aims: Several drugs increase the risk of ventricular fibrillation and sudden cardiac death (SCD). We aimed to investigate in detail the toxicological findings of all young SCD throughout Denmark. Methods and results: Deaths in persons aged 1-49 years were included over a 10-year period. Death...... certificates and autopsy reports were retrieved and read to identify cases of sudden death and establish cause of death. All medico-legal autopsied SCD were included and toxicological reports collected. Positive toxicology was defined as the presence of any substance (licit and/or illicit). All toxicological...... findings had previously been evaluated not to have caused the death (i.e. lethal concentrations were excluded). We identified 620 medico-legal autopsied cases of SCD, of which 77% (n = 477) were toxicologically investigated post-mortem, and 57% (n = 270) had a positive toxicology profile. Sudden cardiac...

IRIS Toxicological Review of Benzo[a]pyrene (Interagency ...

Science.gov (United States)

In January 2017, EPA finalized the IRIS assessment of Benzo[a]pyrene. The Toxicological Review was reviewed internally by EPA and by other federal agencies and White House Offices before public release. Consistent with the May 2009 IRIS assessment development process, all written comments on IRIS assessments submitted by other federal agencies and White House Offices are made publicly available. Accordingly, interagency comments and the interagency science discussion materials provided to other agencies, including interagency review drafts of the IRIS Toxicological Review of Benzo[a]pyrene are posted on this site. EPA is undertaking an update of the Integrated Risk Information System (IRIS) health assessment for benzo[a]pyrene (BaP). The outcome of this project is an updated Toxicological Review and IRIS Summary for BaP that will be entered into the IRIS database.

2007 TOXICOLOGY AND RISK ASSESSMENT ...

Science.gov (United States)

EPA has announced The 2007 Toxicology and Risk Assessment Conference Cincinnati Marriott North, West Chester (Cincinnati), OHApril 23- 26, 2007 - Click to register!The Annual Toxicology and Risk Assessment Conference is a unique meeting where several Government Agencies come together to discuss toxicology and risk assessment issues that are not only of concern to the government, but also to a broader audience including academia and industry. The theme of this year's conference is Emerging Issues and Challenges in Risk Assessment and the preliminary agenda includes: Plenary Sessions and prominent speakers (tentative) include: Issues of Emerging Chemical ContaminantsUncertainty and Variability in Risk Assessment Use of Mechanistic data in IARC evaluationsParallel Sessions:Uncertainty and Variability in Dose-Response Assessment Recent Advances in Toxicity and Risk Assessment of RDX The Use of Epidemiologic Data for Risk Assessment Applications Cumulative Health Risk Assessment:

The impact of composite AUC estimates on the prediction of systemic exposure in toxicology experiments.

Science.gov (United States)

Sahota, Tarjinder; Danhof, Meindert; Della Pasqua, Oscar

2015-06-01

Current toxicity protocols relate measures of systemic exposure (i.e. AUC, Cmax) as obtained by non-compartmental analysis to observed toxicity. A complicating factor in this practice is the potential bias in the estimates defining safe drug exposure. Moreover, it prevents the assessment of variability. The objective of the current investigation was therefore (a) to demonstrate the feasibility of applying nonlinear mixed effects modelling for the evaluation of toxicokinetics and (b) to assess the bias and accuracy in summary measures of systemic exposure for each method. Here, simulation scenarios were evaluated, which mimic toxicology protocols in rodents. To ensure differences in pharmacokinetic properties are accounted for, hypothetical drugs with varying disposition properties were considered. Data analysis was performed using non-compartmental methods and nonlinear mixed effects modelling. Exposure levels were expressed as area under the concentration versus time curve (AUC), peak concentrations (Cmax) and time above a predefined threshold (TAT). Results were then compared with the reference values to assess the bias and precision of parameter estimates. Higher accuracy and precision were observed for model-based estimates (i.e. AUC, Cmax and TAT), irrespective of group or treatment duration, as compared with non-compartmental analysis. Despite the focus of guidelines on establishing safety thresholds for the evaluation of new molecules in humans, current methods neglect uncertainty, lack of precision and bias in parameter estimates. The use of nonlinear mixed effects modelling for the analysis of toxicokinetics provides insight into variability and should be considered for predicting safe exposure in humans.

Assessing the scientific research productivity of a leading toxicology journal: A case study of Human & Experimental Toxicology from 2003 to 2012.

Science.gov (United States)

Zyoud, Sa'ed H; Al-Jabi, Samah W; Sweileh, Waleed M; Awang, Rahmat

2014-01-01

Bibliometric studies are increasingly being used for research assessments. Bibliometric indicators involve the application of statistical methods to scientific publications to obtain the bibliographics for each journal. The main objective of this study was to conduct a bibliometric evaluation of Human & Experimental Toxicology retrieved from the Scopus database. This study obtained data from Scopus published from 1 January 2003 till 31 December 2012. The keywords entered in Scopus to accomplish the objective of this study were 'Human', 'Experimental' and 'Toxicology' as 'Source Title'. Research productivity was evaluated based on a methodology developed and used in other bibliometric studies by analysing (a) total and trends in Human & Experimental Toxicology contributions in research between 2003 and 2012; (b) Human & Experimental Toxicology authorship patterns and productivity; (c) collaboration patterns; and (d) the citations received by the publications. There were 1229 research articles published in Human & Experimental Toxicology. Of the articles included, 947 (77.1%) were original articles and 104 (8.5%) were review articles. The Hirsch-index of the retrieved documents was 35. The largest number of publications in Human & Experimental Toxicology was from the United States (19.6%), followed by India (12.8%) and Turkey (10.9%). The total number of citations was 9119, with a median (interquartile range) of 3 (1-9) in 6797 documents. The highest median (interquartile range) number of citations was 8 (2.7-12.7) for France, followed by 7.5 (2-22.5) for Iran and 6 (3-13.5) for the United Kingdom. The country most often citing articles that were published in Human & Experimental Toxicology was the United States, which made citations in 1508 documents, followed by India with citations in 792 documents. The documents in Human & Experimental Toxicology focus principally on original data, with very few review articles. Review articles tend to have higher citation rates

Standardizing the performance evaluation of short-term wind prediction models

DEFF Research Database (Denmark)

Madsen, Henrik; Pinson, Pierre; Kariniotakis, G.

2005-01-01

Short-term wind power prediction is a primary requirement for efficient large-scale integration of wind generation in power systems and electricity markets. The choice of an appropriate prediction model among the numerous available models is not trivial, and has to be based on an objective...... evaluation of model performance. This paper proposes a standardized protocol for the evaluation of short-term wind-poser preciction systems. A number of reference prediction models are also described, and their use for performance comparison is analysed. The use of the protocol is demonstrated using results...... from both on-shore and off-shore wind forms. The work was developed in the frame of the Anemos project (EU R&D project) where the protocol has been used to evaluate more than 10 prediction systems....

[Research advances in eco-toxicological diagnosis of soil pollution].

Science.gov (United States)

Liu, Feng; Teng, Hong-Hui; Ren, Bai-Xiang; Shi, Shu-Yun

2014-09-01

Soil eco-toxicology provides a theoretical basis for ecological risk assessment of contaminated soils and soil pollution control. Research on eco-toxicological effects and molecular mechanisms of toxic substances in soil environment is the central content of the soil eco-toxicology. Eco-toxicological diagnosis not only gathers all the information of soil pollution, but also provides the overall toxic effects of soil. Therefore, research on the eco-toxicological diagnosis of soil pollution has important theoretical and practical significance. Based on the research of eco-toxicological diagnosis of soil pollution, this paper introduced some common toxicological methods and indicators, with the advantages and disadvantages of various methods discussed. However, conventional biomarkers can only indicate the class of stress, but fail to explain the molecular mechanism of damage or response happened. Biomarkers and molecular diagnostic techniques, which are used to evaluate toxicity of contaminated soil, can explore deeply detoxification mechanisms of organisms under exogenous stress. In this paper, these biomarkers and techniques were introduced systematically, and the future research trends were prospected.

Toxicological evaluation of a novel umami flavour compound: 2-(((3-(2,3-Dimethoxyphenyl-1H-1,2,4-triazol-5-ylthiomethylpyridine

Directory of Open Access Journals (Sweden)

Donald S. Karanewsky

Full Text Available A toxicological evaluation of a umami flavour compound, 2-(((3-(2,3-dimethoxyphenyl-1H-1,2,4-triazol-5-ylthiomethylpyridine (S3643; CAS 902136-79-2, was completed for the purpose of assessing its safety for use in food and beverage applications. S3643 undergoes extensive oxidative metabolism in vitro with rat microsomes producing the S3643-sulfoxide and 4′-hydroxy-S3643 as the major metabolites. In incubations with human microsomes, the O-demethyl-S3643 and S3643-sulfoxide were produced as the major metabolites. In pharmacokinetic studies in rats, the S3643-sulfoxide represents the dominant biotransformation product. S3643 was not found to be mutagenic or clastogenic in vitro, and did not induce micronuclei in CHO-WBL cells. In subchronic oral toxicity studies in rats, the no-observed-adverse-effect-level (NOAEL for S3643 was 100 mg/kg bw/day (highest dose tested when administered in the diet for 90 consecutive days. Keywords: Umami flavour, S3643, FEMA GRAS, Subchronic toxicological evaluation, Genetic toxicological evaluation

Application of Model Animals in the Study of Drug Toxicology

Science.gov (United States)

Song, Yagang; Miao, Mingsan

2018-01-01

Drug safety is a key factor in drug research and development, Drug toxicology test is the main method to evaluate the safety of drugs, The body condition of an animal has important implications for the results of the study, Previous toxicological studies of drugs were carried out in normal animals in the past, There is a great deviation from the clinical practice.The purpose of this study is to investigate the necessity of model animals as a substitute for normal animals for toxicological studies, It is expected to provide exact guidance for future drug safety evaluation.

EKORISK project - an information system for prediction and expert evaluation of environmental impact

International Nuclear Information System (INIS)

Zaimov, V.; Antonov, A.

1993-01-01

The aim of this project is to create an expert system for prediction, evaluation and decision making support in case of accidents. The system consists of the following modules: 1) A data base containing information about the situation - geographical and demographical data for the region of the accident as well as data about the contaminants. The data about geographic objects (boundaries, rivers, roads, towns, soils, etc.) is managed and visualized by a geographic information system (GIS), which produces multi-layer geographical maps, showing different viewpoints of the region of interest. Information about the pollutants, their use and storage, as well as data about the available resources for action in case of accidents, are stored in relational data bases which guarantee easy access, search, sorting and proper visualisation. 2) Predicting the propagation of contamination by using actual meteorological information and applying mathematical models for propagation of the spilled substances in the air, water and ground. They calculate the concentration of the substance as a function of time and distance from the initial spill location. The choice of the proper model is made by applying expert knowledge for evaluation of situation and comparing the model characteristics. 3) Suggesting actions for minimising the accident's impact. Expert knowledge is used for recommendations concerning deactivating of the region as well as actions for reducing the absorbed radiation doses of population. The modern technologies for knowledge processing and the object-oriented approach ensure flexibility and integration of all subsystems. (author)

Toxicology screen

Science.gov (United States)

... this page: //medlineplus.gov/ency/article/003578.htm Toxicology screen To use the sharing features on this page, please enable JavaScript. A toxicology screen refers to various tests that determine the ...

ECLogger: Cross-Project Catch-Block Logging Prediction Using Ensemble of Classifiers

Directory of Open Access Journals (Sweden)

Sangeeta Lal

2017-01-01

Full Text Available Background: Software developers insert log statements in the source code to record program execution information. However, optimizing the number of log statements in the source code is challenging. Machine learning based within-project logging prediction tools, proposed in previous studies, may not be suitable for new or small software projects. For such software projects, we can use cross-project logging prediction. Aim: The aim of the study presented here is to investigate cross-project logging prediction methods and techniques. Method: The proposed method is ECLogger, which is a novel, ensemble-based, cross-project, catch-block logging prediction model. In the research We use 9 base classifiers were used and combined using ensemble techniques. The performance of ECLogger was evaluated on on three open-source Java projects: Tomcat, CloudStack and Hadoop. Results: ECLogger Bagging, ECLogger AverageVote, and ECLogger MajorityVote show a considerable improvement in the average Logged F-measure (LF on 3, 5, and 4 source -> target project pairs, respectively, compared to the baseline classifiers. ECLogger AverageVote performs best and shows improvements of 3.12% (average LF and 6.08% (average ACC – Accuracy. Conclusion: The classifier based on ensemble techniques, such as bagging, average vote, and majority vote outperforms the baseline classifier. Overall, the ECLogger AverageVote model performs best. The results show that the CloudStack project is more generalizable than the other projects.

An Integrated Chemical Environment to Support 21st-Century Toxicology.

Science.gov (United States)

Bell, Shannon M; Phillips, Jason; Sedykh, Alexander; Tandon, Arpit; Sprankle, Catherine; Morefield, Stephen Q; Shapiro, Andy; Allen, David; Shah, Ruchir; Maull, Elizabeth A; Casey, Warren M; Kleinstreuer, Nicole C

2017-05-25

SUMMARY : Access to high-quality reference data is essential for the development, validation, and implementation of in vitro and in silico approaches that reduce and replace the use of animals in toxicity testing. Currently, these data must often be pooled from a variety of disparate sources to efficiently link a set of assay responses and model predictions to an outcome or hazard classification. To provide a central access point for these purposes, the National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods developed the Integrated Chemical Environment (ICE) web resource. The ICE data integrator allows users to retrieve and combine data sets and to develop hypotheses through data exploration. Open-source computational workflows and models will be available for download and application to local data. ICE currently includes curated in vivo test data, reference chemical information, in vitro assay data (including Tox21 TM /ToxCast™ high-throughput screening data), and in silico model predictions. Users can query these data collections focusing on end points of interest such as acute systemic toxicity, endocrine disruption, skin sensitization, and many others. ICE is publicly accessible at https://ice.ntp.niehs.nih.gov. https://doi.org/10.1289/EHP1759.

[Toxicological evaluation in the childhood].

Science.gov (United States)

Arroyo, Amparo; Rodrigo, Carlos; Marrón, M Teresa

2014-03-01

Intoxications in infancy require urgent medical treatment within national health systems. In our country they represent 0.3% of paediatric urgencies. Most of them are accidental intoxications but is not infrequent to find some related to child abuse or to suicidal intentions, especially in adolescence. The objectives of the study are to evaluate both clinical health care and medical legal aspects in intoxications in infancy. Medical assistance is described and it includes clinical diagnosis, typology of the more common toxics, percentages and referral to social work and emergency care equipment units of the Ministry of Social Welfare and the Department of Health or, where appropriate, directly to prosecutors and courts for their intervention. In cases of detection of alcohol, drugs or medication in infants, the importance of the correct interpretation of the results of toxicological findings is discussed. Several studies for the interpretation of results concerning the detection of these toxics are reported. Both legal aspects and the forensic medical opinion are assessed. The findings will be analysed by the judicial authority in order to circumscribe responsibilities or to take appropriate decisions concerning the protection of infants' interests. In conclusion intoxication in infancy can lead to legal proceedings requiring specific actions for their protection. Both physicians and hospitals must comply with the legal requirement of the submission to the court of judicial parties. On the other hand, this information is an interesting step toward reinforcing public health surveillance. Copyright © 2014 Elsevier España, S.L. All rights reserved.

Natural uranium toxicology - evaluation of internal contamination in man

International Nuclear Information System (INIS)

Chalabreysse, J.

1968-01-01

After reminding the physical and chemical properties of natural uranium which might affect its toxicology, a comprehensive investigation upon natural uranium metabolism and toxicity and after applying occupational exposure standards to this particular poison, it has been determined, from accident reports and human experience reported in the related literature, a series of formulae obtained by theoretical mathematical development giving principles for internal contamination monitoring and disclosure by determining uranium in the urine of occupationally exposed individuals. An assay is performed to determine individual internal contamination according to the various contamination cases. The outlined purposes, mainly practical, required some options and extrapolations. The proposed formula allows a preliminary approach and also to determine shortly a contamination extent or to discuss the systematical urinalysis results as compared with individual radio-toxicology monitoring professional standards. (author) [fr

University Clinic of Toxicology--historical note and present work.

Science.gov (United States)

Bozinovska, C

2013-01-01

The University Clinic of Toxicology (UCT) in Skopje was founded as the Clinic for Toxicology and Emergency Internal Medicine on January 15th 1976. Today UCT has a modern building with office space of 1,300 m2 on 4 floors, 40 hospital beds and 72 employees including 18 doctors. UCT works in accordance with the public healthcare services in the Republic of Macedonia through the use of specialist/consultative and hospital healthcare for people over the age of 14 years. The Clinic also provides services in the field of emergency internal medicine, acute poisoning with medications, pesticides, corrosives, poisonous gases and mushrooms, heavy metals and other chemicals. The Clinic takes an active part in the detoxification programme for users of opiates and psychotropic substances, protocols for enteral and parenteral nutrition and guides for home treatment. Yearly there are more than 14,000 ambulance admissions, over 1,400 hospitalized patients, over 4,000 urgent EHO checks, more than 1,000 urgent upper endoscopies and over 700 other toxicological analyses and other interventions. The educational services and activities are realized through the chair for internal medicine. The Clinic offers undergraduate and graduate level education for medical students and dentists, for medical nurses, radiology technicians, speech therapists and physiotherapists. Over 300 papers and reports have been published to date by the medical staff at the UCT in the form of abstracts and integrated projects in the Republic of Macedonia and aboard. 8 doctorates have been successfully completed by employees from the Clinic as well as 4 master's theses and 1 in-depth project. UCT employees are the authors of some textbooks and monographs. UCT have undertaken some scientific projects. Employees from the Clinic of Toxicology are members taking an active part in many domestic and international associations.

Chick embryo chorioallantoic membrane (CAM): an alternative predictive model in acute toxicological studies for anti-cancer drugs.

Science.gov (United States)

Kue, Chin Siang; Tan, Kae Yi; Lam, May Lynn; Lee, Hong Boon

2015-01-01

The chick embryo chorioallantoic membrane (CAM) is a preclinical model widely used for vascular and anti-vascular effects of therapeutic agents in vivo. In this study, we examine the suitability of CAM as a predictive model for acute toxicology studies of drugs by comparing it to conventional mouse and rat models for 10 FDA-approved anticancer drugs (paclitaxel, carmustine, camptothecin, cyclophosphamide, vincristine, cisplatin, aloin, mitomycin C, actinomycin-D, melphalan). Suitable formulations for intravenous administration were determined before the average of median lethal dose (LD50) and median survival dose (SD(50)) in the CAM were measured and calculated for these drugs. The resultant ideal LD(50) values were correlated to those reported in the literature using Pearson's correlation test for both intravenous and intraperitoneal routes of injection in rodents. Our results showed moderate correlations (r(2)=0.42 - 0.68, PLD(50) values obtained using the CAM model with LD(50) values from mice and rats models for both intravenous and intraperitoneal administrations, suggesting that the chick embryo may be a suitable alternative model for acute drug toxicity screening before embarking on full toxicological investigations in rodents in development of anticancer drugs.

Forensic Toxicology: An Introduction.

Science.gov (United States)

Smith, Michael P; Bluth, Martin H

2016-12-01

This article presents an overview of forensic toxicology. The authors describe the three components that make up forensic toxicology: workplace drug testing, postmortem toxicology, and human performance toxicology. Also discussed are the specimens that are tested, the methods used, and how the results are interpreted in this particular discipline. Copyright © 2016 Elsevier Inc. All rights reserved.

CERAPP: Collaborative Estrogen Receptor Activity Prediction Project

Data.gov (United States)

U.S. Environmental Protection Agency — Data from a large-scale modeling project called CERAPP (Collaborative Estrogen Receptor Activity Prediction Project) demonstrating using predictive computational...

Genetic Toxicology in the 21st Century: Reflections and Future Directions

Science.gov (United States)

Mahadevan, Brinda; Snyder, Ronald D.; Waters, Michael D.; Benz, R. Daniel; Kemper, Raymond A.; Tice, Raymond R.; Richard, Ann M.

2011-01-01

A symposium at the 40th anniversary of the Environmental Mutagen Society, held from October 24–28, 2009 in St. Louis, MO, surveyed the current status and future directions of genetic toxicology. This article summarizes the presentations and provides a perspective on the future. An abbreviated history is presented, highlighting the current standard battery of genotoxicity assays and persistent challenges. Application of computational toxicology to safety testing within a regulatory setting is discussed as a means for reducing the need for animal testing and human clinical trials, and current approaches and applications of in silico genotoxicity screening approaches across the pharmaceutical industry were surveyed and are reported here. The expanded use of toxicogenomics to illuminate mechanisms and bridge genotoxicity and carcinogenicity, and new public efforts to use high-throughput screening technologies to address lack of toxicity evaluation for the backlog of thousands of industrial chemicals in the environment are detailed. The Tox21 project involves coordinated efforts of four U.S. Government regulatory/research entities to use new and innovative assays to characterize key steps in toxicity pathways, including genotoxic and nongenotoxic mechanisms for carcinogenesis. Progress to date, highlighting preliminary test results from the National Toxicology Program is summarized. Finally, an overview is presented of ToxCast™, a related research program of the U.S. Environmental Protection Agency, using a broad array of high throughput and high content technologies for toxicity profiling of environmental chemicals, and computational toxicology modeling. Progress and challenges, including the pressing need to incorporate metabolic activation capability, are summarized. PMID:21538556

Databases applicable to quantitative hazard/risk assessment-Towards a predictive systems toxicology

International Nuclear Information System (INIS)

Waters, Michael; Jackson, Marcus

2008-01-01

The Workshop on The Power of Aggregated Toxicity Data addressed the requirement for distributed databases to support quantitative hazard and risk assessment. The authors have conceived and constructed with federal support several databases that have been used in hazard identification and risk assessment. The first of these databases, the EPA Gene-Tox Database was developed for the EPA Office of Toxic Substances by the Oak Ridge National Laboratory, and is currently hosted by the National Library of Medicine. This public resource is based on the collaborative evaluation, by government, academia, and industry, of short-term tests for the detection of mutagens and presumptive carcinogens. The two-phased evaluation process resulted in more than 50 peer-reviewed publications on test system performance and a qualitative database on thousands of chemicals. Subsequently, the graphic and quantitative EPA/IARC Genetic Activity Profile (GAP) Database was developed in collaboration with the International Agency for Research on Cancer (IARC). A chemical database driven by consideration of the lowest effective dose, GAP has served IARC for many years in support of hazard classification of potential human carcinogens. The Toxicological Activity Profile (TAP) prototype database was patterned after GAP and utilized acute, subchronic, and chronic data from the Office of Air Quality Planning and Standards. TAP demonstrated the flexibility of the GAP format for air toxics, water pollutants and other environmental agents. The GAP format was also applied to developmental toxicants and was modified to represent quantitative results from the rodent carcinogen bioassay. More recently, the authors have constructed: 1) the NIEHS Genetic Alterations in Cancer (GAC) Database which quantifies specific mutations found in cancers induced by environmental agents, and 2) the NIEHS Chemical Effects in Biological Systems (CEBS) Knowledgebase that integrates genomic and other biological data including

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.

TOXNET: Toxicology Data Network

Science.gov (United States)

... to TOXNET Your resource for searching databases on toxicology, hazardous chemicals, environmental health, and toxic releases SEARCH ... over 3,000 chemicals (1991-1998) Environmental Health & Toxicology Resources on environmental health and toxicology Visit Site ...

A predictive data-driven framework for endocrine prioritization: a triazole fungicide case study

Science.gov (United States)

Paul Friedman, Katie; Papineni, Sabitha; Marty, M. Sue; Yi, Kun Don; Goetz, Amber K.; Rasoulpour, Reza J.; Kwiatkowski, Pat; Wolf, Douglas C.; Blacker, Ann M.; Peffer, Richard C.

2016-01-01

Abstract The US Environmental Protection Agency Endocrine Disruptor Screening Program (EDSP) is a tiered screening approach to determine the potential for a chemical to interact with estrogen, androgen, or thyroid hormone systems and/or perturb steroidogenesis. Use of high-throughput screening (HTS) to predict hazard and exposure is shifting the EDSP approach to (1) prioritization of chemicals for further screening; and (2) targeted use of EDSP Tier 1 assays to inform specific data needs. In this work, toxicology data for three triazole fungicides (triadimefon, propiconazole, and myclobutanil) were evaluated, including HTS results, EDSP Tier 1 screening (and other scientifically relevant information), and EPA guideline mammalian toxicology study data. The endocrine-related bioactivity predictions from HTS and information that satisfied the EDSP Tier 1 requirements were qualitatively concordant. Current limitations in the available HTS battery for thyroid and steroidogenesis pathways were mitigated by inclusion of guideline toxicology studies in this analysis. Similar margins (3–5 orders of magnitude) were observed between HTS-predicted human bioactivity and exposure values and between in vivo mammalian bioactivity and EPA chronic human exposure estimates for these products’ registered uses. Combined HTS hazard and human exposure predictions suggest low priority for higher-tiered endocrine testing of these triazoles. Comparison with the mammalian toxicology database indicated that this HTS-based prioritization would have been protective for any potential in vivo effects that form the basis of current risk assessment for these chemicals. This example demonstrates an effective, human health protective roadmap for EDSP evaluation of pesticide active ingredients via prioritization using HTS and guideline toxicology information. PMID:27347635

Feature Subset Selection and Instance Filtering for Cross-project Defect Prediction - Classification and Ranking

Directory of Open Access Journals (Sweden)

Faimison Porto

2016-12-01

Full Text Available The defect prediction models can be a good tool on organizing the project's test resources. The models can be constructed with two main goals: 1 to classify the software parts - defective or not; or 2 to rank the most defective parts in a decreasing order. However, not all companies maintain an appropriate set of historical defect data. In this case, a company can build an appropriate dataset from known external projects - called Cross-project Defect Prediction (CPDP. The CPDP models, however, present low prediction performances due to the heterogeneity of data. Recently, Instance Filtering methods were proposed in order to reduce this heterogeneity by selecting the most similar instances from the training dataset. Originally, the similarity is calculated based on all the available dataset features (or independent variables. We propose that using only the most relevant features on the similarity calculation can result in more accurate filtered datasets and better prediction performances. In this study we extend our previous work. We analyse both prediction goals - Classification and Ranking. We present an empirical evaluation of 41 different methods by associating Instance Filtering methods with Feature Selection methods. We used 36 versions of 11 open source projects on experiments. The results show similar evidences for both prediction goals. First, the defect prediction performance of CPDP models can be improved by associating Feature Selection and Instance Filtering. Second, no evaluated method presented general better performances. Indeed, the most appropriate method can vary according to the characteristics of the project being predicted.

Coastal marine pollution and toxicology : overview of current research and future needs

International Nuclear Information System (INIS)

Zubir Din

1996-01-01

The contents are marine pollution and toxicology studies at Universiti Sains Malaysia, their facilities, and research projects have been done on this subject. In coastal pollution monitoring and baseline studies, the emphasis have been on determination of levels of trace-metals in the coastal marine environment, in relation to other physico-chemical parameters. The future needs and goals of marine pollution and toxicology studies in Malaysia also discussed

Coastal marine pollution and toxicology : overview of current research and future needs

Energy Technology Data Exchange (ETDEWEB)

Din, Zubir [Science Univ. of Malaysia, Minden, Pulau Pinang (Malaysia). Centre for Marine and Coastal Studies

1997-12-31

The contents are marine pollution and toxicology studies at Universiti Sains Malaysia, their facilities, and research projects have been done on this subject. In coastal pollution monitoring and baseline studies, the emphasis have been on determination of levels of trace-metals in the coastal marine environment, in relation to other physico-chemical parameters. The future needs and goals of marine pollution and toxicology studies in Malaysia also discussed.

Development and Application of Computational/In Vitro Toxicological Methods for Chemical Hazard Risk Reduction of New Materials for Advanced Weapon Systems

Science.gov (United States)

Frazier, John M.; Mattie, D. R.; Hussain, Saber; Pachter, Ruth; Boatz, Jerry; Hawkins, T. W.

2000-01-01

The development of quantitative structure-activity relationship (QSAR) is essential for reducing the chemical hazards of new weapon systems. The current collaboration between HEST (toxicology research and testing), MLPJ (computational chemistry) and PRS (computational chemistry, new propellant synthesis) is focusing R&D efforts on basic research goals that will rapidly transition to useful products for propellant development. Computational methods are being investigated that will assist in forecasting cellular toxicological end-points. Models developed from these chemical structure-toxicity relationships are useful for the prediction of the toxicological endpoints of new related compounds. Research is focusing on the evaluation tools to be used for the discovery of such relationships and the development of models of the mechanisms of action. Combinations of computational chemistry techniques, in vitro toxicity methods, and statistical correlations, will be employed to develop and explore potential predictive relationships; results for series of molecular systems that demonstrate the viability of this approach are reported. A number of hydrazine salts have been synthesized for evaluation. Computational chemistry methods are being used to elucidate the mechanism of action of these salts. Toxicity endpoints such as viability (LDH) and changes in enzyme activity (glutahoione peroxidase and catalase) are being experimentally measured as indicators of cellular damage. Extrapolation from computational/in vitro studies to human toxicity, is the ultimate goal. The product of this program will be a predictive tool to assist in the development of new, less toxic propellants.

Updates on EPA’s High-Throughput Exposure Forecast (ExpoCast) Research Project (CPCP)

Science.gov (United States)

Recent research advances by the ORD ExpoCast project (CSS Rapid Exposure and Dosimetry) are presented to the computational toxicology community in the context of prioritizing chemicals on a risk-basis using joint ExpoCast and ToxCast predictions. Recent publications by Wambaugh e...

US Climate Variability and Predictability Project

Energy Technology Data Exchange (ETDEWEB)

Patterson, Mike [University Corporation for Atmospheric Research (UCAR), Boulder, CO (United States)

2017-11-14

The US CLIVAR Project Office administers the US CLIVAR Program with its mission to advance understanding and prediction of climate variability and change across timescales with an emphasis on the role of the ocean and its interaction with other elements of the Earth system. The Project Office promotes and facilitates scientific collaboration within the US and international climate and Earth science communities, addressing priority topics from subseasonal to centennial climate variability and change; the global energy imbalance; the ocean’s role in climate, water, and carbon cycles; climate and weather extremes; and polar climate changes. This project provides essential one-year support of the Project Office, enabling the participation of US scientists in the meetings of the US CLIVAR bodies that guide scientific planning and implementation, including the scientific steering committee that establishes program goals and evaluates progress of activities to address them, the science team of funded investigators studying the ocean overturning circulation in the Atlantic, and two working groups tackling the priority research topics of Arctic change influence on midlatitude climate and weather extremes and the decadal-scale widening of the tropical belt.

Assessing the scientific research productivity of a leading toxicology journal: A case study of Human & Experimental Toxicology from 2003 to 2012

Science.gov (United States)

Al-Jabi, Samah W; Sweileh, Waleed M; Awang, Rahmat

2014-01-01

Background: Bibliometric studies are increasingly being used for research assessments. Bibliometric indicators involve the application of statistical methods to scientific publications to obtain the bibliographics for each journal. The main objective of this study was to conduct a bibliometric evaluation of Human & Experimental Toxicology retrieved from the Scopus database. Methods: This study obtained data from Scopus published from 1 January 2003 till 31 December 2012. The keywords entered in Scopus to accomplish the objective of this study were ‘Human’, ‘Experimental’ and ‘Toxicology’ as ‘Source Title’. Research productivity was evaluated based on a methodology developed and used in other bibliometric studies by analysing (a) total and trends in Human & Experimental Toxicology contributions in research between 2003 and 2012; (b) Human & Experimental Toxicology authorship patterns and productivity; (c) collaboration patterns; and (d) the citations received by the publications. Results: There were 1229 research articles published in Human & Experimental Toxicology. Of the articles included, 947 (77.1%) were original articles and 104 (8.5%) were review articles. The Hirsch-index of the retrieved documents was 35. The largest number of publications in Human & Experimental Toxicology was from the United States (19.6%), followed by India (12.8%) and Turkey (10.9%). The total number of citations was 9119, with a median (interquartile range) of 3 (1–9) in 6797 documents. The highest median (interquartile range) number of citations was 8 (2.7–12.7) for France, followed by 7.5 (2–22.5) for Iran and 6 (3–13.5) for the United Kingdom. The country most often citing articles that were published in Human & Experimental Toxicology was the United States, which made citations in 1508 documents, followed by India with citations in 792 documents. Conclusion: The documents in Human & Experimental Toxicology focus principally on original data, with very few

Oleoresin Capsicum toxicology evaluation and hazard review

Energy Technology Data Exchange (ETDEWEB)

Archuleta, M.M.

1995-10-01

Oleoresin Capsicum (OC) is an extract of the pepper plant used for centuries as a culinary spice (hot peppers). This material has been identified as a safe and effective Less-Than- Lethal weapon for use by Law enforcement and security professionals against assault. The National Institute of Justice (NIJ) is currently also evaluating its use in conjunction with other Less-Than-Lethal agents such as aqueous foam for use in corrections applications. Therefore, a comprehensive toxicological review of the literature was performed for the National Institute of Justice Less-Than-Lethal Force program to review and update the information available on the toxicity and adverse health effects associated with OC exposure. The results of this evaluation indicate that exposure to OC can result in dermatitis, as well as adverse nasal, pulmonary, and gastrointestinal effects in humans. The primary effects of OC exposure include pain and irritation of the mucous membranes of the eyes, nose, and lining of the mouth. Blistering and rash have been shown to occur after chronic or prolonged dermal exposure. Ingestion of capsicum may cause acute stinging of the lips, tongue, and oral mucosa and may lead to vomiting and diarrhea with large doses. OC vapors may also cause significant pulmonary irritation and prolonged cough. There is no evidence of long term effects associated with an acute exposure to OC, and extensive use as a culinary additive and medicinal ointment has further provided no evidence of long term adverse effects following repeated or prolonged exposure.

"Seeing is believing": perspectives of applying imaging technology in discovery toxicology.

Science.gov (United States)

Xu, Jinghai James; Dunn, Margaret Condon; Smith, Arthur Russell

2009-11-01

Efficiency and accuracy in addressing drug safety issues proactively are critical in minimizing late-stage drug attritions. Discovery toxicology has become a specialty subdivision of toxicology seeking to effectively provide early predictions and safety assessment in the drug discovery process. Among the many technologies utilized to select safer compounds for further development, in vitro imaging technology is one of the best characterized and validated to provide translatable biomarkers towards clinically-relevant outcomes of drug safety. By carefully applying imaging technologies in genetic, hepatic, and cardiac toxicology, and integrating them with the rest of the drug discovery processes, it was possible to demonstrate significant impact of imaging technology on drug research and development and substantial returns on investment.

Toxicología Vegetal

OpenAIRE

García Fernández, Antonio Juan

2010-01-01

Presentaciones de clase de los temas de Toxicología Vegetal de la licenciatura de Veterinaria de la Universidad de Murcia del curso 2011/12. Presentaciones de Toxicología Vegetal de la asignatura de Toxicología de la Licenciatura de Veterinaria del curso 2011/12

Evaluation of sampling methods for toxicological testing of indoor air particulate matter.

Science.gov (United States)

Tirkkonen, Jenni; Täubel, Martin; Hirvonen, Maija-Riitta; Leppänen, Hanna; Lindsley, William G; Chen, Bean T; Hyvärinen, Anne; Huttunen, Kati

2016-09-01

There is a need for toxicity tests capable of recognizing indoor environments with compromised air quality, especially in the context of moisture damage. One of the key issues is sampling, which should both provide meaningful material for analyses and fulfill requirements imposed by practitioners using toxicity tests for health risk assessment. We aimed to evaluate different existing methods of sampling indoor particulate matter (PM) to develop a suitable sampling strategy for a toxicological assay. During three sampling campaigns in moisture-damaged and non-damaged school buildings, we evaluated one passive and three active sampling methods: the Settled Dust Box (SDB), the Button Aerosol Sampler, the Harvard Impactor and the National Institute for Occupational Safety and Health (NIOSH) Bioaerosol Cyclone Sampler. Mouse RAW264.7 macrophages were exposed to particle suspensions and cell metabolic activity (CMA), production of nitric oxide (NO) and tumor necrosis factor (TNFα) were determined after 24 h of exposure. The repeatability of the toxicological analyses was very good for all tested sampler types. Variability within the schools was found to be high especially between different classrooms in the moisture-damaged school. Passively collected settled dust and PM collected actively with the NIOSH Sampler (Stage 1) caused a clear response in exposed cells. The results suggested the higher relative immunotoxicological activity of dust from the moisture-damaged school. The NIOSH Sampler is a promising candidate for the collection of size-fractionated PM to be used in toxicity testing. The applicability of such sampling strategy in grading moisture damage severity in buildings needs to be developed further in a larger cohort of buildings.

The nematode Caenorhabditis elegans as a tool to predict chemical activity on mammalian development and identify mechanisms influencing toxicological outcome.

Science.gov (United States)

Harlow, Philippa H; Perry, Simon J; Widdison, Stephanie; Daniels, Shannon; Bondo, Eddie; Lamberth, Clemens; Currie, Richard A; Flemming, Anthony J

2016-03-18

To determine whether a C. elegans bioassay could predict mammalian developmental activity, we selected diverse compounds known and known not to elicit such activity and measured their effect on C. elegans egg viability. 89% of compounds that reduced C. elegans egg viability also had mammalian developmental activity. Conversely only 25% of compounds found not to reduce egg viability in C. elegans were also inactive in mammals. We conclude that the C. elegans egg viability assay is an accurate positive predictor, but an inaccurate negative predictor, of mammalian developmental activity. We then evaluated C. elegans as a tool to identify mechanisms affecting toxicological outcomes among related compounds. The difference in developmental activity of structurally related fungicides in C. elegans correlated with their rate of metabolism. Knockdown of the cytochrome P450s cyp-35A3 and cyp-35A4 increased the toxicity to C. elegans of the least developmentally active compounds to the level of the most developmentally active. This indicated that these P450s were involved in the greater rate of metabolism of the less toxic of these compounds. We conclude that C. elegans based approaches can predict mammalian developmental activity and can yield plausible hypotheses for factors affecting the biological potency of compounds in mammals.

The principle of safety evaluation in medicinal drug - how can toxicology contribute to drug discovery and development as a multidisciplinary science?

Science.gov (United States)

Horii, Ikuo

2016-01-01

Pharmaceutical (drug) safety assessment covers a diverse science-field in the drug discovery and development including the post-approval and post-marketing phases in order to evaluate safety and risk management. The principle in toxicological science is to be placed on both of pure and applied sciences that are derived from past/present scientific knowledge and coming new science and technology. In general, adverse drug reactions are presented as "biological responses to foreign substances." This is the basic concept of thinking about the manifestation of adverse drug reactions. Whether or not toxic expressions are extensions of the pharmacological effect, adverse drug reactions as seen from molecular targets are captured in the category of "on-target" or "off-target", and are normally expressed as a biological defense reaction. Accordingly, reactions induced by pharmaceuticals can be broadly said to be defensive reactions. Recent molecular biological conception is in line with the new, remarkable scientific and technological developments in the medical and pharmaceutical areas, and the viewpoints in the field of toxicology have shown that they are approaching toward the same direction as well. This paper refers to the basic concept of pharmaceutical toxicology, the differences for safety assessment in each stage of drug discovery and development, regulatory submission, and the concept of scientific considerations for risk assessment and management from the viewpoint of "how can multidisciplinary toxicology contribute to innovative drug discovery and development?" And also realistic translational research from preclinical to clinical application is required to have a significant risk management in post market by utilizing whole scientific data derived from basic and applied scientific research works. In addition, the significance for employing the systems toxicology based on AOP (Adverse Outcome Pathway) analysis is introduced, and coming challenges on precision

Electronic cigarettes in the USA: a summary of available toxicology data and suggestions for the future.

Science.gov (United States)

Orr, Michael S

2014-05-01

To review the available evidence evaluating the toxicological profiles of electronic cigarettes (e-cigarettes) in order to understand the potential impact of e-cigarettes on individual users and the public health. Systematic literature searches were conducted between October 2012 and October 2013 using five electronic databases. Search terms such as 'e-cigarettes' and 'electronic delivery devices' were used to identify the toxicology information for e-cigarettes. As of October 2013, the scientific literature contains very limited information regarding the toxicity of e-cigarettes commercially available in the USA. While some preliminary toxicology data suggests that e-cigarette users are exposed to lower levels of toxicants relative to cigarette smokers, the data available is extremely limited at this time. At present, there is insufficient toxicological data available to perform thorough risk assessment analyses for e-cigarettes; few toxicology studies evaluating e-cigarettes have been conducted to date, and standard toxicological testing paradigms have not been developed for comparing disparate types of tobacco products such as e-cigarettes and traditional cigarettes. Overall, the limited toxicology data on e-cigarettes in the public domain is insufficient to allow a thorough toxicological evaluation of this new type of tobacco product. In the future, the acquisition of scientific datasets that are derived from scientifically robust standard testing paradigms, include comprehensive chemical characterisation of the aerosol, provide information on users' toxicant exposure levels, and from studies replicated by independent researchers will improve the scientific community's ability to perform robust toxicological evaluations of e-cigarettes.

Metabolism and toxicology of plutonium-239 - evaluation of the internal contamination of persons professionally exposed (1963)

International Nuclear Information System (INIS)

Henry, Ph.

1963-01-01

After reviewing the main metabolic and toxicological properties of plutonium 239 as well as the professional norms now in force, the report considers the difficult problem of the evaluation of the internal contamination of persons professionally exposed. This evaluation is dependent on the practical organisation of the supervision involved: - systematic supervision by periodic analysis of urinary Pu and special supervision in the case of incidents by an examination adapted to each case. A simple interpretation of the systematic analyses, as well as the evaluation methods used in the main cases of occidental contamination are outlined. (author) [fr

Toxicology Education Foundation

Science.gov (United States)

... bodies and our world. Welcome to the Toxicology Education Foundation! Our mission is to enhance public understanding ... In with us, follow our Tweets, choose Toxicology Education Foundation as your preferred charity through Smile.Amazon. ...

National Toxicology Program

Science.gov (United States)

... NTP? NTP develops and applies tools of modern toxicology and molecular biology to identify substances in the ... depend on for decisions that matter. The National Toxicology Program provides the scientific basis for programs, activities, ...

The four cornerstones of Evolutionary Toxicology.

Science.gov (United States)

Bickham, John W

2011-05-01

Evolutionary Toxicology is the study of the effects of chemical pollutants on the genetics of natural populations. Research in Evolutionary Toxicology uses experimental designs familiar to the ecotoxicologist with matched reference and contaminated sites and the selection of sentinel species. It uses the methods of molecular genetics and population genetics, and is based on the theories and concepts of evolutionary biology and conservation genetics. Although it is a relatively young field, interest is rapidly growing among ecotoxicologists and more and more field studies and even controlled laboratory experiments are appearing in the literature. A number of population genetic impacts have been observed in organisms exposed to pollutants which I refer to here as the four cornerstones of Evolutionary Toxicology. These include (1) genome-wide changes in genetic diversity, (2) changes in allelic or genotypic frequencies caused by contaminant-induced selection acting at survivorship loci, (3) changes in dispersal patterns or gene flow which alter the genetic relationships among populations, and (4) changes in allelic or genotypic frequencies caused by increased mutation rates. It is concluded that population genetic impacts of pollution exposure are emergent effects that are not necessarily predictable from the mode of toxicity of the pollutant. Thus, to attribute an effect to a particular contaminant requires a careful experimental design which includes selection of appropriate reference sites, detailed chemistry analyses of environmental samples and tissues, and the use of appropriate biomarkers to establish exposure and effect. This paper describes the field of Evolutionary Toxicology and discusses relevant field studies and their findings. © Springer Science+Business Media, LLC 2011

Systems Toxicology of Embryo Development (9th Copenhagen Workshop)

Science.gov (United States)

An important consideration for predictive toxicology is to identify developmental hazards utilizing mechanism-based in vitro assays (e.g., ToxCast) and in silico multiscale models. Steady progress has been made with agent-based models that recapitulate morphogenetic drivers for a...

Mass Spectrometry Applications for Toxicology.

Science.gov (United States)

Mbughuni, Michael M; Jannetto, Paul J; Langman, Loralie J

2016-12-01

Toxicology is a multidisciplinary study of poisons, aimed to correlate the quantitative and qualitative relationships between poisons and their physiological and behavioural effects in living systems. Other key aspects of toxicology focus on elucidation of the mechanisms of action of poisons and development of remedies and treatment plans for associated toxic effects. In these endeavours, Mass spectrometry (MS) has become a powerful analytical technique with a wide range of application used in the Toxicological analysis of drugs, poisons, and metabolites of both. To date, MS applications have permeated all fields of toxicology which include; environmental, clinical, and forensic toxicology. While many different analytical applications are used in these fields, MS and its hyphenated applications such as; gas chromatography MS (GC-MS), liquid chromatography MS (LC-MS), inductively coupled plasma ionization MS (ICP-MS), tandem mass spectrometry (MS/MS and MS n ) have emerged as powerful tools used in toxicology laboratories. This review will focus on these hyphenated MS technologies and their applications for toxicology.

Mass Spectrometry Applications for Toxicology

Science.gov (United States)

Mbughuni, Michael M.; Jannetto, Paul J.

2016-01-01

Toxicology is a multidisciplinary study of poisons, aimed to correlate the quantitative and qualitative relationships between poisons and their physiological and behavioural effects in living systems. Other key aspects of toxicology focus on elucidation of the mechanisms of action of poisons and development of remedies and treatment plans for associated toxic effects. In these endeavours, Mass spectrometry (MS) has become a powerful analytical technique with a wide range of application used in the Toxicological analysis of drugs, poisons, and metabolites of both. To date, MS applications have permeated all fields of toxicology which include; environmental, clinical, and forensic toxicology. While many different analytical applications are used in these fields, MS and its hyphenated applications such as; gas chromatography MS (GC-MS), liquid chromatography MS (LC-MS), inductively coupled plasma ionization MS (ICP-MS), tandem mass spectrometry (MS/MS and MSn) have emerged as powerful tools used in toxicology laboratories. This review will focus on these hyphenated MS technologies and their applications for toxicology. PMID:28149262

Toxicological benchmarks for wildlife: 1996 Revision

International Nuclear Information System (INIS)

Sample, B.E.; Opresko, D.M.; Suter, G.W., II.

1996-06-01

The purpose of this report is to present toxicological benchmarks for assessment of effects of certain chemicals on mammalian and avian wildlife species. Publication of this document meets a milestone for the Environmental Restoration (ER) Risk Assessment Program. This document provides the ER Program with toxicological benchmarks that may be used as comparative tools in screening assessments as well as lines of evidence to support or refute the presence of ecological effects in ecological risk assessments. The chemicals considered in this report are some that occur at US DOE waste sites, and the wildlife species evaluated herein were chosen because they represent a range of body sizes and diets

Toxicological benchmarks for wildlife: 1996 Revision

Energy Technology Data Exchange (ETDEWEB)

Sample, B.E.; Opresko, D.M.; Suter, G.W., II

1996-06-01

The purpose of this report is to present toxicological benchmarks for assessment of effects of certain chemicals on mammalian and avian wildlife species. Publication of this document meets a milestone for the Environmental Restoration (ER) Risk Assessment Program. This document provides the ER Program with toxicological benchmarks that may be used as comparative tools in screening assessments as well as lines of evidence to support or refute the presence of ecological effects in ecological risk assessments. The chemicals considered in this report are some that occur at US DOE waste sites, and the wildlife species evaluated herein were chosen because they represent a range of body sizes and diets.

Green Toxicology: a strategy for sustainable chemical and material development.

Science.gov (United States)

Crawford, Sarah E; Hartung, Thomas; Hollert, Henner; Mathes, Björn; van Ravenzwaay, Bennard; Steger-Hartmann, Thomas; Studer, Christoph; Krug, Harald F

2017-01-01

Green Toxicology refers to the application of predictive toxicology in the sustainable development and production of new less harmful materials and chemicals, subsequently reducing waste and exposure. Built upon the foundation of "Green Chemistry" and "Green Engineering", "Green Toxicology" aims to shape future manufacturing processes and safe synthesis of chemicals in terms of environmental and human health impacts. Being an integral part of Green Chemistry, the principles of Green Toxicology amplify the role of health-related aspects for the benefit of consumers and the environment, in addition to being economical for manufacturing companies. Due to the costly development and preparation of new materials and chemicals for market entry, it is no longer practical to ignore the safety and environmental status of new products during product development stages. However, this is only possible if toxicologists and chemists work together early on in the development of materials and chemicals to utilize safe design strategies and innovative in vitro and in silico tools. This paper discusses some of the most relevant aspects, advances and limitations of the emergence of Green Toxicology from the perspective of different industry and research groups. The integration of new testing methods and strategies in product development, testing and regulation stages are presented with examples of the application of in silico, omics and in vitro methods. Other tools for Green Toxicology, including the reduction of animal testing, alternative test methods, and read-across approaches are also discussed.

Evaluation of Cases Consulted to Forensic Toxicology Laboratory between 2008 and 2012

Directory of Open Access Journals (Sweden)

Ismail Ethem Goren

2013-08-01

Full Text Available Purpose: In this study, we aimed to determine annual and seasonal distribution of cases and affecting factors of the distribution in Cukurova University Hospital, Forensic Toxicology Laboratory. Method: Five-year (up to 2012 from 2008 archives of cases consulted to our forensic toxicology laboratory was investigated and classified according to gender, situation of case, type of poisoning, seasonal distribution, findings were statistically evaluated by SPSS v20.0 software Results: After screening five-year archives using laboratory registration book, we determined that of 608 cases 49.5 % were from emergency medicine, 19.6 % from pediatric, 7.4 % from psychiatry, 4.4 % 4.4 from neurology, 2.3 % from other units of the hospital, 7.9 % from judicial authorities, 4.8 % from special requests and 6.1 % from circumjacent hospitals. 57.9 % of the cases are male and 42.1 % are female. 87.3 % of 608 cases were clinical cases, 7.9 % were forensic cases, 4.8 % special requests. 95.8 % of judicial cases were male and 85.4 % were drugs of abuse cases. 28.1 % of clinical cases were the carbon monoxide poisoning and 64.3 % of the carbon monoxide poisoning cases were female. Conclusion: When five-year data were evaluated, we determine that numbers of case are increasing every year. Males are more than in females. Forensic cases which were mostly drugs of abuse were most commonly have seen in male. When our data were investigated together with TUBIM’s data belong to 2009, 2010, 2011 and 2012 (Turkey Monitoring Centre for Drugs and Drugs Addiction, the use of drug abuse were seen most commonly in male. Also carbon monoxide poisoning in clinical cases were evaluated and we see that Carbon monoxide intoxication in winter was more than in summer due to heating. Women who exposed to carbon monoxide were more than men to be much more at home according to men. [Cukurova Med J 2013; 38(4.000: 675-680

Toxicological evaluation of the aqueous extract of Allium sativum ...

African Journals Online (AJOL)

The possible toxicological risks of Allium sativum aqueous extract upon consumption were assessed in mice and rats using acute and sub-chronic treatments. 36 male Swiss albino mice were used, and the various doses administered were 0, 2, 4, 8, 16 and 32 g/kg body weight. Mice were observed for behavioural changes ...

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

Computational Toxicology as Implemented by the US EPA ...

Science.gov (United States)

Computational toxicology is the application of mathematical and computer models to help assess chemical hazards and risks to human health and the environment. Supported by advances in informatics, high-throughput screening (HTS) technologies, and systems biology, the U.S. Environmental Protection Agency EPA is developing robust and flexible computational tools that can be applied to the thousands of chemicals in commerce, and contaminant mixtures found in air, water, and hazardous-waste sites. The Office of Research and Development (ORD) Computational Toxicology Research Program (CTRP) is composed of three main elements. The largest component is the National Center for Computational Toxicology (NCCT), which was established in 2005 to coordinate research on chemical screening and prioritization, informatics, and systems modeling. The second element consists of related activities in the National Health and Environmental Effects Research Laboratory (NHEERL) and the National Exposure Research Laboratory (NERL). The third and final component consists of academic centers working on various aspects of computational toxicology and funded by the U.S. EPA Science to Achieve Results (STAR) program. Together these elements form the key components in the implementation of both the initial strategy, A Framework for a Computational Toxicology Research Program (U.S. EPA, 2003), and the newly released The U.S. Environmental Protection Agency's Strategic Plan for Evaluating the T

TRIM timber projections: an evaluation based on forest inventory measurements.

Science.gov (United States)

John R. Mills

1989-01-01

Two consecutive timberland inventories collected from permanent plots in the natural pine type in North Carolina were used to evaluate the timber resource inventory model (TRIM). This study compares model predictions with field measurements and examines the effect of inventory data aggregation on the accuracy of projections. Projections were repeated for two geographic...

Toxicological risk assessment of complex mixtures through the Wtox model

Directory of Open Access Journals (Sweden)

William Gerson Matias

2015-01-01

Full Text Available Mathematical models are important tools for environmental management and risk assessment. Predictions about the toxicity of chemical mixtures must be enhanced due to the complexity of eects that can be caused to the living species. In this work, the environmental risk was accessed addressing the need to study the relationship between the organism and xenobiotics. Therefore, ve toxicological endpoints were applied through the WTox Model, and with this methodology we obtained the risk classication of potentially toxic substances. Acute and chronic toxicity, citotoxicity and genotoxicity were observed in the organisms Daphnia magna, Vibrio scheri and Oreochromis niloticus. A case study was conducted with solid wastes from textile, metal-mechanic and pulp and paper industries. The results have shown that several industrial wastes induced mortality, reproductive eects, micronucleus formation and increases in the rate of lipid peroxidation and DNA methylation of the organisms tested. These results, analyzed together through the WTox Model, allowed the classication of the environmental risk of industrial wastes. The evaluation showed that the toxicological environmental risk of the samples analyzed can be classied as signicant or critical.

Experimental and mathematical modeling methods for the investigation of toxicological interactions

International Nuclear Information System (INIS)

El-Masri, Hisham A.

2007-01-01

While procedures have been developed and used for many years to assess risk and determine acceptable exposure levels to individual chemicals, most cases of environmental contamination can result in concurrent or sequential exposure to more than one chemical. Toxicological predictions of such combinations must be based on an understanding of the mechanisms of action and interaction of the components of the mixtures. Statistical and experimental methods test the existence of toxicological interactions in a mixture. However, these methods are limited to experimental data ranges for which they are derived, in addition to limitations caused by response differences from experimental animals to humans. Empirical methods such as isobolograms, median-effect principle and response surface methodology (RSM) are based on statistical experimental design and regression of data. For that reason, the predicted response surfaces can be used for extrapolation across dose regions where interaction mechanisms are not anticipated to change. In general, using these methods for predictions can be problematic without including biologically based mechanistic descriptions that can account for dose and species differences. Mechanistically based models, such as physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) models, include explicit descriptions of interaction mechanisms which are related to target tissues levels. These models include dose-dependent mechanistic hypotheses of toxicological interactions which can be tested by model-directed experimental design and used to identify dose regions where interactions are not significant

How Adverse Outcome Pathways Can Aid the Development and Use of Computational Prediction Models for Regulatory Toxicology

Energy Technology Data Exchange (ETDEWEB)

Wittwehr, Clemens; Aladjov, Hristo; Ankley, Gerald; Byrne, Hugh J.; de Knecht, Joop; Heinzle, Elmar; Klambauer, Günter; Landesmann, Brigitte; Luijten, Mirjam; MacKay, Cameron; Maxwell, Gavin; Meek, M. E. (Bette); Paini, Alicia; Perkins, Edward; Sobanski, Tomasz; Villeneuve, Dan; Waters, Katrina M.; Whelan, Maurice

2016-12-19

Efforts are underway to transform regulatory toxicology and chemical safety assessment from a largely empirical science based on direct observation of apical toxicity outcomes in whole organism toxicity tests to a predictive one in which outcomes and risk are inferred from accumulated mechanistic understanding. The adverse outcome pathway (AOP) framework has emerged as a systematic approach for organizing knowledge that supports such inference. We argue that this systematic organization of knowledge can inform and help direct the design and development of computational prediction models that can further enhance the utility of mechanistic and in silico data for chemical safety assessment. Examples of AOP-informed model development and its application to the assessment of chemicals for skin sensitization and multiple modes of endocrine disruption are provided. The role of problem formulation, not only as a critical phase of risk assessment, but also as guide for both AOP and complementary model development described. Finally, a proposal for actively engaging the modeling community in AOP-informed computational model development is made. The contents serve as a vision for how AOPs can be leveraged to facilitate development of computational prediction models needed to support the next generation of chemical safety assessment.

Environmental Toxicology Research Facility

Data.gov (United States)

Federal Laboratory Consortium — Fully-equipped facilities for environmental toxicology researchThe Environmental Toxicology Research Facility (ETRF) located in Vicksburg, MS provides over 8,200 ft...

The PredictAD project

DEFF Research Database (Denmark)

Antila, Kari; Lötjönen, Jyrki; Thurfjell, Lennart

2013-01-01

Alzheimer's disease (AD) is the most common cause of dementia affecting 36 million people worldwide. As the demographic transition in the developed countries progresses towards older population, the worsening ratio of workers per retirees and the growing number of patients with age-related illnes...... candidates and implement the framework in software. The results are currently used in several research projects, licensed to commercial use and being tested for clinical use in several trials....... objective of the PredictAD project was to find and integrate efficient biomarkers from heterogeneous patient data to make early diagnosis and to monitor the progress of AD in a more efficient, reliable and objective manner. The project focused on discovering biomarkers from biomolecular data...

21 CFR 862.3200 - Clinical toxicology calibrator.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Clinical toxicology calibrator. 862.3200 Section... (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Toxicology Test Systems § 862.3200 Clinical toxicology calibrator. (a) Identification. A clinical toxicology calibrator is...

Information resources in toxicology--Italy

International Nuclear Information System (INIS)

Preziosi, Paolo; Dracos, Adriana; Marcello, Ida

2003-01-01

The purpose of the present paper is to provide an overview of current resources in the field of toxicology in Italy. The discussion will begin with a brief history of toxicology in this country, which includes the study of the toxicity of plants and other natural substances, and the birth of industrial and forensic toxicology. We will also provide information on research, education, and hazard control in the field of toxicology. Within this context we will examine the public bodies responsible for surveillance and regulatory activities, state-owned and private structures involved in toxicological research, and the educational programs and research activities of universities. Particular emphasis will be placed on the activities of the National Health Service, which plays an important role in areas such as clinical toxicology, food safety, and animal health, as well as those of national and regional agencies dedicated to the protection of the environment. The presentation will be organized as follows: - A Brief History of Toxicology in Italy; - Professional Societies; - National Health Service; - National Bodies; - Resources for the Environment; - Biomedical Websites; - Recent Publications; - Research Structures; - Graduate and Postgraduate Programs; - Legislation

Toxicology research for precautionary decision-making and the role of Human & Experimental Toxicology.

Science.gov (United States)

Grandjean, P

2015-12-01

A key aim of toxicology is the prevention of adverse effects due to toxic hazards. Therefore, the dissemination of toxicology research findings must confront two important challenges: one being the lack of information on the vast majority of potentially toxic industrial chemicals and the other being the strict criteria for scientific proof usually required for decision-making in regard to prevention. The present study ascertains the coverage of environmental chemicals in four volumes of Human & Experimental Toxicology and the presentation and interpretation of research findings in published articles. Links in SciFinder showed that the 530 articles published in four selected volumes between 1984 and 2014 primarily dealt with metals (126 links) and other toxicants that have received substantial attention in the past. Thirteen compounds identified by US authorities in 2006 as high-priority substances, for which toxicology documentation is badly needed, were not covered in the journal issues at all. When reviewing published articles, reliance on p values was standard, and non-significant findings were often called 'negative.' This tradition may contribute to the perceived need to extend existing research on toxic hazards that have already been well characterized. Several sources of bias towards the null hypothesis can affect toxicology research, but are generally not considered, thus adding to the current inclination to avoid false positive findings. In this regard, toxicology is particularly prone to bias because of the known paucity of false positives and, in particular, the existence of a vast number of toxic hazards which by default are considered innocuous due to lack of documentation. The Precautionary Principle could inspire decision-making on the basis of incomplete documentation and should stimulate a change in toxicology traditions and in toxicology research publication. © The Author(s) 2015.

Handbook of systems toxicology

National Research Council Canada - National Science Library

Casciano, Daniel A; Sahu, Saura C

2011-01-01

"In the first handbook to comprehensively cover the emerging area of systems toxicology, the Handbook of Systems Toxicology provides an authoritative compilation of up-to-date developments presented...

42 CFR 493.937 - Toxicology.

Science.gov (United States)

2010-10-01

... 42 Public Health 5 2010-10-01 2010-10-01 false Toxicology. 493.937 Section 493.937 Public Health... Proficiency Testing Programs by Specialty and Subspecialty § 493.937 Toxicology. (a) Program content and frequency of challenge. To be approved for proficiency testing for toxicology, the annual program must...

Inhalation Toxicology Research Institute. Annual report, October 1, 1992--September 30, 1993

Energy Technology Data Exchange (ETDEWEB)

Nikula, K.J.; Belinsky, S.A.; Bradley, P.L. [eds.

1993-11-01

This annual report for the Inhalation Toxicology Research Institute for 1992-1993 consists of 60 individual reports prepared separately by investigators describing progress in their own projects. Most papers are 2-5 pages long.

Toxicological awakenings: the rebirth of hormesis as a central pillar of toxicology

International Nuclear Information System (INIS)

Calabrese, Edward J.

2005-01-01

This paper assesses historical reasons that may account for the marginalization of hormesis as a dose-response model in the biomedical sciences in general and toxicology in particular. The most significant and enduring explanatory factors are the early and close association of the concept of hormesis with the highly controversial medical practice of homeopathy and the difficulty in assessing hormesis with high-dose testing protocols which have dominated the discipline of toxicology, especially regulatory toxicology. The long-standing and intensely acrimonious conflict between homeopathy and 'traditional' medicine (allopathy) lead to the exclusion of the hormesis concept from a vast array of medical- and public health-related activities including research, teaching, grant funding, publishing, professional societal meetings, and regulatory initiatives of governmental agencies and their advisory bodies. Recent publications indicate that the hormetic dose-response is far more common and fundamental than the dose-response models [threshold/linear no threshold (LNT)] used in toxicology and risk assessment, and by governmental regulatory agencies in the establishment of exposure standards for workers and the general public. Acceptance of the possibility of hormesis has the potential to profoundly affect the practice of toxicology and risk assessment, especially with respect to carcinogen assessment

A comprehensive evaluation of the toxicology of monogram inks added to experimental cigarettes.

Science.gov (United States)

Smith, Donna C; Wiecinski, Paige N; Coggins, Christopher R E; Banty, Tamara H; Oldham, Michael J

2013-01-01

Cigarettes often have a small identifying mark (monogram) printed either on the cigarette paper toward the filter end of the cigarette or on the tipping paper. A battery of tests was used to compare the toxicology of mainstream smoke from experimental cigarettes manufactured with different monogram inks. Cigarettes with different concentrations of different pigments were compared with cigarettes without ink, and with a control ink. Smoke from each of the experimental cigarettes was evaluated using analytical chemistry and in vitro bacterial mutagenicity (Salmonella, five strains, ± S9) and cytotoxicity (neutral red uptake) assays. No differences were observed between experimental cigarettes printed with three different pigment loads of iron oxide-based Black pigment and non-printed cigarettes. In general, no dose response was observed. However, increases in certain smoke constituents were found to correlate with Pigment Yellow 14 (also known as benzidine yellow) and Pigment Blue 15 (copper phthalocyanine). Increases in bacterial mutagenicity were observed for high-level print of Pigment Yellow 14 in TA98 and TA1537 and the high-level print of Pigment Blue 15 in TA98. In vitro cytotoxicity of mainstream smoke was unaffected by the presence of monogram ink on cigarettes. Statistically significant dose-responsive constituent changes and an increase in mutagenicity were observed with inclusion of Pigment Yellow 14 and Pigment Blue 15. Other pigments showed minimal toxicological activity.

COMPUTATIONAL TOXICOLOGY-WHERE IS THE DATA? ...

Science.gov (United States)

This talk will briefly describe the state of the data world for computational toxicology and one approach to improve the situation, called ACToR (Aggregated Computational Toxicology Resource). This talk will briefly describe the state of the data world for computational toxicology and one approach to improve the situation, called ACToR (Aggregated Computational Toxicology Resource).

Design of a testing strategy using non-animal based test methods: lessons learnt from the ACuteTox project.

Science.gov (United States)

Kopp-Schneider, Annette; Prieto, Pilar; Kinsner-Ovaskainen, Agnieszka; Stanzel, Sven

2013-06-01

In the framework of toxicology, a testing strategy can be viewed as a series of steps which are taken to come to a final prediction about a characteristic of a compound under study. The testing strategy is performed as a single-step procedure, usually called a test battery, using simultaneously all information collected on different endpoints, or as tiered approach in which a decision tree is followed. Design of a testing strategy involves statistical considerations, such as the development of a statistical prediction model. During the EU FP6 ACuteTox project, several prediction models were proposed on the basis of statistical classification algorithms which we illustrate here. The final choice of testing strategies was not based on statistical considerations alone. However, without thorough statistical evaluations a testing strategy cannot be identified. We present here a number of observations made from the statistical viewpoint which relate to the development of testing strategies. The points we make were derived from problems we had to deal with during the evaluation of this large research project. A central issue during the development of a prediction model is the danger of overfitting. Procedures are presented to deal with this challenge. Copyright © 2012 Elsevier Ltd. All rights reserved.

IRIS Toxicological Review of n-Butanol (Interagency Science ...

Science.gov (United States)

On September 8, 2011, the Toxicological Review of n-Butanol (External Review Draft) was released for external peer review and public comment. The Toxicological Review and charge were reviewed internally by EPA and by other federal agencies and White House Offices before public release. In the new IRIS process, introduced by the EPA Administrator, all written comments on IRIS assessments submitted by other federal agencies and White House Offices will be made publicly available. Accordingly, interagency comments with EPA's response and the interagency science consultation draft of the IRIS Toxicological Review of n-Butanol and the charge to external peer reviewers are posted on this site. EPA is undertaking an Integrated Risk Information System (IRIS) health assessment for n-butanol. IRIS is an EPA database containing Agency scientific positions on potential adverse human health effects that may result from chronic (or lifetime) exposure to chemicals in the environment. IRIS contains chemical-specific summaries of qualitative and quantitative health information in support of two steps of the risk assessment paradigm, i.e., hazard identification and dose-response evaluation. IRIS assessments are used in combination with specific situational exposure assessment information to evaluate potential public health risk associated with environmental contaminants.

Distance learning in toxicology: Australia's RMIT program

International Nuclear Information System (INIS)

Ahokas, Jorma; Donohue, Diana; Rix, Colin; Wright, Paul

2005-01-01

RMIT University was the first to offer a comprehensive Masters of Toxicology in Australasia 19 years ago. In 2001 the program was transformed into two stages, leading to a Graduate Diploma and Master of Applied Science in Toxicology. Now, these programs are fully online and suitable for graduates living and working anywhere in the world. The modular distance-learning courses are specifically designed to equip students with essential skills for entering fields such as chemical and drug evaluation; risk assessment of chemicals in the workplace; environmental and food toxicology. RMIT's online course delivery system has made it possible to deliver the toxicology programs, both nationally and internationally. The learning material and interactive activities (tests and quizzes, discussion boards, chat sessions) use Blackboard and WebBoard, each with a different educational function. Students log in to a Learning Hub to access their courses. The Learning Hub enables students to extend their learning beyond the classroom to the home, workplace, library and any other location with Internet access. The teaching staff log in to the Learning Hub to maintain and administer the online programs and courses which they have developed and/or which they teach. The Learning Hub is also a communication tool for students and staff, providing access to email, a diary and announcements. The early experience of delivering a full toxicology program online is very positive. However this mode of teaching continues to present many interesting technical, educational and cultural challenges, including: the design and presentation of the material; copyright issues; internationalisation of content; interactive participation; and the assessment procedures

Gordon Research Conference on Genetic Toxicology

Energy Technology Data Exchange (ETDEWEB)

Project Director Penelope Jeggo

2003-02-15

Genetic toxicology represents a study of the genetic damage that a cell can incur, the agents that induce such damage, the damage response mechanisms available to cells and organisms, and the potential consequences of such damage. Genotoxic agents are abundant in the environment and are also induced endogenously. The consequences of such damage can include carcinogenesis and teratogenesis. An understanding of genetic toxicology is essential to carry out risk evaluations of the impact of genotoxic agents and to assess how individual genetic differences influence the response to genotoxic damage. In recent years, the importance of maintaining genomic stability has become increasingly recognized, in part by the realization that failure of the damage response mechanisms underlies many, if not all, cancer incidence. The importance of these mechanisms is also underscored by their remarkable conservation between species, allowing the study of simple organisms to provide significant input into our understanding of the underlying mechanisms. It has also become clear that the damage response mechanisms interface closely with other aspects of cellular metabolism including replication, transcription and cell cycle regulation. Moreover, defects in many of these mechanisms, as observed for example in ataxia telangiectasia patients, confer disorders with associated developmental abnormalities demonstrating their essential roles during growth and development. In short, while a decade ago, a study of the impact of DNA damage was seen as a compartmentalized area of cellular research, it is now appreciated to lie at the centre of an array of cellular responses of crucial importance to human health. Consequently, this has become a dynamic and rapidly advancing area of research. The Genetic Toxicology Gordon Research Conference is biannual with an evolving change in the emphasis of the meetings. From evaluating the nature of genotoxic chemicals, which lay at the centre of the early

Current status and prospects of the toxicological assessment of engineered nanomaterials

International Nuclear Information System (INIS)

Pacchiarotti, Francesca; Grollino, Maria Giuseppa; Leter, Giorgio

2015-01-01

Nano toxicology is a branch of experimental toxicology dealing with identification and characterization of the harmful biological effects of engineered nanomaterials. The physico-chemical properties of these materials affect their biological level interactions. From the first generation of experimental studies it showed the need for adaptation to nanomaterials methodologies and toxicological evaluation of current strategies. Special challenges are presented by the variety of materials to be tested, from the definition of relevant dose quantities, by the standardization of the preparation and characterization of the nanomaterial in the biological sample matrices, by techniques for the determination of the biodistribution in the body. 'Omics' technologies are now an innovative tool for toxicological approach based on understanding the mechanisms of action, which will allow the most advanced laboratories to implement high-performance screening test. [it

The application of capillary microsampling in GLP toxicology studies.

Science.gov (United States)

Verhaeghe, Tom; Dillen, Lieve; Stieltjes, Hans; Zwart, Loeckie de; Feyen, Bianca; Diels, Luc; Vroman, Ann; Timmerman, Philip

2017-04-01

Capillary microsampling (CMS) to collect microplasma volumes is gradually replacing traditional, larger volume sampling from rats in GLP toxicology studies. About 32 µl of blood is collected with a capillary, processed to plasma and stored in a 10- or 4-µl capillary which is washed out further downstream in the laboratory. CMS has been standardized with respect to materials, assay validation experiments and application for sample analysis. The implementation of CMS has resulted in blood volume reductions in the rat from 300 to 32 µl per time point and the elimination of toxicokinetic satellite groups in the majority of the rat GLP toxicology studies. The technique has been successfully applied in 26 GLP studies for 12 different projects thus far.

Latin America's present and future challenges in toxicology education

International Nuclear Information System (INIS)

Rojas, M.

2005-01-01

Industrialization that Latin America has experienced during the past 50 years, the increase of population and the growth of chemical-related industries has generated a variety of environmental problems that must be addressed. After assessing these profound changes, greater emphasis should be placed on the study of environmental health and toxicology. Latin American countries face many problems that are common to other developing nations. Therefore, there is a demand for safety assessment and regulatory control of chemicals that create a need for increasing numbers of toxicologists. To meet this demand, educational programs in toxicology have to be designed. This paper utilizes a consultation questionnaire that includes toxicology-network members, scientists and educational institutions where toxicology is taught. An analysis of the information collected is made, with an emphasis on what we currently lack and on future challenges for toxicology professionals. Although the response from the study institutions was 65% (13 countries out of 20), the paper aims to assess the present situation of toxicology. The convenience for a certification/recognition for toxicologists is also evaluated. Action needs to be taken to promote scientific development based on regional specific needs that require increasing at the number of toxicology programs, and promoting of cooperation between academics and researchers. Among the limitations we have are the variability of curricula, objectives and priorities. The increasing globalization of markets and regulations requires the harmonization of graduate/postgraduate programs to ensure that risk assessment and management are dealt with uniformly. Cooperation among our countries and international assistance should play a more prominent role in the promotion of regional integration and the more efficient utilization of international experience in defining educational policies

Four Approaches to Project Evaluation

DEFF Research Database (Denmark)

Laursen, Markus; Svejvig, Per; Rode, Anna Le Gerstrøm

. Each of the framework’s four approaches provides a distinct evaluation that sheds light on some issues while leaving others unattended. Following these lines, the paper calls for more multi-faceted project evaluations. Introducing a framework that can help analyze existing evaluations and structure......There are many theoretical and practical reasons for evaluating projects – including explorative arguments focusing on expanding descriptive knowledge on project work as well as normative arguments focusing on improving prescriptive models of project performance. Despite the need for project...... management methodologies that work and combat project failure, and research methods that can assess effective project management and methodologies, as well as empirical research on the actuality of projects as practice, evaluation research on projects including project management and methodologies is scarce...

Extracorporeal Membrane Oxygenation (ECMO) for Severe Toxicological Exposures: Review of the Toxicology Investigators Consortium (ToxIC).

Science.gov (United States)

Wang, G S; Levitan, R; Wiegand, T J; Lowry, J; Schult, R F; Yin, S

2016-03-01

Although there have been many developments related to specific strategies for treating patients after poisoning exposures, the mainstay of therapy remains symptomatic and supportive care. One of the most aggressive supportive modalities is extracorporeal membrane oxygenation (ECMO). Our goal was to describe the use of ECMO for toxicological exposures reported to the American College of Medical Toxicology (ACMT) Toxicology Investigators Consortium (ToxIC). We performed a retrospective review of the ACMT ToxIC Registry from January 1, 2010 to December 31, 2013. Inclusion criteria included patients aged 0 to 89 years, evaluated between January 2010 through December 2013, and received ECMO for toxicological exposure. There were 26,271 exposures (60 % female) reported to the ToxIC Registry, 10 (0.0004 %) received ECMO: 4 pediatric (18 years). Time of initiation of ECMO ranged from 4 h to 4 days, with duration from 15 h to 12 days. Exposures included carbon monoxide/smoke inhalation (2), bitter almonds, methanol, and several medications including antihistamines (2), antipsychotic/antidepressant (2), cardiovascular drugs (2), analgesics (2), sedative/hypnotics (2), and antidiabetics (2). Four ECMO patients received cardiopulmonary resuscitation (CPR) during their hospital course, and the overall survival rate was 80 %. ECMO was rarely used for poisoning exposures in the ACMT ToxIC Registry. ECMO was utilized for a variety of ages and for pharmaceutical and non-pharmaceutical exposures. In most cases, ECMO was administered prior to cardiovascular failure, and survival rate was high. If available, ECMO may be a valid treatment modality.

Radiological/toxicological sabotage assessments at the Savannah River Site

International Nuclear Information System (INIS)

Johnson, H.D.; Pascal, M.D.; Richardson, D.L.

1995-01-01

This paper describes the methods being employed by Westinghouse Savannah River Company (WSRC) to perform graded assessments of radiological and toxicological sabotage vulnerability at Savannah River Site (SRS) facilities. These assessments are conducted to ensure that effective measures are in place to prevent, mitigate, and respond to a potential sabotage event which may cause an airborne release of radiological/toxicological material, causing an adverse effect on the health and safety of employees, the public, and the environment. Department of Energy (DOE) Notice 5630.3A, open-quotes Protection of Departmental Facilities Against Radiological and Toxicological Sabotage,close quotes and the associated April 1993 DOE-Headquarters guidance provide the requirements and outline an eight-step process for hazardous material evaluation. The process requires the integration of information from a variety of disciplines, including safety, safeguards and security, and emergency preparedness. This paper summarizes WSRC's approach towards implementation of the DOE requirements, and explains the inter-relationships between the Radiological and Toxicological Assessments developed using this process, and facility Hazard Assessment Reports (HAs), Safety Analysis Reports (SARs), and Facility Vulnerability Assessments (VAs)

Research Project Evaluation-Learnings from the PATHWAYS Project Experience.

Science.gov (United States)

Galas, Aleksander; Pilat, Aleksandra; Leonardi, Matilde; Tobiasz-Adamczyk, Beata

2018-05-25

Every research project faces challenges regarding how to achieve its goals in a timely and effective manner. The purpose of this paper is to present a project evaluation methodology gathered during the implementation of the Participation to Healthy Workplaces and Inclusive Strategies in the Work Sector (the EU PATHWAYS Project). The PATHWAYS project involved multiple countries and multi-cultural aspects of re/integrating chronically ill patients into labor markets in different countries. This paper describes key project's evaluation issues including: (1) purposes, (2) advisability, (3) tools, (4) implementation, and (5) possible benefits and presents the advantages of a continuous monitoring. Project evaluation tool to assess structure and resources, process, management and communication, achievements, and outcomes. The project used a mixed evaluation approach and included Strengths (S), Weaknesses (W), Opportunities (O), and Threats (SWOT) analysis. A methodology for longitudinal EU projects' evaluation is described. The evaluation process allowed to highlight strengths and weaknesses and highlighted good coordination and communication between project partners as well as some key issues such as: the need for a shared glossary covering areas investigated by the project, problematic issues related to the involvement of stakeholders from outside the project, and issues with timing. Numerical SWOT analysis showed improvement in project performance over time. The proportion of participating project partners in the evaluation varied from 100% to 83.3%. There is a need for the implementation of a structured evaluation process in multidisciplinary projects involving different stakeholders in diverse socio-environmental and political conditions. Based on the PATHWAYS experience, a clear monitoring methodology is suggested as essential in every multidisciplinary research projects.

Occupational medicine and toxicology

Directory of Open Access Journals (Sweden)

Fischer Axel

2006-02-01

Full Text Available Abstract This editorial is to announce the Journal of Occupational Medicine and Toxicology, a new Open Access, peer-reviewed, online journal published by BioMed Central. Occupational medicine and toxicology belong to the most wide ranging disciplines of all medical specialties. The field is devoted to the diagnosis, prevention, management and scientific analysis of diseases from the fields of occupational and environmental medicine and toxicology. It also covers the promotion of occupational and environmental health. The complexity of modern industrial processes has dramatically changed over the past years and today's areas include effects of atmospheric pollution, carcinogenesis, biological monitoring, ergonomics, epidemiology, product safety and health promotion. We hope that the launch of the Journal of Occupational Medicine and Toxicology will aid in the advance of these important areas of research bringing together multi-disciplinary research findings.

Agenda of behavioral toxicology

Energy Technology Data Exchange (ETDEWEB)

Weiss, B

1978-01-01

The author describes behavioral toxicology as a new discipline and contrasts it to the fields of physics and pharmacology. Several questions are raised and discussed concerning the field of behavioral toxicology. Some of these questions are: (1) how is an adverse behavioral effect recognized; (2) how can the non-specific be specified; (3) are standardized test batteries feasible. The problem of chronic intake is discussed as well as drawing information from other related disciplines such as neurochemistry, neuropathology and neurophysiology. The author concludes with several statements concerning new directions in the discipline of behavioral toxicology.

EXPERIMENTAL AND MATHEMATICAL MODELING METHODS FOR THE INVESTIGATION OF TOXICOLOGICAL INTERACTIONS

Science.gov (United States)

While procedures have been developed and used for many years to assess risk and determine acceptable exposure levels to individual chemicals, most cases of environmental contamination can result in concurrent or sequential exposure to more than one chemical. Toxicological predict...

High Throughput Transcriptomics @ USEPA (Toxicology ...

Science.gov (United States)

The ideal chemical testing approach will provide complete coverage of all relevant toxicological responses. It should be sensitive and specific It should identify the mechanism/mode-of-action (with dose-dependence). It should identify responses relevant to the species of interest. Responses should ideally be translated into tissue-, organ-, and organism-level effects. It must be economical and scalable. Using a High Throughput Transcriptomics platform within US EPA provides broader coverage of biological activity space and toxicological MOAs and helps fill the toxicological data gap. Slide presentation at the 2016 ToxForum on using High Throughput Transcriptomics at US EPA for broader coverage biological activity space and toxicological MOAs.

Summary introduction to environmental toxicology

International Nuclear Information System (INIS)

Heinzow, B.; Jessen, H.; Wendorff, D.

1986-01-01

The increasing environmental consciousness and the increasing public interest in environmental medicine and toxicology is much appreciated by the Research Institute for Environmental Toxicology. This information brochure gives the reader some insight into the importance of environmental toxicology and into the waste of the Research Institute. In response to the current situation, the authors have included an appendix on radiation protection. (orig./PW) [de

An empirical evaluation of classification algorithms for fault prediction in open source projects

Directory of Open Access Journals (Sweden)

Arvinder Kaur

2018-01-01

Full Text Available Creating software with high quality has become difficult these days with the fact that size and complexity of the developed software is high. Predicting the quality of software in early phases helps to reduce testing resources. Various statistical and machine learning techniques are used for prediction of the quality of the software. In this paper, six machine learning models have been used for software quality prediction on five open source software. Varieties of metrics have been evaluated for the software including C & K, Henderson & Sellers, McCabe etc. Results show that Random Forest and Bagging produce good results while Naïve Bayes is least preferable for prediction.

The Emergence of Systematic Review in Toxicology.

Science.gov (United States)

Stephens, Martin L; Betts, Kellyn; Beck, Nancy B; Cogliano, Vincent; Dickersin, Kay; Fitzpatrick, Suzanne; Freeman, James; Gray, George; Hartung, Thomas; McPartland, Jennifer; Rooney, Andrew A; Scherer, Roberta W; Verloo, Didier; Hoffmann, Sebastian

2016-07-01

The Evidence-based Toxicology Collaboration hosted a workshop on "The Emergence of Systematic Review and Related Evidence-based Approaches in Toxicology," on November 21, 2014 in Baltimore, Maryland. The workshop featured speakers from agencies and organizations applying systematic review approaches to questions in toxicology, speakers with experience in conducting systematic reviews in medicine and healthcare, and stakeholders in industry, government, academia, and non-governmental organizations. Based on the workshop presentations and discussion, here we address the state of systematic review methods in toxicology, historical antecedents in both medicine and toxicology, challenges to the translation of systematic review from medicine to toxicology, and thoughts on the way forward. We conclude with a recommendation that as various agencies and organizations adapt systematic review methods, they continue to work together to ensure that there is a harmonized process for how the basic elements of systematic review methods are applied in toxicology. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology.

Finding toxicological information: An approach for occupational health professionals

Directory of Open Access Journals (Sweden)

Franco Giuliano

2008-08-01

Full Text Available Abstract Background It can be difficult for occupational health professionals to assess which toxicological databases available on the Internet are the most useful for answering their questions. Therefore we evaluated toxicological databases for their ability to answer practical questions about exposure and prevention. We also propose recommended practices for searching for toxicological properties of chemicals. Methods We used a systematic search to find databases available on the Internet. Our criteria for the databases were the following: has a search engine, includes factual information on toxic and hazardous chemicals harmful for human health, and is free of charge. We developed both a qualitative and a quantitative rating method, which was used by four independent assessors to determine appropriateness, the quality of content, and ease of use of the database. Final ratings were based on a consensus of at least two evaluators. Results Out of 822 results we found 21 databases that met our inclusion criteria. Out of these 21 databases 14 are administered in the US, five in Europe, one in Australia, and one in Canada. Nine are administered by a governmental organization. No database achieved the maximum score of 27. The databases GESTIS, ESIS, Hazardous Substances Data Bank, TOXNET and NIOSH Pocket Guide to Chemical Hazards all scored more than 20 points. The following approach was developed for occupational health professionals searching for the toxicological properties of chemicals: start with the identity of the chemical; then search for health hazards, exposure route and measurement; next the limit values; and finally look for the preventive measures. Conclusion A rating system of toxicological databases to assess their value for occupational health professionals discriminated well between databases in terms of their appropriateness, quality of information, and ease of use. Several American and European databases yielded high scores and

Bottlenecks in Software Defect Prediction Implementation in Industrial Projects

OpenAIRE

Hryszko Jarosław; Madeyski Lech

2015-01-01

Case studies focused on software defect prediction in real, industrial software development projects are extremely rare. We report on dedicated R&D project established in cooperation between Wroclaw University of Technology and one of the leading automotive software development companies to research possibilities of introduction of software defect prediction using an open source, extensible software measurement and defect prediction framework called DePress (Defect Prediction in Software Syst...

Metabolomics in Toxicology and Preclinical Research

Science.gov (United States)

Ramirez, Tzutzuy; Daneshian, Mardas; Kamp, Hennicke; Bois, Frederic Y.; Clench, Malcolm R.; Coen, Muireann; Donley, Beth; Fischer, Steven M.; Ekman, Drew R.; Fabian, Eric; Guillou, Claude; Heuer, Joachim; Hogberg, Helena T.; Jungnickel, Harald; Keun, Hector C.; Krennrich, Gerhard; Krupp, Eckart; Luch, Andreas; Noor, Fozia; Peter, Erik; Riefke, Bjoern; Seymour, Mark; Skinner, Nigel; Smirnova, Lena; Verheij, Elwin; Wagner, Silvia; Hartung, Thomas; van Ravenzwaay, Bennard; Leist, Marcel

2013-01-01

Summary Metabolomics, the comprehensive analysis of metabolites in a biological system, provides detailed information about the biochemical/physiological status of a biological system, and about the changes caused by chemicals. Metabolomics analysis is used in many fields, ranging from the analysis of the physiological status of genetically modified organisms in safety science to the evaluation of human health conditions. In toxicology, metabolomics is the -omics discipline that is most closely related to classical knowledge of disturbed biochemical pathways. It allows rapid identification of the potential targets of a hazardous compound. It can give information on target organs and often can help to improve our understanding regarding the mode-of-action of a given compound. Such insights aid the discovery of biomarkers that either indicate pathophysiological conditions or help the monitoring of the efficacy of drug therapies. The first toxicological applications of metabolomics were for mechanistic research, but different ways to use the technology in a regulatory context are being explored. Ideally, further progress in that direction will position the metabolomics approach to address the challenges of toxicology of the 21st century. To address these issues, scientists from academia, industry, and regulatory bodies came together in a workshop to discuss the current status of applied metabolomics and its potential in the safety assessment of compounds. We report here on the conclusions of three working groups addressing questions regarding 1) metabolomics for in vitro studies 2) the appropriate use of metabolomics in systems toxicology, and 3) use of metabolomics in a regulatory context. PMID:23665807

Integrating Personalized Technology in Toxicology: Sensors, Smart Glass, and Social Media Applications in Toxicology Research.

Science.gov (United States)

Carreiro, Stephanie; Chai, Peter R; Carey, Jennifer; Chapman, Brittany; Boyer, Edward W

2017-06-01

Rapid proliferation of mobile technologies in social and healthcare spaces create an opportunity for advancement in research and clinical practice. The application of mobile, personalized technology in healthcare, referred to as mHealth, has not yet become routine in toxicology. However, key features of our practice environment, such as frequent need for remote evaluation, unreliable historical data from patients, and sensitive subject matter, make mHealth tools appealing solutions in comparison to traditional methods that collect retrospective or indirect data. This manuscript describes the features, uses, and costs associated with several of common sectors of mHealth research including wearable biosensors, ingestible biosensors, head-mounted devices, and social media applications. The benefits and novel challenges associated with the study and use of these applications are then discussed. Finally, opportunities for further research and integration are explored with a particular focus on toxicology-based applications.

History of Japanese Society of Toxicology.

Science.gov (United States)

Satoh, Tetsuo

2016-01-01

Founded in 1981, the Japanese Society of Toxicology (JSOT) has grown into an organization of nearly 3,000 members working together to advance the nation's scientific knowledge and understanding of toxicology through the implementation of planning that ensures a systematic and efficient expenditure of energies and resources, and is closely aligned with a strategy for accomplishing the Society's long-range plans. To promote public education in toxicology, the Society organizes public lectures during each year's annual meeting. Other activities include hosting scientific conferences, promoting continuing education, and facilitating international collaboration. Internally, the JSOT operates five standing committees: General Affairs, Educational, Editorial, Finance, and Science and Publicity to handle its necessary relationships. To bestow official recognition, the Society established its Toxicologist Certification Program in 1997, and has certified 536 members as Diplomat Toxicologists (DJSOT) as of May 1, 2016. Furthermore, on the same date, 43 JSOT members were certified as Emeritus Diplomats of the JSOT (EDJSOT). The Society has launched two official journals, the "Journal of Toxicological Sciences (JTS)" in 1981 and "Fundamental Toxicological Sciences (Fundam. Toxicol. Sci.)" in 2014. As for participation in the international organizations, the JSOT (then known as the Toxicological Research Group) joined the International Union of Toxicology as a charter member in 1980, and became a founding member of the Asian Society of Toxicology at its inauguration in 1994. Into the future, the JSOT will continue working diligently to advance knowledge and understanding of toxicology and secure its place among the interdisciplinary fields of science, humane studies, and ethics.

SERS as a tool for in vitro toxicology.

Science.gov (United States)

Fisher, Kate M; McLeish, Jennifer A; Jamieson, Lauren E; Jiang, Jing; Hopgood, James R; McLaughlin, Stephen; Donaldson, Ken; Campbell, Colin J

2016-06-23

Measuring markers of stress such as pH and redox potential are important when studying toxicology in in vitro models because they are markers of oxidative stress, apoptosis and viability. While surface enhanced Raman spectroscopy is ideally suited to the measurement of redox potential and pH in live cells, the time-intensive nature and perceived difficulty in signal analysis and interpretation can be a barrier to its broad uptake by the biological community. In this paper we detail the development of signal processing and analysis algorithms that allow SERS spectra to be automatically processed so that the output of the processing is a pH or redox potential value. By automating signal processing we were able to carry out a comparative evaluation of the toxicology of silver and zinc oxide nanoparticles and correlate our findings with qPCR analysis. The combination of these two analytical techniques sheds light on the differences in toxicology between these two materials from the perspective of oxidative stress.

Animal-free toxicology

DEFF Research Database (Denmark)

Knudsen, Lisbeth E

2013-01-01

Human data on exposure and adverse effects are the most appropriate for human risk assessment, and modern toxicology focuses on human pathway analysis and the development of human biomarkers. Human biomonitoring and human placental transport studies provide necessary information for human risk...... assessment, in accordance with the legislation on chemical, medicine and food safety. Toxicology studies based on human mechanistic and exposure information can replace animal studies. These animal-free approaches can be further supplemented by new in silico methods and chemical structure......-activity relationships. The inclusion of replacement expertise in the international Three Rs centres, the ongoing exploration of alternatives to animal research, and the improvement of conditions for research animals, all imply the beginning of a paradigm shift in toxicology research toward the use of human data....

42 CFR 493.1213 - Condition: Toxicology.

Science.gov (United States)

2010-10-01

... 42 Public Health 5 2010-10-01 2010-10-01 false Condition: Toxicology. 493.1213 Section 493.1213 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES....1213 Condition: Toxicology. If the laboratory provides services in the subspecialty of Toxicology, the...

Toxicology in Asia--Past, present, and future.

Science.gov (United States)

Satoh, T

2015-12-01

The Asian Society of Toxicology (ASIATOX), which consists of the seven national toxicology member societies of Japan, Korea, China, Taiwan, Thailand, Singapore, and Iran, now boasts of more than 3,000 members from a variety of industries, academia, and regulatory organizations. ASIATOX congresses are spaced three years apart and rotated among the member societies. In 1995, ASIATOX joined the International Union of Toxicology (IUTOX) as a regional society, and now serves as the scientific voice of toxicology in Asia under the IUTOX umbrella. Since its inauguration, the society has worked diligently to handle matters deemed essential to promoting the vision set fourth by its founders. Future perspectives of ASIATOX include the establishment of education and training programs, and the certification and accreditation of toxicologists. As the leading voice of toxicology in Asia, the society seeks to extend knowledge of toxicological issues to developing nations in Asia based on the following missions and goals: (1) to provide leadership as a worldwide scientific organization that objectively addresses global issues involving the toxicological sciences, (2) to broaden the geographical base of toxicology as a discipline and profession to all countries of the world, and (3) to pursue capacity building in toxicology, particularly in developing countries, while utilizing its global perspective and network to contribute to the enhancement of toxicology education and the career development of young toxicologists. © The Author(s) 2015.

Diagnostic yield of hair and urine toxicology testing in potential child abuse cases.

Science.gov (United States)

Stauffer, Stephanie L; Wood, Stephanie M; Krasowski, Matthew D

2015-07-01

Detection of drugs in a child may be the first objective finding that can be reported in cases of suspected child abuse. Hair and urine toxicology testing, when performed as part of the initial clinical evaluation for suspected child abuse or maltreatment, may serve to facilitate the identification of at-risk children. Furthermore, significant environmental exposure to a drug (considered by law to constitute child abuse in some states) may be identified by toxicology testing of unwashed hair specimens. In order to determine the clinical utility of hair and urine toxicology testing in this population we performed a retrospective chart review on all children for whom hair toxicology testing was ordered at our academic medical center between January 2004 and April 2014. The medical records of 616 children aged 0-17.5 years were reviewed for injury history, previous medication and illicit drug use by caregiver(s), urine drug screen result (if performed), hair toxicology result, medication list, and outcome of any child abuse evaluation. Hair toxicology testing was positive for at least one compound in 106 cases (17.2%), with unexplained drugs in 82 cases (13.3%). Of these, there were 48 cases in which multiple compounds (including combination of parent drugs and/or metabolites within the same drug class) were identified in the sample of one patient. The compounds most frequently identified in the hair of our study population included cocaine, benzoylecgonine, native (unmetabolized) tetrahydrocannabinol, and methamphetamine. There were 68 instances in which a parent drug was identified in the hair without any of its potential metabolites, suggesting environmental exposure. Among the 82 cases in which hair toxicology testing was positive for unexplained drugs, a change in clinical outcome was noted in 71 cases (86.5%). Urine drug screens (UDS) were performed in 457 of the 616 reviewed cases. Of these, over 95% of positive UDS results could be explained by iatrogenic drug

Characterization and validation of an in silico toxicology model to predict the mutagenic potential of drug impurities*

Energy Technology Data Exchange (ETDEWEB)

Valerio, Luis G., E-mail: luis.valerio@fda.hhs.gov [Science and Research Staff, Office of Pharmaceutical Science, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD 20993–0002 (United States); Cross, Kevin P. [Leadscope, Inc., 1393 Dublin Road, Columbus, OH, 43215–1084 (United States)

2012-05-01

Control and minimization of human exposure to potential genotoxic impurities found in drug substances and products is an important part of preclinical safety assessments of new drug products. The FDA's 2008 draft guidance on genotoxic and carcinogenic impurities in drug substances and products allows use of computational quantitative structure–activity relationships (QSAR) to identify structural alerts for known and expected impurities present at levels below qualified thresholds. This study provides the information necessary to establish the practical use of a new in silico toxicology model for predicting Salmonella t. mutagenicity (Ames assay outcome) of drug impurities and other chemicals. We describe the model's chemical content and toxicity fingerprint in terms of compound space, molecular and structural toxicophores, and have rigorously tested its predictive power using both cross-validation and external validation experiments, as well as case studies. Consistent with desired regulatory use, the model performs with high sensitivity (81%) and high negative predictivity (81%) based on external validation with 2368 compounds foreign to the model and having known mutagenicity. A database of drug impurities was created from proprietary FDA submissions and the public literature which found significant overlap between the structural features of drug impurities and training set chemicals in the QSAR model. Overall, the model's predictive performance was found to be acceptable for screening drug impurities for Salmonella mutagenicity. -- Highlights: ► We characterize a new in silico model to predict mutagenicity of drug impurities. ► The model predicts Salmonella mutagenicity and will be useful for safety assessment. ► We examine toxicity fingerprints and toxicophores of this Ames assay model. ► We compare these attributes to those found in drug impurities known to FDA/CDER. ► We validate the model and find it has a desired predictive

Characterization and validation of an in silico toxicology model to predict the mutagenic potential of drug impurities*

International Nuclear Information System (INIS)

Valerio, Luis G.; Cross, Kevin P.

2012-01-01

Control and minimization of human exposure to potential genotoxic impurities found in drug substances and products is an important part of preclinical safety assessments of new drug products. The FDA's 2008 draft guidance on genotoxic and carcinogenic impurities in drug substances and products allows use of computational quantitative structure–activity relationships (QSAR) to identify structural alerts for known and expected impurities present at levels below qualified thresholds. This study provides the information necessary to establish the practical use of a new in silico toxicology model for predicting Salmonella t. mutagenicity (Ames assay outcome) of drug impurities and other chemicals. We describe the model's chemical content and toxicity fingerprint in terms of compound space, molecular and structural toxicophores, and have rigorously tested its predictive power using both cross-validation and external validation experiments, as well as case studies. Consistent with desired regulatory use, the model performs with high sensitivity (81%) and high negative predictivity (81%) based on external validation with 2368 compounds foreign to the model and having known mutagenicity. A database of drug impurities was created from proprietary FDA submissions and the public literature which found significant overlap between the structural features of drug impurities and training set chemicals in the QSAR model. Overall, the model's predictive performance was found to be acceptable for screening drug impurities for Salmonella mutagenicity. -- Highlights: ► We characterize a new in silico model to predict mutagenicity of drug impurities. ► The model predicts Salmonella mutagenicity and will be useful for safety assessment. ► We examine toxicity fingerprints and toxicophores of this Ames assay model. ► We compare these attributes to those found in drug impurities known to FDA/CDER. ► We validate the model and find it has a desired predictive performance.

Toxicological benchmarks for wildlife: 1994 Revision

International Nuclear Information System (INIS)

Opresko, D.M.; Sample, B.E.; Suter, G.W. II.

1994-09-01

The process by which ecological risks of environmental contaminants are evaluated is two-tiered. The first tier is a screening assessment where concentrations of contaminants in the environment are compared to toxicological benchmarks which represent concentrations of chemicals in environmental media (water, sediment, soil, food, etc.) that are presumed to be nonhazardous to the surrounding biota. The second tier is a baseline ecological risk assessment where toxicological benchmarks are one of several lines of evidence used to support or refute the presence of ecological effects. The report presents toxicological benchmarks for assessment of effects of 76 chemicals on 8 representative mammalian wildlife species and 31 chemicals on 9 avian wildlife species. The chemicals are some of those that occur at United States Department of Energy waste sites; the wildlife species were chosen because they are widely distributed and provide a representative range of body sizes and diets. Further descriptions of the chosen wildlife species and chemicals are provided in the report. The benchmarks presented in this report represent values believed to be nonhazardous for the listed wildlife species. These benchmarks only consider contaminant exposure through oral ingestion of contaminated media; exposure through inhalation or direct dermal exposure are not considered in this report

Toxicological benchmarks for wildlife: 1994 Revision

Energy Technology Data Exchange (ETDEWEB)

Opresko, D.M.; Sample, B.E.; Suter, G.W. II

1994-09-01

The process by which ecological risks of environmental contaminants are evaluated is two-tiered. The first tier is a screening assessment where concentrations of contaminants in the environment are compared to toxicological benchmarks which represent concentrations of chemicals in environmental media (water, sediment, soil, food, etc.) that are presumed to be nonhazardous to the surrounding biota. The second tier is a baseline ecological risk assessment where toxicological benchmarks are one of several lines of evidence used to support or refute the presence of ecological effects. The report presents toxicological benchmarks for assessment of effects of 76 chemicals on 8 representative mammalian wildlife species and 31 chemicals on 9 avian wildlife species. The chemicals are some of those that occur at United States Department of Energy waste sites; the wildlife species were chosen because they are widely distributed and provide a representative range of body sizes and diets. Further descriptions of the chosen wildlife species and chemicals are provided in the report. The benchmarks presented in this report represent values believed to be nonhazardous for the listed wildlife species. These benchmarks only consider contaminant exposure through oral ingestion of contaminated media; exposure through inhalation or direct dermal exposure are not considered in this report.

Toxicological evaluation of natural rubber latex film vulcanized with ionizing radiation

International Nuclear Information System (INIS)

Campos, Vania E.; Higa, Olga Z.; Guedes, Selma M.L.; Hanada, Seico

1999-01-01

The industrial vulcanization of natural rubber latex (NRL) is made worldwide by conventional process using sulphur, but it can be made by an alternative process using ionizing radiation. The main advantages of this process are related to absence of toxic effect promoted by chemical substances added to the NRL on the conventional process. In this research was tested the toxicological properties of the films vulcanized by the alternative process in relation to that vulcanized by the conventional process. The toxicity was evaluated by in vitro cytotoxicity assay and in vivo systemic toxicity assay. The results showed that vulcanized films by gamma ray are less cytotoxic. The systemic toxicity assay showed that only the vulcanized film using sulphur induced allaying and motor in coordination on the animals for a short period of time. these results evidence the less cytotoxic properties of vulcanized films by gamma ray in relation to that vulcanized by conventional process using sulphur. (author)

[Interest of toxicological analysis for poisonings].

Science.gov (United States)

Mégarbane, Bruno; Baud, Frédéric J

2008-04-30

The clinical approach of the poisoned patients is mainly based on the analysis of the circumstances of intoxication and the search for toxidromes. Toxicological analysis aims to detect the toxicants or measure their concentrations, in order to confirm the hypothesis of poisoning, to evaluate its severity and to help the follow-up regarding the treatment efficiency. Emergent toxicological analysis appears only useful if the method is specific and the results rapidly obtained. Therefore, systematic screening using immunochesmistry-based tests is not recommended in the situation of emergency. Measurement of blood concentrations of the toxicants is only indicated if it may influence the patient management. However, in the perspective of research, the study of toxicokinetic/toxicodynamic relationships, i.e. the relationships between the toxicant effects and its blood concentrations, may be helpful to understand the inter-individual variability of the response to a toxicant.

Evaluating the Impact of the U.S. National Toxicology Program: A Case Study on Hexavalent Chromium.

Science.gov (United States)

Xie, Yun; Holmgren, Stephanie; Andrews, Danica M K; Wolfe, Mary S

2017-02-01

Evaluating the impact of federally funded research with a broad, methodical, and objective approach is important to ensure that public funds advance the mission of federal agencies. We aimed to develop a methodical approach that would yield a broad assessment of National Toxicology Program's (NTP's) effectiveness across multiple sectors and demonstrate the utility of the approach through a case study. A conceptual model was developed with defined activities, outputs (products), and outcomes (proximal, intermediate, distal) and applied retrospectively to NTP's research on hexavalent chromium (CrVI). Proximal outcomes were measured by counting views of and requests for NTP's products by external stakeholders. Intermediate outcomes were measured by bibliometric analysis. Distal outcomes were assessed through Web and LexisNexis searches for documents related to legislation or regulation changes. The approach identified awareness of NTP's work on CrVI by external stakeholders (proximal outcome) and citations of NTP's research in scientific publications, reports, congressional testimonies, and legal and policy documents (intermediate outcome). NTP's research was key to the nation's first-ever drinking water standard for CrVI adopted by California in 2014 (distal outcome). By applying this approach to a case study, the utility and limitations of the approach were identified, including challenges to evaluating the outcomes of a research program. This study identified a broad and objective approach for assessing NTP's effectiveness, including methodological needs for more thorough and efficient impact assessments in the future. Citation: Xie Y, Holmgren S, Andrews DMK, Wolfe MS. 2017. Evaluating the impact of the U.S. National Toxicology Program: a case study on hexavalent chromium. Environ Health Perspect 125:181-188; http://dx.doi.org/10.1289/EHP21.

Aerospace Toxicology and Microbiology

Science.gov (United States)

James, John T.; Parmet, A. J.; Pierson, Duane L.

2007-01-01

Toxicology dates to the very earliest history of humanity with various poisons and venom being recognized as a method of hunting or waging war with the earliest documentation in the Evers papyrus (circa 1500 BCE). The Greeks identified specific poisons such as hemlock, a method of state execution, and the Greek word toxos (arrow) became the root of our modern science. The first scientific approach to the understanding of poisons and toxicology was the work during the late middle ages of Paracelsus. He formulated what were then revolutionary views that a specific toxic agent or "toxicon" caused specific dose-related effects. His principles have established the basis of modern pharmacology and toxicology. In 1700, Bernardo Ramazzini published the book De Morbis Artificum Diatriba (The Diseases of Workers) describing specific illnesses associated with certain labor, particularly metal workers exposed to mercury, lead, arsenic, and rock dust. Modern toxicology dates from development of the modern industrial chemical processes, the earliest involving an analytical method for arsenic by Marsh in 1836. Industrial organic chemicals were synthesized in the late 1800 s along with anesthetics and disinfectants. In 1908, Hamilton began the long study of occupational toxicology issues, and by WW I the scientific use of toxicants saw Haber creating war gases and defining time-dosage relationships that are used even today.

The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project

DEFF Research Database (Denmark)

Hudson, Lawrence N; Newbold, Tim; Contu, Sara

2017-01-01

The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity ...

Toxicological Benchmarks for Wildlife

Energy Technology Data Exchange (ETDEWEB)

Sample, B.E. Opresko, D.M. Suter, G.W.

1993-01-01

Ecological risks of environmental contaminants are evaluated by using a two-tiered process. In the first tier, a screening assessment is performed where concentrations of contaminants in the environment are compared to no observed adverse effects level (NOAEL)-based toxicological benchmarks. These benchmarks represent concentrations of chemicals (i.e., concentrations presumed to be nonhazardous to the biota) in environmental media (water, sediment, soil, food, etc.). While exceedance of these benchmarks does not indicate any particular level or type of risk, concentrations below the benchmarks should not result in significant effects. In practice, when contaminant concentrations in food or water resources are less than these toxicological benchmarks, the contaminants may be excluded from further consideration. However, if the concentration of a contaminant exceeds a benchmark, that contaminant should be retained as a contaminant of potential concern (COPC) and investigated further. The second tier in ecological risk assessment, the baseline ecological risk assessment, may use toxicological benchmarks as part of a weight-of-evidence approach (Suter 1993). Under this approach, based toxicological benchmarks are one of several lines of evidence used to support or refute the presence of ecological effects. Other sources of evidence include media toxicity tests, surveys of biota (abundance and diversity), measures of contaminant body burdens, and biomarkers. This report presents NOAEL- and lowest observed adverse effects level (LOAEL)-based toxicological benchmarks for assessment of effects of 85 chemicals on 9 representative mammalian wildlife species (short-tailed shrew, little brown bat, meadow vole, white-footed mouse, cottontail rabbit, mink, red fox, and whitetail deer) or 11 avian wildlife species (American robin, rough-winged swallow, American woodcock, wild turkey, belted kingfisher, great blue heron, barred owl, barn owl, Cooper's hawk, and red

IRIS Toxicological Review of Hexahydro-1,3,5-Trinitro-1,3,5 ...

Science.gov (United States)

The IRIS Toxicological Review of Hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) was released for external peer review in September 2016. The EPA’s Science Advisory Board’s (SAB) Chemical Assessment Advisory Committee (CAAC) will conduct a peer review of the scientific basis supporting the RDX assessment and release a final report of their review. Information regarding the peer review can be found on the SAB website. EPA is undertaking an update of the Integrated Risk Information System (IRIS) health assessment for RDX. The outcome of this project is an updated Toxicological Review and IRIS Summary for RDX that will be entered into the IRIS database.

Research on cross - Project software defect prediction based on transfer learning

Science.gov (United States)

Chen, Ya; Ding, Xiaoming

2018-04-01

According to the two challenges in the prediction of cross-project software defects, the distribution differences between the source project and the target project dataset and the class imbalance in the dataset, proposing a cross-project software defect prediction method based on transfer learning, named NTrA. Firstly, solving the source project data's class imbalance based on the Augmented Neighborhood Cleaning Algorithm. Secondly, the data gravity method is used to give different weights on the basis of the attribute similarity of source project and target project data. Finally, a defect prediction model is constructed by using Trad boost algorithm. Experiments were conducted using data, come from NASA and SOFTLAB respectively, from a published PROMISE dataset. The results show that the method has achieved good values of recall and F-measure, and achieved good prediction results.

Non-precautionary aspects of toxicology

International Nuclear Information System (INIS)

Grandjean, Philippe

2005-01-01

Empirical studies in toxicology aim at deciphering complex causal relationships, especially in regard to human disease etiologies. Several scientific traditions limit the usefulness of documentation from current toxicological research, in regard to decision-making based on the precautionary principle. Among non-precautionary aspects of toxicology are the focus on simplified model systems and the effects of single hazards, one by one. Thus, less attention is paid to sources of variability and uncertainty, including individual susceptibility, impacts of mixed and variable exposures, susceptible life-stages, and vulnerable communities. In emphasizing the need for confirmatory evidence, toxicology tends to penalize false positives more than false negatives. An important source of uncertainty is measurement error that results in misclassification, especially in regard to exposure assessment. Standard statistical analysis assumes that the exposure is measured without error, and imprecisions will usually result in an underestimation of the dose-effect relationship. In testing whether an effect could be considered a possible result of natural variability, a 5% limit for 'statistical significance' is usually applied, even though it may rule out many findings of causal associations, simply because the study was too small (and thus lacked statistical power) or because some imprecision or limited sensitivity of the parameters precluded a more definitive observation. These limitations may be aggravated when toxicology is influenced by vested interests. Because current toxicology overlooks the important goal of achieving a better characterization of uncertainties and their implications, research approaches should be revised and strengthened to counteract the innate ideological biases, thereby supporting our confidence in using toxicology as a main source of documentation and in using the precautionary principle as a decision procedure in the public policy arena

Project evaluation: one framework - four approaches

DEFF Research Database (Denmark)

Rode, Anna Le Gerstrøm; Svejvig, Per

. Introducing a framework that can help structure such evaluations, the aim of this paper is to contribute to project theory and practice by inspiring project researchers and aiding project workers in their efforts to open up the black box of projects and deliver relevant and valuable results......There are many theoretical and practical reasons for evaluating projects – including explorative arguments focusing on expanding descriptive knowledge on projects as well as normative arguments focusing on developing prescriptive knowledge of project management. Despite the need for effective...... project management and research methods that can assess effective project management methodologies, extant literature on evaluation procedures or guidelines on how to evaluate projects and/or project management is scarce. To address this challenge, this paper introduces an evaluation framework consisting...

Computational toxicology as implemented by the U.S. EPA: providing high throughput decision support tools for screening and assessing chemical exposure, hazard and risk.

Science.gov (United States)

Kavlock, Robert; Dix, David

2010-02-01

Computational toxicology is the application of mathematical and computer models to help assess chemical hazards and risks to human health and the environment. Supported by advances in informatics, high-throughput screening (HTS) technologies, and systems biology, the U.S. Environmental Protection Agency EPA is developing robust and flexible computational tools that can be applied to the thousands of chemicals in commerce, and contaminant mixtures found in air, water, and hazardous-waste sites. The Office of Research and Development (ORD) Computational Toxicology Research Program (CTRP) is composed of three main elements. The largest component is the National Center for Computational Toxicology (NCCT), which was established in 2005 to coordinate research on chemical screening and prioritization, informatics, and systems modeling. The second element consists of related activities in the National Health and Environmental Effects Research Laboratory (NHEERL) and the National Exposure Research Laboratory (NERL). The third and final component consists of academic centers working on various aspects of computational toxicology and funded by the U.S. EPA Science to Achieve Results (STAR) program. Together these elements form the key components in the implementation of both the initial strategy, A Framework for a Computational Toxicology Research Program (U.S. EPA, 2003), and the newly released The U.S. Environmental Protection Agency's Strategic Plan for Evaluating the Toxicity of Chemicals (U.S. EPA, 2009a). Key intramural projects of the CTRP include digitizing legacy toxicity testing information toxicity reference database (ToxRefDB), predicting toxicity (ToxCast) and exposure (ExpoCast), and creating virtual liver (v-Liver) and virtual embryo (v-Embryo) systems models. U.S. EPA-funded STAR centers are also providing bioinformatics, computational toxicology data and models, and developmental toxicity data and models. The models and underlying data are being made publicly

Regulatory issues in accreditation of toxicology laboratories.

Science.gov (United States)

Bissell, Michael G

2012-09-01

Clinical toxicology laboratories and forensic toxicology laboratories operate in a highly regulated environment. This article outlines major US legal/regulatory issues and requirements relevant to accreditation of toxicology laboratories (state and local regulations are not covered in any depth). The most fundamental regulatory distinction involves the purposes for which the laboratory operates: clinical versus nonclinical. The applicable regulations and the requirements and options for operations depend most basically on this consideration, with clinical toxicology laboratories being directly subject to federal law including mandated options for accreditation and forensic toxicology laboratories being subject to degrees of voluntary or state government–required accreditation.

The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project

NARCIS (Netherlands)

Hudson, Lawrence N; Newbold, Tim; Contu, Sara; Hill, Samantha L L; Lysenko, Igor; De Palma, Adriana; Phillips, Helen R P; Alhusseini, Tamera I; Bedford, Felicity E; Bennett, Dominic J; Booth, Hollie; Burton, Victoria J; Chng, Charlotte W T; Choimes, Argyrios; Correia, David L P; Day, Julie; Echeverría-Londoño, Susy; Emerson, Susan R; Gao, Di; Garon, Morgan; Harrison, Michelle L K; Ingram, Daniel J; Jung, Martin; Kemp, Victoria; Kirkpatrick, Lucinda; Martin, Callum D; Pan, Yuan; Pask-Hale, Gwilym D; Pynegar, Edwin L; Robinson, Alexandra N; Sanchez-Ortiz, Katia; Senior, Rebecca A; Simmons, Benno I; White, Hannah J; Zhang, Hanbin; Aben, Job; Abrahamczyk, Stefan; Adum, Gilbert B; Aguilar-Barquero, Virginia; Aizen, Marcelo A; Albertos, Belén; Alcala, E L; Del Mar Alguacil, Maria; Alignier, Audrey; Ancrenaz, Marc; Andersen, Alan N; Arbeláez-Cortés, Enrique; Armbrecht, Inge; Arroyo-Rodríguez, Víctor; Aumann, Tom; Axmacher, Jan C; Azhar, Badrul; Azpiroz, Adrián B; Baeten, Lander; Bakayoko, Adama; Báldi, András; Banks, John E; Baral, Sharad K; Barlow, Jos; Barratt, Barbara I P; Barrico, Lurdes; Bartolommei, Paola; Barton, Diane M; Basset, Yves; Batáry, Péter; Bates, Adam J; Baur, Bruno; Bayne, Erin M; Beja, Pedro; Benedick, Suzan; Berg, Åke; Bernard, Henry; Berry, Nicholas J; Bhatt, Dinesh; Bicknell, Jake E; Bihn, Jochen H; Blake, Robin J; Bobo, Kadiri S; Bóçon, Roberto; Boekhout, Teun; Böhning-Gaese, Katrin; Bonham, Kevin J; Borges, Paulo A V; Borges, Sérgio H; Boutin, Céline; Bouyer, Jérémy; Bragagnolo, Cibele; Brandt, Jodi S; Brearley, Francis Q; Brito, Isabel; Bros, Vicenç; Brunet, Jörg; Buczkowski, Grzegorz; Buddle, Christopher M; Bugter, Rob; Buscardo, Erika; Buse, Jörn; Cabra-García, Jimmy; Cáceres, Nilton C; Cagle, Nicolette L; Calviño-Cancela, María; Cameron, Sydney A; Cancello, Eliana M; Caparrós, Rut; Cardoso, Pedro; Carpenter, Dan; Carrijo, Tiago F; Carvalho, Anelena L; Cassano, Camila R; Castro, Helena; Castro-Luna, Alejandro A; Rolando, Cerda B; Cerezo, Alexis; Chapman, Kim Alan; Chauvat, Matthieu; Christensen, Morten; Clarke, Francis M; Cleary, Daniel F R; Colombo, Giorgio; Connop, Stuart P; Craig, Michael D; Cruz-López, Leopoldo; Cunningham, Saul A; D'Aniello, Biagio; D'Cruze, Neil; da Silva, Pedro Giovâni; Dallimer, Martin; Danquah, Emmanuel; Darvill, Ben; Dauber, Jens; Davis, Adrian L V; Dawson, Jeff; de Sassi, Claudio; de Thoisy, Benoit; Deheuvels, Olivier; Dejean, Alain; Devineau, Jean-Louis; Diekötter, Tim; Dolia, Jignasu V; Domínguez, Erwin; Dominguez-Haydar, Yamileth; Dorn, Silvia; Draper, Isabel; Dreber, Niels; Dumont, Bertrand; Dures, Simon G; Dynesius, Mats; Edenius, Lars; Eggleton, Paul; Eigenbrod, Felix; Elek, Zoltán; Entling, Martin H; Esler, Karen J; de Lima, Ricardo F; Faruk, Aisyah; Farwig, Nina; Fayle, Tom M; Felicioli, Antonio; Felton, Annika M; Fensham, Roderick J; Fernandez, Ignacio C; Ferreira, Catarina C; Ficetola, Gentile F; Fiera, Cristina; Filgueiras, Bruno K C; Fırıncıoğlu, Hüseyin K; Flaspohler, David; Floren, Andreas; Fonte, Steven J; Fournier, Anne; Fowler, Robert E; Franzén, Markus; Fraser, Lauchlan H; Fredriksson, Gabriella M; Freire, Geraldo B; Frizzo, Tiago L M; Fukuda, Daisuke; Furlani, Dario; Gaigher, René; Ganzhorn, Jörg U; García, Karla P; Garcia-R, Juan C; Garden, Jenni G; Garilleti, Ricardo; Ge, Bao-Ming; Gendreau-Berthiaume, Benoit; Gerard, Philippa J; Gheler-Costa, Carla; Gilbert, Benjamin; Giordani, Paolo; Giordano, Simonetta; Golodets, Carly; Gomes, Laurens G L; Gould, Rachelle K; Goulson, Dave; Gove, Aaron D; Granjon, Laurent; Grass, Ingo; Gray, Claudia L; Grogan, James; Gu, Weibin; Guardiola, Moisès; Gunawardene, Nihara R; Gutierrez, Alvaro G; Gutiérrez-Lamus, Doris L; Haarmeyer, Daniela H; Hanley, Mick E; Hanson, Thor; Hashim, Nor R; Hassan, Shombe N; Hatfield, Richard G; Hawes, Joseph E; Hayward, Matt W; Hébert, Christian; Helden, Alvin J; Henden, John-André; Henschel, Philipp; Hernández, Lionel; Herrera, James P; Herrmann, Farina; Herzog, Felix; Higuera-Diaz, Diego; Hilje, Branko; Höfer, Hubert; Hoffmann, Anke; Horgan, Finbarr G; Hornung, Elisabeth; Horváth, Roland; Hylander, Kristoffer; Isaacs-Cubides, Paola; Ishida, Hiroaki; Ishitani, Masahiro; Jacobs, Carmen T; Jaramillo, Víctor J; Jauker, Birgit; Hernández, F Jiménez; Johnson, McKenzie F; Jolli, Virat; Jonsell, Mats; Juliani, S Nur; Jung, Thomas S; Kapoor, Vena; Kappes, Heike; Kati, Vassiliki; Katovai, Eric; Kellner, Klaus; Kessler, Michael; Kirby, Kathryn R; Kittle, Andrew M; Knight, Mairi E; Knop, Eva; Kohler, Florian; Koivula, Matti; Kolb, Annette; Kone, Mouhamadou; Kőrösi, Ádám; Krauss, Jochen; Kumar, Ajith; Kumar, Raman; Kurz, David J; Kutt, Alex S; Lachat, Thibault; Lantschner, Victoria; Lara, Francisco; Lasky, Jesse R; Latta, Steven C; Laurance, William F; Lavelle, Patrick; Le Féon, Violette; LeBuhn, Gretchen; Légaré, Jean-Philippe; Lehouck, Valérie; Lencinas, María V; Lentini, Pia E; Letcher, Susan G; Li, Qi; Litchwark, Simon A; Littlewood, Nick A; Liu, Yunhui; Lo-Man-Hung, Nancy; López-Quintero, Carlos A; Louhaichi, Mounir; Lövei, Gabor L; Lucas-Borja, Manuel Esteban; Luja, Victor H; Luskin, Matthew S; MacSwiney G, M Cristina; Maeto, Kaoru; Magura, Tibor; Mallari, Neil Aldrin; Malone, Louise A; Malonza, Patrick K; Malumbres-Olarte, Jagoba; Mandujano, Salvador; Måren, Inger E; Marin-Spiotta, Erika; Marsh, Charles J; Marshall, E J P; Martínez, Eliana; Martínez Pastur, Guillermo; Moreno Mateos, David; Mayfield, Margaret M; Mazimpaka, Vicente; McCarthy, Jennifer L; McCarthy, Kyle P; McFrederick, Quinn S; McNamara, Sean; Medina, Nagore G; Medina, Rafael; Mena, Jose L; Mico, Estefania; Mikusinski, Grzegorz; Milder, Jeffrey C; Miller, James R; Miranda-Esquivel, Daniel R; Moir, Melinda L; Morales, Carolina L; Muchane, Mary N; Muchane, Muchai; Mudri-Stojnic, Sonja; Munira, A Nur; Muoñz-Alonso, Antonio; Munyekenye, B F; Naidoo, Robin; Naithani, A; Nakagawa, Michiko; Nakamura, Akihiro; Nakashima, Yoshihiro; Naoe, Shoji; Nates-Parra, Guiomar; Navarrete Gutierrez, Dario A; Navarro-Iriarte, Luis; Ndang'ang'a, Paul K; Neuschulz, Eike L; Ngai, Jacqueline T; Nicolas, Violaine; Nilsson, Sven G; Noreika, Norbertas; Norfolk, Olivia; Noriega, Jorge Ari; Norton, David A; Nöske, Nicole M; Nowakowski, A Justin; Numa, Catherine; O'Dea, Niall; O'Farrell, Patrick J; Oduro, William; Oertli, Sabine; Ofori-Boateng, Caleb; Oke, Christopher Omamoke; Oostra, Vicencio; Osgathorpe, Lynne M; Otavo, Samuel Eduardo; Page, Navendu V; Paritsis, Juan; Parra-H, Alejandro; Parry, Luke; Pe'er, Guy; Pearman, Peter B; Pelegrin, Nicolás; Pélissier, Raphaël; Peres, Carlos A; Peri, Pablo L; Persson, Anna S; Petanidou, Theodora; Peters, Marcell K; Pethiyagoda, Rohan S; Phalan, Ben; Philips, T Keith; Pillsbury, Finn C; Pincheira-Ulbrich, Jimmy; Pineda, Eduardo; Pino, Joan; Pizarro-Araya, Jaime; Plumptre, A J; Poggio, Santiago L; Politi, Natalia; Pons, Pere; Poveda, Katja; Power, Eileen F; Presley, Steven J; Proença, Vânia; Quaranta, Marino; Quintero, Carolina; Rader, Romina; Ramesh, B R; Ramirez-Pinilla, Martha P; Ranganathan, Jai; Rasmussen, Claus; Redpath-Downing, Nicola A; Reid, J Leighton; Reis, Yana T; Rey Benayas, José M; Rey-Velasco, Juan Carlos; Reynolds, Chevonne; Ribeiro, Danilo Bandini; Richards, Miriam H; Richardson, Barbara A; Richardson, Michael J; Ríos, Rodrigo Macip; Robinson, Richard; Robles, Carolina A; Römbke, Jörg; Romero-Duque, Luz Piedad; Rös, Matthias; Rosselli, Loreta; Rossiter, Stephen J; Roth, Dana S; Roulston, T'ai H; Rousseau, Laurent; Rubio, André V; Ruel, Jean-Claude; Sadler, Jonathan P; Sáfián, Szabolcs; Saldaña-Vázquez, Romeo A; Sam, Katerina; Samnegård, Ulrika; Santana, Joana; Santos, Xavier; Savage, Jade; Schellhorn, Nancy A; Schilthuizen, Menno; Schmiedel, Ute; Schmitt, Christine B; Schon, Nicole L; Schüepp, Christof; Schumann, Katharina; Schweiger, Oliver; Scott, Dawn M; Scott, Kenneth A; Sedlock, Jodi L; Seefeldt, Steven S; Shahabuddin, Ghazala; Shannon, Graeme; Sheil, Douglas; Sheldon, Frederick H; Shochat, Eyal; Siebert, Stefan J; Silva, Fernando A B; Simonetti, Javier A; Slade, Eleanor M; Smith, Jo; Smith-Pardo, Allan H; Sodhi, Navjot S; Somarriba, Eduardo J; Sosa, Ramón A; Soto Quiroga, Grimaldo; St-Laurent, Martin-Hugues; Starzomski, Brian M; Stefanescu, Constanti; Steffan-Dewenter, Ingolf; Stouffer, Philip C; Stout, Jane C; Strauch, Ayron M; Struebig, Matthew J; Su, Zhimin; Suarez-Rubio, Marcela; Sugiura, Shinji; Summerville, Keith S; Sung, Yik-Hei; Sutrisno, Hari; Svenning, Jens-Christian; Teder, Tiit; Threlfall, Caragh G; Tiitsaar, Anu; Todd, Jacqui H; Tonietto, Rebecca K; Torre, Ignasi; Tóthmérész, Béla; Tscharntke, Teja; Turner, Edgar C; Tylianakis, Jason M; Uehara-Prado, Marcio; Urbina-Cardona, Nicolas; Vallan, Denis; Vanbergen, Adam J; Vasconcelos, Heraldo L; Vassilev, Kiril; Verboven, Hans A F; Verdasca, Maria João; Verdú, José R; Vergara, Carlos H; Vergara, Pablo M; Verhulst, Jort; Virgilio, Massimiliano; Vu, Lien Van; Waite, Edward M; Walker, Tony R; Wang, Hua-Feng; Wang, Yanping; Watling, James I; Weller, Britta; Wells, Konstans; Westphal, Catrin; Wiafe, Edward D; Williams, Christopher D; Willig, Michael R; Woinarski, John C Z; Wolf, Jan H D; Wolters, Volkmar; Woodcock, Ben A; Wu, Jihua; Wunderle, Joseph M; Yamaura, Yuichi; Yoshikura, Satoko; Yu, Douglas W; Zaitsev, Andrey S; Zeidler, Juliane; Zou, Fasheng; Collen, Ben; Ewers, Rob M; Mace, Georgina M; Purves, Drew W; Scharlemann, Jörn P W; Purvis, Andy

The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of

TOXICOLOGICAL EVALUATION OF REALISTIC EMISSIONS OF SOURCE AEROSOLS (TERESA): APPLICATION TO POWER PLANT-DERIVED PM2.5

Energy Technology Data Exchange (ETDEWEB)

Annette C. Rohr; Petros Koutrakis; John Godleski

2011-03-31

Determining the health impacts of different sources and components of fine particulate matter (PM2.5) is an important scientific goal, because PM is a complex mixture of both inorganic and organic constituents that likely differ in their potential to cause adverse health outcomes. The TERESA (Toxicological Evaluation of Realistic Emissions of Source Aerosols) study focused on two PM sources - coal-fired power plants and mobile sources - and sought to investigate the toxicological effects of exposure to realistic emissions from these sources. The DOE-EPRI Cooperative Agreement covered the performance and analysis of field experiments at three power plants. The mobile source component consisted of experiments conducted at a traffic tunnel in Boston; these activities were funded through the Harvard-EPA Particulate Matter Research Center and will be reported separately in the peer-reviewed literature. TERESA attempted to delineate health effects of primary particles, secondary (aged) particles, and mixtures of these with common atmospheric constituents. The study involved withdrawal of emissions directly from power plant stacks, followed by aging and atmospheric transformation of emissions in a mobile laboratory in a manner that simulated downwind power plant plume processing. Secondary organic aerosol (SOA) derived from the biogenic volatile organic compound {alpha}-pinene was added in some experiments, and in others ammonia was added to neutralize strong acidity. Specifically, four scenarios were studied at each plant: primary particles (P); secondary (oxidized) particles (PO); oxidized particles + secondary organic aerosol (SOA) (POS); and oxidized and neutralized particles + SOA (PONS). Extensive exposure characterization was carried out, including gas-phase and particulate species. Male Sprague Dawley rats were exposed for 6 hours to filtered air or different atmospheric mixtures. Toxicological endpoints included (1) breathing pattern; (2) bronchoalveolar lavage

The eTOX Data-Sharing Project to Advance in Silico Drug-Induced Toxicity Prediction

Directory of Open Access Journals (Sweden)

Montserrat Cases

2014-11-01

Full Text Available The high-quality in vivo preclinical safety data produced by the pharmaceutical industry during drug development, which follows numerous strict guidelines, are mostly not available in the public domain. These safety data are sometimes published as a condensed summary for the few compounds that reach the market, but the majority of studies are never made public and are often difficult to access in an automated way, even sometimes within the owning company itself. It is evident from many academic and industrial examples, that useful data mining and model development requires large and representative data sets and careful curation of the collected data. In 2010, under the auspices of the Innovative Medicines Initiative, the eTOX project started with the objective of extracting and sharing preclinical study data from paper or pdf archives of toxicology departments of the 13 participating pharmaceutical companies and using such data for establishing a detailed, well-curated database, which could then serve as source for read-across approaches (early assessment of the potential toxicity of a drug candidate by comparison of similar structure and/or effects and training of predictive models. The paper describes the efforts undertaken to allow effective data sharing intellectual property (IP protection and set up of adequate controlled vocabularies and to establish the database (currently with over 4000 studies contributed by the pharma companies corresponding to more than 1400 compounds. In addition, the status of predictive models building and some specific features of the eTOX predictive system (eTOXsys are presented as decision support knowledge-based tools for drug development process at an early stage.

ATMOSPHERIC DISPERSION COEFFICIENTS AND RADIOLOGICAL AND TOXICOLOGICAL EXPOSURE METHODOLOGY FOR USE IN TANK FARMS

Energy Technology Data Exchange (ETDEWEB)

GRIGSBY KM

2011-04-07

This report presents the atmospheric dispersion coefficients used in Tank Farms safety analysis. The basis equations for calculating radiological and toxicological exposures are also included. In this revision, the time averaging for toxicological consequence evaluations is clarified based on a review of DOE complex guidance and a review of tank farm chemicals.

Measuring Impact of EPAs Computational Toxicology Research (BOSC)

Science.gov (United States)

Computational Toxicology (CompTox) research at the EPA was initiated in 2005. Since 2005, CompTox research efforts have made tremendous advances in developing new approaches to evaluate thousands of chemicals for potential health effects. The purpose of this case study is to trac...

TOXICOLOGICAL EVALUATION OF REALISTIC EMISSIONS OF SOURCE AEROSOLS (TERESA): APPLICATION TO POWER PLANT-DERIVED PM2.5

Energy Technology Data Exchange (ETDEWEB)

Annette Rohr

2005-03-31

This report documents progress made on the subject project during the period of September 1, 2004 through February 28, 2005. The TERESA Study is designed to investigate the role played by specific emissions sources and components in the induction of adverse health effects by examining the relative toxicity of coal combustion and mobile source (gasoline and/or diesel engine) emissions and their oxidative products. The study involves on-site sampling, dilution, and aging of coal combustion emissions at three coal-fired power plants, as well as mobile source emissions, followed by animal exposures incorporating a number of toxicological endpoints. The DOE-EPRI Cooperative Agreement (henceforth referred to as ''the Agreement'') for which this technical progress report has been prepared covers the performance and analysis of field experiments at the first TERESA plant, located in the Upper Midwest and henceforth referred to as Plant 0, and at two additional coal-fired power plants (Plants 1 and 2) utilizing different coal types and with different plant configurations. During this reporting period, all fieldwork at Plant 0 was completed. Stack sampling was conducted in October to determine if there were significant differences between the in-stack PM concentrations and the diluted concentrations used for the animal exposures. Results indicated no significant differences and therefore confidence that the revised stack sampling methodology described in the previous semiannual report is appropriate for use in the Project. Animal exposures to three atmospheric scenarios were carried out. From October 4-7, we conducted exposures to oxidized emissions with the addition of secondary organic aerosol (SOA). Later in October, exposures to the most complex scenario (oxidized, neutralized emissions plus SOA) were repeated to ensure comparability with the results of the June/July exposures where a different stack sampling setup was employed. In November, exposures

The DOE policy for protection against radiological and toxicological sabotage

International Nuclear Information System (INIS)

Hassell, C. Jr.; Callahan, S.; Myers, D.

1995-01-01

In response to a Department of Energy Office of Security Evaluations study on radiological and toxicological sabotage, the Under Secretary of Energy has directed that all departmental elements initiate analyses to determine the extent of radiological and toxicological sabotage threats within the department. To accomplish this, a plan was adopted whereby radioactive and other hazardous materials at DOE sites would be assessed by an interdisciplinary team as to quantities, ranked according to their hazards, subjected to a vulnerability assessment, and appropriate upgrades selected and monitored. This paper is a discussion of those efforts

Toxicological profile for uranium. Final report

International Nuclear Information System (INIS)

1990-12-01

The ATSDR Toxicological Profile for Uranium is intended to characterize succinctly the toxicological and health effects information for the substance. It identifies and reviews the key literature that describes the substances's toxicological properties. Other literature is presented but described in less detail. The profile is not intended to be an exhaustive document; however, more comprehensive sources of specialty information are referenced. The profile begins with a public health statement, which describes in nontechnical language the substance's relevant toxicological properties. Following the statement is material that presents levels of significant human exposure and, where known, significant health effects. The adequacy of information to determine the substance's health effects is described. Research gaps in nontoxic and health effects information are described. Research gaps that are of significance to the protection of public health will be identified in a separate effort. The focus of the document is on health and toxicological information

Toxicological profile for radon. Final report

International Nuclear Information System (INIS)

1990-12-01

The ATSDR Toxicological Profile for Radon is intended to characterize succinctly the toxicological and health effects information for the substance. It identifies and reviews the key literature that describes the substance's toxicological properties. Other literature is presented but described in less detail. The profile is not intended to be an exhaustive document; however, more comprehensive sources of specialty information are referenced. The profile begins with a public health statement, which describes in nontechnical language the substance's relevant toxicological properties. Following the statement is material that presents levels of significant human exposure and, where known, significant health effects. The adequacy of information to determine the substance's health effects is described. Research gaps in nontoxic and health effects information are described. Research gaps that are of significance to the protection of public health will be identified in a separate effort. The focus of the document is on health and toxicological information

Toxicological profile for plutonium. Final report

International Nuclear Information System (INIS)

1990-12-01

The ATSDR Toxicological Profile for Plutonium is intended to characterize succinctly the toxicological and health effects information for the substance. It identifies and reviews the key literature that describes the substance's toxicological properties. Other literature is presented but described in less detail. The profile is not intended to be an exhaustive document; however, more comprehensive sources of specialty information are referenced. The profile begins with a public health statement, which describes in nontechnical language the substance's relevant toxicological properties. Following the statement is material that presents levels of significant human exposure and, where known, significant health effects. The adequacy of information to determine the substance's health effects is described. Research gaps in nontoxic and health effects information are described. Research gaps that are of significance to the protection of public health will be identified in a separate effort. The focus of the document is on health and toxicological information

Toxicological profile for radium. Final report

International Nuclear Information System (INIS)

1990-12-01

The ATSDR Toxicological Profile for Radium is intended to characterize succinctly the toxicological and health effects information for the substance. It identifies and reviews the key literature that describes the substances' toxicological properties. Other literature is presented but described in less detail. The profile is not intended to be an exhaustive document; however, more comprehensive sources of specialty information are referenced. The profile begins with a public health statement, which describes in nontechnical language the substance's relevant toxicological properties. Following the statement is material that presents levels of significant human exposure and, where known, significant health effects. The adequacy of information to determine the substance's health effects is described. Research gaps in nontoxic and health effects information are described. Research gaps that are of significance to the protection of public health will be identified in a separate effort. The focus of the document is on health and toxicological information

Resource Guide to Careers in Toxicology, 3rd Edition.

Science.gov (United States)

Society of Toxicology, Reston, VA.

This resource guide was prepared by the Tox 90's Educational Issues Task Force of the Society of Toxicology. The introduction provides information on the Society of Toxicology and financial support for graduate students in toxicology. Other sections include career opportunities in toxicology, academic and postdoctoral programs in toxicology, and…

Advancing Toxicology Research Using In Vivo High Throughput Toxicology with Small Fish Models

Science.gov (United States)

Planchart, Antonio; Mattingly, Carolyn J.; Allen, David; Ceger, Patricia; Casey, Warren; Hinton, David; Kanungo, Jyotshna; Kullman, Seth W.; Tal, Tamara; Bondesson, Maria; Burgess, Shawn M.; Sullivan, Con; Kim, Carol; Behl, Mamta; Padilla, Stephanie; Reif, David M.; Tanguay, Robert L.; Hamm, Jon

2017-01-01

Summary Small freshwater fish models, especially zebrafish, offer advantages over traditional rodent models, including low maintenance and husbandry costs, high fecundity, genetic diversity, physiology similar to that of traditional biomedical models, and reduced animal welfare concerns. The Collaborative Workshop on Aquatic Models and 21st Century Toxicology was held at North Carolina State University on May 5-6, 2014, in Raleigh, North Carolina, USA. Participants discussed the ways in which small fish are being used as models to screen toxicants and understand mechanisms of toxicity. Workshop participants agreed that the lack of standardized protocols is an impediment to broader acceptance of these models, whereas development of standardized protocols, validation, and subsequent regulatory acceptance would facilitate greater usage. Given the advantages and increasing application of small fish models, there was widespread interest in follow-up workshops to review and discuss developments in their use. In this article, we summarize the recommendations formulated by workshop participants to enhance the utility of small fish species in toxicology studies, as well as many of the advances in the field of toxicology that resulted from using small fish species, including advances in developmental toxicology, cardiovascular toxicology, neurotoxicology, and immunotoxicology. We also review many emerging issues that will benefit from using small fish species, especially zebrafish, and new technologies that will enable using these organisms to yield results unprecedented in their information content to better understand how toxicants affect development and health. PMID:27328013

[A toxicologic hygiene evaluation of electrolytic oxygen obtained from the water in a system with a solid polymeric electrolyte].

Science.gov (United States)

Bardov, V G; Koziarin, I P; Suk, V G; Maslenko, A A; Shmuter, G M

1990-01-01

The authors evaluated the problems of hygienic aspects of oxygen obtained by the method of electrolytic decomposition of water with a different content of chemical substances in the system with a hard polymere electrolyte. On the basis of sanitary-chemical qualities and toxicological properties electrolysis gaseous oxygen may be recommended for use in creating an artificial gaseous atmosphere in hermetically sealed compartments in mixture with gaseous nitrogen (ratio 1:4).

Evaluation of the Inhalation Toxicology Research Institute beagle dog closed breeding colony: a progress report

International Nuclear Information System (INIS)

Lustgarten, C.S.; Hobbs, C.H.; Muggenburg, B.A.; Benjamin, S.A.; Slauson, D.O.; Hahn, F.F.

1974-01-01

Since early 1968, a closed breeding colony has been in operation at the Inhalation Toxicology Research Institute to produce experimental dogs for inhalation toxicology studies and to replace colony breeding stock for producing dogs with a stable gene pool. From March 1, 1968 through July 15, 1974, 123 bitches were bred 613 times, resulting in 540 litters and 2809 puppies: a conception rate for this period of 88.9 percent. An average of 3.74 pups survived to one year of age. (U.S.)

Evaluation of high-resolution mass spectrometry for urine toxicology screening in a pain management setting.

Science.gov (United States)

Crews, Bridgit O; Pesce, Amadeo J; West, Robert; Nguyen, Hugh; Fitzgerald, Robert L

2012-01-01

To evaluate liquid chromatography-high-resolution mass spectrometry (LC-HR-MS) for urine toxicology screening, 29 analytes were quantitated in 152 urine specimens from patients with chronic pain using two unique mass spectrometry platforms. De-identified specimens were quantitated in April of 2011 by liquid chromatography-triple quadrupole mass spectrometry (LC-MS-MS) and by full-scan LC-HR-MS at Millennium Laboratories. Considering LC-MS-MS as the reference method, false positive results were identified in 19 specimens measured by LC-HR-MS. Application of relative retention times using deuterium labeled internal standards improved the rate of false positive detection to only five specimens, with four occurring for the same analyte. Ultra-high-resolution mass spectrometry (R = 100,000 at m/z 200) showed no improvement over high-resolution mass spectrometry (R = 10,000 at m/z 200) in the number of false positives detected. Quantitative results measured by LC-MS-MS and LC-HR-MS showed good agreement over four orders of dynamic range. This study demonstrates that LC-HR-MS is a suitable platform for toxicology screening for a pain management population and that quantitative accuracy and sensitivity are comparable to that achieved with LC-MS-MS. The specificity of LC-HR-MS is improved by the addition of deuterium labeled internal standards and the implementation of relative retention time matching.

Mind the Gap! A Journey towards Computational Toxicology.

Science.gov (United States)

Mangiatordi, Giuseppe Felice; Alberga, Domenico; Altomare, Cosimo Damiano; Carotti, Angelo; Catto, Marco; Cellamare, Saverio; Gadaleta, Domenico; Lattanzi, Gianluca; Leonetti, Francesco; Pisani, Leonardo; Stefanachi, Angela; Trisciuzzi, Daniela; Nicolotti, Orazio

2016-09-01

Computational methods have advanced toxicology towards the development of target-specific models based on a clear cause-effect rationale. However, the predictive potential of these models presents strengths and weaknesses. On the good side, in silico models are valuable cheap alternatives to in vitro and in vivo experiments. On the other, the unconscious use of in silico methods can mislead end-users with elusive results. The focus of this review is on the basic scientific and regulatory recommendations in the derivation and application of computational models. Attention is paid to examine the interplay between computational toxicology and drug discovery and development. Avoiding the easy temptation of an overoptimistic future, we report our view on what can, or cannot, realistically be done. Indeed, studies of safety/toxicity represent a key element of chemical prioritization programs carried out by chemical industries, and primarily by pharmaceutical companies. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Toxicological aspects of fuel and exhaust gas

International Nuclear Information System (INIS)

Avella, F.

1993-01-01

Some aspects concerning fuels (gasoline) and gas exhaust vehicle emissions toxicology are briefly examined in light of the results reported in recent literature on this argument. Many experimental studies carried out on animals and men turn out incomplete and do not allow thorough evaluations, for every aspect, of the risk to which men and the environment are subjected

Ninth Triennial Toxicology Salary Survey.

Science.gov (United States)

Gad, Shayne Cox; Sullivan, Dexter Wayne

2016-01-01

This survey serves as the ninth in a series of toxicology salary surveys conducted at 3-year intervals and beginning in 1988. An electronic survey instrument was distributed to 5919 individuals including members of the Society of Toxicology, American College of Toxicology, and 23 additional professional organizations. Question items inquired about gender, age, degree, years of experience, certifications held, areas of specialization, society membership, employment and income. Overall, 1293 responses were received (response rate 21.8%). The results of the 2014 survey provide insight into the job market and career path for current and future toxicologists. © The Author(s) 2016.

Distance learning and toxicology: New horizons for Paracelsus

International Nuclear Information System (INIS)

Huggins, Jane; Morris, John; Peterson, C. Erik

2005-01-01

Distance learning offers many advantages to students and teachers of almost any scientific discipline. Toxicology is no exception. For example, should Paracelsus be interested in learning more about toxicology at Drexel University, he would have the opportunity to take two courses in this subject utilizing the content management software, WebCT. The two courses would offer a website from which he could view and/or download his notes for each class. He could correspond with the instructor as well as fellow students, participate in discussions about timely topics, and make presentations to the class, all via electronic communication. Moreover, his examinations would also be computerized. Although he might have the option of attending traditional 'face-to-face' lectures with other students in the class, he could also access these lectures at any time from a remote location by using the archive of taped lectures on the class website. Overall, Paracelsus would have access to many tools to enhance his understanding of toxicology, and he probably would never have to worry about parking before class (!). The two WebCT modules in toxicology that we have developed at Drexel represent the successful migration of two courses from a traditional 'face-to-face' model of classroom instruction to hybrid models that combine 'face-to-face' interaction with online instruction. Student and faculty evaluations of these courses have been very positive. Future plans include linking the two modules together so that students in the advanced class can do 'review' or 'remedial' work in the basic module. Furthermore, a library of video clips is also planned in which researchers will be discussing their work on various toxicologic topics. Students will be able to access these clips as resources from which to write research papers

Multiscale Toxicology- Building the Next Generation Tools for Toxicology

Energy Technology Data Exchange (ETDEWEB)

Retterer, S. T. [ORNL; Holsapple, M. P. [Battelle Memorial Institute

2013-10-31

toxicity in vitro. The second research track within the MSTI CRADA focused on the development of ex vivo animal models for examining druginduced cardiotoxicity. ORNL's role in the second track was limited initially, but was later expanded to include the development of microfluidic platforms that might facilitate the translation of Cardiac 'Microwire' technologies developed at the University of Toronto into a functional platform for drug screening and predictive assessment of cardiotoxicity via highthroughput measurements of contractility. This work was coordinated by BMI with the Centre for the Commercialization of Regenerative Medicine (CCRM) and the University of Toronto (U Toronto). This partnership was expanded and culminated in the submission of proposal to Work for Others (WFO) agencies to explore the development of a broader set of microphysiological systems, a so call human-on-a-chip, that could be used for toxicity screening and the evaluation of bio-threat countermeasures.

Cell-based in vitro models in environmental toxicology: a review

Directory of Open Access Journals (Sweden)

Poteser Michael

2017-10-01

Full Text Available An analysis of biological effects induced by environmental toxins and exposure-related evaluation of potential risks for health and environment represent central tasks in classical biomonitoring. While epidemiological data and population surveys are clearly the methodological frontline of this scientific field, cellbased in vitro assays provide information on toxin-affected cellular pathways and mechanisms, and are important sources for the identification of relevant biomarkers. This review provides an overview on currently available in vitro methods based on cultured cells, as well as some limitations and considerations that are of specific interest in the context of environmental toxicology. Today, a large number of different endpoints can be determined to pinpoint basal and specific toxicological cellular effects. Technological progress and increasingly refined protocols are extending the possibilities of cell-based in vitro assays in environmental toxicology and promoting their increasingly important role in biomonitoring.

Impact evaluation in multicultural educational projects : case: ADAPTYKES project

OpenAIRE

Kuusisto, Miika

2014-01-01

The objective of this thesis was to examine the common evaluation concepts of the European Union’s funded projects. Such concepts inter alia are effectiveness, impacts and sustainability. The aim was to study how these are realized in multicultural educational case–project in a context, where the project is funded by the European Commission’s Leonardo DaVinci Programme. Thesis introduces two evaluation approaches, which are Logical Framework Approach and Realistic evaluation model. The fi...

The role of toxicology to characterize biomarkers for agrochemicals with potential endocrine activities.

Science.gov (United States)

Mantovani, Alberto; Maranghi, Francesca; La Rocca, Cinzia; Tiboni, Gian Mario; Clementi, Maurizio

2008-09-01

The paper discusses current knowledge and possible research priorities on biomarkers of exposure, effect and susceptibility for potential endocrine activities of agrochemicals (dicarboximides, ethylene bisdithiocarbammates, triazoles, etc.). Possible widespread, multiple-pathway exposure to agrochemicals highlights the need to assess internal exposure of animals or humans, which is the most relevant exposure measure for hazard and risk estimation; however, exposure data should be integrated by early indicators predictive of possible health effects, particularly for vulnerable groups such as mother-child pairs. Research need include: non-invasive biomarkers for children biomonitoring; novel biomarkers of total exposure to measure whole endocrine disrupter-related burden; characterization of biomarkers of susceptibility, including the role of markers of nutritional status; anchoring early molecular markers to established toxicological endpoints to support their predictivity; integrating "omics"-based approaches in a system-toxicology framework. As biomonitoring becomes increasingly important in the environment-and-health scenario, toxicologists can substantially contribute both to the characterization of new biomarkers and to the predictivity assessment and improvement of the existing ones.

Developmental and Reproductive Toxicology Database (DART)

Data.gov (United States)

U.S. Department of Health & Human Services — A bibliographic database on the National Library of Medicine's (NLM) Toxicology Data Network (TOXNET) with references to developmental and reproductive toxicology...

On-line sources of toxicological information in Canada

International Nuclear Information System (INIS)

Racz, William J.; Ecobichon, Donald J.; Baril, Marc

2003-01-01

This paper will provide an overview of the on-line resources available in toxicology in Canada. It will describe a brief history of The Society of Toxicology of Canada, with reference to other societies and also provide information on education, research and other resources related to toxicology. Toxicology in Canada emerged as a distinct and vibrant discipline following the thalidomide tragedy of the 1960s. In the pharmaceutical industry and government, toxicology was readily established as an essential component of drug development and safety, and as the need for toxicologists expanded, training programs were established, usually in collaboration with departments of pharmacology. In the last two to three decades other disciplines, environmental biology, analytical chemistry and epidemiology joined the ranks of toxicology. The on-line sources of toxicology information are rapidly expanding. This article describes those sources considered by the authors to be important from a national and international perspective. The majority of these sources are professional organizations and government agencies

The DLESE Evaluation Toolkit Project

Science.gov (United States)

Buhr, S. M.; Barker, L. J.; Marlino, M.

2002-12-01

The Evaluation Toolkit and Community project is a new Digital Library for Earth System Education (DLESE) collection designed to raise awareness of project evaluation within the geoscience education community, and to enable principal investigators, teachers, and evaluators to implement project evaluation more readily. This new resource is grounded in the needs of geoscience educators, and will provide a virtual home for a geoscience education evaluation community. The goals of the project are to 1) provide a robust collection of evaluation resources useful for Earth systems educators, 2) establish a forum and community for evaluation dialogue within DLESE, and 3) disseminate the resources through the DLESE infrastructure and through professional society workshops and proceedings. Collaboration and expertise in education, geoscience and evaluation are necessary if we are to conduct the best possible geoscience education. The Toolkit allows users to engage in evaluation at whichever level best suits their needs, get more evaluation professional development if desired, and access the expertise of other segments of the community. To date, a test web site has been built and populated, initial community feedback from the DLESE and broader community is being garnered, and we have begun to heighten awareness of geoscience education evaluation within our community. The web site contains features that allow users to access professional development about evaluation, search and find evaluation resources, submit resources, find or offer evaluation services, sign up for upcoming workshops, take the user survey, and submit calendar items. The evaluation resource matrix currently contains resources that have met our initial review. The resources are currently organized by type; they will become searchable on multiple dimensions of project type, audience, objectives and evaluation resource type as efforts to develop a collection-specific search engine mature. The peer review

Toxicological evaluation of proteins introduced into food crops

Science.gov (United States)

Kough, John; Herouet-Guicheney, Corinne; Jez, Joseph M.

2013-01-01

This manuscript focuses on the toxicological evaluation of proteins introduced into GM crops to impart desired traits. In many cases, introduced proteins can be shown to have a history of safe use. Where modifications have been made to proteins, experience has shown that it is highly unlikely that modification of amino acid sequences can make a non-toxic protein toxic. Moreover, if the modified protein still retains its biological function, and this function is found in related proteins that have a history of safe use (HOSU) in food, and the exposure level is similar to functionally related proteins, then the modified protein could also be considered to be “as-safe-as” those that have a HOSU. Within nature, there can be considerable evolutionary changes in the amino acid sequence of proteins within the same family, yet these proteins share the same biological function. In general, food crops such as maize, soy, rice, canola etc. are subjected to a variety of processing conditions to generate different food products. Processing conditions such as cooking, modification of pH conditions, and mechanical shearing can often denature proteins in these crops resulting in a loss of functional activity. These same processing conditions can also markedly lower human dietary exposure to (functionally active) proteins. Safety testing of an introduced protein could be indicated if its biological function was not adequately characterized and/or it was shown to be structurally/functionally related to proteins that are known to be toxic to mammals. PMID:24164515

40 CFR 161.340 - Toxicology data requirements.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Toxicology data requirements. 161.340... Toxicology data requirements. (a) Table. Sections 161.100 through 161.102 describe how to use this table to determine the toxicology data requirements and the substance to be tested. Kind of data required (b) Notes...

Antioxidant and toxicological evaluation of a Tamarindus indica L. leaf fluid extract.

Science.gov (United States)

Escalona-Arranz, J C; Perez-Rosés, R; Rodríguez-Amado, J; Morris-Quevedo, H J; Mwasi, L B; Cabrera-Sotomayor, O; Machado-García, R; Fong-Lórez, O; Alfonso-Castillo, A; Puente-Zapata, E

2016-01-01

In the scientific community, there is a growing interest in Tamarindus indica L. leaves, both as a valuable nutrient and as a functional food. This paper focuses on exploring its safety and antioxidant properties. A tamarind leaf fluid extract (TFE) wholly characterised was evaluated for its anti-DPPH activity (IC50 = 44.36 μg/mL) and its reducing power activity (IC50 = 60.87 μg/mL). TFE also exhibited a high ferrous ion-chelating capacity, with an estimated binding constant of 1.085 mol L(-1) while its influence over nitric oxide production in human leucocytes was irregular. At low concentrations, TFE stimulated NO output, but it significantly inhibited it when there was an increase in concentration. TFE was also classified as a non-toxic substance in two toxicity tests: the acute oral toxicity test and the oral mucous irritability test. Further toxicological assays are needed, although results so far suggest that TFE might become a functional dietary supplement.

The Annapolis Accords on the use of toxicology in decision-making. Annapolis Center Workshop Report.

Energy Technology Data Exchange (ETDEWEB)

Gray, G.M.; Baskin, S.I.; Charnley, G.; Cohen, J.T.; Gold, L.S.; Kerkvliet, N.I.; Koenig, H.M.; Lewis, S.C.; McClain, R.M.; Rhomberg, L.R.; Snyder, J.W.; Weekley, L.B.

2000-12-01

The science of toxicology plays an important role in identifying safe conditions of use or exposure for many different kinds of environmental agents. The use of toxicologic information in risk assessment requires careful analysis, evaluation of data, and scientific judgment. These Annapolis Accords are intended to guide appropriate use in risk assessment of the scientific information from toxicology. We believe that application of these principles will improve the scientific credibility of risk assessment and the quality of decisions aimed at reducing and eliminating risks to human health and the environment.

Current role of ICP-MS in clinical toxicology and forensic toxicology: a metallic profile.

Science.gov (United States)

Goullé, Jean-Pierre; Saussereau, Elodie; Mahieu, Loïc; Guerbet, Michel

2014-08-01

As metal/metalloid exposure is inevitable owing to its omnipresence, it may exert toxicity in humans. Recent advances in metal/metalloid analysis have been made moving from flame atomic absorption spectrometry and electrothermal atomic absorption spectrometry to the multi-elemental inductively coupled plasma (ICP) techniques as ICP atomic emission spectrometry and ICP-MS. ICP-MS has now emerged as a major technique in inorganic analytical chemistry owing to its flexibility, high sensitivity and good reproducibility. This in depth review explores the ICP-MS metallic profile in human toxicology. It is now routinely used and of great importance, in clinical toxicology and forensic toxicology to explore biological matrices, specifically whole blood, plasma, urine, hair, nail, biopsy samples and tissues.

Evaluation of miR-122 as a Serum Biomarker for Hepatotoxicity in Investigative Rat Toxicology Studies.

Science.gov (United States)

Sharapova, T; Devanarayan, V; LeRoy, B; Liguori, M J; Blomme, E; Buck, W; Maher, J

2016-01-01

MicroRNAs are short noncoding RNAs involved in regulation of gene expression. Certain microRNAs, including miR-122, seem to have ideal properties as biomarkers due to good stability, high tissue specificity, and ease of detection across multiple species. Recent reports have indicated that miR-122 is a highly liver-specific marker detectable in serum after liver injury. The purpose of the current study was to assess the performance of miR-122 as a serum biomarker for hepatotoxicity in short-term (5-28 days) repeat-dose rat toxicology studies when benchmarked against routine clinical chemistry and histopathology. A total of 23 studies with multiple dose levels of experimental compounds were examined, and they included animals with or without liver injury and with various hepatic histopathologic changes. Serum miR-122 levels were quantified by reverse transcription quantitative polymerase chain reaction. Increases in circulating miR-122 levels highly correlated with serum elevations of liver enzymes, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST) and glutamate dehydrogenase (GLDH). Statistical analysis showed that miR-122 outperformed ALT as a biomarker for histopathologically confirmed liver toxicity and was equivalent in performance to AST and GLDH. Additionally, an increase of 4% in predictive accuracy was obtained using a multiparameter approach incorporating miR-122 with ALT, AST, and GLDH. In conclusion, serum miR-122 levels can be utilized as a biomarker of hepatotoxicity in acute and subacute rat toxicology studies, and its performance can rival or exceed those of standard enzyme biomarkers such as the liver transaminases. © The Author(s) 2015.

A bibliometric analysis of toxicology research productivity in Middle Eastern Arab countries during a 10-year period (2003-2012).

Science.gov (United States)

Zyoud, Sa'ed H; Al-Jabi, Samah W; Sweileh, Waleed M; Awang, Rahmat

2014-01-21

Bibliometric studies are increasingly being used for research assessment by involving the application of statistical methods to scientific publications to obtain the bibliographics for each country. The main objective of this study was to analyse the research productivity originating from 13 Middle Eastern Arab (MEA) countries with articles published in toxicology journals. Data from January 1, 2003 till December 31, 2012 were searched for documents with specific words in the toxicology field as a "source title" in any one of the 13 MEA countries. Research productivity was evaluated based on a methodology developed and used in other bibliometric studies. Research productivity was adjusted to the national population and nominal gross domestic product (GDP) per capita. Documents (n = 1,240) were retrieved from 73 international peer-reviewed toxicology journals. The h-index of the retrieved documents was 39. Of the 73 journal titles, 52 (69.9%) have their IF listed in the ISI Journal Citation Reports 2012; 198 documents (16.0%) were published in journals that had no official IF. After adjusting for economy and population power, Egypt (193.6), Palestine (18.1), Kingdom of Saudi Arabia (KSA) (13.0), and Jordan (11.5) had the highest research productivity. Countries with large economies, such as the Kuwait, United Arab Emirates (UAE), and Oman, tended to rank relatively low after adjustment of GDP. The total number of citations at the time of data analysis (August 4, 2013) was 10,991, with a median (interquartile range) of 4 (1-11). MEA collaborated more with countries in the MEA regions (16.7%), especially KSA, Egypt, and UAE, followed by Europe (14.4%), especially with the United Kingdom and Germany. The present data show a promising rise and a good start for toxicology research activity in toxicology journals in the Arab world. Research output is low in some countries, which can be improved by investing in more international and national collaborative research

The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project

Science.gov (United States)

Lawrence N. Hudson; Joseph Wunderle M.; And Others

2016-01-01

The PREDICTS project—Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)—has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to...

Innovative non-animal testing strategies for reproductive toxicology: the contribution of Italian partners within the EU project ReProTect

Directory of Open Access Journals (Sweden)

Stefano Lorenzetti

2011-12-01

Full Text Available Reproductive toxicity, with its many targets and mechanisms, is a complex area of toxicology; thus, the screening and identification of reproductive toxicants is a main scientific challenge for the safety assessment of chemicals, including the European Regulation on Chemicals (REACH. Regulatory agencies recommend the implementation of the 3Rs principle (refinement, reduction, replacement as well as of intelligent testing strategies, through the development of in vitro methods and the use of mechanistic information in the hazard identification and characterization steps of the risk assessment process. The EU Integrated Project ReProTect (6th Framework Programme implemented an array of in vitro tests to study different building blocks of the mammalian reproductive cycle: methodological developments and results on male and female germ cells, prostate and placenta are presented.

Safety and toxicological evaluation of a novel Citrus sudachi extract powder

Directory of Open Access Journals (Sweden)

Yasuhiro Shikishima

2016-10-01

Full Text Available Background: Citrus sudachi, an evergreen tree primarily found in the prefecture of Tokushima, Japan, is a widely used popular citrus fruit used in cooking and consumed as a juice. Citrus sudachi peels are rich in flavonoids including sudachitin (5,7,4’-trihydroxy- 6,8,3’- trimethoxyflavone, and exhibit potent antioxidant, antimicrobial and anti-diabetic properties; additionally, several limonoids and their glucosides are found in its seeds. We examined the broad spectrum safety of a novel light yellow to golden yellow Citrus sudachi Extract Powder (CSEP, organic, nutritive from the dried fruit rind (25:1 herbs to extract ratio containing no less than 1% sudachitin in various toxicology models in GLP-approved laboratories. Methods: The acute oral toxicity study was conducted in female Sprague-Dawley rats with an up and down procedure. The single dose acute dermal LD 50 of CSEP was assessed in both male and female rats. The primary skin irritation toxicity of CSEP was assessed in female New Zealand Albino rabbits in order to determine the potential for CSEP to produce irritation after a single topical application, while primary eye irritation index of CSEP was conducted in female New Zealand Albino rabbits. Ames’ bacterial reverse mutation assay was conducted to determine the ability of CSEP to induce reverse mutation at selected histidine loci in five tester strains of Salmonella typhimurium viz. TA1535, TA97a, TA98, TA100, and TA102 in the presence and absence of a metabolic activation system (S9 at the doses of 5000, 1500, 500, 150 and 50 mg/plate. The mutagenic potential of CSEP was also evaluated in an in vitro mammalian cell gene mutation test using the thymidine kinase gene of L5178 Tk+/- 3.7.2C mouse lymphoma cell line. Results: The acute oral LD 50 of CSEP was found to be greater than 5000 mg/kg body weight. The single dose acute dermal LD 50 of CSEP was found to be greater than 2000 mg/kg body weight in both male and female rats

A computational approach to mechanistic and predictive toxicology of pesticides

DEFF Research Database (Denmark)

Kongsbak, Kristine Grønning; Vinggaard, Anne Marie; Hadrup, Niels

2014-01-01

Emerging challenges of managing and interpreting large amounts of complex biological data have given rise to the growing field of computational biology. We investigated the applicability of an integrated systems toxicology approach on five selected pesticides to get an overview of their modes...... of action in humans, to group them according to their modes of action, and to hypothesize on their potential effects on human health. We extracted human proteins associated to prochloraz, tebuconazole, epoxiconazole, procymidone, and mancozeb and enriched each protein set by using a high confidence human......, and procymidone exerted their effects mainly via interference with steroidogenesis and nuclear receptors. Prochloraz was associated to a large number of human diseases, and together with tebuconazole showed several significant associations to Testicular Dysgenesis Syndrome. Mancozeb showed a differential mode...

Operationalization of Prediction, Hindcast, and Evaluation Systems using the Freie Univ Evaluation System Framework (Freva) incl. a Showcase in Decadal Climate Prediction

Science.gov (United States)

Kadow, Christopher; Illing, Sebastian; Schartner, Thomas; Ulbrich, Uwe; Cubasch, Ulrich

2017-04-01

Operationalization processes are important for Weather and Climate Services. Complex data and work flows need to be combined fast to fulfill the needs of service centers. Standards in data and software formats help in automatic solutions. In this study we show a software solution in between hindcasts, forecasts, and validation to be operationalized. Freva (see below) structures data and evaluation procedures and can easily be monitored. Especially in the development process of operationalized services, Freva supports scientists and project partners. The showcase of the decadal climate prediction project MiKlip (fona-miklip.de) shows such a complex development process. Different predictions, scientists input, tasks, and time evolving adjustments need to be combined to host precise climate informations in a web environment without losing track of its evolution. The Freie Univ Evaluation System Framework (Freva - freva.met.fu-berlin.de) is a software infrastructure for standardized data and tool solutions in Earth system science. Freva runs on high performance computers to handle customizable evaluation systems of research projects, institutes or universities. It combines different software technologies into one common hybrid infrastructure, including all features present in the shell and web environment. The database interface satisfies the international standards provided by the Earth System Grid Federation (ESGF). Freva indexes different data projects into one common search environment by storing the meta data information of the self-describing model, reanalysis and observational data sets in a database. This implemented meta data system with its advanced but easy-to-handle search tool supports users, developers and their plugins to retrieve the required information. A generic application programming interface (API) allows scientific developers to connect their analysis tools with the evaluation system independently of the programming language used. Users of the

Antimicrobial and toxicological evaluation of the leaves of Baissea axillaries Hua used in the management of HIV/AIDS patients

Directory of Open Access Journals (Sweden)

Agoreyo Freddy O

2006-06-01

Full Text Available Abstract Background Persistent diarrhea is a common endemic disease with high incidence among the Africans including Nigerians. It also represents a frequent opportunistic disease in people living with HIV. Diarrhea represents one of the most distressful and persistent symptoms of HIV/AIDS, which may or may not be accompanied by an infection. The leaves decoction of Baissea axillaries Hua (Apocynaceae is used by traditional herbalists in Edo state, Nigeria for the management of people living with HIV/AIDS. Determination of its antimicrobial activity and toxicological profile will provide supportive scientific evidence in favour of its continuous usage. Method Chemical and chromatographic tests were employed in phytochemical investigations. Inhibitory activities of aqueous and ethanolic extracts against clinical strains of Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Streptococcus faecalis were compared with Togamycin (Spectinomycin. Our report includes minimum inhibitory concentration (MIC against the test organisms. Toxicological evaluation was determined by administering 250 mg/kg and 500 mg/kg of extracts on male Wister rats for 14 days with normal saline as control. The kidneys, liver, heart and testis tissues were examined. Results Phytochemical studies revealed the presence of alkaloids, tannins, and cyanogenetic glycosides. The extracts inhibited the growth of Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus to varying extents, but only the ethanolic extract inhibited growth in Streptococcus faecalis. The LD50 of the extract in mice was above 5000 mg/kg body weight when administered intraperitoneally. Toxicological evaluation showed mere ballooning degeneration of the liver at 250 mg/kg while at 500 mg/kg there was tissue necrosis. The low and high doses showed ill-defined leydig cells in the testis and no remarkable changes in the heart and kidneys. Conclusion Extracts of Baissea axillaries have

Moving beyond a descriptive aquatic toxicology: the value of biological process and trait information.

Science.gov (United States)

Segner, Helmut

2011-10-01

In order to improve the ability to link chemical exposure to toxicological and ecological effects, aquatic toxicology will have to move from observing what chemical concentrations induce adverse effects to more explanatory approaches, that are concepts which build on knowledge of biological processes and pathways leading from exposure to adverse effects, as well as on knowledge on stressor vulnerability as given by the genetic, physiological and ecological (e.g., life history) traits of biota. Developing aquatic toxicology in this direction faces a number of challenges, including (i) taking into account species differences in toxicant responses on the basis of the evolutionarily developed diversity of phenotypic vulnerability to environmental stressors, (ii) utilizing diversified biological response profiles to serve as biological read across for prioritizing chemicals, categorizing them according to modes of action, and for guiding targeted toxicity evaluation; (iii) prediction of ecological consequences of toxic exposure from knowledge of how biological processes and phenotypic traits lead to effect propagation across the levels of biological hierarchy; and (iv) the search for concepts to assess the cumulative impact of multiple stressors. An underlying theme in these challenges is that, in addition to the question of what the chemical does to the biological receptor, we should give increasing emphasis to the question how the biological receptor handles the chemicals, i.e., through which pathways the initial chemical-biological interaction extends to the adverse effects, how this extension is modulated by adaptive or compensatory processes as well as by phenotypic traits of the biological receptor. 2011 Elsevier B.V. All rights reserved.

Is the Factor-of-2 Rule Broadly Applicable for Evaluating the Prediction Accuracy of Metal-Toxicity Models?

Science.gov (United States)

Meyer, Joseph S; Traudt, Elizabeth M; Ranville, James F

2018-01-01

In aquatic toxicology, a toxicity-prediction model is generally deemed acceptable if its predicted median lethal concentrations (LC50 values) or median effect concentrations (EC50 values) are within a factor of 2 of their paired, observed LC50 or EC50 values. However, that rule of thumb is based on results from only two studies: multiple LC50 values for the fathead minnow (Pimephales promelas) exposed to Cu in one type of exposure water, and multiple EC50 values for Daphnia magna exposed to Zn in another type of exposure water. We tested whether the factor-of-2 rule of thumb also is supported in a different dataset in which D. magna were exposed separately to Cd, Cu, Ni, or Zn. Overall, the factor-of-2 rule of thumb appeared to be a good guide to evaluating the acceptability of a toxicity model's underprediction or overprediction of observed LC50 or EC50 values in these acute toxicity tests.

Toxicological perspectives on perfluorinated compounds in avian species

Energy Technology Data Exchange (ETDEWEB)

Giesy, J.; Jones, P. [Michigan State Univ., East Lansing, MI (United States)

2004-09-15

Perfluorinated chemicals have been widely used in commerce for the last few decades. Until recently little was known about their environmental fate and even less was known about their potential environmental effects. Since Giesy and co-workers first demonstrated the widespread occurrence of perfluorooctane sulfonic acid (PFOS) in wildlife there has been renewed interest in determining the biological and possible ecological effects of these compounds. The assessment of possible effects of these chemicals has been hampered by a limited understanding of their mode of action and by a lack of toxicological data for wildlife species. Here we summarize recently obtained toxicological studies available for perfluorinated compounds (PFCs) in two avian species and use this information and environmental concentration data to evaluate the potential for environmental risk that these compounds pose.

Occupational risk and toxicology evaluations of industrial water conditioning.

Science.gov (United States)

Broussard, G; Bramanti, O; Marchese, F M

1997-08-01

This study addresses the chemical and toxicological questions due to the wide use of chemical treatment programmes for industrial cooling water. First, natural problems encountered in cooling tower systems were presented and grouped into three categories: (i) scaling; (ii) corrosion and (iii) biofouling. Chemical solutions adopted in industrial plants were outlined for each one in order to minimize damage and categorized as shut-down, production loss, heat transfer reduction, upsets, etc. Above all, the purpose of the work was to identify the most dangerous chemicals normally used, which means sources of chemical risk for safety workers and their environment; thus, symptoms of exposure, prevention measures and protection tools are also described.

Toxicological effect of consumption of extract of Jatropha ...

African Journals Online (AJOL)

Background: The leaves of J. tanjorensis are locally consumed as vegetable added to daily foods and has also served a medicinal purpose, however, it toxicological effects is yet to be fully evaluated in our environment. Aim: The present research was to assess the effects of the extract of the leaf of Jatropha tanjorensis on ...

Toxicological profile for thorium. Draft report (Final)

International Nuclear Information System (INIS)

1990-10-01

The ATSDR Toxicological Profile for Thorium is intended to characterize succinctly the toxicological and health effects information for the substance. It identifies and reviews the key literature that describes the substance's toxicological properties. Other literature is presented but described in less detail. The profile is not intended to be an exhaustive document; however, more comprehensive sources of specialty information are referenced. The profile begins with a public health statement, which describes in nontechnical language the substance's relevant toxicological properties. Following the statement is material that presents levels of significant human exposure and, where known, significant health effects. The adequacy of information to determine the substance's health effects is described. Research gaps in nontoxic and health effects information are described. Research gaps that are of significance to the protection of public health will be identified in a separate effort. The focus of the document is on health and toxicological information

Regenerative toxicology: the role of stem cells in the development of chronic toxicities

NARCIS (Netherlands)

Canovas-Jorda, D.; Louisse, J.; Pistollato, F.; Zagoura, D.; Bremer, S.

2014-01-01

Introduction: Human stem cell lines and their derivatives, as alternatives to the use of animal cells or cancer cell lines, have been widely discussed as cellular models in predictive toxicology. However, the role of stem cells in the development of long-term toxicities and carcinogenesis has not

PREDICTS: Projecting Responses of Ecological Diversity in Changing Terrestrial Systems

Directory of Open Access Journals (Sweden)

Georgina Mace

2012-12-01

Full Text Available The PREDICTS project (www.predicts.org.uk is a three-year NERC-funded project to model and predict at a global scale how local terrestrial diversity responds to human pressures such as land use, land cover, pollution, invasive species and infrastructure. PREDICTS is a collaboration between Imperial College London, the UNEP World Conservation Monitoring Centre, Microsoft Research Cambridge, UCL and the University of Sussex. In order to meet its aims, the project relies on extensive data describing the diversity and composition of biological communities at a local scale. Such data are collected on a vast scale through the committed efforts of field ecologists. If you have appropriate data that you would be willing to share with us, please get in touch (enquiries@predicts.org.uk. All contributions will be acknowledged appropriately and all data contributors will be included as co-authors on an open-access paper describing the database.

Evaluating the mutagenic potential of aerosol organic compounds using informatics-based screening

Science.gov (United States)

Decesari, Stefano; Kovarich, Simona; Pavan, Manuela; Bassan, Arianna; Ciacci, Andrea; Topping, David

2018-02-01

Whilst general policy objectives to reduce airborne particulate matter (PM) health effects are to reduce exposure to PM as a whole, emerging evidence suggests that more detailed metrics associating impacts with different aerosol components might be needed. Since it is impossible to conduct toxicological screening on all possible molecular species expected to occur in aerosol, in this study we perform a proof-of-concept evaluation on the information retrieved from in silico toxicological predictions, in which a subset (N = 104) of secondary organic aerosol (SOA) compounds were screened for their mutagenicity potential. An extensive database search showed that experimental data are available for 13 % of the compounds, while reliable predictions were obtained for 82 %. A multivariate statistical analysis of the compounds based on their physico-chemical, structural, and mechanistic properties showed that 80 % of the compounds predicted as mutagenic were grouped into six clusters, three of which (five-membered lactones from monoterpene oxidation, oxygenated multifunctional compounds from substituted benzene oxidation, and hydroperoxides from several precursors) represent new candidate groups of compounds for future toxicological screenings. These results demonstrate that coupling model-generated compositions to in silico toxicological screening might enable more comprehensive exploration of the mutagenic potential of specific SOA components.

Improvement of risk assessment by integrating toxicological and epidemiological approaches: the case of isoflavones

NARCIS (Netherlands)

Islam, M.A.

2015-01-01

Improvement of risk assessment by integrating toxicological and epidemiological approaches: the case of isoflavones

PhD-thesis Mohammed Ariful Islam

This thesis describes the results of a research project that aimed at the improvement of

A bibliometric analysis of toxicology research productivity in Middle Eastern Arab countries during a 10-year period (2003–2012)

Science.gov (United States)

2014-01-01

Background Bibliometric studies are increasingly being used for research assessment by involving the application of statistical methods to scientific publications to obtain the bibliographics for each country. The main objective of this study was to analyse the research productivity originating from 13 Middle Eastern Arab (MEA) countries with articles published in toxicology journals. Methods Data from January 1, 2003 till December 31, 2012 were searched for documents with specific words in the toxicology field as a “source title” in any one of the 13 MEA countries. Research productivity was evaluated based on a methodology developed and used in other bibliometric studies. Research productivity was adjusted to the national population and nominal gross domestic product (GDP) per capita. Results Documents (n = 1,240) were retrieved from 73 international peer-reviewed toxicology journals. The h-index of the retrieved documents was 39. Of the 73 journal titles, 52 (69.9%) have their IF listed in the ISI Journal Citation Reports 2012; 198 documents (16.0%) were published in journals that had no official IF. After adjusting for economy and population power, Egypt (193.6), Palestine (18.1), Kingdom of Saudi Arabia (KSA) (13.0), and Jordan (11.5) had the highest research productivity. Countries with large economies, such as the Kuwait, United Arab Emirates (UAE), and Oman, tended to rank relatively low after adjustment of GDP. The total number of citations at the time of data analysis (August 4, 2013) was 10,991, with a median (interquartile range) of 4 (1–11). MEA collaborated more with countries in the MEA regions (16.7%), especially KSA, Egypt, and UAE, followed by Europe (14.4%), especially with the United Kingdom and Germany. Conclusions The present data show a promising rise and a good start for toxicology research activity in toxicology journals in the Arab world. Research output is low in some countries, which can be improved by investing in more

Integration of QSAR and in vitro toxicology.

Science.gov (United States)

Barratt, M D

1998-01-01

The principles of quantitative structure-activity relationships (QSAR) are based on the premise that the properties of a chemical are implicit in its molecular structure. Therefore, if a mechanistic hypothesis can be proposed linking a group of related chemicals with a particular toxic end point, the hypothesis can be used to define relevant parameters to establish a QSAR. Ways in which QSAR and in vitro toxicology can complement each other in development of alternatives to live animal experiments are described and illustrated by examples from acute toxicological end points. Integration of QSAR and in vitro methods is examined in the context of assessing mechanistic competence and improving the design of in vitro assays and the development of prediction models. The nature of biological variability is explored together with its implications for the selection of sets of chemicals for test development, optimization, and validation. Methods are described to support the use of data from in vivo tests that do not meet today's stringent requirements of acceptability. Integration of QSAR and in vitro methods into strategic approaches for the replacement, reduction, and refinement of the use of animals is described with examples. PMID:9599692

Assessment of predictivity of volatile organic compounds carcinogenicity and mutagenicity by freeware in silico models.

Science.gov (United States)

Guerra, Lília Ribeiro; de Souza, Alessandra Mendonça Teles; Côrtes, Juliana Alves; Lione, Viviane de Oliveira Freitas; Castro, Helena Carla; Alves, Gutemberg Gomes

2017-12-01

The application of in silico methods is increasing on toxicological risk prediction for human and environmental health. This work aimed to evaluate the performance of three in silico freeware models (OSIRIS v.2.0, LAZAR, and Toxtree) on the prediction of carcinogenicity and mutagenicity of thirty-eight volatile organic compounds (VOC) related to chemical risk assessment for occupational exposure. Theoretical data were compared with assessments available in international databases. Confusion matrices and ROC curves were used to evaluate the sensitivity, specificity, and accuracy of each model. All three models (OSIRIS, LAZAR and Toxtree) were able to identify VOC with a potential carcinogenicity or mutagenicity risk for humans, however presenting differences concerning the specificity, sensitivity, and accuracy. The best predictive performances were found for OSIRIS and LAZAR for carcinogenicity and OSIRIS for mutagenicity, as these softwares presented a combination of negative predictive power and lower risk of false positives (high specificity) for those endpoints. The heterogeneity of results found with different softwares reinforce the importance of using a combination of in silico models to occupational toxicological risk assessment. Copyright © 2017 Elsevier Inc. All rights reserved.

Toxicología clínica comunitaria Community Clinical Toxicology

Directory of Open Access Journals (Sweden)

María Elena Leal

2011-08-01

Full Text Available En algunos países de América Latina las intoxicaciones agudas se manejan de manera profesional por médicos especialistas en la mate-ria. Algo similar ocurre con las intoxicaciones crónicas de origen laboral en el sector formal. No obstante, una realidad diferente ocurre en cuanto a la evaluación de las intoxicaciones crónicas de origen ambiental, dado que éstas por su naturaleza, son más difíciles de diagnosticar. Para el tratamiento de las intoxicaciones agudas se han organizado Centros de Información y Atención Toxicológica, pero para las intoxicaciones crónicas ambientales no se ha generado organismos semejantes. Por consiguiente, en este trabajo sugerimos un modelo de atención de la intoxicaciones crónicas a través de grupos multidisciplinarios bajo el esquema de una nueva disciplina: la Toxicología Clínica Comunitaria, cuyo objetivo sería la atención simultánea de las intoxicaciones agudas que generalmente se atienden en un ámbito hospitalario y de las intoxicaciones ambientales que por lo normal se presentan a nivel comunitario. El objetivo final es aprovechar la experiencia que existe en la Región en cuanto a Toxicología Clínica para organizar el trabajo comunitario.In some Latin American countries acute intoxication is professionally managed by specialized physicians qualified in the area. Something similar occurs with work-related chronic intoxication in the formal sector. However, a different reality prevails for the assessment of chronic intoxication of environmental origin, since it is by definition more difficult to diagnose. For treatment of acute intoxication, Toxicological Information and Care Centers have been set up, though similar bodies have not been created for chronic environmental intoxication. Therefore, in this study a model of chronic intoxication care is proposed, using multidisciplinary teams adopting a new approach, namely Community Clinical Toxicology, the goal of which would be the

Prediction of optimal deployment projection for transcatheter aortic valve replacement: angiographic 3-dimensional reconstruction of the aortic root versus multidetector computed tomography.

Science.gov (United States)

Binder, Ronald K; Leipsic, Jonathon; Wood, David; Moore, Teri; Toggweiler, Stefan; Willson, Alex; Gurvitch, Ronen; Freeman, Melanie; Webb, John G

2012-04-01

Identifying the optimal fluoroscopic projection of the aortic valve is important for successful transcatheter aortic valve replacement (TAVR). Various imaging modalities, including multidetector computed tomography (MDCT), have been proposed for prediction of the optimal deployment projection. We evaluated a method that provides 3-dimensional angiographic reconstructions (3DA) of the aortic root for prediction of the optimal deployment angle and compared it with MDCT. Forty patients undergoing transfemoral TAVR at St Paul's Hospital, Vancouver, Canada, were evaluated. All underwent preimplant 3DA and 68% underwent preimplant MDCT. Three-dimensional angiographic reconstructions were generated from images of a C-arm rotational aortic root angiogram during breath-hold, rapid ventricular pacing, and injection of 32 mL contrast medium at 8 mL/s. Two independent operators prospectively predicted perpendicular valve projections. The implant angle was chosen at the discretion of the physician performing TAVR. The angles from 3DA, from MDCT, the implant angle, and the postdeployment perpendicular prosthesis view were compared. The shortest distance from the postdeployment perpendicular prosthesis projection to the regression line of predicted perpendicular projections was calculated. All but 1 patient had adequate image quality for reproducible angle predictions. There was a significant correlation between 3DA and MDCT for prediction of perpendicular valve projections (r=0.682, Pregression line of predicted angles to the postdeployment prosthesis view was 5.1±4.6° for 3DA and 7.9±4.9° for MDCT (P=0.01). Three-dimensional angiographic reconstructions and MDCT are safe, practical, and accurate imaging modalities for identifying the optimal perpendicular valve deployment projection during TAVR.

Use of read-across and computer-based predictive analysis for the safety assessment of PEG cocamines.

Science.gov (United States)

Skare, Julie A; Blackburn, Karen; Wu, Shengde; Re, Thomas A; Duche, Daniel; Ringeissen, Stephanie; Bjerke, Donald L; Srinivasan, Viny; Eisenmann, Carol

2015-04-01

In the European Union animal testing has been eliminated for cosmetic ingredients while the US Cosmetic Ingredient Review Expert Panel may request data from animal studies. The use of read-across and predictive toxicology provides a path for filling data gaps without additional animal testing. The PEG cocamines are tertiary amines with an alkyl group derived from coconut fatty acids and two PEG chains of varying length. Toxicology data gaps for the PEG cocamines can be addressed by read-across based on structure-activity relationship using the framework described by Wu et al. (2010) for identifying suitable structural analogs. Data for structural analogs supports the conclusion that the PEG cocamines are non-genotoxic and not expected to exhibit systemic or developmental/reproductive toxicity with use in cosmetics. Due to lack of reliable dermal sensitization data for suitable analogs, this endpoint was addressed using predictive software (TIMES SS) as a first step (Laboratory of Mathematical Chemistry). The prediction for PEG cocamines was the same as that for PEGs, which have been concluded to not present a significant concern for dermal sensitization. This evaluation for PEG cocamines demonstrates the utility of read-across and predictive toxicology tools to assess the safety of cosmetic ingredients. Copyright © 2015 Elsevier Inc. All rights reserved.

Developmental toxicology: adequacy of current methods.

Science.gov (United States)

Peters, P W

1998-01-01

Toxicology embraces several disciplines such as carcinogenicity, mutagenicity and reproductive toxicity. Reproductive toxicology is concerned with possible effects of substances on the reproductive process, i.e. on sexual organs and their functions, endocrine regulation, fertilization, transport of the fertilized ovum, implantation, and embryonic, fetal and postnatal development, until the end-differentiation of the organs is achieved. Reproductive toxicology is divided into areas related to male and female fertility, and developmental toxicology. Developmental toxicology can be further broken down into prenatal and postnatal toxicology. Today, much new information is available about the origins of developmental disorders resulting from chemical exposure. While these findings seem to promise important new developments in methodology and research, there is a danger of losing sight of the precepts and principles established in the light of existing knowledge. There is also a danger that we may fail to correct shortcomings in our existing procedures and practice. The aim of this presentation is to emphasize the importance of testing substances for their impact in advance of their use and to underline that we must use the best existing tools for carrying out risk assessments. Moreover, it needs to be stressed that there are many substances that are never assessed with respect to reproductive and developmental toxicity. Similarly, our programmes for post-marketing surveillance with respect to developmental toxicology are grossly inadequate. Our ability to identify risks to normal development and reproduction would be much improved, first if a number of straightforward precepts were always followed and second, if we had a clearer understanding of what we mean by risk and acceptable levels of risk in the context of development. Other aims of this paper are: to stress the complexity of the different stages of normal prenatal development; to note the principles that are

Resolution of aviation forensic toxicology findings with the aid of DNA profiling.

Science.gov (United States)

Chaturvedi, Arvind K; Craft, Kristi J; Kupfer, Doris M; Burian, Dennis; Canfield, Dennis V

2011-03-20

Body components of aviation accident fatalities are often scattered, disintegrated, commingled, contaminated, and/or putrefied at accident scenes. These situations may impose difficulties in victim identification/tissue matching. The prevalence of misidentification in relation to aviation accident forensic toxicology has not been well established. Therefore, the Civil Aerospace Medical Institute (CAMI) toxicology database was searched for the 1998-2008 period for those cases wherein DNA profiling was performed to resolve identity issue of the samples submitted to CAMI for toxicological evaluation. During this period, biological samples from the casualties of a total of 3523 accidents were submitted to CAMI. The submitted samples were primarily from pilots. Out of the 3523 accidents, at least, one fatality had occurred in 3366 (≈ 96%) accidents; thus, these accidents were considered fatal accidents. Accordingly, biological samples from 3319 pilots (3319 of the 3366 accidents) were received at CAMI for toxicological testing. Of these 3319 pilots, 3275 (≈ 99%) were fatally injured. DNA profiling was performed in 15 (≈ 0.5%) of the 3319 accidents. The profiling was conducted upon the requests of families in two accidents, accident investigators in three, and pathologists in four. In six accidents, contradictory toxicological findings led CAMI to initiate DNA profiling. The requests made by families and investigators were primarily triggered by inconsistency between the toxicological results and the history of drug use of the victims, while by pathologists because of commingling of samples. In three (20%) of the 15 accidents, at least one submitted sample was misidentified or mislabeled. The present study demonstrated that the number of aviation accident cases requiring DNA profiling was small and this DNA approach was effectively applied in resolving aviation toxicology findings associated with those accidents. Published by Elsevier Ireland Ltd.

[Clinical toxicology of the Academy: yesterday, today and tomorrow].

Science.gov (United States)

Sofronov, G A; Khalimov, Iu Sh; Matveev, S Iu; Kuz'mich, V G; Fomichev, A V

2013-12-01

National toxicology school of the Kirov Military Medical Academy, demonstrates the unity of clinical and experimental approaches related to one purpose throughout its history--saving human life and health from exposure to toxic substances of chemical nature. For more than three centuries the russian science of toxicology has been steadily developing, often ahead of the world science. It helped to create the means of protection and develop methods of treatment for chemical lesions. Currently, toxicology departments of military field therapy and military toxicology and medical protection are actively involved in the current study of military medicine, restructuring policy to provide toxicological aid in the Armed Forces, the development and introduction of Innovative methods of diagnosis and treatment of victims of toxicological etiology.

The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project

OpenAIRE

Hudson, L. N.; Newbold, T.; Contu, S.; Hill, S. L.; Lysenko, I.; De Palma, A.; Phillips, H. R.; Alhusseini, T. I.; Bedford, F. E.; Bennett, D. J.; Booth, H.; Burton, V. J.; Chng, C. W.; Choimes, A.; Correia, D. L.

2017-01-01

The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make free...

Transport Project Evaluation

DEFF Research Database (Denmark)

Leleur, Steen

1996-01-01

Two main project evaluation approaches exist: cost-benefit analysis (CBA) and multi-criteria analysis (MCA). Related to a European road evaluation method (EURET 1.1) and the MCA-method, WARP, the paper proposes a set of so-called segregated investment return rates (SIRR) to integrate advantages...

Safety evaluation of β-glucanase derived from Trichoderma reesei: Summary of toxicological data

NARCIS (Netherlands)

Coenen, T.M.M.; Schoenmakers, A.C.M.; Verhagen, H.

1995-01-01

Barlican, a β-glucanase enzyme obtained from Trichoderma reesei, was produced by a fermentation process and subjected to a series of toxicological tests to document its safety for use as a feed additive. The enzyme product was examined for general oral toxicity, inhalation toxicity, irritation to

Principles and procedures in forensic toxicology.

Science.gov (United States)

Wyman, John F

2012-09-01

The principles and procedures employed in a modern forensic toxicology lab are detailed in this review. Aspects of Behavioral and Postmortem toxicology, including certification of analysts and accreditation of labs, chain of custody requirements, typical testing services provided, rationale for specimen selection, and principles of quality assurance are discussed. Interpretation of toxicology results in postmortem specimens requires the toxicologist and pathologist to be cognizant of drug-drug interactions, drug polymorphisms and pharmacogenomics, the gross signs of toxic pathology, postmortem redistribution, confirmation of systemic toxicity in suspected overdoses, the possibility of developed tolerance, and the effects of decomposition on drug concentration.

Project evaluation: main characteristics

OpenAIRE

Moutinho, Nuno

2010-01-01

— The evaluation process of real investment projects must consider not only the traditional financial approach, but also non-financial aspects. Non financial analysis can provide additional relevant information about projects. We investigate financial and non-financial areas most relevant in project appraisal. We present main critical success factors and areas of analysis that lead to the perception of project success. Finally, companies are segmented to verify its financial and non-financial...

Three lessons for genetic toxicology from baseball analytics.

Science.gov (United States)

Dertinger, Stephen D

2017-07-01

In many respects the evolution of baseball statistics mirrors advances made in the field of genetic toxicology. From its inception, baseball and statistics have been inextricably linked. Generations of players and fans have used a number of relatively simple measurements to describe team and individual player's current performance, as well as for historical record-keeping purposes. Over the years, baseball analytics has progressed in several important ways. Early advances were based on deriving more meaningful metrics from simpler forerunners. Now, technological innovations are delivering much deeper insights. Videography, radar, and other advances that include automatic player recognition capabilities provide the means to measure more complex and useful factors. Fielders' reaction times, efficiency of the route taken to reach a batted ball, and pitch-framing effectiveness come to mind. With the current availability of complex measurements from multiple data streams, multifactorial analyses occurring via machine learning algorithms have become necessary to make sense of the terabytes of data that are now being captured in every Major League Baseball game. Collectively, these advances have transformed baseball statistics from being largely descriptive in nature to serving data-driven, predictive roles. Whereas genetic toxicology has charted a somewhat parallel course, a case can be made that greater utilization of baseball's mindset and strategies would serve our scientific field well. This paper describes three useful lessons for genetic toxicology, courtesy of the field of baseball analytics: seek objective knowledge; incorporate multiple data streams; and embrace machine learning. Environ. Mol. Mutagen. 58:390-397, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Toxicological aspects of energy production

International Nuclear Information System (INIS)

Sanders, C.L.

1986-01-01

Part I reviews the principles of toxicology, describes the biological fate of chemicals in the body, discusses basic pathobiology, and reviews short-term toxicity tests. Part II describes the toxicology and pathology of pollutants in several important organ systems. The greatest emphasis is placed on the respiratory tract because of its high probability as a route of exposure to pollutants from energy technologies and its high sensitivity to pollutant related tissue damage. Part III describes the toxicological aspects of specific chemical classes associated with fossil fuels; these include polycyclic hydrocarbons, gases and metals. Part IV describes the biomedical effects associated with each energy technology, including coal and oil, fossil fuel and biomass conversions, solar and geothermal and radiological health aspects associated with uranium mining, nuclear fission and fusion, and with nonionising radiations and electromagnetic fields

Shuttle Lesson Learned - Toxicology

Science.gov (United States)

James, John T.

2010-01-01

This is a script for a video about toxicology and the space shuttle. The first segment is deals with dust in the space vehicle. The next segment will be about archival samples. Then we'll look at real time on-board analyzers that give us a lot of capability in terms of monitoring for combustion products and the ability to monitor volatile organics on the station. Finally we will look at other issues that are about setting limits and dealing with ground based lessons that pertain to toxicology.

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

Systems Toxicology: Real World Applications and Opportunities

Science.gov (United States)

2017-01-01

Systems Toxicology aims to change the basis of how adverse biological effects of xenobiotics are characterized from empirical end points to describing modes of action as adverse outcome pathways and perturbed networks. Toward this aim, Systems Toxicology entails the integration of in vitro and in vivo toxicity data with computational modeling. This evolving approach depends critically on data reliability and relevance, which in turn depends on the quality of experimental models and bioanalysis techniques used to generate toxicological data. Systems Toxicology involves the use of large-scale data streams (“big data”), such as those derived from omics measurements that require computational means for obtaining informative results. Thus, integrative analysis of multiple molecular measurements, particularly acquired by omics strategies, is a key approach in Systems Toxicology. In recent years, there have been significant advances centered on in vitro test systems and bioanalytical strategies, yet a frontier challenge concerns linking observed network perturbations to phenotypes, which will require understanding pathways and networks that give rise to adverse responses. This summary perspective from a 2016 Systems Toxicology meeting, an international conference held in the Alps of Switzerland, describes the limitations and opportunities of selected emerging applications in this rapidly advancing field. Systems Toxicology aims to change the basis of how adverse biological effects of xenobiotics are characterized, from empirical end points to pathways of toxicity. This requires the integration of in vitro and in vivo data with computational modeling. Test systems and bioanalytical technologies have made significant advances, but ensuring data reliability and relevance is an ongoing concern. The major challenge facing the new pathway approach is determining how to link observed network perturbations to phenotypic toxicity. PMID:28362102

Systems Toxicology: Real World Applications and Opportunities.

Science.gov (United States)

Hartung, Thomas; FitzGerald, Rex E; Jennings, Paul; Mirams, Gary R; Peitsch, Manuel C; Rostami-Hodjegan, Amin; Shah, Imran; Wilks, Martin F; Sturla, Shana J

2017-04-17

Systems Toxicology aims to change the basis of how adverse biological effects of xenobiotics are characterized from empirical end points to describing modes of action as adverse outcome pathways and perturbed networks. Toward this aim, Systems Toxicology entails the integration of in vitro and in vivo toxicity data with computational modeling. This evolving approach depends critically on data reliability and relevance, which in turn depends on the quality of experimental models and bioanalysis techniques used to generate toxicological data. Systems Toxicology involves the use of large-scale data streams ("big data"), such as those derived from omics measurements that require computational means for obtaining informative results. Thus, integrative analysis of multiple molecular measurements, particularly acquired by omics strategies, is a key approach in Systems Toxicology. In recent years, there have been significant advances centered on in vitro test systems and bioanalytical strategies, yet a frontier challenge concerns linking observed network perturbations to phenotypes, which will require understanding pathways and networks that give rise to adverse responses. This summary perspective from a 2016 Systems Toxicology meeting, an international conference held in the Alps of Switzerland, describes the limitations and opportunities of selected emerging applications in this rapidly advancing field. Systems Toxicology aims to change the basis of how adverse biological effects of xenobiotics are characterized, from empirical end points to pathways of toxicity. This requires the integration of in vitro and in vivo data with computational modeling. Test systems and bioanalytical technologies have made significant advances, but ensuring data reliability and relevance is an ongoing concern. The major challenge facing the new pathway approach is determining how to link observed network perturbations to phenotypic toxicity.

Food applications and the toxicological and nutritional implications of amorphous silicon dioxide.

Science.gov (United States)

Villota, R; Hawkes, J G

1986-01-01

The chemical and physical characteristics of the different types of amorphous silicon dioxide contribute to the versatility of these compounds in a variety of commercial applications. Traditionally, silicas have had a broad spectra of product usage including such areas as viscosity control agents in inks, paints, corrosion-resistant coatings, etc. and as excipients in pharmaceuticals and cosmetics. In the food industry, the most important application has been as an anticaking agent in powdered mixes, seasonings, and coffee whiteners. However, amorphous silica has multifunctional properties that would allow it to act as a viscosity control agent, emulsion stabilizer, suspension and dispersion agent, desiccant, etc. The utilization of silicas in these potential applications, however, has not been undertaken, partially because of the limited knowledge of their physiochemical interactions with other food components and partially due to their controversial status from a toxicological point of view. The main goal of this review is to compile current information on the incorporation of amorphous silicon dioxide as a highly functional and viable additive in the food processing industry as well as to discuss the most recent toxicological investigations of silica in an attempt to present some of the potential food applications and their concomitant toxicological implications. Some of the more significant differences between various silicas and their surface chemistries are presented to elucidate some of their mechanisms of interaction with food components and other biological systems and to aid in the prediction of their rheological or toxicological behavior.

Research Planning and Evaluation Project

International Nuclear Information System (INIS)

Song, Seunghyun; Kim, Doyang; Ryu, Byunghoon; Lim, Chaeyoung; Song, Leeyoung; Lee, Youngchul; Han, Changsun; Kim, Hackchoon

2011-12-01

- To activate R and D through a systematic and impartial evaluation by using information on efficient distribution of research resource, setting project priorities, and measuring achievement against goals produced after research on planning and evaluation system for the government-funded project for KAERI was conducted. - Nuclear R and D project is the representative national R and D project which has been implemented in Korea. For the sustainable development of nuclear energy which supplies about 40% of total electricity generation and the enhancement of it innovative ability in the future, a systematic and efficient strategy in the planning stage is required

Project Management Personnel Competencies Evaluation

Directory of Open Access Journals (Sweden)

Paul POCATILU

2006-01-01

Full Text Available An important factor for the success management of IT projects is the human resource. People involved in the project management process have to be evaluated. In order to do that, same criteria has to be specified. This paper describes some aspects regarding the personnel evaluation.

42 CFR 493.845 - Standard; Toxicology.

Science.gov (United States)

2010-10-01

... 42 Public Health 5 2010-10-01 2010-10-01 false Standard; Toxicology. 493.845 Section 493.845 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... These Tests § 493.845 Standard; Toxicology. (a) Failure to attain a score of at least 80 percent of...

A QSAR, Pharmacokinetic and Toxicological Study of New Artemisinin Compounds with Anticancer Activity

Directory of Open Access Journals (Sweden)

Josinete B. Vieira

2014-07-01

Full Text Available The Density Functional Theory (DFT method and the 6-31G** basis set were employed to calculate the molecular properties of artemisinin and 20 derivatives with different degrees of cytotoxicity against the human hepatocellular carcinoma HepG2 line. Principal component analysis (PCA and hierarchical cluster analysis (HCA were employed to select the most important descriptors related to anticancer activity. The significant molecular descriptors related to the compounds with anticancer activity were the ALOGPS_log, Mor29m, IC5 and GAP energy. The Pearson correlation between activity and most important descriptors were used for the regression partial least squares (PLS and principal component regression (PCR models built. The regression PLS and PCR were very close, with variation between PLS and PCR of R2 = ±0.0106, R2ajust = ±0.0125, s = ±0.0234, F(4,11 = ±12.7802, Q2 = ±0.0088, SEV = ±0.0132, PRESS = ±0.4808 and SPRESS = ±0.0057. These models were used to predict the anticancer activity of eight new artemisinin compounds (test set with unknown activity, and for these new compounds were predicted pharmacokinetic properties: human intestinal absorption (HIA, cellular permeability (PCaCO2, cell permeability Maden Darby Canine Kidney (PMDCK, skin permeability (PSkin, plasma protein binding (PPB and penetration of the blood-brain barrier (CBrain/Blood, and toxicological: mutagenicity and carcinogenicity. The test set showed for two new artemisinin compounds satisfactory results for anticancer activity and pharmacokinetic and toxicological properties. Consequently, further studies need be done to evaluate the different proposals as well as their actions, toxicity, and potential use for treatment of cancers.

IT Project Evaluation and Investment Decision

Institute of Scientific and Technical Information of China (English)

黄东兵; 张世英

2004-01-01

There are many kinds of real options,which are valuable,in each phase of the lifetime of an information technology(IT)project.However,in the current IT investment decision theory,real options that embedded in IT projects are not considered. In this paper, the process of IT project decision and implementation is fully analyzed, the real options that may be embedded in an IT project are identified, and a real option analysis (ROA) method is proposed for evaluation of an IT project under uncertain business environment. ROA employs Black-Scholes expansion model and cancels the assumption that the cost of project is certain. The numerical example manifests that the ROA can better evaluate IT project and select the IT investment alternative. Finally, a road map is provided to help selecting the suitable evaluation method to make IT investment decision.

Toxicology of plutonium

International Nuclear Information System (INIS)

Bair, W.J.

1974-01-01

Data are reviewed from studies on the toxicity of Pu in experimental animals. Of the several plutonium isotopes, only 238 Pu and 239 Pu have been studied well. Sufficient results have been obtained to show that the behavior of 238 Pu in biological systems and the resulting biological effects cannot be precisely predicted from studies of 239 Pu. This probably applies also to other radiologically important plutonium isotopes which have half-lives ranging from 45 days to 10 7 years and decay by β-emission, electron capture, and spontaneous fission, as well as by emission of α-particles. All the biological effects of plutonium described in this review are attributed to alpha-particle radiation emitted by the plutonium. However, since plutonium is a chemically active heavy metal, one cannot ignore the possibility of chemical toxicity of the low-specific-activity isotopes, 239 Pu, 242 Pu, and 244 Pu. The preponderance of our knowledge of plutonium toxicology has come from short-term studies of relatively high dosage levels in several animal species. The consequences of high-level internal exposures can be predicted with confidence in experimental animals and probably also in man. However, considering the care with which plutonium is handled in the nuclear industry, a high-level contamination event is unlikely. Considerably less is known about the long-term effects of low levels of contamination. (250 references) (U.S.)

Development of methodology for alternative testing strategies for the assessment of the toxicological profile of nanoparticles used in medical diagnostics. NanoTEST - EC FP7 project

International Nuclear Information System (INIS)

Dusinska, Maria; Fjellsbo, Lise Maria; Heimstad, Eldbjorg; Harju, Mikael; Bartonova, Alena; Tran, Lang; Juillerat-Jeanneret, Lucienne; Halamoda, Blanka; Marano, Francelyne; Boland, Sonja; Saunders, Margaret; Cartwright, Laura; Carreira, Sara; Thawley, Susan; Whelan, Maurice; Klein, Christoph; Housiadas, Christos; Volkovova, Katarina; Tulinska, Jana; Beno, Milan

2009-01-01

Nanoparticles (NPs) have unique, potentially beneficial properties, but their possible impact on human health is still not known. The area of nanomedicine brings humans into direct contact with NPs and it is essential for both public confidence and the nanotech companies that appropriate risk assessments are undertaken in relation to health and safety. There is a pressing need to understand how engineered NPs can interact with the human body following exposure. The FP7 project NanoTEST (www.nanotest-fp7.eu) addresses these requirements in relation to the toxicological profile of NPs used in medical diagnostics.

Increasing Prediction the Original Final Year Project of Student Using Genetic Algorithm

Science.gov (United States)

Saragih, Rijois Iboy Erwin; Turnip, Mardi; Sitanggang, Delima; Aritonang, Mendarissan; Harianja, Eva

2018-04-01

Final year project is very important forgraduation study of a student. Unfortunately, many students are not seriouslydidtheir final projects. Many of studentsask for someone to do it for them. In this paper, an application of genetic algorithms to predict the original final year project of a studentis proposed. In the simulation, the data of the final project for the last 5 years is collected. The genetic algorithm has several operators namely population, selection, crossover, and mutation. The result suggest that genetic algorithm can do better prediction than other comparable model. Experimental results of predicting showed that 70% was more accurate than the previous researched.

Mass Spectrometry Applications for Toxicology

OpenAIRE

Mbughuni, Michael M.; Jannetto, Paul J.; Langman, Loralie J.

2016-01-01

Toxicology is a multidisciplinary study of poisons, aimed to correlate the quantitative and qualitative relationships between poisons and their physiological and behavioural effects in living systems. Other key aspects of toxicology focus on elucidation of the mechanisms of action of poisons and development of remedies and treatment plans for associated toxic effects. In these endeavours, Mass spectrometry (MS) has become a powerful analytical technique with a wide range of application used i...

IRIS Toxicological Review of Acrolein (2003 Final)

Science.gov (United States)

EPA announced the release of the final report, Toxicological Review of Acrolein: in support of the Integrated Risk Information System (IRIS). The updated Summary for Acrolein and accompanying toxicological review have been added to the IRIS Database.

Creating Robust Evaluation of ATE Projects

Science.gov (United States)

Eddy, Pamela L.

2017-01-01

Funded grant projects all involve some form of evaluation, and Advanced Technological Education (ATE) grants are no exception. Program evaluation serves as a critical component not only for evaluating if a project has met its intended and desired outcomes, but the evaluation process is also a central feature of the grant application itself.…

Evaluation of a Hungarian acaricide original molecule based on its environmental toxicological studies.

Science.gov (United States)

Szamosi, D; Oláh, B; Hirka, G; Pap, L; Gáty, S

2000-07-01

The results of the environmental toxicological investigations and their results of a new hungarian acaricide molecule (SZI-121) developed by the CHINOIN were summarized. The toxicological effects of the test item on different ecotoxicological test systems were investigated in the following tests: Bacterium, alga, and plant growth inhibition tests, acute immobilization and 21 days reproduction tests on Daphnia magna, acute fish test, closed bottle test, mobility, aerob degradation and adsorption/desorption tests on three different soils. No toxic effect was found in the bacterium, alga, plant growth inhibition and acute fish tests in the highest concentrations used. In the Daphnia immobilization test 0.14 mg/l LC50 value was established in the concentration range of 0.0128-40 mg/l applied. The test item showed similar characteristics as the reference item during the mobility test in soils, the adsorption/desorption study and the degradation investigations. In order to determine the environmental degradation rate further degradation investigations, as well as the nitrogen mineralization test and the model of concentration change in natural waters were performed.

Importance of clinical toxicology teaching and its impact in improving knowledge: sharing experience from a workshop

International Nuclear Information System (INIS)

Khan, N.U.; Fayyaz, J.; Khan, U.R.; Feroze, A.

2013-01-01

Objective: To assess the impact of a one-day clinical toxicology workshop in improving knowledge. Methods: A one-day clinical toxicology workshop was conducted as a pre-conference workshop of the Annual Emergency Medicine Conference at the Aga Khan University Hospital, Karachi, in April 2012. The course was composed of poisoning-related common clinical scenarios. The pre-test and post-test understanding was used to assess the impact of the course in improving knowledge. The participants also evaluated the workshop as a whole thorough written evaluation forms. SPSS 19 was used for statistical analysis of the data. Result: There were 22 participants in the course. The pre-test mean score was 31.6+-15.1% (95% CI; 24-40; n=19) compared to the post-test the mean score of 56.0+-10.8% (95% CI; 47- 61; n=17). The positive difference was also statistically significant (p<0.001). The overall workshop was evaluated as excellent by 08 (47.46%) and very good by 10 (52.63%) participants. Conclusion: Short training in clinical toxicology improved knowledge of the participants. (author)

Evaluation of microfinance projects.

Science.gov (United States)

Johnson, S

1999-08-01

This paper criticizes the quick system proposed by Henk Moll for evaluating microfinance projects in the article ¿How to Pre-Evaluate Credit Projects in Ten Minutes¿. The author contended that there is a need to emphasize the objectives of the project. The procedure used by Moll, he contended, is applicable only to projects that have only two key objectives, such as credit operations, and the provision of services. Arguments are presented on the three specific questions proposed by Moll, ranging from the availability of externally audited financial reports, the performance of interest rate on loans vis-a-vis the inflation rate, and the provision of loans according to the individual requirements of the borrowers. Lastly, the author emphasizes that the overall approach is not useful and suggests that careful considerations should be observed in the use or abuse of a simple scoring system or checklist such as the one proposed by Moll.

Diversification in toxicology: man and environment. EUROTOX proceedings

Energy Technology Data Exchange (ETDEWEB)

Seiler, J.P. [Intercantonal Office for the Control of Medicines (IOCM), Bern (Switzerland); Autrup, J.L.; Autrup, H. [eds.] [Aarhus Univ. (Denmark). Steno Inst. of Public Health

1998-12-31

This volume contains the main papers presented at the 1997 EUROTOX Congress, Aaarhus, Denmark, 24-28 June 1997. Diversification in toxicology is not seen as splitting into subfields, but as the application of basic science to such diverse areas as man and his environment. The pressing issues which have been dealt with not only include reproductive effects of environmental chemicals (`xenoestrogens`), but also receptor-mediated toxic responses, new frontiers in human and ecological toxicology, chemoprevention of cancer and molecular approaches in toxicological research. The practical and ethical facets of toxicology, e.g. ecotoxicological risk assessment, biomarkers of exposure, complex chemical mixtures as well as animal welfare and the ethics of animal experimentation, are also treated. (orig.)

Developing a stochastic traffic volume prediction model for public-private partnership projects

Science.gov (United States)

Phong, Nguyen Thanh; Likhitruangsilp, Veerasak; Onishi, Masamitsu

2017-11-01

Transportation projects require an enormous amount of capital investment resulting from their tremendous size, complexity, and risk. Due to the limitation of public finances, the private sector is invited to participate in transportation project development. The private sector can entirely or partially invest in transportation projects in the form of Public-Private Partnership (PPP) scheme, which has been an attractive option for several developing countries, including Vietnam. There are many factors affecting the success of PPP projects. The accurate prediction of traffic volume is considered one of the key success factors of PPP transportation projects. However, only few research works investigated how to predict traffic volume over a long period of time. Moreover, conventional traffic volume forecasting methods are usually based on deterministic models which predict a single value of traffic volume but do not consider risk and uncertainty. This knowledge gap makes it difficult for concessionaires to estimate PPP transportation project revenues accurately. The objective of this paper is to develop a probabilistic traffic volume prediction model. First, traffic volumes were estimated following the Geometric Brownian Motion (GBM) process. Monte Carlo technique is then applied to simulate different scenarios. The results show that this stochastic approach can systematically analyze variations in the traffic volume and yield more reliable estimates for PPP projects.

Inhalation Toxicology Research Institute. Annual report, October 1, 1978-September 30, 1979

International Nuclear Information System (INIS)

Henderson, R.F.; Diel, J.H.; Martinez, B.S.

1979-12-01

Research information is given by the annual report from the Inhalation Toxicology Research Institute with abstracts for each of the 109 papers. Major sections of interest are nuclear energy toxicology, solar energy toxicology, diesel technology toxicology, coal technology toxicology, and conservation technology toxicology. Also included are seven appendices covering publications of technical reports and publications in open literature, abstracts publications in the open literature, seminars presented by visiting scientists and presentations before scientific meetings, organization of the Inhalation Toxicology Research Institute, and the status of experiments using beagle dogs

Veterinary Forensic Toxicology.

Science.gov (United States)

Gwaltney-Brant, S M

2016-09-01

Veterinary pathologists working in diagnostic laboratories are sometimes presented with cases involving animal poisonings that become the object of criminal or civil litigation. Forensic veterinary toxicology cases can include cases involving animal cruelty (malicious poisoning), regulatory issues (eg, contamination of the food supply), insurance litigation, or poisoning of wildlife. An understanding of the appropriate approach to these types of cases, including proper sample collection, handling, and transport, is essential so that chain of custody rules are followed and proper samples are obtained for toxicological analysis. Consultation with veterinary toxicologists at the diagnostic laboratory that will be processing the samples before, during, and after the forensic necropsy can help to ensure that the analytical tests performed are appropriate for the circumstances and findings surrounding the individual case. © The Author(s) 2016.

La toxicología en la Universidad de Sevilla

OpenAIRE

Puerto Rodríguez, María; Cameán Fernández, Ana María; Moreno Navarro, Isabel María; Pichardo Sánchez, Silvia; Prieto Ortega, Ana Isabel; Jos Gallego, Ángeles Mencía

2010-01-01

La docencia del Área de Toxicología en la Universidad de Sevilla se desarrolla en la actualidad en dos titulaciones, Farmacia y Bioquímica. En los planes de estudios actuales la carga lectiva del Área viene dada por las asignaturas de Toxicología (asignatura troncal), y Toxicología Alimentaria (asignatura optativa) en la Licenciatura de Farmacia, y de Toxicología Molecular (asignatura optativa) en la Licenciatura de Bioquímica. Una vez aprobados por la Agencia Nacional de la Evaluación de la ...

Space Toxicology: Human Health during Space Operations

Science.gov (United States)

Khan-Mayberry, Noreen; James, John T.; Tyl, ROchelle; Lam, Chiu-Wing

2010-01-01

Space Toxicology is a unique and targeted discipline for spaceflight, space habitation and occupation of celestial bodies including planets, moons and asteroids. Astronaut explorers face distinctive health challenges and limited resources for rescue and medical care during space operation. A central goal of space toxicology is to protect the health of the astronaut by assessing potential chemical exposures during spaceflight and setting safe limits that will protect the astronaut against chemical exposures, in a physiologically altered state. In order to maintain sustained occupation in space on the International Space Station (ISS), toxicological risks must be assessed and managed within the context of isolation continuous exposures, reuse of air and water, limited rescue options, and the need to use highly toxic compounds for propulsion. As we begin to explore other celestial bodies in situ toxicological risks, such as inhalation of reactive mineral dusts, must also be managed.

Techniques for Investigating Molecular Toxicology of Nanomaterials.

Science.gov (United States)

Wang, Yanli; Li, Chenchen; Yao, Chenjie; Ding, Lin; Lei, Zhendong; Wu, Minghong

2016-06-01

Nanotechnology has been a rapidly developing field in the past few decades, resulting in the more and more exposure of nanomaterials to human. The increased applications of nanomaterials for industrial, commercial and life purposes, such as fillers, catalysts, semiconductors, paints, cosmetic additives and drug carriers, have caused both obvious and potential impacts on human health and environment. Nanotoxicology is used to study the safety of nanomaterials and has grown at the historic moment. Molecular toxicology is a new subdiscipline to study the interactions and impacts of materials at the molecular level. To better understand the relationship between the molecular toxicology and nanomaterials, this review summarizes the typical techniques and methods in molecular toxicology which are applied when investigating the toxicology of nanomaterials and include six categories: namely; genetic mutation detection, gene expression analysis, DNA damage detection, chromosomal aberration analysis, proteomics, and metabolomics. Each category involves several experimental techniques and methods.

[Forensic medicine as the cradle of toxicology in Russia].

Science.gov (United States)

Popov, V L; Grebeniuk, A N; Pigolkin, Iu I; Tolmachev, I A; Bozhchenko, A P; Timoshevskiĭ, A A

2013-01-01

Modern toxicology as a science and educational subject originated from forensic medicine in the middle of the XIXth century. In the beginning, selected toxicological problems were taught in the Emperor's Medical Surgical Academy (presently S.M. Kirov Military Medical Academy, Sankt-Peterburg) and at the Medical Faculty of the Moscow University (presently I.M. Sechenov First Moscow State Medical University, Moscow). The greatest contribution to the development of toxicology was made by such outstanding scientists as professors S.A. Gromov, P.P. Pelekhin, P.P. Zablotsky-Desyatovsky, E.V. Pelikan, Ya.A. Chistovich, G.I. Blosfel'd, I.M. Sorokin, D.P. Kosorotov, A.V. Grigoriev, V.V. Andreev, A.A. Glebovich, A.N. Grigoriev, B.I. Predtechensky, V.M. Rozhkov, S.S. Vail, M.N. Lubotsky, etc. The works of these researchers predetermined the further development of toxicology in this country, its main purpose being provision of medical aid in case of poisoning and diseases of chemical etiology. Another line of toxicological research became industrial and environmental toxicology having the purpose of hygienic rating and prevention of poisoning. Nevertheless, all aspects of the multifaceted science of toxicology are related to forensic medicine as the cradle in which it originated, evolved, and turned into a self-consistent science.

Predicting Software Projects Cost Estimation Based on Mining Historical Data

OpenAIRE

Najadat, Hassan; Alsmadi, Izzat; Shboul, Yazan

2012-01-01

In this research, a hybrid cost estimation model is proposed to produce a realistic prediction model that takes into consideration software project, product, process, and environmental elements. A cost estimation dataset is built from a large number of open source projects. Those projects are divided into three domains: communication, finance, and game projects. Several data mining techniques are used to classify software projects in terms of their development complexity. Data mining techniqu...

Toxicological effects of pyrethroids on non-target aquatic insects.

Science.gov (United States)

Antwi, Frank B; Reddy, Gadi V P

2015-11-01

The toxicological effects of pyrethroids on non-target aquatic insects are mediated by several modes of entry of pyrethroids into aquatic ecosystems, as well as the toxicological characteristics of particular pyrethroids under field conditions. Toxicokinetics, movement across the integument of aquatic insects, and the toxicodynamics of pyrethroids are discussed, and their physiological, symptomatic and ecological effects evaluated. The relationship between pyrethroid toxicity and insecticide uptake is not fully defined. Based on laboratory and field data, it is likely that the susceptibility of aquatic insects (vector and non-vector) is related to biochemical and physiological constraints associated with life in aquatic ecosystems. Understanding factors that influence aquatic insects susceptibility to pyrethroids is critical for the effective and safe use of these compounds in areas adjacent to aquatic environments. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Predicting Defects Using Information Intelligence Process Models in the Software Technology Project.

Science.gov (United States)

Selvaraj, Manjula Gandhi; Jayabal, Devi Shree; Srinivasan, Thenmozhi; Balasubramanie, Palanisamy

2015-01-01

A key differentiator in a competitive market place is customer satisfaction. As per Gartner 2012 report, only 75%-80% of IT projects are successful. Customer satisfaction should be considered as a part of business strategy. The associated project parameters should be proactively managed and the project outcome needs to be predicted by a technical manager. There is lot of focus on the end state and on minimizing defect leakage as much as possible. Focus should be on proactively managing and shifting left in the software life cycle engineering model. Identify the problem upfront in the project cycle and do not wait for lessons to be learnt and take reactive steps. This paper gives the practical applicability of using predictive models and illustrates use of these models in a project to predict system testing defects thus helping to reduce residual defects.

Uranium resource evaluation project quality assurance evaluation

International Nuclear Information System (INIS)

Grimes, J.G.

1981-01-01

This evaluation was conducted over an eight-month period from February 4 through October 1, 1980. During this time, field sampling was suspended for an indefinite time period while the National Uranium Resource Evaluation (NURE) Program underwent restructuring. In addition, the Uranium Resource Evaluation (URE) Project archives are being restructured. Since it is difficult to evaluate quality assurance needs of a program that is undergoing drastic change and because sections of the evaluation were well along before these changes were announced, this evaluation reflects the situation as it was during February 1980. The following quality assurance related programs are continuing to date: (1) periodic checks of field sampling procedures by the Supervising Field Geologist and the Director of Field Operations; (2) verification of field form information and laboratory analytical data verification for all geochemical surveys; (3) URE Project laboratory quality control program (all elements routinely analyzed); and (4) Ames interlaboratory quality control program (uranium only). UCC-ND was given the responsibility of conducting a Hydrogeochemical and Stream Sediment Reconnaissance (HSSR) survey in the Central United States (Illinois, Indiana, Iowa, Kansas, Michigan, Minnesota, Nebraska, North Dakota, Oklahoma, Texas, South Dakota, and Wisconsin). During 1979 and 1980, 13 detailed surveys were conducted by the URE Project in the Central and Western United States to characterize the hydrogeochemistry, stream sediment geochemistry, and/or radiometric patterns of known or potential uranium occurrences. Beginning in 1980, the HSSR surveys were modified to the Regional Hydrogeochemical and Stream Sediment (RHSS) surveys

Prediction of rodent carcinogenic potential of naturally occurring chemicals in the human diet using high-throughput QSAR predictive modeling

International Nuclear Information System (INIS)

Valerio, Luis G.; Arvidson, Kirk B.; Chanderbhan, Ronald F.; Contrera, Joseph F.

2007-01-01

Consistent with the U.S. Food and Drug Administration (FDA) Critical Path Initiative, predictive toxicology software programs employing quantitative structure-activity relationship (QSAR) models are currently under evaluation for regulatory risk assessment and scientific decision support for highly sensitive endpoints such as carcinogenicity, mutagenicity and reproductive toxicity. At the FDA's Center for Food Safety and Applied Nutrition's Office of Food Additive Safety and the Center for Drug Evaluation and Research's Informatics and Computational Safety Analysis Staff (ICSAS), the use of computational SAR tools for both qualitative and quantitative risk assessment applications are being developed and evaluated. One tool of current interest is MDL-QSAR predictive discriminant analysis modeling of rodent carcinogenicity, which has been previously evaluated for pharmaceutical applications by the FDA ICSAS. The study described in this paper aims to evaluate the utility of this software to estimate the carcinogenic potential of small, organic, naturally occurring chemicals found in the human diet. In addition, a group of 19 known synthetic dietary constituents that were positive in rodent carcinogenicity studies served as a control group. In the test group of naturally occurring chemicals, 101 were found to be suitable for predictive modeling using this software's discriminant analysis modeling approach. Predictions performed on these compounds were compared to published experimental evidence of each compound's carcinogenic potential. Experimental evidence included relevant toxicological studies such as rodent cancer bioassays, rodent anti-carcinogenicity studies, genotoxic studies, and the presence of chemical structural alerts. Statistical indices of predictive performance were calculated to assess the utility of the predictive modeling method. Results revealed good predictive performance using this software's rodent carcinogenicity module of over 1200 chemicals

Prediction of optimal deployment projection for transcatheter aortic valve replacement: angiographic 3-dimensional reconstruction of the aortic root versus multidetector computed tomography.

OpenAIRE

Binder Ronald K; Leipsic Jonathon; Wood David; Moore Teri; Toggweiler Stefan; Willson Alex; Gurvitch Ronen; Freeman Melanie; Webb John G

2012-01-01

BACKGROUND Identifying the optimal fluoroscopic projection of the aortic valve is important for successful transcatheter aortic valve replacement (TAVR). Various imaging modalities including multidetector computed tomography (MDCT) have been proposed for prediction of the optimal deployment projection. We evaluated a method that provides 3 dimensional angiographic reconstructions (3DA) of the aortic root for prediction of the optimal deployment angle and compared it with MDCT. METHODS AND RES...

Toxicological evaluation of the flavour ingredient N-(1-((4-amino-2,2-dioxido-1H-benzo[c][1,2,6]thiadiazin-5-yloxy-2-methylpropan-2-yl-2,6-dimethylisonicotinamide (S2218

Directory of Open Access Journals (Sweden)

Donald S. Karanewsky

Full Text Available A toxicological evaluation of N-(1-((4-amino-2,2-dioxido-1H-benzo[c][1,2,6]thiadiazin-5-yloxy-2-methylpropan-2-yl-2,6-dimethylisonicotinamide (S2218; CAS 1622458-34-7, a flavour with modifying properties, was completed for the purpose of assessing its safety for use in food and beverage applications. S2218 exhibited minimal oxidative metabolism in vitro, and in rat pharmacokinetic studies, the compound was poorly orally bioavailable and rapidly eliminated. S2218 was not found to be mutagenic in an in vitro bacterial reverse mutation assay, and was found to be neither clastogenic nor aneugenic in an in vitro mammalian cell micronucleus assay. In subchronic oral toxicity studies in male and female rats, the NOAEL was 140 mg/kg bw/day (highest dose tested for S2218 sulfate salt (S8069 when administered as a food ad-mix for 13 consecutive weeks. Furthermore, S2218 sulfate salt demonstrated a lack of maternal toxicity, as well as adverse effects on fetal morphology at the highest dose tested, providing a NOAEL of 1000 mg/kg bw/day for both maternal toxicity and embryo/fetal development when administered orally during gestation to pregnant rats. Keywords: Flavours with modifying properties, S2218, FEMA GRAS, Subchronic toxicological evaluation, Genetic toxicological evaluation, Developmental toxicity evaluation

Different approaches to the toxicological evaluation of irradiated starch

International Nuclear Information System (INIS)

Truhaut, R.; Saint-Lebe, L.

1978-01-01

The toxicological evaluation of irradiated starch is performed either through long-term experiments on rats (24 months) and mice (18 months) or through determination of the semichronic toxicity in rats (6 months) of previously identified and determined radiation-induced products. A trial with five groups each of 80 rats (40 males and 40 females; controls receiving the diet raw or cooked; other animals receiving the diet raw after irradiation to 300krad and raw or cooked after irradiation to 600krad) consists of a toxicity test and a study of the reproductive functions. The trial with mice - the same number of animals divided into three groups (standard control, control and 300krad) - consists of a study of the reproductive functions with an examination of teratogenicity and the study of cancerogenic and mutagenic potentiality. In no case have the authors found significant differences between the groups. Of the 35 starch radiolysis products so far identified the authors considered nine (formic acid, hydrogen peroxide, methyl alcohol, acetaldehyde, formaldehyde, glycolaldehyde, glyceraldehyde, malonaldehyde and glyoxal). After an acute and subacute toxicity trial with a mixture of the nine compounds, a six-month semichronic toxicity trial was carried out with four groups of animals (15 males and 15 females). The daily uptake of 0.3g of the mixture per kilogram was found to have no effect on the rats. This daily uptake corresponds to a quantity of radiolytic products 800 times greater than what would be taken up by a baby consuming 30g of irradiated starch (300krad) and is below the threshold of true general toxicity, which is masked here by the caustic effect of the formic acid. (author)

Impacts of Process and Prediction Uncertainties on Projected Hanford Waste Glass Amount

Energy Technology Data Exchange (ETDEWEB)

Gervasio, Vivianaluxa [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Vienna, John D. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Kim, Dong-Sang [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Kruger, Albert A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

2018-02-19

Analyses were performed to evaluate the impacts of using the advanced glass models, constraints (Vienna et al. 2016), and uncertainty descriptions on projected Hanford glass mass. The maximum allowable WOL was estimated for waste compositions while simultaneously satisfying all applicable glass property and composition constraints with sufficient confidence. Different components of prediction and composition/process uncertainties were systematically included in the calculations to evaluate their impacts on glass mass. The analyses estimated the production of 23,360 MT of IHLW glass when no uncertainties were taken into accound. Accounting for prediction and composition/process uncertainties resulted in 5.01 relative percent increase in estimated glass mass 24,531 MT. Roughly equal impacts were found for prediction uncertainties (2.58 RPD) and composition/process uncertainties (2.43 RPD). ILAW mass was predicted to be 282,350 MT without uncertainty and with weaste loading “line” rules in place. Accounting for prediction and composition/process uncertainties resulted in only 0.08 relative percent increase in estimated glass mass of 282,562 MTG. Without application of line rules the glass mass decreases by 10.6 relative percent (252,490 MT) for the case with no uncertainties. Addition of prediction uncertainties increases glass mass by 1.32 relative percent and the addition of composition/process uncertainties increase glass mass by an additional 7.73 relative percent (9.06 relative percent increase combined). The glass mass estimate without line rules (275,359 MT) was 2.55 relative percent lower than that with the line rules (282,562 MT), after accounting for all applicable uncertainties.

Using energy budgets to combine ecology and toxicology in a mammalian sentinel species

Science.gov (United States)

Desforges, Jean-Pierre W.; Sonne, Christian; Dietz, Rune

2017-04-01

Process-driven modelling approaches can resolve many of the shortcomings of traditional descriptive and non-mechanistic toxicology. We developed a simple dynamic energy budget (DEB) model for the mink (Mustela vison), a sentinel species in mammalian toxicology, which coupled animal physiology, ecology and toxicology, in order to mechanistically investigate the accumulation and adverse effects of lifelong dietary exposure to persistent environmental toxicants, most notably polychlorinated biphenyls (PCBs). Our novel mammalian DEB model accurately predicted, based on energy allocations to the interconnected metabolic processes of growth, development, maintenance and reproduction, lifelong patterns in mink growth, reproductive performance and dietary accumulation of PCBs as reported in the literature. Our model results were consistent with empirical data from captive and free-ranging studies in mink and other wildlife and suggest that PCB exposure can have significant population-level impacts resulting from targeted effects on fetal toxicity, kit mortality and growth and development. Our approach provides a simple and cross-species framework to explore the mechanistic interactions of physiological processes and ecotoxicology, thus allowing for a deeper understanding and interpretation of stressor-induced adverse effects at all levels of biological organization.

Overview of Forensic Toxicology, Yesterday, Today and in the Future.

Science.gov (United States)

Chung, Heesun; Choe, Sanggil

2017-01-01

The scope of forensic toxicology has been tremendously expanded over the past 50 years. From two general sections forensic toxicology can be further classified into 8-9 sections. The most outstanding improvement in forensic toxicology is the changes brought by instrumental development. The field of forensic toxicology was revolutionized by the development of immunoassay and benchtop GC-MS in the 1980's and LC-MS-MS in 2000's. Detection of trace amounts of analytes has allowed the use of new specimens such as hair and oral fluids, along with blood and urine. Over a longer period of time, continuous efforts have been made to efficiently extract and separate drug and poison from biological fluids. International endeavors to develop high quality standards and guidelines for drugs and poisons in biological specimens and to promote them in order to increase reliability of laboratories are also part of the recent advancement of forensic toxicology. Interpretation of postmortem toxicology encompasses various factors including postmortem redistribution and stability. Considering the recent trend, the interpretation of toxicological results should account for autopsy findings, crime scene information, and related medical history. The fields of forensic toxicology will continuously develop to improve analysis of target analytes from various specimens, quality assurance program, and results interpretation. In addition, the development of analytical techniques will also contribute further advancement of forensic toxicology. The societies of forensic toxicologists, such as TIAFT, will play an important role for the advancement of forensic toxicology by collaborating and sharing ideas between toxicologists from both developed and developing countries. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Titanium dioxide: inhalation toxicology and epidemiology.

Science.gov (United States)

Hext, Paul M; Tomenson, John A; Thompson, Peter

2005-08-01

Titanium dioxide (TiO(2)) is manufactured worldwide in large quantities for use in a wide range of applications and is normally considered to be toxicologically inert. Findings of tumours in the lungs of rats exposed chronically to high concentrations of TiO(2), but not in similarly exposed mice or hamsters, suggest that the tumorigenic response may be a rat-specific phenomenon but nonetheless raises concerns for potential human health effects. With the limited toxicological understanding of species differences in response to inhaled TiO(2) and a similarly limited amount of epidemiological information with respect to TiO(2) exposure in the workplace, a consortium of TiO(2) manufacturers in Europe (under the European Chemistry Industry Council; CEFIC) and in North America (under the American Chemistry Council; ACC) initiated a programme of research to investigate inter-species differences as a result of exposure to TiO(2) and to conduct detailed epidemiological surveys of the major manufacturing sites. The toxicology studies exposed rats, mice and hamsters to pigment-grade TiO(2) (PG-TiO(2), 0, 10, 50 and 250 mg m(-3)) or ultrafine TiO(2) (UF-TiO(2), 0, 0.5, 2 and 10 mg m(-3)) for 90 days and the lung burdens and tissue responses were evaluated at the end of the exposure period and for up to 1 year after exposure. Results demonstrated clear species differences. Rats and mice had similar lung burdens and clearance rates while hamsters showed high clearance rates. At high lung particle burdens, rats showed a marked progression of histopathological lesions throughout the post-exposure period while mice and hamsters showed minimal initial lesions with recovery apparent during the post-exposure period. Lung neutrophil responses, a sensitive marker of inflammatory changes, reflected the development or recovery of the histopathological lesions. The use of surface area rather than gravimetric lung burden provided closer correlates of the burden to the biological effect

Project management in practice : Evaluating a case project through project management theories

OpenAIRE

Uusitalo, Jenni

2013-01-01

The purpose of this thesis was to evaluate a case project and to study whether it was carried out in a correct manner; meaning that did the case project follow the project management models. In addition, part of the study was to determine what could have been improved in the management of the case project. The case project was about creating and launching a communication channel based on a social media service, on a blog platform called Tumblr, for Team Finland in Spain network. The network p...

Pharmacometabolomic approach to predict QT prolongation in guinea pigs.

Directory of Open Access Journals (Sweden)

Jeonghyeon Park

Full Text Available Drug-induced torsades de pointes (TdP, a life-threatening arrhythmia associated with prolongation of the QT interval, has been a significant reason for withdrawal of several medicines from the market. Prolongation of the QT interval is considered as the best biomarker for predicting the torsadogenic risk of a new chemical entity. Because of the difficulty assessing the risk for TdP during drug development, we evaluated the metabolic phenotype for predicting QT prolongation induced by sparfloxacin, and elucidated the metabolic pathway related to the QT prolongation. We performed electrocardiography analysis and liquid chromatography-mass spectroscopy-based metabolic profiling of plasma samples obtained from 15 guinea pigs after administration of sparfloxacin at doses of 33.3, 100, and 300 mg/kg. Principal component analysis and partial least squares modelling were conducted to select the metabolites that substantially contributed to the prediction of QT prolongation. QTc increased significantly with increasing dose (r = 0.93. From the PLS analysis, the key metabolites that showed the highest variable importance in the projection values (>1.5 were selected, identified, and used to determine the metabolic network. In particular, cytidine-5'-diphosphate (CDP, deoxycorticosterone, L-aspartic acid and stearic acid were found to be final metabolomic phenotypes for the prediction of QT prolongation. Metabolomic phenotypes for predicting drug-induced QT prolongation of sparfloxacin were developed and can be applied to cardiac toxicity screening of other drugs. In addition, this integrative pharmacometabolomic approach would serve as a good tool for predicting pharmacodynamic or toxicological effects caused by changes in dose.

Space Toxicology: Environmental Health Considerations during Spaceflight Operations and Potential Paths for Research

Science.gov (United States)

Khan-Mayberry, Noreen N.; Sundaresan, Alemalu

2009-01-01

Space Toxicology is a specialized discipline for spaceflight, space habitation and occupation of celestial bodies including planets, moons and asteroids [1]. Astronaut explorers face unique challenges to their health while working and living with limited resources for rescue and medical care during space operation. At its core the practice of space toxicology to identify, assess and predict potential chemical contaminants and limit the astronaut s exposure to these environmental factors in order to protect crew health. Space toxicologists are also charged with setting safe exposure limits that will protect the astronaut against a multitude of chemical exposures, in a physiologically altered state. In order to maintain sustained occupation in space, toxicological risks are gauged and managed within the context of isolation, continual exposures, reuse of air and water, limited rescue options, and the necessary use of highly toxic compounds required for propulsion. As the space program move towards human presence and exploration other celestial bodies in situ toxicological risks, such as inhalation of unusual and/or reactive mineral dusts must also be analyzed and controlled. Placing humans for long-term presence in space creates several problems and challenges to the long-term health of the crew, such as bone-loss and immunological challenges and has spurred research into acute, chronic and episodic exposure of the pulmonary system to mineral dusts [2]. NASA has demonstrated that lunar soil contains several types of reactive dusts, including an extremely fine respirable component. In order to protect astronaut health, NASA is now investigating the toxicity of this unique class of dusts. Understanding how these reactive components behave "biochemically" in a moisture-rich pulmonary environment will aid in determining how toxic these particles are to humans. The data obtained from toxicological examination of lunar dusts will determine the human risk criteria for lunar

Current Knowledge on the Use of Computational Toxicology in Hazard Assessment of Metallic Engineered Nanomaterials.

Science.gov (United States)

Chen, Guangchao; Peijnenburg, Willie; Xiao, Yinlong; Vijver, Martina G

2017-07-12

As listed by the European Chemicals Agency, the three elements in evaluating the hazards of engineered nanomaterials (ENMs) include the integration and evaluation of toxicity data, categorization and labeling of ENMs, and derivation of hazard threshold levels for human health and the environment. Assessing the hazards of ENMs solely based on laboratory tests is time-consuming, resource intensive, and constrained by ethical considerations. The adoption of computational toxicology into this task has recently become a priority. Alternative approaches such as (quantitative) structure-activity relationships ((Q)SAR) and read-across are of significant help in predicting nanotoxicity and filling data gaps, and in classifying the hazards of ENMs to individual species. Thereupon, the species sensitivity distribution (SSD) approach is able to serve the establishment of ENM hazard thresholds sufficiently protecting the ecosystem. This article critically reviews the current knowledge on the development of in silico models in predicting and classifying the hazard of metallic ENMs, and the development of SSDs for metallic ENMs. Further discussion includes the significance of well-curated experimental datasets and the interpretation of toxicity mechanisms of metallic ENMs based on reported models. An outlook is also given on future directions of research in this frontier.

Forensic toxicology in drug-facilitated sexual assault.

Science.gov (United States)

Dinis-Oliveira, Ricardo Jorge; Magalhães, Teresa

2013-09-01

The low rates of reporting, prosecution and conviction that characterize sexual assault, is likely even more evident in drug-facilitated cases. Typically, in these crimes, victims are incapacitated and left unable to resist sexual advances, unconscious, unable to fight off the abuser or to say "no" and unable to clearly remember the circumstances surrounding the events due to anterograde amnesia. The consequence is the delay in performing toxicological analysis aggravated by the reluctance of the victim to disclose the crime. Moreover since "date rape drugs" are often consumed with ethanol and exhibit similar toxicodynamic effects, the diagnosis is erroneously performed as being classical ethanol intoxication. Therefore, it is imperative to rapidly consider toxicological analysis in drug-facilitated sexual assaults. The major focus of this review is to harmonize practical approaches and guidelines to rapidly uncover drug-facilitated sexual assault, namely issues related to when to perform toxicological analysis, toxicological requests, samples to be collected, storage, preservation and transport precautions and xenobiotics or endobiotics to be analyzed.

Advancing Risk Assessment through the Application of Systems Toxicology

Science.gov (United States)

Sauer, John Michael; Kleensang, André; Peitsch, Manuel C.; Hayes, A. Wallace

2016-01-01

Risk assessment is the process of quantifying the probability of a harmful effect to individuals or populations from human activities. Mechanistic approaches to risk assessment have been generally referred to as systems toxicology. Systems toxicology makes use of advanced analytical and computational tools to integrate classical toxicology and quantitative analysis of large networks of molecular and functional changes occurring across multiple levels of biological organization. Three presentations including two case studies involving both in vitro and in vivo approaches described the current state of systems toxicology and the potential for its future application in chemical risk assessment. PMID:26977253

Integration of clinical chemistry, expression, and metabolite data leads to better toxicological class separation

DEFF Research Database (Denmark)

Spicker, Jeppe; Brunak, Søren; Frederiksen, K.S.

2008-01-01

A large number of databases are currently being implemented within toxicology aiming to integrate diverse biological data, such as clinical chemistry, expression, and other types of data. However, for these endeavors to be successful, tools for integration, visualization, and interpretation...... are needed. This paper presents a method for data integration using a hierarchical model based on either principal component analysis or partial least squares discriminant analysis of clinical chemistry, expression, and nuclear magnetic resonance data using a toxicological study as case. The study includes...... the three toxicants alpha-naphthyl-isothiocyanate, dimethylnitrosamine, and N-methylformamide administered to rats. Improved predictive ability of the different classes is seen, suggesting that this approach is a suitable method for data integration and visualization of biological data. Furthermore...

Plant Poisonings According to the Czech Toxicological Information Centre from 2005 to 2008

Czech Academy of Sciences Publication Activity Database

Říčařová, B.; Rakovcová, H.; Pelclová, D.; Navrátil, Tomáš

2009-01-01

Roč. 47, č. 5 (2009), s. 473-473 ISSN 1556-3650. [The International Congress of the European Association of Poison Centres and Clinical Toxicologists /29./. 12.05.2009-15.05.2009, Stockholm] R&D Projects: GA AV ČR IAA400400806 Institutional research plan: CEZ:AV0Z40400503 Keywords : Czech Toxicological Information Centre * plant poison ings according Subject RIV: CF - Physical ; Theoretical Chemistry

Systems toxicology: applications of toxicogenomics, transcriptomics, proteomics and metabolomics in toxicology

NARCIS (Netherlands)

Heijne, W.H.M.; Kienhuis, A.S.; Ommen, van B.; Stierum, R.; Groten, J.P.

2005-01-01

Toxicogenomics can facilitate the identification and characterization of toxicity, as illustrated in this review. Toxicogenomics, the application of the functional genomics technologies (transcriptomics, proteomics and metabolomics) in toxicology enables the study of adverse effects of xenobiotic

Africa's present and future needs in toxicology education: Southern African perspective

International Nuclear Information System (INIS)

Gulumian, Mary; Ginsburg, Carren; Stewart, Michael J.

2005-01-01

Degrees and diplomas as well as certificates that are granted by universities and technikons in South Africa in scientific disciplines, such as forensic medicine, pharmacology, marine and veterinary sciences, environmental health, and occupational hygiene, include toxicology as one of the subjects in their overall syllabus. However, aspects of toxicology included in each of these courses are biased towards that particular subdiscipline and basic level of toxicology may be taught. Educational needs in toxicology in South Africa can be summarized as follows: (a) recognition of toxicology as a discipline in its own right at these tertiary education institutions and (b) creation of opportunities to study and obtain higher degrees in one or more of the many subdisciplines of toxicology. The results from a survey conducted on the toxicology syllabi offered at these tertiary education institutions are used to substantiate these needs

Toxicological risks of selected flame-retardant chemicals

National Research Council Canada - National Science Library

2000-01-01

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Toxicological Risks of Selected Flame-Retardant Chemicals

National Research Council Canada - National Science Library

2000-01-01

... Committee on Toxicology Board on Environmental Studies and Toxicology Commission on Life Sciences National Research Council NATIONAL ACADEMY PRESS Washington, D.C. i Copyrighttrue Please breaks inserted. are Page files. accidentally typesetting been have may original from the errors not typographic original retained, and from the created ca...

ACToR - Aggregated Computational Toxicology Resource

International Nuclear Information System (INIS)

Judson, Richard; Richard, Ann; Dix, David; Houck, Keith; Elloumi, Fathi; Martin, Matthew; Cathey, Tommy; Transue, Thomas R.; Spencer, Richard; Wolf, Maritja

2008-01-01

ACToR (Aggregated Computational Toxicology Resource) is a database and set of software applications that bring into one central location many types and sources of data on environmental chemicals. Currently, the ACToR chemical database contains information on chemical structure, in vitro bioassays and in vivo toxicology assays derived from more than 150 sources including the U.S. Environmental Protection Agency (EPA), Centers for Disease Control (CDC), U.S. Food and Drug Administration (FDA), National Institutes of Health (NIH), state agencies, corresponding government agencies in Canada, Europe and Japan, universities, the World Health Organization (WHO) and non-governmental organizations (NGOs). At the EPA National Center for Computational Toxicology, ACToR helps manage large data sets being used in a high-throughput environmental chemical screening and prioritization program called ToxCast TM

Electronic cigarettes in the USA: a summary of available toxicology data and suggestions for the future

OpenAIRE

Orr, Michael S

2014-01-01

Objective To review the available evidence evaluating the toxicological profiles of electronic cigarettes (e-cigarettes) in order to understand the potential impact of e-cigarettes on individual users and the public health. Methods Systematic literature searches were conducted between October 2012 and October 2013 using five electronic databases. Search terms such as ‘e-cigarettes’ and ‘electronic delivery devices’ were used to identify the toxicology information for e-cigarettes. Results As ...

Evaluation of numerical weather predictions performed in the context of the project DAPHNE

Science.gov (United States)

Tegoulias, Ioannis; Pytharoulis, Ioannis; Bampzelis, Dimitris; Karacostas, Theodore

2014-05-01

The region of Thessaly in central Greece is one of the main areas of agricultural production in Greece. Severe weather phenomena affect the agricultural production in this region with adverse effects for farmers and the national economy. For this reason the project DAPHNE aims at tackling the problem of drought by means of weather modification through the development of the necessary tools to support the application of a rainfall enhancement program. In the present study the numerical weather prediction system WRF-ARW is used, in order to assess its ability to represent extreme weather phenomena in the region of Thessaly. WRF is integrated in three domains covering Europe, Eastern Mediterranean and Central-Northern Greece (Thessaly and a large part of Macedonia) using telescoping nesting with grid spacing of 15km, 5km and 1.667km, respectively. The cases examined span throughout the transitional and warm period (April to September) of the years 2008 to 2013, including days with thunderstorm activity. Model results are evaluated against all available surface observations and radar products, taking into account the spatial characteristics and intensity of the storms. Preliminary results indicate a good level of agreement between the simulated and observed fields as far as the standard parameters (such as temperature, humidity and precipitation) are concerned. Moreover, the model generally exhibits a potential to represent the occurrence of the convective activity, but not its exact spatiotemporal characteristics. Acknowledgements This research work has been co-financed by the European Union (European Regional Development Fund) and Greek national funds, through the action "COOPERATION 2011: Partnerships of Production and Research Institutions in Focused Research and Technology Sectors" (contract number 11SYN_8_1088 - DAPHNE) in the framework of the operational programme "Competitiveness and Entrepreneurship" and Regions in Transition (OPC II, NSRF 2007-2013)

A Fuzzy Comprehensive Evaluation Model for Sustainability Risk Evaluation of PPP Projects

Directory of Open Access Journals (Sweden)

Libiao Bai

2017-10-01

Full Text Available Evaluating the sustainability risk level of public–private partnership (PPP projects can reduce project risk incidents and achieve the sustainable development of the organization. However, the existing studies about PPP projects risk management mainly focus on exploring the impact of financial and revenue risks but ignore the sustainability risks, causing the concept of “sustainability” to be missing while evaluating the risk level of PPP projects. To evaluate the sustainability risk level and achieve the most important objective of providing a reference for the public and private sectors when making decisions on PPP project management, this paper constructs a factor system of sustainability risk of PPP projects based on an extensive literature review and develops a mathematical model based on the methods of fuzzy comprehensive evaluation model (FCEM and failure mode, effects and criticality analysis (FMECA for evaluating the sustainability risk level of PPP projects. In addition, this paper conducts computational experiment based on a questionnaire survey to verify the effectiveness and feasibility of this proposed model. The results suggest that this model is reasonable for evaluating the sustainability risk level of PPP projects. To our knowledge, this paper is the first study to evaluate the sustainability risk of PPP projects, which would not only enrich the theories of project risk management, but also serve as a reference for the public and private sectors for the sustainable planning and development. Keywords: sustainability risk eva

Drug screening in clinical or forensic toxicology: are there differences?

Science.gov (United States)

Gerostamoulos, Dimitri; Beyer, Jochen

2010-09-01

Legal and medical practitioners need to remember that, with respect to drug analysis, there are two distinct disciplines in analytical toxicology concerned with human biological matrices, namely clinical and forensic toxicology. Both fields use similar analytical techniques designed to detect and quantify drugs, chemicals and poisons in fluids or tissues. In clinical toxicology, analytical results help to specify the appropriate treatment of a poisoned or intoxicated patient. In forensic toxicology, the results often play a vital role in determining the possible impairment or behavioural changes in an individual, or the contribution of drugs or poisons to death in a medico-legal investigation. This column provides an overview of the similarities and differences inherent in clinical and forensic toxicology.

Reproductive and developmental toxicology

National Research Council Canada - National Science Library

Gupta, Ramesh C

2011-01-01

.... Reproductive and Developmental Toxicology is a comprehensive and authoritative resource providing the latest literature enriched with relevant references describing every aspect of this area of science...

Principles of Pharmacology and Toxicology Also Govern Effects of Chemicals on the Endocrine System.

Science.gov (United States)

Autrup, Herman; Barile, Frank A; Blaauboer, Bas J; Degen, Gisela H; Dekant, Wolfgang; Dietrich, Daniel; Domingo, Jose L; Gori, Gio Batta; Greim, Helmuth; Hengstler, Jan G; Kacew, Sam; Marquardt, Hans; Pelkonen, Olavi; Savolainen, Kai; Vermeulen, Nico P

2015-07-01

The present debate on chemicals with Hormonal activity, often termed 'endocrine disruptors', is highly controversial and includes challenges of the present paradigms used in toxicology and in hazard identification and risk characterization. In our opinion, chemicals with hormonal activity can be subjected to the well-evaluated health risk characterization approach used for many years including adverse outcome pathways. Many of the points arguing for a specific approach for risk characterization of chemicals with hormonal activity are based on highly speculative conclusions. These conclusions are not well supported when evaluating the available information. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Analysis of Statistical Methods Currently used in Toxicology Journals.

Science.gov (United States)

Na, Jihye; Yang, Hyeri; Bae, SeungJin; Lim, Kyung-Min

2014-09-01

Statistical methods are frequently used in toxicology, yet it is not clear whether the methods employed by the studies are used consistently and conducted based on sound statistical grounds. The purpose of this paper is to describe statistical methods used in top toxicology journals. More specifically, we sampled 30 papers published in 2014 from Toxicology and Applied Pharmacology, Archives of Toxicology, and Toxicological Science and described methodologies used to provide descriptive and inferential statistics. One hundred thirteen endpoints were observed in those 30 papers, and most studies had sample size less than 10, with the median and the mode being 6 and 3 & 6, respectively. Mean (105/113, 93%) was dominantly used to measure central tendency, and standard error of the mean (64/113, 57%) and standard deviation (39/113, 34%) were used to measure dispersion, while few studies provide justifications regarding why the methods being selected. Inferential statistics were frequently conducted (93/113, 82%), with one-way ANOVA being most popular (52/93, 56%), yet few studies conducted either normality or equal variance test. These results suggest that more consistent and appropriate use of statistical method is necessary which may enhance the role of toxicology in public health.

[Toxicological consultation data management system based on experience of Pomeranian Center of Toxicology].

Science.gov (United States)

Kabata, Piotr Maciej; Waldman, Wojciech; Sein Anand, Jacek

2015-01-01

In this paper the structure of poisonings is described, based on the material collected from tele-toxicology consults by the Pomeranian Center of Toxicology in Gdańsk and harvested from its Electronic Poison Information Management System. In addition, we analyzed conclusions drawn from a 27-month operation of the system. Data were harvested from the Electronic Poison Information Management System developed in 2012 and used by the Pomeranian Center of Toxicology since then. The research was based on 2550 tele-toxicology consults between January 1 and December 31, 2014. Subsequently the data were electronically cleaned and presented using R programming language. The Pomeranian voivodeship was the prevalent localisation of calls (N = 1879; 73.7%). Most of the calls came from emergency rooms (N = 1495; 58.63%). In the case of 1396 (54.7%) patients the time-lag between intoxication and the consult was less than 6 h. There were no differences in the age distribution between genders. Mean age was 26.3 years. Young people predominated among intoxicated individuals. The majority of intoxications were incidental (N = 888; 34.8%) or suicidal (N = 814; 31.9%) and the most of them took place in the patient's home. Information about Poison Control Center consultations access should be better spread among medical service providers. The extent of poison information collected by Polish Poison Control Centers should be limited and unified. This should contribute to the increased percentage of properly documented consultations. Additional duties stemming from the need of digital archiving of consults provided, require the involvement of additional staff, leading to the increased operation costs incurred by Poison Control Centers. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

Long Non-Coding RNAs: A Novel Paradigm for Toxicology.

Science.gov (United States)

Dempsey, Joseph L; Cui, Julia Yue

2017-01-01

Long non-coding RNAs (lncRNAs) are over 200 nucleotides in length and are transcribed from the mammalian genome in a tissue-specific and developmentally regulated pattern. There is growing recognition that lncRNAs are novel biomarkers and/or key regulators of toxicological responses in humans and animal models. Lacking protein-coding capacity, the numerous types of lncRNAs possess a myriad of transcriptional regulatory functions that include cis and trans gene expression, transcription factor activity, chromatin remodeling, imprinting, and enhancer up-regulation. LncRNAs also influence mRNA processing, post-transcriptional regulation, and protein trafficking. Dysregulation of lncRNAs has been implicated in various human health outcomes such as various cancers, Alzheimer's disease, cardiovascular disease, autoimmune diseases, as well as intermediary metabolism such as glucose, lipid, and bile acid homeostasis. Interestingly, emerging evidence in the literature over the past five years has shown that lncRNA regulation is impacted by exposures to various chemicals such as polycyclic aromatic hydrocarbons, benzene, cadmium, chlorpyrifos-methyl, bisphenol A, phthalates, phenols, and bile acids. Recent technological advancements, including next-generation sequencing technologies and novel computational algorithms, have enabled the profiling and functional characterizations of lncRNAs on a genomic scale. In this review, we summarize the biogenesis and general biological functions of lncRNAs, highlight the important roles of lncRNAs in human diseases and especially during the toxicological responses to various xenobiotics, evaluate current methods for identifying aberrant lncRNA expression and molecular target interactions, and discuss the potential to implement these tools to address fundamental questions in toxicology. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e

Evaluating prediction uncertainty

International Nuclear Information System (INIS)

McKay, M.D.

1995-03-01

The probability distribution of a model prediction is presented as a proper basis for evaluating the uncertainty in a model prediction that arises from uncertainty in input values. Determination of important model inputs and subsets of inputs is made through comparison of the prediction distribution with conditional prediction probability distributions. Replicated Latin hypercube sampling and variance ratios are used in estimation of the distributions and in construction of importance indicators. The assumption of a linear relation between model output and inputs is not necessary for the indicators to be effective. A sequential methodology which includes an independent validation step is applied in two analysis applications to select subsets of input variables which are the dominant causes of uncertainty in the model predictions. Comparison with results from methods which assume linearity shows how those methods may fail. Finally, suggestions for treating structural uncertainty for submodels are presented

Impacts of Process and Prediction Uncertainties on Projected Hanford Waste Glass Amount

Energy Technology Data Exchange (ETDEWEB)

Gervasio, V.; Kim, D. S.; Vienna, J. D.; Kruger, A. A.

2018-03-08

Analyses were performed to evaluate the impacts of using the advanced glass models, constraints (Vienna et al. 2016), and uncertainty descriptions on projected Hanford glass mass. The maximum allowable waste oxide loading (WOL) was estimated for waste compositions while simultaneously satisfying all applicable glass property and composition constraints with sufficient confidence. Different components of prediction and composition/process uncertainties were systematically included in the calculations to evaluate their impacts on glass mass. The analyses estimated the production of 23,360 MT of immobilized high-level waste (IHLW) glass when no uncertainties were taken into account. Accounting for prediction and composition/process uncertainties resulted in 5.01 relative percent increase in estimated glass mass of 24,531 MT. Roughly equal impacts were found for prediction uncertainties (2.58 RPD) and composition/process uncertainties (2.43 RPD). The immobilized low-activity waste (ILAW) mass was predicted to be 282,350 MT without uncertainty and with waste loading “line” rules in place. Accounting for prediction and composition/process uncertainties resulted in only 0.08 relative percent increase in estimated glass mass of 282,562 MT. Without application of line rules the glass mass decreases by 10.6 relative percent (252,490 MT) for the case with no uncertainties. Addition of prediction uncertainties increases glass mass by 1.32 relative percent and the addition of composition/process uncertainties increase glass mass by an additional 7.73 relative percent (9.06 relative percent increase combined). The glass mass estimate without line rules (275,359 MT) was 2.55 relative percent lower than that with the line rules (282,562 MT), after accounting for all applicable uncertainties.

A preliminary approach to quantifying the overall environmental risks posed by development projects during environmental impact assessment.

Science.gov (United States)

Nicol, Sam; Chadès, Iadine

2017-01-01

Environmental impact assessment (EIA) is used globally to manage the impacts of development projects on the environment, so there is an imperative to demonstrate that it can effectively identify risky projects. However, despite the widespread use of quantitative predictive risk models in areas such as toxicology, ecosystem modelling and water quality, the use of predictive risk tools to assess the overall expected environmental impacts of major construction and development proposals is comparatively rare. A risk-based approach has many potential advantages, including improved prediction and attribution of cause and effect; sensitivity analysis; continual learning; and optimal resource allocation. In this paper we investigate the feasibility of using a Bayesian belief network (BBN) to quantify the likelihood and consequence of non-compliance of new projects based on the occurrence probabilities of a set of expert-defined features. The BBN incorporates expert knowledge and continually improves its predictions based on new data as it is collected. We use simulation to explore the trade-off between the number of data points and the prediction accuracy of the BBN, and find that the BBN could predict risk with 90% accuracy using approximately 1000 data points. Although a further pilot test with real project data is required, our results suggest that a BBN is a promising method to monitor overall risks posed by development within an existing EIA process given a modest investment in data collection.

Anti-inflammatory and toxicological evaluation of essential oil from Piper glabratum leaves.

Science.gov (United States)

Branquinho, Lidiane Schultz; Santos, Joyce Alencar; Cardoso, Claudia Andrea Lima; Mota, Jonas da Silva; Junior, Ubirajara Lanza; Kassuya, Cândida Aparecida Leite; Arena, Arielle Cristina

2017-02-23

Although some of the species of the genus Piper exhibit interesting biological properties, studies on Piper glabratum Kunth are very limited. This study investigated the anti-inflammatory activity and the toxicological profile of the essential oil from P. glabratum leaves (OEPG) in mice. The acute toxicity of OEPG was evaluated by oral administration to female mice as single doses of 500, 1000, 2000 or 5000mg/kg/body weight. In the subacute toxicity test, the females received 500 or 1000mg/kg/body weight of OEPG for 28 days. The anti-inflammatory potential of OEPG was evaluated using four models including pleurisy, edema, mechanical hyperalgesia and cold allodynia models in mouse paws. No clinical signs of toxicity were observed in animals after acute treatment, which suggested that the LD 50 is greater than 5000mg/kg. The subacute exposure to OEPG produced no significant changes in the hematological or biochemical parameters. Similarly, the histology of the organs and the estrus cycle displayed no marked alterations. OEPG exhibited anti-inflammatory activity as indicated by inhibition of the leukocyte migration (100, 300, 700mg/kg) and the protein extravasation into the pleural exudates (700mg/kg). After intraplantar injection of carrageenan, it was observed that the 700mg/kg dose of OEPG reduced edema formation and decreased the sensitivity to mechanical stimulation and cold. These results demonstrate the anti-inflammatory potential of the essential oil of P. glabratum leaves in the absence of toxicity in female mice. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

National toxicology program chemical nomination and selection process

Energy Technology Data Exchange (ETDEWEB)

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

1990-12-31

The National Toxicology Program (NTP) was organized to support national public health programs by initiating research designed to understand the physiological, metabolic, and genetic basis for chemical toxicity. The primary mandated responsibilities of NTP were in vivo and vitro toxicity testing of potentially hazardous chemicals; broadening the spectrum of toxicological information on known hazardous chemicals; validating current toxicological assay systems as well as developing new and innovative toxicity testing technology; and rapidly communicating test results to government agencies with regulatory responsibilities and to the medical and scientific communities. 2 figs.

Application of the threshold of toxicological concern (TTC) to the safety evaluation of cosmetic ingredients

NARCIS (Netherlands)

Kroes, R.; Renwick, A.G.; Feron, V.; Galli, C.L.; Gibney, M.; Greim, H.; Guy, R.H.; Lhuguenot, J.C.; Sandt, J.J.M. van de

2007-01-01

The threshold of toxicological concern (TTC) has been used for the safety assessment of packaging migrants and flavouring agents that occur in food. The approach compares the estimated oral intake with a TTC value derived from chronic oral toxicity data for structurally-related compounds.

A comprehensive evaluation of the toxicology of cigarette ingredients: heterocyclic nitrogen compounds.

Science.gov (United States)

Coggins, Christopher R E; Merski, Jerome A; Oldham, Michael J

2011-06-01

Three heterocyclic nitrogen compounds, 2,3-diethylpyrazine (DEP), 2,3,5,6-tetramethylpyrazine (TMP), and 2-acetyl pyridine (AP), are naturally present in tobacco and are also added to tobacco as flavor ingredients. A battery of tests was used to compare the toxicity of mainstream smoke from experimental cigarettes containing the three heterocyclic nitrogen compounds added individually at three different levels. The lowest target inclusion level of the ingredient was 10 ppm, and the highest was 10,000 ppm. Smoke from experimental and control cigarettes was evaluated in analytical smoke chemistry, in vitro cytotoxicity, and mutagenicity assays. The cigarettes with added DEP produced some minor (approximately 10%) changes in smoke chemistry when compared with the cigarettes containing no DEP. Smoke chemistry was effectively unchanged by the addition of either AP or TMP. Cytotoxicity, assessed by the neutral red uptake assay using both gas-vapor and particulate phases of smoke, was unaffected by the addition of any of the test ingredients. Mutagenicity, assessed in five strains of Salmonella treated with mainstream cigarette smoke condensate, also was unaffected by any of the test ingredients. Despite the exaggerated ingredient levels relative to commercial-use levels, there was a lack of a toxicological response for the three heterocyclic nitrogen compounds in the test systems used.

Male Reproductive Toxicology: Environmental Exposures vs Reproductive Competence

Science.gov (United States)

Like the lecture this chapter begins with an overview of male reproductive biology and transitions into male reproductive toxicology. It ends with a brief discussion of the strengths and weaknesses in male reproductive toxicology and epidemiology today. This chapter is highly il...

75 FR 74053 - Availability of Final Toxicological Profiles

Science.gov (United States)

2010-11-30

... CONTACT: Ms. Olga Dawkins, Division of Toxicology and Environmental Medicine, Agency for Toxic Substances... Toxicology and Environmental Medicine, Agency for Toxic Substances and Disease Registry, 4700 Buford Highway..., except legal holidays. Availability This notice announces the availability of one new and six updated...

Modern Instrumental Methods in Forensic Toxicology*

Science.gov (United States)

Smith, Michael L.; Vorce, Shawn P.; Holler, Justin M.; Shimomura, Eric; Magluilo, Joe; Jacobs, Aaron J.; Huestis, Marilyn A.

2009-01-01

This article reviews modern analytical instrumentation in forensic toxicology for identification and quantification of drugs and toxins in biological fluids and tissues. A brief description of the theory and inherent strengths and limitations of each methodology is included. The focus is on new technologies that address current analytical limitations. A goal of this review is to encourage innovations to improve our technological capabilities and to encourage use of these analytical techniques in forensic toxicology practice. PMID:17579968

LC-MS (/MS) in clinical toxicology screening methods.

Science.gov (United States)

Viette, Véronique; Hochstrasser, Denis; Fathi, Marc

2012-01-01

Toxicological screening is the analysis of biological samples to detect and identify unknown compounds. The high selectivity and sensitivity of liquid chromatography (LC) coupled to mass spectrometry (MS) or tandem mass spectrometry (MS/MS) technology provide an attractive alternative to the current methods (LC-UV, GC/MS, etc.). For these reasons, an increasing number of applications are being published. This paper is a brief overview of LC-MS(/MS) screening methods developed for clinical toxicology in recent years. Various sample treatments, chromatographic separations and detection by mass spectrometry can be combined to obtain screening methods adapted to the constraints and needs of clinical toxicology laboratories. Currently the techniques are in the hands of specialists, mainly in academic institutions. However, the evolution in technology should allow application of these techniques as a tool in toxicology laboratories, thus allowing a more widespread exploitation of their potential.

Toxicological risk assessment and prioritization of drinking water relevant contaminants of emerging concern.

Science.gov (United States)

Baken, Kirsten A; Sjerps, Rosa M A; Schriks, Merijn; van Wezel, Annemarie P

2018-06-13

Toxicological risk assessment of contaminants of emerging concern (CEC) in (sources of) drinking water is required to identify potential health risks and prioritize chemicals for abatement or monitoring. In such assessments, concentrations of chemicals in drinking water or sources are compared to either (i) health-based (statutory) drinking water guideline values, (ii) provisional guideline values based on recent toxicity data in absence of drinking water guidelines, or (iii) generic drinking water target values in absence of toxicity data. Here, we performed a toxicological risk assessment for 163 CEC that were selected as relevant for drinking water. This relevance was based on their presence in drinking water and/or groundwater and surface water sources in downstream parts of the Rhine and Meuse, in combination with concentration levels and physicochemical properties. Statutory and provisional drinking water guideline values could be derived from publically available toxicological information for 142 of the CEC. Based on measured concentrations it was concluded that the majority of substances do not occur in concentrations which individually pose an appreciable human health risk. A health concern could however not be excluded for vinylchloride, trichloroethene, bromodichloromethane, aniline, phenol, 2-chlorobenzenamine, mevinphos, 1,4-dioxane, and nitrolotriacetic acid. For part of the selected substances, toxicological risk assessment for drinking water could not be performed since either toxicity data (hazard) or drinking water concentrations (exposure) were lacking. In absence of toxicity data, the Threshold of Toxicological Concern (TTC) approach can be applied for screening level risk assessment. The toxicological information on the selected substances was used to evaluate whether drinking water target values based on existing TTC levels are sufficiently protective for drinking water relevant CEC. Generic drinking water target levels of 37 μg/L for

Zebrafish neurobehavioral phenomics for aquatic neuropharmacology and toxicology research.

Science.gov (United States)

Kalueff, Allan V; Echevarria, David J; Homechaudhuri, Sumit; Stewart, Adam Michael; Collier, Adam D; Kaluyeva, Aleksandra A; Li, Shaomin; Liu, Yingcong; Chen, Peirong; Wang, JiaJia; Yang, Lei; Mitra, Anisa; Pal, Subharthi; Chaudhuri, Adwitiya; Roy, Anwesha; Biswas, Missidona; Roy, Dola; Podder, Anupam; Poudel, Manoj K; Katare, Deepshikha P; Mani, Ruchi J; Kyzar, Evan J; Gaikwad, Siddharth; Nguyen, Michael; Song, Cai

2016-01-01

Zebrafish (Danio rerio) are rapidly emerging as an important model organism for aquatic neuropharmacology and toxicology research. The behavioral/phenotypic complexity of zebrafish allows for thorough dissection of complex human brain disorders and drug-evoked pathological states. As numerous zebrafish models become available with a wide spectrum of behavioral, genetic, and environmental methods to test novel drugs, here we discuss recent zebrafish phenomics methods to facilitate drug discovery, particularly in the field of biological psychiatry. Additionally, behavioral, neurological, and endocrine endpoints are becoming increasingly well-characterized in zebrafish, making them an inexpensive, robust and effective model for toxicology research and pharmacological screening. We also discuss zebrafish behavioral phenotypes, experimental considerations, pharmacological candidates and relevance of zebrafish neurophenomics to other 'omics' (e.g., genomic, proteomic) approaches. Finally, we critically evaluate the limitations of utilizing this model organism, and outline future strategies of research in the field of zebrafish phenomics. Copyright © 2015 Elsevier B.V. All rights reserved.

[Development and Application of Metabonomics in Forensic Toxicology].

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Yan, Hui; Shen, Min

2015-06-01

Metabonomics is an important branch of system biology following the development of genomics, transcriptomics and proteomics. It can perform high-throughput detection and data processing with multiple parameters, potentially enabling the identification and quantification of all small metabolites in a biological system. It can be used to provide comprehensive information on the toxicity effects, toxicological mechanisms and biomarkers, sensitively finding the unusual metabolic changes caused by poison. This article mainly reviews application of metabonomics in toxicological studies of abused drugs, pesticides, poisonous plants and poisonous animals, and also illustrates the new direction of forensic toxicology research.

Toxicology of Marine Mammals: New Developments and Opportunities.

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Weijs, Liesbeth; Zaccaroni, Annalisa

2016-01-01

It is widely recognized that marine mammals are exposed to a wide variety of pollutants, with a weight of evidence indicating impacts on their health. Since hundreds of new chemicals enter the global market every year,the methods, approaches and technologies used to characterize pollution levels or impacts are also in a constant state of flux. However, legal and ethical constraints often limit the type and extent of toxicological research being carried out in marine mammals. Nevertheless, new and emerging in vivo, in vitro as well as in silico research opportunities abound in the field of marine mammal toxicology. In the application of findings to population-, species-, or habitat-related risk assessments, the identification of causal relationships which inform source apportionment is important. This, in turn, is informed by a comprehensive understanding of contaminant classes, profiles and fate overspace and time. Such considerations figure prominently in the design and interpretation of marine mammal (eco)-toxicology research. This mini-review attempts to follow the evolution behind marine mammal toxicology until now,highlight some of the research that has been done and suggest opportunities for future research. This Special Issue will showcase new developments in marine mammal toxicology, approaches for exposure-effect research in risk assessment as well as future opportunities.

Project CAREER/CAN. Final Evaluation Report.

Science.gov (United States)

National Educational Evaluation Services, Inc., Chestnut Hill, MA.

A description and evaluation of (1) the development of the 4-column process which completes the behavioral objective data base, (2) the development of the computer retrieval capability, and (3) the pilot testing of the product in high school classrooms are included in this summative evaluation of Project CAREER/CAN. (Goals of Project CAREER/CAN,…

A novel nasal powder formulation of glucagon: toxicology studies in animal models

OpenAIRE

Reno, Frederick E.; Normand, Patrick; McInally, Kevin; Silo, Sherwin; Stotland, Patricia; Triest, Myriam; Carballo, Dolores; Pich?, Claude

2015-01-01

Background Glucagon nasal powder (GNP), a novel intranasal formulation of glucagon being developed to treat insulin-induced severe hypoglycemia, contains synthetic glucagon (10?% w/w), beta-cyclodextrin, and dodecylphosphocholine. The safety of this formulation was evaluated in four studies in animal models. Methods The first study evaluated 28-day sub-chronic toxicology in rats treated intranasally with 1 and 2?mg of GNP/day (0.1 and 0.2?mg glucagon/rat/day). The second study evaluated 28-da...

Predictive toxicology using systemic biology and liver microfluidic “on chip” approaches: Application to acetaminophen injury

International Nuclear Information System (INIS)

Prot, Jean-Matthieu; Bunescu, Andrei; Elena-Herrmann, Bénédicte; Aninat, Caroline; Snouber, Leila Choucha; Griscom, Laurent; Razan, Florence; Bois, Frederic Y.; Legallais, Cécile

2012-01-01

We have analyzed transcriptomic, proteomic and metabolomic profiles of hepatoma cells cultivated inside a microfluidic biochip with or without acetaminophen (APAP). Without APAP, the results show an adaptive cellular response to the microfluidic environment, leading to the induction of anti-oxidative stress and cytoprotective pathways. In presence of APAP, calcium homeostasis perturbation, lipid peroxidation and cell death are observed. These effects can be attributed to APAP metabolism into its highly reactive metabolite, N-acetyl-p-benzoquinone imine (NAPQI). That toxicity pathway was confirmed by the detection of GSH-APAP, the large production of 2-hydroxybutyrate and 3-hydroxybutyrate, and methionine, cystine, and histidine consumption in the treated biochips. Those metabolites have been reported as specific biomarkers of hepatotoxicity and glutathione depletion in the literature. In addition, the integration of the metabolomic, transcriptomic and proteomic collected profiles allowed a more complete reconstruction of the APAP injury pathways. To our knowledge, this work is the first example of a global integration of microfluidic biochip data in toxicity assessment. Our results demonstrate the potential of that new approach to predictive toxicology. -- Highlights: ► We cultivated liver cells in microfluidic biochips ► We integrated transcriptomic, proteomic and metabolomics profiles ► Pathways reconstructions were proposed in control and acetaminophen treated cultures ► Biomarkers were identified ► Comparisons with in vivo studies were proposed.

The Center for Alternatives to Animal Testing - Europe (CAAT-EU): a transatlantic bridge for the paradigm shift in toxicology.

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Daneshian, Mardas; Leist, Marcel; Hartung, Thomas

2010-01-01

The Center for Alternatives to Animal Testing - Europe (CAAT-EU) was founded based collaboration between the Johns Hopkins Bloomberg School of Public Health and the University of Konstanz. CAAT-EU, housed at the University of Konstanz, will coordinate transatlantic activities to promote humane science in research and education, and participate, as partner or coordinator, in publicly and privately funded European projects. Thomas Hartung will serve as program liaison representing Johns Hopkins University and Marcel Leist as the University of Konstanz liaison. CAAT-EU aims to: 1) Set up transatlantic consortia for international research projects on alternative methods. 2) Establish a CAAT Europe faculty and advisory board composed of sponsor representatives and prominent academics from Europe . 3) Participate in the Transatlantic Think Tank for Toxicology (t4) devoted to conceptual work for the paradigm shift in toxicology. 4) Coordinate a series of information days in Europe on relevant developments in the US, similar to the 2009 series CAAT held in the US on EU issues (one on the 7th Amendment to the EU Cosmetics Directive and one on EU and US chemical regulation). 5) Support ALTEX as the official journal of CAAT and CAAT-EU. 6) Develop strategic projects with sponsors to promote humane science and new toxicology, especially with CAAT faculty members. 7) Develop a joint education program between Johns Hopkins and the University of Konstanz, such as e-courses and the existing Humane Science Certificate program developed by CAAT, a student exchange program, and collaboration with the International Graduate School "Cell-based Characterization of De- and Regeneration" in Konstanz.

IRIS Toxicological Review of Trichloroethylene (TCE) ...

Science.gov (United States)

EPA is conducting a peer review and public comment of the scientific basis supporting the human health hazard and dose-response assessment of Trichloroethylene (TCE) that when finalized will appear on the Integrated Risk Information System (IRIS) database. The purpose of this Toxicological Review is to provide scientific support and rationale for the hazard and dose-response assessment in IRIS pertaining to chronic exposure to trichloroethylene. It is not intended to be a comprehensive treatise on the chemical or toxicological nature of trichloroethylene.

TOXICOLOGICAL RESEARCH INVOLVING HUMANS: ETHICAL AND REGULATORY CONSIDERATIONS

Science.gov (United States)

This paper discusses the need for the Society of Toxicology (SOT) to develop a policy for ethical research in humans, and a review for publication of these studies. Observations on human beings have been the foundation upon which toxicologic knowledge has been built since the in...

TOXICOLOGICAL EVALUATION OF REALISTIC EMISSIONS OF SOURCE AEROSOLS (TERESA): APPLICATION TO POWER PLANT-DERIVED PM2.5

Energy Technology Data Exchange (ETDEWEB)

Annette Rohr

2006-03-31

This report documents progress made on the subject project during the period of September 1, 2005 through February 28, 2006. The TERESA Study is designed to investigate the role played by specific emissions sources and components in the induction of adverse health effects by examining the relative toxicity of coal combustion and mobile source (gasoline and/or diesel engine) emissions and their oxidative products. The study involves on-site sampling, dilution, and aging of coal combustion emissions at three coal-fired power plants, as well as mobile source emissions, followed by animal exposures incorporating a number of toxicological endpoints. The DOE-EPRI Cooperative Agreement (henceforth referred to as ''the Agreement'') for which this technical progress report has been prepared covers the performance and analysis of field experiments at the first TERESA plant, located in the Upper Midwest and henceforth referred to as Plant 0, and at two additional coal-fired power plants (Plants 1 and 2) utilizing different coal types and with different plant configurations. During this reporting period, data processing and analyses were completed for exposure and toxicological data collected during the field campaign at Plant 1, located in the Southeast. To recap from the previous progress report, Stage I toxicological assessments were carried out in normal Sprague-Dawley rats, and Stage II assessments were carried out in a compromised model (myocardial infarction-MI-model). Normal rats were exposed to the following atmospheric scenarios: (1) primary particles; (2) oxidized emissions; (3) oxidized emissions + SOA--this scenario was repeated; and (4) oxidized emissions + ammonia + SOA. Compromised animals were exposed to oxidized emissions + SOA (this scenario was also conducted in replicate). Mass concentrations in exposure atmospheres ranged from 13.9 {micro}g/m{sup 3} for the primary particle scenario (P) to 385 {micro}g/m{sup 3} for one of the oxidized

5 CFR 470.317 - Project evaluation.

Science.gov (United States)

2010-01-01

... law and/or regulation should be considered or proposed. Where the project plan provides for agency... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Project evaluation. 470.317 Section 470... MANAGEMENT RESEARCH PROGRAMS AND DEMONSTRATIONS PROJECTS Regulatory Requirements Pertaining to Demonstration...

Toxicodynetics: A new discipline in clinical toxicology.

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Baud, F J; Houzé, P; Villa, A; Borron, S W; Carli, P

2016-05-01

Regarding the different disciplines that encompass the pharmacology and the toxicology, none is specifically dedicated to the description and analysis of the time-course of relevant toxic effects both in experimental and clinical studies. The lack of a discipline devoted to this major field in toxicology results in misconception and even in errors by clinicians. Review of the basic different disciplines that encompass pharmacology toxicology and comparing with the description of the time-course of effects in conditions in which toxicological analysis was not performed or with limited analytical evidence. Review of the literature clearly shows how misleading is the current extrapolation of toxicokinetic data to the description of the time-course of toxic effects. A new discipline entitled toxicodynetics should be developed aiming at a more systematic description of the time-course of effects in acute human and experimental poisonings. Toxicodynetics might help emergency physicians in risk assessment when facing a poisoning and contribute to a better assessment of quality control of data collected by poison control centres. Toxicodynetics would also allow a quantitative approach to the clinical effects resulting from drug-drug interaction. Copyright © 2016. Published by Elsevier Masson SAS.

[Adverse Effect Predictions Based on Computational Toxicology Techniques and Large-scale Databases].

Science.gov (United States)

Uesawa, Yoshihiro

2018-01-01

　Understanding the features of chemical structures related to the adverse effects of drugs is useful for identifying potential adverse effects of new drugs. This can be based on the limited information available from post-marketing surveillance, assessment of the potential toxicities of metabolites and illegal drugs with unclear characteristics, screening of lead compounds at the drug discovery stage, and identification of leads for the discovery of new pharmacological mechanisms. This present paper describes techniques used in computational toxicology to investigate the content of large-scale spontaneous report databases of adverse effects, and it is illustrated with examples. Furthermore, volcano plotting, a new visualization method for clarifying the relationships between drugs and adverse effects via comprehensive analyses, will be introduced. These analyses may produce a great amount of data that can be applied to drug repositioning.

Current Knowledge on the Use of Computational Toxicology in Hazard Assessment of Metallic Engineered Nanomaterials

Directory of Open Access Journals (Sweden)

Guangchao Chen

2017-07-01

Full Text Available As listed by the European Chemicals Agency, the three elements in evaluating the hazards of engineered nanomaterials (ENMs include the integration and evaluation of toxicity data, categorization and labeling of ENMs, and derivation of hazard threshold levels for human health and the environment. Assessing the hazards of ENMs solely based on laboratory tests is time-consuming, resource intensive, and constrained by ethical considerations. The adoption of computational toxicology into this task has recently become a priority. Alternative approaches such as (quantitative structure–activity relationships ((QSAR and read-across are of significant help in predicting nanotoxicity and filling data gaps, and in classifying the hazards of ENMs to individual species. Thereupon, the species sensitivity distribution (SSD approach is able to serve the establishment of ENM hazard thresholds sufficiently protecting the ecosystem. This article critically reviews the current knowledge on the development of in silico models in predicting and classifying the hazard of metallic ENMs, and the development of SSDs for metallic ENMs. Further discussion includes the significance of well-curated experimental datasets and the interpretation of toxicity mechanisms of metallic ENMs based on reported models. An outlook is also given on future directions of research in this frontier.

Downloadable Computational Toxicology Data

Science.gov (United States)

EPA’s computational toxicology research generates data that investigates the potential harm, or hazard of a chemical, the degree of exposure to chemicals as well as the unique chemical characteristics. This data is publicly available here.

The Consultancy Activity on In Silico Models for Genotoxic Prediction of Pharmaceutical Impurities.

Science.gov (United States)

Pavan, Manuela; Kovarich, Simona; Bassan, Arianna; Broccardo, Lorenza; Yang, Chihae; Fioravanzo, Elena

2016-01-01

The toxicological assessment of DNA-reactive/mutagenic or clastogenic impurities plays an important role in the regulatory process for pharmaceuticals; in this context, in silico structure-based approaches are applied as primary tools for the evaluation of the mutagenic potential of the drug impurities. The general recommendations regarding such use of in silico methods are provided in the recent ICH M7 guideline stating that computational (in silico) toxicology assessment should be performed using two (Q)SAR prediction methodologies complementing each other: a statistical-based method and an expert rule-based method.Based on our consultant experience, we describe here a framework for in silico assessment of mutagenic potential of drug impurities. Two main applications of in silico methods are presented: (1) support and optimization of drug synthesis processes by providing early indication of potential genotoxic impurities and (2) regulatory evaluation of genotoxic potential of impurities in compliance with the ICH M7 guideline. Some critical case studies are also discussed.

How is success or failure in river restoration projects evaluated? Feedback from French restoration projects.

Science.gov (United States)

Morandi, Bertrand; Piégay, Hervé; Lamouroux, Nicolas; Vaudor, Lise

2014-05-01

Since the 1990s, French operational managers and scientists have been involved in the environmental restoration of rivers. The European Water Framework Directive (2000) highlights the need for feedback from restoration projects and for evidence-based evaluation of success. Based on 44 French pilot projects that included such an evaluation, the present study includes: 1) an introduction to restoration projects based on their general characteristics 2) a description of evaluation strategies and authorities in charge of their implementation, and 3) a focus on the evaluation of results and the links between these results and evaluation strategies. The results show that: 1) the quality of an evaluation strategy often remains too poor to understand well the link between a restoration project and ecological changes; 2) in many cases, the conclusions drawn are contradictory, making it difficult to determine the success or failure of a restoration project; and 3) the projects with the poorest evaluation strategies generally have the most positive conclusions about the effects of restoration. Recommendations are that evaluation strategies should be designed early in the project planning process and be based on clearly-defined objectives. Copyright © 2014 Elsevier Ltd. All rights reserved.

Toxicological evaluation of ethanolic extract from Stevia rebaudiana Bertoni leaves: Genotoxicity and subchronic oral toxicity.

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Zhang, Qiannan; Yang, Hui; Li, Yongning; Liu, Haibo; Jia, Xudong

2017-06-01

Stevia rebaudiana Bertoni leaves have a long history of use as an abundant source of sweetener. The aqueous extract of stevia leaves and the predominant constitutes steviol glycosides have been intensively investigated. However, rare studies provided toxicological evaluation of bioactive components in the polar extract regarding their safety on human health. This study aimed to evaluate the toxicity of ethanolic extract of Stevia rebaudiana Bertoni leaves through a battery of in vitro and in vivo tests. Negative results were unanimously obtained from bacterial reverse mutation assay, mouse bone marrow micronucleus assay and mouse sperm malformation assay. Oral administration at dietary levels of 1.04%, 2.08% and 3.12% for 90 days did not induce significant behavioral, hematological, clinical, or histopathological changes in rats. Significant reduction of cholesterol, total protein and albumin was observed in female animals only at high dose level. The results demonstrated that Stevia rebaudiana Bertoni leaves ethanolic extract, which is rich in isochlorogenic acids, does not possess adverse effects through oral administration in this study. Our data provided supportive evidence for the safety of Stevia rebaudiana Bertoni leaves that may potentially be used in functional foods as well as nutritional supplements beyond sweetner. Copyright © 2017 Elsevier Inc. All rights reserved.

Geospatial application of the Water Erosion Prediction Project (WEPP) Model

Science.gov (United States)

D. C. Flanagan; J. R. Frankenberger; T. A. Cochrane; C. S. Renschler; W. J. Elliot

2011-01-01

The Water Erosion Prediction Project (WEPP) model is a process-based technology for prediction of soil erosion by water at hillslope profile, field, and small watershed scales. In particular, WEPP utilizes observed or generated daily climate inputs to drive the surface hydrology processes (infiltration, runoff, ET) component, which subsequently impacts the rest of the...

[Continuous challenges in Japanese forensic toxicology practice: strategy to address specific goals].

Science.gov (United States)

Kageura, Mitsuyoshi

2002-09-01

In this paper, the status quo of forensic toxicology in Japan and the West is surveyed and a strategy to address future goals of Japanese forensic toxicology is proposed. Forensic toxicology in the West consists of three main areas--post-mortem forensic toxicology, human-performance forensic toxicology and forensic urine drug testing. In Japan, post-mortem forensic toxicology is practiced in university forensic medicine departments while most of the human-performance forensic toxicology is carried out in police laboratories. However, at least at present, strictly controlled workplace urine drug testing is not being performed, despite the abuse of drugs even by uniformed members of the National Defence Forces and police. For several years, the author has been introducing Western forensic toxicology guidelines and recommendations, translated into Japanese with the help of Western forensic toxicologists, to Japanese forensic toxicologists. Western forensic toxicology practice is at an advanced stage, whereas Japanese practice is in a critical condition and holds many problems awaiting solution, as exemplified by the urine drug testing in police laboratories. There is never any sample left for re-examination by the defence in all cases, though the initial volume of the urine sample available for examination is 30-50 ml. Only one organisation carries out everything from sampling to reporting and, in addition, the parent drug and its metabolites are not quantified. It is clear that the police laboratories do not work within good laboratory practice guidelines, nor do they have quality manuals or standard operating procedures manuals. A basic change in Japanese forensic toxicology practice is now essential. The author strongly recommends that, first of all, Japanese toxicologists should prepare forensic toxicology guidelines based on the Western models. The guidelines would progress the following objectives for forensic toxicology laboratories: 1) to have documented good

Does GLP enhance the quality of toxicological evidence for regulatory decisions?

Science.gov (United States)

Borgert, Christopher J.; Becker, Richard A.; Carlton, Betsy D.; Hanson, Mark; Kwiatkowski, Patricia L.; Sue Marty, Mary; McCarty, Lynn S.; Quill, Terry F.; Solomon, Keith; Van Der Kraak, Glen; Witorsch, Raphael J.; Don Yi, Kun

2016-01-01

There is debate over whether the requirements of GLP are appropriate standards for evaluating the quality of toxicological data used to formulate regulations. A group promoting the importance of non-monotonic dose responses for endocrine disruptors contend that scoring systems giving primacy to GLP are biased against non-GLP studies from the literature and are merely record-keeping exercises to prevent fraudulent reporting of data from non-published guideline toxicology studies. They argue that guideline studies often employ insensitive species and outdated methods, and ignore the perspectives of subject-matter experts in endocrine disruption, who should be the sole arbiters of data quality. We believe regulatory agencies should use both non-GLP and GLP studies, that GLP requirements assure fundamental tenets of study integrity not typically addressed by journal peer-review, and that use of standardized test guidelines and GLP promotes consistency, reliability, comparability, and harmonization of various types of studies used by regulatory agencies worldwide. This debate suffers two impediments to progress: a conflation of different phases of study interpretation and levels of data validity, and a misleading characterization of many essential components of GLP and regulatory toxicology. Herein we provide clarifications critical for removing those impediments. PMID:27208076

The New Toxicology of Sophisticated Materials: Nanotoxicology and Beyond

Science.gov (United States)

Maynard, Andrew D.; Warheit, David B.; Philbert, Martin A.

2011-01-01

It has long been recognized that the physical form of materials can mediate their toxicity—the health impacts of asbestiform materials, industrial aerosols, and ambient particulate matter are prime examples. Yet over the past 20 years, toxicology research has suggested complex and previously unrecognized associations between material physicochemistry at the nanoscale and biological interactions. With the rapid rise of the field of nanotechnology and the design and production of increasingly complex nanoscale materials, it has become ever more important to understand how the physical form and chemical composition of these materials interact synergistically to determine toxicity. As a result, a new field of research has emerged—nanotoxicology. Research within this field is highlighting the importance of material physicochemical properties in how dose is understood, how materials are characterized in a manner that enables quantitative data interpretation and comparison, and how materials move within, interact with, and are transformed by biological systems. Yet many of the substances that are the focus of current nanotoxicology studies are relatively simple materials that are at the vanguard of a new era of complex materials. Over the next 50 years, there will be a need to understand the toxicology of increasingly sophisticated materials that exhibit novel, dynamic and multifaceted functionality. If the toxicology community is to meet the challenge of ensuring the safe use of this new generation of substances, it will need to move beyond “nano” toxicology and toward a new toxicology of sophisticated materials. Here, we present a brief overview of the current state of the science on the toxicology of nanoscale materials and focus on three emerging toxicology-based challenges presented by sophisticated materials that will become increasingly important over the next 50 years: identifying relevant materials for study, physicochemical characterization, and

Evaluation of Health Equity Impact of Structural Policies: Overview of Research Methods Used in the SOPHIE Project.

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Kunst, Anton E

2017-07-01

This article briefly assesses the research methods that were applied in the SOPHIE project to evaluate the impact of structural policies on population health and health inequalities. The evaluation of structural policies is one of the key methodological challenges in today's public health. The experience in the SOPHIE project was that mixed methods are essential to identify, understand, and predict the health impact of structural policies. On the one hand, quantitative studies that included spatial comparisons or time trend analyses, preferably in a quasi-experimental design, showed that some structural policies were associated with improved population health and smaller health inequalities. On the other hand, qualitative studies, often inspired by realist approaches, were important to understand how these policies could have achieved the observed impact and why they would succeed in some settings but fail in others. This review ends with five recommendations for future studies that aim to evaluate, understand, and predict how health inequalities can be reduced through structural policies.

[Forensic toxicology, a growing scientific discipline].

Science.gov (United States)

Augsburger, Marc; Staub, Christian

2008-07-02

Forensic toxicology has to bring evidence of substances that could have been involved directly or indirectly in the cause of death or that could influence the behaviour of somebody. The increase of the consumption of illegal and legal drugs in modern societies during last decades gave a boost to forensic toxicology. Moreover, improvement with analytical technology gave tools with high degrees of sensitivity and specificity for the screening and quantification of a large amount of substances in various biological specimens, even with very low concentration resulting of a single dose of medication.

A preliminary approach to quantifying the overall environmental risks posed by development projects during environmental impact assessment.

Directory of Open Access Journals (Sweden)

Sam Nicol

Full Text Available Environmental impact assessment (EIA is used globally to manage the impacts of development projects on the environment, so there is an imperative to demonstrate that it can effectively identify risky projects. However, despite the widespread use of quantitative predictive risk models in areas such as toxicology, ecosystem modelling and water quality, the use of predictive risk tools to assess the overall expected environmental impacts of major construction and development proposals is comparatively rare. A risk-based approach has many potential advantages, including improved prediction and attribution of cause and effect; sensitivity analysis; continual learning; and optimal resource allocation. In this paper we investigate the feasibility of using a Bayesian belief network (BBN to quantify the likelihood and consequence of non-compliance of new projects based on the occurrence probabilities of a set of expert-defined features. The BBN incorporates expert knowledge and continually improves its predictions based on new data as it is collected. We use simulation to explore the trade-off between the number of data points and the prediction accuracy of the BBN, and find that the BBN could predict risk with 90% accuracy using approximately 1000 data points. Although a further pilot test with real project data is required, our results suggest that a BBN is a promising method to monitor overall risks posed by development within an existing EIA process given a modest investment in data collection.

GEAR UP Aspirations Project Evaluation

Science.gov (United States)

Trimble, Brad A.

2013-01-01

The purpose of this study was to conduct a formative evaluation of the first two years of the Gaining Early Awareness and Readiness for Undergraduate Programs (GEAR UP) Aspirations Project (Aspirations) using a Context, Input, Process, and Product (CIPP) model so as to gain an in-depth understanding of the project during the middle school…

Opinions expressed by Italian National Advisory Toxicological Committee on some active ingredients of pesticides

Energy Technology Data Exchange (ETDEWEB)

Camoni, I [Ist. Superiore di Sanita` , Rome (Italy). Lab. di Tossicologia Applicata

1996-03-01

The opinions expressed by the Italian National Advisory Toxicological Committee (CCTN) on some active ingredients of pesticides are presented. Carcinogenic and mutagenic effects of these substances have been examined and, on this basis, an evaluation and relative classification were expressed.

Evaluation and comparison of mammalian subcellular localization prediction methods

Directory of Open Access Journals (Sweden)

Fink J Lynn

2006-12-01

Full Text Available Abstract Background Determination of the subcellular location of a protein is essential to understanding its biochemical function. This information can provide insight into the function of hypothetical or novel proteins. These data are difficult to obtain experimentally but have become especially important since many whole genome sequencing projects have been finished and many resulting protein sequences are still lacking detailed functional information. In order to address this paucity of data, many computational prediction methods have been developed. However, these methods have varying levels of accuracy and perform differently based on the sequences that are presented to the underlying algorithm. It is therefore useful to compare these methods and monitor their performance. Results In order to perform a comprehensive survey of prediction methods, we selected only methods that accepted large batches of protein sequences, were publicly available, and were able to predict localization to at least nine of the major subcellular locations (nucleus, cytosol, mitochondrion, extracellular region, plasma membrane, Golgi apparatus, endoplasmic reticulum (ER, peroxisome, and lysosome. The selected methods were CELLO, MultiLoc, Proteome Analyst, pTarget and WoLF PSORT. These methods were evaluated using 3763 mouse proteins from SwissProt that represent the source of the training sets used in development of the individual methods. In addition, an independent evaluation set of 2145 mouse proteins from LOCATE with a bias towards the subcellular localization underrepresented in SwissProt was used. The sensitivity and specificity were calculated for each method and compared to a theoretical value based on what might be observed by random chance. Conclusion No individual method had a sufficient level of sensitivity across both evaluation sets that would enable reliable application to hypothetical proteins. All methods showed lower performance on the LOCATE

Toxicological perspectives of inhaled therapeutics and nanoparticles.

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Hayes, Amanda J; Bakand, Shahnaz

2014-07-01

The human respiratory system is an important route for the entry of inhaled therapeutics into the body to treat diseases. Inhaled materials may consist of gases, vapours, aerosols and particulates. In all cases, assessing the toxicological effect of inhaled therapeutics has many challenges. This article provides an overview of in vivo and in vitro models for testing the toxicity of inhaled therapeutics and nanoparticles implemented in drug delivery. Traditionally, inhalation toxicity has been performed on test animals to identify the median lethal concentration of airborne materials. Later maximum tolerable concentration denoted by LC0 has been introduced as a more ethically acceptable end point. More recently, in vitro methods have been developed, allowing the direct exposure of airborne material to cultured human target cells on permeable porous membranes at the air-liquid interface. Modifications of current inhalation therapies, new pulmonary medications for respiratory diseases and implementation of the respiratory tract for systemic drug delivery are providing new challenges when conducting well-designed inhalation toxicology studies. In particular, the area of nanoparticles and nanocarriers is of critical toxicological concern. There is a need to develop toxicological test models, which characterise the toxic response and cellular interaction between inhaled particles and the respiratory system.

Aerospace toxicology overview: aerial application and cabin air quality.

Science.gov (United States)

Chaturvedi, Arvind K

2011-01-01

encountered chemicals, or aircraft cabin air contaminants and point out the need for future research to better address toxicological evaluation of aircraft-engine oil additives.

Course constructions: A case-base of forensic toxicology.

Science.gov (United States)

Zhou, Nan; Wu, Yeda; Su, Terry; Zhang, Liyong; Yin, Kun; Zheng, Da; Zheng, Jingjing; Huang, Lei; Wu, Qiuping; Cheng, Jianding

2017-08-01

Forensic toxicology education in China is limited by insufficient teaching methods and resources, resulting in students with adequate theoretical principles but lacking practice experience. Typical cases used as teaching materials vividly represent intoxication and provide students with an opportunity to practice and hone resolving skills. In 2013, the Department of Forensic Pathology at Zhongshan School of Medicine began to construct top-quality courses in forensic toxicology, with its first step, creating a base containing typical cases of intoxication. This essay reviews the construction process of said cases-base, which is intended to set an example of forensic toxicology education. Copyright © 2017 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

Stakeholder approach for evaluating organizational change projects.

Science.gov (United States)

Peltokorpi, Antti; Alho, Antti; Kujala, Jaakko; Aitamurto, Johanna; Parvinen, Petri

2008-01-01

This paper aims to create a model for evaluating organizational change initiatives from a stakeholder resistance viewpoint. The paper presents a model to evaluate change projects and their expected benefits. Factors affecting the challenge to implement change were defined based on stakeholder theory literature. The authors test the model's practical validity for screening change initiatives to improve operating room productivity. Change initiatives can be evaluated using six factors: the effect of the planned intervention on stakeholders' actions and position; stakeholders' capability to influence the project's implementation; motivation to participate; capability to change; change complexity; and management capability. The presented model's generalizability should be explored by filtering presented factors through a larger number of historical cases operating in different healthcare contexts. The link between stakeholders, the change challenge and the outcomes of change projects needs to be empirically tested. The proposed model can be used to prioritize change projects, manage stakeholder resistance and establish a better organizational and professional competence for managing healthcare organization change projects. New insights into existing stakeholder-related understanding of change project successes are provided.

Applicability of Computational Systems Biology in Toxicology

DEFF Research Database (Denmark)

Kongsbak, Kristine Grønning; Hadrup, Niels; Audouze, Karine Marie Laure

2014-01-01

be used to establish hypotheses on links between the chemical and human diseases. Such information can also be applied for designing more intelligent animal/cell experiments that can test the established hypotheses. Here, we describe how and why to apply an integrative systems biology method......Systems biology as a research field has emerged within the last few decades. Systems biology, often defined as the antithesis of the reductionist approach, integrates information about individual components of a biological system. In integrative systems biology, large data sets from various sources...... and databases are used to model and predict effects of chemicals on, for instance, human health. In toxicology, computational systems biology enables identification of important pathways and molecules from large data sets; tasks that can be extremely laborious when performed by a classical literature search...

The adverse outcome pathway concept: a pragmatic tool in toxicology.

Science.gov (United States)

Vinken, Mathieu

2013-10-04

Adverse outcome pathways (AOPs) are novel tools in toxicology and human risk assessment with broad potential. AOPs are designed to provide a clear-cut mechanistic representation of critical toxicological effects that span over different layers of biological organization. AOPs share a common structure consisting of a molecular initiating event, a series of intermediate steps and key events, and an adverse outcome. Development of AOPs ideally complies with OECD guidelines. This also holds true for AOP evaluation, which includes consideration of the Bradford Hill criteria for weight-of-evidence assessment and meeting a set of key questions defined by the OECD. Elaborate AOP frameworks have yet been proposed for chemical-induced skin sensitization, cholestasis, liver fibrosis and liver steatosis. These newly postulated AOPs can serve a number of ubiquitous purposes, including the establishment of (quantitative) structure-activity relationships, the development of novel in vitro toxicity screening tests and the elaboration of prioritization strategies. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

IRIS Toxicological Review of Trichloroethylene (Interagency Science Consultation Draft)

Science.gov (United States)

On November 3, 2009, the Toxicological Review of Trichloroethylene and the charge to external peer reviewers were released for external peer review and public comment. The Toxicological Review and charge were reviewed internally by EPA and by other federal agencies and White Hous...

Prospects for Applying Synthetic Biology to Toxicology: Future Opportunities and Current Limitations for the Repurposing of Cytochrome P450 Systems.

Science.gov (United States)

Behrendorff, James B Y H; Gillam, Elizabeth M J

2017-01-17

The 30 years since the inception of Chemical Research in Toxicology, game-changing advances in chemical and molecular biology, the fundamental disciplines underpinning molecular toxicology, have been made. While these have led to important advances in the study of mechanisms by which chemicals damage cells and systems, there has been less focus on applying these advances to prediction, detection, and mitigation of toxicity. Over the last ∼15 years, synthetic biology, the repurposing of biological "parts" in systems engineered for useful ends, has been explored in other areas of the biomedical and life sciences, for such applications as detecting metabolites, drug discovery and delivery, investigating disease mechanisms, improving medical treatment, and producing useful chemicals. These examples provide models for the application of synthetic biology to toxicology, which, for the most part, has not yet benefited from such approaches. In this perspective, we review the synthetic biology approaches that have been applied to date and speculate on possible short to medium term and "blue sky" aspirations for synthetic biology, particularly in clinical and environmental toxicology. Finally, we point out key hurdles that must be overcome for the full potential of synthetic biology to be realized.

The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project

OpenAIRE

Hudson, LN; Newbold, T; Contu, S; Hill, SLL; Lysenko, I; De Palma, A; Phillips, HRP; Alhusseini, TI; Bedford, FE; Bennett, DJ; Booth, H; Burton, VJ; Chng, CWT; Choimes, A; Correia, DLP

2017-01-01

The PREDICTS project—Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)—has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make free...

Sustainability, natural and organic cosmetics: consumer, products, efficacy, toxicological and regulatory considerations

Directory of Open Access Journals (Sweden)

Bruno Fonseca-Santos

2015-03-01

Full Text Available The interest in sustainable products has increased along the years, since the choice of products, packaging and production processes have a great impact on the environment. These products are classified by regulatory agencies in different categories, aggregating advantages to the product and increasing the demand by consumers. However, there is no harmonization in guidelines of these certifying agencies and each cosmetic industry formulates their product and packaging in a more rational way, which causes less damage to the environment. Many cosmetic products have in their formulation natural products that perform a specific biological function, but these products should be evaluated on efficacy and toxicological aspects. The aim of this article is to approach sustainability, natural and organic cosmetics, considering the consumer and the efficacy, toxicological and regulatory aspects.

75 FR 2545 - National Toxicology Program (NTP); Center for the Evaluation of Risks to Human Reproduction...

Science.gov (United States)

2010-01-15

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Toxicology Program... Environmental Health Sciences (NIEHS); National Institutes of Health (NIH); HHS. ACTION: Announcement of report...: Background Soy infant formula is fed to infants as a supplement or replacement for human milk or cow milk...

Overview of the "epigenetic end points in toxicologic pathology and relevance to human health" session of the 2014 Society Of Toxicologic Pathology Annual Symposium.

Science.gov (United States)

Hoenerhoff, Mark J; Hartke, James

2015-01-01

The theme of the Society of Toxicologic Pathology 2014 Annual Symposium was "Translational Pathology: Relevance of Toxicologic Pathology to Human Health." The 5th session focused on epigenetic end points in biology, toxicity, and carcinogenicity, and how those end points are relevant to human exposures. This overview highlights the various presentations in this session, discussing integration of epigenetics end points in toxicologic pathology studies, investigating the role of epigenetics in product safety assessment, epigenetic changes in cancers, methodologies to detect them, and potential therapies, chromatin remodeling in development and disease, and epigenomics and the microbiome. The purpose of this overview is to discuss the application of epigenetics to toxicologic pathology and its utility in preclinical or mechanistic based safety, efficacy, and carcinogenicity studies. © 2014 by The Author(s).

Development of a wind farm noise propagation prediction model - project progress to date

International Nuclear Information System (INIS)

Robinson, P.; Bullmore, A.; Bass, J.; Sloth, E.

1998-01-01

This paper describes a twelve month measurement campaign which is part of a European project (CEC Project JOR3-CT95-0051) with the aim to substantially reduce the uncertainties involved in predicting environmentally radiated noise levels from wind farms (1). This will be achieved by comparing noise levels measure at varying distances from single and multiple sources over differing complexities of terrain with those predicted using a number of currently adopted sound propagation models. Specific objectives within the project are to: establish the important parameters controlling the propagation of wind farm noise to the far field; develop a planning tool for predicting wind farm noise emission levels under practically encountered conditions; place confidence limits on the upper and lower bounds of the noise levels predicted, thus enabling developers to quantify the risk whether noise emission from wind farms will cause nuisance to nearby residents. (Author)

High-resolution mass spectrometry in toxicology: current status and future perspectives.

Science.gov (United States)

Maurer, H H; Meyer, Markus R

2016-09-01

This paper reviews high-resolution mass spectrometry (HRMS) approaches using time-of-flight or Orbitrap techniques for research and application in various toxicology fields, particularly in clinical toxicology and forensic toxicology published since 2013 and referenced in PubMed. In the introduction, an overview on applications of HRMS in various toxicology fields is given with reference to current review articles. Papers concerning HRMS in metabolism, screening, and quantification of pharmaceuticals, drugs of abuse, and toxins in human body samples are critically reviewed. Finally, a discussion on advantages as well as limitations and future perspectives of these methods is included.

Proceedings of the 2016 National Toxicology Program Satellite Symposium.

Science.gov (United States)

Elmore, Susan A; Chen, Vivian S; Hayes-Bouknight, Schantel; Hoane, Jessica S; Janardhan, Kyathanahalli; Kooistra, Linda H; Nolte, Thomas; Szabo, Kathleen A; Willson, Gabrielle A; Wolf, Jeffrey C; Malarkey, David E

2017-01-01

The 2016 annual National Toxicology Program Satellite Symposium, entitled "Pathology Potpourri" was held in San Diego, CA, at the Society of Toxicologic Pathology's (STP) 35th annual meeting. The goal of this symposium was to present and discuss challenging diagnostic pathology and/or nomenclature issues. This article presents summaries of the speakers' talks, along with select images that were used by the audience for voting and discussion. Some lesions and topics covered during the symposium included malignant glioma and histiocytic sarcoma in the rodent brain; a new statistical method designed for histopathology data evaluation; uterine stromal/glandular polyp in a rat; malignant plasma cell tumor in a mouse brain; Schwann cell proliferative lesions in rat hearts; axillary schwannoma in a cat; necrosis and granulomatous inflammation in a rat brain; adenoma/carcinoma in a rat adrenal gland; hepatocyte maturation defect and liver/spleen hematopoietic defects in an embryonic mouse; distinguishing malignant glioma, malignant mixed glioma, and malignant oligodendroglioma in the rat; comparison of mammary gland whole mounts and histopathology from mice; and discussion of the International Harmonization of Nomenclature and Diagnostic Criteria collaborations.

Toxicological evaluation of vegetable oils and biodiesel in soil during the biodegradation process

Directory of Open Access Journals (Sweden)

Ivo S. Tamada

2012-12-01

Full Text Available Vegetable oils and their derivatives, like biodiesel, are used extensively throughout the world, thus posing an environmental risk when disposed. Toxicity testing using test organisms shows how these residues affect ecosystems. Toxicity tests using earthworms (Eisenia foetida. are widespread because they are a practical resource for analyzing terrestrial organisms. For phytotoxicological analysis, we used seeds of arugula (Eruca sativa and lettuce (Lactuca sativa. to analyze the germination of seeds in contaminated soil samples. The toxicological experiment was conducted with four different periods of biodegradation in soil: zero days, 60 days, 120 days and 180 days. The studied contaminants were soybean oil (new and used and biodiesel (B100. An evaluation of the germination of both seeds showed an increased toxicity for all contaminants as the biodegradation occurred, biodiesel being the most toxic among the contaminants. On the other hand, for the tests using earthworms, the biodiesel was the only contaminant that proved to be toxic. Therefore, the higher toxicity of the sample containing these hydrocarbons over time can be attributed to the secondary compounds formed by microbial action. Thus, we conclude that the biodegradation in soil of the studied compounds requires longer periods for the sample toxicity to be decreased with the action of microorganisms.

IRIS Toxicological Review of Tetrahydrofuran (THF) ...

Science.gov (United States)

EPA is releasing the draft report, Toxicological Review of Tetrahydrofuran, that was distributed to Federal agencies and White House Offices for comment during the Science Discussion step of the IRIS Assessment Development Process. Comments received from other Federal agencies and White House Offices are provided below with external peer review panel comments. EPA is undertaking an Integrated Risk Information System (IRIS) health assessment for tetrahydrofuran. IRIS is an EPA database containing Agency scientific positions on potential adverse human health effects that may result from chronic (or lifetime) exposure to chemicals in the environment. IRIS contains chemical-specific summaries of qualitative and quantitative health information in support of two steps of the risk assessment paradigm, i.e., hazard identification and dose-response evaluation. IRIS assessments are used in combination with specific situational exposure assessment information to evaluate potential public health risk associated with environmental contaminants.

Aggregated Computational Toxicology Resource (ACTOR)

Data.gov (United States)

U.S. Environmental Protection Agency — The Aggregated Computational Toxicology Resource (ACTOR) is a database on environmental chemicals that is searchable by chemical name and other identifiers, and by...

Project SEARCH UK--Evaluating Its Employment Outcomes

Science.gov (United States)

Kaehne, Axel

2016-01-01

Background: The study reports the findings of an evaluation of Project SEARCH UK. The programme develops internships for young people with intellectual disabilities who are about to leave school or college. The aim of the evaluation was to investigate at what rate Project SEARCH provided employment opportunities to participants. Methods: The…

INTEGRAL BENCHMARKS AVAILABLE THROUGH THE INTERNATIONAL REACTOR PHYSICS EXPERIMENT EVALUATION PROJECT AND THE INTERNATIONAL CRITICALITY SAFETY BENCHMARK EVALUATION PROJECT

Energy Technology Data Exchange (ETDEWEB)

J. Blair Briggs; Lori Scott; Enrico Sartori; Yolanda Rugama

2008-09-01

Interest in high-quality integral benchmark data is increasing as efforts to quantify and reduce calculational uncertainties accelerate to meet the demands of next generation reactor and advanced fuel cycle concepts. The International Reactor Physics Experiment Evaluation Project (IRPhEP) and the International Criticality Safety Benchmark Evaluation Project (ICSBEP) continue to expand their efforts and broaden their scope to identify, evaluate, and provide integral benchmark data for method and data validation. Benchmark model specifications provided by these two projects are used heavily by the international reactor physics, nuclear data, and criticality safety communities. Thus far, 14 countries have contributed to the IRPhEP, and 20 have contributed to the ICSBEP. The status of the IRPhEP and ICSBEP is discussed in this paper, and the future of the two projects is outlined and discussed. Selected benchmarks that have been added to the IRPhEP and ICSBEP handbooks since PHYSOR’06 are highlighted, and the future of the two projects is discussed.

INTEGRAL BENCHMARKS AVAILABLE THROUGH THE INTERNATIONAL REACTOR PHYSICS EXPERIMENT EVALUATION PROJECT AND THE INTERNATIONAL CRITICALITY SAFETY BENCHMARK EVALUATION PROJECT

International Nuclear Information System (INIS)

J. Blair Briggs; Lori Scott; Enrico Sartori; Yolanda Rugama

2008-01-01

Interest in high-quality integral benchmark data is increasing as efforts to quantify and reduce calculational uncertainties accelerate to meet the demands of next generation reactor and advanced fuel cycle concepts. The International Reactor Physics Experiment Evaluation Project (IRPhEP) and the International Criticality Safety Benchmark Evaluation Project (ICSBEP) continue to expand their efforts and broaden their scope to identify, evaluate, and provide integral benchmark data for method and data validation. Benchmark model specifications provided by these two projects are used heavily by the international reactor physics, nuclear data, and criticality safety communities. Thus far, 14 countries have contributed to the IRPhEP, and 20 have contributed to the ICSBEP. The status of the IRPhEP and ICSBEP is discussed in this paper, and the future of the two projects is outlined and discussed. Selected benchmarks that have been added to the IRPhEP and ICSBEP handbooks since PHYSOR-06 are highlighted, and the future of the two projects is discussed

Synthetic vitreous fibers: a review toxicology, epidemiology and regulations.

Science.gov (United States)

Bernstein, David M

2007-01-01

This review addresses the characteristics which differentiate synthetic vitreous fibers (SVFs, e.g., fiber glass, stonewool, slagwool, refractory ceramic fibers, etc.), how these influence the potential biopersistence and toxicity, the most recent epidemiological results and the integration of these findings into the health and safety regulations in Europe and the United States. Also presented is the historical basis for the European classification directive. The use and equivalence of the chronic inhalation toxicology and chronic intraperitoneal injection studies in laboratory rodents for evaluation of fiber toxicology is assessed as well as the impact of dose selection and design on the validity of the study. While synthetic vitreous fibers can span a wide range of chemistries, recognition and understanding of the importance of biopersistence (ability to persist in the lung) in fiber toxicity has led to the development of more and more biosoluble fibers (that break down rapidly in the lung). Still, the epidemiological data available which are largely based upon the use of fibers in past decades, indicate that the SVF do not present a human health risk at current exposure levels. The animal toxicology and biopersistence data provide a coherent basis for understanding and evaluating the parameters which affect SVF toxicity. The current regulations are based upon an extensive knowledge base of chronic studies in laboratory rodents which confirm the relationship between chronic adverse effects and the biopersistence of the longer fibers that can not be fully phagocytised and efficiently cleared from the lung. The amorphous structure of synthetic vitreous fibers facilitates designing fibers in use today with low biopersistence. Both the epidemiological data and the animal studies database provide strong assurance that there is little if any health risk associated with the use of SVFs of low biopersistence. IARC (2001) reclassified these fibers from Category 2b to

The inhalation toxicology of p-aramid fibrils.

Science.gov (United States)

Donaldson, Ken

2009-01-01

The pandemic of lung disease caused by asbestos has cast suspicion on any industrial fibrous material that can become airborne in respirable form in workplaces, such that the respirable fibres might be inhaled. Fibre toxicology arose as a sub-specialty of particle toxicology to address the specialised nature of fibre effects and has evolved substantially in the last 25 years. It has yielded valuable information on the dosimetry, structure-activity relationships, and mechanism involved in toxicological effects of a range of fibrous materials, including asbestos, other naturally occurring fibrous materials, and synthetic vitreous fibres. A robust structure/activity paradigm has emerged from this research that highlights fibre length, thinness, and biopersistence as major factors in determining the pathogenicity of a fibre. p-Aramid is a manufactured fibre composed of synthetic polyamide (poly paraphenylene terephthalamide) manufactured on a commercial scale since 1970 by polymerisation and spinning steps. It is used as an advanced composite and in fabrics, body armour, friction materials, etc. Respirable fibrils of p-aramid can be released from the fibres during working and can become airborne. A considerable body of research has been carried out into the hazard posed by inhaled p-aramid fibrils, and this review considers this body of literature and summarises the state-of-the-science in the toxicology of p-aramid fibrils in the light of the existing overarching fibre toxicology paradigm. The peer-reviewed studies demonstrate that p-aramid fibrils can be long and thin but that the fibrils are not biopersistent. Residence in the milieu of the lungs leads to fibre shortening, allowing efficient and complete phagocytosis and effective clearance. Subsequently the p-aramid hazard is low, and this is confirmed in animal studies. The mechanism of shortening of p-aramid fibrils is not well-understood, but may involve the action of macrophages on the fibrils following

A desk evaluation review of project RAF/4/004 nuclear instruments maintenance. Project desk evaluation

Energy Technology Data Exchange (ETDEWEB)

NONE

1994-04-15

A Project Desk Evaluation (PDE) is an intensive review process, using agreed guidelines, of the design, implementation, and the outputs of a project. This project was originally intended for six selected countries in Africa, namely, Algeria, Egypt, Ghana, Libya, Zaire and Zambia. Ethiopia and Tanzania joined in 1993 and it has now been extended to two other countries, Madagascar and Sudan. This is a step forward towards developing the infrastructure for nuclear instrumentation and maintenance is as many countries in Africa as require this service. A project summary along with financial data and recommendations for improvements are given. A table where total assistance provided to ten selected african countries is included.

A desk evaluation review of project RAF/4/004 nuclear instruments maintenance. Project desk evaluation

International Nuclear Information System (INIS)

1994-01-01

A Project Desk Evaluation (PDE) is an intensive review process, using agreed guidelines, of the design, implementation, and the outputs of a project. This project was originally intended for six selected countries in Africa, namely, Algeria, Egypt, Ghana, Libya, Zaire and Zambia. Ethiopia and Tanzania joined in 1993 and it has now been extended to two other countries, Madagascar and Sudan. This is a step forward towards developing the infrastructure for nuclear instrumentation and maintenance is as many countries in Africa as require this service. A project summary along with financial data and recommendations for improvements are given. A table where total assistance provided to ten selected african countries is included

History of the Journal of the American College of Toxicology.

Science.gov (United States)

Christian, Mildred S

2004-01-01

This companion article to the History of the American College of Toxicology also is written in celebration of the 25th Anniversary of the American College of Toxicology (ACT). It relates how the official journal of the College evolved from a privately owned publication, the Journal of Environmental Pathology and Toxicology (JEPT), into publications owned and managed by the College and its Board, for the first 17 years as the Journal of the American College of Toxicology (JACT) and currently as The International Journal of Toxicology (IJT). It relates how the first journal focused on toxicological studies, potential cancer causes and concerns associated with environmental contamination and chemical exposure safety issues. It tells how this journal was replaced by one more broadly based that addressed multiple industries and regulatory approaches, accepted previously unpublishable "no-effect" studies, so important in eliminating unwarranted animal use, and provided review articles, rather than only original research. It also described how the JACT evolved into an international journal finally recognized for its quality reviews and peer-reviewed research. Each of the three journals that represented the College is described, as well as interesting events associated with their development and publication, including the activities and contributions of the first four editors in chief, Drs. Myron A. Mehlman, Mildred S. Christian, Robert M. Diener and Harihara Mehendale.

Aggregated Computational Toxicology Online Resource

Data.gov (United States)

U.S. Environmental Protection Agency — Aggregated Computational Toxicology Online Resource (AcTOR) is EPA's online aggregator of all the public sources of chemical toxicity data. ACToR aggregates data...

Criticality safety benchmark evaluation project: Recovering the past

Energy Technology Data Exchange (ETDEWEB)

Trumble, E.F.

1997-06-01

A very brief summary of the Criticality Safety Benchmark Evaluation Project of the Westinghouse Savannah River Company is provided in this paper. The purpose of the project is to provide a source of evaluated criticality safety experiments in an easily usable format. Another project goal is to search for any experiments that may have been lost or contain discrepancies, and to determine if they can be used. Results of evaluated experiments are being published as US DOE handbooks.

Renal studies in safety pharmacology and toxicology: A survey conducted in the top 15 pharmaceutical companies.

Science.gov (United States)

Benjamin, Amanda; Gallacher, David J; Greiter-Wilke, Andrea; Guillon, Jean-Michel; Kasai, Cheiko; Ledieu, David; Levesque, Paul; Prelle, Katja; Ratcliffe, Sian; Sannajust, Frederick; Valentin, Jean-Pierre

2015-01-01

With the recent development of more sensitive biomarkers to assess kidney injury preclinically, a survey was designed i) to investigate what strategies are used to investigate renal toxicity in both ICH S7A compliant Safety Pharmacology (SP) studies after a single dose of a compound and within repeat-dose toxicity studies by large pharmaceutical companies today; ii) to understand whether renal SP studies have impact or utility in drug development and/or if it may be more appropriate to assess renal effects after multiple doses of compounds; iii) to ascertain how much mechanistic work is performed by the top 15 largest pharmaceutical companies (as determined by R&D revenue size); iv) to gain an insight into the impact of the validation of DIKI biomarkers and their introduction in the safety evaluation paradigm; and v) to understand the impact of renal/urinary safety study data on progression of projects. Two short anonymous surveys were submitted to SP leaders of the top 15 pharmaceutical companies, as defined by 2012 R&D portfolio size. Fourteen multiple choice questions were designed to explore the strategies used to investigate renal effects in both ICH S7A compliant SP studies and within toxicology studies. A 67% and 60% response rate was obtained in the first and second surveys, respectively. Nine out of ten respondent companies conduct renal excretory measurements (eg. urine analysis) in toxicology studies whereas only five out of ten conduct specific renal SP studies; and all of those 5 also conduct the renal excretory measurements in toxicology studies. These companies measure and/or calculate a variety of parameters as part of these studies, and also on a case by case basis include regulatory qualified and non-qualified DIKI biomarkers. Finally, only one company has used renal/urinary functional data alone to stop a project, whereas the majority of respondents combine renal data with other target organ assessments to form an integrated decision-making set

Mizunami Underground Research Laboratory project. A project on research stage of investigating prediction from ground surface. Project report at fiscal year of 2000 to 2004

International Nuclear Information System (INIS)

2000-04-01

This was a detailed plan after fiscal year 2000 on the first stage of the Research stage at investigating prediction from ground surface' in three researches carried out at the Mizunami Underground Research Laboratory (MIU) according to the 'Basic plan on research of underground science at MIU', based on progress of investigation and research before fiscal year 1999. This project contains following three items as its general targets; establishment of general investigating techniques for geological environment, collection of informations on deep underground environment, and development on foundation of engineering technology at super-deep underground. And, targets at investigating prediction stage from ground surface contain acquisition of geological environment data through investigations from ground surface to predict changes of the environment accompanied with underground geological environment and construction of experimental tunnel, to determine evaluating method on prediction results, and to determine plannings of an investigating stage accompanied with excavation of the tunnel by carrying out detail design of the tunnel. Here were introduced about results and problems on the investigation of the first phase, the integration of investigating results, and the investigation and researches on geology/geological structure, hydrology and geochemistry of groundwater, mechanical properties of rocks, and the mass transfer. (G.K.)

Good cell culture practices &in vitro toxicology.

Science.gov (United States)

Eskes, Chantra; Boström, Ann-Charlotte; Bowe, Gerhard; Coecke, Sandra; Hartung, Thomas; Hendriks, Giel; Pamies, David; Piton, Alain; Rovida, Costanza

2017-12-01

Good Cell Culture Practices (GCCP) is of high relevance to in vitro toxicology. The European Society of Toxicology In Vitro (ESTIV), the Center for Alternatives for Animal Testing (CAAT) and the In Vitro Toxicology Industrial Platform (IVTIP) joined forces to address by means of an ESTIV 2016 pre-congress session the different aspects and applications of GCCP. The covered aspects comprised the current status of the OECD guidance document on Good In Vitro Method Practices, the importance of quality assurance for new technological advances in in vitro toxicology including stem cells, and the optimized implementation of Good Manufacturing Practices and Good Laboratory Practices for regulatory testing purposes. General discussions raised the duality related to the difficulties in implementing GCCP in an academic innovative research framework on one hand, and on the other hand, the need for such GCCP principles in order to ensure reproducibility and robustness of in vitro test methods for toxicity testing. Indeed, if good cell culture principles are critical to take into consideration for all uses of in vitro test methods for toxicity testing, the level of application of such principles may depend on the stage of development of the test method as well as on the applications of the test methods, i.e., academic innovative research vs. regulatory standardized test method. Copyright © 2017 Elsevier Ltd. All rights reserved.

DIGGING DEEPER INTO DEEP DATA: MOLECULAR DOCKING AS A HYPOTHESIS-DRIVEN BIOPHYSICAL INTERROGATION SYSTEM IN COMPUTATIONAL TOXICOLOGY.

Science.gov (United States)

Developing and evaluating prediactive strategies to elucidate the mode of biological activity of environmental chemicals is a major objective of the concerted efforts of the US-EPA's computational toxicology program.

Exploring new pharmacology and toxicological screening and safety evaluation of one widely used formulation of Nidrakar Bati from South Asia region.

Science.gov (United States)

Zaman, Afria; Khan, Md Shamsuddin Sultan; Akter, Lucky; Syeed, Sharif Hossain; Akter, Jakia; Al Mamun, Abdullah; Alam, Md Ershad; Habib, Md Ahsan; Jalil, Md Abdul

2015-04-16

Nidrakar Bati (NKB) is an herbal remedy consisted with seven medicinal herbs widely used to cure Somnifacient (sleeping aid) in South Asia as Ayurvedic medicinal system. In the present study, pharmacological and toxicological effects of this medicine was investigated in mice to validate the safety and efficacy of the herb. Organic solvent extracts NKB were prepared using maceration method. Effect of extracts on the central nervous system was evaluated using hypnotic activity assay. Effect of the extracts on metabolic activity, assessing involvement of thyroid was conducted using hypoxia test. analgesic and anti-inflammatory activities were assessed in mice using acetic acid induced writhing, formalin induced paw edema, xylene induced ear edema assays. Anxiolytic activity was performed using plus maze, climbing out and forced swimming tests. Effect of the extracts on psychopharmacological effect was carried out using locomotor activity tests (open field, Hole-board and Hole-cross tests). Neuropharmacological effect of the extracts was performed using motor coordination (rotarod test). Toxicological potential of the extract was evaluated using gastro-intestinal activity (gastric emptying and gastrointestinal motility tests). The studied formulation reduced the CNS stimulant effects dose independently. In the hypoxia test, only a dose of 100 mg/kg of NKB decreased the survival time. Orally administration of the NKB (200 and 400 mg/kg) produced significant inhibition (P acetic acid-induced writhing in mice and suppressed xylene induced ear edema and formalin-induced licking response of animals in both phases of the test. NKB showed locomotor activity (p < 0.05) both in higher and lower doses (100 and 400 mg/kg). NKB increased the total ambulation dose dependently (p < 0.05). NKB, at all tested doses (100, 200 and 400 mg/kg) increased some locomotion activity parameters (ambulation, head dipping and emotional defecation) in hole board test. At higher doses (200 and 400

The minipig as a platform for new technologies in toxicology

DEFF Research Database (Denmark)

Forster, Roy; Ancian, Philippe; Fredholm, Merete

2010-01-01

The potential of the minipig as a platform for future developments in genomics, high density biology, transgenic technology, in vitro toxicology and related emerging technologies was reviewed. Commercial interests in the pig as an agricultural production species have driven scientific progress...... pigs and humans suggest that minipigs will be useful for the testing of biotechnology products (and possibly for in silico toxicology) and (iii) the minipig is the only non-rodent toxicology model where transgenic animals can be readily generated, and reproductive technologies are well developed...... in the pig. These properties should also make the minipig an interesting model for the testing of biotechnology products. These factors all support the idea that the minipig is well placed to meet the challenges of the emerging technologies and the toxicology of the future; it also seems likely...

Workforce development and effective evaluation of projects.

Science.gov (United States)

Dickerson, Claire; Green, Tess; Blass, Eddie

The success of a project or programme is typically determined in relation to outputs. However, there is a commitment among UK public services to spending public funds efficiently and on activities that provide the greatest benefit to society. Skills for Health recognised the need for a tool to manage the complex process of evaluating project benefits. An integrated evaluation framework was developed to help practitioners identify, describe, measure and evaluate the benefits of workforce development projects. Practitioners tested the framework on projects within three NHS trusts and provided valuable feedback to support its development. The prospective approach taken to identify benefits and collect baseline data to support evaluation was positively received and the clarity and completeness of the framework, as well as the relevance of the questions, were commended. Users reported that the framework was difficult to complete; an online version could be developed, which might help to improve usability. Effective implementation of this approach will depend on the quality and usability of the framework, the willingness of organisations to implement it, and the presence or establishment of an effective change management culture.

Toxicological and performance aspects of oxygenated motor vehicle fuels

National Research Council Canada - National Science Library

National Research Council Staff; Commission on Life Sciences; Division on Earth and Life Studies; National Research Council; National Academy of Sciences

... COMMITTEE ON TOXICOLOGICAL PERFORMANCE ASPECTS OXYGENATED MOTOR VEHICLE FUELS ENVIRONMENTAL STUDIES TOXICOLOGY COMMISSION LIFE SCIENCES NATIONAL RESEARCH COUNCIL AND OF BOARD ON AND ON NATIONAL ACADEMY PRESS Washington, D.C. 1996 i Copyrightoriginal retained, the be not from cannot book, paper original however, for version formatting, authoritative the t...

Equitable Financial Evaluation Method for Public-Private Partnership Projects

Institute of Scientific and Technical Information of China (English)

KE Yongjian; LIU Xinping; WANG Shouqing

2008-01-01

The feasibility study of a public-private partnership (PPP) project is regarded as one of the critical factors for successful implementation,but unfortunately the common financial evaluation methods currently used only represent the benefits of the private sector.There is,therefore,an urgent need to develop an equitable financial evaluation method for PPP projects.This paper presents a comprehensive literature review that examines international practices.An equitable financial evaluation method was then developed taking into account the inherent characteristics of PPP projects using six separate indicators and Monte Carlo simulations.The result for a bridge project in Romania shows that the method combines the viewpoints of all the relevant stakeholders to achieve an equitable financial evaluation of PPP projects.

IRIS Toxicological Review of Trichloroacetic Acid (Tca) (Final ...

Science.gov (United States)

EPA has finalized the Toxicological Review of Trichloroacetic Acid: in support of the Integrated Risk Information System (IRIS). Now final, this assessment may be used by EPA’s program and regional offices to inform decisions to protect human health. The draft Toxicological Review of Trichloroacetic Acid provides scientific support and rationale for the hazard identification and dose-response assessment pertaining to chronic exposure to trichloroacetic acid.

Pharmacological and Toxicological Profile of Harmane-β-Carboline Alkaloid: Friend or Foe.

Science.gov (United States)

Khan, Haroon; Patel, Seema; Kamal, Mohammad A

2017-01-01

The plant secondary metabolites have an outstanding therapeutic potential and success over the years. In fact, it is the foundation of numerous clinically used drugs. Similarly, these is a general perception that these products are inherent safety. However, such products might have toxic/unwanted lethal effects therefore, along with biological relevance, toxicological evaluation is equally important for clinical applications. Therefore, harmane- β-carboline alkaloid was investigated for both therapeutic and toxicological potential. The literature related to the therapeutic/toxicological effects of the alkaloid was searched using various scientific data bases including Google, ScienceDirect, PubMed, SpringerLink, ASC. The peer reviewed articles were only selected. The harmane-β-carboline alkaloid has shown several pharmacological activities such as antianxiety, antidepressant, antiplatelet, antidiabetic, acetylcholinesterase and myeloperoxidase inhibition, antioxidant, antiparasitic, hypotensive, morphine withdrawal syndrome alleviation, and antinociceptive effects. On the other hand, it exhibited tremorogenic effect, for a symptom of Parkinson's disease. Adverse effect of the alkaloid on learning and memory have also been observed. All together, it is, concluded in this review that harmane elicited marked pharmacological effects but simultaneously, it possessed some serious side effects that could be the primary hurdle in the way of its clinical testing. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Development of Procedures for Assessing the Impact of Vocational Education Research and Development on Vocational Education (Project IMPACT). Volume 8--A Field Study of Predicting Impact of Research and Development Projects in Vocational and Technical Education.

Science.gov (United States)

Malhorta, Man Mohanlal

As part of Project IMPACT's effort to identify and develop procedures for complying with the impact requirements of Public Law 94-482, a field study was conducted to identify and validate variables and their order of importance in predicting and evaluating impact of research and development (R&D) projects in vocational and technical education.…

MicroRNAs and toxicology: A love marriage

Directory of Open Access Journals (Sweden)

Elisabeth Schraml

Full Text Available With the dawn of personalized medicine, secreted microRNAs (miRNAs have come into the very focus of biomarker development for various diseases. MiRNAs fulfil key requirements of diagnostic tools such as i non or minimally invasive accessibility, ii robust, standardized and non-expensive quantitative analysis, iii rapid turnaround of the test result and iv most importantly because they provide a comprehensive snapshot of the ongoing physiologic processes in cells and tissues that package and release miRNAs into cell-free space. These characteristics have also established circulating miRNAs as promising biomarker candidates for toxicological studies, where they are used as biomarkers of drug-, or chemical-induced tissue injury for safety assessment. The tissue-specificity and early release of circulating miRNAs upon tissue injury, when damage is still reversible, are main factors for their clinical utility in toxicology. Here we summarize in brief, current knowledge of this field. Keywords: microRNAs, Biomarker, Toxicology, Minimal-invasive, DILI

Systems Toxicology of Male Reproductive Development ...

Science.gov (United States)

Adverse trends in male reproductive health have been reported for increased rates of testicular germ cell tumor, low semen quality, cryptorchidism, and hypospadias. An association with prenatal environmental exposure has been inferred from human and animal studies underlying male reproductive developmental defects. The present study established the links between environmental chemicals, molecular targets, and adverse outcomes using U.S. EPA animal study (ToxRefDB) and high-throughput screening (ToxCast) databases. This systems-based approach revealed a phenotypic hierarchy across 63 chemicals and a pleiotropic in vitro bioactivity profile. Although estrogenic and anti-androgenic activities have been extensively studied in male reproductive developmental toxicity, the present study showed these receptor targets to be only a subset of the potential landscape of molecular targets. A variety of chemical (e.g. phthalates, conazoles, carbamates, and phenol compounds) and bioactivity (e.g. nuclear receptors, vascular remodeling proteins, and cytochrome-P450 reductases) clusters further suggested multiple pathways leading to the adverse outcomes. This points to the need for multi-scale systems models to predict whether the occurrence of one adverse outcome may predict the risk of another. Imbalances in androgen and estrogen signaling have been a general focus in male reproductive toxicology research. While a number of recent studies have demonstrated that both hormonal

Program Evaluation - Automotive Lightweighting Materials Program Research and Development Projects Assessment of Benefits - Case Studies No. 2

Energy Technology Data Exchange (ETDEWEB)

Das, S.

2003-01-23

This report is the second of a series of studies to evaluate research and development (R&D) projects funded by the Automotive Lightweighting Materials (ALM) Program of the Office of Advanced Automotive Technologies (OAAT) of the U.S. Department of Energy (DOE). The objectives of the program evaluation are to assess short-run outputs and long-run outcomes that may be attributable to the ALM R&D projects. The ALM program focuses on the development and validation of advanced technologies that significantly reduce automotive vehicle body and chassis weight without compromising other attributes such as safety, performance, recyclability, and cost. Funded projects range from fundamental materials science research to applied research in production environments. Collaborators on these projects include national laboratories, universities, and private sector firms, such as leading automobile manufacturers and their suppliers. Three ALM R&D projects were chosen for this evaluation: Design and Product Optimization for Cast Light Metals, Durability of Lightweight Composite Structures, and Rapid Tooling for Functional Prototyping of Metal Mold Processes. These projects were chosen because they have already been completed. The first project resulted in development of a comprehensive cast light metal property database, an automotive application design guide, computerized predictive models, process monitoring sensors, and quality assurance methods. The second project, the durability of lightweight composite structures, produced durability-based design criteria documents, predictive models for creep deformation, and minimum test requirements and suggested test methods for establishing durability properties and characteristics of random glass-fiber composites for automotive structural composites. The durability project supported Focal Project II, a validation activity that demonstrates ALM program goals and reduces the lead time for bringing new technology into the marketplace. Focal

Effects of iron oxide contrast agent in combination with various transfection agents during mesenchymal stem cells labelling: An in vitro toxicological evaluation.

Science.gov (United States)

Mishra, Sushanta Kumar; Khushu, Subash; Gangenahalli, Gurudutta

2018-03-22

The use of iron oxide nanoparticles for different biomedical applications, hold immense promise to develop negative tissue contrast in magnetic resonance imaging (MRI). Previously, we have optimized the labelling of mesenchymal stem cells (MSCs) with iron oxide nanoparticles complexed to different transfection agents like poly-l-lysine (IO-PLL) and protamine sulfate (Fe-Pro) on the basis of relaxation behaviour and its biological expressions. However, there is a distinct need to investigate the biocompatibility and biosafety concerns coupled with its cytotoxicity and genotoxicity. This study was prepared to evaluate the viability of cells, generation of ROS, changes in actin cytoskeleton, investigation of cell death, level of GSH and TAC, activities of SOD and GPx, and stability of DNA in MSCs after labelling. Results demonstrated a marginal alteration in toxicological parameters like ROS generation, cell length, actin cytoskeleton, total apoptosis and DNA damage was detected after stem cell labelling. Insignificant depletion of GSH and SOD level, and increase in GPx and TAC level in MSCs were measured after labelling with IO-PLL and Fe-Pro complexes, which later on recovered and normalized to its baseline. This MSCs labelling could provide a reference guideline for toxicological analysis and relaxometry based in vivo MRI detection. Copyright © 2018. Published by Elsevier Ltd.

RPERT: Repetitive-Projects Evaluation and Review Technique

Directory of Open Access Journals (Sweden)

Remon Fayek Aziz

2014-03-01

Full Text Available Estimating expected completion probability of any repetitive construction project with a specified/certain duration including repetitive identical activities by using program evaluation and review technique is the most essential part in construction areas since the activities were had optimistic, most likely and pessimistic durations. This paper focuses on the calculation of expected completion probability of any repetitive construction project within a specified/certain duration (contract duration by using Line Of Balance technique (LOB in case of single or multiple number of crews integrated with Program Evaluation and Review Technique (PERT. Repetitive-Projects Evaluation and Review Technique (RPERT, which is a simplified software, will generate the expected project completion probability of a specified/certain duration (contract duration. RPERT software is designed by java programming code system to provide a number of new and unique capabilities, including: (1 Viewing the expected project completion probability according to a set of specified durations per each identical activity (optimistic time, most likely time, and pessimistic time in the analyzed project; (2 Providing seamless integration with available project time calculations. In order to provide the aforementioned capabilities of RPERT, the system is implemented and developed in four main modules: (1 A user interface module; (2 A database module; (3 A running module; and (4 A processing module. At the end, an illustrative example will be presented to demonstrate and verify the applications of proposed software (RPERT, by using probabilistic calculations for repetitive construction projects.

Evaluation of the MiKlip decadal prediction system using satellite based cloud products

Directory of Open Access Journals (Sweden)

Thomas Spangehl

2016-12-01

Full Text Available The decadal hindcast simulations performed for the Mittelfristige Klimaprognosen (MiKlip project are evaluated using satellite-retrieved cloud parameters from the CM SAF cLoud, Albedo and RAdiation dataset from AVHRR data (CLARA-A1 provided by the EUMETSAT Satellite Application Facility on Climate Monitoring (CM SAF and from the International Satellite Cloud Climatology Project (ISCCP. The forecast quality of two sets of hindcasts, Baseline-1-LR and Baseline-0, which use differing initialisations, is assessed. Basic evaluation focuses on multi-year ensemble mean fields and cloud-type histograms utilizing satellite simulator output. Additionally, ensemble evaluation employing analysis of variance (ANOVA, analysis rank histograms (ARH and a deterministic correlation score is performed. Satellite simulator output is available for a subset of the full hindcast ensembles only. Therefore, the raw model cloud cover is complementary used. The new Baseline-1-LR hindcasts are closer to satellite data with respect to the simulated tropical/subtropical mean cloud cover pattern than the reference hindcasts (Baseline-0 emphasizing improvements of the new MiKlip initialisation procedure. A slightly overestimated occurrence rate of optically thick cloud-types is analysed for different experiments including hindcasts and simulations using realistic sea surface boundaries according to the Atmospheric Model Intercomparison Project (AMIP. By contrast, the evaluation of cirrus and cirrostratus clouds is complicated by observational based uncertainties. Time series of the 3-year mean total cloud cover averaged over the tropical warm pool (TWP region show some correlation with the CLARA-A1 cloud fractional cover. Moreover, ensemble evaluation of the Baseline-1-LR hindcasts reveals potential predictability of the 2–5 lead year averaged total cloud cover for a large part of this region when regarding the full observational period. However, the hindcasts show only

Opportunity for Collaboration Between Radiation Injury Treatment Network Centers and Medical Toxicology Specialists.

Science.gov (United States)

Davlantes, Elizabeth; Shartar, Samuel; Venero, Jennifer; Steck, Alaina; Langston, Amelia; Kazzi, Ziad N

2017-08-01

The Radiation Injury Treatment Network (RITN) comprises >50 centers across the United States that are poised to care for victims of a radiation emergency. The network is organized around bone marrow transplant centers because these facilities excel in both radiation medicine and the care of patients with severe bone marrow depression. A radiation emergency may cause not only irradiation from an external source but also internal contamination with radioactive material. Because medical toxicologists are trained in radiation injury management and have expertise in the management of internal contamination, RITN centers may benefit from partnerships with medical toxicology resources, which may be located at academic medical centers, hospital inpatient clinical services, outpatient clinics, or poison control centers. We determined the locations of existing RITN centers and assessed their proximity to various medical toxicology resources, including medical toxicology fellowship programs, inpatient toxicology services, outpatient toxicology clinics, and poison control centers. Data were derived from publicly available Internet sources in March 2015. The majority of RITN centers do not have a medical toxicology fellowship, an inpatient toxicology service, or an outpatient toxicology clinic within the same institution. Fifty-seven percent of RITN centers have at least one of these resources located in the same city, however, and 73% of centers have at least one of these resources or a poison control center within the same city. Ninety-five percent of RITN centers have at least one medical toxicology resource within the state. Most RITN centers are located in the same city as at least one medical toxicology resource. Establishing relationships between RITN centers and medical toxicologists needs to be explored further.

Zebrafish neurotransmitter systems as potential pharmacological and toxicological targets.

Science.gov (United States)

Rico, E P; Rosemberg, D B; Seibt, K J; Capiotti, K M; Da Silva, R S; Bonan, C D

2011-01-01

Recent advances in neurobiology have emphasized the study of brain structure and function and its association with numerous pathological and toxicological events. Neurotransmitters are substances that relay, amplify, and modulate electrical signals between neurons and other cells. Neurotransmitter signaling mediates rapid intercellular communication by interacting with cell surface receptors, activating second messenger systems and regulating the activity of ion channels. Changes in the functional balance of neurotransmitters have been implicated in the failure of central nervous system function. In addition, abnormalities in neurotransmitter production or functioning can be induced by several toxicological compounds, many of which are found in the environment. The zebrafish has been increasingly used as an animal model for biomedical research, primarily due to its genetic tractability and ease of maintenance. These features make this species a versatile tool for pre-clinical drug discovery and toxicological investigations. Here, we present a review regarding the role of different excitatory and inhibitory neurotransmitter systems in zebrafish, such as dopaminergic, serotoninergic, cholinergic, purinergic, histaminergic, nitrergic, glutamatergic, glycinergic, and GABAergic systems, and emphasizing their features as pharmacological and toxicological targets. The increase in the global knowledge of neurotransmitter systems in zebrafish and the elucidation of their pharmacological and toxicological aspects may lead to new strategies and appropriate research priorities to offer insights for biomedical and environmental research. Copyright © 2011 Elsevier Inc. All rights reserved.

Historical perspectives on cadmium toxicology

International Nuclear Information System (INIS)

Nordberg, Gunnar F.

2009-01-01

The first health effects of cadmium (Cd) were reported already in 1858. Respiratory and gastrointestinal symptoms occurred among persons using Cd-containing polishing agent. The first experimental toxicological studies are from 1919. Bone effects and proteinuria in humans were reported in the 1940's. After World War II, a bone disease with fractures and severe pain, the itai-itai disease, a form of Cd-induced renal osteomalacia, was identified in Japan. Subsequently, the toxicokinetics and toxicodynamics of Cd were described including its binding to the protein metallothionein. International warnings of health risks from Cd-pollution were issued in the 1970's. Reproductive and carcinogenic effects were studied at an early stage, but a quantitative assessment of these effects in humans is still subject to considerable uncertainty. The World Health Organization in its International Program on Chemical Safety, WHO/IPCS (1992) (Cadmium. Environmental Health Criteria Document 134, IPCS. WHO, Geneva, 1-280.) identified renal dysfunction as the critical effect and a crude quantitative evaluation was presented. In the 1990's and 2000 several epidemiological studies have reported adverse health effects, sometimes at low environmental exposures to Cd, in population groups in Japan, China, Europe and USA (reviewed in other contributions to the present volume). The early identification of an important role of metallothionein in cadmium toxicology formed the basis for recent studies using biomarkers of susceptibility to development of Cd-related renal dysfunction such as gene expression of metallothionein in peripheral lymphocytes and autoantibodies against metallothionein in blood plasma. Findings in these studies indicate that very low exposure levels to cadmium may give rise to renal dysfunction among sensitive subgroups of human populations such as persons with diabetes.

Subsite Awareness in Neuropathology Evaluation of National Toxicology Program (NTP) Studies: A Review of Select Neuroanatomical Structures with their Functional Significance in Rodents

Science.gov (United States)

Rao, Deepa B.; Little, Peter B.; Sills, Robert

2013-01-01

This review manuscript is designed to serve as an introductory guide in neuroanatomy for toxicologic pathologists evaluating general toxicity studies. The manuscript provides an overview of approximately 50 neuroanatomical subsites and their functional significance across seven coronal sections of the brain. Also reviewed are three sections of the spinal cord, cranial and peripheral nerves (trigeminal and sciatic respectively), and intestinal autonomic ganglia. The review is limited to the evaluation of hematoxylin and eosin (H&E) stained tissue sections, as light microscopic evaluation of these sections is an integral part of the first-tier toxicity screening of environmental chemicals, drugs, and other agents. Prominent neuroanatomical sites associated with major neurological disorders are noted. This guide, when used in conjunction with detailed neuroanatomic atlases may aid in an understanding of the significance of functional neuroanatomy, thereby improving the characterization of neurotoxicity in general toxicity and safety evaluation studies. PMID:24135464

Operational Toxicology Research

Science.gov (United States)

2006-08-01

techniques for perchlorate in water, groundwater, soil and biological matrices such as blood, urine, milk . thyroid and other tissues required for...toxicity when they are inhaled or ingested and they are irritating to the skin and mucus membranes (Committee on Toxicology, 1996). When compared to...the data collected. Develop analytical techniques for perchlorate in water, groundwater, soil, and biological matrices such as blood, urine, milk

Traffic Predictive Control: Case Study and Evaluation

Science.gov (United States)

2017-06-26

This project developed a quantile regression method for predicting future traffic flow at a signalized intersection by combining both historical and real-time data. The algorithm exploits nonlinear correlations in historical measurements and efficien...

Evaluation of cloud prediction and determination of critical relative humidity for a mesoscale numerical weather prediction model

Energy Technology Data Exchange (ETDEWEB)

Seaman, N.L.; Guo, Z.; Ackerman, T.P. [Pennsylvania State Univ., University Park, PA (United States)

1996-04-01

Predictions of cloud occurrence and vertical location from the Pennsylvannia State University/National Center for Atmospheric Research nonhydrostatic mesoscale model (MM5) were evaluated statistically using cloud observations obtained at Coffeyville, Kansas, as part of the Second International satellite Cloud Climatology Project Regional Experiment campaign. Seventeen cases were selected for simulation during a November-December 1991 field study. MM5 was used to produce two sets of 36-km simulations, one with and one without four-dimensional data assimilation (FDDA), and a set of 12-km simulations without FDDA, but nested within the 36-km FDDA runs.

Rainfall and Extratropical Transition of Tropical Cyclones: Simulation, Prediction, and Projection

Science.gov (United States)

Liu, Maofeng

Rainfall and associated flood hazards are one of the major threats of tropical cyclones (TCs) to coastal and inland regions. The interaction of TCs with extratropical systems can lead to enhanced precipitation over enlarged areas through extratropical transition (ET). To achieve a comprehensive understanding of rainfall and ET associated with TCs, this thesis conducts weather-scale analyses by focusing on individual storms and climate-scale analyses by focusing on seasonal predictability and changing properties of climatology under global warming. The temporal and spatial rainfall evolution of individual storms, including Hurricane Irene (2011), Hurricane Hanna (2008), and Hurricane Sandy (2012), is explored using the Weather Research and Forecast (WRF) model and a variety of hydrometeorological datasets. ET and Orographic mechanism are two key players in the rainfall distribution of Irene over regions experiencing most severe flooding. The change of TC rainfall under global warming is explored with the Forecast-oriented Low Ocean Resolution (FLOR) climate model under representative concentration pathway (RCP) 4.5 scenario. Despite decreased TC frequency, FLOR projects increased landfalling TC rainfall over most regions of eastern United States, highlighting the risk of increased flood hazards. Increased storm rain rate is an important player of increased landfalling TC rainfall. A higher atmospheric resolution version of FLOR (HiFLOR) model projects increased TC rainfall at global scales. The increase of TC intensity and environmental water vapor content scaled by the Clausius-Clapeyron relation are two key factors that explain the projected increase of TC rainfall. Analyses on the simulation, prediction, and projection of the ET activity with FLOR are conducted in the North Atlantic. FLOR model exhibits good skills in simulating many aspects of present-day ET climatology. The 21st-century-projection under RCP4.5 scenario demonstrates the dominant role of ET