Computational Toxicology (S)

EPA Science Inventory

The emerging field of computational toxicology applies mathematical and computer models and molecular biological and chemical approaches to explore both qualitative and quantitative relationships between sources of environmental pollutant exposure and adverse health outcomes. Th...

THE USE OF STEM CELLS FOR TOXICOLOGY STUDIES AND RISK ASSESSMENTS

EPA Science Inventory

In general terms, toxicology studies are used in support of risk assessments of adverse health outcomes as a result of exposures to chemical and physical agents. In particular, toxicological data are used to provide information that aids in the assessment of disease outcomes at e...

Chemical effects in biological systems (CEBS) object model for toxicology data, SysTox-OM: design and application.

PubMed

Xirasagar, Sandhya; Gustafson, Scott F; Huang, Cheng-Cheng; Pan, Qinyan; Fostel, Jennifer; Boyer, Paul; Merrick, B Alex; Tomer, Kenneth B; Chan, Denny D; Yost, Kenneth J; Choi, Danielle; Xiao, Nianqing; Stasiewicz, Stanley; Bushel, Pierre; Waters, Michael D

2006-04-01

The CEBS data repository is being developed to promote a systems biology approach to understand the biological effects of environmental stressors. CEBS will house data from multiple gene expression platforms (transcriptomics), protein expression and protein-protein interaction (proteomics), and changes in low molecular weight metabolite levels (metabolomics) aligned by their detailed toxicological context. The system will accommodate extensive complex querying in a user-friendly manner. CEBS will store toxicological contexts including the study design details, treatment protocols, animal characteristics and conventional toxicological endpoints such as histopathology findings and clinical chemistry measures. All of these data types can be integrated in a seamless fashion to enable data query and analysis in a biologically meaningful manner. An object model, the SysBio-OM (Xirasagar et al., 2004) has been designed to facilitate the integration of microarray gene expression, proteomics and metabolomics data in the CEBS database system. We now report SysTox-OM as an open source systems toxicology model designed to integrate toxicological context into gene expression experiments. The SysTox-OM model is comprehensive and leverages other open source efforts, namely, the Standard for Exchange of Nonclinical Data (http://www.cdisc.org/models/send/v2/index.html) which is a data standard for capturing toxicological information for animal studies and Clinical Data Interchange Standards Consortium (http://www.cdisc.org/models/sdtm/index.html) that serves as a standard for the exchange of clinical data. Such standardization increases the accuracy of data mining, interpretation and exchange. The open source SysTox-OM model, which can be implemented on various software platforms, is presented here. A universal modeling language (UML) depiction of the entire SysTox-OM is available at http://cebs.niehs.nih.gov and the Rational Rose object model package is distributed under an open source license that permits unrestricted academic and commercial use and is available at http://cebs.niehs.nih.gov/cebsdownloads. Currently, the public toxicological data in CEBS can be queried via a web application based on the SysTox-OM at http://cebs.niehs.nih.gov xirasagars@saic.com Supplementary data are available at Bioinformatics online.

Computational toxicology using the OpenTox application programming interface and Bioclipse

PubMed Central

2011-01-01

Background Toxicity is a complex phenomenon involving the potential adverse effect on a range of biological functions. Predicting toxicity involves using a combination of experimental data (endpoints) and computational methods to generate a set of predictive models. Such models rely strongly on being able to integrate information from many sources. The required integration of biological and chemical information sources requires, however, a common language to express our knowledge ontologically, and interoperating services to build reliable predictive toxicology applications. Findings This article describes progress in extending the integrative bio- and cheminformatics platform Bioclipse to interoperate with OpenTox, a semantic web framework which supports open data exchange and toxicology model building. The Bioclipse workbench environment enables functionality from OpenTox web services and easy access to OpenTox resources for evaluating toxicity properties of query molecules. Relevant cases and interfaces based on ten neurotoxins are described to demonstrate the capabilities provided to the user. The integration takes advantage of semantic web technologies, thereby providing an open and simplifying communication standard. Additionally, the use of ontologies ensures proper interoperation and reliable integration of toxicity information from both experimental and computational sources. Conclusions A novel computational toxicity assessment platform was generated from integration of two open science platforms related to toxicology: Bioclipse, that combines a rich scriptable and graphical workbench environment for integration of diverse sets of information sources, and OpenTox, a platform for interoperable toxicology data and computational services. The combination provides improved reliability and operability for handling large data sets by the use of the Open Standards from the OpenTox Application Programming Interface. This enables simultaneous access to a variety of distributed predictive toxicology databases, and algorithm and model resources, taking advantage of the Bioclipse workbench handling the technical layers. PMID:22075173

ACToR – Aggregated Computational Toxicology Resource ...

EPA Pesticide Factsheets

ACToR (Aggregated Computational Toxicology Resource) is a collection of databases collated or developed by the US EPA National Center for Computational Toxicology (NCCT). More than 200 sources of publicly available data on environmental chemicals have been brought together and made searchable by chemical name and other identifiers, and by chemical structure. Data includes chemical structure, physico-chemical values, in vitro assay data and in vivo toxicology data. Chemicals include, but are not limited to, high and medium production volume industrial chemicals, pesticides (active and inert ingredients), and potential ground and drinking water contaminants.

A DATABASE FOR TRACKING TOXICOGENOMIC SAMPLES AND PROCEDURES

EPA Science Inventory

Reproductive toxicogenomic studies generate large amounts of toxicological and genomic data. On the toxicology side, a substantial quantity of data accumulates from conventional endpoints such as histology, reproductive physiology and biochemistry. The largest source of genomics...

Toxicology of Biodiesel Combustion products

EPA Science Inventory

1. Introduction The toxicology of combusted biodiesel is an emerging field. Much of the current knowledge about biological responses and health effects stems from studies of exposures to other fuel sources (typically petroleum diesel, gasoline, and wood) incompletely combusted. ...

Computational Toxicology

EPA Science Inventory

‘Computational toxicology’ is a broad term that encompasses all manner of computer-facilitated informatics, data-mining, and modeling endeavors in relation to toxicology, including exposure modeling, physiologically based pharmacokinetic (PBPK) modeling, dose-response modeling, ...

Exposure Science and the US EPA National Center for Computational Toxicology

EPA Science Inventory

The emerging field of computational toxicology applies mathematical and computer models and molecular biological and chemical approaches to explore both qualitative and quantitative relationships between sources of environmental pollutant exposure and adverse health outcomes. The...

Toxicological Evaluation of Realistic Emission Source Aerosols (TERESA): Introduction and overview

PubMed Central

Godleski, John J.; Rohr, Annette C.; Kang, Choong M.; Diaz, Edgar A.; Ruiz, Pablo A.; Koutrakis, Petros

2013-01-01

Determining the health impacts of sources and components of fine particulate matter (PM2.5) is an important scientific goal. PM2.5 is a complex mixture of inorganic and organic constituents that are likely to differ in their potential to cause adverse health outcomes. The Toxicological Evaluation of Realistic Emissions of Source Aerosols (TERESA) study focused on two PM sources—coal-fired power plants and mobile sources—and sought to investigate the toxicological effects of exposure to emissions from these sources. The set of papers published here document the power plant experiments. TERESA attempted to delineate health effects of primary particles, secondary (aged) particles, and mixtures of these with common atmospheric constituents. TERESA involved withdrawal of emissions from the stacks of three coal-fired power plants in the United States. The emissions were aged and atmospherically transformed in a mobile laboratory simulating downwind power plant plume processing. Toxicological evaluations were carried out in laboratory rats exposed to different emission scenarios with extensive exposure characterization. The approach employed in TERESA was ambitious and innovative. Technical challenges included the development of stack sampling technology that prevented condensation of water vapor from the power plant exhaust during sampling and transfer, while minimizing losses of primary particles; development and optimization of a photochemical chamber to provide an aged aerosol for animal exposures; development and evaluation of a denuder system to remove excess gaseous components; and development of a mobile toxicology laboratory. This paper provides an overview of the conceptual framework, design, and methods employed in the study. PMID:21639692

Computational toxicology and in silico modeling of embryogenesis

EPA Science Inventory

High-throughput screening (HTS) is providing a rich source of in vitro data for predictive toxicology. ToxCast™ HTS data presently covers 1060 broad-use chemicals and captures >650 in vitro features for diverse biochemical and receptor binding activities, multiplexed reporter gen...

ACToR: Aggregated Computational Toxicology Resource (T) ...

EPA Pesticide Factsheets

The EPA Aggregated Computational Toxicology Resource (ACToR) is a set of databases compiling information on chemicals in the environment from a large number of public and in-house EPA sources. ACToR has 3 main goals: (1) The serve as a repository of public toxicology information on chemicals of interest to the EPA, and in particular to be a central source for the testing data on all chemicals regulated by all EPA programs; (2) To be a source of in vivo training data sets for building in vitro to in vivo computational models; (3) To serve as a central source of chemical structure and identity information for the ToxCastTM and Tox21 programs. There are 4 main databases, all linked through a common set of chemical information and a common structure linking chemicals to assay data: the public ACToR system (available at http://actor.epa.gov), the ToxMiner database holding ToxCast and Tox21 data, along with results form statistical analyses on these data; the Tox21 chemical repository which is managing the ordering and sample tracking process for the larger Tox21 project; and the public version of ToxRefDB. The public ACToR system contains information on ~500K compounds with toxicology, exposure and chemical property information from >400 public sources. The web site is visited by ~1,000 unique users per month and generates ~1,000 page requests per day on average. The databases are built on open source technology, which has allowed us to export them to a number of col

PRN 96-8: Toxicologically Significant Levels of Pesticide Active Ingredients

EPA Pesticide Factsheets

This notice sets out EPA's interpretation of the term toxicologically significant as it applies to contaminants in pesticide products that are also pesticide active ingredients. It provides risk-based concentration levels of such contaminants.

Integrated Disinfection By-Products Mixtures Research: Disinfection of Drinking Waters by Chlorination and Ozonation/Postchlorination Treatment Scenarios

EPA Science Inventory

This article describes disinfection of the same source water by two commonly used disinfection treatment scenarios for purposes of subsequent concentration, chemical analysis, and toxicological evaluation. Accompanying articles in this issue of the Journal of Toxicology and Envir...

INTEGRATED TECHNOLOGY-BASED TOXICOLOGY STUDIES ON DRINKING WATER DISINFECTION BYPRODUCTS (DBPS)

EPA Science Inventory

DBPs are formed by reactions of chemical disinfectants with natural organic matter in the source water. Although more than 300 DBPs are known, many remain unidentified; for chlorination, known DBPs account for ~50% of the mass of total organic halide. Toxicological evaluation o...

Day and night variation in chemical composition and toxicological responses of size segregated urban air PM samples in a high air pollution situation

NASA Astrophysics Data System (ADS)

Jalava, P. I.; Wang, Q.; Kuuspalo, K.; Ruusunen, J.; Hao, L.; Fang, D.; Väisänen, O.; Ruuskanen, A.; Sippula, O.; Happo, M. S.; Uski, O.; Kasurinen, S.; Torvela, T.; Koponen, H.; Lehtinen, K. E. J.; Komppula, M.; Gu, C.; Jokiniemi, J.; Hirvonen, M.-R.

2015-11-01

Urban air particulate pollution is a known cause for adverse human health effects worldwide. China has encountered air quality problems in recent years due to rapid industrialization. Toxicological effects induced by particulate air pollution vary with particle sizes and season. However, it is not known how distinctively different photochemical activity and different emission sources during the day and the night affect the chemical composition of the PM size ranges and subsequently how it is reflected to the toxicological properties of the PM exposures. The particulate matter (PM) samples were collected in four different size ranges (PM10-2.5; PM2.5-1; PM1-0.2 and PM0.2) with a high volume cascade impactor. The PM samples were extracted with methanol, dried and thereafter used in the chemical and toxicological analyses. RAW264.7 macrophages were exposed to the particulate samples in four different doses for 24 h. Cytotoxicity, inflammatory parameters, cell cycle and genotoxicity were measured after exposure of the cells to particulate samples. Particles were characterized for their chemical composition, including ions, element and PAH compounds, and transmission electron microscopy (TEM) was used to take images of the PM samples. Chemical composition and the induced toxicological responses of the size segregated PM samples showed considerable size dependent differences as well as day to night variation. The PM10-2.5 and the PM0.2 samples had the highest inflammatory potency among the size ranges. Instead, almost all the PM samples were equally cytotoxic and only minor differences were seen in genotoxicity and cell cycle effects. Overall, the PM0.2 samples had the highest toxic potential among the different size ranges in many parameters. PAH compounds in the samples and were generally more abundant during the night than the day, indicating possible photo-oxidation of the PAH compounds due to solar radiation. This was reflected to different toxicity in the PM samples. Some of the day to night difference may have been caused also by differing wind directions transporting air masses from different emission sources during the day and the night. The present findings indicate the important role of the local particle sources and atmospheric processes on the health related toxicological properties of the PM. The varying toxicological responses evoked by the PM samples showed the importance of examining various particle sizes. Especially the detected considerable toxicological activity by PM0.2 size range suggests they're attributable to combustion sources, new particle formation and atmospheric processes.

Use of short-term toxicity data for prediction of long-term health effects

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hartley, W.R.; Ohanian, E.V.

1988-01-01

Under the Safe Drinking Water Act Amendments of 1986, the US Environmental Protection Agency determines Maximum Contaminant Level Goals (MCLGs) and enforceable Maximum Contaminant Levels (MCLs) or provides lifetime health advisories (HAs) in the absence of regulatory standards. The critical value for calculation of the lifetime level is the reference dose (RfD). The RfD is an estimate of a lifetime dose which is likely to be without significant risk to human populations. The RfD is determined by dividing the no-observed-adverse-effect level (NOAEL) or the lowest-observed-adverse-effect level (LOAEL) by an uncertainty factor (UF). The NOAEL or LOAEL is determined from toxicologicalmore » or epidemiological studies. For many chemicals, human toxicological or epidemiological data are not available. Chronic mammalian studies are sometimes unavailable. Faced with the need for providing guidance for the increasing number of chemicals threatening our drinking water sources, this paper considers the possibility of providing provisional RfDs using data from toxicological studies of less than ninety days duration. The current UF approach is reviewed along with some proposed mathematical models for extrapolation of NOAELs from dose-response data. The current UF approach to developing the RfD is protective and conservative. More research is needed on the relationship of short- and long-term toxicity data to improve our current approach.« less

Aggregated Computational Toxicology Online Resource

EPA Pesticide Factsheets

Aggregated Computational Toxicology Online Resource (AcTOR) is EPA's online aggregator of all the public sources of chemical toxicity data. ACToR aggregates data from over 1,000 public sources on over 500,000 chemicals and is searchable by chemical name, other identifiers and by chemical structure. It can be used to query a specific chemical and find all publicly available hazard, exposure and risk assessment data. It also provides access to EPA's ToxCast, ToxRefDB, DSSTox, Dashboard and DSSTox data.

ACToR-Aggregated Computational Resource | Science ...

EPA Pesticide Factsheets

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 & 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).

IRIS Toxicological Review of Benzo[a]pyrene (Final Report)

EPA Science Inventory

EPA has finalized the Integrated Risk Information System (IRIS) assessment of benzo[a]pyrene. This assessment addresses the potential cancer and noncancer human health effects from long-term exposure to benzo[a]pyrene. Now final, this assessment will update the toxicological info...

Serbia National Poison Control Centre: organization and current activities.

PubMed

Jovanović, Dugan; Joksović, Dragan; Vucinić, Savica; Todorović, Veljko; Segrt, Zoran; Kilibarda, Vesna; Bokonjić, Dubravko

2005-01-01

Ministry of Health of the former Federal Republic of Yugoslavia established the National Poison Control Centre in 1995. However, that was only the formally solution since clinical, analytical and experimental services in toxicology had worked independently for at least 40 years. Besides the Headquarters, NPCC has currently 2 main units, the Clinic of Emergency and Clinical Toxicology and Pharmacology and the Institute of Toxicology and Pharmacology. The latter is consisted of Toxicological Information Department, Department of Analytical Toxicology and Department of Experimental Toxicology and Pharmacology. The Mobile Toxicological Chemical Unit is a separate department that is activated from personnel of the NPCC in a case of chemical accidents and/or disasters. Clinical, information and analytical parts of NPCC have a 365-day/24-hour working service. The Clinic of Emergency and Clinical Toxicology and Pharmacology is a place where the intoxicated patients are treated, including those that need the intensive care measures. Toxicological Information Department uses the data from a self-made computer Database for different information purposes. Department of Analytical Toxicology is equipped with a lot of contemporary analytical equipment that is giving the opportunity of identification and quantification of chemicals/metabolites/degradation products in biological material, food, water, air and soil. Basic pharmacological and toxicological research of chemicals and pre-clinical investigations of antidotes are realized in the Department of Experimental Toxicology and Pharmacology. In terms of medical prevention and rational treatment of human poison exposures in Serbia, the current organization of NPCC has so far proven to be effective.

OpenTox predictive toxicology framework: toxicological ontology and semantic media wiki-based OpenToxipedia

PubMed Central

2012-01-01

Background The OpenTox Framework, developed by the partners in the OpenTox project (http://www.opentox.org), aims at providing a unified access to toxicity data, predictive models and validation procedures. Interoperability of resources is achieved using a common information model, based on the OpenTox ontologies, describing predictive algorithms, models and toxicity data. As toxicological data may come from different, heterogeneous sources, a deployed ontology, unifying the terminology and the resources, is critical for the rational and reliable organization of the data, and its automatic processing. Results The following related ontologies have been developed for OpenTox: a) Toxicological ontology – listing the toxicological endpoints; b) Organs system and Effects ontology – addressing organs, targets/examinations and effects observed in in vivo studies; c) ToxML ontology – representing semi-automatic conversion of the ToxML schema; d) OpenTox ontology– representation of OpenTox framework components: chemical compounds, datasets, types of algorithms, models and validation web services; e) ToxLink–ToxCast assays ontology and f) OpenToxipedia community knowledge resource on toxicology terminology. OpenTox components are made available through standardized REST web services, where every compound, data set, and predictive method has a unique resolvable address (URI), used to retrieve its Resource Description Framework (RDF) representation, or to initiate the associated calculations and generate new RDF-based resources. The services support the integration of toxicity and chemical data from various sources, the generation and validation of computer models for toxic effects, seamless integration of new algorithms and scientifically sound validation routines and provide a flexible framework, which allows building arbitrary number of applications, tailored to solving different problems by end users (e.g. toxicologists). Availability The OpenTox toxicological ontology projects may be accessed via the OpenTox ontology development page http://www.opentox.org/dev/ontology; the OpenTox ontology is available as OWL at http://opentox.org/api/1 1/opentox.owl, the ToxML - OWL conversion utility is an open source resource available at http://ambit.svn.sourceforge.net/viewvc/ambit/branches/toxml-utils/ PMID:22541598

OpenTox predictive toxicology framework: toxicological ontology and semantic media wiki-based OpenToxipedia.

PubMed

Tcheremenskaia, Olga; Benigni, Romualdo; Nikolova, Ivelina; Jeliazkova, Nina; Escher, Sylvia E; Batke, Monika; Baier, Thomas; Poroikov, Vladimir; Lagunin, Alexey; Rautenberg, Micha; Hardy, Barry

2012-04-24

The OpenTox Framework, developed by the partners in the OpenTox project (http://www.opentox.org), aims at providing a unified access to toxicity data, predictive models and validation procedures. Interoperability of resources is achieved using a common information model, based on the OpenTox ontologies, describing predictive algorithms, models and toxicity data. As toxicological data may come from different, heterogeneous sources, a deployed ontology, unifying the terminology and the resources, is critical for the rational and reliable organization of the data, and its automatic processing. The following related ontologies have been developed for OpenTox: a) Toxicological ontology - listing the toxicological endpoints; b) Organs system and Effects ontology - addressing organs, targets/examinations and effects observed in in vivo studies; c) ToxML ontology - representing semi-automatic conversion of the ToxML schema; d) OpenTox ontology- representation of OpenTox framework components: chemical compounds, datasets, types of algorithms, models and validation web services; e) ToxLink-ToxCast assays ontology and f) OpenToxipedia community knowledge resource on toxicology terminology.OpenTox components are made available through standardized REST web services, where every compound, data set, and predictive method has a unique resolvable address (URI), used to retrieve its Resource Description Framework (RDF) representation, or to initiate the associated calculations and generate new RDF-based resources.The services support the integration of toxicity and chemical data from various sources, the generation and validation of computer models for toxic effects, seamless integration of new algorithms and scientifically sound validation routines and provide a flexible framework, which allows building arbitrary number of applications, tailored to solving different problems by end users (e.g. toxicologists). The OpenTox toxicological ontology projects may be accessed via the OpenTox ontology development page http://www.opentox.org/dev/ontology; the OpenTox ontology is available as OWL at http://opentox.org/api/1 1/opentox.owl, the ToxML - OWL conversion utility is an open source resource available at http://ambit.svn.sourceforge.net/viewvc/ambit/branches/toxml-utils/

Retrospective Mining of Toxicology Data to Discover Multispecies Effects: Anemia as a Case Study (SOT)

EPA Science Inventory

In vivo toxicology data is subject to multiple sources of uncertainty: observer severity bias (a pathologist may record only more severe effects and ignore less severe ones); dose spacing issues (this can lead to missing data, e.g. if a severe effect has a less severe precursor, ...

Shuttle Lesson Learned - Toxicology

NASA Technical Reports Server (NTRS)

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.

Toxicoproteomics in Aquatic Toxicology: iTRAQ Reveals Insight into Proteins Affected by 17alpha-ethinylestradiol, Dieldrin, and 17â-trenbolone

EPA Science Inventory

Toxicoproteomics is an emerging discipline in toxicology for characterizing chemical modes of action at the molecular level. We have successfully utilized a quantitative proteomics method termed isobaric tagging for relative and absolute quantitation (iTRAQ) to measure protein re...

Data Aggregation, Curation and Modeling Approaches to Deliver Prediction Models to Support Computational Toxicology at the EPA (ACS Fall meeting)

EPA Science Inventory

The U.S. Environmental Protection Agency (EPA) Computational Toxicology Program develops and utilizes QSAR modeling approaches across a broad range of applications. In terms of physical chemistry we have a particular interest in the prediction of basic physicochemical parameters ...

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

PubMed

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 Cramer class I substances and 4 μg/L for Cramer class III substances in drinking water were derived based on these CEC. These levels are in line with previously reported generic drinking water target levels based on original TTC values and are shown to be protective for health effects of the majority of contaminants of emerging concern evaluated in the present study. Since the human health impact of many chemicals appearing in the water cycle has been studied insufficiently, generic drinking water target levels are useful for early warning and prioritization of CEC with unknown toxicity in drinking water and its sources for future monitoring. Copyright © 2018 Elsevier Ltd. All rights reserved.

Bio-medicolegal scientific research in Europe. A country-based analysis.

PubMed

Viel, Guido; Boscolo-Berto, Rafael; Cecchi, Rossana; Bajanowski, Thomas; Vieira, Nuno Duarte; Ferrara, Santo Davide

2011-09-01

The European mosaic of socio-cultural, economic and legal realities is reflected in forensic and legal medicine, in which a great variety of operational modes of forensic medical services, organisational systems, structures, functional competences and scientific research strategies can be observed. The present work analyses the European bio-medicolegal scientific output of the last 5.5 years (exact time window, January 1, 2005-June 1, 2010), categorising papers by nationality of the corresponding author and forensic sub-discipline in question, in order to identify the peculiarities of national sub-specialised competences and to build up international research projects. This country-based bibliometric analysis, based on the number of articles and the impact factor produced by each European country, also considering its economic profile (gross domestic product and per capita gross domestic product), highlights the prevailing productive role of Western and Southern Europe (Germany, Great Britain, Italy, Switzerland, Spain and France). Categorising scientific output by forensic sub-discipline and branch, significant in terms of impact factor are contributions from Germany (coming first in Pathology, Toxicology, Genetics, Anthropology and Biological Criminalistics), Great Britain (first in Clinical Forensic Medicine, Malpractice and Invalidity-Social Insurance), Switzerland (first in Criminology), Italy (second in Toxicology, Anthropology and Invalidity-Social Insurance), The Netherlands (third in Clinical Forensic Medicine and Medical Law and Ethics), Spain (third in Genetics, Criminalistics and Invalidity-Social Insurance) and France (third in Toxicology and Malpractice). Interestingly, several countries with low gross domestic product, such as Poland, Turkey and other Eastern European nations, show notable scientific production in specific sub-disciplines such as Pathology, Toxicology and Forensic Genetics, suggesting that fruitful international cooperation could be planned and be of interest to funding sources within the European Community, also taking into account funds reserved for depressed areas undergoing development.

Arsenic in the groundwater: Occurrence, toxicological activities, and remedies.

PubMed

Jha, S K; Mishra, V K; Damodaran, T; Sharma, D K; Kumar, Parveen

2017-04-03

Arsenic (As) contamination in groundwater has become a geo-environmental as well as a toxicological problem across the globe affecting more than 100-million people in nearly 21 countries with its associated disease "arsenicosis." Arsenic poisoning may lead to fatal skin and internal cancers. In present review, an attempt has been made to generate awareness among the readers about various sources of occurrence of arsenic, its geochemistry and speciation, mobilization, metabolism, genotoxicity, and toxicological exposure on humans. The article also emphasizes the possible remedies for combating the problem. The knowledge of these facts may help to work on some workable remedial measure.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Templin-Branner, Wilma

The purpose of this training is to familiarize participants with reliable online environmental health and toxicology information, from the National Library of Medicine and other reliable sources. Skills and knowledge acquired in this training class will enable participants to access, utilize, and refer others to environmental health and toxicology information. After completing this course, participants will be able to: (1) Identify quality, accurate, and authoritative online resources pertaining to environmental health, toxicology, and related medical information; (2) Demonstrate the ability to perform strategic search techniques to find relevant online information; and (3) Apply the skills and knowledge obtained in thismore » class to their organization's health information needs. NLMs TOXNET (Toxicology Data Network) is a free, Web-based system of databases on toxicology, environmental health, hazardous chemicals, toxic releases, chemical nomenclatures, and specialty areas such as occupational health and consumer products. Types of information in the TOXNET databases include: (1) Specific chemicals, mixtures, and products; (2) Unknown chemicals; and (3) Special toxic effects of chemicals in humans and/or animals.« less

Essential Nursing References.

ERIC Educational Resources Information Center

Nursing and Health Care Perspectives, 2000

2000-01-01

This partially annotated bibliography contains these categories: abstract sources, archives, audiovisuals, bibliographies, databases, dictionaries, directories, drugs/toxicology/environmental health, grant resources, histories, indexes, Internet resources, reviews, statistical sources, and writers' manuals and guides. A supplement lists Canadian…

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

PubMed

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.

Translational toxicology: a developmental focus for integrated research strategies.

PubMed

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.

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

PubMed

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.

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

PubMed Central

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 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. Conclusions 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. PMID:24732158

Drug and alcohol use by homicide victims in Trinidad and Tobago, 2001-2007.

PubMed

Kuhns, Joseph B; Maguire, Edward R

2012-09-01

This paper examines toxicology results from homicide victims in Trinidad and Tobago to explore patterns in pre-mortem drug and alcohol use. Toxicology test results were obtained for 1,780 homicide victims. Toxicology data from the coroner's office were linked with police data on homicide incidents to examine patterns in drug use and homicide. Trinidad and Tobago homicide victims tested positive for cannabis at a significantly higher rate (32%) than the average rate among other drug toxicology studies. Victims tested positive for alcohol (29%), cocaine (7%), and opioids (1.5%) at rates that were either comparable with or lower than those of homicide victims examined in other studies. The proportion of victims testing positive for cannabis grew significantly from 2001 to 2007; the proportions for alcohol and other drugs were fairly stable over time. Toxicology results also varied by homicide motive, weapon type, and the demographic characteristics of the victim. Toxicology data are a useful source for understanding patterns in drug use and homicide. Though such data have limitations, when combined with other types of data, they can often provide unique insights about a community's drug and violence problems.

IRIS Toxicological Review of Trimethylbenzenes (Final Report ...

EPA Pesticide Factsheets

EPA has finalized the Integrated Risk Information System (IRIS) Assessment of Trimethylbenzenes (TMBs). This assessment addresses the potential non-cancer and cancer human health effects from long-term exposure to TMBs. Now final, this assessment will be the first IRIS assessment for TMBs that may be used by EPA’s program and regional offices to inform decisions to protect human health. The IRIS Toxicological Review of Trimethylbenzenes was originally released for a 60-day public comment period on June 29, 2012. EPA revised the toxicological review in response to the public comments received and released the finalized TMB assessment.

Health effects of carbon-containing particulate matter: focus on sources and recent research program results.

PubMed

Rohr, Annette; McDonald, Jacob

2016-02-01

Air pollution is a complex mixture of gas-, vapor-, and particulate-phase materials comprised of inorganic and organic species. Many of these components have been associated with adverse health effects in epidemiological and toxicological studies, including a broad spectrum of carbonaceous atmospheric components. This paper reviews recent literature on the health impacts of organic aerosols, with a focus on specific sources of organic material; it is not intended to be a comprehensive review of all the available literature. Specific emission sources reviewed include engine emissions, wood/biomass combustion emissions, biogenic emissions and secondary organic aerosol (SOA), resuspended road dust, tire and brake wear, and cooking emissions. In addition, recent findings from large toxicological and epidemiological research programs are reviewed in the context of organic PM, including SPHERES, NPACT, NERC, ACES, and TERESA. A review of the extant literature suggests that there are clear health impacts from emissions containing carbon-containing PM, but difficulty remains in apportioning responses to certain groupings of carbonaceous materials, such as organic and elemental carbon, condensed and gas phases, and primary and secondary material. More focused epidemiological and toxicological studies, including increased characterization of organic materials, would increase understanding of this issue.

Formaldehyde Concentration Dynamics of the International Space Station Cabin Atmosphere

NASA Technical Reports Server (NTRS)

Perry, J. L.

2005-01-01

Formaldehyde presents a significant challenge to maintaining cabin air quality on board crewed spacecraft. Generation sources include offgassing from a variety of non-metallic materials as well as human metabolism. Because generation sources are pervasive and human health can be affected by continual exposure to low concentrations, toxicology and air quality control engineering experts jointly identified formaldehyde as a key compound to be monitored as part the International Space Station's (ISS) environmental health monitoring and maintenance program. Data acquired from in-flight air quality monitoring methods are the basis for assessing the cabin environment's suitability for long-term habitation and monitoring the performance of passive and active controls that are in place to minimize crew exposure. Formaldehyde concentration trends and dynamics served in the ISS cabin atmosphere are reviewed implications to present and future flight operations discussed.

Compilation of Physicochemical and Toxicological Information ...

EPA Pesticide Factsheets

The purpose of this product is to make accessible the information about the 1,173 hydraulic fracturing-related chemicals that were listed in the external review draft of the Hydraulic Fracturing Drinking Water Assessment that was released recently. The product consists of a series of spreadsheets with physicochemical and toxicological information pulled from several sources of information, including: EPI Suite, LeadScope, QikiProp, Reaxys, IRIS, PPRTV, ATSDR, among other sources. The spreadsheets also contain background information about how the list of chemicals were compiled, what the different sources of chemical information are, and definitions and descriptions of the values presented. The purpose of this product is to compile and make accessible information about the 1,173 hydraulic fracturing-related chemicals listed in the external review draft of the Hydraulic Fracturing Drinking Water Assessment.

Computational Toxicology: Application in Environmental Chemicals

EPA Science Inventory

This chapter provides an overview of computational models that describe various aspects of the source-to-health effect continuum. Fate and transport models describe the release, transportation, and transformation of chemicals from sources of emission throughout the general envir...

Ecological risk assessment of cheese whey effluents along a medium-sized river in southwest Greece.

PubMed

Karadima, Constantina; Theodoropoulos, Chris; Rouvalis, Angela; Iliopoulou-Georgudaki, Joan

2010-01-01

An ecological risk assessment of cheese whey effluents was applied in three critical sampling sites located in Vouraikos river (southwest Greece), while ecological classification using Water Framework Directive 2000/60/EU criteria allowed a direct comparison of toxicological and ecological data. Two invertebrates (Daphnia magna and Thamnocephalus platyurus) and the zebra fish Danio rerio were used for toxicological analyses, while the aquatic risk was calculated on the basis of the risk quotient (RQ = PEC/PNEC). Chemical classification of sites was carried out using the Nutrient Classification System, while benthic invertebrates were collected and analyzed for biological classification. Toxicological results revealed the heavy pollution load of the two sites, nearest to the point pollution source, as the PEC/PNEC ratio exceeded 1.0, while unexpectedly, no risk was detected for the most downstream site, due to the consequent interference of the riparian flora. These toxicological results were in agreement with the ecological analysis: the ecological quality of the two heavily impacted sites ranged from moderate to bad, whereas it was found good for the most downstream site. The results of the study indicate major ecological risk for almost 15 km downstream of the point pollution source and the potentiality of the water quality remediation by the riparian vegetation, proving the significance of its maintenance.

Online resources for news about toxicology and other environmental topics.

PubMed

South, J C

2001-01-12

Technology has revolutionized researchers' ability to find and retrieve news stories and press releases. Thanks to electronic library systems and telecommunications--notably the Internet--computer users in seconds can sift through millions of articles to locate mainstream articles about toxicology and other environmental topics. But that does not mean it is easy to find what one is looking for. There is a confusing array of databases and services that archive news articles and press releases: (1) some are free; others cost thousands of dollars a year to access, (2) some include hundreds of newspaper and magazine titles; others cover only one publication, (3) some contain archives going back decades; others have just the latest news, (4) some offer only journalistically balanced reports from mainstream news sources; others mix news with opinions and advocacy and include reports from obscure or biased sources. This article explores ways to find news online - particularly news about toxicology, hazardous chemicals, environmental health and the environment in general. The article covers web sites devoted to environmental news; sites and search engines for general-interest news; newspaper archives; commercial information services; press release distribution services and archives; and other resources and strategies for finding articles in the popular press about toxicology and the environment.

Long-term chemical carcinogenesis experiments for identifying potential human cancer hazards: collective database of the National Cancer Institute and National Toxicology Program (1976-1991).

PubMed Central

Huff, J; Haseman, J

1991-01-01

The carcinogenicity database used for this paper originated in the late 1960s by the National Cancer Institute (NCI) and since 1978 has been continued and made more comprehensive by the National Toxicology Program (NTP). The extensive files contain, among other sets of information, detailed pathology data on more than 400 long-term (most often 24-month) chemical carcinogenesis studies, comprising nearly 1600 individual experiments having at least 10 million tissue sections that have been evaluated for toxicity and carcinogenicity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1820269

PAHs and PCBs in an Eastern Mediterranean megacity, Istanbul: Their spatial and temporal distributions, air-soil exchange and toxicological effects.

PubMed

Cetin, Banu; Ozturk, Fatma; Keles, Melek; Yurdakul, Sema

2017-01-01

Istanbul, one of the mega cities in the world located between Asia and Europe, has suffered from severe air pollution problems due to rapid population growth, traffic and industry. Atmospheric levels of PAHs and PCBs were investigated in Istanbul at 22 sampling sites during four different sampling periods using PUF disk passive air samplers and spatial and temporal variations of these chemicals were determined. Soil samples were also taken at the air sampling sites. At all sites, the average ambient air Σ 15 PAH and Σ 41 PCB concentrations were found as 85.6 ± 68.3 ng m -3 and 246 ± 122 pg m -3 , respectively. Phenanthrene and anthracene were the predominant PAHs and low molecular weight congeners dominated the PCBs. The PAH concentrations were higher especially at urban sites close to highways. However, the PCBs showed moderately uniform spatial variations. Except four sites, the PAH concentrations were increased with decreasing temperatures during the sampling period, indicating the contributions of combustion sources for residential heating, while PCB concentrations were mostly increased with the temperature, probably due to enhanced volatilization at higher temperatures from their sources. The results of the Factor Analysis represented the impact of traffic, petroleum, coal/biomass and natural gas combustion and medical waste incineration plants on ambient air concentrations. A similar spatial distribution trend was observed in the soil samples. Fugacity ratio results indicated that the source/sink tendency of soil for PAHs and PCBs depends on their volatility and temperature; soil generally acts as a source for lighter PAHs and PCBs particularly in higher temperatures while atmospheric deposition is a main source for higher molecular weight compounds in local soils. Toxicological effect studies also revealed the severity of air and soil pollution especially in terms of PAHs in Istanbul. Copyright © 2016 Elsevier Ltd. All rights reserved.

ACToR Chemical Structure processing using Open Source ...

EPA Pesticide Factsheets

ACToR (Aggregated Computational Toxicology Resource) is a centralized database repository developed by the National Center for Computational Toxicology (NCCT) at the U.S. Environmental Protection Agency (EPA). Free and open source tools were used to compile toxicity data from over 1,950 public sources. ACToR contains chemical structure information and toxicological data for over 558,000 unique chemicals. The database primarily includes data from NCCT research programs, in vivo toxicity data from ToxRef, human exposure data from ExpoCast, high-throughput screening data from ToxCast and high quality chemical structure information from the EPA DSSTox program. The DSSTox database is a chemical structure inventory for the NCCT programs and currently has about 16,000 unique structures. Included are also data from PubChem, ChemSpider, USDA, FDA, NIH and several other public data sources. ACToR has been a resource to various international and national research groups. Most of our recent efforts on ACToR are focused on improving the structural identifiers and Physico-Chemical properties of the chemicals in the database. Organizing this huge collection of data and improving the chemical structure quality of the database has posed some major challenges. Workflows have been developed to process structures, calculate chemical properties and identify relationships between CAS numbers. The Structure processing workflow integrates web services (PubChem and NIH NCI Cactus) to d

IRIS Toxicological Review of Benzo[a]pyrene (Final Report) ...

EPA Pesticide Factsheets

EPA has finalized the Integrated Risk Information System (IRIS) assessment of benzo[a]pyrene. This assessment addresses the potential cancer and noncancer human health effects from long-term exposure to benzo[a]pyrene. Now final, this assessment will update the toxicological information on benzo[a]pyrene posted in 1987. EPA’s program and regional offices may use this assessment to inform decisions to protect human health. 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.

Economic and toxicological aspects of copper industry in Katanga, DR Congo.

PubMed

Kalenga, John Ngoy

2013-02-01

The Katanga province is well known for its copper and cobalt reserves. During the early 2000s a boom of mining projects in Katanga brought again hope for better future to Congolese people. The paper aims to evaluate the impact of recent production recovery on economy and environment. We collected primary and secondary sources on copper industry for economic analysis. We use results of laboratory analysis conducted at the Congolese Office of Control by provincial division of environment for toxicological analysis. The comparison of heavy metal concentration to standards shows that mining industry is the main source of environmental pollution in Katanga. Copper industry generates income for economic growth of the region.

Toxicology of the air in closed spaces

NASA Technical Reports Server (NTRS)

Wands, R. C.

1975-01-01

Sources and identification of contaminants in artificial gas atmospheres are discussed. They include biological sources (microflora and man), materials, processes, aerosols, and malfunctions. Acute or chronic toxicity may result from spacecraft air contamination. Air quality standards are presented in tabular form.

TOXICOLOGIC AND CHEMICAL EVALUATION OF ALTERNATIVE DISINFECTION TREATMENT SCENARIOS

EPA Science Inventory

More than 500 disinfecting byproducts have been identified. They result from the reaction of the disinfectants with the natural organic matter present in source waters. The concentrations and bromo/chloro speciation of these disinfection byproducts (DBPs) are influenced by source...

Toxicological Risks During Human Space Exploration

NASA Technical Reports Server (NTRS)

James, John T.; Limero, T. F.; Lam, C. W.; Billica, Roger (Technical Monitor)

2000-01-01

The goal of toxicological risk assessment of human space flight is to identify and quantify significant risks to astronaut health from air pollution inside the vehicle or habitat, and to develop a strategy for control of those risks. The approach to completing a toxicological risk assessment involves data and experience on the frequency and severity of toxicological incidents that have occurred during space flight. Control of these incidents depends on being able to understand their cause from in-flight and ground-based analysis of air samples, crew reports of air quality, and known failures in containment of toxic chemicals. Toxicological risk assessment in exploration missions must be based on an evaluation of the unique toxic hazards presented by the habitat location. For example, lunar and Martian dust must be toxicologically evaluated to determine the appropriate control measures for exploration missions. Experience with near-earth flights has shown that the toxic products from fires present the highest risk to crew health from air pollution. Systems and payload leaks also present a significant hazard. The health risk from toxicity associated with materials offgassing or accumulation of human metabolites is generally well controlled. Early tests of lunar and Martian dust simulants have shown that each posses the potential to cause fibrosis in the lung in a murine model. Toxicological risks from air pollutants in space habitats originate from many sources. A number of risks have been identified through near-earth operations; however, the evaluation of additional new risks present during exploration missions will be a challenge.

Foundation and progress of Japanese society of toxicologic pathology*.

PubMed

Konishi, Yoichi; Enomoto, Makoto; Hayashi, Yuzo

2011-03-01

The Japanese Society of Toxicologic Pathology (JSTP) has a differing conceptual framework from the Japanese Society of Pathology (JSP) and Japanese Society of Toxicology (JST) and was founded in 1985 by the leadership of late Dr. Yasukazu Nishiyama with the cooperation of several founding members and the support of JSP. The aim of the JSTP is to improve the human and animal health using an interdisciplinary scientific approach based on pathology and toxicology. In its development as a professional society, the JSTP has established society rules and activities. The JSTP has grown in terms of membership and financial aspects and is now recognized not only domestically but also internationally as a well-organized scientific society. To maintain the high professional standard and visibility of JSTP, we here provide the historical background of the society as a basis for current members to contribute to the continued improvement of our scientific organization.

Robust Bayesian Algorithm for Targeted Compound Screening in Forensic Toxicology.

PubMed

Woldegebriel, Michael; Gonsalves, John; van Asten, Arian; Vivó-Truyols, Gabriel

2016-02-16

As part of forensic toxicological investigation of cases involving unexpected death of an individual, targeted or untargeted xenobiotic screening of post-mortem samples is normally conducted. To this end, liquid chromatography (LC) coupled to high-resolution mass spectrometry (MS) is typically employed. For data analysis, almost all commonly applied algorithms are threshold-based (frequentist). These algorithms examine the value of a certain measurement (e.g., peak height) to decide whether a certain xenobiotic of interest (XOI) is present/absent, yielding a binary output. Frequentist methods pose a problem when several sources of information [e.g., shape of the chromatographic peak, isotopic distribution, estimated mass-to-charge ratio (m/z), adduct, etc.] need to be combined, requiring the approach to make arbitrary decisions at substep levels of data analysis. We hereby introduce a novel Bayesian probabilistic algorithm for toxicological screening. The method tackles the problem with a different strategy. It is not aimed at reaching a final conclusion regarding the presence of the XOI, but it estimates its probability. The algorithm effectively and efficiently combines all possible pieces of evidence from the chromatogram and calculates the posterior probability of the presence/absence of XOI features. This way, the model can accommodate more information by updating the probability if extra evidence is acquired. The final probabilistic result assists the end user to make a final decision with respect to the presence/absence of the xenobiotic. The Bayesian method was validated and found to perform better (in terms of false positives and false negatives) than the vendor-supplied software package.

Physiological evaluation of men wearing three different toxicological protective systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Levine, L.; Cadarette, B.S.; Sawka, M.N.

1989-08-01

This study examined the physiological responses of seven volunteers exercising in the heat while wearing three different toxicological protective systems. The Toxicological Agent Protective (TAP) suit has been available for use for more than 30 years while the other two protective systems are developmental efforts. The Self-Contained Toxicological Environmental Protection Outfit (STEPO) includes either a backpack-rebreather (with CO{sub 2} scrubber) and ice-cooling vest (STEPO-R), or a tether system which supplies breathing/cooling air inside the suit (STEPO-T). After the volunteers were heat acclimated, the three toxicological protection systems were evaluated utilizing a counter-balanced experimental design initially in a hot and thenmore » in a cool environment while subjects walked at 1.12 m/s, 0% grade for an attempted two hours. There was no statistical advantage of any one system in terms of exercise time in the cool environment. While evaporated sweating rate was greater for the STEPO-T in the cool environment compared to both STEPO-R and TAP. Development efforts to improve the STEPO system designs continue, and physiological evaluation of new developmental models is underway.« less

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

PubMed

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 than original articles, and hence, the editors and authors of Human & Experimental Toxicology might usefully promote the submission of reviews in the future to improve the impact of the journal.

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

PubMed

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.

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

NASA Technical Reports Server (NTRS)

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 dust exposure and produce a lunar health standard.

Chromium: a review of environmental and occupational toxicology.

PubMed

Bencko, V

1985-01-01

The following topics are covered in this brief review on the environmental and occupational toxicology of chromium: occurrence, production and uses of chromium and chromium compounds; experimental toxicology; chromium toxicity for man; hygienic and ecologic aspects of chromium contamination of the environment. The review provides a conclusive evidence which suggests that chromium, especially its hexavalent form, is both toxic and carcinogenic, but its trivalent form is physiologically essential in the metabolism of insulin. It is also emphasized that among the major sources of environmental chromium today are the cement industry and the increasingly widespread use of chromium compounds added as an anticorrosion admixture to a variety of cooling systems, e.g. in large power plants, which may greatly contribute to the overall pollution of outdoor air at the sites.

Special Issue of Inhalation Toxicology for Air Pollution and Health: Bridging the Gap from Sources-to-Health Outcomes

EPA Science Inventory

Pollution and Health: Bridging the Gap from Sources to Health Outcomes”, an international specialty conference by the American Association for Aerosol Research (AAAR) (http://aaar.2010specialty.org/), provided one such opportunity for these interactions. The Conference was organi...

ToxPi GUI: An interactive visualization tool for transparent integration of data from diverse sources of evidence

EPA Science Inventory

Motivation: Scientists and regulators are often faced with complex decisions, where use of scarce resources must be prioritized using collections of diverse information. The Toxicological Prioritization Index (ToxPi™) was developed to enable integration of multiple sources of evi...

Aggregating Data for Computational Toxicology Applications: The U.S. Environmental Protection Agency (EPA) Aggregated Computational Toxicology Resource (ACToR) System

PubMed Central

Judson, Richard S.; Martin, Matthew T.; Egeghy, Peter; Gangwal, Sumit; Reif, David M.; Kothiya, Parth; Wolf, Maritja; Cathey, Tommy; Transue, Thomas; Smith, Doris; Vail, James; Frame, Alicia; Mosher, Shad; Cohen Hubal, Elaine A.; Richard, Ann M.

2012-01-01

Computational toxicology combines data from high-throughput test methods, chemical structure analyses and other biological domains (e.g., genes, proteins, cells, tissues) with the goals of predicting and understanding the underlying mechanistic causes of chemical toxicity and for predicting toxicity of new chemicals and products. A key feature of such approaches is their reliance on knowledge extracted from large collections of data and data sets in computable formats. The U.S. Environmental Protection Agency (EPA) has developed a large data resource called ACToR (Aggregated Computational Toxicology Resource) to support these data-intensive efforts. ACToR comprises four main repositories: core ACToR (chemical identifiers and structures, and summary data on hazard, exposure, use, and other domains), ToxRefDB (Toxicity Reference Database, a compilation of detailed in vivo toxicity data from guideline studies), ExpoCastDB (detailed human exposure data from observational studies of selected chemicals), and ToxCastDB (data from high-throughput screening programs, including links to underlying biological information related to genes and pathways). The EPA DSSTox (Distributed Structure-Searchable Toxicity) program provides expert-reviewed chemical structures and associated information for these and other high-interest public inventories. Overall, the ACToR system contains information on about 400,000 chemicals from 1100 different sources. The entire system is built using open source tools and is freely available to download. This review describes the organization of the data repository and provides selected examples of use cases. PMID:22408426

Aggregating data for computational toxicology applications: The U.S. Environmental Protection Agency (EPA) Aggregated Computational Toxicology Resource (ACToR) System.

PubMed

Judson, Richard S; Martin, Matthew T; Egeghy, Peter; Gangwal, Sumit; Reif, David M; Kothiya, Parth; Wolf, Maritja; Cathey, Tommy; Transue, Thomas; Smith, Doris; Vail, James; Frame, Alicia; Mosher, Shad; Cohen Hubal, Elaine A; Richard, Ann M

2012-01-01

Computational toxicology combines data from high-throughput test methods, chemical structure analyses and other biological domains (e.g., genes, proteins, cells, tissues) with the goals of predicting and understanding the underlying mechanistic causes of chemical toxicity and for predicting toxicity of new chemicals and products. A key feature of such approaches is their reliance on knowledge extracted from large collections of data and data sets in computable formats. The U.S. Environmental Protection Agency (EPA) has developed a large data resource called ACToR (Aggregated Computational Toxicology Resource) to support these data-intensive efforts. ACToR comprises four main repositories: core ACToR (chemical identifiers and structures, and summary data on hazard, exposure, use, and other domains), ToxRefDB (Toxicity Reference Database, a compilation of detailed in vivo toxicity data from guideline studies), ExpoCastDB (detailed human exposure data from observational studies of selected chemicals), and ToxCastDB (data from high-throughput screening programs, including links to underlying biological information related to genes and pathways). The EPA DSSTox (Distributed Structure-Searchable Toxicity) program provides expert-reviewed chemical structures and associated information for these and other high-interest public inventories. Overall, the ACToR system contains information on about 400,000 chemicals from 1100 different sources. The entire system is built using open source tools and is freely available to download. This review describes the organization of the data repository and provides selected examples of use cases.

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

PubMed Central

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 review articles. Review articles tend to have higher citation rates than original articles, and hence, the editors and authors of Human & Experimental Toxicology might usefully promote the submission of reviews in the future to improve the impact of the journal. PMID:26770709

Using zebrafish in systems toxicology for developmental toxicity testing.

PubMed

Nishimura, Yuhei; Inoue, Atsuto; Sasagawa, Shota; Koiwa, Junko; Kawaguchi, Koki; Kawase, Reiko; Maruyama, Toru; Kim, Soonih; Tanaka, Toshio

2016-01-01

With the high cost and the long-term assessment of developmental toxicity testing in mammals, the vertebrate zebrafish has become a useful alternative model organism for high-throughput developmental toxicity testing. Zebrafish is also very favorable for the 3R perspective in toxicology; however, the methodologies used by research groups vary greatly, posing considerable challenges to integrative analysis. In this review, we discuss zebrafish developmental toxicity testing, focusing on the methods of chemical exposure, the assessment of morphological abnormalities, housing conditions and their effects on the production of healthy embryos, and future directions. Zebrafish as a systems toxicology model has the potential to elucidate developmental toxicity pathways, and to provide a sound basis for human health risk assessments. © 2015 Japanese Teratology Society.

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

PubMed

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.

Approach for environmental baseline water sampling

USGS Publications Warehouse

Smith, K.S.

2011-01-01

Samples collected during the exploration phase of mining represent baseline conditions at the site. As such, they can be very important in forecasting potential environmental impacts should mining proceed, and can become measurements against which future changes are compared. Constituents in stream water draining mined and mineralized areas tend to be geochemically, spatially, and temporally variable, which presents challenges in collecting both exploration and baseline water-quality samples. Because short-term (daily) variations can complicate long-term trends, it is important to consider recent findings concerning geochemical variability of stream-water constituents at short-term timescales in designing sampling plans. Also, adequate water-quality information is key to forecasting potential ecological impacts from mining. Therefore, it is useful to collect baseline water samples adequate tor geochemical and toxicological modeling. This requires complete chemical analyses of dissolved constituents that include major and minor chemical elements as well as physicochemical properties (including pH, specific conductance, dissolved oxygen) and dissolved organic carbon. Applying chemical-equilibrium and appropriate toxicological models to water-quality information leads to an understanding of the speciation, transport, sequestration, bioavailability, and aquatic toxicity of potential contaminants. Insights gained from geochemical and toxicological modeling of water-quality data can be used to design appropriate mitigation and for economic planning for future mining activities.

Special-purpose fiber type 475--toxicological assessment.

PubMed

Bernstein, D M

2007-02-01

Type 475 special-purpose glass fiber is rather unique among the family of synthetic mineral fibers. It is used not for insulation but for "high-end" filtration products designed for high and ultra-high purity filtration of air and liquids. The designation for these types of filters varies with country and includes HEPA, ULPA, EU 10-13, EN1822, and S3. In its evaluation, type 475 has been grouped together with E-glass another special-purpose fibre often with little distinction made in terms of its chemistry and corresponding toxicological response. The detailed review of the available toxicology data on type 475 glass fibers clearly shows that following inhalation of this fiber even at relatively high doses, which likely exceed that at which lung overload in the rat is known to occur, type 475 glass fibers are not fibrogenic and do not cause tumors. These data clearly show an important differentiation in potency between type 475 glass fibers and E-glass and support treating these two types of fibers independently and not equating them though the term "special-purpose fibers." Analysis of the intraperitoneal studies taking into account fibre dimensions shows that at 109 fibers injected, there was a 0.3 tumor incidence. While these studies indicate according to the European Commission (EC) classification criteria that 475 should not be fully exonerated as a carcinogen, the results of the inhalation study fully support classification in category 3. The IP results are more difficult to interpret, however, the IP study itself provides no toxicological basis for determining what range of dose-response should correspond to EU category 3 or 2. Following the EC classification criteria, the toxicological data clearly indicate that 475 fibers are appropriately classified in EC category 3.

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

PubMed

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.

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

PubMed

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.

An Integrated Chemical Environment to Support 21st-Century Toxicology

PubMed Central

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.

2017-01-01

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 Tox21TM/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 PMID:28557712

Billing and reimbursement for a bedside toxicology service at a tertiary care academic center during its first fiscal year.

PubMed

Wiegand, Timothy J; Crane, Peter W; Kamali, Michael; Reif, Marilynn; Wratni, Rose; Montante, Ronald; Loveland, Tracey

2015-03-01

A bedside toxicology consult service may improve clinical care, facilitate patient clearance and disposition, and result in potential cost savings for poisoning exposures. Despite this, there is scant data regarding economic feasibility for such a service. Previously published information suggests low hourly reimbursement at approximately $26.00/h at the bedside for toxicology consultations. A bedside toxicology consultant service was initiated in 2011. Coverage was available 24 h a day for 50 out of 52 weeks. Bedside rounding on toxicology consult patients was available 6/7 days per week. The practice is associated with >800 bed teaching institution in a large upstate NY region with elements of urban and suburban practice. Demographic and billing data was collected for all patients consulted upon from July 1, 2011 to June 31, 2012. In charges of $514,941 were generated during the period of data collection. Monthly average was $42,912. Net reimbursement of charges was 29 % of overall charges at $147,792. In terms of total encounters, net collection rate in which something was reimbursed or "paid" against charges for that encounter was 82.6 % of all encounters at 999/1,210. Average encounter time for inpatients, including critical care, was 1.05 h, and the average time spent for outpatients was 1.18 h. Reimbursement rates appear higher than previously reported. Revenue generated from reimbursement from toxicology consultation can result in recouping a substantial portion of a toxicologist's salary or potentially fund fellowship positions and salaries or toxicology division infrastructure.

Safety and Toxicology of Cannabinoids.

PubMed

Sachs, Jane; McGlade, Erin; Yurgelun-Todd, Deborah

2015-10-01

There is extensive research on the safety, toxicology, potency, and therapeutic potential of cannabis. However, uncertainty remains facilitating continued debate on medical and recreational cannabis policies at the state and federal levels. This review will include a brief description of cannabinoids and the endocannabinoid system; a summary of the acute and long-term effects of cannabis; and a discussion of the therapeutic potential of cannabis. The conclusions about safety and efficacy will then be compared with the current social and political climate to suggest future policy directions and general guidelines.

Summary of information on aquatic biota and their habitats in the Willamette Basin, Oregon, through 1995

USGS Publications Warehouse

Altman, Bob; Henson, C.M.; Waite, I.R.

1997-01-01

Aquatic toxicological investigations in the basin have focused primarily on fish. These studies have addressed chlorinated pesticides, polychlorinated biphenyls (PCBs), dioxins and furans, polycyclic aromatic hydrocarbons (PAHs), and trace elements in aquatic tissue, as well as fish health assessments, skeletal abnormalities, and aquatic toxicological responses. Several pesticides exceeded U.S. Environmental Protection Agency and State water-quality criteria for the protection of aquatic life. Elevated PCB, dioxin, and furan concentrations were associated with point sources, such as pulp and paper mills. Elevated concentrations of mercury in aquatic tissue were associated with several reservoirs. Fish health assessments and skeletal abnormality studies detected high levels of abnormalities in fish from the main stem Willamette River. Few investigations have examined aquatic toxicological responses, such as enzyme induction assays, growth assays, and biomarker studies.

Potential carcinogenic hazards of non-regulated disinfection by-products: haloquinones, halo-cyclopentene and cyclohexene derivatives, N-halamines, halonitriles, and heterocyclic amines.

PubMed

Bull, Richard J; Reckhow, David A; Li, Xingfang; Humpage, Andrew R; Joll, Cynthia; Hrudey, Steve E

2011-08-15

Drinking water disinfectants react with natural organic material (NOM) present in source waters used for drinking water to produce a wide variety of by-products. Several hundred disinfections by-products (DBPs) have been identified, but none have been identified with sufficient carcinogenic potency to account for the cancer risks projected from epidemiological studies. In a search for DBPs that might fill this risk gap, the present study projected reactions of chlorine and chloramine that could occur with substructures present in NOM to produce novel by-products. A review of toxicological data on related compounds, supplemented by use of a quantitative structure toxicity relationship (QSTR) program TOPKAT®) identified chemicals with a high probability of being chronically toxic and/or carcinogenic among 489 established and novel DBPs. Classes of DBPs that were specifically examined were haloquinones (HQs), related halo-cyclopentene and cyclohexene (HCP&H) derivatives, halonitriles (HNs), organic N-chloramines (NCls), haloacetamides (HAMs), and nitrosamines (NAs). A review of toxicological data available for quinones suggested that HQs and HCP&H derivatives appeared likely to be of health concern and were predicted to have chronic lowest observed adverse effect levels (LOAELs) in the low μg/kg day range. Several HQs were predicted to be carcinogenic. Some have now been identified in drinking water. The broader class of HNs was explored by considering current toxicological data on haloacetonitriles and extending this to halopropionitriles. 2,2-dichloropropionitrile has been identified in drinking water at low concentrations, as well as the more widely recognized haloacetonitriles. The occurrence of HAMs has been previously documented. The very limited toxicological data on HAMs suggests that this class would have toxicological potencies similar to the dihaloacetic acids. Organic N-halamines are also known to be produced in drinking water treatment and have biological properties of concern, but no member has ever been characterized toxicologically beyond bacterial or in vitro studies of genotoxicity. The documented formation of several nitrosamines from secondary amines from both natural and industrial sources prompted exploration of the formation of additional nitrosamines. N-diphenylnitrosamine was identified in drinking waters. Of more interest, however, was the formation of phenazine (and subsequently N-chorophenazine) in a competing reaction. These are the first heterocyclic amines that have been identified as chlorination by-products. Consideration of the amounts detected of members of these by-product classes and their probable toxicological potency suggest a prioritization for obtaining more detailed toxicological data of HQs>HCP&H derivatives>NCls>HNs. Based upon a ubiquitous occurrence and virtual lack of in vivo toxicological data, NCls are the most difficult group to assign a priority as potential carcinogenic risks. This analysis indicates that research on the general problem of DBPs requires a more systematic approach than has been pursued in the past. Utilization of predictive chemical tools to guide further research can help bring resolution to the DBP issue by identifying likely DBPs with high toxicological potency. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

On the chemistry, toxicology and genetics of the cyanobacterial toxins, microcystin, nodularin, saxitoxin and cylindrospermopsin.

PubMed

Pearson, Leanne; Mihali, Troco; Moffitt, Michelle; Kellmann, Ralf; Neilan, Brett

2010-05-10

The cyanobacteria or "blue-green algae", as they are commonly termed, comprise a diverse group of oxygenic photosynthetic bacteria that inhabit a wide range of aquatic and terrestrial environments, and display incredible morphological diversity. Many aquatic, bloom-forming species of cyanobacteria are capable of producing biologically active secondary metabolites, which are highly toxic to humans and other animals. From a toxicological viewpoint, the cyanotoxins span four major classes: the neurotoxins, hepatotoxins, cytotoxins, and dermatoxins (irritant toxins). However, structurally they are quite diverse. Over the past decade, the biosynthesis pathways of the four major cyanotoxins: microcystin, nodularin, saxitoxin and cylindrospermopsin, have been genetically and biochemically elucidated. This review provides an overview of these biosynthesis pathways and additionally summarizes the chemistry and toxicology of these remarkable secondary metabolites.

Toxicological assessment of ambient and traffic-related particulate matter: a review of recent studies.

PubMed

de Kok, Theo M C M; Driece, Hermen A L; Hogervorst, Janneke G F; Briedé, Jacob J

2006-01-01

Particulate air pollution (PM) is an important environmental health risk factor for many different diseases. This is indicated by numerous epidemiological studies on associations between PM exposure and occurrence of acute respiratory infections, lung cancer and chronic respiratory and cardiovascular diseases. The biological mechanisms behind these associations are not fully understood, but the results of in vitro toxicological research have shown that PM induces several types of adverse cellular effects, including cytotoxicity, mutagenicity, DNA damage and stimulation of proinflammatory cytokine production. Because traffic is an important source of PM emission, it seems obvious that traffic intensity has an important impact on both quantitative and qualitative aspects of ambient PM, including its chemical, physical and toxicological characteristics. In this review, the results are summarized of the most recent studies investigating physical and chemical characteristics of ambient and traffic-related PM in relation to its toxicological activity. This evaluation shows that, in general, the smaller PM size fractions (

A bittersweet story: the true nature of the laurel of the Oracle of Delphi.

PubMed

Harissis, Haralampos V

2014-01-01

It is known from ancient sources that "laurel," identified with sweet bay, was used at the ancient Greek oracle of Delphi. The Pythia, the priestess who spoke the prophecies, purportedly used laurel as a means to inspire her divine frenzy. However, the clinical symptoms of the Pythia, as described in ancient sources, cannot be attributed to the use of sweet bay, which is harmless. A review of contemporary toxicological literature indicates that it is oleander that causes symptoms similar to those of the Pythia, while a closer examination of ancient literary texts indicates that oleander was often included under the generic term laurel. It is therefore likely that it was oleander, not sweet bay, that the Pythia used before the oracular procedure. This explanation could also shed light on other ancient accounts regarding the alleged spirit and chasm of Delphi, accounts that have been the subject of intense debate and interdisciplinary research for the last hundred years.

Future directions in training veterinarians for careers in toxicological pathology in the United Kingdom.

PubMed

Scudamore, Cheryl L; Smith, Sionagh H

2007-01-01

There is currently a global shortage of veterinary pathologists in all sectors of the discipline, and recruitment of toxicological pathologists is a particular problem for the pharmaceutical industry. Efforts to encourage veterinarians to consider alternative career paths to general practice must start at the undergraduate level, with provision of structured career guidance and strong role models from pathology and research disciplines. It is also imperative that both the importance of biomedical research and the role of animal models be clearly understood by both university staff and undergraduates. Traditionally, much post-graduate training in toxicological pathology is done "on the job" in the United Kingdom, but completion of a residency and/or PhD program is recognized as a good foundation for a career in industry and for successful completion of professional pathology examinations. New models of residency training in veterinary pathology must be considered in the United Kingdom to enable a more tailored approach to training toward specific career goals. A modular approach to residency training would allow core skills to be maintained, while additional training would target specific training requirements in toxicological pathology. Exposure to laboratory-animal pathology, toxicology, research methodology, and management skills would all be of benefit as an introduction to a career in toxicological pathology. However, long-term funding for UK residencies remains a problem that must be resolved if future recruitment needs in veterinary pathology are to be met.

Pro-inflammatory effects and oxidative stress in lung macrophages and epithelial cells induced by ambient particulate matter.

PubMed

Michael, S; Montag, M; Dott, W

2013-12-01

The objective of this study was to compare the toxicological effects of different source-related ambient PM10 samples in regard to their chemical composition. In this context we investigated airborne PM from different sites in Aachen, Germany. For the toxicological investigation human alveolar epithelial cells (A549) and murine macrophages (RAW264.7) were exposed from 0 to 96 h to increasing PM concentrations (0-100 μg/ml) followed by analyses of cell viability, pro-inflammatory and oxidative stress responses. The chemical analysis of these particles indicated the presence of 21 elements, water-soluble ions and PAHs. The toxicological investigations of the PM10 samples demonstrated a concentration- and time-dependent decrease in cell viability and an increase in pro-inflammatory and oxidative stress markers. Copyright © 2013 Elsevier Ltd. All rights reserved.

Hair: a complementary source of bioanalytical information in forensic toxicology.

PubMed

Barroso, Mário; Gallardo, Eugenia; Vieira, Duarte Nuno; López-Rivadulla, Manuel; Queiroz, João António

2011-01-01

Hair has been used for years in the assessment and documentation of human exposure to drugs, as it presents characteristics that make it extremely valuable for this purpose, namely the fact that sample collection is performed in a noninvasive manner, under close supervision, the possibility of collecting a specimen reflecting a similar timeline in the case of claims or suspicion of a leak in the chain of custody, and the increased window of detection for the drugs. For these reasons, testing for drugs in hair provides unique and useful information in several fields of toxicology, from which the most prominent is the possibility of studying individual drug use histories by means of segmental analysis. This paper will review the unique role of hair as a complementary sample in documenting human exposure to drugs in the fields of clinical and forensic toxicology and workplace drug testing.

Toxicological and radiological safety of chicken meat irradiated with 7.5 MeV X-rays

NASA Astrophysics Data System (ADS)

Song, Beom-Seok; Lee, Yunjong; Park, Jong-Heum; Kim, Jae-Kyung; Park, Ha-Young; Kim, Dong-Ho; Kim, Chang-Jong; Kang, Il-Jun

2018-03-01

This study was conducted to evaluate the toxicological and radiological safety of chicken meat that had been irradiated at 30 kGy with 7.5 MeV X-rays. In a sub-chronic toxicity study, ICR mice were fed X-ray-irradiated chicken meat at 2500 mg/kg body weight daily for 90 days, and no mortality or abnormal clinical signs were observed throughout the study period. However, several hematological and serum biochemical parameters of the ICR mice differed significantly from those in the control group; nevertheless, the observed values were all within the normal range for the respective parameters. In addition, no toxicological effects were determined in male or female mice. Furthermore, no differences in gamma-ray spectrometric patterns were detected between the non-irradiated and irradiated samples, indicating that the radioactivity induced by 7.5 MeV X-ray irradiation was below the detection limit. These results tentatively suggest that chicken meat irradiated with 7.5 MeV X-rays would be safe for human consumption in terms of toxicology and radiology.

Opioids in the Frame of New Psychoactive Substances Network: A Complex Pharmacological and Toxicological Issue.

PubMed

Ventura, Ludovic; Carvalho, Felix; Dinis-Oliveira, Ricardo Jorge

2018-01-01

New psychoactive substances (NPS), often referred to as "legal highs" or "designer drugs", are derivatives and analogues of existing psychoactive drugs that are introduced in the recreational market to circumvent existing legislation on drugs of abuse. This systematic review aims to gather the state of the art regarding chemical, molecular pharmacology and toxicological information of opioid class of NPS. Chemical, pharmacological, toxicological and clinical effects of opioid class of NPS were searched in books and in PubMed (U.S. National Library of Medicine) without a limiting period. Within this class, fentanyl analogues are among the most frequently abused and pose several clinical concerns and therefore will be thoroughly discussed. Other opioid sub-categories of NPS frequently misused include AH-7921, MT-45, U-47700, U-50488, desomorphine, mitragynine, tramadol, tapentadol, salvinorin A and its analogue herkinorin. Due to inefficient monitoring techniques, as well as limited knowledge regarding the acute and long-term effects of opioids NPS, further clinical and forensic toxicological studies are required. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Retracted: Long-term copper toxicity in apple trees (Malus pumila Mill) and bioaccumulation in fruits.

PubMed

Sun, Bai-Ye; Kan, Shi-Hong; Zhang, Yan-Zong; Wu, Jun; Deng, Shi-Huai; Liu, Chun-Sheng; Yang, Gang

2010-01-15

The following article from Environmental Toxicology, 'Long-term Copper Toxicity in Apple Trees (Malus pumila Mill) and Bioaccumulation in Fruits' by Bai-Ye Sun, Shi- Hong Kan, Yan-Zong Zhang, Jun Wu, Shi-Huai Deng, Chun-Sheng Liu and Gang Yang, published online on January 15, 2010 in Wiley InterScience (www.interscience.wiley.com; DOI: 10.1002/tox.20565), has been retracted by agreement between the authors, the journal Editor in Chief, Dr. Paul Tchounwou, and Wiley Periodicals, Inc. The retraction has been agreed at the request of the authors due to overlap with 'Copper Toxicity and Bioaccumulation in Chinese Cabbage (Brassica pekinensis Rupr.)' by Zhi-Ting Xiong and Hai Wang, published in Environmental Toxicology, Volume 20, pages 188-194, 2005.

Understanding the toxicological potential of aerosol organic compounds using informatics based screening

NASA Astrophysics Data System (ADS)

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

2016-04-01

Exposure to atmospheric particulate matter is responsible for both short-term and long-term adverse health effects. So far, all efforts spent in achieving a systematic epidemiological evidence of specific aerosol compounds determining the overall aerosol toxicity were unsuccessful. The results of the epidemiological studies apparently conflict with the laboratory toxicological analyses which have highlighted very different chemical and toxicological potentials for speciated aerosol compounds. Speciation remains a problem, especially for organic compounds: it is impossible to conduct screening on all possible molecular species. At the same time, research on toxic compounds risks to be biased towards the already known compounds, such as PAHs and dioxins. In this study we present results from an initial assessment of the use of in silico methods (i.e. (Q)SAR, read-across) to predict toxicity of atmospheric organic compounds including evaluation of applicability of a variety of popular tools (e.g. OECD QSAR Toolbox) for selected endpoints (e.g. genotoxicity). Compounds are categorised based on the need of new experimental data for the development of in silico approaches for toxicity prediction covering this specific chemical space, namely the atmospheric aerosols. Whilst only an initial investigation, we present recommendations for continuation of this work.

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

PubMed

Kappus, H; Yang, R S

1996-01-01

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

On the Chemistry, Toxicology and Genetics of the Cyanobacterial Toxins, Microcystin, Nodularin, Saxitoxin and Cylindrospermopsin

PubMed Central

Pearson, Leanne; Mihali, Troco; Moffitt, Michelle; Kellmann, Ralf; Neilan, Brett

2010-01-01

The cyanobacteria or “blue-green algae”, as they are commonly termed, comprise a diverse group of oxygenic photosynthetic bacteria that inhabit a wide range of aquatic and terrestrial environments, and display incredible morphological diversity. Many aquatic, bloom-forming species of cyanobacteria are capable of producing biologically active secondary metabolites, which are highly toxic to humans and other animals. From a toxicological viewpoint, the cyanotoxins span four major classes: the neurotoxins, hepatotoxins, cytotoxins, and dermatoxins (irritant toxins). However, structurally they are quite diverse. Over the past decade, the biosynthesis pathways of the four major cyanotoxins: microcystin, nodularin, saxitoxin and cylindrospermopsin, have been genetically and biochemically elucidated. This review provides an overview of these biosynthesis pathways and additionally summarizes the chemistry and toxicology of these remarkable secondary metabolites. PMID:20559491

Fire test methodology for aerospace materials. 1: Thermal and smoke toxicological assessments of graphite/bismaleimide and graphite/epoxy systems

NASA Technical Reports Server (NTRS)

Kanakia, M. D.; Switzer, W. G.; Hartzell, G. E.; Kaplan, H. L.

1980-01-01

Both materials possess a high degree of thermal stability, with total heat release values being essentially identical under piloted ignition conditions over a range of 5 to 10 W/sq cm incident heat flux. The graphite/epoxy material had a tendency to auto-ignite at a lower heat flux (about 7 W/sq cm) and produced about 23 percent higher peak heat release rates, approximately 42 percent more carbon monoxide and considerably more smoke than the graphite/bismaleimide under conditions of piloted ignition. Toxicological potencies of smoke produced from the two composites were equivalent for 30 minute exposures. Potencies were also comparable to many common materials, such as wood. There was no evidence for the formation of an "unusual toxicant" nor for any short term post-exposure toxicological effects.

Comparative toxicity and mutagenicity of soy-biodiesel and petroleum-diesel emissions: overview of studies from the U.S. EPA, Research Triangle Park, NC.

PubMed

Madden, Michael C

2015-01-01

Biodiesel use as a fuel is increasing globally as an alternate to petroleum sources. To comprehensively assess the effects of the use of biodiesel as an energy source, end stage uses of biodiesel such as the effects of inhalation of combusted products on human health must be incorporated. To date, few reports concerning the toxicological effects of the emissions of combusted biodiesel or blends of biodiesel on surrogates of health effects have been published. The relative toxicity of the combusted biodiesel emissions compared to petroleum diesel emissions with short term exposures is also not well known. To address the paucity of findings on the toxicity of combusted biodiesel emissions, studies were undertaken at the U.S. Environmental Protection Agency laboratories in Research Triangle Park, North Carolina. The studies used a variety of approaches with nonhuman animal models to examine biological responses of the lung and cardiovascular systems induced by acute and repeated exposures to pure biodiesel and biodiesel blended with petroleum diesel. Effects of the emissions on induction of mutations in bacterial test strains and mammalian DNA adducts were also characterized and normalized to engine work load. The emissions were characterized as to the physicochemical composition in order to determine the magnitude of the differences among the emissions utilized in the studies. This article summarizes the major finding of these studies which are contained within this special issue of Inhalation Toxicology. The findings provided in these articles provide information about the toxicity of biodiesel emissions relative to petroleum diesel emissions and which can be utilized in a life cycle analyses of the effects of increased biodiesel usage.

Toxicological characteristics of edible insects in China: A historical review.

PubMed

Gao, Yu; Wang, Di; Xu, Meng-Lei; Shi, Shu-Sen; Xiong, Jin-Feng

2018-04-10

Edible insects are ideal food sources, which contain important nutrients and health-promoting compounds. With a rapid development of industrial insect farming, insect-derived food is a novel and emerging food industry. Edible insects have been traditionally consumed in various communities, while continuously gaining relevance in today's society; however, they currently remain underutilized. Although there are a large number of literature on edible insects, these literature primarily focus on the nutritional value edible insects. The toxicity assessment data of edible insects remain incomprehensive, especially for the new national standard that is currently in effect; and many data and conclusions are not accurately specified/reported. Therefore, we performed a literature review and summarized the data on the toxicological assessment of edible insects in China. The review first describes the research progress on safety toxicological assessment, and then offers references regarding the development of 34 edible insect species in China. These data can be a platform for the development of future toxicological assessment strategies, which can be carried out by a multidisciplinary team, possibly consisting of food engineers, agronomists, farmers, and so on, to improve the acceptability of edible insects. Copyright © 2018 Elsevier Ltd. All rights reserved.

Postmortem ethanol in the setting of ethanol-containing automotive fuel.

PubMed

Garber, Mitchell A; Canfield, Dennis V; Lewis, Russell J; Simmons, Samuel D; Radisch, Deborah L

2013-03-01

The pilot of a light aircraft that crashed after a loss of power was found to have ethanol in the vitreous and the blood, but almost none in the urine. The globes of the eyes were intact, and the body was refrigerated after recovery until the autopsy was performed the following morning. The pilot was described as a "nondrinker," and additional specialized toxicology testing results were inconsistent with ethanol ingestion. The pilot's body was extensively exposed to fuel during the prolonged extraction. Investigation determined that the aircraft had been fueled with gasoline that contained 10% ethanol. Although exposure to automotive fuel has not been previously described as a source of ethanol in postmortem specimens, it may represent a source for the ethanol detected during postmortem toxicology testing in this case, and this finding may be relevant to other cases with similar exposure.

GENOTOXICITY AND METABOLISM OF THE SOURCE-WATER CONTAMINANT 1,1-DICHLOROPROPENE: ACTIVATION BY GSTT1-1 AND STRUCTURE-ACTIVITY CONSIDERATIONS

EPA Science Inventory

1, 1 -Dichloropropene (1,1-DCPe) is a contaminant of some source waters used to make drinking water. Because of this and the fact that no toxicological data were available for this compound, which is structurally similar to the rodent carcinogen 1,3-dichloropropene (1,3DCPe), 1,1...

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

PubMed

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 projects in the field of toxicology.

A bibliometric analysis of research productivity of Malaysian publications in leading toxicology journals during a 10-year period (2003-2012).

PubMed

Zyoud, Sh; Al-Jabi, Sw; Sweileh, Wm; Awang, R

2014-12-01

Toxicology in Malaysia has experienced rapid development and made great progress in education and research in conjunction with economic development in Malaysia over the past two decades. The main objectives of this study were to analyse the research originating from Malaysia and published in toxicology journals and to examine the authorship pattern and the citations retrieved from the Scopus database. Data from 1 January 2003 till 31 December 2012 were searched for documents with specific words in the toxicology field as a 'source title' and Malaysia as an affiliation country. Research productivity was evaluated based on a methodology we developed and used in other bibliometric studies by analysing: (a) total and trends of contributions in toxicology fields between 2003 and 2012; (b) Malaysian authorship pattern and productivity; (c) collaboration patterns; (d) journals in which Malaysian researchers publish; (e) the classification of journals to Institute for Scientific Information (ISI) or non-ISI; (f) impact factors (IFs) of all publications; and (g) citations received by the publications. In total, 290 documents were retrieved from 55 international peer-reviewed toxicology journals. The quantity of publication increased by around 10-fold from 2003 to 2012. The h-index of the retrieved documents was 20. Of the 55 journal titles, 42 (76.4%) have their IF listed in the journal citation reports 2012. Forty-two documents (14.5%) were published in journals that had no official IF. The total number of citations, at the time of manuscript writing (5 August 2013), was 1707, with a median (interquartile range) of 3 (0-7). Malaysia collaborated mostly with countries in the Asia-Pacific regions (18.3%), especially India and Japan, followed by the Middle East and Africa (10.0%), especially Palestine and Yemen. The present data show a promising rise and a good start for toxicology research activity in Malaysia. The sharing of relevant research questions by developed and developing countries can lead to research opportunities in the field of toxicology. © The Author(s) 2014.

Green Toxicology-Know Early About and Avoid Toxic Product Liabilities.

PubMed

Maertens, Alexandra; Hartung, Thomas

2018-02-01

Toxicology uniquely among the life sciences relies largely on methods which are more than 40-years old. Over the last 3 decades with more or less success some additions to and few replacements in this toolbox took place, mainly as alternatives to animal testing. The acceptance of such new approaches faces the needs of formal validation and the conservative attitude toward change in safety assessments. Only recently, there is growing awareness that the same alternative methods, especially in silico and in vitro tools can also much earlier and before validation inform decision-taking in the product life cycle. As similar thoughts developed in the context of Green Chemistry, the term of Green Toxicology was coined to describe this change in approach. Here, the current developments in the alternative field, especially computational and more organo-typic cell cultures are reviewed, as they lend themselves to front-loaded chemical safety assessments. The initiatives of the Center for Alternatives to Animal Testing Green Toxicology Collaboration are presented. They aim first of all for forming a community to promote this concept and then for a cultural change in companies with the necessary training of chemists, product stewards and later regulators. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Quantitative Predictive Models for Systemic Toxicity (SOT)

EPA Science Inventory

Models to identify systemic and specific target organ toxicity were developed to help transition the field of toxicology towards computational models. By leveraging multiple data sources to incorporate read-across and machine learning approaches, a quantitative model of systemic ...

Informing Mechanistic Toxicology with Computational Molecular Models

EPA Science Inventory

Computational molecular models of chemicals interacting with biomolecular targets provides toxicologists a valuable, affordable, and sustainable source of in silico molecular level information that augments, enriches, and complements in vitro and in vivo effo...

Screening for an Allergic Response to 2nd Generation Biofuel Sources

EPA Science Inventory

Abstract for March 2014 Society of Toxicology Annual Meeting The use of cellulosic biofuels crops can potentially reduce our carbon footprint. However, they may have unintended ecological and health effects such as increased competitiveness and allergenicity...

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

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 derivedmore » 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 scenarios utilizing secondary particles (oxidized emissions) ranged from 70-256 {micro}g/m{sup 3}, and some of the atmospheres contained high acidity levels (up to 49 {micro}g/m{sup 3} equivalent of sulfuric acid). However, caution must be used in generalizing these results to other power plants utilizing different coal types and with different plant configurations, as the emissions may vary based on these factors.« less

Risk assessment of Soulatrolide and Mammea (A/BA+A/BB) coumarins from Calophyllum brasiliense by a toxicogenomic and toxicological approach.

PubMed

Gomez-Verjan, J C; Estrella-Parra, E; Vazquez-Martinez, E R; Gonzalez-Sanchez, I; Guerrero-Magos, G; Mendoza-Villanueva, D; Isus, L; Alfaro, A; Cerbón-Cervantes, M; Aloy, P; Reyes-Chilpa, R

2016-05-01

Calophyllum brasiliense (Calophyllaceae) is a tropical rain forest tree distributed in Central and South America. It is an important source of tetracyclic dipyrano coumarins (Soulatrolide) and Mammea type coumarins. Soulatrolide is a potent inhibitor of HIV-1 reverse transcriptase and displays activity against Mycobacterium tuberculosis. Meanwhile, Mammea A/BA and A/BB, pure or as a mixture, are highly active against several human leukemia cell lines, Trypanosoma cruzi and Leishmania amazonensis. Nevertheless, there are few studies evaluating their safety profile. In the present work we performed toxicogenomic and toxicological analysis for both type of compounds. Soulatrolide, and the Mammea A/BA + A/BB mixture (2.1) were slightly toxic accordingly to Lorke assay classification (DL50 > 3000 mg/kg). After a short-term administration (100 mg/kg/daily, orally, 1 week) liver toxicogenomic analysis revealed 46 up and 72 downregulated genes for Mammea coumarins, and 665 up and 1077 downregulated genes for Soulatrolide. Gene enrichment analysis identified transcripts involved in drug metabolism for both compounds. In addition, network analysis through protein-protein interactions, tissue evaluation by TUNEL assay, and histological examination revealed no tissue damage on liver, kidney and spleen after treatments. Our results indicate that both type of coumarins displayed a safety profile, supporting their use in further preclinical studies to determine its therapeutic potential. Copyright © 2016 Elsevier Ltd. All rights reserved.

Possible long-term health effects of short-term exposure to chemical agents. Volume 2. Cholinesterase reactivators, psychochemicals, and irritants and vesicants. Final report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1984-01-01

The present report evaluates toxicologic and epidemiologic data relevant to the testing of approximately 750 subjects exposed to cholinesterase reactivators, about 260 exposed to psychochemicals, and 1,500 exposed to irritants or vesicants. A remaining group of subjects used largely in tests involving placebo or innocuous chemicals or conditions is available for comparison and will be discussed later. The report is the work of three panels of scientists--the Panel on Cholinesterase Reactivator Chemicals, the Panel on Psychochemicals, and the Panel on Irritants and Vesicants. The chairman of each panel was selected from the Committee on Toxicology, and the members were selectedmore » on the basis of their knowledge of the compounds in question or because they represented required disciplines.« less

Toxicologic information resources for reptile envenomations.

PubMed

McNally, Jude; Boesen, Keith; Boyer, Leslie

2008-05-01

The United States is the largest importer of reptiles in the world, with an estimated 1.5 to 2.0 million households keeping one or more reptiles. Snakes account for about 11% of these imports and it has been estimated that as many as 9% of these reptiles are venomous. Envenomations by nonindigenous venomous species are a rare but often serious medical emergency. Bites may occur during the care and handling of legitimate collections found in universities, zoos, or museums. The other predominant source of exotic envenomation is from amateur collectors participating in importation, propagation, and trade of non-native species. This article provides toxicologic information resources for snake envenomations.

Behavior within fortuitous environments: The entwined history of Division 28 and the fields of behavioral pharmacology and toxicology.

PubMed

Campbell, Nancy D

2016-08-01

Behavioral pharmacology emerged in the early to mid-20th century as an experimental and observational science, helping to consolidate an empirically based psychological science of behavior. Behavioral psychologists came to play significant roles in toxicology, neuropharmacology, and psychopharmacology. This article traces the first 3 decades of American Psychological Association Division 28. Sources include the Division 28 Oral History Project; formal interviews conducted by the author in the early 2000s with behavioral, experimental, and clinical pharmacologists; and the archived newsletters of Division 28. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Collaborative development of predictive toxicology applications

PubMed Central

2010-01-01

OpenTox provides an interoperable, standards-based Framework for the support of predictive toxicology data management, algorithms, modelling, validation and reporting. It is relevant to satisfying the chemical safety assessment requirements of the REACH legislation as it supports access to experimental data, (Quantitative) Structure-Activity Relationship models, and toxicological information through an integrating platform that adheres to regulatory requirements and OECD validation principles. Initial research defined the essential components of the Framework including the approach to data access, schema and management, use of controlled vocabularies and ontologies, architecture, web service and communications protocols, and selection and integration of algorithms for predictive modelling. OpenTox provides end-user oriented tools to non-computational specialists, risk assessors, and toxicological experts in addition to Application Programming Interfaces (APIs) for developers of new applications. OpenTox actively supports public standards for data representation, interfaces, vocabularies and ontologies, Open Source approaches to core platform components, and community-based collaboration approaches, so as to progress system interoperability goals. The OpenTox Framework includes APIs and services for compounds, datasets, features, algorithms, models, ontologies, tasks, validation, and reporting which may be combined into multiple applications satisfying a variety of different user needs. OpenTox applications are based on a set of distributed, interoperable OpenTox API-compliant REST web services. The OpenTox approach to ontology allows for efficient mapping of complementary data coming from different datasets into a unifying structure having a shared terminology and representation. Two initial OpenTox applications are presented as an illustration of the potential impact of OpenTox for high-quality and consistent structure-activity relationship modelling of REACH-relevant endpoints: ToxPredict which predicts and reports on toxicities for endpoints for an input chemical structure, and ToxCreate which builds and validates a predictive toxicity model based on an input toxicology dataset. Because of the extensible nature of the standardised Framework design, barriers of interoperability between applications and content are removed, as the user may combine data, models and validation from multiple sources in a dependable and time-effective way. PMID:20807436

Collaborative development of predictive toxicology applications.

PubMed

Hardy, Barry; Douglas, Nicki; Helma, Christoph; Rautenberg, Micha; Jeliazkova, Nina; Jeliazkov, Vedrin; Nikolova, Ivelina; Benigni, Romualdo; Tcheremenskaia, Olga; Kramer, Stefan; Girschick, Tobias; Buchwald, Fabian; Wicker, Joerg; Karwath, Andreas; Gütlein, Martin; Maunz, Andreas; Sarimveis, Haralambos; Melagraki, Georgia; Afantitis, Antreas; Sopasakis, Pantelis; Gallagher, David; Poroikov, Vladimir; Filimonov, Dmitry; Zakharov, Alexey; Lagunin, Alexey; Gloriozova, Tatyana; Novikov, Sergey; Skvortsova, Natalia; Druzhilovsky, Dmitry; Chawla, Sunil; Ghosh, Indira; Ray, Surajit; Patel, Hitesh; Escher, Sylvia

2010-08-31

OpenTox provides an interoperable, standards-based Framework for the support of predictive toxicology data management, algorithms, modelling, validation and reporting. It is relevant to satisfying the chemical safety assessment requirements of the REACH legislation as it supports access to experimental data, (Quantitative) Structure-Activity Relationship models, and toxicological information through an integrating platform that adheres to regulatory requirements and OECD validation principles. Initial research defined the essential components of the Framework including the approach to data access, schema and management, use of controlled vocabularies and ontologies, architecture, web service and communications protocols, and selection and integration of algorithms for predictive modelling. OpenTox provides end-user oriented tools to non-computational specialists, risk assessors, and toxicological experts in addition to Application Programming Interfaces (APIs) for developers of new applications. OpenTox actively supports public standards for data representation, interfaces, vocabularies and ontologies, Open Source approaches to core platform components, and community-based collaboration approaches, so as to progress system interoperability goals.The OpenTox Framework includes APIs and services for compounds, datasets, features, algorithms, models, ontologies, tasks, validation, and reporting which may be combined into multiple applications satisfying a variety of different user needs. OpenTox applications are based on a set of distributed, interoperable OpenTox API-compliant REST web services. The OpenTox approach to ontology allows for efficient mapping of complementary data coming from different datasets into a unifying structure having a shared terminology and representation.Two initial OpenTox applications are presented as an illustration of the potential impact of OpenTox for high-quality and consistent structure-activity relationship modelling of REACH-relevant endpoints: ToxPredict which predicts and reports on toxicities for endpoints for an input chemical structure, and ToxCreate which builds and validates a predictive toxicity model based on an input toxicology dataset. Because of the extensible nature of the standardised Framework design, barriers of interoperability between applications and content are removed, as the user may combine data, models and validation from multiple sources in a dependable and time-effective way.

The Toxicology Investigators Consortium Case Registry-the 2015 Experience.

PubMed

Farrugia, Lynn A; Rhyee, Sean H; Campleman, Sharan L; Ruha, Anne-Michelle; Weigand, Timothy; Wax, Paul M; Brent, Jeffrey

2016-09-01

The American College of Medical Toxicology established the Toxicology Investigators Consortium (ToxIC) Case Registry in 2010. The Registry contains all medical toxicology consultations performed at participating sites. The Registry has continued to grow since its inception, and as of December 31, 2015, contains 43,099 cases. This is the sixth annual report of the ToxIC Registry, summarizing the additional 8115 cases entered in 2015. Cases were identified by a query of the Registry for all cases entered between January 1 and December 31, 2015. Specific data reviewed for analysis included demographics (age, race, gender), source of consultation, reason for consultation, agents and agent classes involved in exposures, signs, symptoms, clinical findings, fatalities, and treatment. By the end of 2015, there were 50 active sites, consisting of 101 separate health-care facilities; 51.2 % of cases involved females. Adults between the ages of 19 and 65 made up the majority (64.2 %) of Registry cases. Caucasian race was the most commonly reported (55.6 %); 9.6 % of cases were identified as Hispanic ethnicity. Inpatient and emergency department referrals were by far the most common referral sources (92.9 %). Intentional pharmaceutical exposures remained the most frequent reason for consultation, making up 52.3 % of cases. Of these intentional pharmaceutical exposures, 69 % represented an attempt at self-harm, and 85.6 % of these were a suicide attempt. Nonopioid analgesics, sedative-hypnotics, and antidepressant agents were the most commonly reported agent classes in 2015. Almost one-third of Registry cases involved a diagnosed toxidrome (32.8 %), with a sedative-hypnotic toxidrome being the most frequently described. Significant vital sign abnormalities were recorded in 25.3 % of cases. There were 98 fatalities reported in the Registry (1.2 %). Adverse drug reactions were reported in 4.3 % of cases. Toxicological treatment was given in 65.3 % of cases, with 33.0 % receiving specific antidotal therapy. Exposure characteristics and trends overall were similar to prior years. While treatment interventions were required in the majority of cases, fatalities were rare.

A view at the interface between particle chemistry and toxicology

EPA Science Inventory

Air pollution includes a complex mixture of carbonaceous gases and particles emitted from multiple anthropogenic, biogenic, and biomass burning sources, and also includes secondary organic components that form during atmospheric aging of these emissions. Exposure to these mixture...

Evidence-based causation in toxicology: A 10-year retrospective.

PubMed

James, R C; Britt, J K; Halmes, N C; Guzelian, P S

2015-12-01

We introduced Evidence-based Toxicology (EBT) in 2005 to address the disparities that exist between the various Weight-of-Evidence (WOE) methods typically applied in the regulatory hazard decision-making arena and urged toxicologists to adopt the evidence-based guidelines long-utilized in medicine (i.e., Evidence-Based Medicine or EBM). This review of the activities leading to the adoption of evidence-based methods and EBT during the last decade demonstrates how fundamental concepts that form EBT, such as the use of systematic reviews to capture and consider all available information, are improving toxicological evaluations performed by various groups and agencies. We reiterate how the EBT framework, a process that provides a method for performing human chemical causation analyses in an objective, transparent and reproducible manner, differs significantly from past and current regulatory WOE approaches. We also discuss why the uncertainties associated with regulatory WOE schemes lead to a definition of the term "risk" that contains unquantifiable uncertainties not present in this term as it is used in epidemiology and medicine. We believe this distinctly different meaning of "risk" should be clearly conveyed to those not familiar with this difference (e.g., the lay public), when theoretical/nomologic risks associated with chemical-induced toxicities are presented outside of regulatory and related scientific parlance. © The Author(s) 2015.

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

PubMed

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

2013-12-01

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

Improving substance information in USEtox® , part 1: Discussion on data and approaches for estimating freshwater ecotoxicity effect factors.

PubMed

Saouter, Erwan; Aschberger, Karin; Fantke, Peter; Hauschild, Michael Z; Bopp, Stephanie K; Kienzler, Aude; Paini, Alicia; Pant, Rana; Secchi, Michela; Sala, Serenella

2017-12-01

The scientific consensus model USEtox ® is recommended by the European Commission as the reference model to characterize life cycle chemical emissions in terms of their potential human toxicity and freshwater aquatic ecotoxicity impacts in the context of the International Reference Life Cycle Data System Handbook and the Environmental Footprint pilot phase looking at products (PEF) and organizations (OEF). Consequently, this model has been systematically used within the PEF/OEF pilot phase by 25 European Union industry sectors, which manufacture a wide variety of consumer products. This testing phase has raised some questions regarding the derivation of and the data used for the chemical-specific freshwater ecotoxicity effect factor in USEtox. For calculating the potential freshwater aquatic ecotoxicity impacts, USEtox bases the effect factor on the chronic hazard concentration (HC50) value for a chemical calculated as the arithmetic mean of all logarithmized geometric means of species-specific chronic median lethal (or effect) concentrations (L[E]C50). We investigated the dependency of the USEtox effect factor on the selection of ecotoxicological data source and toxicological endpoints, and we found that both influence the ecotoxicity ranking of chemicals and may hence influence the conclusions of a PEF/OEF study. We furthermore compared the average measure (HC50) with other types of ecotoxicity effect indicators, such as the lowest species EC50 or no-observable-effect concentration, frequently used in regulatory risk assessment, and demonstrated how they may also influence the ecotoxicity ranking of chemicals. We acknowledge that these indicators represent different aspects of a chemical's ecotoxicity potential and discuss their pros and cons for a comparative chemical assessment as performed in life cycle assessment and in particular within the PEF/OEF context. Environ Toxicol Chem 2017;36:3450-3462. © 2017 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC. © 2017 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC.

ADVANCED COMPUTATIONAL METHODS IN DOSE MODELING

EPA Science Inventory

The overall goal of the EPA-ORD NERL research program on Computational Toxicology (CompTox) is to provide the Agency with the tools of modern chemistry, biology, and computing to improve quantitative risk assessments and reduce uncertainties in the source-to-adverse outcome conti...

Natural toxins for use in pest management

USDA-ARS?s Scientific Manuscript database

Natural toxins are a source of new chemical classes of pesticides, as well as environmentally and toxicologically safer molecules than many of the currently used pesticides. Furthermore, they often have molecular target sites that are not exploited by currently marketed pesticides. There are highly ...

Dose-mortality assessment upon reuse and recycling of industrial sludge.

PubMed

Lin, Kae-Long; Chen, Bor-Yann

2007-09-05

This study provides a novel attempt to put forward, in general toxicological terms, quantitative ranking of toxicity of various sources of sludge for possible reusability in further applications. The high leaching concentrations of copper in printed circuit board (PCB) sludge and chromium in leather sludge apparently exceeded current Taiwan's EPA regulatory thresholds and should be classified as hazardous wastes. Dose-mortality analysis indicated that the toxicity ranking of different sources of sludge was PCB sludge>CaF(2) sludge>leather sludge. PCB sludge was also confirmed as a hazardous waste since the toxicity potency of PCB sludge was nearly identical to CdCl(2). However, leather sludge seemed to be much less toxic than as anticipated, perhaps due to a significant decrease of toxic species bioavailable in the aqueous phase to the reporter bacterium Escherichia coli DH5alpha. For possible reusability of sludge, maximum concentrations allowable to be considered "safe" (ca. EC(100)/100) were 9.68, 42.1 and 176 mgL(-1) for CaF(2) sludge, PCB sludge and leather sludge, respectively.

Compositional and toxicological evaluation of the diazotrophic cyanobacterium, Cyanothece sp. strain ATCC 51142

NASA Technical Reports Server (NTRS)

Schneegurt, M. A.; Arieli, B.; McKeehen, J. D.; Stephens, S. D.; Nielsen, S. S.; Saha, P. R.; Trumbo, P. R.; Sherman, L. A.; Mitchell, C. A. (Principal Investigator)

1995-01-01

Compositional analyses of Cyanothece sp. strain ATCC 51142 showed high protein (50-60%) and low fat (0.4-1%) content, and the ability to synthesize vitamin B12. The amino acid profile indicated that Cyanothece sp. was a balanced protein source. Fatty acids of the 18:3n-3 type were also present. Mineral analyses indicated that the cellular biomass may be a good source of Fe, Zn and Na. Caloric content was 4.5 to 5.1 kcal g dry weight-1 and the carbon content was approximately 40% on a dry weight basis. Nitrogen content was 8 to 9% on a dry weight basis and total nucleic acids were 1.3% on a dry weight basis. Short-term feeding studies in rats followed by histopathology found no toxicity or dietary incompatibility problems. The level of uric acid and allantoin in urine and tissues was low, suggesting no excess of nucleic acids, as sometimes reported in the past for a cyanobacteria-containing diet. The current work discusses the potential implications of these results for human nutrition applications.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Annette Rohr

2004-12-02

This report documents progress made on the subject project during the period of March 1, 2004 through August 31, 2004. 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 Agreementmore » (henceforth referred to as ''the Agreement'') for which this technical progress report has been prepared covers the analysis and interpretation of the field data collected at the first power plant (henceforth referred to as Plant 0, and located in the Upper Midwest), followed by the performance and analysis of similar field experiments at two additional coal-fired power plants (Plants 1 and 2) utilizing different coal types and with different plant configurations. Significant progress was made on the Project during this reporting period, with field work being initiated at Plant 0. Initial testing of the stack sampling system and reaction apparatus revealed that primary particle concentrations were lower than expected in the emissions entering the mobile chemical laboratory. Initial animal exposures to primary emissions were carried out (Scenario 1) to ensure successful implementation of all study methodologies and toxicological assessments. Results indicated no significant toxicological effects in response to primary emissions exposures. Exposures were then carried out to diluted, oxidized, neutralized emissions with the addition of secondary organic aerosol (Scenario 5), both during the day and also at night when primary particle concentrations in the sampled stack emissions 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.« less

Are we in the dark ages of environmental toxicology?

PubMed

McCarty, L S

2013-12-01

Environmental toxicity is judged to be in a "dark ages" period due to longstanding limitations in the implementation of the simple conceptual model that is the basis of current aquatic toxicity testing protocols. Fortunately, the environmental regulatory revolution of the last half-century is not substantially compromised as development of past regulatory guidance was designed to deal with limited amounts of relatively poor quality toxicity data. However, as regulatory objectives have substantially increased in breadth and depth, aquatic toxicity data derived with old testing methods are no longer adequate. In the near-term explicit model description and routine assumption validation should be mandatory. Updated testing methods could provide some improvements in toxicological data quality. A thorough reevaluation of toxicity testing objectives and methods resulting in substantially revised standard testing methods, plus a comprehensive scheme for classification of modes/mechanisms of toxic action, should be the long-term objective. Copyright © 2013 Elsevier Inc. All rights reserved.

Approaches to developing alternative and predictive toxicology based on PBPK/PD and QSAR modeling.

PubMed Central

Yang, R S; Thomas, R S; Gustafson, D L; Campain, J; Benjamin, S A; Verhaar, H J; Mumtaz, M M

1998-01-01

Systematic toxicity testing, using conventional toxicology methodologies, of single chemicals and chemical mixtures is highly impractical because of the immense numbers of chemicals and chemical mixtures involved and the limited scientific resources. Therefore, the development of unconventional, efficient, and predictive toxicology methods is imperative. Using carcinogenicity as an end point, we present approaches for developing predictive tools for toxicologic evaluation of chemicals and chemical mixtures relevant to environmental contamination. Central to the approaches presented is the integration of physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) and quantitative structure--activity relationship (QSAR) modeling with focused mechanistically based experimental toxicology. In this development, molecular and cellular biomarkers critical to the carcinogenesis process are evaluated quantitatively between different chemicals and/or chemical mixtures. Examples presented include the integration of PBPK/PD and QSAR modeling with a time-course medium-term liver foci assay, molecular biology and cell proliferation studies. Fourier transform infrared spectroscopic analyses of DNA changes, and cancer modeling to assess and attempt to predict the carcinogenicity of the series of 12 chlorobenzene isomers. Also presented is an ongoing effort to develop and apply a similar approach to chemical mixtures using in vitro cell culture (Syrian hamster embryo cell transformation assay and human keratinocytes) methodologies and in vivo studies. The promise and pitfalls of these developments are elaborated. When successfully applied, these approaches may greatly reduce animal usage, personnel, resources, and time required to evaluate the carcinogenicity of chemicals and chemical mixtures. Images Figure 6 PMID:9860897

A series of forensic toxicology and drug seizure cases involving illicit fentanyl alone and in combination with heroin, cocaine or heroin and cocaine.

PubMed

Marinetti, Laureen J; Ehlers, Brooke J

2014-10-01

The Montgomery County Coroner's Office Toxicology Section and the Miami Valley Regional Crime Lab (MVRCL) Drug Chemistry Section have been receiving case work in drug seizures, death cases and human performance cases involving products marketed as heroin or as illicit fentanyl. Upon analysis by the Drug Chemistry Section, these products were found to contain various drug(s) including illicit fentanyl only, illicit fentanyl and heroin, illicit fentanyl and cocaine and illicit fentanyl, heroin and cocaine. Both the Chemistry and Toxicology Sections began seeing these combinations starting in late October 2013. The percentage of the combinations encountered by the MVRCL as well as the physical appearance of the product, and the results of presumptive screening tests will be discussed. The demographics of the users and the results of toxicology and autopsy findings on the decedents will also be discussed. According to regional drug task force undercover agents, there is evidence that some of the products are being sold as illicit fentanyl and not just as a heroin product. Also, there is no evidence to support that the fentanyl source is being diverted from pharmaceutical grade fentanyl. The chemistry section currently has over 109 confirmed cases, and the toxicology section currently has 81 confirmed drug deaths, 8 driving under the influence of drugs and 1 suicidal hanging. Both sections are continuing to see these cases at the present time. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Annette C. Rohr; Petros Koutrakis; John Godleski

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 sourcemore » 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 (BAL) fluid cytology and biochemistry; (3) blood cytology; (4) in vivo oxidative stress in heart and lung tissue; and (5) heart and lung histopathology. In addition, at one plant, cardiac arrhythmias and heart rate variability (HRV) were evaluated in a rat model of myocardial infarction. Statistical analyses included analyses of variance (ANOVA) to determine differences between exposed and control animals in response to different scenario/plant combinations; univariate analyses to link individual scenario components to responses; and multivariate analyses (Random Forest analyses) to evaluate component effects in a multipollutant setting. Results from the power plant studies indicated some biological responses to some plant/scenario combinations. A number of significant breathing pattern changes were observed; however, significant clinical changes such as specific irritant effects were not readily apparent, and effects tended to be isolated changes in certain respiratory parameters. Some individual exposure scenario components appeared to be more strongly and consistently related to respiratory parameter changes; however, the specific scenario investigated remained a better predictor of response than individual components of that scenario. Bronchoalveolar lavage indicated some changes in cellularity of BAL fluid in response to the POS and PONS scenarios; these responses were considered toxicologically mild in magnitude. No changes in blood cytology were observed at any plant or scenario. Lung oxidative stress was increased with the POS scenario at one plant, and cardiac oxidative stress was increased with the PONS scenario also at one plant, suggesting limited oxidative stress in response to power plant emissions with added atmospheric constituents. There were some mild histological findings in lung tissue in response to the P and PONS scenarios. Finally, the MI model experiments indicated that premature ventricular beat frequency was increased at the plant studied, while no changes in heart rate, HRV, or electrocardiographic intervals were observed. Overall, the TERESA results should be interpreted as indicating toxicologically mild adverse responses to some scenarios. The varied responses among the three plants indicate heterogeneity in emissions. Ongoing studies using the TERESA approach to evaluate the toxicity of traffic-related pollution will yield valuable data for comparative toxicity assessment and will give us a better understanding of the contribution of different sources to the morbidity and mortality associated with exposure to air pollution.« less

Occupational risk and toxicology evaluations of industrial water conditioning.

PubMed

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.

Letter from Gregory Dolan requesting action on RFC #10005

EPA Pesticide Factsheets

Letter from Gregory Dolan reiterating request for the removal of the EPA's draft toxicological review of methanol, and all other documents and assessments related to the methanol study conducted by the Ramazzini Institues from the IRIS database and other EPA public dissemination sources.

Mobilizing EPA's Comptox Chemistry Dashboard Data on Mobile Devices (ACS Spring Meeting)

EPA Science Inventory

The EPA’s National Center of Computational Toxicology (NCCT) Chemistry Dashboard provides access to chemistry data for about 720,000 chemical substances. The application is used to source, for example: physicochemical property data, bioassay screening data and functional use, and...

Ignition of a human body by a modest external source: a case report.

PubMed

Palmiere, Cristian; Staub, Christian; La Harpe, Romano; Mangin, Patrice

2009-07-01

A case of sustained combustion of a human body that occurred in 2006 in Geneva, Switzerland, is presented. The body of a man was discovered at home and found to have been almost completely incinerated between the knees and the mid-chest, with less damage to the head, arms, lower legs and feet. His dog was also found dead just behind the house door. The external source of ignition was most likely a cigarette or a cigar. The chair in which the man had been sitting was largely consumed while other objects in the room exhibited only a brown oily or greasy coating and were virtually undamaged. Toxicological analyses carried out on the blood from the lower legs showed low levels of desalkylflurazepam. Alcohol concentration was 1.10 per thousand, carboxyhaemoglobin levels were 12% and cyanide concentration was 0.05 mg/L. Toxicological analyses carried out on the dog's blood showed carboxyhaemoglobin levels at 65%.

Neural Differentiation of Human Pluripotent Stem Cells for Nontherapeutic Applications: Toxicology, Pharmacology, and In Vitro Disease Modeling.

PubMed

Yap, May Shin; Nathan, Kavitha R; Yeo, Yin; Lim, Lee Wei; Poh, Chit Laa; Richards, Mark; Lim, Wei Ling; Othman, Iekhsan; Heng, Boon Chin

2015-01-01

Human pluripotent stem cells (hPSCs) derived from either blastocyst stage embryos (hESCs) or reprogrammed somatic cells (iPSCs) can provide an abundant source of human neuronal lineages that were previously sourced from human cadavers, abortuses, and discarded surgical waste. In addition to the well-known potential therapeutic application of these cells in regenerative medicine, these are also various promising nontherapeutic applications in toxicological and pharmacological screening of neuroactive compounds, as well as for in vitro modeling of neurodegenerative and neurodevelopmental disorders. Compared to alternative research models based on laboratory animals and immortalized cancer-derived human neural cell lines, neuronal cells differentiated from hPSCs possess the advantages of species specificity together with genetic and physiological normality, which could more closely recapitulate in vivo conditions within the human central nervous system. This review critically examines the various potential nontherapeutic applications of hPSC-derived neuronal lineages and gives a brief overview of differentiation protocols utilized to generate these cells from hESCs and iPSCs.

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

PubMed Central

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 international and national collaborative research projects in the field of toxicology. PMID:24443999

QSAR Methods.

PubMed

Gini, Giuseppina

2016-01-01

In this chapter, we introduce the basis of computational chemistry and discuss how computational methods have been extended to some biological properties and toxicology, in particular. Since about 20 years, chemical experimentation is more and more replaced by modeling and virtual experimentation, using a large core of mathematics, chemistry, physics, and algorithms. Then we see how animal experiments, aimed at providing a standardized result about a biological property, can be mimicked by new in silico methods. Our emphasis here is on toxicology and on predicting properties through chemical structures. Two main streams of such models are available: models that consider the whole molecular structure to predict a value, namely QSAR (Quantitative Structure Activity Relationships), and models that find relevant substructures to predict a class, namely SAR. The term in silico discovery is applied to chemical design, to computational toxicology, and to drug discovery. We discuss how the experimental practice in biological science is moving more and more toward modeling and simulation. Such virtual experiments confirm hypotheses, provide data for regulation, and help in designing new chemicals.

EMERGING DISINFECTION BY-PRODUCTS OF TOXICOLOGICAL INTEREST: RESULTS OF A NATIONWIDE OCCURRENCE STUDY

EPA Science Inventory

The Safe Drinking Water Act and Amendments requires that EPA address disinfection by-products (DBPs) in drinking water. DBPs are formed when a disinfectant (such as chlorine) reacts with organic matter and/or bromide naturally present in source waters. Drinking water disinfecti...

Characterization of Soy Biodiesel Exhaust and Toxicological Effects in Mice

EPA Science Inventory

Although biofuel use across the world is increasing, very little is known about possible health effects resulting from biofuel exhaust (BE) from this relatively new source of transportation fuel. The U.S. EPA has instigated an in vivo screening approach in rodents to examine whet...

SEDIMENT TOXICOLOGY TESTING, ISSUES AND METHODS

EPA Science Inventory

The significant role that sediments play in aquatic ecosystems is well known. They serve as both a sink and a source of organic and inorganic materials, where critical cycling processes for organic matter and the critical elements (e.g., C, N, P, and S). The majority of decomposi...

Standardizing Acute Toxicity Data for use in Ecotoxicology Models: Influence of Test Type, Life Stage, and Concentration Reporting

EPA Science Inventory

Ecotoxicological models generally have large data requirements and are frequently based on existing information from diverse sources. Standardizing data for toxicological models may be necessary to reduce extraneous variation and to ensure models reflect intrinsic relationships. ...

Toxicological risk of melamine and cyanuric acid in food and feed

PubMed Central

Suchý, Pavel; Straková, Eva; Herzig, Ivan; Staňa, Jaroslav; Kalusová, Renata; Pospíchalová, Markéta

2009-01-01

From the toxicological point of view, in the last two years melamine and cyanuric acid have become matters of great interest. These substances, especially melamine, have been abused during food and feed adulteration by increasing the content of nitrogen compounds in these products. Melamine and cyanuric acid as individual substances do not pose any serious risk in terms of toxicology. From the point of view of toxicology, it is especially the complex of melamine with cyanuric acid that is important. This complex, also known as the melamine-cyanurate complex, is a cause of human and animal health problems. In this work we present two examples of the incidence of melamine and cyanuric acid in two feed products originating from China. They were rice and the pea concentrates intended for animal nutrition. Protein concentrates can be the main risk factor for food chain contamination with melamine and cyanuric acid, especially those of unknown origin. Feed with a high content of nitrogen compounds and low content of aminoacids can be regarded as particularly suspicious. A comparison of results for determining nitrogen compounds and amines can be used as proof of adulteration of protein feeds. These feeds must be subjected to further analysis to determine melamine and cyanuric acid. PMID:21217848

Supporting read-across using biological data.

PubMed

Zhu, Hao; Bouhifd, Mounir; Donley, Elizabeth; Egnash, Laura; Kleinstreuer, Nicole; Kroese, E Dinant; Liu, Zhichao; Luechtefeld, Thomas; Palmer, Jessica; Pamies, David; Shen, Jie; Strauss, Volker; Wu, Shengde; Hartung, Thomas

2016-01-01

Read-across, i.e. filling toxicological data gaps by relating to similar chemicals, for which test data are available, is usually done based on chemical similarity. Besides structure and physico-chemical properties, however, biological similarity based on biological data adds extra strength to this process. In the context of developing Good Read-Across Practice guidance, a number of case studies were evaluated to demonstrate the use of biological data to enrich read-across. In the simplest case, chemically similar substances also show similar test results in relevant in vitro assays. This is a well-established method for the read-across of e.g. genotoxicity assays. Larger datasets of biological and toxicological properties of hundreds and thousands of substances become increasingly available enabling big data approaches in read-across studies. Several case studies using various big data sources are described in this paper. An example is given for the US EPA's ToxCast dataset allowing read-across for high quality uterotrophic assays for estrogenic endocrine disruption. Similarly, an example for REACH registration data enhancing read-across for acute toxicity studies is given. A different approach is taken using omics data to establish biological similarity: Examples are given for stem cell models in vitro and short-term repeated dose studies in rats in vivo to support read-across and category formation. These preliminary biological data-driven read-across studies highlight the road to the new generation of read-across approaches that can be applied in chemical safety assessment.

Functional toxicity and tolerance patterns of bioavailable Pd(II), Pt(II), and Rh(III) on suspended Saccharomyces cerevisiae cells assayed in tandem by a respirometric biosensor.

PubMed

Frazzoli, Chiara; Dragone, Roberto; Mantovani, Alberto; Massimi, Cristiana; Campanella, Luigi

2007-12-01

Toxicological implications of exposure to bioavailable platinum group metals, here Pd, Pt, and Rh, are still to be clarified. This study obtained by a biosensor-based method preliminary information on potential effects on cellular metabolism as well as on possible tolerance mechanisms. Aerobic respiration was taken as the toxicological end point to perform tandem tests, namely functional toxicity test and tolerance test. Cells were suspended in the absence of essential constituents for growth. The dose-response curves obtained by exposure (2 h) to the metals (nanogram per gram range) suggested the same mechanisms of action, with Rh showing the greatest curve steepness and the lowest EC50 value. Conservative (95% lower confidence interval) EC10 values were 187, 85 and 51 ng g(-1) for Pt, Pd, and Rh respectively. Tolerance patterns were tested during the same runs. The full tolerance obtained after 12 h of exposure to each metal suggested mitochondrial inhibition of aerobic respiration as a target effect. The hazard rating of the metals in the tolerance test changed in the Rh EC50 range, where Rh showed the lowest toxicity. The observed tolerance might suggest a protective mechanism such as metallothionein induction at concentrations around the EC50 values. The performance of the bioassay was satisfactory, in terms of the limit of detection, repeatability, reproducibility, roboustness, sensibility, and stability; the method's critical uncertainty sources were identified for improvements.

Assessment of herbal medicinal products: Challenges, and opportunities to increase the knowledge base for safety assessment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jordan, Scott A., E-mail: scott.jordan@hc-sc.gc.c; Cunningham, David G.; Marles, Robin J.

Although herbal medicinal products (HMP) have been perceived by the public as relatively low risk, there has been more recognition of the potential risks associated with this type of product as the use of HMPs increases. Potential harm can occur via inherent toxicity of herbs, as well as from contamination, adulteration, plant misidentification, and interactions with other herbal products or pharmaceutical drugs. Regulatory safety assessment for HMPs relies on both the assessment of cases of adverse reactions and the review of published toxicity information. However, the conduct of such an integrated investigation has many challenges in terms of the quantitymore » and quality of information. Adverse reactions are under-reported, product quality may be less than ideal, herbs have a complex composition and there is lack of information on the toxicity of medicinal herbs or their constituents. Nevertheless, opportunities exist to capitalise on newer information to increase the current body of scientific evidence. Novel sources of information are reviewed, such as the use of poison control data to augment adverse reaction information from national pharmacovigilance databases, and the use of more recent toxicological assessment techniques such as predictive toxicology and omics. The integration of all available information can reduce the uncertainty in decision making with respect to herbal medicinal products. The example of Aristolochia and aristolochic acids is used to highlight the challenges related to safety assessment, and the opportunities that exist to more accurately elucidate the toxicity of herbal medicines.« less

t4 report1

PubMed Central

Zhu, Hao; Bouhifd, Mounir; Kleinstreuer, Nicole; Kroese, E. Dinant; Liu, Zhichao; Luechtefeld, Thomas; Pamies, David; Shen, Jie; Strauss, Volker; Wu, Shengde; Hartung, Thomas

2016-01-01

Summary Read-across, i.e. filling toxicological data gaps by relating to similar chemicals, for which test data are available, is usually done based on chemical similarity. Besides structure and physico-chemical properties, however, biological similarity based on biological data adds extra strength to this process. In the context of developing Good Read-Across Practice guidance, a number of case studies were evaluated to demonstrate the use of biological data to enrich read-across. In the simplest case, chemically similar substances also show similar test results in relevant in vitro assays. This is a well-established method for the read-across of e.g. genotoxicity assays. Larger datasets of biological and toxicological properties of hundreds and thousands of substances become increasingly available enabling big data approaches in read-across studies. Several case studies using various big data sources are described in this paper. An example is given for the US EPA’s ToxCast dataset allowing read-across for high quality uterotrophic assays for estrogenic endocrine disruption. Similarly, an example for REACH registration data enhancing read-across for acute toxicity studies is given. A different approach is taken using omics data to establish biological similarity: Examples are given for stem cell models in vitro and short-term repeated dose studies in rats in vivo to support read-across and category formation. These preliminary biological data-driven read-across studies highlight the road to the new generation of read-across approaches that can be applied in chemical safety assessment. PMID:26863516

Calculational note for the radiological and toxicological effects of a UO{sub 3} release from the T-hopper storage pad

DOE Office of Scientific and Technical Information (OSTI.GOV)

Goldberg, H.J.

1998-06-18

UO{sub 3} powder is stored at the T-hopper storage area associated with the 2714-U building in the 200 west area. The T-hopper containers and 13 drums containing this material are used to store the powder on pads immediately north of the building. An interim safety basis document (WHC,1996) was issued in 1996 for the UO{sub 3} powder storage area. In this document the isotope {sup 99}Tc was not included in the source term used to calculate the radiological consequences of a postulated release of the powder. A calculations note (HNF, 1998) was issued to remedy that deficiency. The present documentmore » is a revision to that document to reflect updated data concerning the solubility of UO{sub 3} in simulated lung fluid and to utilize more realistic powder release fractions.« less

Drug shortages: Implications for medical toxicology.

PubMed

Mazer-Amirshahi, Maryann; Hawley, Kristy L; Zocchi, Mark; Fox, Erin; Pines, Jesse M; Nelson, Lewis S

2015-07-01

Drug shortages have significantly increased over the past decade. There are limited data describing how shortages impact medical toxicology of drugs. To characterize drug shortages affecting the management of poisoned patients. Drug shortage data from January 2001 to December 2013 were obtained from the University of Utah Drug Information Service. Shortage data for agents used to treat poisonings were analyzed. Information on drug type, formulation, reason for shortage, shortage duration, marketing, and whether the drug was available from a single source was collected. The availability of a substitute therapy and whether substitutes were in shortage during the study period were also investigated. Of 1,751 shortages, 141 (8.1%) impacted drugs used to treat poisoned patients, and as of December 2013, 21 (14.9%) remained unresolved. New toxicology shortages increased steadily from the mid-2000s, reaching a high of 26 in 2011. Median shortage duration was 164 days (interquartile range: 76-434). Generic drugs were involved in 85.1% of shortages and 41.1% were single-source products. Parenteral formulations were often involved in shortages (89.4%). The most common medications in shortage were sedative/hypnotics (15.6%). An alternative agent was available for 121 (85.8%) drugs; however, 88 (72.7%) alternatives were also affected by shortages at some point during the study period. When present, the most common reasons reported were manufacturing delays (22.0%) and supply/demand issues (17.0%). Shortage reason was not reported for 48.2% of drugs. Toxicology drug shortages are becoming increasingly prevalent, which can result in both suboptimal treatment and medication errors from using less familiar alternatives. Drug shortages affected a substantial number of critical agents used in the management of poisoned patients. Shortages were often of long duration and for drugs without alternatives. Providers caring for poisoned patients should be aware of current shortages and implement mitigation strategies to safeguard patient care.

Improving substance information in USEtox® , part 2: Data for estimating fate and ecosystem exposure factors.

PubMed

Saouter, Erwan; Aschberger, Karin; Fantke, Peter; Hauschild, Michael Z; Kienzler, Aude; Paini, Alicia; Pant, Rana; Radovnikovic, Anita; Secchi, Michela; Sala, Serenella

2017-12-01

The scientific consensus model USEtox ® has been developed since 2003 under the auspices of the United Nations Environment Programme-Society of Environmental Toxicology and Chemistry Life Cycle Initiative as a harmonized approach for characterizing human and freshwater toxicity in life cycle assessment and other comparative assessment frameworks. Using physicochemical substance properties, USEtox quantifies potential human toxicity and freshwater ecotoxicity impacts by combining environmental fate, exposure, and toxicity effects information, considering multimedia fate and multipathway exposure processes. The main source to obtain substance properties for USEtox 1.01 and 2.0 is the Estimation Program Interface (EPI Suite™) from the US Environmental Protection Agency. However, since the development of the original USEtox substance databases, new chemical regulations have been enforced in Europe, such as the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) and the Plant Protection Products regulations. These regulations require that a chemical risk assessment for humans and the environment is performed before a chemical is placed on the European market. Consequently, additional physicochemical property data and new toxicological endpoints are now available for thousands of chemical substances. The aim of the present study was to explore the extent to which the new available data can be used as input for USEtox-especially for application in environmental footprint studies-and to discuss how this would influence the quantification of fate and exposure factors. Initial results show that the choice of data source and the parameters selected can greatly influence fate and exposure factors, leading to potentially different rankings and relative contributions of substances to overall human toxicity and ecotoxicity impacts. Moreover, it is crucial to discuss the relevance of the exposure factor for freshwater ecotoxicity impacts, particularly for persistent highly adsorbing and bioaccumulating substances. Environ Toxicol Chem 2017;36:3463-3470. © 2017 The Authors. Environmental Toxicology and Chemistry Published by Wiley Periodicals, Inc. on behalf of SETAC. © 2017 The Authors. Environmental Toxicology and Chemistry Published by Wiley Periodicals, Inc. on behalf of SETAC.

IRIS Toxicological Review of Ammonia Noncancer Inhalation (Final Report)

EPA Science Inventory

EPA has finalized the Integrated Risk Information System (IRIS) Assessment of Ammonia (Noncancer Inhalation). This assessment addresses the potential noncancer human health effects from long-term inhalation exposure to ammonia. Now final, this assessment will update the ...

Environmental Deflection: The Impact of Toxicant Exposures on the Aging Epigenome.

PubMed

Kochmanski, Joseph; Montrose, Luke; Goodrich, Jaclyn M; Dolinoy, Dana C

2017-04-01

Epigenetic drift and age-related methylation have both been used in the literature to describe changes in DNA methylation that occurs with aging. However, ambiguity remains regarding the exact definition of both of these terms, and neither of these fields of study explicitly considers the impact of environmental factors on the aging epigenome. Recent twin studies have demonstrated longitudinal, pair-specific discordance in DNA methylation patterns, suggesting an effect of the environment on age-related methylation and/or epigenetic drift. Supporting this idea, other new reports have shown clear environment- and toxicant-mediated shifts away from the baseline rates of age-related methylation and epigenetic drift within an organism, a process we now term "environmental deflection." By defining and delineating environmental deflection, this contemporary review aims to highlight the effects of specific toxicological factors on the rate of DNA methylation changes that occur over the life course. In an effort to inform future epigenetics-based toxicology studies, a field of research now classified as toxicoepigenetics, we provide clear definitions and examples of "epigenetic drift" and "age-related methylation," summarize the recent evidence for environmental deflection of the aging epigenome, and discuss the potential functional effects of environmental deflection. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

The Toxicological Evaluation of Realistic Emissions of Source Aerosols Study: Statistical Methods

PubMed Central

Coull, Brent A.; Wellenius, Gregory A.; Gonzalez-Flecha, Beatriz; Diaz, Edgar; Koutrakis, Petros; Godleski, John J.

2013-01-01

The Toxicological Evaluation of Realistic Emissions of Source Aerosols (TERESA) study involved withdrawal, aging, and atmospheric transformation of emissions of three coal-fired power plants. Toxicological evaluations were carried out in rats exposed to different emission scenarios with extensive exposure characterization. Data generated had multiple levels of resolution: exposure, scenario and constituent chemical composition. Here, we outline a multilayered approach to analyze the associations between exposure and health effects beginning with standard ANOVA models that treat exposure as a categorical variable. The model assessed differences in exposure effects across scenarios (by plant). To assess unadjusted associations between pollutant concentrations and health, univariate analyses were conducted using the difference between the response means under exposed and control conditions and a single constituent concentration as the predictor. Then, a novel multivariate analysis of exposure composition and health was used based on random forests, a recent extension of classification and regression trees that were applied to the outcome differences. For each exposure constituent, this approach yielded a nonparametric measure of the importance of that constituent in predicting differences in response on a given day, controlling for the other measured constituent concentrations in the model. Finally, an R2 analysis compared the relative importance of exposure scenario, plant, and constituent concentrations on each outcome. Peak expiratory flow is used to demonstrate how the multiple levels of the analysis complement each other to assess constituents most strongly associated with health effects. PMID:21913820

The toxicological evaluation of realistic emissions of source aerosols study: statistical methods.

PubMed

Coull, Brent A; Wellenius, Gregory A; Gonzalez-Flecha, Beatriz; Diaz, Edgar; Koutrakis, Petros; Godleski, John J

2011-08-01

The Toxicological Evaluation of Realistic Emissions of Source Aerosols (TERESA) study involved withdrawal, aging, and atmospheric transformation of emissions of three coal-fired power plants. Toxicological evaluations were carried out in rats exposed to different emission scenarios with extensive exposure characterization. Data generated had multiple levels of resolution: exposure, scenario, and constituent chemical composition. Here, we outline a multilayered approach to analyze the associations between exposure and health effects beginning with standard ANOVA models that treat exposure as a categorical variable. The model assessed differences in exposure effects across scenarios (by plant). To assess unadjusted associations between pollutant concentrations and health, univariate analyses were conducted using the difference between the response means under exposed and control conditions and a single constituent concentration as the predictor. Then, a novel multivariate analysis of exposure composition and health was used based on Random Forests(™), a recent extension of classification and regression trees that were applied to the outcome differences. For each exposure constituent, this approach yielded a nonparametric measure of the importance of that constituent in predicting differences in response on a given day, controlling for the other measured constituent concentrations in the model. Finally, an R(2) analysis compared the relative importance of exposure scenario, plant, and constituent concentrations on each outcome. Peak expiratory flow (PEF) is used to demonstrate how the multiple levels of the analysis complement each other to assess constituents most strongly associated with health effects.

[Antidotes: use guidelines and minimun stock in an emergency department].

PubMed

García-Martín, A; Torres Santos-Olmos, R

2012-01-01

To develop a guide for antidotes and other medications used to counteract poisoning, and define the stock in an emergency department, as a safety priority for the part-time pharmacist assigned to the unit. A search of specialist databases and web portals of the Spanish Society of Toxicology and the British National Poisons Information Service, as well as toxicology databases, TOXICONET, information from other hospitals, tertiary sources, Micromedex and Medline. The Guide contains 42 active ingredients and is accessible to the Pharmacy and Emergency departments in electronic format. A minimum emergency stock was agreed based on the daily treatment of a 100 kg patient. This information, including updated expiry dates, is available at the emergency department antidote stock facilities and in electronic format. On a monthly basis, the pharmacist reviews the need to replace any drugs, due to their expiry date or lack of use. The lack of evidence from high quality antidote studies, the variability due to the difficulties of updating sources and some geographical differences in their use means that decision-making can be difficult. It would be useful to have minimum quantity recommendations from societies of toxicology, regulatory agencies and organisations such as the Joint Commission on the Accreditation of Healthcare Organisations. It would also be useful to have a suprahospital risk assessment to optimise management and ensure the availability of antidotes which are expensive, have a limited shelf life, or of which demand is difficult to forecast. Copyright © 2011 SEFH. Published by Elsevier Espana. All rights reserved.

New views on the hypothesis of respiratory cancer risk from soluble nickel exposure; and reconsideration of this risk's historical sources in nickel refineries

PubMed Central

Heller, James G; Thornhill, Philip G; Conard, Bruce R

2009-01-01

Introduction While epidemiological methods have grown in sophistication during the 20th century, their application in historical occupational (and environmental) health research has also led to a corresponding growth in uncertainty in the validity and reliability of the attribution of risk in the resulting studies, particularly where study periods extend back in time to the immediate postwar era (1945–70) when exposure measurements were sporadic, unsystematically collected and primitive in technique; and, more so, to the pre-WWII era (when exposure data were essentially non-existent). These uncertainties propagate with animal studies that are designed to confirm the carcinogenicity by inhalation exposure of a chemical putatively responsible for historical workplace cancers since exact exposure conditions were never well characterized. In this report, we present a weight of scientific evidence examination of the human and toxicological evidence to show that soluble nickel is not carcinogenic; and, furthermore, that the carcinogenic potencies previously assigned by regulators to sulphidic and oxidic nickel compounds for the purposes of developing occupational exposure limits have likely been overestimated. Methods Published, file and archival evidence covering the pertinent epidemiology, biostatistics, confounding factors, toxicology, industrial hygiene and exposure factors, and other risky exposures were examined to evaluate the soluble nickel carcinogenicity hypothesis; and the likely contribution of a competing workplace carcinogen (arsenic) on sulphidic and oxidic nickel risk estimates. Findings Sharp contrasts in available land area and topography, and consequent intensity of production and refinery process layouts, likely account for differences in nickel species exposures in the Kristiansand (KNR) and Port Colborne (PCNR) refineries. These differences indicate mixed sulphidic and oxidic nickel and arsenic exposures in KNR's historical electrolysis department that were previously overlooked in favour of only soluble nickel exposure; and the absence of comparable insoluble nickel exposures in PCNR's tankhouse, a finding that is consistent with the absence of respiratory cancer risk there. The most recent KNR evidence linking soluble nickel with lung cancer risk arose in a reconfiguration of KNR's historical exposures. But the resulting job exposure matrix lacks an objective, protocol-driven rationale that could provide a valid and reliable basis for analyzing the relationship of KNR lung cancer risk with any nickel species. Evidence of significant arsenic exposure during the processing step in the Clydach refinery's hydrometallurgy department in the 1902–1934 time period likely accounts for most of the elevated respiratory cancer risk observed at that time. An understanding of the mechanism for nickel carcinogenicity remains an elusive goal of toxicological research; as does its capacity to confirm the human health evidence on this subject with animal studies. Concluding remarks Epidemiological methods have failed to accurately identify the source(s) of observed lung cancer risk in at least one nickel refinery (KNR). This failure, together with the negative long-term animal inhalation studies on soluble nickel and other toxicological evidence, strongly suggest that the designation of soluble nickel as carcinogenic should be reconsidered, and that the true causes of historical lung cancer risk at certain nickel refineries lie in other exposures, including insoluble nickel compounds, arsenic, sulphuric acid mists and smoking. PMID:19698165

Global change impact on oxidative potential and toxicity of atmospheric particles from the East Mediterranean basin: the ARCHIMEDES initiative

NASA Astrophysics Data System (ADS)

Alleman, Laurent; Anthérieu, Sébastien; Baeza-Squiban, Armelle; Garçon, Guillaume; Lo Guidice, Jean-Marc; Hamonou, Eric; Öztürk, Fatma; Perdrix, Esperanza; Rudich, Yinon; Sciare, Jean; Sauvage, Stéphane

2017-04-01

Climate change (CC) has important social, economical and health implications, notably in accordance with variation in air pollution or microbiome modification and its related toxicity mechanisms. CC will have a strong influence on meteorology, inducing dryer and warmer conditions in some regions. The Mediterranean basin is foreseen as a hotspot for regional climate warming, favoring larger dust episodes, wild fire events, vegetation emissions and changes in air pollution physic-chemical characteristics due to enhanced photochemical reactivity. Increasing concentrations of biogenic volatile organic compounds (VOCs), ozone, and radicals will be associated with rising concentrations of secondary organic aerosols (SOA) and other oxidized aerosols. These expected changes in aerosol composition are currently studied within the international ChArMEx (Chemistry-aerosol Mediterranean Experiment) program, part of the interdisciplinary MISTRALS metaprogramme (Mediterranean Integrated STudies at Regional And Local Scales). According to the LIFE/MED-PARTICLES (LIFE) project, this might result in more adverse effects on health. However, toxicologists are far from having a detailed mechanistic knowledge of the quantitative causal relations between particles (PM) and health effects suggested by epidemiological evidences. Detailed toxicological studies looking at contrasted PM origins and chemical compositions are highly needed, particularly on strongly aged SOA suspected to increase the oxidative potential (OP) and to enhance the toxicity of airborne particles. Intensive researches onto the underlying mechanisms of inflammation started to describe the outlines of the intricate relationship between oxidative stress and inflammation. It is therefore, of great importance to better determine the OP of PM from contrasted surroundings, its relationship with CC through PM's physical, chemical and microbial characteristics, and its toxicological consequences within the lungs. Recently, several projects under the ARCHIMEDES (Envi-MED funded) initiative including various research groups from Eastern Mediterranean countries have been submitted to French research calls. Their objectives are to develop an integrated testing strategy (ITS) through a combination of high throughput screening (HTS) methods based on acellular and lung cellular systems evaluating the respective OP (DTT, ascorbic acid and GSH depletion, DCFH oxidation) of various PM samples according to their origins in terms of sources and CC forecast. In order to ensure significant variability in ageing of the size segregated PM (fine, coarse) tested, samples from both northern (France) and southern countries (Cyprus, Israel, Turkey) should be collected at different seasons and site typologies, searching for various compositions and mixing states in SOA (biogenic, anthropogenic), metals and PAHs. These projects will combine relevant chemical, microbiological (DNA extract) and toxicological experiments (transcriptome, epigenome and secretome). A joint toxicological analysis related to their harmful effects on relevant oxidative (ATP, TAS, GSH/GSSG, gammaH2AX), inflammatory, genetic, and epigenetic endpoints within novel tissue-engineering tools will help in recapturing the native lung environment ex vivo. In the CC context, such projects will help to (1) better understand the cellular and molecular mechanisms of PM toxicity, (2) detect and predict their respiratory effects, (3) better comprehend the relationship between the physicochemical characteristics and the toxicological effects of PM, (4) provide innovative biomarkers that could be subsequently validated in humans and thereby contribute to the predictive toxicology.

EU Framework 6 Project: Predictive Toxicology (PredTox)-overview and outcome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Suter, Laura, E-mail: Laura.suter-dick@roche.com; Schroeder, Susanne; Meyer, Kirstin

2011-04-15

In this publication, we report the outcome of the integrated EU Framework 6 Project: Predictive Toxicology (PredTox), including methodological aspects and overall conclusions. Specific details including data analysis and interpretation are reported in separate articles in this issue. The project, partly funded by the EU, was carried out by a consortium of 15 pharmaceutical companies, 2 SMEs, and 3 universities. The effects of 16 test compounds were characterized using conventional toxicological parameters and 'omics' technologies. The three major observed toxicities, liver hypertrophy, bile duct necrosis and/or cholestasis, and kidney proximal tubular damage were analyzed in detail. The combined approach ofmore » 'omics' and conventional toxicology proved a useful tool for mechanistic investigations and the identification of putative biomarkers. In our hands and in combination with histopathological assessment, target organ transcriptomics was the most prolific approach for the generation of mechanistic hypotheses. Proteomics approaches were relatively time-consuming and required careful standardization. NMR-based metabolomics detected metabolite changes accompanying histopathological findings, providing limited additional mechanistic information. Conversely, targeted metabolite profiling with LC/GC-MS was very useful for the investigation of bile duct necrosis/cholestasis. In general, both proteomics and metabolomics were supportive of other findings. Thus, the outcome of this program indicates that 'omics' technologies can help toxicologists to make better informed decisions during exploratory toxicological studies. The data support that hypothesis on mode of action and discovery of putative biomarkers are tangible outcomes of integrated 'omics' analysis. Qualification of biomarkers remains challenging, in particular in terms of identification, mechanistic anchoring, appropriate specificity, and sensitivity.« less

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

USGS Publications Warehouse

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

2011-01-01

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

RECOMMENDATIONS FOR RESEARCH RELATED TO BIOLOGICAL, CHEMICAL, AND ECOLOGICAL ASPECTS OF SEDIMENT PORE WATER: THE WAY FORWARD

EPA Science Inventory

Toxicity tests are useful and reliable tools for evaluating the adverse effects of chemicals discharged into aquatic ecosystems. The science of sediment toxicology evolved rapidly following the realization that sediments are a sink and a source for contaminants and that they can ...

Incorporating Nondrug Social & Recreational Activities in Outpatient Chemical Dependency Treatment

ERIC Educational Resources Information Center

Siporin, Sheldon; Baron, Lisa

2012-01-01

"Contingency Management programs (CMP) and non-drug social and recreational activities (NDSRA) are interventions premised on behavior theory that rely on external sources of reinforcement alternative to drug-based forms to decrease drug use. CMP usually employs vouchers as reinforcement for negative toxicologies. Despite research support, CMP…

A paler shade of green? The toxicology of biodiesel emissions: recent findings from studies with this alternative fuel

EPA Science Inventory

Background: Biodiesel produced primarily from plants and algal feedstocks is believed to have advantages for production and use compared to petroleum and to some other fuel sources. There is some speculation that exposure to biodiesel combustion emissions may not induce biologic...

PERCHLORATE ENVIRONMENTAL CONTAMINATION: TOXICOLOGICAL REVIEW AND RISK CHARACTERIZATION (EXTERNAL REVIEW DRAFT) 2002

EPA Science Inventory

Perchlorate (ClO4-) is an anion that originates as a contaminant in ground water and surface waters when the salts of ammonium, potassium, magnesium, or sodium dissolve in water. One major source of contamination is the manufacture or improper disposal of ammonium perchlorate th...

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wassom, John S.; Malling, Heinrich V.; Sankaranarayanan, K.

This article traces the development of the field of mutagenesis and its metamorphosis into the research area we now call genetic toxicology. In 1969 this transitional event led to the founding of the Environmental Mutagen Society (EMS). The charter of this new Society was to encourage interest in and study of mutagens in the human environment, particularly as these may be of concern to public health. As the mutagenesis field unfolded and expanded, the lexicon changed and new wording appeared to better describe this evolving area of research. The term genetic toxicology was coined and became an important subspecialty ofmore » the broad area of toxicology. Genetic toxicology is now set for a thorough reappraisal of its methods, goals, and priorities to meet the challenges of the 21st Century. To better understand these challenges, we have revisited the primary goal that the EMS founders had in mind for the Society s main mission and objective, namely, the quantitative assessment of genetic (hereditary) risks to human populations exposed to environmental agents. We also have reflected upon some of the seminal events over the last 40 years that have influenced the advancement of the genetic toxicology discipline and the extent to which the Society s major goal and allied objectives have been achieved. Additionally, we have provided suggestions on how EMS can further advance the science of genetic toxicology in the postgenome era. Chronicling all events and publications that influenced the development of the mutagenesis and genetic toxicology research area for this article was not possible, but some key happenings that contributed to the field s development have been reviewed. Events that led to the origin of EMS are also presented in celebration of the Society s 40th anniversary. Any historical accounting will have perceived deficiencies. Key people, publications, or events that some readers may feel have had significant impact on development of the subject under review may have been overlooked and left out. We are sure that such will be the case with the appraisal given in this article. However, any oversight or failure to make proper acknowledgment of individuals, events, or the citation of relevant references is unintentional.« less

IRIS Toxicological Review of Trimethylbenzenes (Final Report)

EPA Science Inventory

EPA has finalized the Integrated Risk Information System (IRIS) Assessment of Trimethylbenzenes (TMBs). This assessment addresses the potential non-cancer and cancer human health effects from long-term exposure to TMBs. Now final, this assessment will be the first IRIS a...

INTEGRATION OF PATHOLOGY AND TOXICOLOGY IN RISK ASSESSMENT

EPA Science Inventory

In order to develop a scientifically defensible assessment of the risk for the development of cancer after long-term exposure to xenobiotics, regulatory agencies have adopted a uniform approach which includes the characterization of a carcinogenic mode of action and its biologica...

EXPOSURE METHODOLOGIES AND SYSTEMS FOR LONG-TERM CHEMICAL CARCINOGENICITY STUDIES WITH SMALL FISH SPECIES

EPA Science Inventory

Testing waterborne chemical carcinogens in fish models requires accurate, reliable, and reproducible exposures. Because carcinogenesis is a chronic toxicological process and is often associated with prolonged latency periods, systems must accommodate lengthy in-life test periods ...

Aquatic exposures of chemical mixtures in urban environments: Approaches to impact assessment.

PubMed

de Zwart, Dick; Adams, William; Galay Burgos, Malyka; Hollender, Juliane; Junghans, Marion; Merrington, Graham; Muir, Derek; Parkerton, Thomas; De Schamphelaere, Karel A C; Whale, Graham; Williams, Richard

2018-03-01

Urban regions of the world are expanding rapidly, placing additional stress on water resources. Urban water bodies serve many purposes, from washing and sources of drinking water to transport and conduits for storm drainage and effluent discharge. These water bodies receive chemical emissions arising from either single or multiple point sources, diffuse sources which can be continuous, intermittent, or seasonal. Thus, aquatic organisms in these water bodies are exposed to temporally and compositionally variable mixtures. We have delineated source-specific signatures of these mixtures for diffuse urban runoff and urban point source exposure scenarios to support risk assessment and management of these mixtures. The first step in a tiered approach to assessing chemical exposure has been developed based on the event mean concentration concept, with chemical concentrations in runoff defined by volumes of water leaving each surface and the chemical exposure mixture profiles for different urban scenarios. Although generalizations can be made about the chemical composition of urban sources and event mean exposure predictions for initial prioritization, such modeling needs to be complemented with biological monitoring data. It is highly unlikely that the current paradigm of routine regulatory chemical monitoring alone will provide a realistic appraisal of urban aquatic chemical mixture exposures. Future consideration is also needed of the role of nonchemical stressors in such highly modified urban water bodies. Environ Toxicol Chem 2018;37:703-714. © 2017 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC. © 2017 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC.

Accessing 3D microtissue metabolism: Lactate and oxygen monitoring in hepatocyte spheroids.

PubMed

Weltin, Andreas; Hammer, Steffen; Noor, Fozia; Kaminski, Yeda; Kieninger, Jochen; Urban, Gerald A

2017-01-15

3D hepatic microtissues, unlike 2D cell cultures, retain many of the in-vivo-like functionalities even after long-term cultivation. Such 3D cultures are increasingly applied to investigate liver damage due to drug exposure in toxicology. However, there is a need for thorough metabolic characterization of these microtissues for mechanistic understanding of effects on culture behaviour. We measured metabolic parameters from single human HepaRG hepatocyte spheroids online and continuously with electrochemical microsensors. A microsensor platform for lactate and oxygen was integrated in a standard 96-well plate. Electrochemical microsensors for lactate and oxygen allow fast, precise and continuous long-term measurement of metabolic parameters directly in the microwell. The demonstrated capability to precisely detect small concentration changes by single spheroids is the key to access their metabolism. Lactate levels in the culture medium starting from 50µM with production rates of 5µMh -1 were monitored and precisely quantified over three days. Parallel long-term oxygen measurements showed no oxygen depletion or hypoxic conditions in the microwell. Increased lactate production by spheroids upon suppression of the aerobic metabolism was observed. The dose-dependent decrease in lactate production caused by the addition of the hepatotoxic drug Bosentan was determined. We showed that in a toxicological application, metabolic monitoring yields quantitative, online information on cell viability, which complements and supports other methods such as microscopy. The demonstrated continuous access to 3D cell culture metabolism within a standard setup improves in vitro toxicology models in replacement strategies of animal experiments. Controlling the microenvironment of such organotypic cultures has impact in tissue engineering, cancer therapy and personalized medicine. Copyright © 2016 Elsevier B.V. All rights reserved.

Sixth plot of the carcinogenic potency database: results of animal bioassays published in the General Literature 1989 to 1990 and by the National Toxicology Program 1990 to 1993.

PubMed Central

Gold, L S; Manley, N B; Slone, T H; Garfinkel, G B; Ames, B N; Rohrbach, L; Stern, B R; Chow, K

1995-01-01

This paper presents two types of information from the Carcinogenic Potency Database (CPDB): (a) the sixth chronological plot of analyses of long-term carcinogenesis bioassays, and (b) an index to chemicals in all six plots, including a summary compendium of positivity and potency for each chemical (Appendix 14). The five earlier plots of the CPDB have appeared in this journal, beginning in 1984 (1-5). Including the plot in this paper, the CPDB reports results of 5002 experiments on 1230 chemicals. This paper includes bioassay results published in the general literature between January 1989 and December 1990, and in Technical Reports of the National Toxicology Program between January 1990 and June 1993. Analyses are included on 17 chemicals tested in nonhuman primates by the Laboratory of Chemical Pharmacology, National Cancer Institute. This plot presents results of 531 long-term, chronic experiments of 182 test compounds and includes the same information about each experiment in the same plot format as the earlier papers: the species and strain of test animal, the route and duration of compound administration, dose level and other aspects of experimental protocol, histopathology and tumor incidence, TD50 (carcinogenic potency) and its statistical significance, dose response, author's opinion about carcinogenicity, and literature citation. We refer the reader to the 1984 publications (1,6,7) for a detailed guide to the plot of the database, a complete description of the numerical index of carcinogenic potency, and a discussion of the sources of data, the rationale for the inclusion of particular experiments and particular target sites, and the conventions adopted in summarizing the literature. The six plots of the CPDB are to be used together since results of individual experiments that were published earlier are not repeated. Appendix 14 is designed to facilitate access to results on all chemicals. References to the published papers that are the source of experimental data are reported in each of the published plots. For readers using the CPDB extensively, a combined plot is available of all results from the six separate plot papers, ordered alphabetically by chemical; the combined plot in printed form or on computer tape or diskette is available from the first author. A SAS database is also available. PMID:8741772

Diuron in water: functional toxicity and intracellular detoxification patterns of active concentrations assayed in tandem by a yeast-based probe.

PubMed

Dragone, Roberto; Cheng, Rachel; Grasso, Gerardo; Frazzoli, Chiara

2015-04-01

A study on the acute and chronic effects of the herbicide diuron was carried out. The test, basing on a yeast cell probe, investigated the interference with cellular catabolism and possible self-detoxification capacity of Saccharomyces cerevisiae. Aerobic respiration was taken as the toxicological end-point. Percentage interference (%r) with cellular respiration was measured in water by increased dissolved O2 concentration (ppm) after exposure to different doses. Interference was calculated through the comparison of respiratory activity of exposed and non-exposed cells. Short-term and long-term (6 and 24 h respectively) exposures were also considered. The test for short-term exposure gave positive %r values except that for 10-6 M (11.11%, 11.76%, 13.33% and 0% for 10-10 M, 10-8 M, 10-7 M and 10-6 M respectively). In the case of long-term exposure the test showed positive %r values, but less effect than short-term exposure until 10-8 M and much higher at 10-6 M (7.41%, 8.82%, 11.76% and 6.06% for 10-10 M, 10-8 M, 10-7 M and 10-6 M respectively). The findings of aerobic respiration as toxicological end-point were in agreement with known mechanisms of toxicity and intracellular detoxification for both the doses and exposure times employed.

Advances In Assessing Bioavailability Of Metal(Loid)s In Contaminated Soils

EPA Science Inventory

The term bioavailability has many different meanings across various disciplines of toxicology and pharmacology. Often bioavailability is concerned with human health aspects such as in the case of lead (Pb) ingestion by children. However, some of the most contaminated sites are ...

Concepts in health evaluation of commercial and industrial chemicals

NASA Technical Reports Server (NTRS)

Mcnamara, B. P.

1975-01-01

A method is described for determining no toxic effect exposure levels based on short-term testing of industrial and commercial chemicals. Procedures for monitoring all organs and body functions for the presence or absence of toxicological effects are demonstrated using various laboratory animals.

DISTRIBUTION OF FITC IMPLANTED SUBCUTANEOUSLY IN CONTROLLED RELEASE MATRICES IN CUNNER (TAUTOGOLABRUS ADSPERSUS)

EPA Science Inventory

Peritoneal injection is a major route for chemical introduction into fish for toxicological studies. This procedure, however, causes rapid exposure to toxicants at levels which aren't environmentally realistic. Long-term studies to determine effects of estrogenic chemicals on fis...

Toxicological and chemical insights into representative source and drinking water in eastern China.

PubMed

Shi, Peng; Zhou, Sicong; Xiao, Hongxia; Qiu, Jingfan; Li, Aimin; Zhou, Qing; Pan, Yang; Hollert, Henner

2018-02-01

Drinking water safety is continuously threatened by the emergence of numerous toxic organic pollutants (TOPs) in environmental waters. In this study, an approach integrating in vitro bioassays and chemical analyses was performed to explore toxicological profiles of representative source and drinking water from waterworks of the Yangtze River (Yz), Taihu Lake (Th), and the Huaihe River (Hh) basins in eastern China. Overall, 34 of 96 TOPs were detected in all water samples, with higher concentrations in both source and drinking water samples of Hh, and pollutant profiles also differed across different river basins. Non-specific bioassays indicated that source water samples of Hh waterworks showed higher genotoxicity and mutagenicity than samples of Yz and Th. An EROD assay demonstrated dioxin-like toxicity which was detected in 5 of 7 source water samples, with toxin concentration levels ranging from 62.40 to 115.51 picograms TCDD equivalents per liter of water (eq./L). PAHs and PCBs were not the main contributors to observed dioxin-like toxicity in detected samples. All source water samples induced estrogenic activities of 8.00-129.00 nanograms 17β-estradiol eq./L, and estrogens, including 17α-ethinylestradiol and estriol, contributed 40.38-84.15% of the observed activities in examined samples. While drinking water treatments efficiently removed TOPs and their toxic effects, and estrogenic activity was still observed in drinking water samples of Hh. Altogether, this study indicated that the representative source water in eastern China, especially that found in Hh, may negatively affect human health, a finding that demonstrates an urgent requirement for advanced drinking water treatments. Copyright © 2017 Elsevier Ltd. All rights reserved.

Combining Chimeric Mice with Humanized Liver, Mass Spectrometry, and Physiologically-Based Pharmacokinetic Modeling in Toxicology.

PubMed

Yamazaki, Hiroshi; Suemizu, Hiroshi; Mitsui, Marina; Shimizu, Makiko; Guengerich, F Peter

2016-12-19

Species differences exist in terms of drug oxidation activities, which are mediated mainly by cytochrome P450 (P450) enzymes. To overcome the problem of species extrapolation, transchromosomic mice containing a human P450 3A cluster or chimeric mice transplanted with human hepatocytes have been introduced into the human toxicology research area. In this review, drug metabolism and disposition mediated by humanized livers in chimeric mice are summarized in terms of biliary/urinary excretions of phthalate and bisphenol A and plasma clearances of the human cocktail probe drugs caffeine, warfarin, omeprazole, metoprolol, and midazolam. Simulation of human plasma concentrations of the teratogen thalidomide and its human metabolites is possible with a simplified physiologically based pharmacokinetic model based on data obtained in chimeric mice, in accordance with reported clinical thalidomide concentrations. In addition, in vivo nonspecific hepatic protein binding parameters of metabolically activated 14 C-drug candidate and hepatotoxic medicines in humanized liver mice can be analyzed by accelerator mass spectrometry and are useful for predictions in humans.

Using High-Content Imaging to Analyze Toxicological Tipping ...

EPA Pesticide Factsheets

Presentation at International Conference on Toxicological Alternatives & Translational Toxicology (ICTATT) held in China and Discussing the possibility of using High Content Imaging to Analyze Toxicological Tipping Points Slide Presentation at International Conference on Toxicological Alternatives & Translational Toxicology (ICTATT) held in China and Discussing the possibility of using High Content Imaging to Analyze Toxicological Tipping Points

Immunological and toxicological risk assessment of e-cigarettes.

PubMed

Kaur, Gagandeep; Pinkston, Rakeysha; Mclemore, Benathel; Dorsey, Waneene C; Batra, Sanjay

2018-03-31

Knowledge of the long-term toxicological and immunological effects of e-cigarette (e-cig) aerosols remains elusive due to the relatively short existence of vaping. Therefore, we performed a systematic search of articles published in public databases and analysed the research evidence in order to provide critical information regarding e-cig safety. Electronic nicotine delivery systems (or e-cigs) are an alternative to traditional cigarettes for the delivery of nicotine and are typically filled with glycerol or propylene glycol-based solutions known as e-liquids. Though present in lower quantities, e-cig aerosols are known to contain many of the harmful chemicals found in tobacco smoke. However, due to the paucity of experimental data and contradictory evidence, it is difficult to draw conclusive outcomes regarding toxicological, immunological and clinical impacts of e-cig aerosols. Excessive vaping has been reported to induce inflammatory responses including mitogen-activated protein kinase, Janus tyrosine kinase/signal transducer and activator of transcription and nuclear factor-κB signalling, similar to that induced by tobacco smoke. Based on recent evidence, prolonged exposure to some constituents of e-cig aerosols might result in respiratory complications such as asthma, chronic obstructive pulmonary disease and inflammation. Future studies are warranted that focus on establishing correlations between e-cig types, generations and e-liquid flavours and immunological and toxicological profiles to broaden our understanding about the effects of vaping. Copyright ©ERS 2018.

SOURCES OF VARIATION IN TOXICOLOGICAL STUDIES AND THEIR EFFECTS ON PRECISION OF RESULTS: INDIVIDUAL DIFFERENCES.

EPA Science Inventory

The ultimate goal of risk assessment is to estimate the adverse effects of exposures to environmental contaminants in the population. However, populations of humans and other species vary widely in many key factors such as age, genetic makeup, gender, and health status. Any or a...

ORD'S FOUR LAB STUDY: TOXICOLOGICAL AND CHEMICAL EVALUATION OF COMPLEX MIXTURES OF DRINKING WATER DISINFECTION BY-PRODUCTS

EPA Science Inventory

Disinfectants used in the production of drinking water react with naturally occurring organic and inorganic material in the source water to produce disinfection by-products (DBPs). Humans are exposed daily to a complex mixture of DBPs via oral, dermal, and inhalation routes. To ...

Inhalation toxicology. III., Evaluation of thermal degradation products from aircraft and automobile engine oils, aircraft hydraulic fluid, and mineral oil.

DOT National Transportation Integrated Search

1983-04-01

A malfunctioning seal in the gear-reduction box of a turboprop aircraft engine could allow oil to enter the turbine's compressor section, which is the source of bleed air used to pressurize the cabin. Oil, or its degradation products, could have a de...

Neural Differentiation of Human Pluripotent Stem Cells for Nontherapeutic Applications: Toxicology, Pharmacology, and In Vitro Disease Modeling

PubMed Central

Yap, May Shin; Nathan, Kavitha R.; Yeo, Yin; Poh, Chit Laa; Richards, Mark; Lim, Wei Ling; Othman, Iekhsan; Heng, Boon Chin

2015-01-01

Human pluripotent stem cells (hPSCs) derived from either blastocyst stage embryos (hESCs) or reprogrammed somatic cells (iPSCs) can provide an abundant source of human neuronal lineages that were previously sourced from human cadavers, abortuses, and discarded surgical waste. In addition to the well-known potential therapeutic application of these cells in regenerative medicine, these are also various promising nontherapeutic applications in toxicological and pharmacological screening of neuroactive compounds, as well as for in vitro modeling of neurodegenerative and neurodevelopmental disorders. Compared to alternative research models based on laboratory animals and immortalized cancer-derived human neural cell lines, neuronal cells differentiated from hPSCs possess the advantages of species specificity together with genetic and physiological normality, which could more closely recapitulate in vivo conditions within the human central nervous system. This review critically examines the various potential nontherapeutic applications of hPSC-derived neuronal lineages and gives a brief overview of differentiation protocols utilized to generate these cells from hESCs and iPSCs. PMID:26089911

Crowd-Sourced Verification of Computational Methods and Data in Systems Toxicology: A Case Study with a Heat-Not-Burn Candidate Modified Risk Tobacco Product.

PubMed

Poussin, Carine; Belcastro, Vincenzo; Martin, Florian; Boué, Stéphanie; Peitsch, Manuel C; Hoeng, Julia

2017-04-17

Systems toxicology intends to quantify the effect of toxic molecules in biological systems and unravel their mechanisms of toxicity. The development of advanced computational methods is required for analyzing and integrating high throughput data generated for this purpose as well as for extrapolating predictive toxicological outcomes and risk estimates. To ensure the performance and reliability of the methods and verify conclusions from systems toxicology data analysis, it is important to conduct unbiased evaluations by independent third parties. As a case study, we report here the results of an independent verification of methods and data in systems toxicology by crowdsourcing. The sbv IMPROVER systems toxicology computational challenge aimed to evaluate computational methods for the development of blood-based gene expression signature classification models with the ability to predict smoking exposure status. Participants created/trained models on blood gene expression data sets including smokers/mice exposed to 3R4F (a reference cigarette) or noncurrent smokers/Sham (mice exposed to air). Participants applied their models on unseen data to predict whether subjects classify closer to smoke-exposed or nonsmoke exposed groups. The data sets also included data from subjects that had been exposed to potential modified risk tobacco products (MRTPs) or that had switched to a MRTP after exposure to conventional cigarette smoke. The scoring of anonymized participants' predictions was done using predefined metrics. The top 3 performers' methods predicted class labels with area under the precision recall scores above 0.9. Furthermore, although various computational approaches were used, the crowd's results confirmed our own data analysis outcomes with regards to the classification of MRTP-related samples. Mice exposed directly to a MRTP were classified closer to the Sham group. After switching to a MRTP, the confidence that subjects belonged to the smoke-exposed group decreased significantly. Smoking exposure gene signatures that contributed to the group separation included a core set of genes highly consistent across teams such as AHRR, LRRN3, SASH1, and P2RY6. In conclusion, crowdsourcing constitutes a pertinent approach, in complement to the classical peer review process, to independently and unbiasedly verify computational methods and data for risk assessment using systems toxicology.

Ecotoxicological impact of MSW landfills: assessment of teratogenic effects by means of an adapted FETAX assay.

PubMed

de Lapuente, J; González-Linares, J; Pique, E; Borràs, M

2014-01-01

The introduction of chemical products into the environment can cause long-term effects on the ecosystems. Increasing efforts are being made to determine the extent of contamination in particularly affected areas using diverse methods to assess the ecotoxicological impact. We used a modified Frog Embrio Toxicity Assay-Xenopus method to determine the extent of toxicological load in different sample soils obtained near three municipal solid waste landfills in Catalonia (Spain). The results show that the Garraf landfill facility produces more embryotoxic damage to the surroundings, than the others ones: Can Mata landfill and Montferrer-Castellbó landfill. The aim of this work is to demonstrate how different management of complex sources of contamination as the controlled dumping sites can modulate the presence of toxics in the environment and their effects and through this, help determine the safer way to treat these wastes. To this effect some conceptual modifications have been made on the established American Society for Testing and Materials protocol. The validity of the new model, both as to model of calculation as to protocol, has been demonstrated in three different sites with complex sources of contamination.

3-D nasal cultures: Systems toxicological assessment of a candidate modified-risk tobacco product.

PubMed

Iskandar, Anita R; Mathis, Carole; Martin, Florian; Leroy, Patrice; Sewer, Alain; Majeed, Shoaib; Kuehn, Diana; Trivedi, Keyur; Grandolfo, Davide; Cabanski, Maciej; Guedj, Emmanuel; Merg, Celine; Frentzel, Stefan; Ivanov, Nikolai V; Peitsch, Manuel C; Hoeng, Julia

2017-01-01

In vitro toxicology approaches have evolved from a focus on molecular changes within a cell to understanding of toxicity-related mechanisms in systems that can mimic the in vivo environment. The recent development of three dimensional (3-D) organotypic nasal epithelial culture models offers a physiologically robust system for studying the effects of exposure through inhalation. Exposure to cigarette smoke (CS) is associated with nasal inflammation; thus, the nasal epithelium is relevant for evaluating the pathophysiological impact of CS exposure. The present study investigated further the application of in vitro human 3-D nasal epithelial culture models for toxicological assessment of inhalation exposure. Aligned with 3Rs strategy, this study aimed to explore the relevance of a human 3-D nasal culture model to assess the toxicological impact of aerosols generated from a candidate modified risk tobacco product (cMRTP), the Tobacco Heating System (THS) 2.2, as compared with smoke generated from reference cigarette 3R4F. A series of experimental repetitions, where multiple concentrations of THS2.2 aerosol and 3R4F smoke were applied, were conducted to obtain reproducible measurements to understand the cellular/molecular changes that occur following exposure. In agreement with "Toxicity Testing in the 21st Century - a Vision and a Strategy", this study implemented a systems toxicology approach and found that for all tested concentrations the impact of 3R4F smoke was substantially greater than that of THS2.2 aerosol in terms of cytotoxicity levels, alterations in tissue morphology, secretion of pro-inflammatory mediators, impaired ciliary function, and increased perturbed transcriptomes and miRNA expression profiles.

TOXICOLOGICAL HIGHLIGHT: SCREENING FOR DEVELOPMENTAL TOXICITY OF TOBACCO SMOKE CONSTITUENTS

EPA Science Inventory

Abstract
Cigarette smoking is unrivaled among developmental toxicants in terms of total adverse impact on the human population. According to the American Lung Association, smoking during pregnancy is estimated to account for 20 to 30 percent of low-weight babies, up to 14 per...

Innovative Reactive and Proactive Graduate Student Recruiting Techniques.

ERIC Educational Resources Information Center

Laird, Hugh E., II

1989-01-01

The evolution of the recruiting techniques used by the University of Arizona's pharmacology and toxicology graduate program are described, considerations in the development of recruitment efforts are discussed, and issues for the profession to examine in developing a long-term strategy for recruiting students are outlined. (MSE)

DISTRIBUTION OF FITC AFTER SUBCUTANEOUS IMPLANTATION OF CONTROLLED RELEASE MATRICES IN CUNNER, TAUTOGOLABRUS ADSPERSUS

EPA Science Inventory

Peritoneal injection is a major route for chemical introduction into fish for toxicological studies. This procedure, however, causes rapid exposure to toxicants at levels which aren't environmentally realistic. Long-term studies to determine effects of estrogenic chemicals on fis...

Occupational hazards of missile operations with special regard to the hydrazine propellants.

PubMed

Back, K C; Carter, V L; Thomas, A A

1978-04-01

The second generation of ballistic missiles and boosters, characterized by increased range and quick reaction capability, required the development of new high-energy storage propellants. This exploration led to the introduction of hydrazine (Hz), monomethylhydrazine (MMH), and 1,1-dimethylhydrazine (UDMH) into the USAF inventory. These compounds are all storable, noncryogenic, high-energy fuels which may be used alone or in combination as mixed amine fuels. Early toxicology experiments were to produce data on acute and subacute effects of the propellants in order to set standards for test and operational procedures to protect propellant handlers. The early work indicated that, despite similar chemical characteristics, there were marked differences between the compounds in terms of toxicological mechanisms. Since the propellant systems have been used for some 15 years, recent emphasis on toxicology has been centered on the more chronic effects and on an increasing body of evidence from animal experiments that the compounds may possess oncogenic potential as well as chronic systemic effects. This paper addresses itself to data leading up to current occupational standards.

21 CFR 862.3200 - Clinical toxicology calibrator.

Code of Federal Regulations, 2010 CFR

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...

21 CFR 862.3200 - Clinical toxicology calibrator.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 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...

21 CFR 862.3200 - Clinical toxicology calibrator.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 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...

21 CFR 862.3200 - Clinical toxicology calibrator.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 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...

Data Mining in the U.S. National Toxicology Program (NTP) Database Reveals a Potential Bias Regarding Liver Tumors in Rodents Irrespective of the Test Agent

PubMed Central

Ring, Matthias; Eskofier, Bjoern M.

2015-01-01

Long-term studies in rodents are the benchmark method to assess carcinogenicity of single substances, mixtures, and multi-compounds. In such a study, mice and rats are exposed to a test agent at different dose levels for a period of two years and the incidence of neoplastic lesions is observed. However, this two-year study is also expensive, time-consuming, and burdensome to the experimental animals. Consequently, various alternatives have been proposed in the literature to assess carcinogenicity on basis of short-term studies. In this paper, we investigated if effects on the rodents’ liver weight in short-term studies can be exploited to predict the incidence of liver tumors in long-term studies. A set of 138 paired short- and long-term studies was compiled from the database of the U.S. National Toxicology Program (NTP), more precisely, from (long-term) two-year carcinogenicity studies and their preceding (short-term) dose finding studies. In this set, data mining methods revealed patterns that can predict the incidence of liver tumors with accuracies of over 80%. However, the results simultaneously indicated a potential bias regarding liver tumors in two-year NTP studies. The incidence of liver tumors does not only depend on the test agent but also on other confounding factors in the study design, e.g., species, sex, type of substance. We recommend considering this bias if the hazard or risk of a test agent is assessed on basis of a NTP carcinogenicity study. PMID:25658102

21 CFR 862.3280 - Clinical toxicology control material.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Clinical toxicology control material. 862.3280... (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Toxicology Test Systems § 862.3280 Clinical toxicology control material. (a) Identification. A clinical toxicology control...

21 CFR 862.3280 - Clinical toxicology control material.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Clinical toxicology control material. 862.3280... (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Toxicology Test Systems § 862.3280 Clinical toxicology control material. (a) Identification. A clinical toxicology control...

21 CFR 862.3280 - Clinical toxicology control material.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Clinical toxicology control material. 862.3280... (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Toxicology Test Systems § 862.3280 Clinical toxicology control material. (a) Identification. A clinical toxicology control...

21 CFR 862.3280 - Clinical toxicology control material.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Clinical toxicology control material. 862.3280... (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Toxicology Test Systems § 862.3280 Clinical toxicology control material. (a) Identification. A clinical toxicology control...

21 CFR 862.3280 - Clinical toxicology control material.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Clinical toxicology control material. 862.3280... (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Toxicology Test Systems § 862.3280 Clinical toxicology control material. (a) Identification. A clinical toxicology control...

Toxicogenomics in regulatory ecotoxicology

USGS Publications Warehouse

Ankley, Gerald T.; Daston, George P.; Degitz, Sigmund J.; Denslow, Nancy D.; Hoke, Robert A.; Kennedy, Sean W.; Miracle, Ann L.; Perkins, Edward J.; Snape, Jason; Tillitt, Donald E.; Tyler, Charles R.; Versteeg, Donald

2006-01-01

Recently, we have witnessed an explosion of different genomic approaches that, through a combination of advanced biological, instrumental, and bioinformatic techniques, can yield a previously unparalleled amount of data concerning the molecular and biochemical status of organisms. Fueled partially by large, well-publicized efforts such as the Human Genome Project, genomic research has become a rapidly growing topical area in multiple biological disciplines. Since 1999, when the term “toxicogenomics” was coined to describe the application of genomics to toxicology (1), a rapid increase in publications on the topic has occurred (Figure 1). The potential utility of toxicogenomics in toxicological research and regulatory activities has been the subject of scientific discussions and, as with any new technology, has evoked a wide range of opinion (2–6).

In silico toxicology for the pharmaceutical sciences

DOE Office of Scientific and Technical Information (OSTI.GOV)

Valerio, Luis G., E-mail: Luis.Valerio@fda.hhs.go

2009-12-15

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 ofmore » 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 prediction of human drug metabolism, mechanisms of action for pharmaceuticals, and newer models for predicting human adverse effects. How accurate are these approaches is both a statistical issue and challenge in toxicology. In this review, fundamental concepts and the current capabilities and limitations of this technology will be critically addressed.« less

Toward a Blended Ontology: Applying Knowledge Systems to Compare Therapeutic and Toxicological Nanoscale Domains

EPA Science Inventory

Bionanomedicine and environmental research share need common terms and ontologies. This study applied knowledge systems, data mining, and bibliometrics used in nano-scale ADME research from 1991 to 2011. The prominence of nano-ADME in environmental research began to exceed the pu...

HEART RATE VARIABILITY IN RODENTS — USES AND CAVEATS IN TOXICOLOGICAL STUDIES

EPA Science Inventory

Heart rate variability (HRV) is a measure of cardiac pacing dynamics that has recently garnered a great deal of interest in environmental health studies. While the use of these measures has become popular, much uncertainty remains in the interpretation of results, both in terms ...

Advances in Assessing Bioavailability of Metal(loid)s in Contaminated Soils

USDA-ARS?s Scientific Manuscript database

The term bioavailability has many different meanings across various disciplines of toxicology and pharmacology. Often bioavailability is concerned with human health aspects such in the case of lead (Pb) ingestion by children. However, some of the most contaminated sites are found in non-public acc...

Toxicity Testing in the 21st Century: Implications for Human Health Risk Assessment

EPA Science Inventory

The risk analysis perspective by Daniel Krewski and colleagues lays out the long-term vision and strategic plan developed by a National Research Council committee (1), sponsored by the U.S. Environmental Protection Agency (EPA) with support from the U.S. National Toxicology Progr...

EVALUATION OF DNA CHIPS (MICROARRAYS) FOR DETERMINING VIRULENCE FACTOR ACTIVITY RELATIONSHIPS (VFARS)

EPA Science Inventory

Computational toxicology is a rapid approach to screening for toxic effects and looking for common outcomes that can result in predictive models. The long term project will result in the development of a database of mRNA responses to known water-borne pathogens. An understanding...

Mixture toxicology in the 21st century: Pathway-based concepts and tools

EPA Science Inventory

The past decade has witnessed notable evolution of approaches focused on predicting chemical hazards and risks in the absence of empirical data from resource-intensive in vivo toxicity tests. In silico models, in vitro high-throughput toxicity assays, and short-term in vivo tests...

Second chronological supplement to the Carcinogenic Potency Database: standardized results of animal bioassays published through December 1984 and by the National Toxicology Program through May 1986.

PubMed Central

Gold, L S; Slone, T H; Backman, G M; Magaw, R; Da Costa, M; Lopipero, P; Blumenthal, M; Ames, B N

1987-01-01

This paper is the second chronological supplement to the Carcinogenic Potency Database, published earlier in this journal (1,2,4). We report here results of carcinogenesis bioassays published in the general literature between January 1983 and December 1984, and in Technical Reports of the National Cancer Institute/National Toxicology Program between January 1983 and May 1986. This supplement includes results of 525 long-term, chronic experiments of 199 test compounds, and reports the same information about each experiment in the same plot format as the earlier papers: e.g., the species and strain of test animal, the route and duration of compound administration, dose level and other aspects of experimental protocol, histopathology and tumor incidence, TD50 (carcinogenic potency) and its statistical significance, dose response, author's opinion about carcinogenicity, and literature citation. We refer the reader to the 1984 publications for a description of the numerical index of carcinogenic potency (TD50), a guide to the plot of the database, and a discussion of the sources of data, the rationale for the inclusion of particular experiments and particular target sites, and the conventions adopted in summarizing the literature. The three plots of the database are to be used together, since results of experiments published in earlier plots are not repeated. Taken together, the three plots include results for more than 3500 experiments on 975 chemicals. Appendix 14 is an index to all chemicals in the database and indicates which plot(s) each chemical appears in. PMID:3691431

Assessment of the histopathological lesions and chemical analysis of feral cats to the smoke from Kuwait oil fires

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moeller, R.B.; Kalasinsky, V.F.; Razzaque, M.

Twenty-six adult or subadult feral cats were collected from Kuwait approximately 8 months after the ignition of the Kuwait oil wells. These animals were obtained from two sources: 12 animals from Kuwait City, a relatively Co smoke-free area, and 14 from the city of Alimadi, an area with heavy smoke. Animals were euthanized and a complete set of tissues consisting of all 0 major organs was taken for histopathology. Samples of lung, liver, kidney, urine, and blood were also taken for toxicology. Histopathological lesions observed in the lung were mild accumulations of anthracotic pigment in the lungs of 17 cats.more » Hyperplasia of the bronchial and bronchiolar gland in 8 cats, and smooth muscle hyperplasia of bronchioles in 14 cats. Iracheal gland hyperplasia was observed in 7 cats, and minimal squamous metaplasia of the tracheal mucosa in 17 cats, Laryngeal lesions consisted of submucosal gland hyperplasia in 2 cats and squamous metaplasia of the mucosa in 5 cats. Hyperplasia of the nasal submucosal glands was observed in 6 animals. The pharyngeal mucosa as well as other organs and organ systems (a) were normal in all cats. Atomic absorption analysis for 11 metals was performed; vanadium and nickel levels (two metals that were present in the smoke from the oil fires) are not indicative of substantial exposure to the oil fires. Based on the histopathological findings and toxicological analysis, it is felt that inhalation of air contaminated with smoke from the oil fires had little or no long-term effect on the animals examined.« less

Assessment of the histopathological lesions and chemical analysis of feral cats to the smoke from the Kuwait oil fires.

PubMed

Moeller, R B; Kalasinsky, V F; Razzaque, M; Centeno, J A; Dick, E J; Abdal, M; Petrov, I I; DeWitt, T W; al-Attar, M; Pletcher, J M

1994-01-01

Twenty-six adult or subadult feral cats were collected from Kuwait approximately 8 months after the ignition of the Kuwait oil wells. These animals were obtained from two sources: 12 animals from Kuwait City, a relatively smoke-free area, and 14 from the city of Ahmadi, an area with heavy smoke. Animals were euthanized and a complete set of tissues consisting of all major organs was taken for histopathology. Samples of lung, liver, kidney, urine, and blood were also taken for toxicology. Histopathological lesions observed in the lung were mild accumulations of anthracotic pigment in the lungs of 17 cats. Hyperplasia of the bronchial and bronchiolar gland in 8 cats, and smooth muscle hyperplasia of bronchioles in 14 cats. Tracheal gland hyperplasia was observed in 7 cats, and minimal squamous metaplasia of the tracheal mucosa in 17 cats, Laryngeal lesions consisted of submucosal gland hyperplasia in 2 cats and squamous metaplasia of the mucosa in 5 cats. Hyperplasia of the nasal submucosal glands was observed in 6 animals. The pharyngeal mucosa as well as other organs and organ systems were normal in all cats. Atomic absorption analysis for 11 metals was performed; vanadium and nickel levels (two metals that were present in the smoke from the oil fires) are not indicative of substantial exposure to the oil fires. Based on the histopathological findings and toxicological analysis, it is felt that inhalation of air contaminated with smoke from the oil fires had little or no long-term effect on the animals examined.

Resource Guide to Careers in Toxicology, 3rd Edition.

ERIC Educational Resources Information Center

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…

Stachybotrys, a mycotoxin-producing fungus of increasing toxicologic importance.

PubMed

Fung, F; Clark, R; Williams, S

1998-01-01

Stachybotrys as a fungus has been implicated as a source of mycotoxins. While the toxicity of several well-known mycotoxins (aflatoxins) is well documented, recent studies on Stachybotrys have raised the question that mycotoxins produced by this fungus may be responsible for the health effects of occupants in water-damaged buildings. Published articles regarding Stachybotrys-related mycotoxins were reviewed with particular focus on human toxicity. A critical review of papers, reports, and studies on Stachybotrys mycotoxins revealed only descriptive reports of suspected animal and human poisoning secondary to consumption of mold-contaminated food products. No studies of good toxicologic and epidemiologic designs answer whether airborne mycotoxins produced by Stachybotrys could produce specific human toxicity. Current data on the toxicology of mycotoxins produced by Stachybotrys demonstrate that this group of mycotoxins is capable of producing immunosuppression and inflammatory insults to gastrointestinal and pulmonary systems. Case control study and case reports have suggested a possible association with environmental exposure to Stachybotrys mycotoxins, although a firm causal relationship has not been firmly established. Additional studies are needed to document that humans with sufficient exposure to these mycotoxins develop compatible clinical and pathologic pictures as demonstrated in animal models.

[Estimation of carbon monoxide poisonings frequency, based on carboxyhemoglobin determinations performed in Toxicology Laboratory in Krakow in years 2002-2010].

PubMed

Gomółka, Ewa; Gawlikowski, Tomasz

2011-01-01

Carboxyhemoglobin is a specific biomarker of carbon monoxide (CO) exposition. The source of CO indoors are most often gas, oil or carbon furnaces and stoves or bathroom gas heaters. CO intoxication during fire or exposition to car fumes are sporadic. The aim of the study was: to present the frequency of CO intoxications diagnosed in Laboratory of Analytical Toxicology UJ Collegium Medicum in years 2002 - 2010, to present the season trends of CO intoxications, show sex and age structure of CO intoxicated patients. Material were Laboratory of Analytical Toxicology and Drug Monitoring data records from years 2002 - 2010. CO intoxication was confirmed and recognized when COHb blood concentration was higher than 10%. Annual number of CO poisonings was stable in the period of time, varied from 209 to 296 (mean 256,2 CO poisonings per year). Sex structure of CO poisoned patients showed little female dominance (54.6%). Carbon monoxide poisonings distribution was seasonal. The season of intensified CO intoxications lasted from October to March, the highest intensity was in December and January. The CO poisoning problem is still actual. Society education about security, recognition, diagnosis and practice in carbon monoxide exposition is still needful.

ACToR A Aggregated Computational Toxicology Resource ...

EPA Pesticide Factsheets

We are developing the ACToR system (Aggregated Computational Toxicology Resource) to serve as a repository for a variety of types of chemical, biological and toxicological data that can be used for predictive modeling of chemical toxicology. We are developing the ACToR system (Aggregated Computational Toxicology Resource) to serve as a repository for a variety of types of chemical, biological and toxicological data that can be used for predictive modeling of chemical toxicology.

ACToR A Aggregated Computational Toxicology Resource (S) ...

EPA Pesticide Factsheets

We are developing the ACToR system (Aggregated Computational Toxicology Resource) to serve as a repository for a variety of types of chemical, biological and toxicological data that can be used for predictive modeling of chemical toxicology. We are developing the ACToR system (Aggregated Computational Toxicology Resource) to serve as a repository for a variety of types of chemical, biological and toxicological data that can be used for predictive modeling of chemical toxicology.

QUANTITATIVE TOXICOLOGIC PATHOLOGY-METHODS AND INTERPRETATION' SESSION AT THE JOINT MEETING OF SOCIETY OF TOXICOLOGIC PATHOLOGISTS AND THE INTERNATIONAL FEDERATION OF SOCIETIES OF TOXICOLOGIC PATHOLOGISTS

EPA Science Inventory

Report of the 'Quantitative Toxicologic Pathology - Methods and Interpretation' session at the Joint meeting of Society of Toxicologic Pathologists and the International Federation of Societies of Toxicologic Pathologists, Orlando, Florida, USA, June 24-28, 2001. Douglas C. Wolf,...

Toxicology of chemical mixtures: Experimental approaches, underlying concepts, and some results

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, R.S.; Long, H.L.; Boorman, G.A.

1990-07-01

The toxicology of chemical mixtures will be the toxicology of the 1990s and beyond. While this branch of toxicology most closely reflects the actual human exposure situation, as yet there is no standard protocol or consensus methodology for investigating the toxicology of mixtures. Thus, in this emerging science, experimentation is required just to develop a broadly applicable evaluation system. Several examples are discussed to illustrate the different experimental designs and the concepts behind each. These include the health effects studies of Love Canal soil samples, the Lake Ontario Coho salmon, the water samples repurified from secondary sewage in the citymore » of Denver Potable Water Reuse Demonstration Plant, and the National Toxicology Program (NTP) effort on a mixture of 25 frequently detected groundwater contaminants derived from hazardous waste disposal sites. In the last instance, an extensive research program has been ongoing for the last two years at the NTP, encompassing general toxicology, immunotoxicology, developmental and reproductive toxicology, biochemical toxicology, myelotoxicology, genetic toxicology, neurobehavioral toxicology, and hepato- and renal toxicology.« less

National Toxicology Program: Review of current DHHS, DOE, and EPA research related to toxicology, Fiscal Year 1991

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1991-06-01

The report represents responses by agencies of DHHS, and by DOE and EPA, to requests by the Director of NTP for information on agency programs in basic toxicology research, toxicology testing, and toxicology methods development. Information on dollar and manpower support for agency activities in basic toxicology research, toxicology testing, and toxicology methods development, by DHHS, DOE and EPA, is summarized on pages 4 to 10. All agencies were requested to provide summary information on their programs related to toxicology methods development, whether essential or peripheral to their missions. The information provided in response to the request is summarized inmore » tables on pages 48 to 81. Information was provided on chemical compounds currently being studied for their toxicological properties in intramural laboratories, or on contracts, or through grants.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hamel, D.R.

This paper identifies the kinds of risk assessments being done by or for the US Department of Agriculture (USDA) Forest Service. Summaries of data sources currently in use and the pesticide risk assessments completed by the agency or its contractors are discussed. An overview is provided of the agency`s standard operating procedures for the conduct of toxicological, ecological, environmental fate, and human health risk assessments.

78 FR 35115 - Listing of Color Additives Exempt From Certification; Mica-Based Pearlescent Pigments

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-12

... (EDI) of the additive from all sources for both the mean and high- intake consumer to an acceptable daily intake (ADI) level established by toxicological data. The EDI is determined by projections based... the issuance of Sec. 73.350 we calculated a cumulative EDI (CEDI) for the use of mica-based...

Diuron in Water: Functional Toxicity and Intracellular Detoxification Patterns of Active Concentrations Assayed in Tandem by a Yeast-Based Probe

PubMed Central

Dragone, Roberto; Cheng, Rachel; Grasso, Gerardo; Frazzoli, Chiara

2015-01-01

A study on the acute and chronic effects of the herbicide diuron was carried out. The test, basing on a yeast cell probe, investigated the interference with cellular catabolism and possible self-detoxification capacity of Saccharomyces cerevisiae. Aerobic respiration was taken as the toxicological end-point. Percentage interference (%ρ) with cellular respiration was measured in water by increased dissolved O2 concentration (ppm) after exposure to different doses. Interference was calculated through the comparison of respiratory activity of exposed and non-exposed cells. Short-term and long-term (6 and 24 h respectively) exposures were also considered. The test for short-term exposure gave positive %ρ values except that for 10−6 M (11.11%, 11.76%, 13.33% and 0% for 10−10 M, 10−8 M, 10−7 M and 10−6 M respectively). In the case of long-term exposure the test showed positive %ρ values, but less effect than short-term exposure until 10−8 M and much higher at 10−6 M (7.41%, 8.82%, 11.76% and 6.06% for 10−10 M, 10−8 M, 10−7 M and 10−6 M respectively). The findings of aerobic respiration as toxicological end-point were in agreement with known mechanisms of toxicity and intracellular detoxification for both the doses and exposure times employed. PMID:25837349

The Evolution of Toxicology and Chemical Regulation ...

EPA Pesticide Factsheets

Presentation for lecture for the 17th Annual Sitlington Lecture in Toxicology at Oklahoma State University Interdisciplinary Toxicology Symposium Presentation for lecture for the 17th Annual Sitlington Lecture in Toxicology at Oklahoma State University Interdisciplinary Toxicology Symposium

Long-term effects of sulfidized silver nanoparticles in sewage sludge on soil microflora.

PubMed

Kraas, Marco; Schlich, Karsten; Knopf, Burkhard; Wege, Franziska; Kägi, Ralf; Terytze, Konstantin; Hund-Rinke, Kerstin

2017-12-01

The use of silver nanoparticles (AgNPs) in consumer products such as textiles leads to their discharge into wastewater and consequently to a transfer of the AgNPs to soil ecosystems via biosolids used as fertilizer. In urban wastewater systems (e.g., sewer, wastewater treatment plant [WWTP], anaerobic digesters) AgNPs are efficiently converted into sparingly soluble silver sulfides (Ag 2 S), mitigating the toxicity of the AgNPs. However, long-term studies on the bioavailability and effects of sulfidized AgNPs on soil microorganisms are lacking. Thus we investigated the bioavailability and long-term effects of AgNPs (spiked in a laboratory WWTP) on soil microorganisms. Before mixing the biosolids into soil, the sludges were either anaerobically digested or directly dewatered. The effects on the ammonium oxidation process were investigated over 140 d. Transmission electron microscopy (TEM) suggested an almost complete sulfidation of the AgNPs analyzed in all biosolid samples and in soil, with Ag 2 S predominantly detected in long-term incubation experiments. However, despite the sulfidation of the AgNPs, soil ammonium oxidation was significantly inhibited, and the degree of inhibition was independent of the sludge treatment. The results revealed that AgNPs sulfidized under environmentally relevant conditions were still bioavailable to soil microorganisms. Consequently, Ag 2 S may exhibit toxic effects over the long term rather than the short term. Environ Toxicol Chem 2017;36:3305-3313. © 2017 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC. © 2017 The Authors. Environmental Toxicology and Chemistry Published by Wiley Periodicals, Inc. on behalf of SETAC.

Toxicology and teratology of the active ingredients of professional therapy MuscleCare products during pregnancy and lactation: a systematic review.

PubMed

Alsaad, Abdulaziz M S; Fox, Colleen; Koren, Gideon

2015-03-05

The rates of muscle aches, sprains, and inflammation are significantly increased during pregnancy. However, women are afraid to use systemic analgesics due to perceptions of fetal risks. Thus, topical products are important alternatives to consider for those women. Of interest, Professional Therapy MuscleCare (PTMC) has shown to be effective in alleviating the myofascial pain as reported in a randomized, placebo-controlled double-blinded comparative clinical study of five topical analgesics. However, to date, there is no complete review or long-term safety studies on the safety of these products during pregnancy and lactation. Thus, the aim of this article was to review toxicological, developmental, and reproductive effects associated with the use of PTMC products. We performed a systematic review on safety of PTMC from all toxicological articles investigating the effects of PTMC's ingredients. This search was conducted through medical and toxicological databases including, Web of Science, EMBASE, Medline, and Micromedix. Both reported and theoretical adverse effects were extensively reviewed. Of the 1500 publications reviewed, 100 papers were retrieved and included in the review. Although some ingredients in PTMC products might cause adverse reproductive effects at high systemic doses, these doses are hundreds to thousands fold greater than those systemically available from topical use at the recommended maximum dose (i.e. 10 g/day). This study provides evidence that, when used as indicated, PTMC is apparently safe for pregnant women and their unborn babies as well as for breastfed infants.

The Toxicology Investigators Consortium Case Registry--the 2014 Experience.

PubMed

Rhyee, Sean H; Farrugia, Lynn; Campleman, Sharan L; Wax, Paul M; Brent, Jeffrey

2015-12-01

The Toxicology Investigators Consortium (ToxIC) Case Registry was established in 2010 by the American College of Medical Toxicology. The Registry includes all medical toxicology consultations performed at participating sites. The Registry was queried for all cases entered between January 1 and December 31, 2014. Specific data reviewed for analysis included demographics (age, gender, ethnicity), source of consultation, reasons for consultation, agents involved in toxicological exposures, signs, symptoms, clinical findings, fatalities, and treatment. In 2014, 9172 cases were entered in the Registry across 47 active member sites. Females accounted for 51.1 % of cases. The majority (65.1 %) of cases were adults between the ages of 19 and 65. Caucasians made up the largest identified ethnic group (48.9 %). Most Registry cases originated from the inpatient setting (93.5 %), with a large majority of these consultations coming from the emergency department or inpatient admission services. Intentional and unintentional pharmaceutical exposures continued to be the most frequent reasons for consultation, accounting for 61.7 % of cases. Among cases of intentional pharmaceutical exposure, 62.4 % were associated with a self-harm attempt. Non-pharmaceutical exposures accounted for 14.1 % of Registry cases. Similar to the past years, non-opioid analgesics, sedative-hypnotics, and opioids were the most commonly encountered agents. Clinical signs or symptoms were noted in 81.9 % of cases. There were 89 recorded fatalities (0.97 %). Medical treatment (e.g., antidotes, antivenom, chelators, supportive care) was rendered in 62.3 % of cases. Patient demographics and exposure characteristics in 2014 Registry cases remain similar to prior years. The majority of consultations arose in the acute care setting (emergency department or inpatient) and involved exposures to pharmaceutical products. Among exposures, non-opioid analgesics, sedative/hypnotics, and opioids were the most frequently encountered. A majority of cases required some form of treatment, but fatalities were rare.

Computational toxicity in 21st century safety sciences (China ...

EPA Pesticide Factsheets

presentation at the Joint Meeting of Analytical Toxicology and Computational Toxicology Committee (Chinese Society of Toxicology) International Workshop on Advanced Chemical Safety Assessment Technologies on 11 May 2016, Fuzhou University, Fuzhou China presentation at the Joint Meeting of Analytical Toxicology and Computational Toxicology Committee (Chinese Society of Toxicology) International Workshop on Advanced Chemical Safety Assessment Technologies on 11 May 2016, Fuzhou University, Fuzhou China

Health Effects of Toxicants: Online Knowledge Support ...

EPA Pesticide Factsheets

Research in toxicology generates vast quantities of data which reside on the Web and are subsequently appropriated and utilized to support further research. This data includes a broad spectrum of information about chemical, biological and radiological agents which can affect health, the nature of the effects, treatment, regulatory measures, and more. Online resources are created and housed by a variety of institutions, including libraries and government agencies. This paper focuses on three such institutions and the tools they offer to the public: the National Library of Medicine (NLM) and its Toxicology and Environmental Health Information Program, the United States Environmental Protection Agency (EPA), and the Organisation for Economic Co-operation and Development (OECD). Reference is also made to other relevant organizations. A review of online public data sources and data resources on health effects of toxicants offered by NLM, EPA and OECD..

TISSUE DISTRIBUTION AND HISTOLOGY OF FITC AND FITC-17B-ESTRADIOL IN CUNNER (TAUTOGOLABRUS ADSPERSUS) AFTER SUBCUTANEOUS IMPLANTATION IN A CONTROL RELEASE MATRIX

EPA Science Inventory

Peritoneal injection is a major route for chemical introduction into fish for toxicological studies. This procedure, however, causes rapid exposure to toxicants. Long-term studies to determine effects of estrogenic chemicals on fish reproduction require a methodology that allows ...

AcuteToxicological Responses of Fischer Rats to Naturally Occurring Asbestos Samples from the United States and Canada

EPA Science Inventory

The potential public health issues related to exposure to natural asbestos deposits (commonly termed naturally occurring asbestos, NO A) has gained the regulatory and media spotlight in recent years. Arguably the most well known example is Libby, Montana, the site of the largest ...

NON-NEOPLASTIC LESIONS: USE OF DATA FROM PRE- OR NON-NEOPLASTIC LESIONS THAT MAY INDICATE POTENTIAL FOR CARCINOGENESIS

EPA Science Inventory

The Toxicology and Microbiology Division of the US EPA, Health Effects Research Laboratory has initiated a research program to develop a matrix of short-term tests to distinguish carcinogens from non-carcinogens among genotoxic substances and to develop methods for predicting rel...

Combining Mass Spectrometry and Toxicology for a Multi-Country European Epidemiologic Study on Drinking Water Disinfection By-Products.

EPA Science Inventory

The HiWATE (Health Impacts of long-term exposure to disinfection by-products in drinking WATEr) project is the first systematic analysis that combines the epidemiology on adverse pregnancy outcomes with analytical chemistry and analytical biology in the European Union. This study...

Combining Mass Spectrometry and Toxicology for a Multi-Country European Epidemiologic Study on Drinking Water Disinfection By-Products

EPA Science Inventory

The HiWATE (Health Impacts of long-term exposure to disinfection by-products in drinking WATEr) project is the first systematic analysis that combines the epidemiology on adverse pregnancy outcomes with analytical chemistry and analytical biology in the European Union. This study...

Pharmacological and toxicological evaluation of Urtica dioica.

PubMed

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 < 0.001; 67.92%) reduced the blood glucose level during GTT in Wistar rats with an effective dose of 300 mg/kg bw in dose-dependent studies. High-performance liquid chromatography with photodiode-array detection (HPLC-DAD) analysis showed the presence of hydroxycinnamic acid derivatives and flavonoids in AEUD. Hexane Fraction-2 (HF2) exhibited both antiinflammatory activity (48.83% after 3 h), comparable to that of indomethacin (53.48%), and potent antibacterial activity with MIC values ranging from 31.25-250 µg/mL against all the tested strains. Gas chromatography-mass spectrometry (GC-MS) analysis showed fatty acid esters and terpenes as the major constituents of HF2. Toxicity tests showed higher safety margin of all the solvent extracts with LC(50) > 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.

The Growing Problem of New Psychoactive Substances (NPS).

PubMed

Madras, Bertha K

The term "new psychoactive substances" (NPS) can be defined as individual drugs in pure form or in complex preparations that are not scheduled under the Single Convention on Narcotic Drugs (1961) or the Convention on Psychotropic Substances (1971). NPS may be categorized by chemical structure, by psychoactive properties, by biological targets, or by source (plant, synthetic, or combined). The emergence of hundreds of NPS in the past decade is challenging for public health and drug policies globally. The novelty of NPS, their ambiguous legal status, ability to evade toxicological tests, swift adaptation to legal restrictions, global Internet marketing, and scant public knowledge of their adverse effects are among the key drivers of this twenty-first century phenomenon. Multi-disciplinary research in areas of biology, epidemiology, prevention, and web analytics are needed to develop effective responses in a domain capable of overwhelming current international conventions and national drug control policies. Ultimately, research-guided prevention education will fortify societies against this tidal wave.

The Toxicology Education Summit: Building the Future of Toxicology Through Education

PubMed Central

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.

2012-01-01

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. PMID:22461448

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

PubMed

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.

Health risk assessment of organic micropollutants in greywater for potable reuse.

PubMed

Etchepare, Ramiro; van der Hoek, Jan Peter

2015-04-01

In light of the increasing interest in development of sustainable potable reuse systems, additional research is needed to elucidate the risks of producing drinking water from new raw water sources. This article investigates the presence and potential health risks of organic micropollutants in greywater, a potential new source for potable water production introduced in this work. An extensive literature survey reveals that almost 280 organic micropollutants have been detected in greywater. A three-tiered approach is applied for the preliminary health risk assessment of these chemicals. Benchmark values are derived from established drinking water standards for compounds grouped in Tier 1, from literature toxicological data for compounds in Tier 2, and from a Threshold of Toxicological Concern approach for compounds in Tier 3. A risk quotient is estimated by comparing the maximum concentration levels reported in greywater to the benchmark values. The results show that for the majority of compounds, risk quotient values were below 0.2, which suggests they would not pose appreciable concern to human health over a lifetime exposure to potable water. Fourteen compounds were identified with risk quotients above 0.2 which may warrant further investigation if greywater is used as a source for potable reuse. The present findings are helpful in prioritizing upcoming greywater quality monitoring and defining the goals of multiple barriers treatment in future water reclamation plants for potable water production. Copyright © 2014 Elsevier Ltd. All rights reserved.

Emerging contaminants in the environment: Risk-based analysis for better management.

PubMed

Naidu, Ravi; Arias Espana, Victor Andres; Liu, Yanju; Jit, Joytishna

2016-07-01

Emerging contaminants (ECs) are chemicals of a synthetic origin or deriving from a natural source that has recently been discovered and for which environmental or public health risks are yet to be established. This is due to limited available information on their interaction and toxicological impacts on receptors. Several types of ECs exist such as antibiotics, pesticides, pharmaceuticals, personal care products, effluents, certain naturally occurring contaminants and more recently nanomaterials. ECs may derive from a known source, for example released directly to the aquatic environment from direct discharges such as those from wastewater treatment plants. Although in most instances the direct source cannot be identified, ECs have been detected in virtually every country's natural environment and as a consequence they represent a global problem. There is very limited information on the fate and transport of ECs in the environment and their toxicological impact. This lack of information can be attributed to limited financial resources and the lack of analytical techniques for detecting their effects on ecosystems and human health on their own or as mixture. We do not know how ECs interact with each other or various contaminants. This paper presents an overview of existing knowledge on ECs, their fate and transport and a risk-based analysis for ECs management and complementary strategies. Copyright © 2016 Elsevier Ltd. All rights reserved.

Placenta-an alternative source of stem cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Matikainen, Tiina; Laine, Jarmo

2005-09-01

The two most promising practical applications of human stem cells are cellular replacement therapies in human disease and toxicological screening of candidate drug molecules. Both require a source of human stem cells that can be isolated, purified, expanded in number and differentiated into the cell type of choice in a controlled manner. Currently, uses of both embryonic and adult stem cells are investigated. While embryonic stem cells are pluripotent and can differentiate into any specialised cell type, their use requires establishment of embryonic stem cell lines using the inner cell mass of an early pre-implantation embryo. As the blastocyst ismore » destroyed during the process, ethical issues need to be carefully considered. The use of embryonic stem cells is also limited by the difficulties in growing large numbers of the cells without inducing spontaneous differentiation, and the problems in controlling directed differentiation of the cells. The use of adult stem cells, typically derived from bone marrow, but also from other tissues, is ethically non-controversial but their differentiation potential is more limited than that of the embryonic stem cells. Since human cord blood, umbilical cord, placenta and amnion are normally discarded at birth, they provide an easily accessible alternative source of stem cells. We review the potential and current status of the use of adult stem cells derived from the placenta or umbilical cord in therapeutic and toxicological applications.« less

Food for Thought … Integrated Testing Strategies for Safety Assessments

PubMed Central

Hartung, Thomas; Luechtefeld, Tom; Maertens, Alexandra; Kleensang, Andre

2013-01-01

Summary Despite the fact that toxicology uses many stand-alone tests, a systematic combination of several information sources very often is required: Examples include: when not all possible outcomes of interest (e.g., modes of action), classes of test substances (applicability domains), or severity classes of effect are covered in a single test; when the positive test result is rare (low prevalence leading to excessive false-positive results); when the gold standard test is too costly or uses too many animals, creating a need for prioritization by screening. Similarly, tests are combined when the human predictivity of a single test is not satisfactory or when existing data and evidence from various tests will be integrated. Increasingly, kinetic information also will be integrated to make an in vivo extrapolation from in vitro data. Integrated Testing Strategies (ITS) offer the solution to these problems. ITS have been discussed for more than a decade, and some attempts have been made in test guidance for regulations. Despite their obvious potential for revamping regulatory toxicology, however, we still have little guidance on the composition, validation, and adaptation of ITS for different purposes. Similarly, Weight of Evidence and Evidence-based Toxicology approaches require different pieces of evidence and test data to be weighed and combined. ITS also represent the logical way of combining pathway-based tests, as suggested in Toxicology for the 21st Century. This paper describes the state of the art of ITS and makes suggestions as to the definition, systematic combination, and quality assurance of ITS. PMID:23338803

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

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-26

... Scientific Advisory Committee on Alternative Toxicological Methods; Announcement of Meeting; Request for... Toxicological Methods (SACATM). SACATM advises the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM), the National Toxicology Program (NTP) Interagency Center for the Evaluation of...

The Role of Toxicology in the Pharmacy Curriculum

ERIC Educational Resources Information Center

Autian, John; Wood, George

1976-01-01

The past history of toxicology courses, recent trends, departments or divisions of toxicology, undergraduate and graduate courses, and residency programs are described. The emphasis of clinical toxicology in the University of Tennessee program is discussed, along with the school's Drug and Toxicology Information Center. (LBH)

Review: putative mutagens and carcinogens in foods. VII. Genetic toxicology of the diet

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hatch, F.T.; MacGregor, J.T.; Zeiger, E.

Individual reviews of approximately 30 papers presented at the Fourth International Conference on Environmental Mutagens are presented in this report. Topics covered include diet in cancer epidemiology; cooked and processed food as a source of mutagens and carcinogens; natural genotoxins in plants and beverages; mutagens within the gastrointestinal tract; and modulation of mutagenesis and carcinogenesis.

Rationale and Methods for Archival Sampling and Analysis of Atmospheric Trace Chemical Contaminants On Board Mir and Recommendations for the International Space Station

NASA Technical Reports Server (NTRS)

Perry, J. L.; James, J. T.; Cole, H. E.; Limero, T. F.; Beck, S. W.

1997-01-01

Collection and analysis of spacecraft cabin air samples are necessary to assess the cabin air quality with respect to crew health. Both toxicology and engineering disciplines work together to achieve an acceptably clean cabin atmosphere. Toxicology is concerned with limiting the risk to crew health from chemical sources, setting exposure limits, and analyzing air samples to determine how well these limits are met. Engineering provides the means for minimizing the contribution of the various contaminant generating sources by providing active contamination control equipment on board spacecraft and adhering to a rigorous material selection and control program during the design and construction of the spacecraft. A review of the rationale and objectives for sampling spacecraft cabin atmospheres is provided. The presently-available sampling equipment and methods are reviewed along with the analytical chemistry methods employed to determine trace contaminant concentrations. These methods are compared and assessed with respect to actual cabin air quality monitoring needs. Recommendations are presented with respect to the basic sampling program necessary to ensure an acceptably clean spacecraft cabin atmosphere. Also, rationale and recommendations for expanding the scope of the basic monitoring program are discussed.

ToxPi Graphical User Interface 2.0: Dynamic exploration, visualization, and sharing of integrated data models.

PubMed

Marvel, Skylar W; To, Kimberly; Grimm, Fabian A; Wright, Fred A; Rusyn, Ivan; Reif, David M

2018-03-05

Drawing integrated conclusions from diverse source data requires synthesis across multiple types of information. The ToxPi (Toxicological Prioritization Index) is an analytical framework that was developed to enable integration of multiple sources of evidence by transforming data into integrated, visual profiles. Methodological improvements have advanced ToxPi and expanded its applicability, necessitating a new, consolidated software platform to provide functionality, while preserving flexibility for future updates. We detail the implementation of a new graphical user interface for ToxPi (Toxicological Prioritization Index) that provides interactive visualization, analysis, reporting, and portability. The interface is deployed as a stand-alone, platform-independent Java application, with a modular design to accommodate inclusion of future analytics. The new ToxPi interface introduces several features, from flexible data import formats (including legacy formats that permit backward compatibility) to similarity-based clustering to options for high-resolution graphical output. We present the new ToxPi interface for dynamic exploration, visualization, and sharing of integrated data models. The ToxPi interface is freely-available as a single compressed download that includes the main Java executable, all libraries, example data files, and a complete user manual from http://toxpi.org .

Toxicological database of soil and derived products (BDT).

PubMed

Uricchio, Vito Felice

2008-01-01

The Toxicological database of soil and derived products is a project firstly proposed by the Regional Environmental Authority of Apulia. Such a project aims to provide comprehensive and updated information on the regional environmental characteristics, on the pollution state of the regional soil, on the main pollutants and on the reclaim techniques to be used in case of both non-point (agricultural activities) and point (industrial activities) sources of pollution. The project's focus is on the soil pollution because of the fundamental role played by the soil in supporting the biological cycle. Furthermore, the reasons for the project are related both to the reduction of human health risks due to toxic substances ingestion (these substances are present in some ring of the eating chain), and to the recognition of the importance of the groundwater quality safety (primary source of fresh water in many Mediterranean Regions). The essential requirements of a data entry are the following: speed and simplicity of the data entry; reliability and stability of the database structures; speed, easiness and pliability of the queries. Free consultation of the database represents one of the most remarkable advantages coming from the use of an "open" system.

Searching fee and non-fee toxicology information resources: an overview of selected databases.

PubMed

Wright, L L

2001-01-12

Toxicology profiles organize information by broad subjects, the first of which affirms identity of the agent studied. Studies here show two non-fee databases (ChemFinder and ChemIDplus) verify the identity of compounds with high efficiency (63% and 73% respectively) with the fee-based Chemical Abstracts Registry file serving well to fill data gaps (100%). Continued searching proceeds using knowledge of structure, scope and content to select databases. Valuable sources for information are factual databases that collect data and facts in special subject areas organized in formats available for analysis or use. Some sources representative of factual files are RTECS, CCRIS, HSDB, GENE-TOX and IRIS. Numerous factual databases offer a wealth of reliable information; however, exhaustive searches probe information published in journal articles and/or technical reports with records residing in bibliographic databases such as BIOSIS, EMBASE, MEDLINE, TOXLINE and Web of Science. Listed with descriptions are numerous factual and bibliographic databases supplied by 11 producers. Given the multitude of options and resources, it is often necessary to seek service desk assistance. Questions were posed by telephone and e-mail to service desks at DIALOG, ISI, MEDLARS, Micromedex and STN International. Results of the survey are reported.

Toxicological benchmarks for screening potential contaminants of concern for effects on aquatic biota: 1996 revision

DOE Office of Scientific and Technical Information (OSTI.GOV)

Suter, G.W. II; Tsao, C.L.

1996-06-01

This report presents potential screening benchmarks for protection of aquatic life form contaminants in water. Because there is no guidance for screening for benchmarks, a set of alternative benchmarks is presented herein. This report presents the alternative benchmarks for chemicals that have been detected on the Oak Ridge Reservation. It also presents the data used to calculate the benchmarks and the sources of the data. It compares the benchmarks and discusses their relative conservatism and utility. Also included is the updates of benchmark values where appropriate, new benchmark values, secondary sources are replaced by primary sources, and a more completemore » documentation of the sources and derivation of all values are presented.« less

Spacecraft Maximum Allowable Concentrations for Airborne Contaminants

NASA Technical Reports Server (NTRS)

James, John T.

2008-01-01

The enclosed table lists official spacecraft maximum allowable concentrations (SMACs), which are guideline values set by the NASA/JSC Toxicology Group in cooperation with the National Research Council Committee on Toxicology (NRCCOT). These values should not be used for situations other than human space flight without careful consideration of the criteria used to set each value. The SMACs take into account a number of unique factors such as the effect of space-flight stress on human physiology, the uniform good health of the astronauts, and the absence of pregnant or very young individuals. Documentation of the values is given in a 5 volume series of books entitled "Spacecraft Maximum Allowable Concentrations for Selected Airborne Contaminants" published by the National Academy Press, Washington, D.C. These books can be viewed electronically at http://books.nap.edu/openbook.php?record_id=9786&page=3. Short-term (1 and 24 hour) SMACs are set to manage accidental releases aboard a spacecraft and permit risk of minor, reversible effects such as mild mucosal irritation. In contrast, the long-term SMACs are set to fully protect healthy crewmembers from adverse effects resulting from continuous exposure to specific air pollutants for up to 1000 days. Crewmembers with allergies or unusual sensitivity to trace pollutants may not be afforded complete protection, even when long-term SMACs are not exceeded. Crewmember exposures involve a mixture of contaminants, each at a specific concentration (C(sub n)). These contaminants could interact to elicit symptoms of toxicity even though individual contaminants do not exceed their respective SMACs. The air quality is considered acceptable when the toxicity index (T(sub grp)) for each toxicological group of compounds is less than 1, where T(sub grp), is calculated as follows: T(sub grp) = C(sub 1)/SMAC(sub 1) + C(sub 2/SMAC(sub 2) + ...+C(sub n)/SMAC(sub n).

Predictive Toxicology: Current Status and Future Outlook (EBI ...

EPA Pesticide Factsheets

Slide presentation at the EBI-EMBL Industry Programme Workshop on Predictive Toxicology and the currently status of Computational Toxicology activities at the US EPA. Slide presentation at the EBI-EMBL Industry Programme Workshop on Predictive Toxicology and the currently status of Computational Toxicology activities at the US EPA.

Cornerstones of Toxicology.

PubMed

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).

Cornerstones of Toxicology

PubMed Central

Hayes, A. Wallace; Dixon, Darlene

2016-01-01

The 35th Annual Society of Toxicologic Pathology Symposium, held in June 2016 in San Diego, CA, 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 was presented that gave an overview of the Cornerstones of Toxicology. 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). PMID:28068892

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

PubMed

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.

COMPUTATIONAL TOXICOLOGY-WHERE IS THE DATA? ...

EPA Pesticide Factsheets

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).

Forensic Toxicology: An Introduction.

PubMed

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.

Effects of miglyol 812 on rats after 4 weeks of gavage as compared with methylcellulose/tween 80.

PubMed

Sellers, Rani S; Antman, M; Phillips, J; Khan, K N; Furst, S M

2005-01-01

Miglyol 812 is a medium-chain triglyceride used in toxicology studies as an excipient to improve test compound solubility/absorption. As part of a larger toxicology study, 15 Wistar Han IGS rats/sex/group were dosed by oral gavage for 4 weeks with 10 mL kg(-1) day(-1) of 100% Miglyol 812 or 0.5% methylcellulose/0.1% Tween 80 in water (MC-T) followed by 4 weeks without treatment to evaluate the potential effects of this excipient in long-term toxicology studies relative to a traditional excipient such as MC-T. Clinical signs evident during the dosing phase included soft and/or mucoid stool in 12/15 males and 11/15 females treated with Miglyol 812 but in no animals treated with MC-T. Animals treated with Miglyol 812 had a 6-7% statistically significant reduction in body weight gain as compared to MC-T-treated animals. Statistically significant changes in clinical chemistry parameters as compared to MC-T included decreased blood urea nitrogen (50% and 29% in males and females, respectively), increased cholesterol (1.6-fold and 1.5-fold in males and females, respectively), decreased total protein (6% and 8% in males and females, respectively), decreased globulins (15% and 11% in males and females, respectively), and increased triglycerides (2.8-fold and 1.7-fold in males and females, respectively). Absolute and relative thymic weights decreased 28% and 24%, respectively, in males, and 18% and 17%, respectively, in females without histological alterations. Histopathology revealed increased alveolar histiocytosis with focal interstitial inflammation in lungs in 5/10 males and 7/10 females treated with Miglyol 812 compared to only 1/10 males and 1/10 females treated with MC-T. All effects were reversible during the recovery period. Results of this study indicate that 100% miglyol 812 produces reversible gastrointestinal effects and decreases in body weight gains along with changes in several serum chemistry parameters. Therefore, it should not be considered innocuous when delivered by oral gavage in long-term rodent toxicology studies.

A multiple testing approach for hazard evaluation of complex mixtures in the aquatic environment: the use of diesel oil as a model

USGS Publications Warehouse

Johnson, B. Thomas

1989-01-01

Traditional single species toxicity tests and multiple component laboratory-scaled microcosm assays were combined to assess the toxicological hazard of diesel oil, a model complex mixture, to a model aquatic environment. The immediate impact of diesel oil dosed on a freshwater community was studied in a model pond microcosm over 14 days: a 7-day dosage and a 7-day recovery period. A multicomponent laboratory microcosm was designed to monitor the biological effects of diesel oil (1·0 mg litre−1) on four components: water, sediment (soil + microbiota), plants (aquatic macrophytes and algae), and animals (zooplanktonic and zoobenthic invertebrates). To determine the sensitivity of each part of the community to diesel oil contamination and how this model community recovered when the oil dissipated, limnological, toxicological, and microbiological variables were considered. Our model revealed these significant occurrences during the spill period: first, a community production and respiration perturbation, characterized in the water column by a decrease in dissolved oxygen and redox potential and a concomitant increase in alkalinity and conductivity; second, marked changes in microbiota of sediments that included bacterial heterotrophic dominance and a high heterotrophic index (0·6), increased bacterial productivity, and the marked increases in numbers of saprophytic bacteria (10 x) and bacterial oil degraders (1000 x); and third, column water acutely toxic (100% mortality) to two model taxa: Selenastrum capricornutum and Daphnia magna. Following the simulated clean-up procedure to remove the oil slick, the recovery period of this freshwater microcosm was characterized by a return to control values. This experimental design emphasized monitoring toxicological responses in aquatic microcosm; hence, we proposed the term ‘toxicosm’ to describe this approach to aquatic toxicological hazard evaluation. The toxicosm as a valuable toxicological tool for screening aquatic contaminants was demonstrated using diesel oil as a model complex mixture.

A global epidemiological perspective on the toxicology of drug-facilitated sexual assault: A systematic review.

PubMed

Anderson, Laura Jane; Flynn, Asher; Pilgrim, Jennifer Lucinda

2017-04-01

A systematic review was undertaken to determine the current global prevalence of drug-facilitated sexual assault (DFSA) reported in adults in order to identify trends in the toxicology findings in DFSA around the world over the past 20 years. Databases PubMed, PsycINFO and Scopus were systematically searched using the terms: "drug-facilitated sexual assault", "chemical submission", "date rape", "rape drugs" and "drink-spiking" to identify relevant studies for inclusion in the review. This study focused on adult victims of suspected DFSA aged 16 years and above in which toxicology results were reported. The majority of studies included were published in the United States, followed by the United Kingdom, with only a single study dedicated to this area in both Australia and Europe. Epidemiology, prevalence rates, and toxicology for DFSA appear broadly commensurate across different continents, although there are some differences in how "drug-facilitated sexual assault" is defined, as well as differences in the sensitivity of toxicological analyses. Nonetheless, alcohol is the most commonly detected substance and co-occurrence with other drugs is common. Aside from alcohol there was no other specific drug category associated with DFSA. Cannabinoids and benzodiazepines were frequently detected, but a lack of contextual information made it difficult to establish the extent that these substances contributed to suspected cases of DFSA. This comprehensive review suggests that alcohol intoxication combined with voluntary drug consumption presents the greatest risk factor for DFSA, despite populist perceptions that covert drink-spiking is a common occurrence. There is a need to develop policies that encourage early responders to suspected DFSA (e.g., law enforcement agencies, medical staff, support agencies, etc), to collect detailed information about the individual's licit and illicit drug consumption history, in order to assist in providing appropriate and more thorough contextual information. Copyright © 2017 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

Aerospace toxicology overview: aerial application and cabin air quality.

PubMed

Chaturvedi, Arvind K

2011-01-01

Aerospace toxicology is a rather recent development and is closely related to aerospace medicine. Aerospace toxicology can be defined as a field of study designed to address the adverse effects of medications, chemicals, and contaminants on humans who fly within or outside the atmosphere in aviation or on space flights. The environment extending above and beyond the surface of the Earth is referred to as aerospace. The term aviation is frequently used interchangeably with aerospace. The focus of the literature review performed to prepare this paper was on aerospace toxicology-related subject matters, aerial application and aircraft cabin air quality. Among the important topics addressed are the following: · Aerial applications of agricultural chemicals, pesticidal toxicity, and exposures to aerially applied mixtures of chemicals and their associated formulating solvents/surfactants The safety of aerially encountered chemicals and the bioanalytical methods used to monitor exposures to some of them · The presence of fumes and smoke, as well as other contaminants that may generally be present in aircraft/space vehicle cabin air · And importantly, the toxic effects of aerially encountered contaminants, with emphasis on the degradation products of oils, fluids, and lubricants used in aircraft, and finally · Analytical methods used for monitoring human exposure to CO and HCN are addressed in the review, as are the signs and symptoms associated with exposures to these combustion gases. Although many agricultural chemical monitoring studies have been published, few have dealt with the occurrence of such chemicals in aircraft cabin air. However, agricultural chemicals do appear in cabin air; indeed, attempts have been made to establish maximum allowable concentrations for several of the more potentially toxic ones that are found in aircraft cabin air. In this article, I emphasize the need for precautionary measures to be taken to minimize exposures to aerially 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.

The Global Educational Toxicology Uniting Project (GETUP): an Analysis of the First Year of a Novel Toxicology Education Project.

PubMed

Wong, Anselm; Vohra, Rais; Ruha, Anne-Michelle; Koutsogiannis, Zeff; Graeme, Kimberlie; Dargan, Paul I; Wood, David M; Greene, Shaun L

2015-09-01

The international boundaries to medical education are becoming less marked as new technologies such as multiuser videoconferencing are developed and become more accessible to help bridge the communication gaps. The Global Educational Toxicology Uniting Project (GETUP) is aimed at connecting clinicians in countries with established clinical toxicology services to clinicians in countries without clinical toxicologists around the globe. Centers that manage or consult on toxicology cases were registered through the American College of Medical Toxicology website via Survey Monkey®. Data was analyzed retrospectively from February 2014 to January 2015. Google hangouts® was used as the main conferencing software, but some sites preferred the use of Skype®. Registration data included contact details and toxicology background and qualifications. Thirty sites in 19 different countries in Australasia, Europe, Africa, and America were registered. Twenty-eight (93 %) sites were located in a major urban center, one (3.5 %) site in a major rural center and one (3.5 %) a private practice. Expectations of GETUP included sharing toxicology cases and education (30, 100 % of sites), assistance with toxicology management guidelines (2, 7 %), assistance with providing a toxicology teaching curriculum in languages other than English (2, 7 %), and managing toxicology presentations in resource-poor settings, international collaboration, and toxicovigilance (2 sites, 7 %). Twenty-two conferences were performed during the first 12 months with a mean of 3 cases per conference. GETUP has connected countries and clinical units with and without toxicology services and will provide a platform to improve international collaboration in clinical toxicology.

Eri silkworm: a source of edible oil with a high content of α-linolenic acid and of significant nutritional value.

PubMed

Longvah, Thingnganing; Manghtya, Korra; Qadri, Syed S Y H

2012-07-01

The study was undertaken to provide value addition to spent eri silkworm as an alternative source of edible oil for the food and feed industry by carrying out a short-term nutritional and toxicological evaluation of eri silkworm pupae oil using Wistar NIN rats. Growth performance of rats fed either sunflower oil (Control) or eri silkworm pupae oil (Experimental) was comparable. Histopathological examination of the various tissues showed no signs of toxicity even after feeding the eri silkworm oil for 18 weeks. Serum cholesterol and triglyceride was significantly reduced (P < 0.05) while high-density lipoprotein cholesterol was significantly increased (P < 0.05) which is attributed to the high α-linolenic acid content of eri silkworm oil. The study showed that eri silkworm pupae oil is safe and nutritionally equivalent to commonly used vegetable oils. Eri silkworm pupae can be harvested to provide a cost effective alternative edible oil that can be used to nutritional advantage in the food and feed industry. Therefore eri silkworm and its host plants offer an excellent example of multiple product crops and of sustainable agricultural practice with excellent opportunity for economic and nutritional benefits. Copyright © 2012 Society of Chemical Industry.

Promising features of Moringa oleifera oil: recent updates and perspectives.

PubMed

Nadeem, Muhammad; Imran, Muhammad

2016-12-08

Lipids are the concentrated source of energy, fat soluble vitamins, essential fatty acids, carriers of flavours and many bio-active compounds with important role in maintaining physiological functions of biological body. Moringa oleifera is native to Himalaya and widely grown in many Asian and African countries with seed oil content range from 35-40%. Moringa oleifera oil (MOO) has light yellow colour with mild nutty flavour and fatty acids composition suggests that MOO is highly suitable for both edible and non-edible applications. MOO is extremely resistant to autoxidation which can be used as an antioxidant for the long term stabilization of commercial edible oils. Thermal stability of MOO is greater than soybean, sunflower, canola and cottonseed oils. High oleic contents of MOO are believed to have the capability of increasing beneficial HDL cholesterol and decreased the serum cholesterol and triglycerides. MOO applications have also been explored in cosmetics, folk medicines and skin care formulations. Overall, this review focuses on commercial production status, food applications, antioxidant characteristics, health benefits, thermal stability, fractionation, cholesterol contents, medicinal, nutraceutical action, toxicological evaluation, biodiesel production, personal care formulations and future perspectives of the MOO for the stake holders to process and utilize MOO as a new source of edible oil for industrial purpose.

Aggregating Data for Computational Toxicology Applications ...

EPA Pesticide Factsheets

Computational toxicology combines data from high-throughput test methods, chemical structure analyses and other biological domains (e.g., genes, proteins, cells, tissues) with the goals of predicting and understanding the underlying mechanistic causes of chemical toxicity and for predicting toxicity of new chemicals and products. A key feature of such approaches is their reliance on knowledge extracted from large collections of data and data sets in computable formats. The U.S. Environmental Protection Agency (EPA) has developed a large data resource called ACToR (Aggregated Computational Toxicology Resource) to support these data-intensive efforts. ACToR comprises four main repositories: core ACToR (chemical identifiers and structures, and summary data on hazard, exposure, use, and other domains), ToxRefDB (Toxicity Reference Database, a compilation of detailed in vivo toxicity data from guideline studies), ExpoCastDB (detailed human exposure data from observational studies of selected chemicals), and ToxCastDB (data from high-throughput screening programs, including links to underlying biological information related to genes and pathways). The EPA DSSTox (Distributed Structure-Searchable Toxicity) program provides expert-reviewed chemical structures and associated information for these and other high-interest public inventories. Overall, the ACToR system contains information on about 400,000 chemicals from 1100 different sources. The entire system is built usi

Evaluation of certain food additives. Seventy-first report of the Joint FAO/WHO Expert Committee on Food Additives.

PubMed

2010-01-01

This report represents the conclusions of a Joint FAO/WHO Expert Committee convened to evaluate the safety of various food additives, with a view to recommending acceptable daily intakes (ADIs) and to preparing specifications for identity and purity. The first part of the report contains a general discussion of the principles governing the toxicological evaluation and assessment of intake of food additives. A summary follows of the Committee's evaluations of technical, toxicological and intake data for certain food additives: branching glycosyltransferase from Rhodothermus obamensis expressed in Bacillus subtilis, cassia gum, cyclamic acid and its salts (dietary exposure assessment), cyclotetraglucose and cyclotetraglucose syrup, ferrous ammonium phosphate, glycerol ester of gum rosin, glycerol ester of tall oil rosin, lycopene from all sources, lycopene extract from tomato, mineral oil (low and medium viscosity) class II and class III, octenyl succinic acid modified gum arabic, sodium hydrogen sulfate and sucrose oligoesters type I and type II. Specifications for the following food additives were revised: diacetyltartaric acid and fatty acid esters of glycerol, ethyl lauroyl arginate, glycerol ester of wood rosin, nisin preparation, nitrous oxide, pectins, starch sodium octenyl succinate, tannic acid, titanium dioxide and triethyl citrate. Annexed to the report are tables summarizing the Committee's recommendations for intakes and toxicological evaluations of the food additives considered.

Using ToxCast in vitro Assays in the Hierarchical Quantitative Structure-Activity Relationship (QSAR) Modeling for Predicting in vivo Toxicity of Chemicals

EPA Science Inventory

The goal of chemical toxicology research is utilizing short term bioassays and/or robust computational methods to predict in vivo toxicity endpoints for chemicals. The ToxCast program established at the US Environmental Protection Agency (EPA) is addressing this goal by using ca....

Update on EPA’s ToxCast Program: Providing High Throughput Decision Support Tools for Chemical Risk Management

EPA Science Inventory

The field of toxicology is on the cusp of a major transformation in how the safety and hazard of chemicals are evaluated for potential effects on human health and the environment. Brought on by the recognition of the limitations of the current paradigm in terms of cost, time, and...

The fifth plot of the Carcinogenic Potency Database: results of animal bioassays published in the general literature through 1988 and by the National Toxicology Program through 1989.

PubMed Central

Gold, L S; Manley, N B; Slone, T H; Garfinkel, G B; Rohrbach, L; Ames, B N

1993-01-01

This paper is the fifth plot of the Carcinogenic Potency Database (CPDB) that first appeared in this journal in 1984 (1-5). We report here results of carcinogenesis bioassays published in the general literature between January 1987 and December 1988, and in technical reports of the National Toxicology Program between July 1987 and December 1989. This supplement includes results of 412 long-term, chronic experiments of 147 test compounds and reports the same information about each experiment in the same plot format as the earlier papers: the species and strain of test animal, the route and duration of compound administration, dose level and other aspects of experimental protocol, histopathology and tumor incidence, TD50 (carcinogenic potency) and its statistical significance, dose response, author's opinion about carcinogenicity, and literature citation. We refer the reader to the 1984 publications (1,5,6) for a guide to the plot of the database, a complete description of the numerical index of carcinogenic potency, and a discussion of the sources of data, the rationale for the inclusion of particular experiments and particular target sites, and the conventions adopted in summarizing the literature. The five plots of the database are to be used together, as results of individual experiments that were published earlier are not repeated. In all, the five plots include results of 4487 experiments on 1136 chemicals. Several analyses based on the CPDB that were published earlier are described briefly, and updated results based on all five plots are given for the following earlier analyses: the most potent TD50 value by species, reproducibility of bioassay results, positivity rates, and prediction between species.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8354183

Third chronological supplement to the carcinogenic potency database: standardized results of animal bioassays published through December 1986 and by the National Toxicology Program through June 1987.

PubMed Central

Gold, L S; Slone, T H; Backman, G M; Eisenberg, S; Da Costa, M; Wong, M; Manley, N B; Rohrbach, L; Ames, B N

1990-01-01

This paper is the third chronological supplement to the Carcinogenic Potency Database that first appeared in this journal in 1984. We report here results of carcinogenesis bioassays published in the general literature between January 1985 and December 1986, and in Technical Reports of the National Toxicology Program between June 1986 and June 1987. This supplement includes results of 337 long-term, chronic experiments of 121 compounds, and reports the same information about each experiment in the same plot format as the earlier papers, e.g., the species and strain of animal, the route and duration of compound administration, dose level, and other aspects of experimental protocol, histopathology, and tumor incidence, TD50 (carcinogenic potency) and its statistical significance, dose response, opinion of the author about carcinogenicity, and literature citation. The reader needs to refer to the 1984 publication for a guide to the plot of the database, a complete description of the numerical index of carcinogenic potency, and a discussion of the sources of data, the rationale for the inclusion of particular experiments and particular target sites, and the conventions adopted in summarizing the literature. The four plots of the database are to be used together as results published earlier are not repeated. In all, the four plots include results for approximately 4000 experiments on 1050 chemicals. Appendix 14 of this paper is an alphabetical index to all chemicals in the database and indicates which plot(s) each chemical appears in. A combined plot of all results from the four separate papers, that is ordered alphabetically by chemical, is available from the first author, in printed form or on computer tape or diskette. PMID:2351123

Assessment of the histopathological lesions and chemical analysis of feral cats to the smoke from the Kuwait oil fires

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moeller, R.B. Jr.; Dick, E.J.; Pletcher, J.M.

Twenty-six adult or subadult feral cats were collected from Kuwait approximately 8 months after the ignition of the Kuwait oil wells. These animals were obtained from two sources: 12 animals from Kuwait City, a relatively smoke-free area, and 14 from the city of Ahmadi, an area with heavy smoke. Animals were euthanized and a complete set of tissues consisting of all major organs was taken for histopathology. Samples of lung, liver, kidney, urine, and blood were also taken for toxicology. Histopathological lesions observed in the lung were mild accumulations of anthracotic pigment in the lungs of 17 cats. Hyperplasia ofmore » the bronchial and bronchiolar gland in 8 cats, and smooth muscle hyperplasia of bronchioles in 14 cats. Tracheal gland hyperplasia was observed in 7 cats, and minimal squamous metaplasia of the tracheal mucosa in 17 cats, Laryngeal lesions consisted of submucosal gland hyperplasia in 2 cats and squamous metaplasia of the mucosa in 5 cats. Hyperplasia of the nasal submucosal glands was observed in 6 animals. The pharyngeal mucosa as well as other organs and organ systems were normal in all cats. Atomic absorption analysis for 11 metals was performed; vanadium and nickel levels (two metals that were present in the smoke from the oil fires) are not indicative of substantial exposure to the oil fires. Based on the histopathological findings and toxicological analysis, it is felt that inhalation of air contaminated with smoke from the oil fires had little or no long-term effect on the animals examined. 36 refs., 3 figs., 7 tabs.« less

Past and present mercury accumulation in the Lake Baikal seal: Temporal trends, effects of life history, and toxicological implications.

PubMed

Poste, Amanda E; Pastukhov, Mikhail V; Braaten, Hans Fredrik Veiteberg; Ozersky, Ted; Moore, Marianne

2018-05-01

Despite global efforts to reduce anthropogenic mercury (Hg) emissions, the timescale and degree to which Hg concentrations in the environment and biota respond to decreased emissions remain challenging to assess or predict. In the present study we characterize long-term trends and life-history patterns in Hg accumulation and toxicological implications of Hg contamination for a freshwater seal from one of the world's largest lakes (Lake Baikal, Siberia, Russia) using contemporary tissues and archival teeth. Stable isotope analysis and Hg analyses of soft tissues (muscle, liver, kidney, blood, brain, heart) and teeth from 22 contemporary seals revealed rapid changes in diet and Hg accumulation in the first year of life with a stable diet and increase in tissue Hg throughout the rest of life. Although maternal transfer of Hg was an important source of Hg to seal pups, reproduction and lactation by female seals did not appear to result in sex-related differences in Hg concentrations or age-related accumulation in adult seals. Based on Hg analysis of archival teeth (n = 114) and reconstructed values for soft tissues, we also assessed temporal trends in seal Hg between the years 1960 and 2013. Seal Hg concentrations in hard (teeth) and soft (e.g., muscle, liver) tissues were highest in the 1960s and 1970s, followed by a decrease. The decline in seal Hg concentrations in recent decades was most likely driven by a reduction in Hg inputs to the lake, suggesting that global and regional efforts to reduce Hg emissions have been successful at reducing ecosystem and human health risks posed by Hg in Lake Baikal. Environ Toxicol Chem 2018;37:1476-1486. © 2018 SETAC. © 2018 SETAC.

ACToR-AGGREGATED COMPUTATIONAL TOXICOLOGY ...

EPA Pesticide Factsheets

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

National Toxicology Program

MedlinePlus

... develops and applies tools of modern toxicology and molecular biology to identify substances in the environment that may ... application of new technologies for modern toxicology and molecular biology. A world leader in toxicology research, NTP has ...

Using High-Content Imaging to Analyze Toxicological Tipping Points (ICTATT meeting China)

EPA Science Inventory

Presentation at International Conference on Toxicological Alternatives & Translational Toxicology (ICTATT) held in China and Discussing the possibility of using High Content Imaging to Analyze Toxicological Tipping Points

The Emergence of Systematic Review in Toxicology.

PubMed

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.

Nanotoxicology: An Emerging Discipline Evolving from Studies of Ultrafine Particles

PubMed Central

Oberdörster, Günter; Oberdörster, Eva; Oberdörster, Jan

2005-01-01

Although humans have been exposed to airborne nanosized particles (NSPs; < 100 nm) throughout their evolutionary stages, such exposure has increased dramatically over the last century due to anthropogenic sources. The rapidly developing field of nanotechnology is likely to become yet another source through inhalation, ingestion, skin uptake, and injection of engineered nanomaterials. Information about safety and potential hazards is urgently needed. Results of older bio-kinetic studies with NSPs and newer epidemiologic and toxicologic studies with airborne ultrafine particles can be viewed as the basis for the expanding field of nanotoxicology, which can be defined as safety evaluation of engineered nanostructures and nanodevices. Collectively, some emerging concepts of nanotoxicology can be identified from the results of these studies. When inhaled, specific sizes of NSPs are efficiently deposited by diffusional mechanisms in all regions of the respiratory tract. The small size facilitates uptake into cells and transcytosis across epithelial and endothelial cells into the blood and lymph circulation to reach potentially sensitive target sites such as bone marrow, lymph nodes, spleen, and heart. Access to the central nervous system and ganglia via translocation along axons and dendrites of neurons has also been observed. NSPs penetrating the skin distribute via uptake into lymphatic channels. Endocytosis and biokinetics are largely dependent on NSP surface chemistry (coating) and in vivo surface modifications. The greater surface area per mass compared with larger-sized particles of the same chemistry renders NSPs more active biologically. This activity includes a potential for inflammatory and pro-oxidant, but also antioxidant, activity, which can explain early findings showing mixed results in terms of toxicity of NSPs to environmentally relevant species. Evidence of mitochondrial distribution and oxidative stress response after NSP endocytosis points to a need for basic research on their interactions with subcellular structures. Additional considerations for assessing safety of engineered NSPs include careful selections of appropriate and relevant doses/concentrations, the likelihood of increased effects in a compromised organism, and also the benefits of possible desirable effects. An interdisciplinary team approach (e.g., toxicology, materials science, medicine, molecular biology, and bioinformatics, to name a few) is mandatory for nanotoxicology research to arrive at an appropriate risk assessment. PMID:16002369

Short-term mechanisms of toxic action of airborne particulates underlie dose-rate dependent health risks and support control of one-hour airborne particle levels

DOE Office of Scientific and Technical Information (OSTI.GOV)

Michaels, R.A.; Kleinman, M.T.

1999-07-01

Twenty-four-hour airborne particle mass levels permissible under the NAAQS have been associated with mortality and morbidity in communities, motivating reconsideration of the standard. Reports of shorter-term mechanisms of toxic action exerted by airborne PM and PM constituents are emerging. The mechanisms are diverse, but have in common a short time frame of toxic action, from minutes to hours. In view of documented PM excursions also lasting minutes to hours, this study inquires whether such short-term mechanisms might contribute to explaining daily morbidity and mortality. Toxicology experiments have demonstrated the harmfulness of brief exposure to PM levels in the range ofmore » observed excursions. This suggests that toxicological processes initiated by short-term inhalation of PM may exert clinically important effects, and that weak associations of 24-hour-average particle mass with mortality and morbidity may represent artifacts of stronger, shorter-term associations whose full magnitude remains to be quantified. In one study, the area of lung surface developing lesions was elevated in rats breathing the same four-hour dose of aerosols, when the four-hour average rate of aerosol delivery included a short-term (five-minute) burst fifty percent above the average dose rate. Elevations were observed with each of two aerosols tested. The magnitude of the effect was higher with one of the two aerosols, whose dose rate included four excursions rather than just one excursion. Particulate matter inhaled or instilled intratracheally has produced morbidity in animals, including apnea and electrophysiological effects in dogs. Other studies reveal that PM can kill rats via electrophysiological and possibly other mechanisms. PM has also adversely affected asthmatic people in controlled clinical settings during exercise or, in one study, at rest.« less

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

PubMed

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

2005-09-01

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.

Space Toxicology

NASA Technical Reports Server (NTRS)

James, John T.

2011-01-01

Safe breathing air for space faring crews is essential whether they are inside an Extravehicular Mobility Suit (EMU), a small capsule such as Soyuz, or the expansive International Space Station (ISS). Sources of air pollution can include entry of propellants, excess offgassing from polymeric materials, leakage of systems compounds, escape of payload compounds, over-use of utility compounds, microbial metabolism, and human metabolism. The toxicological risk posed by a compound is comprised of the probability of escaping to cause air pollution and the magnitude of adverse effects on human health if escape occurs. The risk from highly toxic compounds is controlled by requiring multiple levels of containment to greatly reduce the probability of escape; whereas compounds that are virtually non-toxic may require little or no containment. The potential for toxicity is determined by the inherent toxicity of the compound and the amount that could potentially escape into the breathing air.

Comparative toxicology of laboratory organisms for assessing hazardous-waste sites

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miller, W.E.; Peterson, S.A.; Greene, J.C.

1985-01-01

Multi-media/multi-trophic level bioassays have been proposed to determine the extent and severity of environmental contamination at hazardous waste sites. Comparative toxicological profiles for algae, daphnia, earthworms, microbes, mixed sewage and plants; wheat Stephens, lettuce, butter crunch, radish, Cherry Belle, red clover, Kenland, and cucumber, Spartan Valor are presented for selected heavy metals, herbicides and insecticides. Specific chemical EC50 values are presented for each test organism. Differences in standard deviations were compared between each individual test organism, as well as for the chemical subgroup assayed. Algae and daphnia are the most sensitive test organisms to heavy metals and insecticides followed inmore » order of decreasing sensitivity by Microtox, DO depletion rate, seed germination and earthworms. Differences in toxicity of 2,4-D chemical formulations and commercial sources of insecticides were observed with algae and daphnia tests.« less

The SEURAT-1 approach towards animal free human safety assessment.

PubMed

Gocht, Tilman; Berggren, Elisabet; Ahr, Hans Jürgen; Cotgreave, Ian; Cronin, Mark T D; Daston, George; Hardy, Barry; Heinzle, Elmar; Hescheler, Jürgen; Knight, Derek J; Mahony, Catherine; Peschanski, Marc; Schwarz, Michael; Thomas, Russell S; Verfaillie, Catherine; White, Andrew; Whelan, Maurice

2015-01-01

SEURAT-1 is a European public-private research consortium that is working towards animal-free testing of chemical compounds and the highest level of consumer protection. A research strategy was formulated based on the guiding principle to adopt a toxicological mode-of-action framework to describe how any substance may adversely affect human health.The proof of the initiative will be in demonstrating the applicability of the concepts on which SEURAT-1 is built on three levels:(i) Theoretical prototypes for adverse outcome pathways are formulated based on knowledge already available in the scientific literature on investigating the toxicological mode-of-actions leading to adverse outcomes (addressing mainly liver toxicity);(ii)adverse outcome pathway descriptions are used as a guide for the formulation of case studies to further elucidate the theoretical model and to develop integrated testing strategies for the prediction of certain toxicological effects (i.e., those related to the adverse outcome pathway descriptions);(iii) further case studies target the application of knowledge gained within SEURAT-1 in the context of safety assessment. The ultimate goal would be to perform ab initio predictions based on a complete understanding of toxicological mechanisms. In the near-term, it is more realistic that data from innovative testing methods will support read-across arguments. Both scenarios are addressed with case studies for improved safety assessment. A conceptual framework for a rational integrated assessment strategy emerged from designing the case studies and is discussed in the context of international developments focusing on alternative approaches for evaluating chemicals using the new 21st century tools for toxicity testing.

Zinc hazards to plants and animals with emphasis on fishery and wildlife resources

USGS Publications Warehouse

Eisler, R.; Cheremisinoff, Paul N.

1997-01-01

Ecological and toxicological aspects of zinc in the environment are reviewed with emphasis on natural resources. Subtopics include sources and uses; chemical and biochemical properties; carcinogenicity, mutagenicity, teratogenicity; background concentrations in biological and nonbiological compartments; effects of zinc deficiency; toxic and sublethal effects on terrestrial plants and invertebrates, aquatic organisms, birds, and mammals; and recommendations for the protection of sensitive resources.

Molybdenum Hazards to Fish, Wildlife, and Invertebrates: A Synoptic Review

USGS Publications Warehouse

Eisler, R.

1989-01-01

Ecological and toxicological aspects of molybdenum (Mo) in the environment are briefly reviewed, with emphasis on fish and wildlife. Subtopics include sources and uses, chemical properties, mode of action, background concentrations in biological and nonbiological samples, and lethal and sublethal effects on terrestrial plants and invertebrates, aquatic organisms, birds, and mammals. Current recommendations for Mo and the protection of sensitive living resources are presented.

Advancing alternatives analysis: The role of predictive toxicology in selecting safer chemical products and processes.

PubMed

Malloy, Timothy; Zaunbrecher, Virginia; Beryt, Elizabeth; Judson, Richard; Tice, Raymond; Allard, Patrick; Blake, Ann; Cote, Ila; Godwin, Hilary; Heine, Lauren; Kerzic, Patrick; Kostal, Jakub; Marchant, Gary; McPartland, Jennifer; Moran, Kelly; Nel, Andre; Ogunseitan, Oladele; Rossi, Mark; Thayer, Kristina; Tickner, Joel; Whittaker, Margaret; Zarker, Ken

2017-09-01

Alternatives analysis (AA) is a method used in regulation and product design to identify, assess, and evaluate the safety and viability of potential substitutes for hazardous chemicals. It requires toxicological data for the existing chemical and potential alternatives. Predictive toxicology uses in silico and in vitro approaches, computational models, and other tools to expedite toxicological data generation in a more cost-effective manner than traditional approaches. The present article briefly reviews the challenges associated with using predictive toxicology in regulatory AA, then presents 4 recommendations for its advancement. It recommends using case studies to advance the integration of predictive toxicology into AA, adopting a stepwise process to employing predictive toxicology in AA beginning with prioritization of chemicals of concern, leveraging existing resources to advance the integration of predictive toxicology into the practice of AA, and supporting transdisciplinary efforts. The further incorporation of predictive toxicology into AA would advance the ability of companies and regulators to select alternatives to harmful ingredients, and potentially increase the use of predictive toxicology in regulation more broadly. Integr Environ Assess Manag 2017;13:915-925. © 2017 SETAC. © 2017 SETAC.

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

PubMed

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.

Dioxin equivalency: Challenge to dose extrapolation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brown, J.F. Jr.; Silkworth, J.B.

1995-12-31

Extensive research has shown that all biological effects of dioxin-like agents are mediated via a single biochemical target, the Ah receptor (AhR), and that the relative biologic potencies of such agents in any given system, coupled with their exposure levels, may be described in terms of toxic equivalents (TEQ). It has also shown that the TEQ sources include not only chlorinated species such as the dioxins (PCDDs), PCDFs, and coplanar PCBs, but also non-chlorinated substances such as the PAHs of wood smoke, the AhR agonists of cooked meat, and the indolocarbazol (ICZ) derived from cruciferous vegetables. Humans have probably hadmore » elevated exposures to these non-chlorinated TEQ sources ever since the discoveries of fire, cooking, and the culinary use of Brassica spp. Recent assays of CYP1A2 induction show that these ``natural`` or ``traditional`` AhR agonists are contributing 50--100 times as much to average human TEQ exposures as do the chlorinated xenobiotics. Currently, the safe doses of the xenobiotic TEQ sources are estimated from their NOAELs and large extrapolation factors, derived from arbitrary mathematical models, whereas the NOAELs themselves are regarded as the safe doses for the TEQs of traditional dietary components. Available scientific data can neither support nor refute either approach to assessing the health risk of an individual chemical substance. However, if two substances be toxicologically equivalent, then their TEQ-adjusted health risks must also be equivalent, and the same dose extrapolation procedure should be used for both.« less

ACToR A Aggregated Computational Toxicology Resource

EPA Science Inventory

We are developing the ACToR system (Aggregated Computational Toxicology Resource) to serve as a repository for a variety of types of chemical, biological and toxicological data that can be used for predictive modeling of chemical toxicology.

ACToR A Aggregated Computational Toxicology Resource (S)

EPA Science Inventory

We are developing the ACToR system (Aggregated Computational Toxicology Resource) to serve as a repository for a variety of types of chemical, biological and toxicological data that can be used for predictive modeling of chemical toxicology.

Titanium dioxide in our everyday life; is it safe?

PubMed Central

Skocaj, Matej; Filipic, Metka; Petkovic, Jana; Novak, Sasa

2011-01-01

Background Titanium dioxide (TiO2) is considered as an inert and safe material and has been used in many applications for decades. However, with the development of nanotechnologies TiO2 nanoparticles, with numerous novel and useful properties, are increasingly manufactured and used. Therefore increased human and environmental exposure can be expected, which has put TiO2 nanoparticles under toxicological scrutiny. Mechanistic toxicological studies show that TiO2 nanoparticles predominantly cause adverse effects via induction of oxidative stress resulting in cell damage, genotoxicity, inflammation, immune response etc. The extent and type of damage strongly depends on physical and chemical characteristics of TiO2 nanoparticles, which govern their bioavailability and reactivity. Based on the experimental evidence from animal inhalation studies TiO2 nanoparticles are classified as “possible carcinogenic to humans” by the International Agency for Research on Cancer and as occupational carcinogen by the National Institute for Occupational Safety and Health. The studies on dermal exposure to TiO2 nanoparticles, which is in humans substantial through the use of sunscreens, generally indicate negligible transdermal penetration; however data are needed on long-term exposure and potential adverse effects of photo-oxidation products. Although TiO2 is permitted as an additive (E171) in food and pharmaceutical products we do not have reliable data on its absorption, distribution, excretion and toxicity on oral exposure. TiO2 may also enter environment, and while it exerts low acute toxicity to aquatic organisms, upon long-term exposure it induces a range of sub-lethal effects. Conclusions Until relevant toxicological and human exposure data that would enable reliable risk assessment are obtained, TiO2 nanoparticles should be used with great care. PMID:22933961

The multi-functional roles of GNMT in toxicology and cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yen, Chia-Hung; Lin, Yu-Ting; Chen, Heng-Li

Although glycine N-methyltransferase (GNMT) has been discovered for five decades, its function was not elucidated until recently. In this review, we discuss the multiple roles of GNMT in toxicology and cancer. Besides catalyzing the production of methylglycine (sarcosine) in one carbon metabolism pathway, GNMT was found to be able to bind a number of polycyclic aromatic hydrocarbons and inhibit DNA adducts formation. Moreover, GNMT exerts protective effects against the cytotoxicity and carcinogenicity of benzo(a)pyrene and aflatoxin B{sub 1} in vitro and in vivo. Occupational study showed that workers who had genotypes with higher GNMT promoter activity may have lower contentmore » of oxidative damaged DNA products in their urine. In terms of cancer, recent studies using GNMT knockout mouse models demonstrated that GNMT deficiency has high penetrance in inducing the development of steatohepatitis and hepatocellular carcinoma. In terms of the mechanism, besides dysregulation of epigenetic modification, insights have been provided by recent identification of two novel proteins interacting with GNMT-DEPTOR and NPC2. These studies suggest that GNMT not only is involved in mTOR signaling pathway, but also plays an important role in the intracellular trafficking of cholesterol. The implication of these findings to the preventive medicine and translational research will be discussed. -- Highlights: ► We discuss the critical roles of GNMT in toxicology and cancer biology. ► GNMT binds benzo(a)pyrene and aflatoxin and inhibits their DNA adduct formation. ► GNMT deficiency is related to liver tumorigenesis both in mice and human. ► GNMT deficiency results in epigenetic dysregulation and metabolic diseases. ► GNMT is involved in mTOR pathway and intracellular trafficking of cholesterol.« less

[Assessment of so called organic trace compounds in drinking water from the regulatory, health and aesthetic-quality points of view, with special consideration given to pharmaceuticals].

PubMed

Dieter, H H; Mückter, H

2007-03-01

More than 2500 chemically defined substances are approved as drugs in Germany. Unlike agricultural pesticides, these biologically active structures are not used in open environmental compartments and therefore their environmental toxicological data base is not nearly as complete. Nevertheless, some of them become environmental contaminants after their intended use. Therefore, from the viewpoint of environmental health protection, there are gaps in their health-related environmental risk assessment. Organic trace compounds that lack an adequate toxicological database, and their mixtures, in drinking water can be safely regulated and provisionally assessed by combining the "similar joint action" addition rule with the recommendation of the Federal Environment Agency of March 2003 "Assessing the presence of substances in drinking water without (adequate) toxicological database from the health point of view". The general precautionary value (Gesundheitlicher Orientierungswert GOW1=0.10 microg/l), which is a recommendation for weakly to not genotoxic compounds, re presents a workable compromise between preventive health protection, water management considerations and aesthetic quality claims (purity). Compliance with this value in the long term will only be possible if the chemical and biological degradation of pharmaceuticals and their metabolites in waste water and waste water treatment plants is effectively improved. Alternatively, there is the risk of drinking water degenerating into a sink for highly mobile, polar and persistent compounds. Their elimination at a stage as late as technical drinking water treatment would be neither close to the initial cause nor justifiable in terms of technical effectiveness. The risk assessment of their byproducts would give rise to further uncertainties. Possible conflicts with the therapeutic quality must be solved by developing substitute products which are environmentally sound.

The Emergence of Systematic Review in Toxicology

PubMed Central

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

2016-01-01

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. PMID:27208075

Emerging approaches in predictive toxicology.

PubMed

Zhang, Luoping; McHale, Cliona M; Greene, Nigel; Snyder, Ronald D; Rich, Ivan N; Aardema, Marilyn J; Roy, Shambhu; Pfuhler, Stefan; Venkatactahalam, Sundaresan

2014-12-01

Predictive toxicology plays an important role in the assessment of toxicity of chemicals and the drug development process. While there are several well-established in vitro and in vivo assays that are suitable for predictive toxicology, recent advances in high-throughput analytical technologies and model systems are expected to have a major impact on the field of predictive toxicology. This commentary provides an overview of the state of the current science and a brief discussion on future perspectives for the field of predictive toxicology for human toxicity. Computational models for predictive toxicology, needs for further refinement and obstacles to expand computational models to include additional classes of chemical compounds are highlighted. Functional and comparative genomics approaches in predictive toxicology are discussed with an emphasis on successful utilization of recently developed model systems for high-throughput analysis. The advantages of three-dimensional model systems and stem cells and their use in predictive toxicology testing are also described. © 2014 Wiley Periodicals, Inc.

Emerging Approaches in Predictive Toxicology

PubMed Central

Zhang, Luoping; McHale, Cliona M.; Greene, Nigel; Snyder, Ronald D.; Rich, Ivan N.; Aardema, Marilyn J.; Roy, Shambhu; Pfuhler, Stefan; Venkatactahalam, Sundaresan

2016-01-01

Predictive toxicology plays an important role in the assessment of toxicity of chemicals and the drug development process. While there are several well-established in vitro and in vivo assays that are suitable for predictive toxicology, recent advances in high-throughput analytical technologies and model systems are expected to have a major impact on the field of predictive toxicology. This commentary provides an overview of the state of the current science and a brief discussion on future perspectives for the field of predictive toxicology for human toxicity. Computational models for predictive toxicology, needs for further refinement and obstacles to expand computational models to include additional classes of chemical compounds are highlighted. Functional and comparative genomics approaches in predictive toxicology are discussed with an emphasis on successful utilization of recently developed model systems for high-throughput analysis. The advantages of three-dimensional model systems and stem cells and their use in predictive toxicology testing are also described. PMID:25044351

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

2005-09-01

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) creationmore » 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.« less

Got Mercury?

NASA Technical Reports Server (NTRS)

Meyers, Valerie E.; McCoy, J. Torin; Garcia, Hector D.; James, John T.

2009-01-01

Many of the operational and payload lighting units used in various spacecraft contain elemental mercury. If these devices were damaged on-orbit, elemental mercury could be released into the cabin. Although there are plans to replace operational units with alternate light sources, such as LEDs, that do not contain mercury, mercury-containing lamps efficiently produce high quality illumination and may never be completely replaced on orbit. Therefore, exposure to elemental mercury during spaceflight will remain possible and represents a toxicological hazard. Elemental mercury is a liquid metal that vaporizes slowly at room temperature. However, it may be completely vaporized at the elevated operating temperatures of lamps. Although liquid mercury is not readily absorbed through the skin or digestive tract, mercury vapors are efficiently absorbed through the respiratory tract. Therefore, the amount of mercury in the vapor form must be estimated. For mercury releases from lamps that are not being operated, we utilized a study conducted by the New Jersey Department of Environmental Quality to calculate the amount of mercury vapor expected to form over a 2-week period. For longer missions and for mercury releases occurring when lamps are operating, we conservatively assumed complete volatilization of the available mercury. Because current spacecraft environmental control systems are unable to remove mercury vapors, both short-term and long-term exposures to mercury vapors are possible. Acute exposure to high concentrations of mercury vapors can cause irritation of the respiratory tract and behavioral symptoms, such as irritability and hyperactivity. Chronic exposure can result in damage to the nervous system (tremors, memory loss, insomnia, etc.) and kidneys (proteinurea). Therefore, the JSC Toxicology Group recommends that stringent safety controls and verifications (vibrational testing, etc.) be applied to any hardware that contains elemental mercury that could yield airborne mercury vapor concentrations greater than 0.1 mg/cu m in the total spacecraft atmosphere for exposures lasting 30 days or less or 0.01 mg/cu m mercury vapor for exposures lasting more than 30 days. We also encourage the use of alternative devices that do not contain mercury.

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

PubMed

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.

TOXNET (TOXICOLOGY DATA NETWORK)

EPA Science Inventory

TOXNET (Toxicology Data Network) is a computerized system of files oriented to toxicology and related areas. It is managed by the National Library of Medicines Toxicology and Environmental Health Information Program (TEHIP) and runs on a series of microcomputers in a networked cl...

Graduate Training in Toxicology in Colleges of Veterinary Medicine.

ERIC Educational Resources Information Center

Robens, J. F.; Buck, W. B.

1979-01-01

Presented are an American Board of Veterinary Toxicology survey and evaluation of the training resources available in graduate programs in toxicology located in colleges of veterinary medicine. Regulatory toxicology, number of toxicologists needed, and curriculum are also discussed. (JMD)

Regulatory issues in accreditation of toxicology laboratories.

PubMed

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.

Expanding on Successful Concepts, Models, and Organization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Teeguarden, Justin G.; Tan, Yu-Mei; Edwards, Stephen W.

In her letter to the editor1 regarding our recent Feature Article “Completing the Link between Exposure Science and Toxicology for Improved Environmental Health Decision Making: The Aggregate Exposure Pathway Framework” 2, Dr. von Göetz expressed several concerns about terminology, and the perception that we propose the replacement of successful approaches and models for exposure assessment with a concept. We are glad to have the opportunity to address these issues here. If the goal of the AEP framework was to replace existing exposure models or databases for organizing exposure data with a concept, we would share Dr. von Göetz concerns. Instead,more » the outcome we promote is broader use of an organizational framework for exposure science. The framework would support improved generation, organization, and interpretation of data as well as modeling and prediction, not replacement of models. The field of toxicology has seen the benefits of wide use of one or more organizational frameworks (e.g., mode and mechanism of action, adverse outcome pathway). These frameworks influence how experiments are designed, data are collected, curated, stored and interpreted and ultimately how data are used in risk assessment. Exposure science is poised to similarly benefit from broader use of a parallel organizational framework, which Dr. von Göetz correctly points out, is currently used in the exposure modeling community. In our view, the concepts used so effectively in the exposure modeling community, expanded upon in the AEP framework, could see wider adoption by the field as a whole. The value of such a framework was recognized by the National Academy of Sciences.3 Replacement of models, databases, or any application with the AEP framework was not proposed in our article. The positive role broader more consistent use of such a framework might have in enabling and advancing “general activities such as data acquisition, organization…,” and exposure modeling was discussed in some detail. Like Dr. von Göetz, we recognized the challenges associated with acceptance of the terminology, definitions, and structure proposed in the paper. To address these challenges, an expert workshop was held in May, 2016 to consider and revise the “basic elements” outlined in the paper. The attendees produced revisions to the terminology (e.g., key events) that align with terminology currently in use in the field. We were also careful in our paper to acknowledge a point raised by Dr. von Göetz, that the term AEP implies aggregation, providing these clarifications: “The simplest form of an AEP represents a single source and a single pathway and may more commonly be referred to as an exposure pathway,”; and “An aggregate exposure pathway may represent multiple sources and transfer through single pathways to the TSE, single sources and transfer through multiple pathways to the target site exposure (TSE), or any combination of these.” These clarifications address the concern that the AEP term is not accurate or logical, and further expands upon the word “aggregate” in a broader context. Our use of AEP is consistent with the definition for “aggregate exposure”, which refers to the combined exposures to a single chemical across multiple routes and pathways.3 The AEP framework embraces existing methods for collection, prediction, organization, and interpretation of human and ecological exposure data cited by Dr. von Göetz. We remain hopeful that wider recognition and use of an organizing concept for exposure information across the exposure science, toxicology and epidemiology communities advances the development of the kind of infrastructure and models Dr. von Göetz discusses. This outcome would be a step forward, rather than a step backward.« less

42 CFR 493.1213 - Condition: Toxicology.

Code of Federal Regulations, 2010 CFR

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...

42 CFR 493.1213 - Condition: Toxicology.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 5 2014-10-01 2014-10-01 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...

42 CFR 493.1213 - Condition: Toxicology.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 5 2011-10-01 2011-10-01 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...

42 CFR 493.1213 - Condition: Toxicology.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 5 2013-10-01 2013-10-01 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...

42 CFR 493.1213 - Condition: Toxicology.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 5 2012-10-01 2012-10-01 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...

CEBS: a comprehensive annotated database of toxicological data

PubMed Central

Lea, Isabel A.; Gong, Hui; Paleja, Anand; Rashid, Asif; Fostel, Jennifer

2017-01-01

The Chemical Effects in Biological Systems database (CEBS) is a comprehensive and unique toxicology resource that compiles individual and summary animal data from the National Toxicology Program (NTP) testing program and other depositors into a single electronic repository. CEBS has undergone significant updates in recent years and currently contains over 11 000 test articles (exposure agents) and over 8000 studies including all available NTP carcinogenicity, short-term toxicity and genetic toxicity studies. Study data provided to CEBS are manually curated, accessioned and subject to quality assurance review prior to release to ensure high quality. The CEBS database has two main components: data collection and data delivery. To accommodate the breadth of data produced by NTP, the CEBS data collection component is an integrated relational design that allows the flexibility to capture any type of electronic data (to date). The data delivery component of the database comprises a series of dedicated user interface tables containing pre-processed data that support each component of the user interface. The user interface has been updated to include a series of nine Guided Search tools that allow access to NTP summary and conclusion data and larger non-NTP datasets. The CEBS database can be accessed online at http://www.niehs.nih.gov/research/resources/databases/cebs/. PMID:27899660

Spice drugs are more than harmless herbal blends: a review of the pharmacology and toxicology of synthetic cannabinoids

PubMed Central

Seely, Kathryn A.; Lapoint, Jeff; Moran, Jeffery H.; Fattore, Liana

2014-01-01

“K2” and “Spice” drugs (collectively hereafter referred to as Spice) represent a relatively new class of designer drugs that have recently emerged as popular alternatives to marijuana, otherwise characterized as “legal highs”. These drugs are readily available on the Internet and sold in many head shops and convenience stores under the disguise of innocuous products like herbal blends, incense, or air fresheners. Although package labels indicate “not for human consumption”, the number of intoxicated people presenting to emergency departments is dramatically increasing. The lack of validated and standardized human testing procedures and an endless supply of potential drugs of abuse are primary reasons why researchers find it difficult to fully characterize clinical consequences associated with Spice. While the exact chemical composition and toxicology of Spice remains to be determined, there is mounting evidence identifying several synthetic cannabinoids as causative agents responsible for psychoactive and adverse physical effects. This review provides updates of the legal status of common synthetic cannabinoids detected in Spice and analytical procedures used to test Spice products and human specimens collected under a variety of clinical circumstances. The pharmacological and toxicological consequences of synthetic cannabinoid abuse are also reviewed to provide a future perspective on potential short- and long-term implications. PMID:22561602

77 FR 40358 - Meeting of the Scientific Advisory Committee on Alternative Toxicological Methods (SACATM)

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-09

... Alternative Toxicological Methods (SACATM) AGENCY: Division of the National Toxicology Program (DNTP.../live ). SACATM advises the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM), the NTP Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM...

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

PubMed

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.

Mass Spectrometry Applications for Toxicology

PubMed Central

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

Using internet search engines and library catalogs to locate toxicology information.

PubMed

Wukovitz, L D

2001-01-12

The increasing importance of the Internet demands that toxicologists become aquainted with its resources. To find information, researchers must be able to effectively use Internet search engines, directories, subject-oriented websites, and library catalogs. The article will explain these resources, explore their benefits and weaknesses, and identify skills that help the researcher to improve search results and critically evaluate sources for their relevancy, validity, accuracy, and timeliness.

Air Force Research Laboratory Success Stories. A Review of 2001

DTIC Science & Technology

2001-01-01

object damage (FOD) and less risk to aircraft and pilots. This technology provides a cost avoidance of over $100 million above and beyond the savings in...semiconductor devices. Consequently, this new generation of lasers results in a substantial reduction of risk in developing compact, efficient sources for...Operational Toxicology Branch in the IPSC ensures that research conducted provides risk managers (Air Force/insulation and logistics, and base

Adverse outcome pathways (AOPs) to enhance EDC ...

EPA Pesticide Factsheets

Screening and testing for endocrine active chemicals was mandated under 1996 amendments to the Safe Drinking Water Act and Food Quality Protection Act. Efficiencies can be gained in the endocrine disruptor screening program by using available biological and toxicological knowledge to facilitate greater use of high throughput screening data and other data sources to inform endocrine disruptor assessments. Likewise, existing knowledge, when properly organized, can help aid interpretation of test results. The adverse outcome pathway (AOP) framework, which organizes information concerning measureable changes that link initial biological interactions with a chemical to adverse effects that are meaningful to risk assessment and management, can aid this process. This presentation outlines the ways in which the AOP framework has already been employed to support EDSP and how it may further enhance endocrine disruptor assessments in the future. Screening and testing for endocrine active chemicals was mandated under 1996 amendments to the Safe Drinking Water Act and Food Quality Protection Act. Efficiencies can be gained in the endocrine disruptor screening program by using available biological and toxicological knowledge to facilitate greater use of high throughput screening data and other data sources to inform endocrine disruptor assessments. Likewise, existing knowledge, when properly organized, can help aid interpretation of test results. The adverse outcome pathway

Petroleum hydrocarbons in a water-sediment system from Yellow River estuary and adjacent coastal area, China: Distribution pattern, risk assessment and sources.

PubMed

Wang, Min; Wang, Chuanyuan; Li, Yuanwei

2017-09-15

Aliphatic hydrocarbons (AHs), biomarker and polycyclic aromatic hydrocarbons (PAHs) concentrations of surface water and sediment samples collected from Yellow River Estuary and adjacent coastal area in China were measured to determine their spatial distributions, analyze their sources and evaluate the ecological risk of PAHs in the water-sediment system. The spatial distributions of n-alkane in sediments are mainly controlled by the mixing inputs of terrigenous and marine components. In comparison with AHs, the total concentrations of Σ16PAHs in surface sediments from a transect of the offshore area were noticeably higher than that of the riverine and estuary areas. Additionally, the AHs and total PAHs concentrations all indicated an overall pattern of a seaward decrease. The PAHs concentrations during the dry season (mainly in the form of dissolved phase) were higher than that of PAHs (mainly dissolved phase and particulate phase form) in the flooding season. In comparison with global concentration levels of PAHs, the level of PAHs in suspended particulate matter and sediments from the Yellow River Estuary was lower than those from other countries, while the concentration of PAHs in the dissolved phase were in the middle range. Petroleum contamination, mainly from oil exploration and discharge of pollutants from rivers, was the main source of n-alkanes. The PAHs in the river were mostly of petrogenic origin, while those in the estuarial and marine areas originated mainly from pyrogenic sources. The results of the toxicology assessment suggested that the PAHs in sediments from Yellow River Estuary and adjacent coastal area exhibited a low potential eco-toxicological contamination level. Copyright © 2017 Elsevier Ltd. All rights reserved.

Historical milestones and discoveries that shaped the toxicology sciences.

PubMed

Hayes, Antoinette N; Gilbert, Steven G

2009-01-01

Knowledge of the toxic and healing properties of plants, animals, and minerals has shaped civilization for millennia. The foundations of modern toxicology are built upon the significant milestones and discoveries of serendipity and crude experimentation. Throughout the ages, toxicological science has provided information that has shaped and guided society. This chapter examines the development of the discipline of toxicology and its influence on civilization by highlighting significant milestones and discoveries related to toxicology. The examples shed light on the beginnings of toxicology, as well as examine lessons learned and re-learned. This chapter also examines how toxicology and the toxicologist have interacted with other scientific and cultural disciplines, including religion, politics, and the government. Toxicology has evolved to a true scientific discipline with its own dedicated scientists, educational institutes, sub-disciplines, professional societies, and journals. It now stands as its own entity while traversing such fields as chemistry, physiology, pharmacology, and molecular biology. We invite you to join us on a path of discovery and to offer our suggestions as to what are the most significant milestones and discoveries in toxicology. Additional information is available on the history section of Toxipedia (www.toxipedia.org).

76 FR 23323 - Meeting of the Scientific Advisory Committee on Alternative Toxicological Methods (SACATM)

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-26

... Alternative Toxicological Methods (SACATM) AGENCY: National Toxicology Program (NTP), National Institute of... the Validation of Alternative Methods (ICCVAM), the NTP Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM), and the Director of the NIEHS and NTP regarding statutorily...

Science: Aquatic Toxicology Matures, Gains Importance.

ERIC Educational Resources Information Center

Dagani, Ron

1980-01-01

Reviews recent advances in aquatic toxicology, whose major goal is to protect diverse aquatic organisms and whole ecological communities from the dire effects of man-made chemicals. Current legislation is reviewed. Differences in mammalian and aquatic toxicology are listed, and examples of research in aquatic toxicology are discussed. (CS)

TOXNET and Beyond: Using the National Library of Medicine's Environmental Health and Toxicology Portal

DOE Office of Scientific and Technical Information (OSTI.GOV)

Templin-Branner, W.

2010-10-20

The National Library of Medicine's Environmental Health and Toxicology Portal provides access to numerous databases that can help you explore environmental chemicals and risks. TOXNET and Beyond: Using NLM's Environmental Health and Toxicology Portal conveys the fundamentals of searching the NLM's TOXNET system of databases in chemistry, toxicology, environmental health, and related fields. In addition to TOXNET, the course will highlight various resources available through the Environmental Health and Toxicology Portal.

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

PubMed

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.

Global warming and environmental contaminants in aquatic organisms: the need of the etho-toxicology approach.

PubMed

Manciocco, Arianna; Calamandrei, Gemma; Alleva, Enrico

2014-04-01

Environmental contaminants are associated with a wide spectrum of pathological effects. Temperature increase affects ambient distribution and toxicity of these chemicals in the water environment, representing a potentially emerging problem for aquatic species with short-, medium- and long-term repercussions on human health through the food chain. We assessed peer-reviewed literature, including primary studies, review articles and organizational reports available. We focused on studies concerning toxicity of environmental pollutants within a global warming scenario. Existing knowledge on the effects that the increase of water temperature in a contaminated situation has on physiological mechanisms of aquatic organisms is presented. Altogether we consider the potential consequences for the human beings due to fish and shellfish consumption. Finally, we propose an etho-toxicological approach to study the effects of toxicants in conditions of thermal increase, using aquatic organisms as experimental models under laboratory controlled conditions. Copyright © 2014 Elsevier Ltd. All rights reserved.

IRIS Toxicological Review of Ammonia Noncancer Inhalation ...

EPA Pesticide Factsheets

EPA has finalized the Integrated Risk Information System (IRIS) Assessment of Ammonia (Noncancer Inhalation). This assessment addresses the potential noncancer human health effects from long-term inhalation exposure to ammonia. Now final, this assessment will update the current toxicological information on ammonia posted in 1991. EPA’s program and regional offices may use this assessment to inform decisions to protect human health. EPA completed the Integrated Risk Information System (IRIS) health assessment for ammonia. 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.

Testing of Binders Toxicological Effects

NASA Astrophysics Data System (ADS)

Strokova, V.; Nelyubova, V.; Rykunova, M.

2017-11-01

The article presents the results of a study of the toxicological effect of binders with different compositions on the vital activity of plant and animal test-objects. The analysis of the effect on plant cultures was made on the basis of the phytotesting data. The study of the effect of binders on objects of animal origin was carried out using the method of short-term testing. Based on the data obtained, binders are ranked according to the degree of increase in the toxic effect: Gypsum → Portland cement → Slag Portland cement. Regardless of the test-object type, the influence of binders is due to the release of various elements (calcium ions or heavy metals) into the solution. In case of plant cultures, the saturation of the solution with elements has a positive effect (there is no inhibitory effect), and in case of animal specimens - an increase in the toxic effect.

Nontargeted multicomponent analytical screening of plastic food contact materials using fast interpretation of deliverables via expert structure-activity relationship software.

PubMed

Rothenbacher, Thorsten; Schwack, Wolfgang

2009-01-01

Plastic packaging materials may release compounds into packed foodstuffs. To identify potential migrants of toxicological concern, resins, and multilayer foils (mainly polyethylene) intended for the production of food contact materials were extracted and analyzed by GC/mass spectrometry. To identify even compounds of low concentrations, AMDIS software was used and data evaluation was safeguarded by the Kovats retention index (RI) system. In this way, 46 compounds were identified as possible migrants. The expert structure-activity relationship software DEREK for Windows was utilized to evaluate all identified substances in terms of carcinogenicity, genotoxicity, thyroid toxicity, and miscellaneous endpoints for humans. Additionally, a literature search for these compounds was performed with Sci-Finder, but relevant data were missing for 28 substances. Seven compounds with adverse toxicological effects were identified. In addition, the RIs of 24 commercial additive standards, measured with a GC capillary column of intermediate polarity, are given.

Evaluation of the Inhalation Carcinogenicity of Ethylene Oxide ...

EPA Pesticide Factsheets

EPA has finalized its Evaluation of the Inhalation Carcinogenicity of Ethylene Oxide. This assessment addresses the potential carcinogenicity from long-term inhalation exposure to ethylene oxide. Now final, this assessment updates the carcinogenicity information in EPA’s 1985 Health Assessment Document. EPA’s program and regional offices may use this assessment to inform decisions to protect human health. The Toxicological Review and charge were 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 consultation materials provided to other agencies, including interagency review drafts of the IRIS Toxicological Review of Ammonia and the charge to external peer reviewers, are posted on this site.

Radix Bupleuri: A Review of Traditional Uses, Botany, Phytochemistry, Pharmacology, and Toxicology.

PubMed

Yang, Fude; Dong, Xiaoxv; Yin, Xingbin; Wang, Wenping; You, Longtai; Ni, Jian

2017-01-01

Radix Bupleuri (Chaihu) has been used as a traditional medicine for more than 2000 years in China, Japan, Korea, and other Asian countries. Phytochemical studies demonstrated that this plant contains essential oils, triterpenoid saponins, polyacetylenes, flavonoids, lignans, fatty acids, and sterols. Crude extracts and pure compounds isolated from Radix Bupleuri exhibited various biological activities, such as anti-inflammatory, anticancer, antipyretic, antimicrobial, antiviral, hepatoprotective, neuroprotective, and immunomodulatory effects. However, Radix Bupleuri could also lead to hepatotoxicity, particularly in high doses and with long-term use. Pharmacokinetic studies have demonstrated that the major bioactive compounds (saikosaponins a, b 2 , c, and d) were absorbed rapidly in rats after oral administration of the extract of Radix Bupleuri . This review aims to comprehensively summarize the traditional uses, botany, phytochemistry, pharmacology, toxicology, and pharmacokinetics of Radix Bupleuri reported to date with an emphasis on its biological properties and mechanisms of action.

Harold Seifried, PhD | Division of Cancer Prevention

Cancer.gov

Dr. Harold Seifried is a member of the American Chemical Society Biological Chemistry Division; American College of Toxicology Industrial Toxicology Subcommittee; American Industrial Hygiene Association; Society of Toxicology; International Society for the Study of Xenobiotics; Diplomate of the American Board of Toxicology since 1980; American Board of Industrial Hygiene,

40 CFR 159.165 - Toxicological and ecological studies.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 24 2011-07-01 2011-07-01 false Toxicological and ecological studies... Information § 159.165 Toxicological and ecological studies. Adverse effects information must be submitted as follows: (a) Toxicological studies. (1) The results of a study of the toxicity of a pesticide to humans or...

40 CFR 159.165 - Toxicological and ecological studies.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Toxicological and ecological studies... Information § 159.165 Toxicological and ecological studies. Adverse effects information must be submitted as follows: (a) Toxicological studies. (1) The results of a study of the toxicity of a pesticide to humans or...

Society of Toxicologic Pathologists (STP) Annual Symposium General Session II: Modem Pathology Methods for Neural Investigations

EPA Science Inventory

This half-day session at the 20I0 Joint Symposium of the Society of Toxicologic Pathology (STP) and the International Federation of Societies of Toxicologic Pathologists (IFSTP) explored many deceptively simple questions related to toxicologic neuropathology. What is the best met...

Solvents and Parkinson disease: A systematic review of toxicological and epidemiological evidence

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lock, Edward A., E-mail: e.lock@ljmu.ac.uk; Zhang, Jing; Checkoway, Harvey

2013-02-01

Parkinson disease (PD) is a debilitating neurodegenerative motor disorder, with its motor symptoms largely attributable to loss of dopaminergic neurons in the substantia nigra. The causes of PD remain poorly understood, although environmental toxicants may play etiologic roles. Solvents are widespread neurotoxicants present in the workplace and ambient environment. Case reports of parkinsonism, including PD, have been associated with exposures to various solvents, most notably trichloroethylene (TCE). Animal toxicology studies have been conducted on various organic solvents, with some, including TCE, demonstrating potential for inducing nigral system damage. However, a confirmed animal model of solvent-induced PD has not been developed.more » Numerous epidemiologic studies have investigated potential links between solvents and PD, yielding mostly null or weak associations. An exception is a recent study of twins indicating possible etiologic relations with TCE and other chlorinated solvents, although findings were based on small numbers, and dose–response gradients were not observed. At present, there is no consistent evidence from either the toxicological or epidemiologic perspective that any specific solvent or class of solvents is a cause of PD. Future toxicological research that addresses mechanisms of nigral damage from TCE and its metabolites, with exposure routes and doses relevant to human exposures, is recommended. Improvements in epidemiologic research, especially with regard to quantitative characterization of long-term exposures to specific solvents, are needed to advance scientific knowledge on this topic. -- Highlights: ► The potential for organic solvents to cause Parkinson's disease has been reviewed. ► Twins study suggests etiologic relations with chlorinated solvents and Parkinson's. ► Animal studies with TCE showed potential to cause damage to dopaminergic neurons. ► Need to determine if effects in animals are relevant to human exposure levels.« less

Meta-analysis of ionic liquid literature and toxicology.

PubMed

Heckenbach, Mary E; Romero, Felicia N; Green, Matthew D; Halden, Rolf U

2016-05-01

A meta-analysis was conducted to compare the total amount of ionic liquid (IL) literature (n = 39,036) to the body of publications dealing with IL toxicity (n = 213) with the goal of establishing the state of knowledge and existing information gaps. Additionally, patent literature pertaining to issued patents utilizing ILs (n = 3358) or dealing with IL toxicity (n = 112) were analyzed. Total publishing activity and patent count served to gauge research activity, industrial usage and toxicology knowledge of ILs. Five of the most commonly studied IL cations were identified and used to establish a relationship between toxicity data and potential of commercial use: imidazolium, ammonium, phosphonium, pyridinium, and pyrrolidinium. Toxicology publications for all IL cations represented 0.55% ± 0.27% of the total publishing activity; compared with other industrial chemicals, these numbers indicate that there is still a paucity of studies on the adverse effects of this class of chemical. Toxicity studies on ILs were dominated by the use of in vitro models (18%) and marine bacteria (15%) as studied biological systems. Whole animal studies (n = 87) comprised 31% of IL toxicity studies, with a subset of in vivo mammalian models consisting of 8%. Human toxicology data were found to be limited to in vitro analyses, indicating substantial knowledge gaps. Risks from long-term and chronic low-level exposure to ILs have not been established yet for any model organisms, reemphasizing the need to fill crucial knowledge gaps concerning human health effects and the environmental safety of ILs. Adding to the existing knowledge of the molecular toxicity characteristics of ILs can help inform the design of greener, less toxic and more benign IL technologies. Copyright © 2016 Elsevier Ltd. All rights reserved.

Meta-Analysis of Ionic Liquid Literature and Toxicology

PubMed Central

Heckenbach, Mary E.; Romero, Felicia N.; Green, Matthew D.; Halden, Rolf U.

2016-01-01

A meta-analysis was conducted to compare the total amount of ionic liquid (IL) literature (n = 39,036) to the body of publications dealing with IL toxicity (n = 213) with the goal of establishing the state of knowledge and existing information gaps. Additionally, patent literature pertaining to issued patents utilizing ILs (n = 3,358) or dealing with IL toxicity (n =112) were analyzed. Total publishing activity and patent count served to gauge research activity, industrial usage and toxicology knowledge of ILs. Five of the most commonly studied IL cations were identified and used to establish a relationship between toxicity data and potential of commercial use: imidazolium, ammonium, phosphonium, pyridinium, and pyrrolidinium. Toxicology publications for all IL cations represented 0.55% ± 0.27% of the total publishing activity; compared with other industrial chemicals, these numbers indicate that there is still a paucity of studies on the adverse effects of this class of chemical. Toxicity studies on ILs were dominated by the use of in vitro models (18%) and marine bacteria (15%) as studied biological systems. Whole animal studies (n = 87) comprised 31% of IL toxicity studies, with a subset of in vivo mammalian models consisting of 8%. Human toxicology data were found to be limited to in vitro analyses, indicating substantial knowledge gaps. Risks from long-term and chronic low-level exposure to ILs have not been established yet for any model organisms, reemphasizing the need to fill crucial knowledge gaps concerning human health effects and the environmental safety of ILs. Adding to the existing knowledge of the molecular toxicity characteristics of ILs can help inform the design of greener, less toxic and more benign IL technologies. PMID:26907595

Occurrences and toxicological risk assessment of eight heavy metals in agricultural soils from Kenya, Eastern Africa.

PubMed

Mungai, Teresiah Muciku; Owino, Anita Awino; Makokha, Victorine Anyango; Gao, Yan; Yan, Xue; Wang, Jun

2016-09-01

The concentration distribution and toxicological assessment of eight heavy metals including lead (Pb), cadmium (Cd), copper (Cu), chromium (Cr), nickel (Ni), mercury (Hg), arsenic (As), and zinc (Zn) in agricultural soils from Kenya, Eastern Africa, were investigated in this study. The results showed mean concentrations of eight heavy metals of Zn, Pb, Cr, Cu, As, Ni, Hg, and Cd in agricultural soils as 247.39, 26.87, 59.69, 88.59, 8.93, 12.56, 8.06, and 0.42 mg kg(-1), respectively. These mean values of eight heavy metals were close to the toxicity threshold limit of USEPA standard values of agricultural soils, indicating potential toxicological risk to the food chain. Pollution index values revealed that eight heavy metals severely decreased in the order Hg > Cd > As > Cu > Pb > Zn > Ni > Cr and the mean value of the overall pollution index of Hg and Cd was 20.31, indicating severe agriculture ecological risk. Potential pollution sources of eight heavy metals in agricultural soils were mainly from anthropogenic activities and natural dissolution. The intensification of human agricultural activities, the growing industrialization, and the rapid urbanization largely influenced the concentration levels of heavy metals in Kenya, Eastern Africa. Moreover, the lack of agricultural normalization management and poor enforcement of environmental laws and regulations further intensified the widespread pollution of agricultural soils in Kenya.

[Contaminants from food packaging : New developments in risk assessment].

PubMed

Pfaff, Karla; Wölfle, Detlef; Luch, Andreas

2017-07-01

Diverse materials intended for contact with food are important sources of food contamination. Harmonised European regulations including whitelists (so-called "positive lists") of substances along with migration limits and restrictions exist for plastics and regenerated cellulose films only. The European Food Safety Authority (EFSA) is responsible for the risk assessment of substances prior to their authorization and inclusion into the positive lists. In 2016 the EFSA issued an opinion on recent developments in the risk assessment of substances migrating into food for public consideration. Also migration related to non-intentionally added substances (NIASs), e. g. impurities, degradations products or oligomers, may be relevant for risk assessment. For substances migrating in quantities up to 50 ppb the requested data are restricted to genotoxicity testing based on a tiered approach for toxicological data requirements. In the case of higher migration levels (>50 ppb) experimental animal studies are also requested. Along with an evaluation of the available information, toxicological data on structurally similar substances may be used for the assessment if sufficiently justified with the aim to reduce animal studies as far as possible. For the risk assessment of NIASs it is possible to apply in silico methods in the absence of experimental toxicological data. Additionally, new technologies such as the use of nanomaterials, active and intelligent packaging and recycled plastics are challenging tasks in EFSA's risk assessment in accordance with the regulations by the European Commission.

Applicability of computational systems biology in toxicology.

PubMed

Kongsbak, Kristine; Hadrup, Niels; Audouze, Karine; Vinggaard, Anne Marie

2014-07-01

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. However, computational systems biology offers more advantages than providing a high-throughput literature search; it may form the basis for establishment of hypotheses on potential links between environmental chemicals and human diseases, which would be very difficult to establish experimentally. This is possible due to the existence of comprehensive databases containing information on networks of human protein-protein interactions and protein-disease associations. Experimentally determined targets of the specific chemical of interest can be fed into these networks to obtain additional information that can 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 in the hypothesis-generating phase of toxicological research. © 2014 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Aquatic toxicology: fact or fiction?

PubMed Central

Macek, K J

1980-01-01

A brief history of the development of the field of aquatic toxicology is provided. In order to provide a perspective on the state-of-the-art in aquatic toxicology relative to classical toxicology, the two fields are compared from the standpoint of the type of scientist practicing each field, the respective objectives of each, the forces which drive the activity in each field, and the major advantages and disadvantages accruing to the practitioner of aquatic toxicology as a result of the differences in objectives and driving forces. PMID:6993200

Merging bioreactor technology with 3D hepatocyte-fibroblast culturing approaches: Improved in vitro models for toxicological applications.

PubMed

Leite, Sofia B; Teixeira, Ana P; Miranda, Joana P; Tostões, Rui M; Clemente, João J; Sousa, Marcos F; Carrondo, Manuel J T; Alves, Paula M

2011-06-01

During the last years an increasing number of in vitro models have been developed for drug screening and toxicity testing. Primary cultures of hepatocytes are, by far, the model of choice for those high-throughput studies but their spontaneous dedifferentiation after some time in culture hinders long-term studies. Thus, novel cell culture systems allowing extended hepatocyte maintenance and more predictive long term in vitro studies are required. It has been shown that hepatocytes functionality can be improved and extended in time when cultured as 3D-cell aggregates in environmental controlled stirred bioreactors. In this work, aiming at further improving hepatocytes functionality in such 3D cellular structures, co-cultures with fibroblasts were performed. An inoculum concentration of 1.2×10(5) cell/mL and a 1:2 hepatocyte:mouse embryonic fibroblast ratio allowed to improve significantly the albumin secretion rate and both ECOD (phase I) and UGT (phase II) enzymatic activities in 3D co-cultures, as compared to the routinely used 2D hepatocyte monocultures. Significant improvements were also observed in relation to 3D monocultures of hepatocytes. Furthermore, hepatocytes were able to respond to the addition of beta-Naphtoflavone by increasing ECOD activity showing CYP1A inducibility. The dependence of CYP activity on oxygen concentration was also observed. In summary, the improved hepatocyte specific functions during long term incubation of 3D co-cultures of hepatocytes with fibroblasts indicate that this system is a promising in vitro model for long term toxicological studies. Copyright © 2011 Elsevier Ltd. All rights reserved.

The International Union of Toxicology (IUTOX): history and its role in information on toxicology.

PubMed

Schou, Jens S; Hodel, Christian M

2003-08-21

The International Union of Toxicology (IUTOX) was founded in 1980 in Brussels. The initiative was started by the Society of Toxicology (SOT), USA, and the European Society of Toxicology in 1975 (EST), and the foundation prepared by an Inter Society Liason Committee. Eight National Societies of Toxicology were founding members of IUTOX besides SOT and EST. It now comprises 43 national/regional Societies from all over the world, representing over 20,000 toxicologists. Information has always been a key element in toxicology. Information exchange in IUTOX has evolved from letters and phone calls to fax, e-mail and the use of the Internet. Initially, newsletters were created which were mailed and later displayed on the Web. The website has been developed as a major information tool with many useful links, thereby providing information for the scientific community, the media and the lay public.

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

PubMed

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.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Annette Rohr

2005-09-30

This report documents progress made on the subject project during the period of March 1, 2005 through August 31, 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 Agreementmore » (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, fieldwork was completed at Plant 1, located in the Southeast. 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 + secondary organic aerosol (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). Stage I assessment endpoints included breathing pattern/pulmonary function; in vivo chemiluminescence (an indicator of oxidative stress); blood cytology; bronchoalveolar lavage (BAL) fluid analysis; and histopathology. Stage II assessments included continuous ECG monitoring via implanted telemeters and blood chemistry (complete blood count, circulating cytokines (interleukins-1 and -6), C-reactive protein (CRP), tumor necrosis factor alpha (TNF-{alpha}), and endothelin-1). Only a subset of exposure data was available at the time of preparation of this report. Continuous PM{sub 2.5} mass (TEOM) results indicate a mass concentration of 14 {micro}g/m{sup 3} for the primary particle scenario, and a range of 151 to 385 {micro}g/m{sup 3} for the oxidized emissions scenarios. Toxicological results obtained to date from Plant 1 indicate subtle biological responses to some of the exposure scenarios. We observed statistically significant changes in several breathing pattern parameters, including tidal volume and frequency. For one scenario (oxidized emissions + SOA), we observed a significant increase in Enhanced Pause (Penh), a parameter that may reflect airflow restriction. However, the respiratory changes are very subtle and do not present a clear picture of a particular respiratory effect (e.g., airway restriction, sensory irritation, or pulmonary irritation). A significant increase in lung chemiluminescence (a marker of oxidative stress in lung tissue) in exposed animals (vs. air-exposed controls) was observed in animals exposed to oxidized emissions + SOA. No changes were observed in heart tissue, nor in any other scenario. Stage II assessments were conducted to the secondary + SOA scenario; ECG and blood analysis data are pending. Planning was initiated for Plant 2, located in the Midwest. Because of the requirement for both the FGD and the SCR to be concurrently operational for appropriate reaction conditions, fieldwork at Plant 2 is scheduled for Summer 2006. During the next reporting period, we will complete all remaining exposure and toxicological analyses for Plant 1, and the next semiannual report will include a detailed description of these data and their interpretation. We are also in the process of preparing a topical report for Plant 0.« less

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

EPA Science Inventory

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...

76 FR 36923 - Meeting of the National Toxicology Program (NTP) Board of Scientific Counselors (BSC): Notice of...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-23

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Meeting of the National Toxicology Program (NTP) Board of Scientific Counselors (BSC): Notice of Cancellation AGENCY: National Toxicology Program (NTP), National... Toxicology Program. [FR Doc. 2011-15656 Filed 6-22-11; 8:45 am] BILLING CODE 4140-01-P ...

76 FR 10906 - Proposed Substances To Be Evaluated for Set 25 Toxicological Profiles

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-28

...-269] Proposed Substances To Be Evaluated for Set 25 Toxicological Profiles AGENCY: Agency for Toxic... comments on the proposed substances to be evaluated for Set 25 toxicological profiles. SUMMARY: ATSDR is initiating the development of its 25th set of toxicological profiles (CERCLA Set 25). This notice announces...

Daily trends and source apportionment of ultrafine particulate mass (PM0.1) over an annual cycle in a typical California city.

PubMed

Kuwayama, Toshihiro; Ruehl, Chris R; Kleeman, Michael J

2013-12-17

Toxicology studies indicate that inhalation of ultrafine particles (Dp < 0.1 μm) causes adverse health effects, presumably due to their large surface area-to-volume ratio that can drive heterogeneous reactions. Epidemiological associations between ultrafine particles and health effects, however, have been difficult to identify due to the lack of appropriate long-term monitoring and exposure data. The majority of the existing ultrafine particle epidemiology studies are based on exposure to particle number, although an independent analysis suggests that ultrafine particle mass (PM0.1) correlates better with particle surface area. More information is needed to characterize PM0.1 exposure to fully evaluate the health effects of ultrafine particles using epidemiology. The present study summarizes 1 year of daily PM0.1 chemistry and source apportionment at Sacramento, CA, USA. Positive matrix factorization (PMF) was used to resolve PM0.1 source contributions from old-technology diesel engines, residential wood burning, rail, regional traffic, and brake wear/road dust. Diesel PM0.1 and total PM0.1 concentrations were reduced by 97 and 26%, respectively, as a result of the adoption of cleaner diesel technology. The strong linear correlation between PM0.1 and particle surface area in central California suggests that the adoption of clean diesel engines reduced particle surface area by similar amounts. PM0.1 sulfate reduction occurred as a result of reduced primary particle surface area available for sulfate condensation. The current study demonstrates the capability of measuring PM0.1 source contributions over a 12 month period and identifies the extended benefits of emissions reduction efforts for diesel engines on ambient concentrations of primary and secondary PM0.1.

Aspects of matrix effects in applications of liquid chromatography-mass spectrometry to forensic and clinical toxicology--a review.

PubMed

Peters, Frank T; Remane, Daniela

2012-06-01

In the last decade, liquid chromatography coupled to (tandem) mass spectrometry (LC-MS(-MS)) has become a versatile technique with many routine applications in clinical and forensic toxicology. However, it is well-known that ionization in LC-MS(-MS) is prone to so-called matrix effects, i.e., alteration in response due to the presence of co-eluting compounds that may increase (ion enhancement) or reduce (ion suppression) ionization of the analyte. Since the first reports on such matrix effects, numerous papers have been published on this matter and the subject has been reviewed several times. However, none of the existing reviews has specifically addressed aspects of matrix effects of particular interest and relevance to clinical and forensic toxicology, for example matrix effects in methods for multi-analyte or systematic toxicological analysis or matrix effects in (alternative) matrices almost exclusively analyzed in clinical and forensic toxicology, for example meconium, hair, oral fluid, or decomposed samples in postmortem toxicology. This review article will therefore focus on these issues, critically discussing experiments and results of matrix effects in LC-MS(-MS) applications in clinical and forensic toxicology. Moreover, it provides guidance on performance of studies on matrix effects in LC-MS(-MS) procedures in systematic toxicological analysis and postmortem toxicology.

Dermal, Eye, and Oral Toxicological Evaluations.

DTIC Science & Technology

1985-06-01

whenever possible. Write out the English equivalent for Greek letters and mathematical symbols in the title (see "Abstracting Scientific and...standard terminology. The DoD "Thesaurus of Engineering and Scientific Terms" (TEST), AD-672 000, can be helpful. I. Block 20. Abstract. The abstract...contains a significant bibliography or literature survey, mentioni, it here. For information on preparing abstracts see "Abstracting Scientific and

History of Japanese Society of Toxicology.

PubMed

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.

Green toxicology.

PubMed

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, the Green Toxicology concept is currently spreading internationally and is being refined via an iterative process.

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

PubMed

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 laboratory practice standards; 2) to have a quality control system including a quality manual and standard operating procedures manual; 3) to have some degree of compulsion to implement quality assurance both through their own internal efforts and by appropriate remedial actions based on the results of an external proficiency testing scheme. For forensic toxicologists, the implications are that they should be: 1) responsible for ensuring that laboratory practices are performed under satisfactory conditions and 2) required to be certified as a forensic toxicology specialist in order to prove their forensic toxicology ability. For their part, governments should: 1) carry out administrative reforms related to forensic toxicology; 2) simplify the procedure for obtaining certified reference materials; 3) introduce a strict workplace urine drug testing programme for government employees, at least for those related to law enforcement. When all of these objectives have been realised, the specific goal will be achieved through which Japanese forensic toxicology is able, in practice, to fulfill its responsibility to society.

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

PubMed

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.

Feasibility of commercialization of Russian thistle, Salsola kali L. , as a fuel source. Final report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Karpiscak, M.M.; Foster, K.E.; Rawles, R.L.

1981-10-01

The use of Russian thistle as an energy resource has been demonstrated. Russian thistle biomass can be harvested, stored and transported using readily available machinery. Propagation seed can be harvested, cleaned and sown using commercially available machines and traditional techniques. In addition, preliminary tests did not detect that burning Russian thistle biomass causes any major toxicological or immunological problems. Many questions remain to be answered, however, concerning use of Russian thistle as a biomass fuel. The lack of confirmed, long-term data, on the agronomics of Russian thistle makes additional research necessary. Additional data are required to produce a sound datamore » base for evaluating the economics of Russian thistle production, for improving agricultural methods, and for fully evaluating the toxic and immunologic properties of Russian thistle. In conclusion, it appears that Russian thistle biomass has a great potential for becoming a fuel source in arid areas that are lacking fossil fuel reserves or where possible reduction of environmental problems associated with the use of fossil fuels is desired. Analyses of economic and energy factors show that there is a significant net gain in energy with the production and processing of Russia thistle biomass into synthetic logs (Tumblelogs), although the cost of Tumblelogs is slightly higher than that of synthetic logs made from wood waste. 10 refs., 12 figs., 17 tabs.« less

Reprint Library for Toxicology Data Bank

ERIC Educational Resources Information Center

Agarwal, S. N.; Khan, R. R.

1975-01-01

The Industrial Toxicology Research Center, Lucknow, India, maintains a register of toxicology and provides its research workers with current information mainly through its collection of reprints. (Author)

Long term imaging of living brain cancer cells

NASA Astrophysics Data System (ADS)

Farias, Patricia M. A.; Galembeck, André; Milani, Raquel; Andrade, Arnaldo C. D. S.; Stingl, Andreas

2018-02-01

QDs synthesized in aqueous medium and functionalized with polyethylene glycol were used as fluorescent probes. They label and monitor living healthy and cancer brain glial cells in culture. Physical-chemical characterization was performed. Toxicological studies were performed by in vivo short and long-term inhalation in animal models. Healthy and cancer glial living cells were incubated in culture media with highly controlled QDs. Specific features of glial cancer cells were enhanced by QD labelling. Cytoplasmic labelling pattern was clearly distinct for healthy and cancer cells. Labelled cells kept their normal activity for same period as non-labelled control samples.

Toxicity assessment of the water used for human consumption from the Cameron/Tuba City abandoned uranium mining area prior/after the combined electrochemical treatment/advanced oxidation.

PubMed

Gajski, Goran; Oreščanin, Višnja; Gerić, Marko; Kollar, Robert; Lovrenčić Mikelić, Ivanka; Garaj-Vrhovac, Vera

2015-01-01

The purpose of this work was detailed physicochemical, radiological, and toxicological characterization of the composite sample of water intended for human consumption in the Cameron/Tuba City abandoned uranium mining area before and after a combined electrochemical/advanced oxidation treatment. Toxicological characterization was conducted on human lymphocytes using a battery of bioassays. On the bases of the tested parameters, it could be concluded that water used for drinking from the tested water sources must be strictly forbidden for human and/or animal consumption since it is extremely cytogenotoxic, with high oxidative stress potential. A combined electrochemical treatment and posttreatment with ozone and UV light decreased the level of all physicochemical and radiological parameters below the regulated values. Consequently, the purified sample was neither cytotoxic nor genotoxic, indicating that the presented method could be used for the improvement of water quality from the sites highly contaminated with the mixture of heavy metals and radionuclides.

Unrecorded alcohol consumption in Russia: toxic denaturants and disinfectants pose additional risks

PubMed Central

Solodun, Yuriy V.; Monakhova, Yulia B.; Kuballa, Thomas; Samokhvalov, Andriy V.; Rehm, Jürgen; Lachenmeier, Dirk W.

2011-01-01

In 2005, 30% of all alcohol consumption in Russia was unrecorded. This paper describes the chemical composition of unrecorded and low cost alcohol, including a toxicological evaluation. Alcohol products (n=22) from both recorded and unrecorded sources were obtained from three Russian cities (Saratov, Lipetsk and Irkutsk) and were chemically analyzed. Unrecorded alcohols included homemade samogons, medicinal alcohols and surrogate alcohols. Analysis included alcoholic strength, levels of volatile compounds (methanol, acetaldehyde, higher alcohols), ethyl carbamate, diethyl phthalate (DEP) and polyhexamethyleneguanidine hydrochloride (PHMG). Single samples showed contamination with DEP (275–1269 mg/l) and PHMG (515 mg/l) above levels of toxicological concern. Our detailed chemical analysis of Russian alcohols showed that the composition of vodka, samogon and medicinal alcohols generally did not raise major public health concerns other than for ethanol. It was shown, however, that concentration levels of DEP and PHMG in some surrogate alcohols make these samples unfit for human consumption as even moderate drinking would exceed acceptable daily intakes. PMID:22319254

Avian toxicologic diagnosis

USGS Publications Warehouse

Sigurdson, C.J.; Franson, J.C.; Fudge, A.M.

2000-01-01

This chapter describes the sources and pathophysiology of some potential poisons that affect birds and summarizes useful laboratory tests. The diagnosis of poisoning in birds, as in mammals, requires a complete and accurate history, careful observation of clinical signs, and a thorough necropsy evaluation. Appropriate sample handling and analysis, based on consultation with the diagnostic toxicologist, are critical (Table 19--1). Veterinary toxicology laboratories are becoming increasingly specialized, with only certain laboratories capable of analyzing for drug residues or anticoagulants, for example. Although a local laboratory may not be able to fulfill a specific test request, they may recommend an alternative laboratory or may be willing to forward the sample. As a general rule in suspect poisoning cases, large tissue samples of liver, kidney, brain, and subcutaneous fat and of crop, proventriculus, and ventriculus contents should be collected at necropsy and frozen. Appropriate samples should be submitted frozen, with the remainder held in the freezer for possible later testing. A second set of tissues should be placed in 10% formalin for histopathologic examination.

Unrecorded alcohol consumption in Russia: toxic denaturants and disinfectants pose additional risks.

PubMed

Solodun, Yuriy V; Monakhova, Yulia B; Kuballa, Thomas; Samokhvalov, Andriy V; Rehm, Jürgen; Lachenmeier, Dirk W

2011-12-01

In 2005, 30% of all alcohol consumption in Russia was unrecorded. This paper describes the chemical composition of unrecorded and low cost alcohol, including a toxicological evaluation. Alcohol products (n=22) from both recorded and unrecorded sources were obtained from three Russian cities (Saratov, Lipetsk and Irkutsk) and were chemically analyzed. Unrecorded alcohols included homemade samogons, medicinal alcohols and surrogate alcohols. Analysis included alcoholic strength, levels of volatile compounds (methanol, acetaldehyde, higher alcohols), ethyl carbamate, diethyl phthalate (DEP) and polyhexamethyleneguanidine hydrochloride (PHMG). Single samples showed contamination with DEP (275-1269 mg/l) and PHMG (515 mg/l) above levels of toxicological concern. Our detailed chemical analysis of Russian alcohols showed that the composition of vodka, samogon and medicinal alcohols generally did not raise major public health concerns other than for ethanol. It was shown, however, that concentration levels of DEP and PHMG in some surrogate alcohols make these samples unfit for human consumption as even moderate drinking would exceed acceptable daily intakes.

Handbook of ecotoxicology

USGS Publications Warehouse

Hoffman, David J.; Rattner, Barnett A.; Burton, G. Allen; Cairns, John

1995-01-01

The Handbook of Ecotoxicology offers 34 chapters with contributions from over 50 selected international experts. The book is divided into four major sections: I. Quantifying and Measuring Ecotoxicological Effects, II. Contaminant Sources and Effects, III. Case Histories and Ecosystem Surveys, and IV. Methods for Making Estimates and Predictability in Ecotoxicology. Concepts and methodology are presented for many types of aquatic and terrestrial ecotoxicity test protocols for both controlled and field assessments. Chapters are offered on such diverse topics as sediment and soil ecotoxicity, landscape indicators, biomonitoring, and use of current bioindicators. The roles of deforestation and global warming, pathogens and disease in ecotoxicology, abiotic factors, urban runoff, predictive ecotoxicology, population modeling, and restoration ecology are discussed. This book was designed to serve as a reference book for students entering the fields of ecotoxicology, aquatic toxicology, terrestrial wildlife toxicology, and other environmental sciences. Many portions of this handbook will serve as a convenient reference text for established investigators, resource managers, and those involved in risk assessment and risk management within regulatory agencies and the private sector.

2C-I-NBOMe, an "N-bomb" that kills with "Smiles". Toxicological and legislative aspects.

PubMed

Nikolaou, Panagiota; Papoutsis, Ioannis; Stefanidou, Maria; Spiliopoulou, Chara; Athanaselis, Sotiris

2015-01-01

Substituted phenethylamines are a class of designer drugs that have recently emerged in the drug abuse market. Such substances remain legal to use, possess, and supply until these compounds become classified as scheduled. 2C-I-NBOMe or 25I-NBOMe is the N-benzyl-derivative of the iodo-substituted dimethoxy-phenethylamine (2C-I) that appeared recently in the drug market under the street name "N-Bomb". Due to its high potency, intoxications and fatal cases related to 2C-I-NBOMe use are increased worldwide. The use and trafficking of this substituted phenethylamine is banned only in some countries. A comprehensive review was performed using PubMed and Medline databases, together with additional non-peer reviewed information sources, including books and publications of state authorities in different countries, regarding chemistry, availability, pharmacology, and toxicology of 2C-I-NBOMe. Intoxications or lethal cases, published or reported, as well as the current legislation on this newly introduced drug are also reviewed.

Urine toxicology screening in an urban stroke and TIA population.

PubMed

Silver, Brian; Miller, Daniel; Jankowski, Michelle; Murshed, Nawaf; Garcia, Patricia; Penstone, Patricia; Straub, Melissa; Logan, Sean P; Sinha, Anita; Morris, Daniel C; Katramados, Angelos; Russman, Andrew N; Mitsias, Panayiotis D; Schultz, Lonni R

2013-04-30

We sought to determine the rate of urine toxicology screening, differences in testing, and outcomes among patients with stroke and TIA presenting to a tertiary care emergency department. In this retrospective cohort study, patients admitted with stroke or TIA to a single tertiary care stroke center between June 2005 and January 2007 were identified through a stroke database. Factors that predicted urine toxicology screening of patients and a positive test, and discharge outcomes of patients based on toxicology result were analyzed. Stroke severity, treatment with tissue plasminogen activator, discharge status, and stroke etiology were compared between toxicology positive and negative patients. A total of 1,024 patients were identified: 704 with ischemic stroke, 133 with intracerebral hemorrhage, and 205 with TIA. Urine toxicology screening was performed in 420 patients (40%); 11% of these studies were positive for cocaine (19% younger than 50 years and 9% 50 years or older). Factors that significantly predicted the performance of a urine toxicology screen were younger age (<50 years) and black race (<0.001). Positive toxicology screens occurred in a broad range of patients. There were no significant differences in admission NIH Stroke Scale score, stroke etiology, and discharge status between toxicology-positive and -negative patients. In this study, patients with stroke and TIA who were young and black were more likely to have urine toxicology screening. Eleven percent of all tested patients (and 9% of patients 50 years or older) were positive for cocaine. To avoid disparities, we suggest that all stroke and TIA patients be tested.

Toxicology ontology perspectives.

PubMed

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.

Multifaceted toxicity assessment of catalyst composites in transgenic zebrafish embryos.

PubMed

Jang, Gun Hyuk; Lee, Keon Yong; Choi, Jaewon; Kim, Sang Hoon; Lee, Kwan Hyi

2016-09-01

Recent development in the field of nanomaterials has given rise into the inquiries regarding the toxicological characteristics of the nanomaterials. While many individual nanomaterials have been screened for their toxicological effects, composites that accompany nanomaterials are not common subjects to such screening through toxicological assessment. One of the widely used composites that accompany nanomaterials is catalyst composite used to reduce air pollution, which was selected as a target composite with nanomaterials for the multifaceted toxicological assessment. As existing studies did not possess any significant data regarding such catalyst composites, this study focuses on investigating toxicological characteristics of catalyst composites from various angles in both in-vitro and in-vivo settings. Initial toxicological assessment on catalyst composites was conducted using HUVECs for cell viability assays, and subsequent in-vivo assay regarding their direct influence on living organisms was done. The zebrafish embryo and its transgenic lines were used in the in-vivo assays to obtain multifaceted analytic results. Data obtained from the in-vivo assays include blood vessel formation, mutated heart morphology, and heart functionality change. Our multifaceted toxicological assessment pointed out that chemical composites augmented with nanomaterials can too have toxicological threat as much as individual nanomaterials do and alarms us with their danger. This manuscript provides a multifaceted assessment for composites augmented with nanomaterials, of which their toxicological threats have been overlooked. Copyright © 2016 Elsevier Ltd. All rights reserved.

Toxicology Testing in Fatally Injured Workers: A Review of Five Years of Iowa FACE Cases

PubMed Central

Ramirez, Marizen; Bedford, Ronald; Sullivan, Ryan; Anthony, T. Renee; Kraemer, John; Faine, Brett; Peek-Asa, Corinne

2013-01-01

Toxicology testing of fatally injured workers is not routinely conducted. We completed a case-series study of 2005–2009 occupational fatalities captured by Iowa’s Fatality Assessment and Control Evaluation (FACE) Program. The goals of our research were to: (1) measure the proportion of FACE cases that undergo toxicology testing, and describe the factors associated with being tested, and (2) measure the rate of positive toxicology tests, the substances identified and the demographics and occupations of victims who tested positive. Case documents and toxicology laboratory reports were reviewed. There were 427 occupational deaths from 2005 to 2009. Only 69% underwent toxicology testing. Younger workers had greater odds of being tested. Among occupational groups, workers in farming, fishing and forestry had half the odds of being tested compared to other occupational groups. Of the 280 cases with toxicology tests completed, 22% (n = 61) were found to have positive toxicology testing. Commonly identified drug classes included cannabinoids and alcohols. Based on the small number of positive tests, older victims (65+ years) tested positive more frequently than younger workers. Management, business, science, arts, service and sales/office workers had proportionately more positive toxicology tests (almost 30%) compared with other workers (18–22%). These results identify an area in need of further research efforts and a potential target for injury prevention strategies. PMID:24240727

Analysis of Sertraline in Postmortem Fluids and Tissues in 11 Aviation Accident Victims

DTIC Science & Technology

2012-11-01

likely undergoes significant postmortem redistribution. 17. Key Words 18. Distribution Statement Forensic Toxicology , Sertraline, Norsertraline... Toxicology .. Forensic Sci Int,.142:.75-100.(2004) . 29 .. Skopp,.G ..Postmortem.Toxicology .. Forensic Sci Med Pathol,.6:.314-25.(2010) . ... toxicological . analysis. on. specimens.from.….aircraft.accident.fatalities”.and.“in- vestigate.….general.aviation.and.air.carrier.accidents. and. search

International Recommendations for Training Future Toxicologic Pathologists Participating in Regulatory-Type, Nonclinical Toxicity Studies*

PubMed Central

Bolon, Brad; Barale-Thomas, Erio; Bradley, Alys; Ettlin, Robert A.; Franchi, Carla A.S.; George, Catherine; Giusti, Anna Maria; Hall, Robert; Jacobsen, Matthew; Konishi, Yoichi; Ledieu, David; Morton, Daniel; Park, Jae-Hak; Scudamore, Cheryl L.; Tsuda, Hiroyuki; Vijayasarathi, S.K.; Wijnands, Marcel V.W.

2010-01-01

The International Federation of Societies of Toxicologic Pathologists (IFSTP) proposes a common global framework for training future toxicologic pathologists who will support regulatory-type nonclinical toxicology studies. Trainees optimally should undertake a scientific curriculum of at least 5 years at an accredited institution leading to a clinical degree (veterinary medicine or medicine). Trainees should then obtain 4 or more years of intensive pathology practice during a residency and/or on-the-job “apprenticeship,” at least 2 years of which must be focused on regulatory-type toxicologic pathology topics. Possession of a recognized pathology qualification (i.e., certification) is highly recommended. A non-clinical pathway (e.g., a graduate degree in medical biology or pathology) may be possible if medically trained pathologists are scarce, but this option is not optimal. Regular, lifelong continuing education (peer review of nonclinical studies, professional meetings, reading, short courses) will be necessary to maintain and enhance one’s understanding of current toxicologic pathology knowledge, skills, and tools. This framework should provide a rigorous yet flexible way to reliably train future toxicologic pathologists to generate, interpret, integrate, and communicate data in regulatory-type, nonclinical toxicology studies. PMID:22272030

A primer on systematic reviews in toxicology.

PubMed

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.

Evidence-Based Toxicology.

PubMed

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.

Forensic toxicology.

PubMed

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.

42 CFR 493.937 - Toxicology.

Code of Federal Regulations, 2011 CFR

2011-10-01

... a laboratory's responses for quantitative toxicology tests or analytes, the program must compare the... sample in toxicology is the score determined under paragraph (c)(2) of this section. (2) For quantitative...

42 CFR 493.937 - Toxicology.

Code of Federal Regulations, 2013 CFR

2013-10-01

... a laboratory's responses for quantitative toxicology tests or analytes, the program must compare the... sample in toxicology is the score determined under paragraph (c)(2) of this section. (2) For quantitative...

42 CFR 493.937 - Toxicology.

Code of Federal Regulations, 2014 CFR

2014-10-01

... a laboratory's responses for quantitative toxicology tests or analytes, the program must compare the... sample in toxicology is the score determined under paragraph (c)(2) of this section. (2) For quantitative...

42 CFR 493.937 - Toxicology.

Code of Federal Regulations, 2012 CFR

2012-10-01

... a laboratory's responses for quantitative toxicology tests or analytes, the program must compare the... sample in toxicology is the score determined under paragraph (c)(2) of this section. (2) For quantitative...

42 CFR 493.937 - Toxicology.

Code of Federal Regulations, 2010 CFR

2010-10-01

... a laboratory's responses for quantitative toxicology tests or analytes, the program must compare the... sample in toxicology is the score determined under paragraph (c)(2) of this section. (2) For quantitative...

National toxicology program review of current DHHS, DOE, and EPA research related to toxicology, fiscal year 1996

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

1996-11-01

The Annual Plan for the National Toxicology Program requires an annual review of toxicology-related research supported by DHHS agencies. Four of the five Public Health Service Agencies support research related to toxicology. Within the National Institutes of Health alone, sixteen separate institutes and several other components support relevant research. Toxicology-related research is also conducted by other Federal agencies--particularly the Department of Energy (DOE) and the Environmental Protection Agency (EPA). An overall review is thought to be of considerable interest to research managers for purposes of coordinating research and reducing unnecessary duplication. This is the seventeenth review responding to this requirement.more » For the fifteenth time a survey of similar research at DOE and the EPA is included.« less

Differential Effects of Source-Specific Particulate Matter on Emergency Hospitalizations for Ischemic Heart Disease in Hong Kong

PubMed Central

Pun, Vivian Chit; Yu, Ignatius Tak-sun; Ho, Kin-fai; Qiu, Hong; Sun, Zhiwei

2014-01-01

Background: Ischemic heart disease (IHD) is a major public health concern. Although many epidemiologic studies have reported evidence of adverse effects of particulate matter (PM) mass on IHD, significant knowledge gaps remain regarding the potential impacts of different PM sources. Much the same as PM size, PM sources may influence toxicological characteristics. Objectives: We identified contributing sources to PM10 mass and estimated the acute effects of PM10 sources on daily emergency IHD hospitalizations in Hong Kong. Methods: We analyzed the concentration data of 19 PM10 chemical components measured between 2001 and 2007 by positive matrix factorization to apportion PM10 mass, and used generalized additive models to estimate associations of interquartile range (IQR) increases in PM10 exposures with IHD hospitalization for different lag periods (up to 5 days), adjusted for potential confounders. Results: We identified 8 PM10 sources: vehicle exhaust, soil/road dust, regional combustion, residual oil, fresh sea salt, aged sea salt, secondary nitrate, and secondary sulfate. Vehicle exhaust, secondary nitrate, and secondary sulfate contributed more than half of the PM10 mass. Although associations with IQR increases in 2-day moving averages (lag01) were statistically significant for most sources based on single-source models, only PM10 from vehicle exhaust [1.87% (95% CI: 0.66, 3.10); IQR = 4.9 μg/m3], secondary nitrate [2.28% (95% CI: 1.15, 3.42); IQR = 8.6 μg/m3], and aged sea salt [1.19% (95% CI: 0.04, 2.36); IQR = 5.9 μg/m3] were significantly associated with IHD hospitalizations in the multisource model. Analysis using chemical components provided similar findings. Conclusion: Emergency IHD hospitalization was significantly linked with PM10 from vehicle exhaust, nitrate-rich secondary PM, and sea salt–related PM. Findings may help prioritize toxicological research and guide future monitoring and emission-control polices. Citation: Pun VC, Yu IT, Ho KF, Qiu H, Sun Z, Tian L. 2014. Differential effects of source-specific particulate matter on emergency hospitalizations for ischemic heart disease in Hong Kong. Environ Health Perspect 122:391–396; http://dx.doi.org/10.1289/ehp.1307213 PMID:24509062

Advancing Risk Assessment through the Application of Systems Toxicology

PubMed Central

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

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

PubMed

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.

Report on the Consensus Workshop on Formaldehyde.

PubMed Central

1984-01-01

The Consensus Workshop on Formaldehyde consisted of bringing together scientists from academia, government, industry and public interest groups to address some important toxicological questions concerning the health effects of formaldehyde. The participants in the workshop, the Executive Panel which coordinated the meeting, and the questions posed, all were chosen through a broadly based nomination process in order to achieve as comprehensive a consensus as possible. The subcommittees considered the toxicological problems associated with formaldehyde in the areas of exposure, epidemiology, carcinogenicity/histology/genotoxicity, immunology/sensitization/irritation, structure activity/biochemistry/metabolism, reproduction/teratology, behavior/neurotoxicity/psychology and risk estimation. Some questions considered included the possible human carcinogenicity of formaldehyde, as well as other human health effects, and the interpretation of pathology induced by formaldehyde. These reports, plus introductory material on the procedures used in setting up the Consensus Workshop are presented here. Additionally, there is included a listing of the data base that was made available to the panel chairmen prior to the meeting and was readily accessible to the participants during their deliberations in the meeting. This data base, since it was computerized, was also capable of being searched for important terms. These materials were supplemented by information brought by the panelists. The workshop has defined the consensus concerning a number of major points in formaldehyde toxicology and has identified a number of major deficits in understanding which are important guides to future research. PMID:6525992

Recommendations from a global cross-company data sharing initiative on the incorporation of recovery phase animals in safety assessment studies to support first-in-human clinical trials.

PubMed

Sewell, Fiona; Chapman, Kathryn; Baldrick, Paul; Brewster, David; Broadmeadow, Alan; Brown, Paul; Burns-Naas, Leigh Ann; Clarke, Janet; Constan, Alex; Couch, Jessica; Czupalla, Oliver; Danks, Andy; DeGeorge, Joseph; de Haan, Lolke; Hettinger, Klaudia; Hill, Marilyn; Festag, Matthias; Jacobs, Abby; Jacobson-Kram, David; Kopytek, Stephan; Lorenz, Helga; Moesgaard, Sophia Gry; Moore, Emma; Pasanen, Markku; Perry, Rick; Ragan, Ian; Robinson, Sally; Schmitt, Petra M; Short, Brian; Lima, Beatriz Silva; Smith, Diane; Sparrow, Sue; van Bekkum, Yvette; Jones, David

2014-10-01

An international expert group which includes 30 organisations (pharmaceutical companies, contract research organisations, academic institutions and regulatory bodies) has shared data on the use of recovery animals in the assessment of pharmaceutical safety for early development. These data have been used as an evidence-base to make recommendations on the inclusion of recovery animals in toxicology studies to achieve scientific objectives, while reducing animal use. Recovery animals are used in pharmaceutical development to provide information on the potential for a toxic effect to translate into long-term human risk. They are included on toxicology studies to assess whether effects observed during dosing persist or reverse once treatment ends. The group devised a questionnaire to collect information on the use of recovery animals in general regulatory toxicology studies to support first-in-human studies. Questions focused on study design, the rationale behind inclusion or exclusion and the impact this had on internal and regulatory decisions. Data on 137 compounds (including 53 biologicals and 78 small molecules) from 259 studies showed wide variation in where, when and why recovery animals were included. An analysis of individual study and programme design shows that there are opportunities to reduce the use of recovery animals without impacting drug development. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Recommendations from the INHAND Apoptosis/Necrosis Working Group.

PubMed

Elmore, Susan A; Dixon, Darlene; Hailey, James R; Harada, Takanori; Herbert, Ronald A; Maronpot, Robert R; Nolte, Thomas; Rehg, Jerold E; Rittinghausen, Susanne; Rosol, Thomas J; Satoh, Hiroshi; Vidal, Justin D; Willard-Mack, Cynthia L; Creasy, Dianne M

2016-02-01

Historically, there has been confusion relating to the diagnostic nomenclature for individual cell death. Toxicologic pathologists have generally used the terms "single cell necrosis" and "apoptosis" interchangeably. Increased research on the mechanisms of cell death in recent years has led to the understanding that apoptosis and necrosis involve different cellular pathways and that these differences can have important implications when considering overall mechanisms of toxicity, and, for these reasons, the separate terms of apoptosis and necrosis should be used whenever differentiation is possible. However, it is also recognized that differentiation of the precise pathway of cell death may not be important, necessary, or possible in routine toxicity studies and so a more general term to indicate cell death is warranted in these situations. Morphological distinction between these two forms of cell death can sometimes be straightforward but can also be challenging. This article provides a brief discussion of the cellular mechanisms and morphological features of apoptosis and necrosis as well as guidance on when the pathologist should use these terms. It provides recommended nomenclature along with diagnostic criteria (in hematoxylin and eosin [H&E]-stained sections) for the most common forms of cell death (apoptosis and necrosis). This document is intended to serve as current guidance for the nomenclature of cell death for the International Harmonization of Nomenclature and Diagnostic Criteria Organ Working Groups and the toxicologic pathology community at large. The specific recommendations are:Use necrosis and apoptosis as separate diagnostic terms.Use modifiers to denote the distribution of necrosis (e.g., necrosis, single cell; necrosis, focal; necrosis, diffuse; etc.).Use the combined term apoptosis/single cell necrosis whenThere is no requirement or need to split the processes, orWhen the nature of cell death cannot be determined with certainty, orWhen both processes are present together. The diagnosis should be based primarily on the morphological features in H&E-stained sections. When needed, additional, special techniques to identify and characterize apoptosis can also be used. © The Author(s) 2016.

Applications of High-Nitrogen Energetics in Pyrotechnics: Development of Perchlorate-Free Red Star M126A1 Hand-Held Signal Formulations with Superior Luminous Intensities and Burn Times

DTIC Science & Technology

2011-03-25

short-term administration of 3-amino- triazole. The US Army Public Health Command has stated that quantitative structure activity relationship ( QSAR ...modeling is not a useful tool in determining the toxic nature of high nitrogen salts such as bis-tetrazolate 1. Therefore, no data on the toxicology of

THE USE OF THE ELEVATED PLUS MAZE IN THE TOXICOLOGY LABORAOTRY: PILOT STUDIES AND ASSESSMENT OF ANXIETY IN RATS EXPOSED TO LEAD ACETATE OR SUB-CHRONIC LEVELS OF TOLUENE.

EPA Science Inventory

A common complaint of individuals exposed to neurotoxic agents is increased anxiety.

Rat models of the effects of long-term exposure to environmental chemicals on anxiety

are lacking. The elevated plus-maze (EPM) is a widely used tool in the search for new

Biomarkers of Exposure to Toxic Substances: Volume 4: Metabonomics Biomarkers to Liver and Organ Damage

DTIC Science & Technology

2009-05-01

examined the urinary metabolite profiles from rats following a single exposure to the kidney toxicants D- serine, puromycin, hippuric acid and...15. SUBJECT TERMS Amphotericin B, bioinformatics, cell cycle regulation, clinical, clustering analysis, D-serine, glomerular injury, hippuric acid ...puromycin, hippuric acid and amphotericin B at various doses, and as a function of time post-dose. In toxicology, such dose-time metabonomics studies are

Use of Biodescriptors and Chemodescriptors in Predictive Toxicology: A Mathematical/Computational Approach

DTIC Science & Technology

2005-01-01

proteomic gel analyses. The research group has explored the use of chemodescriptors calculated using high-level ab initio quantum chemical basis sets...descriptors that characterize the entire proteomics map, local descriptors that characterize a subset of the proteins present in the gel, and spectrum...techniques for analyzing the full set of proteins present in a proteomics map. 14. SUBJECT TERMS 1S. NUMBER OF PAGES Topological indices

Ethyl carbamate induces cell death through its effects on multiple metabolic pathways.

PubMed

Liu, Huichang; Cui, Bo; Xu, Yi; Hu, Chaoyang; Liu, Ying; Qu, Guorun; Li, Dawei; Wu, Yongning; Zhang, Dabing; Quan, Sheng; Shi, Jianxin

2017-11-01

Ethyl carbamate (EC), a multisite carcinogenic chemical causing tumors in various animal species, is probably carcinogenic to humans. However, information about the possible carcinogenic and toxicological effects of EC in humans is quite limited. Because EC is found in many dietary foods (such as fermented foods) and tobacco and its products, and exposure of humans to EC often occurs inevitably, its toxicological effects in humans need to be studied. This study was conducted to understand the metabolomic and transcriptomic changes in human hepatocellular carcinoma cells (HepG2) exposed to 100 mM EC for short term (4 h) and long term (12 h) period, respectively. The results revealed multiple influences of EC on the metabolome and transcriptome of HepG2 cells, which was exposure time-dependent and well correlated with the kinetic changes of cell viability and mortality. EC treatment affected multiple metabolic pathways, inducing oxidative stress, reducing detoxification capacity, depleting energy, decreasing reducing power, disrupting membrane integrity, and damaging DNA and protein. These metabolomic and transcriptomic biomarkers of EC on human cell metabolism identified in this study would facilitate further studies on the risk assessment and the mitigation of dietary EC. Copyright © 2017 Elsevier B.V. All rights reserved.

Synthetic Cannabinoids: Psychopharmacology, Clinical Aspects, Psychotic Onset.

PubMed

Martinotti, Giovanni; Santacroce, Rita; Papanti, Duccio; Elgharably, Yasmine; Prilutskaya, Mariya; Corazza, Ornella

2017-01-01

Synthetic Cannabinoids (SC) are the widest and most diffused class of Novel Psychoactive Substances. The short- and long- term health risks associated with the consumption of SC are often unknown to both users and health professionals. This review aims to provide a synthesis of the most recent and relevant insights on the pharmacology, clinical and psychopathological aspects of SC. A structured search of two bibliographic databases (PubMed and Scopus) was undertaken according to inclusion/exclusion criteria. The following terms "synthetic cannabinoid*", "synthetic cannabimimetic*", "synthetic cannabis", "synthetic marijuana" and "Spice AND cannabinoid*" were used as search strings. 162 relevant results, mainly published in the past two years were revealed. Most results emerged for the keyword "synthetic cannabinoid*", followed by the combination "Spice* AND "cannabinoid*". Most papers were epidemiological, forensic, toxicologic, or analytical. The results of studies were systematized according their contribution to the comprehension of pharmacological, clinical and psychopathological effects of SC. Fifteen SC-related fatality cases were reviewed according to their histories, pathology and toxicology findings. The findings of this review confirm the importance of prompt and reliable information available for health professionals More specific analytic techniques and designed preventive strategies are required to face unprecedented SC challenge. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Respiratory Toxicology: 1981

DTIC Science & Technology

1981-08-01

AFAMRL-TR-81-81 D /a , 𔄁 RESPIRATORY TOXICOLOGY Annual Technical Report: 1981 P. E. NEWTON, Ph.D. UNIVERSITY OF CALIFORNIA, IRVINE OVERLOOK BRANCH...OF REPORT & PERIOD COVERED RESPIRATORY TOXICOLOGY: 1981 Annual Technical June 1980 through May 198 Ś. PERFORMING ORG. REPORT NUMBER 7. AUTHOR(s) 8...ABSTRACT (Continue on reverse side if necessary and Identify by block number) The Respiratory Toxicology research programs conducted at the Toxic Hazards

75 FR 51815 - National Toxicology Program (NTP); Center for the Evaluation of Risks to Human Reproduction...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-23

... water, consumption of contaminated food, ingestion of lead dust, eating of paint flakes by children..., renal toxicology, immunotoxicology, epidemiology, general toxicology, medicine, pharmacokinetics...

TOXLINE (TOXICOLOGY INFORMATION ONLINE)

EPA Science Inventory

TOXLINE? (TOXicology information onLINE) are the National Library of Medicines extensive collection of online bibliographic information covering the pharmacological, biochemical, physiological, and toxicological effects of drugs and other chemicals. TOXLINE and TOXLINE65 together...

Pharmacology and toxicology of pahayokolide A, a bioactive metabolite from a freshwater species of Lyngbya isolated from the Florida Everglades

PubMed Central

Berry, John P.; Gantar, Miroslav; Gawley, Robert E.; Wang, Minglei; Rein, Kathleen S.

2008-01-01

The genus of filamentous cyanobacteria, Lyngbya, has been found to be a rich source of bioactive metabolites. However, identification of such compounds from Lyngbya has largely focused on a few marine representatives. Here, we report on the pharmacology and toxicology of pahayokolide A from a freshwater isolate, Lyngbya sp. strain 15−2, from the Florida Everglades. Specifically, we investigated inhibition of microbial representatives and mammalian cell lines, as well as toxicity of the compound to both invertebrate and vertebrate models. Pahayokolide A inhibited representatives of Bacillus, as well as the yeast, Saccharomyces cerevisiae. Interestingly, the compound also inhibited several representatives of green algae that were also isolated from the Everglades. Pahayokolide A was shown to inhibit a number of cancer cell lines over a range of concentrations (IC50 varied from 2.13 to 44.57 μM) depending on the cell-type. When tested against brine shrimp, pahayokolide was only marginally toxic at the highest concentrations tested (1 mg/mL). The compound was, however, acutely toxic to zebrafish embryos (LC50=2.15 μM). Possible biomedical and environmental health aspects of the pahayokolides remain to be investigated; however, the identification of bioactive metabolites such as these demonstrates the potential of the Florida Everglades as source of new toxins and drugs. PMID:15683832

COMPUTATIONAL TOXICOLOGY

EPA Science Inventory

Over the last several years, there has been increased pressure to utilize novel technologies derived from computational chemistry, molecular biology and systems biology in toxicological risk assessment. This new area has been referred to as "Computational Toxicology". Our resear...

An audit of the toxicology findings in 555 medico-legal autopsies finds manner of death changed in 5 cases.

PubMed

Langlois, Neil E I; Gilbert, John D; Heath, Karen J; Winskog, Calle; Kostakis, Chris

2013-03-01

An audit of toxicological analysis in Coronial autopsies performed at Forensic Science South Australia was conducted on the cases of three pathologists. Toxicological analysis had been performed in 555 (68 %) from a total of 815 autopsies. It was found that the proffered manner of death was changed from the provisional report (provided immediately after the post-mortem examination) in five cases (just under 1 %) as a consequence of the toxicological findings. This is a limited study as it is retrospective, not all cases had toxicological analysis and the findings are constrained by the range of the substances that could be detected. Nonetheless, the audit supports the application of toxicological analysis in medico-legal death investigation and suggests that an inclusive policy should be adopted.

Poisonings and clinical toxicology: a template for Ireland.

PubMed

Tormey, W P; Moore, T

2013-03-01

Poisons information is accessed around the clock in the British Isles from six centres of which two are in Ireland at Dublin and Belfast accompanied by consultant toxicologist advisory service. The numbers of calls in Ireland are down to about 40 per day due to easy access to online data bases. Access to Toxbase, the clinical toxicology database of the National Poisons Information Service is available to National Health Service (NHS) health professionals and to Emergency Departments and Intensive Care units in the Republic of Ireland. There are 59 Toxbase users in the Republic of Ireland and 99 % of activity originates in Emergency Departments. All United States Poison Control Centres primarily use Poisindex which is a commercial database from Thomson Reuters. Information on paracetamol, diazepam, analgesics and psycho-active compounds are the commonest queries. Data from telephone and computer accesses provide an indicator of future trends in both licit and illicit drug poisons which may direct laboratory analytical service developments. Data from National Drug-Related Deaths Index is the most accurate information on toxicological deaths in Ireland. Laboratory toxicology requirements to support emergency departments are listed. Recommendations are made for a web-based open access Toxbase or equivalent; for a co-location of poisons information and laboratory clinical toxicology; for the establishment of a National Clinical Toxicology Institute for Ireland; for a list of accredited medical advisors in clinical toxicology; for multidisciplinary case conferences in complex toxicology cases for coroners; for the establishment of a national clinical toxicology referral out-patients service in Ireland.

Federal environmental and occupational toxicology regulations and reporting requirements: a practical approach to what the medical toxicologist needs to know, part 1.

PubMed

Schwartz, Michael D; Dell'Aglio, Damon M; Nickle, Richard; Hornsby-Myers, Jennifer

2014-09-01

Toxicologists are often called upon to assist in environmental, industrial, occupational and public health assessments. Accordingly, medical toxicologists may find it prudent to be aware of applicable federal toxicological regulations and reporting requirements and of the roles of relevant federal agencies. These regulations are numerous, complex, and have evolved and expanded over time, making it difficult for toxicologists to sustain a current knowledge base. This article reviews the pertinent federal toxicological reporting requirements with regard to the Toxic Substances Control Act (TSCA), the Atomic Energy Act (AEA), the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), the Resource Conservation and Recovery Act (RCRA), the Clean Air Act, the Clean Water Act, the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA), the Emergency Planning and Community Right to Know Act (EPCRA), the Occupational Safety and Health Act, the Department of Transportation, and information about the National Response Center. We reference internet-based government resources and offer direct links to applicable websites in an attempt to offer rapid and current sources of practical information. The format of the article is a series of hypothetical scenarios followed by commentary. Discussions of the Safe Drinking Water Act, the Food, Drug, and Cosmetic Act, and the Dietary Supplement Health and Education Act are beyond the scope of this paper. For those desiring a more in-depth discussion of the relevant federal environmental laws and statutes and applicable case law, the reader is directed to resources such as the Environmental Law Handbook, the websites of individual laws found at www.epa.gov and the decisions of individual courts of appeal. It is our hope that this article provides not only useful practical information for the practicing toxicologist but also serves as a key reference for medical toxicology core content on environmental laws and regulations.

Federal environmental and occupational toxicology regulations and reporting requirements: a practical approach to what the medical toxicologist needs to know, part 2.

PubMed

Schwartz, Michael D; Dell'Aglio, Damon M; Nickle, Richard; Hornsby-Myers, Jennifer

2014-12-01

Toxicologists are often called upon to assist in environmental, industrial, occupational and public health assessments. Accordingly, medical toxicologists may find it prudent to be aware of applicable federal toxicological regulations and reporting requirements and of the roles of relevant federal agencies. These regulations are numerous, complex, and have evolved and expanded over time, making it difficult for toxicologists to sustain a current knowledge base. This article reviews the pertinent federal toxicological reporting requirements with regards to the Toxic Substances Control Act (TSCA), the Atomic Energy Act (AEA), the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), the Resource Conservation and Recovery Act (RCRA), the Clean Air Act, the Clean Water Act, the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA), the Emergency Planning and Community Right to Know Act (EPCRA), the Occupational Safety and Health Act, the Department of Transportation, and information about the National Response Center. We reference internet-based government resources and offer direct links to applicable websites in an attempt to offer rapid and current sources of practical information. The format of the article is a series of hypothetical scenarios followed by commentary. Discussions of the Safe Drinking Water Act and the Food, Drug, and Cosmetic Act and the Dietary Supplement Health and Education Act are beyond the scope of this paper. For those desiring a more in depth discussion of the relevant federal environmental laws and statutes, and applicable case law, the reader is directed to resources such as the Environmental Law Handbook, the websites of individual laws found at www.epa.gov and the decisions of individual courts of appeal. It is our hope that this article provides not only useful practical information for the practicing toxicologist, but also serves as a key reference for Medical Toxicology core content on environmental laws and regulations.

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

PubMed

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.

High Throughput Transcriptomics @ USEPA (Toxicology ...

EPA Pesticide Factsheets

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.

Integrating the Principles of Toxicology into a Chemistry Curriculum

EPA Science Inventory

Designing safer products, processes and materials requires a commitment to engaging a transdisciplinary, systems approach utilizing the principles of chemistry, toxicology, environmental sciences and other allied disciplines. Chemistry and toxicology are inherently complementary ...

Biomarkers in Computational Toxicology

EPA Science Inventory

Biomarkers are a means to evaluate chemical exposure and/or the subsequent impacts on toxicity pathways that lead to adverse health outcomes. Computational toxicology can integrate biomarker data with knowledge of exposure, chemistry, biology, pharmacokinetics, toxicology, and e...

Diesel fumes do kill: a case of fatal carbon monoxide poisoning directly attributed to diesel fuel exhaust with a 10-year retrospective case and literature review*.

PubMed

Griffin, Sean M; Ward, Michael K; Terrell, Andrea R; Stewart, Donna

2008-09-01

While it is known that diesel fuel combustion engines produce much lower concentrations of carbon monoxide (CO) than gasoline engines, these emissions could certainly generate lethal ambient concentrations given a sufficient amount of time in an enclosed space and under suitable environmental conditions. The authors report a case of CO poisoning which was initially referred for autopsy as a presumed natural death of a truck driver found in the secure cab of a running diesel tractor trailer truck. Completion of the preliminary investigation ascribed death to complications of ischemic heart disease (IHD), pending toxicological analysis that included quantification of CO. When the toxicology results showed lethal blood COHbg, the cause of death was re-certified as CO intoxication secondary to inhalation of (diesel) vehicular exhaust fumes. Because of the unique source of fatal CO intoxication in this case, the contributory IHD and the possible contaminants in the putrefied blood, a 10-year retrospective review was conducted on all nonfire related CO deaths autopsied (n = 94) at the Office of the Chief Medical Examiner in Louisville, KY from 1994 to 2003. For validation of the COHbg detection method used by the Kentucky Office of Forensic Toxicology (KYOFT), blood samples from these cases along with controls were submitted to three laboratories using various analytical methods yielding no statistically significant differences. Lastly, an extensive literature review produced no scientifically reported cases of fatal CO poisoning attributed to diesel fuel exhaust.

Toxicological evaluation of genetically modified cotton (Bollgard) and Dipel WP on the non-target soil mite Scheloribates praeincisus (Acari: Oribatida).

PubMed

Oliveira, Anibal R; Castro, Thiago R; Capalbo, Deise M F; Delalibera, Italo

2007-01-01

Insecticides derived from the bacterium Bacillus thuringiensis (Bt) and plants genetically modified (GM) to express B. thuringiensis toxins are important alternatives for insect pest control worldwide. Risk assessment of B. thuringiensis toxins to non-target organisms has been extensively studied but few toxicological tests have considered soil invertebrates. Oribatid mites are one of the most diverse and abundant arthropod groups in the upper layers of soil and litter in natural and agricultural systems. These mites are exposed to the toxic compounds of GM crops or pesticides mainly when they feed on vegetal products incorporated in the soil. Although some effects of B. thuringiensis products on Acari have been reported, effects on oribatid mites are still unknown. This study investigated the effects of the ingestion of Bt cotton Bollgard and of the B. thuringiensis commercial product Dipel WP on the pantropical species Scheloribates praeincisus (Scheloribatidae). Ingestion of Bollgard and Dipel did not affect adult and immature survivorship and food consumption (estimated by number of fecal pellets produced daily) or developmental time of immature stages of S. praeincisus. These results indicate the safety of Bollgard and Dipel to S. praeincisus under field conditions where exposition is lower and other food sources besides leaves of Bt plants are available. The method for toxicological tests described here can be adapted to other species of Oribatida, consisting on a new option to risk assessment studies.

Toxicity Ranking and Toxic Mode of Action Evaluation of Commonly Used Agricultural Adjuvants on the Basis of Bacterial Gene Expression Profiles

PubMed Central

Nobels, Ingrid; Spanoghe, Pieter; Haesaert, Geert; Robbens, Johan; Blust, Ronny

2011-01-01

The omnipresent group of pesticide adjuvants are often referred to as “inert” ingredients, a rather misleading term since consumers associate this term with “safe”. The upcoming new EU regulation concerning the introduction of plant protection products on the market (EC1107/2009) includes for the first time the demand for information on the possible negative effects of not only the active ingredients but also the used adjuvants. This new regulation requires basic toxicological information that allows decisions on the use/ban or preference of use of available adjuvants. In this study we obtained toxicological relevant information through a multiple endpoint reporter assay for a broad selection of commonly used adjuvants including several solvents (e.g. isophorone) and non-ionic surfactants (e.g. ethoxylated alcohols). The used assay allows the toxicity screening in a mechanistic way, with direct measurement of specific toxicological responses (e.g. oxidative stress, DNA damage, membrane damage and general cell lesions). The results show that the selected solvents are less toxic than the surfactants, suggesting that solvents may have a preference of use, but further research on more compounds is needed to confirm this observation. The gene expression profiles of the selected surfactants reveal that a phenol (ethoxylated tristyrylphenol) and an organosilicone surfactant (ethoxylated trisiloxane) show little or no inductions at EC20 concentrations, making them preferred surfactants for use in different applications. The organosilicone surfactant shows little or no toxicity and good adjuvant properties. However, this study also illustrates possible genotoxicity (induction of the bacterial SOS response) for several surfactants (POEA, AE, tri-EO, EO FA and EO NP) and one solvent (gamma-butyrolactone). Although the number of compounds that were evaluated is rather limited (13), the results show that the used reporter assay is a promising tool to rank commonly used agricultural adjuvants based on toxicity and toxic mode of action data. PMID:22125591

Progress in computational toxicology.

PubMed

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.

A practice analysis of toxicology.

PubMed

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.

Educational Challenges in Toxicology.

ERIC Educational Resources Information Center

Dixon, Robert L.

1984-01-01

Issues and topics related to educational challenges in toxicology at all levels are discussed. They include public awareness and understanding, general approach to toxicology, quality structure-activity relationships, epidemiological studies, quantification of risk, and the types of toxicants studied. (JN)

Computational toxicity in 21st century safety sciences (China talk - Fuzhou China)

EPA Science Inventory

presentation at the Joint Meeting of Analytical Toxicology and Computational Toxicology Committee (Chinese Society of Toxicology) International Workshop on Advanced Chemical Safety Assessment Technologies on 11 May 2016, Fuzhou University, Fuzhou China

Humidifier disinfectant-associated specific diseases should be called together as “humidifier disinfectant syndrome”

PubMed Central

Lee, Jong-Hyeon

2017-01-01

Humidifier disinfectant (HD) damage was terrible chemical damage caused by household goods that happened in only South Korea, but still very little is known in HD damage. Up to now, previous research tried to focus on interstitial fibrosis on terminal bronchioles and alveoli because it is a specific finding, compared with other diseases. To figure out whole effects from HDs, much epidemiologic and toxicologic research is underway. HDs were shown to give rise to typical toxicologic effects on various target organs, such as skin, conjunctiva, naval mucosa, bronchial mucosa, alveoli and so on, which shared common toxicological responses. On a specific target, specific toxicologic effects existed. Diverse diseases along exposure pathways can occur at the same time with a common toxicologic mechanism and cause of HDs, which can be called as HD syndrome. To gain stronger scientific evidence about it, further epidemiological and toxicological studies should be applied. PMID:29026061

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

PubMed

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).

IRIS Toxicological Review of Naphthalene (1998 Final)

EPA Science Inventory

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

Methodology for Uncertainty Analysis of Dynamic Computational Toxicology Models

EPA Science Inventory

The task of quantifying the uncertainty in both parameter estimates and model predictions has become more important with the increased use of dynamic computational toxicology models by the EPA. Dynamic toxicological models include physiologically-based pharmacokinetic (PBPK) mode...

IRIS Toxicological Review of Phosgene (Final Report)

EPA Science Inventory

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

Environmental toxicology: Interconnections between human health and ecological integrity

EPA Science Inventory

This presentation will discuss what has made a career in environmental toxicology rewarding, environmental and scientific challenges for the 21st century, paradigm shift in regulatory toxicology, adverse outcome framework, interconnections between human health and ecological inte...

IRIS Toxicological Review of Acrolein (2003 Final)

EPA Science Inventory

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.

Applications of Proteomic Technologies to Toxicology

EPA Science Inventory

Proteomics is the large-scale study of gene expression at the protein level. This cutting edge technology has been extensively applied to toxicology research recently. The up-to-date development of proteomics has presented the toxicology community with an unprecedented opportunit...

Parkinson’s disease and pesticides: a toxicological perspective

PubMed Central

Hatcher, Jaime M.; Pennell, Kurt D.; Miller, Gary W.

2017-01-01

Environmental factors have been shown to contribute to the incidence of Parkinson’s disease (PD). Pesticides, which represent one of the primary classes of environmental agents associated with PD, share the common feature of being intentionally released into the environment to control or eliminate pests. Pesticides consist of multiple classes and subclasses of insecticides, herbicides, rodenticides, fungicides, fumigants and others and exhibit a vast array of chemically diverse structures. In this review we examine the evidence regarding the ability of each of the major pesticide subclasses to increase the incidence of PD. We propose that, from a toxicological perspective, it would be beneficial to identify specific subclasses, common structural features and the propensity for widespread human exposure when considering the potential role in PD, rather than using the overly broad term of ‘pesticides’ to describe this diverse group of chemicals. Furthermore, these chemicals and their environmentally relevant combinations should be evaluated for their ability to promote or accelerate PD and not merely for being singular causative agents. PMID:18453001

Single chemical entity legal highs: assessing the risk for long term harm.

PubMed

McNabb, Carolyn B; Russell, Bruce R; Caprioli, Daniele; Nutt, David J; Gibbons, Simon; Dalley, Jeffrey W

2012-12-01

A recent and dramatic increase in the emergence of novel psychoactive substances ('legal highs') has left many governments unable to provide a timely response to an increasing number of potentially harmful drugs now available to the public. In response to this rapid increase in lawful drug use, the UK government intends to implement temporary class drug orders, whereby substances with a potential for misuse and harm can be regulated for a 12 month period. During this period an investigation of the potential for harms induced by these drugs will take place. However, the short time-frame in which information must be gathered, and the paucity of data available on novel psychoactive substances, means that robust pharmacological and toxicological analyses may be replaced by extrapolating data from illegal drugs with similar chemical structures. This review explores the potential pharmacology and toxicology of past and present 'legal highs' and discusses the risks of failing to carry out in-depth scientific research on individual substances.

Utilizing an Orally Dissolving Strip for Pharmacological and Toxicological Studies: A Simple and Humane Alternative to Oral Gavage for Animals

PubMed Central

Lieu, Dustin; Asatryan, Liana; Davies, Daryl L.

2016-01-01

Prior to testing novel therapeutics in humans, short and long term preclinical (i.e., animal), repetitive pharmacological and toxicological testing is required. In most cases, the preferred route of administration is via oral delivery. At the present time, oral delivery is mostly accomplished using an oral gavage procedure, in part, because it can achieve consistent and precise dosing in the animal model. Although this method is well established it does have complications that can result in a high rate of animal attrition. To this end, the procedure introduced here describes an alternative to the oral gavage method in which the desired drug is incorporated into a tastant, orally dissolving strip (ODS) that can simply be presented to the test animal where it is then rapidly taken up with minimal manipulation of the test subject. Herein, we demonstrate that preclinical, oral drug delivery using the ODS method represents a safe, convenient, and humane alternative to oral gavage. PMID:27078261

Are chlorine-free compounds a solution for health problems caused by ozone-depleting substances?

PubMed

Valić, F; Beritić-Stahuljak, D

1996-01-01

In January 1996, the Government of Croatia and United Nations Environment Programme (UNEP) signed an agreement on the phasing out of ozone-depleting substances in Croatia, making the problem of identifying adequate substitutes a high priority. In this paper, the main ecologic characteristics of chlorine-containing fully halogenated chlorofluorocarbons (CFCs) and partially halogenated chlorofluorocarbons (HCFCs) compared with chlorine-free hydrofluorocarbons (HFCs) are presented. The data showed HCFCs to be ecologically more acceptable than CFCs, particularly regarding the ozone-depleting potential (ODP), and have therefore been proposed as substitutes for CFCs. However, although having lower ODP, long-term they could still harm the stratospheric ozone layer, and are therefore hardly acceptable. HFCs are promising substitutes which, having no chlorine, have no ODP. Six were toxicologically evaluated; three of them were found flammable. Toxicological characteristics of three nonflammable compounds (HFC 125, HFC 134a and HFC 227ea) are presented. Their toxicity, not yet completely evaluated, appears to be low.

A Gas Chromotographic-Mass Spectrometric Approach to Examining Stereoselective Interaction of Human Plasma Proteins with Soman

DTIC Science & Technology

2008-02-01

ABSTRACT See reprint. 15. SUBJECT TERMS Human plasma proteins, soman, nerve agent , bioscavenger, gas chromatography, mass spectrometry 16. SECURITY...usually referred to as nerve agents ) are tabun (ethyl dimethylamidocyanophosphate, or GA ), sarin (iso- propyl methylfluorophosphonate, or GB), soman...Pharmacology and toxicology of chemical warfare agents Ann. Acad. Med. Singapore 2&: 104-107 (1997). 11. C Macilwain. Study proves Iraq used nerve gas . Nature 3

Proceedings of the Conference on Environmental Toxicology (14th) Held at Dayton, OH on 15-17 November 1983

DTIC Science & Technology

1984-08-01

be a safe level. Men exposed to dibromo- chloropropane for less than 3 months have normal sperm density in ejaculates. Those men exposed between 1 ...FERTILIZATION FURTHER EVALUATION I ~ II SPERMATOGENIC EVALUATION SEMEN BIOCHEMISTRY* MEASURE UNSCHEDULED I DNA SYNTHESIS 1 ) SPERM COUNT 2) SPERM... 1 JiAN 73 IOWBSSOLETE. SECURITY CLASSIFICATION OF THIS PAGE SECURITY CLASSIFICATION OF THIS PAGE 18. Subject Terms Occupational Health

Metabonomics and toxicology.

PubMed

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.

Inhalation Toxicology. 11. The Effect of Elevated Temperature on Carbon Monoxide Toxicity

DTIC Science & Technology

1990-12-01

DOT/FAA/AM-90/16 Inhalation Toxicology : XI. The Effect of Elevated Temperature on Carbon Office of Aviation Medicine Washington, D.C. 20591 M onoxide...Accession No. 3. Recipient’s Catalog No. DOT/FAA/AM-90/16 4. Title and Subtitie S. Report Date INHALATION TOXICOLOGY : XI. THE EFFECT OF ELEVATED December...Statement Combustion toxicology , carbon monoxide, This document is available to the public heat, thermal effects, time-to- through the National Technical

A Design Basis for Spacecraft Cabin Trace Contaminant Control

NASA Technical Reports Server (NTRS)

Perry, Jay L.

2009-01-01

Successful trace chemical contamination control is one of the components necessary for achieving good cabin atmospheric quality. While employing seemingly simple process technologies, sizing the active contamination control equipment must employ a reliable design basis for the trace chemical load in the cabin atmosphere. A simplified design basis that draws on experience gained from the International Space Station program is presented. The trace chemical contamination control design load refines generation source magnitudes and includes key chemical functional groups representing both engineering and toxicology challenges.

THE ART OF DATA MINING THE MINEFIELDS OF TOXICITY ...

EPA Pesticide Factsheets

Toxicity databases have a special role in predictive toxicology, providing ready access to historical information throughout the workflow of discovery, development, and product safety processes in drug development as well as in review by regulatory agencies. To provide accurate information within a hypothesesbuilding environment, the content of the databases needs to be rigorously modeled using standards and controlled vocabulary. The utilitarian purposes of databases widely vary, ranging from a source for (Q)SAR datasets for modelers to a basis for

Studies in neuroendocrine pharmacology

NASA Technical Reports Server (NTRS)

Maickel, R. P.

1976-01-01

The expertise and facilities available within the Medical Sciences Program section on Pharmacology were used along with informational input from various NASA sources to study areas relevant to the manned space effort. Topics discussed include effects of drugs on deprivation-induced fluid consumption, brain biogenic amines, biochemical responses to stressful stimuli, biochemical and behavioral pharmacology of amphetamines, biochemical and pharmacological studies of analogues to biologically active indole compounds, chemical pharmacology: drug metabolism and disposition, toxicology, and chemical methodology. Appendices include a bibliography, and papers submitted for publication or already published.

Pentachlorophenol Hazards to Fish, Wildlife, and Invertebrates: A Synoptic Review

USGS Publications Warehouse

Eisler, R.

1989-01-01

Pentachlorophenol (PCP) is now widely used as a wood preservative, and this has contributed to the detection of PCP residues in air, rain, groundwaters, surface waters, fish and aquatic invertebrates, and in human urine, blood, and milk of nursing mothers. This report briefly reviews the technical literature on ecological and toxicological aspects of PCP in the environment, with emphasis on fishery and wildlife resources. Subtopics include sources and uses, chemical properties, fate, background concentrations, lethal and sublethal effects, and current recommendations for resource protection

Environmental-Toxicological Characteristics of Waters and Their Sources at Magnitogorsk With the Its Iron and Steel Industry

NASA Astrophysics Data System (ADS)

Koshkina, V. S.; Serova, A. A.; Timofeev, V. Yu

2016-08-01

This study summarizes the information necessary to characterize and assess the quality of drinking and industrial water supply in industrial centers with metallurgical engineering and provides information about the pollution impact on the natural environment. The study shows the influence of air pollution, of the soil pollution on the environment of water objects; it also demonstrates the role of the quality of water supply for establishing a higher risk of health problems for children.

Modern Environmental Health Hazards: A Public Health Issue of Increasing Significance in Africa

PubMed Central

Nweke, Onyemaechi C.; Sanders III, William H.

2009-01-01

Objectives Traditional hazards such as poor sanitation currently account for most of Africa’s environmentally related disease burden. However, with rapid development absent appropriate safeguards for environment and health, modern environmental health hazards (MEHHs) may emerge as critical contributors to the continent’s disease burden. We review recent evidence of human exposure to and health effects from MEHHs, and their occurrence in environmental media and consumer products. Our purpose is to highlight the growing significance of these hazards as African countries experience urbanization, industrial growth, and development. Data sources We reviewed published epidemiologic, exposure, and environmental studies of chemical agents such as heavy metals and pesticides. Data synthesis The body of evidence demonstrates ongoing environmental releases of MEHHs and human exposures sometimes at toxicologically relevant levels. Several sources of MEHHs in environmental media have been identified, including natural resource mining and processing and automobile exhaust. Biomonitoring studies provided direct evidence of human exposure to metals such as mercury and lead and pesticides such as p,p′-dichlorodiphenyltrichloroethane (DDT) and organophosphates. Land and water resource pollution and industrial air toxics are areas of significant data gaps, notwithstanding the presence of several emitting sources. Conclusion Unmitigated MEHH releases and human exposure have implications for Africa’s disease burden. For Africans encumbered by conditions such as malnutrition that impair resilience to toxicologic challenges, the burden may be higher. A shift in public health policy toward accommodating the emerging diversity in Africa’s environmental health issues is necessary to successfully alleviate the burden of avoidable ill health and premature death for all its communities now and in the future. PMID:19590675

PREDICTING TOXICOLOGICAL ENDPOINTS OF CHEMICALS USING QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIPS (QSARS)

EPA Science Inventory

Quantitative structure-activity relationships (QSARs) are being developed to predict the toxicological endpoints for untested chemicals similar in structure to chemicals that have known experimental toxicological data. Based on a very large number of predetermined descriptors, a...

IRIS Toxicological Review of Decabromodiphenyl Ether (Final Report)

EPA Science Inventory

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

The U.S. "Tox21 Community" and the Future of Toxicology

EPA Science Inventory

In early 2008, the National Institute of Environmental Health Sciences/National Toxicology Program, the NIH Chemical Genomics Center, and the Environmental Protection Agency’s National Center for Computational Toxicology entered into a Memorandum of Understanding to collaborate o...

A Graduate Program in Toxicology: Administrative and Educational Benefits of Interdepartmental Management.

ERIC Educational Resources Information Center

Masten, Lawrence W.

1979-01-01

The University of Mississippi School of Pharmacy's Department of Pharmacology offers masters and doctoral programs in toxicology. Its programs and toxicology courses are described, and the administration of these interdisciplinary programs within one department is discussed. (JMD)

Acute Toxicological Study of Ampicillin Anhydrate Microcapsules in Sprague-Dawley Rats.

DTIC Science & Technology

This document contains the results of an acute toxicological study to determine the toxicologic potential of ampicillin anhydrate microcapsules on...various organs of the rat. Keywords: Wound treatment; Antibiotic microcapsule ; Controlled release; Experimental data; Tables data. (aw)

20180129 - Computational Embryology: Translational Tools for Modeling in vitro Data (Toxicology Forum)

EPA Science Inventory

Integrative models are needed to "decode the toxicological blueprint of active substances that interact with living systems" (Systems toxicology). Computational biology is uniquely positioned to capture this connectivity and help shift decision-making to mechanistic pre...

Analysis of Statistical Methods Currently used in Toxicology Journals

PubMed Central

Na, Jihye; Yang, Hyeri

2014-01-01

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. PMID:25343012

Analysis of Statistical Methods Currently used in Toxicology Journals.

PubMed

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.

Urban stormwater harvesting and reuse: a probe into the chemical, toxicology and microbiological contaminants in water quality.

PubMed

Chong, Meng Nan; Sidhu, Jatinder; Aryal, Rupak; Tang, Janet; Gernjak, Wolfgang; Escher, Beate; Toze, Simon

2013-08-01

Stormwater is one of the last major untapped urban water resources that can be exploited as an alternative water source in Australia. The information in the current Australian Guidelines for Water Recycling relating to stormwater harvesting and reuse only emphasises on a limited number of stormwater quality parameters. In order to supply stormwater as a source for higher value end-uses, a more comprehensive assessment on the potential public health risks has to be undertaken. Owing to the stochastic variations in rainfall, catchment hydrology and also the types of non-point pollution sources that can provide contaminants relating to different anthropogenic activities and catchment land uses, the characterisation of public health risks in stormwater is complex, tedious and not always possible through the conventional detection and analytical methods. In this study, a holistic approach was undertaken to assess the potential public health risks in urban stormwater samples from a medium-density residential catchment. A combined chemical-toxicological assessment was used to characterise the potential health risks arising from chemical contaminants, while a combination of standard culture methods and quantitative polymerase chain reaction (qPCR) methods was used for detection and quantification of faecal indicator bacteria (FIB) and pathogens in urban stormwater. Results showed that the concentration of chemical contaminants and associated toxicity were relatively low when benchmarked against other alternative water sources such as recycled wastewater. However, the concentrations of heavy metals particularly cadmium and lead have exceeded the Australian guideline values, indicating potential public health risks. Also, high numbers of FIB were detected in urban stormwater samples obtained from wet weather events. In addition, qPCR detection of human-related pathogens suggested there are frequent sewage ingressions into the urban stormwater runoff during wet weather events. Further water quality monitoring study will be conducted at different contrasting urban catchments in order to undertake a more comprehensive public health risk assessment for urban stormwater.

IRIS Toxicological Review of Methanol (Noncancer) (Interagency Science Discussion Draft)

EPA Science Inventory

On May 3, 2013, the Toxicological Review of Methanol (noncancer) (Revised External Review Draft) was posted for public review and comment. Subsequently, the draft Toxicological Review, Appendices, and draft IRIS Summary were reviewed internally by EPA and by other federal agenci...

DockScreen: A database of in silico biomolecular interactions to support computational toxicology

EPA Science Inventory

We have developed DockScreen, a database of in silico biomolecular interactions designed to enable rational molecular toxicological insight within a computational toxicology framework. This database is composed of chemical/target (receptor and enzyme) binding scores calculated by...

Using Computational Toxicology to Enable Risk-Based ...

EPA Pesticide Factsheets

presentation at Drug Safety Gordon Research Conference 2016 on research efforts in NCCT to enable Computational Toxicology to support risk assessment. Slide presentation at Drug Safety Gordon Research Conference 2016 on research efforts in NCCT to enable Computational Toxicology to support risk assessment.

IRIS Toxicological Review of 2-Methylnaphthalene (2003, Final)

EPA Science Inventory

EPA announced the release of the final report, Toxicological Review of 2-Methylnaphthalene: in support of the Integrated Risk Information System (IRIS). The updated Summary for 2-Methylnaphthalene and accompanying toxicological review have also been added to the IRIS Datab...

Toward the Rational Use of Exposure Information in Mixtures Toxicology

EPA Science Inventory

Of all the disciplines of toxicology, perhaps none is as dependent on exposure information as Mixtures Toxicology. Identifying real world mixtures and replicating them in the laboratory (or in silico) is critical to understanding their risks. Complex mixtures such as cigarett...

Male Reproductive Toxicology: Environmental Exposures vs Reproductive Competence

EPA Science Inventory

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...

IRIS Toxicological Review and Summary Documents for Chloroethane (Peer Review Plan)

EPA Science Inventory

Toxicological data in the published literature on Chloroethane (CE) will be assimilated, reviewed, and integated into a Toxicological Review of CE (assessment document), which seeks to characterize the key cancer, and non cancer health effect hazards from environmental exposures...

THE FUTURE OF TOXICOLOGY-PREDICTIVE TOXICOLOGY: AN EXPANDED VIEW OF CHEMICAL TOXICITY

EPA Science Inventory

A chemistry approach to predictive toxicology relies on structure−activity relationship (SAR) modeling to predict biological activity from chemical structure. Such approaches have proven capabilities when applied to well-defined toxicity end points or regions of chemical space. T...

Inhalation Toxicology. VI. Evaluation of the Relative Toxicity of Thermal Decomposition Products from Nine Aircraft Panel Materials.

DTIC Science & Technology

1986-02-01

AD-R168 250 INHALATION TOXICOLOGY VI EVALUATION OF THE RELATIVE i/I TOXICITY OF THERMAL D. (U) FEDERAL AVIATION ADMINISTRATION WASHINGTON DC OFFICE...FAA/AM-8613 INHALATION TOXICOLOGY : (0 Office of Aviation Medicine Vi. Evaluation of the Relative Washington, D.C. 20591 Toxicity of Thermal...Government Accession No. 3. Recipient’s Catalog No. /XO/FAA/AM-86/3 /1j, 14 4F d Y_0 4. Title and Subtitle 5. Report Date INHALATION TOXICOLOGY : VI

Inhalation Toxicology. VII. Times To Incapacitation and Death for Rats Exposed Continuously to Atmospheric Acrolein Vapor

DTIC Science & Technology

1986-05-01

DOT FMAM-6/5INHALATION TOXICOLOGY : Office of Aviation Medicine VII. Times to Incapacitation and Washington, D.C. 20591 D ahfrR t x oe Continuously to...Accession No. 3. Recipient’s Catalog No. pOT/FAA/AM-86/5 ,4%__ _____ 4. T,tle and Subtoie S. Report Doate INHALATION TOXICOLOGY : VII. TIMES TO...Statement " Combustion toxicology ; smoke; irritant This document is available to the public gas; time-to-incapacitation; time-to- through the National

Clinical lead poisoning in England: an analysis of routine sources of data.

PubMed

Elliott, P; Arnold, R; Barltrop, D; Thornton, I; House, I M; Henry, J A

1999-12-01

To examine the occurrence of clinical lead poisoning in England based on routine sources of data. Three routine data sources were examined, over different periods according to availability of data: (a) mortality for England, 1981-96; (b) hospital episode statistics data for England, for the 3 years 1 April 1992-31 March 1995; (c) statutory returns to the Health and Safety Executive under the reporting of injuries, diseases, and dangerous occurrences regulations (RIDDOR), also for the period 1 April 1992-31 March 1995. Also, analyses of blood lead concentrations carried out by the Medical Toxicology Unit, Guy's and St Thomas' Hospital Trust in London during the period 1 January 1991-31 December 1997 were examined. The analyses were performed both for industrial screening purposes and in response to clinicians' requests where lead poisoning was suspected. This is one of several laboratories carrying out such analyses in the United Kingdom. One death, of a 2 year old girl, was coded to lead poisoning in England during 1981-96. Analysis of hospital episode statistics data identified 83 hospital cases (124 admissions) over 3 years with any mention of lead poisoning, excluding two with admissions dating from 1965 and 1969. For these 83 cases the median hospital stay per admission was 3 days (range 0-115 days). Five were coded as having received intravenous treatment. Further clinical details of these cases beyond what is routinely recorded on the hospital episode statistics database were not available, except for blood lead concentrations in cases also identified on the Medical Toxicology Unit database. Eighteen cases (22%) were below 5 years of age of whom 10 (56%) came from the most deprived quintile of electoral wards. There was evidence to suggest spatial clustering of cases (p = 0.02). Six occupational cases were reported under RIDDOR in England during the period of study, two of whom were identified on the hospital episode statistics database. One further occupational case was identified on hospital episode statistics. Blood lead analyses for 4424 people carried out by the Medical Toxicology Unit (estimated at about 5% of such analyses in England over 7 years) found that among 547 children aged 0-4, 45 (8.2%) had a blood lead concentration in excess of 25 micrograms/dl, the action level in the United Kingdom for investigation, or removal of environmental sources of lead. At all ages, there were 419 (9.5%) such people, including 106 adults with no mention of industrial exposure. Both mortality and hospital admission ascribed to lead poisoning in England are rare, but cases continue to occur and some, at least, seem to be associated with considerable morbidity. Lead poisoning was confirmed as a probable cause of clinical signs and symptoms in only a small proportion of those in whom a blood lead concentration was requested. Where indicated, appropriate remedial action for the safe removal of environmental sources of lead should be taken.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tian, Dayong; Department of Chemical and Environmental Engineering, Anyang Institute of Technology, Anyang 455000; Lin, Zhifen, E-mail: lzhifen@tongji.edu.cn

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

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

PubMed

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.

IRIS Toxicological Review of Trimethylbenzenes (Interagency Science Consultation Draft)

EPA Science Inventory

On June 26, 2012, the draft Toxicological Review of Trimethylbenzenes and the draft 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 W...

Advancing adverse outcome pathways for integrated toxicology and regulatory applications

EPA Science Inventory

Recent regulatory efforts in many countries have focused on a toxicological pathway-based vision for human health assessments relying on in vitro systems and predictive models to generate the toxicological data needed to evaluate chemical hazard. A pathway-based vision is equally...

IRIS Toxicological Review of Trichloroethylene (Interagency Science Consultation Draft)

EPA Science Inventory

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...

IRIS Toxicological Review of Formaldehyde (Interagency Science Consultation Draft)

EPA Science Inventory

On June 2, 2010, the Toxicological Review of Formaldehyde 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 House Offices...

IRIS Toxicological Review of Biphenyl (Interagency Science Consultation Draft)

EPA Science Inventory

On September 30, 2011, the draft Toxicological Review of Biphenyl 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 House...

IRIS Toxicological Review of Methyl Ethyl Ketone (2003 Final)

EPA Science Inventory

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

IRIS Toxicological Review of Acrylonitrile (Interagency Science Consultation Draft)

EPA Science Inventory

On June 30, 2011, the draft Toxicological Review of Acrylonitrile 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 House...

The toxic effects of calories

USDA-ARS?s Scientific Manuscript database

This is a new chapter in the Graduate School textbook "Cassarett & Doull's Toxicology". It is intended as a teaching text for graduate students in toxicology departments and programs and for the examination for professional certification as a Diplomate of the American Board of Toxicology (D.A.B.T.)...

Automatic sorting of toxicological information into the IUCLID (International Uniform Chemical Information Database) endpoint-categories making use of the semantic search engine Go3R.

PubMed

Sauer, Ursula G; Wächter, Thomas; Hareng, Lars; Wareing, Britta; Langsch, Angelika; Zschunke, Matthias; Alvers, Michael R; Landsiedel, Robert

2014-06-01

The knowledge-based search engine Go3R, www.Go3R.org, has been developed to assist scientists from industry and regulatory authorities in collecting comprehensive toxicological information with a special focus on identifying available alternatives to animal testing. The semantic search paradigm of Go3R makes use of expert knowledge on 3Rs methods and regulatory toxicology, laid down in the ontology, a network of concepts, terms, and synonyms, to recognize the contents of documents. Search results are automatically sorted into a dynamic table of contents presented alongside the list of documents retrieved. This table of contents allows the user to quickly filter the set of documents by topics of interest. Documents containing hazard information are automatically assigned to a user interface following the endpoint-specific IUCLID5 categorization scheme required, e.g. for REACH registration dossiers. For this purpose, complex endpoint-specific search queries were compiled and integrated into the search engine (based upon a gold standard of 310 references that had been assigned manually to the different endpoint categories). Go3R sorts 87% of the references concordantly into the respective IUCLID5 categories. Currently, Go3R searches in the 22 million documents available in the PubMed and TOXNET databases. However, it can be customized to search in other databases including in-house databanks. Copyright © 2013 Elsevier Ltd. All rights reserved.

The synthetic cathinone α-pyrrolidinovalerophenone (α-PVP): pharmacokinetic and pharmacodynamic clinical and forensic aspects.

PubMed

Nóbrega, Leandro; Dinis-Oliveira, Ricardo Jorge

2018-05-01

New psychoactive substances (NPS), often referred as 'legal highs' or 'designer drugs', are derivatives and analogs of existing psychoactive drugs that are introduced in the recreational market to circumvent existing legislation on drugs of abuse. This work aims to review the state-of-the-art regarding chemical, molecular pharmacology, and in vitro and in vivo data on toxicokinetics of the potent synthetic cathinone α-pyrrolidinovalerophenone (α-PVP or flakka or zombie drug). Chemical, pharmacological, toxicological, and clinical effects of α-PVP were searched in PubMed (U.S. National Library of Medicine) and governmental websites without limitation of the period. α-PVP is a wide spread and easy to get special type of synthetic cathinone with seemingly powerful cocaine-like stimulant effects, high brain penetration, high liability for abuse and with increased risk of adverse effects such as tachycardia, agitation, hypertension, hallucinations, delirium, mydriasis, self-injury, aggressive behavior, and suicidal ideations. α-PVP undergoes extensive metabolism via different pathways and the α-PVP itself or its metabolites β-hydroxy-α-PVP and α-PVP lactam represent the main targets for toxicological analysis in urine. There is a limited knowledge regarding the short- and long-term effects of α-PVP and metabolites, and pharmacogenetic influence, hence further clinical and forensic toxicological studies are required. Moreover, since α-PVP cannot be detected with classic routine analysis procedures, statements on the frequency of their consumption cannot be made.

Data-Driven Method to Estimate Nonlinear Chemical Equivalence.

PubMed

Mayo, Michael; Collier, Zachary A; Winton, Corey; Chappell, Mark A

2015-01-01

There is great need to express the impacts of chemicals found in the environment in terms of effects from alternative chemicals of interest. Methods currently employed in fields such as life-cycle assessment, risk assessment, mixtures toxicology, and pharmacology rely mostly on heuristic arguments to justify the use of linear relationships in the construction of "equivalency factors," which aim to model these concentration-concentration correlations. However, the use of linear models, even at low concentrations, oversimplifies the nonlinear nature of the concentration-response curve, therefore introducing error into calculations involving these factors. We address this problem by reporting a method to determine a concentration-concentration relationship between two chemicals based on the full extent of experimentally derived concentration-response curves. Although this method can be easily generalized, we develop and illustrate it from the perspective of toxicology, in which we provide equations relating the sigmoid and non-monotone, or "biphasic," responses typical of the field. The resulting concentration-concentration relationships are manifestly nonlinear for nearly any chemical level, even at the very low concentrations common to environmental measurements. We demonstrate the method using real-world examples of toxicological data which may exhibit sigmoid and biphasic mortality curves. Finally, we use our models to calculate equivalency factors, and show that traditional results are recovered only when the concentration-response curves are "parallel," which has been noted before, but we make formal here by providing mathematical conditions on the validity of this approach.

Subject matter expert and public evaluations of a veterinary toxicology course brochure-writing assignment.

PubMed

Dorman, David C; Alpi, Kristine M; Chappell, Kimberly H

2013-01-01

Veterinary schools are increasingly developing students' communication skills, with an emphasis placed on practice conveying medical and scientific knowledge to different audiences. We describe how patient-centered written communication has been integrated into the training of veterinary students using toxicology-related preventive materials. Third-year veterinary students were given an assignment to prepare a client-focused brochure related to veterinary toxicology. Since 2010, 148 students have completed this assignment, with an average score of 93.4%. Use of a grading rubric was instituted in 2011 and resulted in a more rigorous assessment of the brochures by the course instructors. In this study, we evaluated a sample (n=6) selected from 10 brochures volunteered for further public and expert assessment. Each brochure was measured for readability and assessed with a rubric for perceived usefulness and acceptability by 12 veterinary toxicologists and 10 or 11 adult members of the public attending a college of veterinary medicine open house. Veterinary toxicologist review anticipated that the brochures would be useful for most clients, and the public reviewers confirmed this assessment. Evaluation of the brochures using set marking criteria and readability indexes showed that students had successfully targeted the chosen audiences. Feedback showed that the general public rated the sample brochures highly in terms of quality, usefulness, and interest. Completion of this study has resulted in revision of the grading rubric, an increased use of brochure examples, and additional instruction in readability assessment and brochure development, thereby improving the assignment as a learning exercise.

Which Fish Should I Eat? Perspectives Influencing Fish Consumption Choices

PubMed Central

Choi, Anna L.; Karagas, Margaret R.; Mariën, Koenraad; Rheinberger, Christoph M.; Schoeny, Rita; Sunderland, Elsie; Korrick, Susan

2012-01-01

Background: Diverse perspectives have influenced fish consumption choices. Objectives: We summarized the issue of fish consumption choice from toxicological, nutritional, ecological, and economic points of view; identified areas of overlap and disagreement among these viewpoints; and reviewed effects of previous fish consumption advisories. Methods: We reviewed published scientific literature, public health guidelines, and advisories related to fish consumption, focusing on advisories targeted at U.S. populations. However, our conclusions apply to groups having similar fish consumption patterns. Discussion: There are many possible combinations of matters related to fish consumption, but few, if any, fish consumption patterns optimize all domains. Fish provides a rich source of protein and other nutrients, but because of contamination by methylmercury and other toxicants, higher fish intake often leads to greater toxicant exposure. Furthermore, stocks of wild fish are not adequate to meet the nutrient demands of the growing world population, and fish consumption choices also have a broad economic impact on the fishing industry. Most guidance does not account for ecological and economic impacts of different fish consumption choices. Conclusion: Despite the relative lack of information integrating the health, ecological, and economic impacts of different fish choices, clear and simple guidance is necessary to effect desired changes. Thus, more comprehensive advice can be developed to describe the multiple impacts of fish consumption. In addition, policy and fishery management inter-ventions will be necessary to ensure long-term availability of fish as an important source of human nutrition. PMID:22534056

Evaluation of the health impact of nanoparticles emitted from combustion sources: Comprehensive characterization of the physicochemical properties of nanoparticle emissions from wood combustion compliances, car- and ship diesel-engines as well as investigation of their toxicological effects on human lung cells and macrophages.

NASA Astrophysics Data System (ADS)

Zimmermann, R.; Dittmar, G.; Kanashova, T.; Buters, J.; Öder, S.; Paur, H. R.; Mülhopt, S.; Dilger, M.; Weiss, C.; Harndorf, H.; Stengel, B.; Hirvonen, M. R.; Jokiniemi, J.; Hiller, K.; Sapcariu, S.; Sippula, O.; Streibel, T.; Karg, E.; Weggler, B.; Schnelle-Kreis, J.; Lintelmann, J.; Sklorz, M.; Orasche, J.; Müller, L.; Passig, J.; Gröger, T.; BéruBé, K.; Krebs, T.

2016-12-01

Combustion emissions cause health effects. The HICE-Aerosol and Health project team studies the physicochemical properties as well as biological and toxicological effects on lung cells of combustion particle emissions. The chemical composition and physical parameters thoroughly characterized. Human lung cells are exposed to the diluted combustion exhaust fumes at the air-liquid interface (ALI), allowing a realistic lung-cell exposure by simulation of the lung situation. After exposure, cellular responses of the exposed lung cells are studied by multi-omics molecular biological analyses on transcriptomic, proteomic and metabolomic level. Emissions of wood combustion (log wood, pellet heater), ship diesel engines and car gasoline engines are addressed. Special field deployable ALI-exposition systems in a mobile S2-biological laboratory were set up and applied. Human alveolar epithelial cells (A549, BEAS2B and primary cells) as well as murine macrophages were ALI-exposed to diluted emissions. The cellular effects were then comprehensively characterized (viability, cyto-toxicology, multi-omics effects monitoring) and put in context with the chemical and physical aerosol data. The following order of overall cellular response-strength was observed: A relatively mild cellular effect is observed for the diluted wood combustion emissions. Interestingly the effects-strength for log-wood and pellet burner emissions are similar, although PM-concentrations are much higher for the log-wood heater. Similar mild biological effects are observed for the gasoline car emissions. The ship diesel engine emissions induced the most intense biological responses. A surprising result in this context is, that heavy fuel oil (HFO)-emissions showed lower biological effect strengths than the supposedly cleaner diesel fuel emissions (DF). The HFO-emission contain high concentrations of known toxicants (transition metals, polycyclic aromatics). This result was recently confirmed by experiments with murine RAW macrophages. Detailed analyses of the activated cellular response pathways, such as pro-inflammatory responses, xenobiotic metabolism, phagocytosis and oxidative stress were performed. The data is suggesting a large difference in relative toxicity for different combustion sources.

Pharmaceuticals and personal care products (PPCPs) in Arctic environments: indicator contaminants for assessing local and remote anthropogenic sources in a pristine ecosystem in change.

PubMed

Kallenborn, Roland; Brorström-Lundén, Eva; Reiersen, Lars-Otto; Wilson, Simon

2017-07-31

A first review on occurrence and distribution of pharmaceuticals and personal care products (PPCPs) is presented. The literature survey conducted here was initiated by the current Assessment of the Arctic Monitoring and Assessment Programme (AMAP). This first review on the occurrence and environmental profile of PPCPs in the Arctic identified the presence of 110 related substances in the Arctic environment based on the reports from scientific publications, national and regional assessments and surveys, as well as academic research studies (i.e., PhD theses). PPCP residues were reported in virtually all environmental compartments from coastal seawater to high trophic level biota. For Arctic environments, domestic and municipal wastes as well as sewage are identified as primary release sources. However, the absence of modern waste water treatment plants (WWTPs), even in larger settlements in the Arctic, is resulting in relatively high release rates for selected PPCPs into the receiving Arctic (mainly) aquatic environment. Pharmaceuticals are designed with specific biochemical functions as a part of an integrated therapeutically procedure. This biochemical effect may cause unwanted environmental toxicological effects on non-target organisms when the compound is released into the environment. In the Arctic environments, pharmaceutical residues are released into low to very low ambient temperatures mainly into aqueous environments. Low biodegradability and, thus, prolonged residence time must be expected for the majority of the pharmaceuticals entering the aquatic system. The environmental toxicological consequence of the continuous PPCP release is, thus, expected to be different in the Arctic compared to the temperate regions of the globe. Exposure risks for Arctic human populations due to consumption of contaminated local fish and invertebrates or through exposure to resistant microbial communities cannot be excluded. However, the scientific results reported and summarized here, published in 23 relevant papers and reports (see Table S1 and following references), must still be considered as indication only. Comprehensive environmental studies on the fate, environmental toxicology, and distribution profiles of pharmaceuticals applied in high volumes and released into the Nordic environment under cold Northern climate conditions should be given high priority by national and international authorities.

2009 TOXICOLOGY AND RISK ASSESSMENT CONFERENCE

EPA Science Inventory

EPA has announced

The 2009 Toxicology and Risk Assessment Conference
Cincinnati Marriott North, West Chester (Cincinnati), OH
April 27-30, 2009 - Click to register!

The Annual Toxicology and Risk Ass...

IRIS TOXICOLOGICAL REVIEW OF HEXAVALENT CHROMIUM (INTERAGENCY SCIENCE CONSULTATION DRAFT)

EPA Science Inventory

On Septemeber 30, 2010, the draft Toxicological Review of Hexavalent Chromium 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 agenc...

IRIS Toxicological Review of 1,4-Dioxane (Final Report)

EPA Science Inventory

EPA announced the release of the final report, Toxicological Review of 1,4-Dioxane (CAS No. 123-91-1): In Support of Summary Information on the Integrated Risk Information System (IRIS). The final Toxicological Review of 1,4-dioxane provides scientific support and rationa...

IRIS Toxicological Review of Libby Amphibole Asbestos (Interagency Science Consultation Draft)

EPA Science Inventory

On August 25, 2011, the draft Toxicological Review of Libby Amphibole Asbestos 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 an...

IRIS Toxicological Review of Urea (Interagency Science Consultation Draft)

EPA Science Inventory

On September 28, 2010, the Toxicological Review of Urea 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 House Of...

2008 TOXICOLOGY AND RISK ASSESSMENT CONFERENCE

EPA Science Inventory

EPA has announced

The 2008 Toxicology and Risk Assessment Conference
Cincinnati Marriott North, West Chester (Cincinnati), OH
April 14 - 17, 2008 - Click to register!

The Annual Toxicology and Risk ...

IRIS Toxicological Review of 2-Hexanone (Interagency Science Discussion Draft)

EPA Science Inventory

On September 25, 2009, the IRIS Summary and Toxicological Review of 2-hexanone was finalized and loaded onto the IRIS database. The Toxicological Review of 2-hexanone was reviewed internally by EPA, by other federal agencies and White House Offices, by expert external peer revie...

IRIS Toxicological Review of Ammonia (Interagency Science Consultation Draft)

EPA Science Inventory

On June 1, 2012, the draft Toxicological Review of Ammonia and the draft 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 House ...

IRIS Toxicological Review of 1,4-Dioxane (Interagency Science Consultation Draft)

EPA Science Inventory

On September 9, 2011, the Toxicological Review of 1,4-Dioxane (with inhalation update) (External Review Draft) was posted 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...

2007 TOXICOLOGY AND RISK ASSESSMENT CONFERENCE

EPA Science Inventory

EPA has announced

The 2007 Toxicology and Risk Assessment Conference
Cincinnati Marriott North, West Chester (Cincinnati), OH
April 23- 26, 2007 - Click to register!

The Annual Toxicology and Risk Ass...

IRIS TOXICOLOGICAL REVIEW AND SUMMARY DOCUMENTS FOR 2-HEXANONE

EPA Science Inventory

EPA will conduct an assessment of the noncancer health effects of 2-hexanone. The IRIS program will prepare an IRIS assessment for 2-hexanone. The IRIS assessment for 2-hexanone will consist of a Toxicological Review and an IRIS Summary. The Toxicological Review is a critical ...

The Salmonella Mutagenicity Assay: The Stethoscope of Genetic Toxicology for the 21 st Century

EPA Science Inventory

OBJECTIVES: According to the 2007 National Research Council report Toxicology for the Twenty-first Century, modem methods ("omics," in vitro assays, high-throughput testing, computational methods, etc.) will lead to the emergence of a new approach to toxicology. The Salmonella ma...

TOXICOLOGICAL RESEARCH INVOLVING HUMANS: ETHICAL AND REGULATORY CONSIDERATIONS

EPA Science Inventory

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...

The Whole Wildlife Toxicology Catalog: a Web Portal for Wildlife Toxicology Data

EPA Science Inventory

In 2007, the Smithsonian Institution sponsored a Wildlife Toxicology Workshop attended by over 50 scientists and administrators from academia, government and conservation entities, and the private sector. One of the action items from the meeting was to develop a web portal that ...

IRIS Toxicological Review of n-Butanol (Interagency Science Consultation Draft)

EPA Science Inventory

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 re...

IRIS Toxicological Review of Vanadium Pentoxide (Interagency Science Consultation Draft)

EPA Science Inventory

On September 30, 2011, the draft Toxicological Review of Vanadium Pentoxide 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 W...

Studies in the behavioral toxicology of environmental contaminants.

PubMed Central

Weiss, B; Levine, T E

1976-01-01

Behavioral toxicology represents a relatively new research area in the West, and a new source of information pertinent to standard setting. Despite this abbreviated history, however, it can call on a rather advanced technology, largely provided by the rapid and extensive development of behavioral pharmacology during the past two decades. As exemplified by the U.S. contribution to the joint study of carbon disulfide, the approach derived from this background relies on the acquisition of dose--effect data with a preparation yielding stable baseline performance. The first study in this collaborative series employed pigeons trained to peck a response device consisting of a transilluminnated plastic disk. Various relationships between this response and the occasions on which it led to the delivery of food were explored in order to ascertain which behavioral variables were most sensitive to acute exposures. In addition, a central nervous system drug, whose neurochemical mode of action is believed to parallel that of carbon disulfide, was tested in the same preparations. Further research on these questions is being continued with monkeys. Images FIGURE 1. FIGURE 2. PMID:1269505

Completing the Link between Exposure Science and Toxicology for Improved Environmental Health Decision Making: The Aggregate Exposure Pathway Framework.

PubMed

Teeguarden, Justin G; Tan, Yu-Mei; Edwards, Stephen W; Leonard, Jeremy A; Anderson, Kim A; Corley, Richard A; Kile, Molly L; Simonich, Staci M; Stone, David; Tanguay, Robert L; Waters, Katrina M; Harper, Stacey L; Williams, David E

2016-05-03

Driven by major scientific advances in analytical methods, biomonitoring, computation, and a newly articulated vision for a greater impact in public health, the field of exposure science is undergoing a rapid transition from a field of observation to a field of prediction. Deployment of an organizational and predictive framework for exposure science analogous to the "systems approaches" used in the biological sciences is a necessary step in this evolution. Here we propose the aggregate exposure pathway (AEP) concept as the natural and complementary companion in the exposure sciences to the adverse outcome pathway (AOP) concept in the toxicological sciences. Aggregate exposure pathways offer an intuitive framework to organize exposure data within individual units of prediction common to the field, setting the stage for exposure forecasting. Looking farther ahead, we envision direct linkages between aggregate exposure pathways and adverse outcome pathways, completing the source to outcome continuum for more meaningful integration of exposure assessment and hazard identification. Together, the two frameworks form and inform a decision-making framework with the flexibility for risk-based, hazard-based, or exposure-based decision making.

Integrated testing strategies can be optimal for chemical risk classification.

PubMed

Raseta, Marko; Pitchford, Jon; Cussens, James; Doe, John

2017-08-01

There is an urgent need to refine strategies for testing the safety of chemical compounds. This need arises both from the financial and ethical costs of animal tests, but also from the opportunities presented by new in-vitro and in-silico alternatives. Here we explore the mathematical theory underpinning the formulation of optimal testing strategies in toxicology. We show how the costs and imprecisions of the various tests, and the variability in exposures and responses of individuals, can be assembled rationally to form a Markov Decision Problem. We compute the corresponding optimal policies using well developed theory based on Dynamic Programming, thereby identifying and overcoming some methodological and logical inconsistencies which may exist in the current toxicological testing. By illustrating our methods for two simple but readily generalisable examples we show how so-called integrated testing strategies, where information of different precisions from different sources is combined and where different initial test outcomes lead to different sets of future tests, can arise naturally as optimal policies. Copyright © 2017 Elsevier Inc. All rights reserved.

The (non)sense of routinely analysing beta-hydroxybutyric acid in forensic toxicology casework.

PubMed

Sadones, Nele; Lambert, Willy E; Stove, Christophe P

2017-05-01

Beta-hydroxybutyric acid (BHB) is a ketone body which is generated from fatty acids as an alternative energy source when glucose is not available. Determination of this compound may be relevant in the forensic laboratory as ketoacidosis - an elevated level of ketone bodies - may contribute to the cause of death. In this study, we aimed at determining the relevance of routinely implementing BHB analysis in the forensic toxicological laboratory, as BHB analysis typically requires an additional workload. We therefore performed an unbiased retrospective analysis of BHB in 599 cases, comprising 553 blood, 232 urine and 62 vitreous humour samples. Cases with BHB concentrations above 100mg/L (in blood, urine and/or vitreous humour) were invariably associated with elevated levels of acetone, another ketone body, the detection of which is already implemented in most forensic laboratories using the gas chromatographic procedure for ethanol quantification. Our retrospective analysis did not reveal any positive case that had been missed initially and confirms that BHB analysis can be limited to acetone positive cases. Copyright © 2017 Elsevier B.V. All rights reserved.

Proceedings of the Annual Conference on Environmental Toxicology (8th) held at Dayton, OH, 4-6 October 1977

DTIC Science & Technology

1977-12-01

generated citrate to the cyto- plasmic fatty acid synthesizing system (Kirsten et al., 1971). As shown in Table 1 , preincubation of mitochondria ( 1 mg...fatty acid bio- synthesis is independent from aconitase in terms of metabolic pathways. 127 TABLE 1 . INHIBITION OF MITOCHONDRIAL CITRATE ENTRY AND... carboxylic acid substrates of the Krebs 132 cycle enzymes revealed that none of them formed covalent adducts with membrane proteins. It was therefore

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

PubMed

Canovas-Jorda, David; Louisse, Jochem; Pistollato, Francesca; Zagoura, Dimitra; Bremer, Susanne

2014-01-01

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 received great attention so far, despite growing evidence indicating the relationship of stem cell damage to adverse effects later in life. However, testing this in vitro is a scientific/technical challenge in particular due to the complex interplay of factors existing under physiological conditions. Current major research programs in stem cell toxicity are not aiming to demonstrate that stem cells can be targeted by toxicants. Therefore, this knowledge gap needs to be addressed in additional research activities developing technical solutions and defining appropriate experimental designs. The current review describes selected examples of the role of stem cells in the development of long-term toxicities in the brain, heart or liver and in the development of cancer. The presented examples illustrate the need to analyze the contribution of stem cells to chronic toxicity in order to make a final conclusion whether stem cell toxicities are an underestimated risk in mechanism-based safety assessments. This requires the development of predictive in vitro models allowing the assessment of adverse effects to stem cells on chronic toxicity and carcinogenicity.

Development of an in-house mixed-mode solid-phase extraction for the determination of 16 basic drugs in urine by High Performance Liquid Chromatography-Ion Trap Mass Spectrometry.

PubMed

Musile, Giacomo; Cenci, Lucia; Piletska, Elena; Gottardo, Rossella; Bossi, Alessandra M; Bortolotti, Federica

2018-07-27

The aim of the present work was to develop a novel in-house mixed-mode SPE sorbent to be used for the HPLC-Ion TrapMS determination of 16 basic drugs in urine. By using a computational modelling, a virtual monomer library was screened identifying three suitable functional monomers, methacrylic acid (MAA), itaconic acid (IA) and 2-acrylamide-2-methylpropane sulfonic acid (AMPSA), respectively. Three different sorbents were then synthetized based on these monomers, and using as cross-linker trimethylolpropane trimethacrylate (TMPTMA). The sorbent characterization analyses brought to the selection of the AMPSA based phase. Using this novel in-house sorbent, a SPE-HPLC-Ion TrapMS method for drug analysis in urine was validated proving to be selective and accurate and showing a sensitivity adequate for toxicological urine analysis. The comparison of the in-house mixed-mode SPE sorbent with two analogous commercial mixed-mode SPE phases showed that the first one was better not only in terms of process efficiency, but also in terms of quality-price rate. To the best of our knowledge, this is the first time in which an in-house SPE procedure has been applied to the toxicological analysis of a complex matrix, such as urine. Copyright © 2018 Elsevier B.V. All rights reserved.

Pathology and toxicology findings for search-and-rescue dogs deployed to the September 11, 2001, terrorist attack sites: initial five-year surveillance.

PubMed

Fitzgerald, Scott D; Rumbeiha, Wilson K; Emmett Braselton, W; Downend, Amanda B; Otto, Cynthia M

2008-07-01

A long-term surveillance study was conducted on 95 search-and-rescue (S&R) dogs deployed to the September 11, 2001, terrorist attack sites; an additional 55 nondeployed S&R dogs served as controls. After 5 years of surveillance, 32% of the deployed dogs have died and 24% of the nondeployed dogs. The mean age at the time of death in these 2 groups of dogs is not significantly different. Causes of death in both groups of dogs include inflammatory, degenerative, and proliferative conditions. No primary pulmonary tumors have been identified to date nor has any significant level of toxicant been found in the tissues from these dogs using assays for general organic compounds and metals or, specifically, for polychlorinated biphenyls. However, significant numbers of both deployed and nondeployed dogs have evidence of inhaled matter as demonstrated by the presence of anthracotic pigments or refractile particulate matter in pulmonary tissue. Although S&R activities in response to the 9/11 terrorist attacks exposed dogs to a wide variety of potentially toxic compounds, to date, these dogs do not appear to suffer from higher mortality or increased pulmonary disease compared with nondeployed dogs. To the authors' knowledge, the current survey represents the first long-term and large-scale survey of the pathology and toxicology of S&R dogs deployed to a major disaster site.

Impact of ammunition and military explosives on human health and the environment.

PubMed

Lima, Débora R S; Bezerra, Marcio L S; Neves, Eduardo B; Moreira, Fátima R

2011-01-01

To review the literature concerning the risks associated with the main xenobiotics contained in military ammunition and explosive residues and damage to human and environmental health. Using "ammunition", "military", "environmental", "health", "explosive", "metal", "TNT", "RDX", "pollution", and "contamination" as search terms, a large database, namely ISI Web of Knowledge and PubMed, was searched for studies on military ammunition and explosive residues from 1989 to 2010. Other sources used to conduct the search included the library of the Toxicology Laboratory of the Center for Workers' Health and Human Ecology (CESTEH) at the National School of Public Health. In total, 15 different combinations were used with the search words above and 708 papers were found. Among them, 76 papers concerned this review. More than 12 references of interest were discovered in the library of the CESTEH. The results were organized into metals, dinitrotoluene, trinitrotoluene (TNT), and royal demolition explosive (RDX), showing their main uses, occurrence in the environment, the current toxic effects to human and environmental health, and remediation possibilities. Because military activities can cause the acute and chronic exposure of human beings, the public administration must aim politics towards suitable environmental management.

Mercury pollution in vegetables, grains and soils from areas surrounding coal-fired power plants

NASA Astrophysics Data System (ADS)

Li, Rui; Wu, Han; Ding, Jing; Fu, Weimin; Gan, Lijun; Li, Yi

2017-05-01

Mercury contamination in food can pose serious health risks to consumers and coal-fired power plants have been identified as the major source of mercury emissions. To assess the current state of mercury pollution in food crops grown near coal-fired power plants, we measured the total mercury concentration in vegetables and grain crops collected from farms located near two coal-fired power plants. We found that 79% of vegetable samples and 67% of grain samples exceeded the PTWI's food safety standards. The mercury concentrations of soil samples were negatively correlated with distances from the studied coal-fired power plants, and the mercury contents in lettuce, amaranth, water spinach, cowpea and rice samples were correlated with the mercury contents in soil samples, respectively. Also, the mercury concentrations in vegetable leaves were much higher than those in roots and the mercury content of vegetable leaves decreased significantly after water rinses. Our calculation suggests that probable weekly intake of mercury for local residents, assuming all of their vegetables and grains are from their own farmland, may exceed the toxicologically tolerable values allowed, and therefore long-term consumptions of these contaminated vegetables and grains may pose serious health risks.

UBIQUITOUS POLLUTANTS FROM CUMULATIVE ...

EPA Pesticide Factsheets

The occurrence of pharmaceuticals and personal care products (PPCPS) as environmental pollutants is a multifaceted issue whose scope continues to become better delineated since the escalation of concerted attention beginning in the 1980s. PPCPs typically occur as trace environmental pollutants (primarily in surface but also in ground waters) as a result of their widespread, continuous, combined usage in a broad range of human and veterinary therapeutic activities and practices. With respect to the risk-assessment paradigm, the growing body of published work has focused primarily on the origin and occurrence of these substances. Comparatively less is known about human and ecological exposure, and even less about the known or even potential hazards associated with exposure to these anthropogenic substances, many of which are highly bioactive. The continually growing, worldwide importance of freshwater resources underscores the need for ensuring that any aggregate or cumulative impacts on water supplies and resultant potential for human or ecological exposure be minimized. This has prompted the more recent investigations on waste treatment processes for one of the major sources of environmental disposition, namely sewage. Despite the paucity of health effects data for long-term, simultaneous exposure to multiple xenobiotics (particularly PPCPS) at low doses (a major toxicological issue that can be described by the