Science.gov

Sample records for 585-429-2264 advanced toxicology

  1. Advanced urine toxicology testing.

    PubMed

    Tenore, Peter L

    2010-10-01

    Urine toxicology screening testing is an important standard of care in the addiction and pain treatment setting, offering a reproducible, unbiased, and accurate laboratory test to monitor patients and provide objective support for clinical observations. It has been shown that physicians do not have proficiency in the ordering or interpretation of these tests. This article is an attempt to respond to that need. Current antibody-based enzymatic immunoassays (EIAs) used for urine toxicology screening are useful to detect classes of drugs (ex., opiate) but cannot determine which specific drug (ex., morphine) is present. Gas chromatography and mass spectroscopy can determine exactly which drugs are present, allowing prescribed (or illicit) opiates and benzodiazepines to be identified. This article will discuss principles and details of opiate and benzodiazepine EIA and gas chromatography and mass spectroscopy urine toxicology testing. The approach to detecting patients attributing positive opiate EIAs to prescription opiates who are using heroin or other opioids will be reviewed. Cases of controlled prescription drugs that do not produce the expected positive urine tests (ex., oxycodone producing negative opiate screening tests) will be discussed. How to differentiate codeine from heroin and the role of poppy seeds in toxicology will be examined. The case of an anti-depressant drug that produces false-positive benzodiazepine results and antibiotics that cause positive opiate urine toxicology results will be reviewed. Common benzodiazepines (ex., clonazepam and lorazepam) that do not reliably produce positive benzodiazepine EIAs will be discussed. The approach to detection and management of all these types of toxicology cases will be reviewed, and it is hoped that the analyses presented will impart an adequate information base to medical providers and staff members of drug treatment and pain centers, enabling them to order and interpret these tests in the clinic more

  2. 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

  3. Advancing toxicology research using in vivo high throughput toxicology with small fish models.

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2017-01-01

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

  5. Functional toxicology: tools to advance the future of toxicity testing

    PubMed Central

    Gaytán, Brandon D.; Vulpe, Chris D.

    2014-01-01

    The increased presence of chemical contaminants in the environment is an undeniable concern to human health and ecosystems. Historically, by relying heavily upon costly and laborious animal-based toxicity assays, the field of toxicology has often neglected examinations of the cellular and molecular mechanisms of toxicity for the majority of compounds—information that, if available, would strengthen risk assessment analyses. Functional toxicology, where cells or organisms with gene deletions or depleted proteins are used to assess genetic requirements for chemical tolerance, can advance the field of toxicity testing by contributing data regarding chemical mechanisms of toxicity. Functional toxicology can be accomplished using available genetic tools in yeasts, other fungi and bacteria, and eukaryotes of increased complexity, including zebrafish, fruit flies, rodents, and human cell lines. Underscored is the value of using less complex systems such as yeasts to direct further studies in more complex systems such as human cell lines. Functional techniques can yield (1) novel insights into chemical toxicity; (2) pathways and mechanisms deserving of further study; and (3) candidate human toxicant susceptibility or resistance genes. PMID:24847352

  6. 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; Oguseitan, Oladele; Rossi, Mark; Thayer, Kristina; Tickner, Joel; Whittaker, Margaret; Zarker, Ken

    2017-03-01

    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 more cost-effective manner than traditional approaches. This article briefly reviews the challenges associated with using predictive toxicology in regulatory AA, then presents four recommendations for its advancement. It recommends using case studies to advance the integration of predictive toxicology into AA; adopting a stepwise process to employing predicative 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 trans-disciplinary 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. This article is protected by copyright. All rights reserved.

  7. 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...

  8. [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.

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

    PubMed

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

    2016-12-01

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

  10. COMPUTATIONAL TOXICOLOGY ADVANCES: EMERGING CAPABILITIES FOR DATA EXPLORATION AND SAR MODEL DEVELOPMENT

    EPA Science Inventory

    Computational Toxicology Advances: Emerging capabilities for data exploration and SAR model development
    Ann M. Richard and ClarLynda R. Williams, National Health & Environmental Effects Research Laboratory, US EPA, Research Triangle Park, NC, USA; email: richard.ann@epa.gov

  11. Pharmacokinetics and toxicology of therapeutic proteins: Advances and challenges

    PubMed Central

    Vugmeyster, Yulia; Xu, Xin; Theil, Frank-Peter; Khawli, Leslie A; Leach, Michael W

    2012-01-01

    Significant progress has been made in understanding pharmacokinetics (PK), pharmacodynamics (PD), as well as toxicity profiles of therapeutic proteins in animals and humans, which have been in commercial development for more than three decades. However, in the PK arena, many fundamental questions remain to be resolved. Investigative and bioanalytical tools need to be established to improve the translation of PK data from animals to humans, and from in vitro assays to in vivo readouts, which would ultimately lead to a higher success rate in drug development. In toxicology, it is known, in general, what studies are needed to safely develop therapeutic proteins, and what studies do not provide relevant information. One of the major complicating factors in nonclinical and clinical programs for therapeutic proteins is the impact of immunogenicity. In this review, we will highlight the emerging science and technology, as well as the challenges around the pharmacokinetic- and safety-related issues in drug development of mAbs and other therapeutic proteins. PMID:22558487

  12. RNA interference: Applications and advances in insect toxicology and insect pest management.

    PubMed

    Kim, Young Ho; Soumaila Issa, Moustapha; Cooper, Anastasia M W; Zhu, Kun Yan

    2015-05-01

    Since its discovery, RNA interference (RNAi) has revolutionized functional genomic studies due to its sequence-specific nature of post-transcriptional gene silencing. In this paper, we provide a comprehensive review of the recent literature and summarize the current knowledge and advances in the applications of RNAi technologies in the field of insect toxicology and insect pest management. Many recent studies have focused on identification and validation of the genes encoding insecticide target proteins, such as acetylcholinesterases, ion channels, Bacillus thuringiensis receptors, and other receptors in the nervous system. RNAi technologies have also been widely applied to reveal the role of genes encoding cytochrome P450 monooxygenases, carboxylesterases, and glutathione S-transferases in insecticide detoxification and resistance. More recently, studies have focused on understanding the mechanism of insecticide-mediated up-regulation of detoxification genes in insects. As RNAi has already shown great potentials for insect pest management, many recent studies have also focused on host-induced gene silencing, in which several RNAi-based transgenic plants have been developed and tested as proof of concept for insect pest management. These studies indicate that RNAi is a valuable tool to address various fundamental questions in insect toxicology and may soon become an effective strategy for insect pest management.

  13. Building Shared Experience to Advance Practical Application of Pathway-Based Toxicology: Liver Toxicity Mode-of-Action

    PubMed Central

    Willett, Catherine; Rae, Jessica Caverly; Goyak, Katy O.; Minsavage, Gary; Westmoreland, Carl; Andersen, Melvin; Avigan, Mark; Duché, Daniel; Harris, Georgina; Hartung, Thomas; Jaeschke, Hartmut; Kleensang, Andre; Landesmann, Brigitte; Martos, Suzanne; Matevia, Marilyn; Toole, Colleen; Rowan, Andrew; Schultz, Terry; Seed, Jennifer; Senior, John; Shah, Imran; Subramanian, Kalyanasundaram; Vinken, Mathieu; Watkins, Paul

    2016-01-01

    Summary A workshop sponsored by the Human Toxicology Project Consortium (HTPC), “Building Shared Experience to Advance Practical Application of Pathway-Based Toxicology: Liver Toxicity Mode-of-Action” brought together experts from a wide range of perspectives to inform the process of pathway development and to advance two prototype pathways initially developed by the European Commission Joint Research Center (JRC): liver-specific fibrosis and steatosis. The first half of the workshop focused on the theory and practice of pathway development; the second on liver disease and the two prototype pathways. Participants agreed pathway development is extremely useful for organizing information and found that focusing the theoretical discussion on a specific AOP is helpful. It is important to include several perspectives during pathway development, including information specialists, pathologists, human health and environmental risk assessors, and chemical and product manufacturers, to ensure the biology is well captured and end use is considered. PMID:24535319

  14. Toxicological and chemical assessment of arsenic-contaminated groundwater after electrochemical and advanced oxidation treatments.

    PubMed

    Radić, Sandra; Crnojević, Helena; Vujčić, Valerija; Gajski, Goran; Gerić, Marko; Cvetković, Želimira; Petra, Cvjetko; Garaj-Vrhovac, Vera; Oreščanin, Višnja

    2016-02-01

    Owing to its proven toxicity and mutagenicity, arsenic is regarded a principal pollutant in water used for drinking. The objective of this study was the toxicological and chemical evaluation of groundwater samples obtained from arsenic enriched drinking water wells before and after electrochemical and ozone-UV-H2O2-based advanced oxidation processes (EAOP). For this purpose, acute toxicity test with Daphnia magna and chronic toxicity test with Lemna minor L. were employed as well as in vitro bioassays using human peripheral blood lymphocytes (HPBLs). Several oxidative stress parameters were estimated in L.minor. Physicochemical analysis showed that EAOP treatment was highly efficient in arsenic but also in ammonia and organic compound removal from contaminated groundwater. Untreated groundwater caused only slight toxicity to HPBLs and D. magna in acute experiments. However, 7-day exposure of L. minor to raw groundwater elicited genotoxicity, a significant growth inhibition and oxidative stress injury. The observed genotoxicity and toxicity of raw groundwater samples was almost completely eliminated by EAOP treatment. Generally, the results obtained with L. minor were in agreement with those obtained in the chemical analysis suggesting the sensitivity of the model organism in monitoring of arsenic-contaminated groundwater. In parallel to chemical analysis, the implementation of chronic toxicity bioassays in a battery is recommended in the assessment of the toxic and genotoxic potential of such complex mixtures.

  15. Some critical issues and concerns related to research advances on toxicology of chemical mixtures.

    PubMed Central

    Yang, R S

    1998-01-01

    This paper addresses some of the issues and concerns on research advances on the toxicology of chemical mixtures. Emphases will be selectively given to the following questions and answers: Can mechanistic studies be conducted on chemical mixtures? The fact that any studies, including mechanistic studies, of single chemicals are really the study of the parent chemical plus its metabolites underscores the relevance of mechanistic studies on chemical mixtures. Can predictions be made on the health effects of chemical mixtures? Some successes are already evident in the literature on simpler chemical mixtures. For more complex mixtures, it is possible and we propose an approach here. What can we learn from other disciplines (the importance of interdisciplinary collaboration)? Two aspects, the knowledge and methodologies available in clinical pharmacology and the latest advances in structure-oriented lumping in chemical engineering, are discussed in detail. Unrepeatable results: The possibility of magnification of biologic variability because of low-level exposures to chemical mixtures is suggested with special reference to some known examples, including the controversial study on synergistic interactions of endocrine disruptors. Is the driving force for scientific investigations on chemical mixtures the legislative and regulatory atmosphere? Two laws with chemical mixtures specifically in the language are quoted and discussed. Their implications regarding research funding and activities are described. What are the pitfalls of applying for research funding on investigating chemical mixtures? The dilemma at least one investigator faces in pursuing research funding is elaborated. The questions and issues listed above are not all inclusive, but they represent some of the aspects that need to be brought into the open in the scientific community for discussion and/or debate. Thus, the primary objective of this paper is to provide some momentum for the beginning of a fruitful

  16. [Research advances on eco-chemical behaviors and toxicological effects of cadmium in root-soil interface].

    PubMed

    Jin, Caixia; Zhou, Qixing; Sun, Ruilian; Ren, Liping

    2005-08-01

    Many active substances such as organic acids and enzymes excreted by living plant roots could induce a great difference of Eh and pH values between root-soil interface and non-rhizosphere soil, forming a special root-soil interface miniature environment. As a mini-type ecological area with most frequent exchanges of substances, root-soil interface plays a crucial role in their absorption, transformation, migration and eco-toxicological effects. In this paper, the eco-chemical behaviors of Cd in root-soil interface affected by the change of pH, Eh and root secretion, and its eco-toxicological effects on microorganisms and enzymes in root-soil interface were reviewed, based on the related research advances in recent decade. The shortages in relevant fields were pointed out, and the scientific problems to be researched in the future were suggested.

  17. Advances in Toxico-Cheminformatics: Supporting a New Paradigm for Predictive Toxicology

    EPA Science Inventory

    EPA’s National Center for Computational Toxicology is building capabilities to support a new paradigm for toxicity screening and prediction through the harnessing of legacy toxicity data, creation of data linkages, and generation of new high-throughput screening (HTS) data. The D...

  18. Recent advances of liquid chromatography-(tandem) mass spectrometry in clinical and forensic toxicology - An update.

    PubMed

    Remane, Daniela; Wissenbach, Dirk K; Peters, Frank T

    2016-09-01

    Liquid chromatography (LC) coupled to mass spectrometry (MS) or tandem mass spectrometry (MS/MS) is a well-established and widely used technique in clinical and forensic toxicology as well as doping control especially for quantitative analysis. In recent years, many applications for so-called multi-target screening and/or quantification of drugs, poisons, and or their metabolites in biological matrices have been developed. Such methods have proven particularly useful for analysis of so-called new psychoactive substances that have appeared on recreational drug markets throughout the world. Moreover, the evolvement of high resolution MS techniques and the development of data-independent detection modes have opened new possibilities for applications of LC-(MS/MS) in systematic toxicological screening analysis in the so called general unknown setting. The present paper will provide an overview and discuss these recent developments focusing on the literature published after 2010.

  19. 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.

  20. Advances in forensic toxicology for establishing causality between Great Lakes epizootics and specific persistent toxic chemicals

    SciTech Connect

    Gilbertson, M.

    1997-09-01

    Populations of fish, wildlife, and humans in the Great Lakes basin have been injured during this century by exposures to organochlorine pollutants such as PCBs and dioxin. The evidence presented by scientists working on these outbreaks of chemically induced disease has been received with skepticism among officials, who have expressed a desire for a proven cause and effect before further costly regulatory and remedial action is taken. Scientists have adapted epidemiological criteria to infer causal relationships between the injury and exposures to specific chemicals. These forensic statements are different from traditional toxicological statements about potential effects. There is a priority need to institutionalize this methodology within governments to complement established risk assessment techniques.

  1. Toxicology: then and now.

    PubMed

    Langman, Loralie J; Kapur, Bhushan M

    2006-05-01

    Toxicology is "the science of poisons"; more specifically the chemical and physical properties of poisons, their physiological or behavioral effects on living organisms, qualitative, and quantitative methods for their analysis and the development of procedures for the treatment of poisoning. Although the history of poisons dates to the earliest times, the study and the science of toxicology can be traced to Paracelsus (1493-1541) and Orfila (1757-1853). Modern toxicology is characterized by sophisticated scientific investigation and evaluation of toxic exposures. The 20th century is marked by an advanced level of understanding of toxicology. DNA and various biochemicals that maintain cellular functions were discovered. Our level of knowledge of toxic effects on organs and cells is now being revealed at the molecular level. This paper will review the historical progress of clinical and forensic toxicology by exploring analytical techniques in drug analysis, differing biological matrices, clinical toxicology, therapeutic drug management, workplace drug testing, and pharmacodynamic monitoring and pharmacogenetics.

  2. Advanced Clinical Imaging and Tissue-based Biomarkers of the Eye for Toxicology Studies in Minipigs.

    PubMed

    Atzpodien, Elke-Astrid; Jacobsen, Bjoern; Funk, Juergen; Altmann, Bernd; Silva Munoz, Manuel A; Singer, Thomas; Gyger, Cyrill; Hasler, Pascal; Maloca, Peter

    2016-04-01

    There is increased interest to use minipigs in ocular toxicology studies due to their anatomical similarities with human eyes and as a substitute for nonhuman primates. This requires adaptation of enhanced optical coherence tomography (OCT) techniques and of ocular relevant immunohistochemistry (IHC) or in situ hybridization (ISH) markers to porcine eyes. In this study, OCT and OCT angiography (AngioOCT) were performed on adult Göttingen minipigs. To increase structural information on retinal and choroidal vasculature, OCT data were speckle denoized and choroidal blood vessels were segmented with threshold filtering. In addition, we established a set of IHC and ISH markers on Davidson's fixed paraffin-embedded minipig eyes: neurofilament-160, neuronal nuclei, calretinin, protein kinase C-α, vimentin, glial fibrillary acidic protein, glutamine synthetase, ionized calcium-binding adaptor molecule-1, rhodopsin, synaptophysin, postsynaptic density protein-95, retinal pigment epithelium (RPE)-specific protein-65, von Willebrand factor, α-smooth muscle actin, desmin, and Ki-67, thus enabling visualization of retinal neuronal and glial cells, photoreceptors, synapses, RPE, blood vessels, myocytes, macrophages, or cell proliferation. Using ISH, transcripts of vascular endothelial growth factor A, angiopoietin-2, and endothelial tyrosine kinase were visualized. This article describes for the first time in minipig eyes speckle noise-free OCT, AngioOCT, and a set of IHC/ISH markers on Davidson's fixed paraffin-embedded tissues and helps to establish the minipig for ocular toxicology and pharmacology studies.

  3. Recent Advances in Particulate Matter and Nanoparticle Toxicology: A Review of the In Vivo and In Vitro Studies

    PubMed Central

    Nemmar, Abderrahim; Holme, Jørn A.; Rosas, Irma; Schwarze, Per E.

    2013-01-01

    Epidemiological and clinical studies have linked exposure to particulate matter (PM) to adverse health effects, which may be registered as increased mortality and morbidity from various cardiopulmonary diseases. Despite the evidence relating PM to health effects, the physiological, cellular, and molecular mechanisms causing such effects are still not fully characterized. Two main approaches are used to elucidate the mechanisms of toxicity. One is the use of in vivo experimental models, where various effects of PM on respiratory, cardiovascular, and nervous systems can be evaluated. To more closely examine the molecular and cellular mechanisms behind the different physiological effects, the use of various in vitro models has proven to be valuable. In the present review, we discuss the current advances on the toxicology of particulate matter and nanoparticles based on these techniques. PMID:23865044

  4. Advancing toxicology in RiskMAPP: setting ADEs based on the subsequent drug substance.

    PubMed

    Bercu, Joel P; Sharnez, Rizwan; Dolan, David G

    2013-02-01

    Cleaning validation programs are developed to demonstrate acceptable carryover of drug substances/products when multiple drug substances are manufactured in shared process equipment. The International Society of Pharmaceutical Engineers (ISPE) developed a guidance document in 2010 describing the Risk-Based Manufacture of Pharmaceutical Products (referred to as RiskMAPP) (ISPE, 2010). This guidance document developed the concept of an acceptable daily exposure (ADE), which is the toxicologically acceptable daily dose for the first drug substance used in processing drug equipment (DS(A)) without prior knowledge of the subsequent drug substance (DS(B)). This paper discusses an extension of the ADE methodology called the product-specific ADE (PSADE) which is derived when DS(B) is known. Four case studies demonstrate examples in which the PSADE can be scientifically supported in lieu of the ADE and highlight some limitations in its application. The PSADE approach can be used to justify higher acceptance limits for cleaning validation when the ADE based acceptance limits are below the process capability limit of the cleaning process or limit of quantitation of the analytical method.

  5. Proteomics for systems toxicology

    PubMed Central

    Titz, Bjoern; Elamin, Ashraf; Martin, Florian; Schneider, Thomas; Dijon, Sophie; Ivanov, Nikolai V.; Hoeng, Julia; Peitsch, Manuel C.

    2014-01-01

    Current toxicology studies frequently lack measurements at molecular resolution to enable a more mechanism-based and predictive toxicological assessment. Recently, a systems toxicology assessment framework has been proposed, which combines conventional toxicological assessment strategies with system-wide measurement methods and computational analysis approaches from the field of systems biology. Proteomic measurements are an integral component of this integrative strategy because protein alterations closely mirror biological effects, such as biological stress responses or global tissue alterations. Here, we provide an overview of the technical foundations and highlight select applications of proteomics for systems toxicology studies. With a focus on mass spectrometry-based proteomics, we summarize the experimental methods for quantitative proteomics and describe the computational approaches used to derive biological/mechanistic insights from these datasets. To illustrate how proteomics has been successfully employed to address mechanistic questions in toxicology, we summarized several case studies. Overall, we provide the technical and conceptual foundation for the integration of proteomic measurements in a more comprehensive systems toxicology assessment framework. We conclude that, owing to the critical importance of protein-level measurements and recent technological advances, proteomics will be an integral part of integrative systems toxicology approaches in the future. PMID:25379146

  6. 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

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

    SciTech Connect

    Gunasekar, Palur G.; Stanek, Lindsay W.

    2011-07-15

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

  8. 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)

  9. 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, ...

  10. Developmental Toxicology##

    EPA Science Inventory

    Developmental toxicology encompasses the study of developmental exposures, pharmacokinetics, mechanisms, pathogenesis, and outcomes potentially leading to adverse health effects. Manifestations of developmental toxicity include structural malformations, growth retardation, functi...

  11. Spaceflight Toxicology

    NASA Technical Reports Server (NTRS)

    Meyers, Valerie

    2008-01-01

    This viewgraph presentation provides a review of NASA Johnson Space Center's Toxicology program. The mission of this program is to protect crews from toxic exposures during spaceflight. The presentation reviews some of the health hazards. A toxicological hazard level chart is presented that reviews the rating of hazard level, irritancy, systemic effects and containability. The program also participates in the Lunar Airborne Dust Toxicity Advisory Group.

  12. 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

  13. Toxicology Education Foundation

    MedlinePlus

    ... public understanding of toxicology through access to objective, science-based information on the safety of chemicals and ... as an Independent Charity! What is Toxicology? The Science Toxicology is the study of the adverse effects ...

  14. 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.

  15. Alcohols toxicology

    SciTech Connect

    Wimer, W.W.; Russell, J.A.; Kaplan, H.L.

    1984-01-01

    A comprehensive reference volume which summarizes literature reports of the known consequences of human and animal contact with alcohols and alcohol-derived substances is presented. Following a discussion of alcohol nomenclature and a brief history of alcohols, the authors have provided detailed chapters on the toxicology of methanol, ethanol, normal and isopropanol, and the butanols. Properties of these alcohols are compared; industrial hygiene and exposure limits are discussed. Additional sections are included covering processing and production technology and exhaust emissions studies. Of particular interest are the section containing abstracts and synopses of principal works and the extensive bibliography of studies dating from the 1800s. 331 references, 26 figures, 56 tables

  16. [Food toxicology].

    PubMed

    Würzner, H P

    1984-02-01

    The complex problems of food toxicology and especially of mutagenesis and carcinogenesis require continuing efforts for a better understanding of the mechanisms, risk evaluation and prevention. Essential progress was the recognition of mutation. In vitro tests now provide reproducible results within a short time. Risk evaluation remains a difficult problem, since is has not been possible yet to establish thresholds values for genotoxic substances. However, threshold levels for carcinogen promoters gain increasing importance as demonstrated for 3 representative classes of substances: mycotoxines , nitrosamines and pesticides.

  17. Behavioral toxicology

    SciTech Connect

    Needleman, H.L.

    1995-09-01

    The new fields of behavioral toxicology and behavioral teratology investigate the outcome of specific toxic exposures in humans and animals on learning, memory, and behavioral characteristics. Three important classes of behavioral neurotoxicants are metals, solvents, and pesticides. The clearest data on the deleterious effects of prenatal exposure to toxicants comes from the study of two metals, lead and mercury, and form epidemiological investigations of the effects of alcohol taken during pregnancy. Less complete data are available for two other groups of agents, solvents, and pesticides. What we do know about their effects on the fetal brain is convincing enough to make us demand caution in their distribution. 15 refs.

  18. Computational Toxicology at the US EPA

    EPA Science Inventory

    Computational toxicology is the application of mathematical and computer models to help assess chemical hazards and risks to human health and the environment. Supported by advances in informatics, high-throughput screening (HTS) technologies, and systems biology, EPA is developin...

  19. 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.

  20. Systems toxicology.

    PubMed

    Hartung, Thomas; van Vliet, Erwin; Jaworska, Joanna; Bonilla, Leo; Skinner, Nigel; Thomas, Russell

    2012-01-01

    The need for a more mechanistic understanding of the ways in which chemicals modulate biological pathways is urgent if we are to identify and better assess safety issues relating to a wide range of substances developed by the pharmaceutical, chemical, agri-bio, and cosmetic industries. Omics technologies provide a valuable opportunity to refine existing methods and provide information for so-called integrated testing strategies via the creation of signatures of toxicity. By mapping these signatures to underlying pathways of toxicity, some of which have been identified by toxicologists over the last few decades, and bringing them together with pathway information determined from biochemistry and molecular biology, a "systems toxicology" approach will enable virtual experiments to be conducted that can improve the prediction of hazard and the assessment of compound toxicity.

  1. 2007 TOXICOLOGY AND RISK ASSESSMENT ...

    EPA Pesticide Factsheets

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

  2. Forensic toxicology.

    PubMed

    Drummer, Olaf H

    2010-01-01

    Forensic toxicology has developed as a forensic science in recent years and is now widely used to assist in death investigations, in civil and criminal matters involving drug use, in drugs of abuse testing in correctional settings and custodial medicine, in road and workplace safety, in matters involving environmental pollution, as well as in sports doping. Drugs most commonly targeted include amphetamines, benzodiazepines, cannabis, cocaine and the opiates, but can be any other illicit substance or almost any over-the-counter or prescribed drug, as well as poisons available to the community. The discipline requires high level skills in analytical techniques with a solid knowledge of pharmacology and pharmacokinetics. Modern techniques rely heavily on immunoassay screening analyses and mass spectrometry (MS) for confirmatory analyses using either high-performance liquid chromatography or gas chromatography as the separation technique. Tandem MS has become more and more popular compared to single-stage MS. It is essential that analytical systems are fully validated and fit for the purpose and the assay batches are monitored with quality controls. External proficiency programs monitor both the assay and the personnel performing the work. For a laboratory to perform optimally, it is vital that the circumstances and context of the case are known and the laboratory understands the limitations of the analytical systems used, including drug stability. Drugs and poisons can change concentration postmortem due to poor or unequal quality of blood and other specimens, anaerobic metabolism and redistribution. The latter provides the largest handicap in the interpretation of postmortem results.

  3. 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...

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

    NASA Technical Reports Server (NTRS)

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

    2000-01-01

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

  5. Genetic toxicology: web resources.

    PubMed

    Young, Robert R

    2002-04-25

    Genetic toxicology is the scientific discipline dealing with the effects of chemical, physical and biological agents on the heredity of living organisms. The Internet offers a wide range of online digital resources for the field of Genetic Toxicology. The history of genetic toxicology and electronic data collections are reviewed. Web-based resources at US National Library of Medicine (NLM), including MEDLINE, PUBMED, Gateway, Entrez, and TOXNET, are discussed. Search strategies and Medical Subject Headings (MeSH) are reviewed in the context of genetic toxicology. The TOXNET group of databases are discussed with emphasis on those databases with genetic toxicology content including GENE-TOX, TOXLINE, Hazardous Substances Data Bank, Integrated Risk Information System, and Chemical Carcinogenesis Research Information System. Location of chemical information including chemical structure and linkage to health and regulatory information using CHEMIDPLUS at NLM and other databases is reviewed. Various government agencies have active genetic toxicology research programs or use genetic toxicology data to assist fulfilling the agency's mission. Online resources at the US Food and Drug Administration (FDA), the US Environmental Protection Agency (EPA), the National Institutes of Environmental Health Sciences, and the National Toxicology Program (NTP) are outlined. Much of the genetic toxicology for pharmaceuticals, industrial chemicals and pesticides that is performed in the world is regulatory-driven. Regulatory web resources are presented for the laws mandating testing, guidelines on study design, Good Laboratory Practice (GLP) regulations, and requirements for electronic data collection and reporting. The Internet provides a range of other supporting resources to the field of genetic toxicology. The web links for key professional societies and journals in genetic toxicology are listed. Distance education, educational media resources, and job placement services are also

  6. Transgenic mice in developmental toxicology

    SciTech Connect

    Woychik, R.P.

    1992-01-01

    Advances in molecular biology and embryology are being utilized for the generation of transgenic mice, animals that contain specific additions, deletions, or modifications of genes or sequences in their DNA. Mouse embryonic stem cells and homologous recombination procedures have made it possible to target specific DNA structural alterations to highly localized region in the host chromosomes. The majority of the DNA structural rearrangements in transgenic mice can be passed through the germ line and used to establish new genetic traits in the carrier animals. Since the use of transgenic mice is having such an enormous impact on so many areas of mammalian biological research, including developmental toxicology, the objective of this review is to briefly describe the fundamental methodologies for generating transgenic mice and to describe one particular application that has direct relevance to the field of genetic toxicology.

  7. Transgenic mice in developmental toxicology

    SciTech Connect

    Woychik, R.P.

    1992-12-31

    Advances in molecular biology and embryology are being utilized for the generation of transgenic mice, animals that contain specific additions, deletions, or modifications of genes or sequences in their DNA. Mouse embryonic stem cells and homologous recombination procedures have made it possible to target specific DNA structural alterations to highly localized region in the host chromosomes. The majority of the DNA structural rearrangements in transgenic mice can be passed through the germ line and used to establish new genetic traits in the carrier animals. Since the use of transgenic mice is having such an enormous impact on so many areas of mammalian biological research, including developmental toxicology, the objective of this review is to briefly describe the fundamental methodologies for generating transgenic mice and to describe one particular application that has direct relevance to the field of genetic toxicology.

  8. Aquatic toxicology: fact or fiction

    SciTech Connect

    Macek, K.J.

    1980-02-01

    The science of aquatic toxicology is a relatively new science. The development of the field of aquatic toxicology since 1930 is traced. The state of the art of aquatic toxicology compared with that of classical toxicology is evaluated. The science of aquatic toxicology is expected to undergo a significant period of rapid growth and development, leading ultimately to the formation of a mature science.

  9. Systems Toxicology: Real World Applications and Opportunities.

    PubMed

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

    2017-03-31

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

  10. Microbiology & Toxicology: Space Environment

    NASA Video Gallery

    One key aspect in maintaining crew health and performance during spaceflight missions is the provision of a habitable environment with acceptably low concentrations of microbiological and toxicolog...

  11. Food for thought ... A toxicology ontology roadmap.

    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

    Foreign substances can have a dramatic and unpredictable adverse effect on human health. In the development of new therapeutic agents, it is essential that the potential adverse effects of all candidates be identified as early as possible. The field of predictive toxicology strives to profile the potential for adverse effects of novel chemical substances before they occur, both with traditional in vivo experimental approaches and increasingly through the development of in vitro and computational methods which can supplement and reduce the need for animal testing. To be maximally effective, the field needs access to the largest possible knowledge base of previous toxicology findings, and such results need to be made available in such a fashion so as to be interoperable, comparable, and compatible with standard toolkits. This necessitates the development of open, public, computable, and standardized toxicology vocabularies and ontologies so as to support the applications required by in silico, in vitro, and in vivo toxicology methods and related analysis and reporting activities. Such ontology development will support data management, model building, integrated analysis, validation and reporting, including regulatory reporting and alternative testing submission requirements as required by guidelines such as the REACH legislation, leading to new scientific advances in a mechanistically-based predictive toxicology. Numerous existing ontology and standards initiatives can contribute to the creation of a toxicology ontology supporting the needs of predictive toxicology and risk assessment. Additionally, new ontologies are needed to satisfy practical use cases and scenarios where gaps currently exist. Developing and integrating these resources will require a well-coordinated and sustained effort across numerous stakeholders engaged in a public-private partnership. In this communication, we set out a roadmap for the development of an integrated toxicology ontology

  12. Operational Toxicology Research

    DTIC Science & Technology

    2006-08-01

    AFRL-HE-WP-TR-2006-0082 Operational Toxicology Research Darol E. Dodd MaryAnn Angell Alion Science and Technology Wright-Patterson AFB, OH 45433...CONTRACT NUMBER Operational Toxicology Research Contract F336l5-00-C-6060 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHORISI 5d. PROJECT NUMBER...AFRLlWS 06-1865 14. ABSTRACT This is a final report for the Operational Toxicology Research (OTR) Contract F33615-00-C-6060 initiated in March, 2001 to

  13. Data governance in predictive toxicology: A review

    PubMed Central

    2011-01-01

    Background Due to recent advances in data storage and sharing for further data processing in predictive toxicology, there is an increasing need for flexible data representations, secure and consistent data curation and automated data quality checking. Toxicity prediction involves multidisciplinary data. There are hundreds of collections of chemical, biological and toxicological data that are widely dispersed, mostly in the open literature, professional research bodies and commercial companies. In order to better manage and make full use of such large amount of toxicity data, there is a trend to develop functionalities aiming towards data governance in predictive toxicology to formalise a set of processes to guarantee high data quality and better data management. In this paper, data quality mainly refers in a data storage sense (e.g. accuracy, completeness and integrity) and not in a toxicological sense (e.g. the quality of experimental results). Results This paper reviews seven widely used predictive toxicology data sources and applications, with a particular focus on their data governance aspects, including: data accuracy, data completeness, data integrity, metadata and its management, data availability and data authorisation. This review reveals the current problems (e.g. lack of systematic and standard measures of data quality) and desirable needs (e.g. better management and further use of captured metadata and the development of flexible multi-level user access authorisation schemas) of predictive toxicology data sources development. The analytical results will help to address a significant gap in toxicology data quality assessment and lead to the development of novel frameworks for predictive toxicology data and model governance. Conclusions While the discussed public data sources are well developed, there nevertheless remain some gaps in the development of a data governance framework to support predictive toxicology. In this paper, data governance is

  14. Evolution of toxicology information systems

    SciTech Connect

    Wassom, J.S.; Lu, P.Y.

    1990-12-31

    Society today is faced with new health risk situations that have been brought about by recent scientific and technical advances. Federal and state governments are required to assess the many potential health risks to exposed populations from the products (chemicals) and by-products (pollutants) of these advances. Because a sound analysis of any potential health risk should be based on the use of relevant information, it behooves those individuals responsible for making the risk assessments to know where to obtain needed information. This paper reviews the origins of toxicology information systems and explores the specialized information center concept that was proposed in 1963 as a means of providing ready access to scientific and technical information. As a means of illustrating this concept, the operation of one specialized information center (the Environmental Mutagen Information Center at Oak Ridge National Laboratory) will be discussed. Insights into how toxicological information resources came into being, their design and makeup, will be of value to those seeking to acquire information for risk assessment purposes. 7 refs., 1 fig., 4 tabs.

  15. National Toxicology Program

    MedlinePlus

    ... Initiative Public Health Public Health Impact Report on Carcinogens Evaluation of Alternative Toxicological Methods Health Assessment and ... 04/2016 HHS Releases the 14th Report on Carcinogens 11/03/2016 Board of Scientific Counselors Meeting ...

  16. Downloadable Computational Toxicology Data

    EPA Pesticide Factsheets

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

  17. 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...

  18. National Toxicology Program

    MedlinePlus

    ... Initiative Public Health Public Health Impact Report on Carcinogens Evaluation of Alternative Toxicological Methods Health Assessment and ... Tables for Peer Review Reports & Publications Report on Carcinogens Search Substances Studied by NTP Tox21 NTP at ...

  19. Nanosilver: application and novel aspects of toxicology.

    PubMed

    Schluesener, Jan K; Schluesener, Hermann J

    2013-04-01

    Nanomaterials are a challenge to toxicology. The high diversity of novel materials and products will require extensive expertize for evaluation and regulatory efforts. Nanomaterials are of substantial scientific and economic potential. Here, we will focus on nanosilver, a material not only with medical applications, but a rapidly increasing use in surprisingly many products. Consequently, toxicological evaluation has to cover an increasing range of complex topics. The toxicology of nanosilver is advancing rapidly; regulatory efforts by Federal Drug Agency and European Environment Protection Agencies are substantial. Current toxicological data, ranging from in vitro studies with cell lines to rodent experiments and ecological evaluation, are numerous, and many groups are providing continuously new data. However, standard classification based on nanosize only is neglecting nanoshape, which adds another level of complexity to the analysis of biological effects. A surprising neglect in nanosilver toxicology so far is the analysis of effects of nanosilver on amyloidosis. Amyloid diseases are widespread in humans and a severe health hazard. The known potential of silver to stimulate amyloidosis in rodents will require a timely and balanced evaluation of nanosilvers.

  20. Aerospace Toxicology and Microbiology

    NASA Technical Reports Server (NTRS)

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

    2007-01-01

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

  1. Aviation combustion toxicology: an overview.

    PubMed

    Chaturvedi, Arvind K

    2010-01-01

    Aviation combustion toxicology is a subspecialty of the field of aerospace toxicology, which is composed of aerospace and toxicology. The term aerospace, that is, the environment extending above and beyond the surface of the Earth, is also used to represent the combined fields of aeronautics and astronautics. Aviation is another term interchangeably used with aerospace and aeronautics and is explained as the science and art of operating powered aircraft. Toxicology deals with the adverse effects of substances on living organisms. Although toxicology borrows knowledge from biology, chemistry, immunology, pathology, physiology, and public health, the most closely related field to toxicology is pharmacology. Economic toxicology, environmental toxicology, and forensic toxicology, including combustion toxicology, are the three main branches of toxicology. In this overview, a literature search for the period of 1960-2007 was performed and information related to aviation combustion toxicology collected. The overview included introduction; combustion, fire, and smoke; smoke gas toxicity; aircraft material testing; fire gases and their interactive effects; result interpretation; carboxyhemoglobin and blood cyanide ion levels; pyrolytic products of aircraft engine oils, fluids, and lubricants; and references. This review is anticipated to be an informative resource for aviation combustion toxicology and fire-related casualties.

  2. Oral-toxicology

    PubMed Central

    Gowda, B. K. Charan; Sundharam, B. Sivapatha; Mahadesh, Jyothi; Mukund

    2014-01-01

    Forensic toxicology deals with the investigation of toxic substances, poisonous products or with the environmental chemicals. This field of science helps to identify poison substance and hazardous chemicals. Forensic toxicology deals with the way that substances are absorbed, distributed or eliminated in the body – the metabolism of substances. This paper reviews the manifestations that each poisonous substance presents concentrating toward the commonly used poisonous substance especially in India. It also explains the Indian Penal Code, which is main criminal code intended to cover all substantive aspects of criminal law regarding poison. PMID:24696586

  3. 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.

  4. Toxicology and Chemical Safety.

    ERIC Educational Resources Information Center

    Hall, Stephen K.

    1983-01-01

    Topics addressed in this discussion of toxicology and chemical safety include routes of exposure, dose/response relationships, action of toxic substances, and effects of exposure to chemicals. Specific examples are used to illustrate the principles discussed. Suggests prudence in handling any chemicals, whether or not toxicity is known. (JN)

  5. Behavioral Screening for Toxicology

    EPA Science Inventory

    Screening for behavioral toxicity, or neurotoxicity, has been in use for decades; however, only in the past 20 years has this become a standard practice in toxicology. Current screening batteries, such as the functional observational battery (FOB), are derived from protocols use...

  6. Regulatory forum opinion piece: Tox21 and toxicologic pathology.

    PubMed

    Bucher, John R

    2013-01-01

    Tox21 is a transformative effort on the part of several U.S. Federal agencies (the National Toxicology Program/National Institute of Environmental Health Sciences [NTP], the National Institutes of Health (NIH) Chemical Genomics Center/National Human Genome Research Institute [NCGC; now called the NIH Center for Translational Therapeutics, National Center for Advancing Translational Sciences] the Environmental Protection Agency's (EPA) National Center for Computational Toxicology, and recently the Food and Drug Administration) that are partnering to fundamentally change the science of safety toxicology. These agencies bring a comprehensive suite of capabilities and are working diligently together to develop, evaluate, and ultimately implement a new safety assessment paradigm. Toxicologic pathology has an important ongoing role in establishing the validity of this transformation, and may ultimately benefit as a discipline through an enhanced understanding of chemically induced disease mechanisms.

  7. Progress in nickel toxicology

    SciTech Connect

    Brown, S.S.; Sunderman, F.W.

    1985-01-01

    The Third International Conference on Nickel Metabolism and Toxicology was held at the PLM St Jacques Hotel in Paris in September 1984, under the joint sponsorship of the International Union of Pure and Applied Chemistry (IUPAC), the Association of Clinical Scientists, and the Nickel Producers Environmental Research Association (NiPERA). The Paris Conference was attended by 150 participants from 19 countries, including many of the world's authorities on nickel in the areas of trace analysis, biochemistry, radiochemistry, pharmacology, toxicology, pathology, immunology, industrial hygiene, epidemiology, occupational health and clinical medicine. The text of the Richard T. Barton memorial lecture and synopses of the scientific papers that were presented at the Conference are published in this volume.

  8. [Toxicology of the hydrosphere].

    PubMed

    Tolokontsev, N A

    1991-01-01

    The data are available on a superexponential growth in the production of chemicals the penetration of which into the earth surface water essentially deteriorates its quality. In addition to anthropogenic substances (biogens and xenobiotics alien to biosphere), hydrosphere is contaminated with algotoxin products of hydrobionts. The paper focuses on two important problems of hydrospheric toxicology--toxicological aspects of progressively growing process of anthropogenic eutrophia of the earth surface water and toxic damage to photosynthesis primary products. It is concluded that predominant ideas of the leading role of phosphorus in eutrophia and relevant theories as well as water quality standards based on trophism of water basin require correction. When assessed by trophism, water may appear oligotrophic but unsafe for population being contaminated with toxic substances and thus unfit for drinking, household and recreation purposes.

  9. Novel and future applications of microarrays in toxicological research.

    PubMed

    Gant, Timothy W

    2007-08-01

    Microarray technologies have both fascinated and frustrated the toxicological community since their introduction around a decade ago. Fascination arose from the possibility offered by the technology to gain a profound insight into the cellular response to chemically mediated stress, and the potential that this genomic signature would be indicative of the biological mechanism by which that stress was induced. Frustrations have arisen primarily from technical factors such as data variance, the requirement for the application of advanced statistical and mathematical analysis, and difficulties associated with actually recognising signature gene expression patterns, and discerning mechanisms. Toxicogenomics was predicted to make toxicological assessment and extrapolation easier, faster and cheaper. The reality has been somewhat different; toxicogenomics is difficult. However, its potential when properly applied has been indicated by some well designed toxicogenomics studies, particularly in the differentiation of genotoxins from non-genotoxins. Technology waits though for no man. While the toxicological community has been working to apply transcriptomics (mRNA levels) in toxicology, the technology has moved beyond this application into new arenas. Some have application to toxicology and are reviewed here, except transcriptomics which has been extensively written about before. This review discusses the application of microarray technologies applied to the genome per se (amplifications, deletions, epigenetic change), mRNA translation and its control mechanisms through miRNA. Which of the new genomics technoï¿(1/2)logies will find most application in toxicology? In the opinion of the author there are three potentially major applications: i) arrayCGH in assessment and recognition of genotoxicity; ii) epigenetic assessment in developmental and transgenerational toxicology; and iii) miRNA assessment in all toxicology types, but particularly developmental toxicology.

  10. Toxicological Benchmarks for Wildlife

    SciTech Connect

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

    1993-01-01

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

  11. 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

  12. Ion channels in toxicology.

    PubMed

    Restrepo-Angulo, Iván; De Vizcaya-Ruiz, Andrea; Camacho, Javier

    2010-08-01

    Ion channels play essential roles in human physiology and toxicology. Cardiac contraction, neural transmission, temperature sensing, insulin release, regulation of apoptosis, cellular pH and oxidative stress, as well as detection of active compounds from chilli, are some of the processes in which ion channels have an important role. Regulation of ion channels by several chemicals including those found in air, water and soil represents an interesting potential link between environmental pollution and human diseases; for instance, de novo expression of ion channels in response to exposure to carcinogens is being considered as a potential tool for cancer diagnosis and therapy. Non-specific binding of several drugs to ion channels is responsible for a huge number of undesirable side-effects, and testing guidelines for several drugs now require ion channel screening for pharmaceutical safety. Animal toxins targeting human ion channels have serious effects on the population and have also provided a remarkable tool to study the molecular structure and function of ion channels. In this review, we will summarize the participation of ion channels in biological processes extensively used in toxicological studies, including cardiac function, apoptosis and cell proliferation. Major findings on the adverse effects of drugs on ion channels as well as the regulation of these proteins by different chemicals, including some pesticides, are also reviewed. Association of ion channels and toxicology in several biological processes strongly suggests these proteins to be excellent candidates to follow the toxic effects of xenobiotics, and as potential early indicators of life-threatening situations including chronic degenerative diseases.

  13. Systems Toxicology: From Basic Research to Risk Assessment

    PubMed Central

    2014-01-01

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

  14. [Antidotes in clinical toxicology].

    PubMed

    Hruby, K

    2013-09-01

    This overview describes antidotes, and their clinical pharmacology, that have an established significance in the currently practiced clinical toxicology because of their proven effectiveness in the treatment of serious poisonings. For the proper, efficient, and targeted use of an antidote, pharmacological knowledge is required, which is a central subject of this article. Current data from the literature are used as reference along with the accumulated experiences about possible adverse effects in order to include them in therapeutic considerations. The dosage of antidotes is the subject of several other review articles and is therefore not included in this synopsis.

  15. Molecular Toxicology of Chromatin

    DTIC Science & Technology

    1992-01-01

    FINAL 01 Jan 89 TO 31 Dec 91 4. ITL ANO SUS Y, L RE %UMAS MOLECULAR TOXICOLOGY OF CHROMATIN AFOSR-89-0231 PE - 61102F AUT PR - 2312 TA - A5 Dr Ernest Kun...Waterbury, CT), 2-mercaptoethanol, NAD+, NADPH, nucleo- tides, sodium tungstate , hydrogen peroxide, Tris and MES buffers from Sigma (St. Louis, MO...ml) with sodium tungstate (5.93 g, in 20 ml H20) for 1.5 h followed by extraction of the green product into ethyl acetate, washing with 0.1 N HCl, and

  16. Arsenic Exposure and Toxicology: A Historical Perspective

    PubMed Central

    Hughes, Michael F.; Beck, Barbara D.; Chen, Yu; Lewis, Ari S.; Thomas, David J.

    2011-01-01

    The metalloid arsenic is a natural environmental contaminant to which humans are routinely exposed in food, water, air, and soil. Arsenic has a long history of use as a homicidal agent, but in the past 100 years arsenic, has been used as a pesticide, a chemotherapeutic agent and a constituent of consumer products. In some areas of the world, high levels of arsenic are naturally present in drinking water and are a toxicological concern. There are several structural forms and oxidation states of arsenic because it forms alloys with metals and covalent bonds with hydrogen, oxygen, carbon, and other elements. Environmentally relevant forms of arsenic are inorganic and organic existing in the trivalent or pentavalent state. Metabolism of arsenic, catalyzed by arsenic (+3 oxidation state) methyltransferase, is a sequential process of reduction from pentavalency to trivalency followed by oxidative methylation back to pentavalency. Trivalent arsenic is generally more toxicologically potent than pentavalent arsenic. Acute effects of arsenic range from gastrointestinal distress to death. Depending on the dose, chronic arsenic exposure may affect several major organ systems. A major concern of ingested arsenic is cancer, primarily of skin, bladder, and lung. The mode of action of arsenic for its disease endpoints is currently under study. Two key areas are the interaction of trivalent arsenicals with sulfur in proteins and the ability of arsenic to generate oxidative stress. With advances in technology and the recent development of animal models for arsenic carcinogenicity, understanding of the toxicology of arsenic will continue to improve. PMID:21750349

  17. Toxicology: Old Art, New Science.

    ERIC Educational Resources Information Center

    Timbrell, John A.

    1983-01-01

    Examines the need for a science of toxicology and training at both the undergraduate and graduate levels in response to legislation controlling drugs, food additives and toxic substances in the work environment, and concern about effects on man. Stresses need for putting toxicology on a scientific base with adequate funding. (JM)

  18. Advances in pediatric pharmacology, therapeutics, and toxicology.

    PubMed

    Gonzalez, Daniel; Paul, Ian M; Benjamin, Daniel K; Cohen-Wolkowiez, Michael

    2014-08-01

    In the United States, passage of the FDASIA legislation made BPCA and PREA permanent, no longer requiring reauthorization every 5 years. This landmark legislation also stressed the importance of performing clinical trials in neonates when appropriate. In Europe the Pediatric Regulation, which went into effect in early 2007, also provides a framework for expanding pediatric clinical research. Although much work remains, as a result of greater regulatory guidance more pediatric data are reaching product labels.

  19. Organophosphorus Xenobiotic Toxicology.

    PubMed

    Casida, John E

    2017-01-06

    Originally, organophosphorus (OP) toxicology consisted of acetylcholinesterase inhibition by insecticides and chemical threat agents acting as phosphorylating agents for serine in the catalytic triad, but this is no longer the case. Other serine hydrolases can be secondary OP targets, depending on the OP structure, and include neuropathy target esterase, lipases, and endocannabinoid hydrolases. The major OP herbicides are glyphosate and glufosinate, which act in plants but not animals to block aromatic amino acid and glutamine biosynthesis, respectively, with safety for crops conferred by their expression of herbicide-tolerant targets and detoxifying enzymes from bacteria. OP fungicides, pharmaceuticals including calcium retention agents, industrial chemicals, and cytochrome P450 inhibitors act by multiple noncholinergic mechanisms, often with high potency and specificity. One type of OP-containing fire retardant forms a highly toxic bicyclophosphate γ-aminobutyric acid receptor antagonist upon combustion. Some OPs are teratogenic, mutagenic, or carcinogenic by known mechanisms that can be avoided as researchers expand knowledge of OP chemistry and toxicology for future developments in bioregulation.

  20. Nanotechnology: Toxicologic Pathology

    PubMed Central

    Hubbs, Ann F.; Sargent, Linda M.; Porter, Dale W.; Sager, Tina M.; Chen, Bean T.; Frazer, David G.; Castranova, Vincent; Sriram, Krishnan; Nurkiewicz, Timothy R.; Reynolds, Steven H.; Battelli, Lori A.; Schwegler-Berry, Diane; McKinney, Walter; Fluharty, Kara L.; Mercer, Robert R.

    2015-01-01

    Nanotechnology involves technology, science, and engineering in dimensions less than 100 nm. A virtually infinite number of potential nanoscale products can be produced from many different molecules and their combinations. The exponentially increasing number of nanoscale products will solve critical needs in engineering, science, and medicine. However, the virtually infinite number of potential nanotechnology products is a challenge for toxicologic pathologists. Because of their size, nanoparticulates can have therapeutic and toxic effects distinct from micron-sized particulates of the same composition. In the nanoscale, distinct intercellular and intracellular translocation pathways may provide a different distribution than that obtained by micron-sized particulates. Nanoparticulates interact with subcellular structures including microtubules, actin filaments, centrosomes, and chromatin; interactions that may be facilitated in the nanoscale. Features that distinguish nanoparticulates from fine particulates include increased surface area per unit mass and quantum effects. In addition, some nanotechnology products, including the fullerenes, have a novel and reactive surface. Augmented microscopic procedures including enhanced dark-field imaging, immunofluorescence, field-emission scanning electron microscopy, transmission electron microscopy, and confocal microscopy are useful when evaluating nanoparticulate toxicologic pathology. Thus, the pathology assessment is facilitated by understanding the unique features at the nanoscale and the tools that can assist in evaluating nanotoxicology studies. PMID:23389777

  1. Toxicological properties of metaflumizone.

    PubMed

    Hempel, K; Hess, F G; Bögi, C; Fabian, E; Hellwig, J; Fegert, I

    2007-12-15

    Metaflumizone is a new insecticide developed for crop protection and urban pest control by BASF. Its mammalian toxicological profile was assessed by conducting multiple toxicity studies in the rat, mouse, and dog, covering all relevant endpoints. Metaflumizone is characterized by very low acute toxicity, is not irritating to the eye or the skin and does not possess a potential to induce skin sensitization. The substance also shows relatively low toxicity following subchronic oral or dermal exposure to mammals. In addition, metaflumizone demonstrates low toxicological potential following chronic oral exposure to rats, mice, and dogs. Overall, the lowest no observed adverse effect level (NOAEL) is 12mg/(kgday) from the 1-year chronic dog study. In a battery of in vitro and in vivo mutagenicity assays, the weight-of-the-evidence indicates a lack of potential genotoxicity for metaflumizone. Furthermore, the compound demonstrated a lack of potential oncogenicity in long-term toxicity studies in rats and mice. Results from the rat multi-generation reproductive toxicity study as well as the rat and rabbit developmental toxicity studies indicate that metaflumizone is not selectively toxic to the offspring or fetus, as compared to the parents. Also, metaflumizone is not teratogenic in the rat or rabbit. Lastly, no neurotoxicity could be detected in acute and subchronic neurotoxicity studies in rats.

  2. [Modern toxicology of magnetic nanomaterials].

    PubMed

    Cywińska, Monika A; Grudziński, Ireneusz P

    2012-01-01

    Current advances in nanobiotechnology have led to the development of new field of nanomedicine, which includes many applications of nano(bio)materials for both diagnostic and therapeutic purposes (theranostics). Major expectations and challenges are on bioengineered magnetic nanoparticles when their come to delivering drug compounds, especially to targeting anticancer drugs to specific molecular endpoints in cancer therapy. The unique physicochemical properties of these nanoparticles offer great promise in modern cancer nanomedicine to provide new technological breakthroughs, such as guided drug and gene delivery, magnetic hyperthermia cancer therapy, tissue engineering, cancer cell tracking and molecular magnetic resonance imaging. Along with the expanding interest in bio-engineered magnetic nanoproducts their potential toxicity has become one of the major concerns. To date, a number of recent scientific evidences suggest that certain properties of magnetic nanoparticles (e.g., enhanced reactive area, ability to cross cell membranes, resistance to biodegradation) may amplify their cytotoxic potential relative to bulk non-nanoscale counterparts. In other words, safety assessment developed for ordinary magnetic materials may be of limited use in determining the health and environmental risks of the novel bio-engineered magnetic nanoproducts. In the present paper we discuss the main directions of research conducted to assess the toxicity of magnetic nanocompounds in experimental in vitro and in vivo models, pointing to the key issues concerning the toxicological analysis of magnetic nanomaterials. In addition new research directions of nanotoxicological studies elucidating the importance of developing alternative methods for testing magnetic nano(bio)products are also presented.

  3. Space Toxicology Challenges and Ethical Considerations

    NASA Technical Reports Server (NTRS)

    James, John T.

    2010-01-01

    Before delineating specific ways that nanotechnology enterprises might contribute to better management of toxicological risks during spaceflight, I will show how ethical considerations and several theories of justice can be applied to nanotechnology strategic plans. The principles that guide an ethical technical enterprise include autonomy, beneficence, non-maleficence, veracity and justice. Veracity (truth) is the underpinning principle; however, beyond this, proponents of nanotechnology must think carefully about balancing conflicting principles. For example, autonomy must yield to beneficence when fearful individuals simply lack knowledge to appreciate nanotechnology's beneficial advances. Justice is a complex topic upon which I will place six models: utilitarian, distributive, free-exchange/choice, individual dignity (social participation), equity vs. greed, and liberation of the poor. After briefly summarizing each model, I will present what I call an iterative-hybrid model of justice to show specifically how our thinking can be applied to nanotechnology enterprises. Within that broad landscape, I will discuss a single feature: how our early effort to understand health risks of carbon nanotubes fits into the iterative model. Finally, I will suggest ways that nanotechnology might advance our management of toxicological risks during spaceflight, but always with an eye toward how such advances might result in a more just world.

  4. The EPA Comptox Chemistry Dashboard: A Web-Based Data Integration Hub for Toxicology Data (SOT)

    EPA Science Inventory

    The U.S. Environmental Protection Agency (EPA) Computational Toxicology Program integrates advances in biology, chemistry, and computer science to help prioritize chemicals for further research based on potential human health risks. This work involves computational and data drive...

  5. 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

  6. Mass Spectrometry Applications for Toxicology.

    PubMed

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

    2016-12-01

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

  7. Toxicology of brotizolam

    PubMed Central

    Hewett, C.; Kreuzer, H.; Köllmer, H.; Niggeschulze, A.; Stötzer, H.

    1983-01-01

    1 Acute studies. Following oral or intraperitoneal administration, toxicity was very low (LD50 in rodents > 10,000 and > 900 mg/kg, respectively). 2 Subacute and chronic studies in rodents. Signs of toxicity were seen only at doses of 400 mg/kg or more. Histopathological changes were found only in the 78-week study. 3 Subacute studies in dogs (intravenous) and primates (oral). In dogs, doses of 0.1 and 0.3 mg/kg produced ataxia, salivation, and diarrhoea. In monkeys doses of 7 mg/kg or higher produced ataxia, increased appetite, hyperreflexive muscular spasms, increase in liver weight, and lipid depletion of the adrenal cortex. 4 Reproductive studies in the rat and rabbit. Repeated doses of up to 30 mg/kg were not associated with any disturbance in fertility; nor were any embryotoxic or teratogenic effects observed. When dams were treated with 400 mg/kg, litter mortality was markedly increased. 5 Mutagenicity studies. The four different tests performed gave no indication of any mutagenic effect. 6 Local tolerance tests in the rabbit. Brotizolam was well tolerated when administered intramuscularly, intra-arterially, or intravenously. 7 Carcinogenicity studies in rodents. The mouse study showed no evidence of a tumourigenic effect. The rat study is still being evaluated. 8 The toxicological studies demonstrate that brotizolam has an unusually wide therapeutic range. Findings of toxicological significance, most of which were reversible, were first recorded at doses of 7-10 mg/kg, i.e. at more than 100-times the intended human therapeutic dose. PMID:6686462

  8. Cannabinoids in postmortem toxicology.

    PubMed

    Lemos, Nikolas P; Ingle, Eric A

    2011-09-01

    Cannabinoids are often excluded from postmortem toxicology screens due to their ubiquitous nature, interpretative difficulties and unanswered questions regarding their postmortem redistribution. In this study, we review 30 postmortem cases where a drug screen gave a positive cannabinoids result and a confirmation identified Δ⁹-tetrahydrocannabinol (THC), 11-hydroxy-Δ⁹-tetrahydrocannabinol (11-OH-THC), and/or 11-nor-9-carboxy-Δ⁹-tetrahydrocannabinol (THC-COOH) in peripheral (BL-P) or cardiac/central blood (BL-C) and/or urine (UR). Had cannabinoids not been included in these toxicologic evaluations, incomplete or erroneous inferences would have been drawn in a substantial number of cases regarding cause/manner of death. THC was detected in 28 BL-C and in all 30 BL-P. THC and THC-COOH were confirmed present in 2 and 23 UR, respectively. 11-OH-THC was detected in 4 BL-C, 6 BL-P, and 0 UR. The mean THC concentrations in BL-C and BL-P were 8.0 and 15.8 ng/mL, respectively. The mean THC-COOH concentrations in BL-C and BL-P were 55.2 and 60.6 ng/mL, respectively. The mean 11-OH-THC concentrations in BL-C and BL-P were 17.0 and 12.5 ng/mL, respectively. Postmortem interval (PMI) for each case was determined and evaluated in relation to BL-C/BL-P concentration ratios with THC-COOH exhibiting a possible trend. This study is the first of its kind and demonstrates the usefulness of cannabinoid analyses as part of death investigations. Furthermore, it provides distribution data that will improve the ability of toxicologists and pathologists to evaluate cannabinoid concentrations in human postmortem specimens.

  9. 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).

  10. Toxicological programmes and teaching methods.

    PubMed

    Bergendorff, A

    2000-03-15

    Toxicological knowledge is required for three main purposes: basic and applied research, toxicity testing, and risk assessment. Curricula and teaching methods designed to meet these demands for knowledge are aimed at appropriation of relevant facts, appreciation of causality and an overall understanding of biological events caused by chemical substances. The Toxicology Programme at Karolinska Institutet is considered as an example for the design of appropriate courses. Teaching methods developed towards more self-tuition are becoming a natural part of such education. Continued escalation in scientific achievements and demands for safe use of chemicals will govern future trends in toxicological education.

  11. Environmental toxicology: Interconnections between human ...

    EPA Pesticide Factsheets

    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 integrity, SOT-SETAC Pellston Workshop findings, concepts for systems thinking in environmental toxicology The Eminent Toxicologist Lectures are historically relevant, high-quality presentations appropriate for senior undergraduate students, graduate students, or the scientifically oriented general public. This series of lectures is produced by the SOT Undergraduate Subcommittee of the Education Committee in conjunction with the Eminent Toxicologist Working Group.

  12. Ninth Triennial Toxicology Salary Survey.

    PubMed

    Gad, Shayne Cox; Sullivan, Dexter Wayne

    2016-01-01

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

  13. Eighth triennial toxicology salary survey.

    PubMed

    Gad, Shayne Cox; Sullivan, Dexter Wayne

    2013-01-01

    This survey serves as the eighth in a series of toxicology salary surveys conducted at 3-year intervals and beginning in 1988. An electronic survey instrument was distributed to 5800 individuals including members of the Society of Toxicology, American College of Toxicology, and 23 additional professional organizations. Question items inquired about gender, age, degree, years of experience, certifications held, areas of specialization, society membership, employment and income. Overall, 2057 responses were received (response rate 35.5%). The results of the 2012 survey provide insight into the job market and career path for current and future toxicologists.

  14. Gordon Research Conference on Genetic Toxicology

    SciTech Connect

    Project Director Penelope Jeggo

    2003-02-15

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

  15. Proceedings of the 2012 National Toxicology Program Satellite Symposium

    PubMed Central

    ELMORE, SUSAN A.; BERRIDGE, BRIAN R.; BOYLE, MICHAEL C.; CORA, MICHELLE C.; HOENERHOFF, MARK J.; KOOISTRA, LINDA; LAAST, VICTORIA A.; MORRISON, JAMES P.; RAO, DEEPA; RINKE, MATTHIAS; YOSHIZAWA, KATSUHIKO

    2014-01-01

    The 2012 annual National Toxicology Program (NTP) Satellite Symposium, entitled “Pathology Potpourri,” was held in Boston in advance of the Society of Toxicologic Pathology’s 31st annual meeting. The goal of the NTP Symposium is to present current diagnostic pathology or nomenclature issues to the toxicologic pathology community. This article presents summaries of the speakers’ presentations, including diagnostic or nomenclature issues that were presented, along with select images that were used for audience voting or discussion. Some lesions and topics covered during the symposium include eosinophilic crystalline pneumonia in a transgenic mouse model; differentiating adrenal cortical cystic degeneration from adenoma; atypical eosinophilic foci of altered hepatocytes; differentiating cardiac schwannoma from cardiomyopathy; diagnosis of cardiac papillary muscle lesions; intrahepatocytic erythrocytes and venous subendothelial hepatocytes; lesions in Rathke’s cleft and pars distalis; pernicious anemia and megaloblastic disorders; embryonic neuroepithelial dysplasia, holoprosencephaly and exencephaly; and INHAND nomenclature for select cardiovascular lesions. PMID:23262640

  16. Predictive Models and Computational Toxicology

    EPA Science Inventory

    Understanding the potential health risks posed by environmental chemicals is a significant challenge elevated by the large number of diverse chemicals with generally uncharacterized exposures, mechanisms, and toxicities. The ToxCast computational toxicology research program was l...

  17. 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. ...

  18. Toxicology of melatonin.

    PubMed

    Guardiola-Lemaître, B

    1997-12-01

    Despite the fact that melatonin has been released for public use in the United States by the Food and Drug Administration and is available over the counter nationwide, there currently is a total lack of information on the toxicology of melatonin. In Europe, melatonin has a completely different status in that it is considered a "neurohormone" and cannot be sold over the counter. Even though administration of melatonin in humans, as well as in animals (even at supraphysiological doses), has not shown evidence of toxicological effects (i.e., no deaths), a drug toxicological file still would need to be prepared and approved by the regulatory authorities. Several features that are specific to this neurohormone need to be taken into consideration. Whatever the species concerned, melatonin is secreted during the night; it is the "hormone of darkness." It presents a circadian rhythm and a circannual rhythm (in photoperiodic species). The duration of these secretions could have an impact on the reproductive system, for example, showing the importance of the pharmacodynamics of melatonin. An inappropriate time schedule of melatonin administration could induce supraphysiological concentrations of the neurohormone and a desensitization of melatonin receptors. A long duration of exposure to melatonin also could mimic an "artificial darkness" condition when a circadian rhythm with a basal zero level during the day needs to be conserved for a physiological function. Furthermore, administration of large doses of melatonin could induce high concentrations of melatonin and of different metabolites that could have deleterious effects per se. Numerous books, magazines, and articles have praised melatonin as a "miraculous cure-all" for ailments ranging from sleeplessness, to aging, without any clinical evidence of efficacy (with the exception of its chronobiotic and resynchronizing effect). Very little attention has been paid to the possible side effects of melatonin. Nightmares

  19. Computational Toxicology as Implemented by the US EPA ...

    EPA Pesticide Factsheets

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

  20. Toxicological properties of nanomaterials.

    PubMed

    Zhang, Mingyi; Jin, Junjiang; Chang, Ya-Nan; Chang, Xueling; Xing, Gengmei

    2014-01-01

    The development of engineered nanomaterials opens tremendous opportunities for their application as therapeutic and diagnostic tools, as well as in the fields of consumer products. As the newly developed material subtype, they exhibit great activities for the high ratio of surface to total atoms. In the bio-system, the activity can render nanomaterials some negative outcomes for their unexpected deposition in organs and cells, the cellular response to the exogenous substance and the interfacial reaction with biomolecules. In this review, we have discussed the evolution of nanotoxicology studies in the past ten years mainly emerging from our laboratory. The early in vivo studies mainly focused on the biokinetic of inhaled nanoparticles and their impacts on mammal tissues, such as the central nervous system, respiratory system, cardiovascular system and so on. Then the scope extended to engineered nanomaterials used as food additives and medicines, as well as their influence on alimentary and reproductive systems. In vitro experiments to study the nanoparticle-cell interaction and nanoparticle-biomolecule interplay are indispensable to reveal the mechanisms behind the macroscopic phenomenon. In addition, novel tools such as new model organisms and synchrotron radiation-based techniques are used to facilitate our understanding of the toxicology profile of nanomaterials.

  1. 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.

  2. The toxicology of chemosterilants

    PubMed Central

    Hayes, Wayland J.

    1964-01-01

    Sterilization of males can in certain circumstances be more efficient than killing as a method for control of insects and perhaps other pests. A number of chemicals (chemosterilants) show promise of producing sexual sterility in insects without some of the practical limitations of radiation. The most important compounds are alkylating agents. These have little immediate pharmacological action, but are notable for their selective action against haematopoietic and some other proliferating tissues. A number of alkylating agents have been shown to be mutagens in insects, bacteria, fungi, and higher plants; carcinogens in mammals; and teratogens in insects, birds, and mammals. Some produce sexual sterility, possibly in mammals as well as in insects, at doses too low to produce the other effects. Some have an established reputation as drugs for palliative treatment of leukaemia and other neoplasms. The development of insect sterilization as a vector control technique has been handicapped in part by lack of scientific information on the acute and long-term hazards that might be associated with the use of chemosterilants. In this paper the author brings together the available knowledge on the toxicology of the alkylating agents. PMID:14278008

  3. [Toxicologic blood emergency screening].

    PubMed

    Cohen, Sabine; Manat, Aurélie; Dumont, Benoit; Bévalot, Fabien; Manchon, Monique; Berny, Claudette

    2010-01-01

    In order to overcome the stop marketing by Biorad company of automated high performance liquid chromatograph with UV detection (Remedi), we developed a gas chromatography-mass spectrometry (GC-MS) to detect and to give an approximation of the overdose of molecules frequently encountered in drug intoxications. Therefore two hundred eighty seventeen blood samples were collected over a period of one year and allowed us to evaluate and compare the performance of these two techniques. As identification, GC-MS does not identify all molecules detected by Remedi in 24.2% of cases; there is a lack of sensitivity for opiates and the systematic absence of certain molecules such as betablockers. However, in 75.8% of cases the GC-MS detects all molecules found by Remedi and other molecules such as meprobamate, paracetamol, benzodiazepines and phenobarbital. The concentrations obtained are interpreted in terms of overdose showed 15.7% of discrepancy and 84.3% of concordance between the two techniques. The GC-MS technique described here is robust, fast and relatively simple to implement; the identification is facilitated by macro commands and the semi quantification remains manual. Despite a sequence of cleaning the column after each sample, carryover of a sample to the next remains possible. This technique can be used for toxicologic screening in acute intoxications. Nevertheless it must be supplemented by a HPLC with UV detection if molecules such as betablockers are suspected.

  4. TOXNET: Toxicology Data Network

    MedlinePlus

    ... Haz-Map Household Products TOXMAP TRI Search Please select a database for ADVANCED SEARCH Search Term Records ... documents added in the last months Language To select more than one component, click while holding the ...

  5. Toxicology of chlorofluorocarbon replacements.

    PubMed

    Dekant, W

    1996-03-01

    Chlorofluorocarbons (CFCs) are stable in the atmosphere and may reach the stratosphere. They are cleaved by UV-radiation in the stratosphere to yield chlorine radicals, which are thought to interfere with the catalytic cycle of ozone formation and destruction and deplete stratospheric ozone concentrations. Due to potential adverse health effects of ozone depletion, chlorofluorocarbon replacements with much lower or absent ozone depleting potential are developed. The toxicology of these compounds that represent chlorofluorohydrocarbons (HCFCs) or fluorohydrocarbons (HFCs) has been intensively studied. All compounds investigated (1, 1-dichloro-1-fluoroethane [HCFC-141b], 1,1,1,2-tetrafluoroethane [HFC-134a], pentafluoroethane [HFC-125], 1-chloro- 1,2,2,2-tetrafluoroethane [HCFC-124], and 1,1-dichloro-2,2,2-trifluoroethane [HCFC-123]) show only a low potential for skin and eye irritation. Chronic adverse effects on the liver (HCFC-123) and the testes (HCFC-141b and HCFC-134a), including tumor formation, were observed in long-term inhalation studies in rodents using very high concentrations of these CFC replacements. All CFC replacements are, to varying extents, biotransformed in the organism, mainly by cytochrome P450-catalyzed oxidation of C-H bonds. The formed acyl halides are hydrolyzed to give excretable carboxylic acids; halogenated aldehydes that are formed may be further oxidized to halogenated carboxylic acids or reduced to halogenated alcohols, which are excretory metabolites in urine from rodents exposed experimentally to CFC replacements. The chronic toxicity of the CFC replacements studied is unlikely to be of relevance for humans exposed during production and application of CFC replacements.

  6. Toxicological approaches to complex mixtures.

    PubMed Central

    Mauderly, J L

    1993-01-01

    This paper reviews the role of toxicological studies in understanding the health effects of environmental exposures to mixtures. The approach taken is to review mixtures that have received the greatest emphasis from toxicology; major mixtures research programs; the toxicologist's view of mixtures and approaches to their study; and the complementary roles of toxicological, clinical, and epidemiological studies. Studies of tobacco smoke, engine exhaust, combustion products, and air pollutants comprise most of the past research on mixtures. Because of their great experimental control over subjects, exposures, and endpoints, toxicologists tend to consider a wider range of toxic interactions among mixture components and sequential exposures than is practical for human studies. The three fundamental experimental approaches used by toxicologists are integrative (studying the mixture as a whole), dissective (dissecting a mixture to determine causative constituents), and synthetic (studying interactions between agents in simple combinations). Toxicology provides information on potential hazards, mechanisms by which mixture constituents interact to cause effects, and exposure dose-effect relationships; but extrapolation from laboratory data to quantitative human health risks is problematic. Toxicological, clinical, and epidemiological approaches are complementary but are seldom coordinated. Fostering synergistic interactions among the disciplines in studying the risks from mixtures could be advantageous. PMID:7515806

  7. Fire toxicology program. JSC methodology

    NASA Technical Reports Server (NTRS)

    Schneider, H.; Bafus, D.

    1978-01-01

    Toxicological testing of spacecraft materials was initiated in 1965. Toxicological evaluations of the pyrolysis/combustion products of candidate spacecraft materials were performed using a modified 142 liter Bethlehem Chamber equipped with a Linberg Model 55031 furnace external to the chamber. In all of the assessments, lethality was chosen as the endpoint. A new pyrolysis/combustion chamber was developed for toxicological testing and ranking of both spacecraft and aircraft materials. The pyrolysis/combustion chamber permits the use of both behavior and physiological measurements as indicators of incapacitation. Methods were developed which employ high resolution gas chromatography/mass spectrometry to generate chamber atmospheric profiles which indicate the reproductibility of pyrolysate concentrations. The atmospheric volatile profiles in combination with CO, CO2, and O2 analysis indicates that small chamber equipped with an internal furnace will give reproducible results.

  8. 40 CFR 158.2230 - Toxicology.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES Antimicrobial Pesticide Data Requirements § 158.2230 Toxicology. (a) General. Subpart B... determine the toxicology data requirements for an antimicrobial pesticide product. Notes that apply to...

  9. 40 CFR 158.2230 - Toxicology.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES Antimicrobial Pesticide Data Requirements § 158.2230 Toxicology. (a) General. Subpart B... determine the toxicology data requirements for an antimicrobial pesticide product. Notes that apply to...

  10. Investigating Impact Metrics for Performance for the US EPA National Center for Computational Toxicology (ACS Fall meeting)

    EPA Science Inventory

    The U.S. Environmental Protection Agency (EPA) Computational Toxicology Program integrates advances in biology, chemistry, and computer science to help prioritize chemicals for further research based on potential human health risks. This work involves computational and data drive...

  11. [Clinical usefulness of toxicology testing].

    PubMed

    Solari G, Sandra; Ríos B, Juan Carlos

    2009-10-01

    A toxicology testing is the search by the laboratory of the possible etiologic agents that can cause poisoning. Given the wide variety of substances that can poison a person, the laboratories should work coordinated with the emergency wards in order to determine the appropriate tests menu and the required turn around time according to the most frequent causes of intoxication in the local population. Toxicology laboratories should provide two tiers of drug testing: selected drug tests in blood/urine and comprehensive or broad-spectrum toxicological testing in the same or other samples. The medical order must always include the suspected diagnosis, which is responsibility of the physician requesting the test. A most important issue in the study of a poisoned patient is the opportunity when the samples are drawn, which should be at the emergency room since a delay in sample collection implies losing unrecoverable information. Samples should be sent to the laboratory for either immediate analysis or later comprehensive toxicological tests, so that laboratories must have procedures for the proper storage and preservation of samples. Poison control centers provide assistance to clinicians in considering certain drugs etiologies and in selecting specific tests.

  12. Public Databases Supporting Computational Toxicology

    EPA Science Inventory

    A major goal of the emerging field of computational toxicology is the development of screening-level models that predict potential toxicity of chemicals from a combination of mechanistic in vitro assay data and chemical structure descriptors. In order to build these models, resea...

  13. Proceedings of the 2010 National Toxicology Program Satellite Symposium

    PubMed Central

    Adams, E. Terence; Auerbach, Scott; Blackshear, Pamela E.; Bradley, Alys; Gruebbel, Margarita M.; Little, Peter B.; Malarkey, David; Maronpot, Robert; McKay, Jennifer S.; Miller, Rodney A.; Moore, Rebecca R.; Morrison, James P.; Nyska, Abraham; Ramot, Yuval; Rao, Deepa; Suttie, Andrew; Wells, Monique Y.; Willson, Gabrielle A.; Elmore, Susan A.

    2011-01-01

    The 2010 annual National Toxicology Program (NTP) Satellite Symposium, entitled “Pathology Potpourri,” was held in Chicago, Illinois, in advance of the scientific symposium sponsored jointly by the Society of Toxicologic Pathology (STP) and the International Federation of Societies of Toxicologic Pathologists (IFSTP). The goal of the annual NTP Symposium is to present current diagnostic pathology or nomenclature issues to the toxicologic pathology community. This article presents summaries of the speakers' presentations, including diagnostic or nomenclature issues that were presented, along with select images that were used for voting or discussion. Some topics covered during the symposium included a comparison of rat and mouse hepatocholangiocarcinoma, a comparison of cholangiofibrosis and cholangiocarcinoma in rats, a mixed pancreatic neoplasm with acinar and islet cell components, an unusual preputial gland tumor, renal hyaline glomerulopathy in rats and mice, eosinophilic substance in the nasal septum of mice, INHAND nomenclature for proliferative and nonproliferative lesions of the CNS/PNS, retinal gliosis in a rat, fibroadnexal hamartoma in rats, intramural plaque in a mouse, a treatment-related chloracne-like lesion in mice, and an overview of mouse ovarian tumors. PMID:21177527

  14. Forensic toxicology in drug-facilitated sexual assault.

    PubMed

    Dinis-Oliveira, Ricardo Jorge; Magalhães, Teresa

    2013-09-01

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

  15. Computational Toxicology at the US EPA | Science Inventory ...

    EPA Pesticide Factsheets

    Computational toxicology is the application of mathematical and computer models to help assess chemical hazards and risks to human health and the environment. Supported by advances in informatics, high-throughput screening (HTS) technologies, and systems biology, EPA is developing robust and flexible computational tools that can be applied to the thousands of chemicals in commerce, and contaminant mixtures found in America’s air, water, and hazardous-waste sites. The ORD Computational Toxicology Research Program (CTRP) is composed of three main elements. The largest component is the National Center for Computational Toxicology (NCCT), which was established in 2005 to coordinate research on chemical screening and prioritization, informatics, and systems modeling. The second element consists of related activities in the National Health and Environmental Effects Research Laboratory (NHEERL) and the National Exposure Research Laboratory (NERL). The third and final component consists of academic centers working on various aspects of computational toxicology and funded by the EPA Science to Achieve Results (STAR) program. Key intramural projects of the CTRP include digitizing legacy toxicity testing information toxicity reference database (ToxRefDB), predicting toxicity (ToxCast™) and exposure (ExpoCast™), and creating virtual liver (v-Liver™) and virtual embryo (v-Embryo™) systems models. The models and underlying data are being made publicly available t

  16. 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

  17. Reflections on the origins and evolution of genetic toxicology and the Environmental Mutagen Society.

    PubMed

    Wassom, John S; Malling, Heinrich V; Sankaranarayanan, K; Lu, Po-Yung

    2010-01-01

    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, new wording appeared to better describe this evolving area of research. The term "genetic toxicology" was coined and became an important subspecialty of 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. Any oversight or failure to make proper acknowledgment of individuals, events, or the citation of relevant references in this article is unintentional.

  18. Distance learning and toxicology: New horizons for Paracelsus

    SciTech Connect

    Huggins, Jane . E-mail: djhug1.1@netzero.com; Morris, John; Peterson, C. Erik

    2005-09-01

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

  19. Distance learning and toxicology: new horizons for Paracelsus.

    PubMed

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

    2005-09-01

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

  20. IRIS Toxicological Review of Tetrachloroethylene ...

    EPA Pesticide Factsheets

    EPA conducted a peer review of the scientific basis supporting the human health hazard and dose-response assessment of tetrachloroethylene that will appear on the Integrated Risk Information System (IRIS) database. Peer review is meant to ensure that science is used credibly and appropriately in derivation of the toxicological characterization and dose-response assessments. This draft health assessment addresses both non-cancer and cancer human health effects that may result from chronic exposure to tetrachloroethylene (also called Perchloroethylene or Perc) . This is an update of an existing assessment posted on IRIS in 1988. This draft Toxicological Review includes a chronic Reference Concentration (RfC) and carcinogenicity assessment, which are not currently available on IRIS, as well as an update of the 1988 IRIS Reference Dose (RfD). Tetrachloroethylene is a chemical solvent that is widely used for dry cleaning of fabrics, metal degreasing, and in making some consumer products and other chemicals.

  1. Amine promiscuity and toxicology analysis.

    PubMed

    Lee, Esther C Y; Steeno, Gregory; Wassermann, Anne Mai; Zhang, Liying; Shah, Falgun; Price, David A

    2017-02-01

    Drug discovery programs often face challenges to obtain sufficient duration of action of the drug (i.e. seek longer half-lives). If the pharmacodynamic response is driven by free plasma concentration of the drug then extending the plasma drug concentration is a valid approach. Half-life is dependent on the volume of distribution, which in turn can be dependent upon the ionization state of the molecule. Basic compounds tend to have a higher volume of distribution leading to longer half-lives. However, it has been shown that bases may also have higher promiscuity. In this work, we describe an analysis of in vitro pharmacological profiling and toxicology data investigating the role of primary, secondary, and tertiary amines in imparting promiscuity and thus off-target toxicity. Primary amines are found to be less promiscuous in in vitro assays and have improved profiles in in vivo toxicology studies compared to secondary and tertiary amines.

  2. Toxicological significance of dihydrodiol metabolites

    SciTech Connect

    Hsia, M.T.

    1982-01-01

    Dihydrodiols are often found as the major organic-extractable metabolites of various olefinic or aromatic xenobiotics in many biological samples. Studies on the chemistry of dihydrodiol metabolites have provided insight into the pharmacokinetic behavior and the mode of action of the parent compound. The toxicology of dihydrodiol is more complex than what can be deduced solely on the basis of diminished bioavailability of the epoxide precursor, and the increased hydrophilicity associated with the dihydrodiol moiety. Dihydrodiols can be intrinsically toxic and may even represent metabolically activated species. Some of the dihydrodiol metabolites may still retain sufficient lipophilic character to serve again as substrates for microsomal oxygenases. Because of the tremendous chemical and biological diversity that existed among the various dihydrodiols, more mechanistic studies are needed to examine the toxicological properties of these compounds. It may be premature to conclude dihydrodiol formation as purely a detoxification route for xenobioties.

  3. DSSTOX NATIONAL TOXICOLOGY PROGRAM BIOASSAY ...

    EPA Pesticide Factsheets

    NTPBSI: National Toxicology Program Bioassay On-line Database Structure-Index Locator File. Database contains the results collected on approxiately 300 toxicity studies from shorter duration test and from genetic toxicity studies, both in vitro and in vivo tests. Database contains the results collected on approxiately 300 toxicity studies from shorter duration test and from genetic toxicity studies, both in vitro and in vivo tests.

  4. Toxicologic studies of SRC materials

    SciTech Connect

    Mahlum, D.D.; Pelroy, R.A.; Drucker, H.; Wilson, B.W.; Massey, M.J.; Schmalzer, D.K.

    1980-02-01

    Investigations on the toxicity of SRC materials are reported. Toxicological studies include: microbial mutageneis (Ames test); in vitro mammalian cell toxicity and transformation assays; epidermal carcinogenesis (skin painting); acute and subchronic oral toxicity; developmental toxicity; dominant lethal assays; inhalation toxicity; and dosimetry and metabolism. The materials tested include: SRC-I process solvent, wash solvent, and light oil; SRC-II heavy distillate, middle distillate, and light distillate; shale oil; crude petroleum; and pure carcinogens. (DC)

  5. Current Toxicology of Ethylene Oxide,

    DTIC Science & Technology

    1982-12-01

    carcinogenicity are presented. The overall toxicological implications and a recommendation on the use of ethylene oxide are briefly discussed. (U...wer exposed to ethylene oxide vapour. A single exposure of the male rats to vapour at 100 ppm for 4 hours resulted in reproduction A abnormalities...oxide causes leukemia. It should be noted also that ethylene oxide in the presence of water produces ethylene glycol. Subchronic and chronic exposures

  6. IRIS TOXICOLOGICAL REVIEW AND SUMMARY ...

    EPA Pesticide Factsheets

    EPA's assessment of the noncancer health effects and carcinogenic potential of Beryllium was added to the IRIS database in 1998. The IRIS program is updating the IRIS assessment for Beryllium. This update will incorporate health effects information published since the last assessment was prepared as well as new risk assessment methods. The IRIS assessment for Beryllium will consist of an updated Toxicological Review and IRIS Summary. The Toxicological Review is a critical review of the physicochemical and toxicokinetic properties of the chemical and its toxicity in humans and experimental systems. The assessment will present reference values for noncancer effects of Beryllium (RfD and RfC) and a cancer assessment. The Toxicological Review and IRIS Summary will be subject to internal peer consultation, Agency and Interagency review, and external scientific peer review. The final products will constitute the Agency's opinion on the toxicity of Beryllium. Beryllium is a light alkaline earth metal used in metal alloys and in high-performance products in the metallurgical, aerospace, and nuclear industries. According to the Superfund database, beryllium is found in over 300 NPL sites

  7. New insights on 'old' toxicants in occupational toxicology (Review).

    PubMed

    Costa, Chiara; Miozzi, Edoardo; Teodoro, Michele; Briguglio, Giusi; Rapisarda, Venerando; Fenga, Concettina

    2017-03-24

    In order to deliver the best possible working environment, it is essential to identify professional conditions that could be harmful for worker's health and prevent (or limit) the occurrence of such conditions. The appropriate use of personal protective equipment and the development of appropriate regulations allowed to reduce the prevalence of 'classic' occupational diseases, such as occupational hearing loss or asbestosis, just to name a few. Nowadays, environmental pollution seems to be one of the most relevant concerns for human and animal health, and toxicology is becoming one of the most prominent fields of interest in occupational settings. An increasing number of studies demonstrate that the presence of toxicants in the workplace could be responsible for the development of chronic diseases, even at doses that were considered 'safe'. The present review summarizes some of the most recent advancements in occupational toxicology, focusing on topics that have long been debated in the past and that have recently returned to the fore.

  8. 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...

  9. 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.

  10. 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)

  11. 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.

  12. Mass spectrometry in environmental toxicology.

    PubMed

    Groh, Ksenia J; Suter, Marc J-F

    2014-01-01

    In environmental toxicology, mass spectrometry can be applied to evaluate both exposure to chemicals as well as their effects in organisms. Various ultra-trace techniques are employed today to measure pollutants in different environmental compartments. Increasingly, effect-directed analysis is being applied to focus chemical monitoring on sites of ecotoxicological concern. Mass spectrometry is also very instrumental for studying the interactions of chemicals with organisms on the molecular and cellular level, providing new insights into mechanisms of toxicity. In the future, diverse mass spectrometry-based techniques are expected to become even more widely used in this field, contributing to the refinement of currently used environmental risk assessment strategies.

  13. 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.

  14. Toxicological evaluation of pure hydroxytyrosol.

    PubMed

    Auñon-Calles, David; Canut, Lourdes; Visioli, Francesco

    2013-05-01

    Of all the phenolic constituents of olives and extra virgin olive oil, hydroxytyrosol is currently being actively exploited as a potential supplement or preservative to be employed in the nutraceutical, cosmeceutical, and food industry. In terms of safety profile, hydroxytyrosol has only been investigated as the predominant part of raw olive mill waste water extracts, due to the previous unavailability of appropriate quantities of the pure compound. We report the toxicological evaluation of hydroxytyrosol and, based on the results, propose a No Observed Adverse Effects Level (NOAEL) of 500mg/kg/d.

  15. 21 CFR 862.3200 - Clinical toxicology calibrator.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Toxicology Test...., ethanol, lidocaine, etc.). (See also § 862.2 in this part.) (b) Classification. Class II....

  16. Proceedings of the 2013 National Toxicology Program Satellite Symposium

    PubMed Central

    Elmore, Susan A.; Boyle, Michael C.; Boyle, Molly H.; Cora, Michelle C.; Crabbs, Torrie A.; Cummings, Connie A.; Gruebbel, Margarita M.; Johnson, Crystal L.; Malarkey, David E.; McInnes, Elizabeth F.; Nolte, Thomas; Shackelford, Cynthia C.; Ward, Jerrold M.

    2014-01-01

    The 2013 annual National Toxicology Program (NTP) Satellite Symposium, entitled “Pathology Potpourri” was held in Portland, Oregon in advance of the Society of Toxicologic Pathology's 32nd annual meeting. The goal of the NTP Symposium is to present current diagnostic pathology or nomenclature issues to the toxicologic pathology community. This article presents summaries of the speakers' presentations, including diagnostic or nomenclature issues that were presented, along with select images that were used for audience voting and discussion. Some lesions and topics covered during the symposium included a caudal tail vertebra duplication in mice; nephroblastematosis in rats; ectopic C cell tumor in a hamster; granular cell aggregates/tumor in the uterus of a hamster; Pneumocystis carinii in the lung of a rat; iatrogenic chronic inflammation in the lungs of control rats; hepatoblastoma arising within an adenoma in a mouse; humoral hypercalcemia of benignancy in a transgenic mouse; acetaminophen induced hepatoxicity in rats; electron microscopy images of iatrogenic intraerythrocytic inclusions in transgenic mice; questionable hepatocellular degeneration/cell death/artifact in rats; atypical endometrial hyperplasia in rats; malignant mixed Müllerian tumors/carcinosarcomas in rats; differential diagnoses of proliferative lesions the intestine of rodents; and finally obstructive nephropathy caused by melamine poisoning in a rat. PMID:24334674

  17. Proceedings of the 2011 National Toxicology Program Satellite Symposium

    PubMed Central

    Boorman, Gary; Crabbs, Torrie A.; Kolenda-Roberts, Holly; Latimer, Ken; Miller, Andrew D.; Muravnick, Kathleen B.; Nyska, Abraham; Ochoa, Ricardo; Pardo, Ingrid D.; Ramot, Yuval; Rao, Deepa B.; Schuh, JoAnn; Suttie, Andrew; Travlos, Greg S.; Ward, Jerrold M.; Wolf, Jeffrey C.; Elmore, Susan A.

    2012-01-01

    The 2011 annual National Toxicology Program (NTP) Satellite Symposium, entitled “Pathology Potpourri,” was held in Denver, Colorado in advance of the Society of Toxicologic Pathology’s 30th Annual Meeting. The goal of the NTP Symposium is to present current diagnostic pathology or nomenclature issues to the toxicologic pathology community. This article presents summaries of the speakers’ presentations, including diagnostic or nomenclature issues that were presented, along with select images that were used for audience voting or discussion. Some lesions and topics covered during the symposium include: proliferative lesions from various fish species including ameloblastoma, gas gland hyperplasia, nodular regenerative hepatocellular hyperplasia, and malignant granulosa cell tumor; spontaneous cystic hyperplasia in the stomach of CD1 mice and histiocytic aggregates in the duodenal villous tips of treated mice; an olfactory neuroblastoma in a cynomolgus monkey; various rodent skin lesions, including follicular parakeratotic hyperkeratosis, adnexal degeneration, and epithelial intracytoplasmic accumulations; oligodendroglioma and microgliomas in rats; a diagnostically challenging microcytic, hypochromic, responsive anemia in rats; a review of microcytes and microcytosis; nasal lesions associated with green tea extract and Ginkgo biloba in rats; corneal dystrophy in Dutch belted rabbits; valvulopathy in rats; and lymphoproliferative disease in a cynomolgus monkey. PMID:22089839

  18. Proceedings of the 2014 National Toxicology Program Satellite Symposium

    PubMed Central

    Elmore, Susan A.; Cora, Michelle C.; Gruebbel, Margarita M.; Hayes, Schantel A.; Hoane, Jessica S.; Koizumi, Haruko; Peters, Rachel; Rosol, Thomas J.; Singh, Bhanu P.; Szabo, Kathleen A.

    2014-01-01

    The 2014 annual National Toxicology Program (NTP) Satellite Symposium, entitled “Pathology Potpourri” was held in Washington DC, in advance of the Society of Toxicologic Pathology’s 33rd annual meeting. The goal of this annual NTP Symposium is to present current diagnostic pathology or nomenclature issues to the toxicologic pathology community. This article presents summaries of the speakers’ presentations, including diagnostic or nomenclature issues that were presented, along with select images that were used for audience voting and discussion. Some lesions and topics covered during the symposium included a pulmonary mucinous adenocarcinoma in a male B6C3F1 mouse; plexiform vasculopathy in Wistar Han rats; staging of the estrous cycle in rats and mice; peri-islet fibrosis, hemorrhage, lobular atrophy and inflammation in male Sprague Dawley rats; retinal dysplasia in Wistar Han rats and B6C3F1 mice; multicentric lymphoma with intravascular microemboli and tumor lysis syndrome, and two cases of myopathy and vascular anomaly in Tg.rasH2 mice; benign thymomas in Wistar Han rats; angiomatous lesions in the mesenteric lymph nodes of Wistar Han rats; an unusual foveal lesion in a cynomolgous monkey; and finally a series of nomenclatures challenges from the endocrine International Harmonization of Nomenclature and Diagnostic Criteria (INHAND) organ working group (OWG). PMID:25385331

  19. 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.

  20. 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...

  1. 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.

  2. 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...

  3. 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.

  4. Toxicologic methods: controlled human exposures.

    PubMed

    Utell, M J; Frampton, M W

    2000-08-01

    The assessment of risk from exposure to environmental air pollutants is complex, and involves the disciplines of epidemiology, animal toxicology, and human inhalation studies. Controlled, quantitative studies of exposed humans help determine health-related effects that result from breathing the atmosphere. The major unique feature of the clinical study is the ability to select, control, and quantify pollutant exposures of subjects of known clinical status, and determine their effects under ideal experimental conditions. The choice of outcomes to be assessed in human clinical studies can be guided by both scientific and practical considerations, but the diversity of human responses and responsiveness must be considered. Subjects considered to be among the most susceptible include those with asthma, chronic obstructive lung disease, and cardiovascular disease. New experimental approaches include exposures to concentrated ambient air particles, diesel engine exhaust, combustion products from smoking machines, and experimental model particles. Future investigations of the health effects of air pollution will benefit from collaborative efforts among the disciplines of epidemiology, animal toxicology, and human clinical studies.

  5. Blood transcriptomics: applications in toxicology

    PubMed Central

    Joseph, Pius; Umbright, Christina; Sellamuthu, Rajendran

    2015-01-01

    The number of new chemicals that are being synthesized each year has been steadily increasing. While chemicals are of immense benefit to mankind, many of them have a significant negative impact, primarily owing to their inherent chemistry and toxicity, on the environment as well as human health. In addition to chemical exposures, human exposures to numerous non-chemical toxic agents take place in the environment and workplace. Given that human exposure to toxic agents is often unavoidable and many of these agents are found to have detrimental human health effects, it is important to develop strategies to prevent the adverse health effects associated with toxic exposures. Early detection of adverse health effects as well as a clear understanding of the mechanisms, especially at the molecular level, underlying these effects are key elements in preventing the adverse health effects associated with human exposure to toxic agents. Recent developments in genomics, especially transcriptomics, have prompted investigations into this important area of toxicology. Previous studies conducted in our laboratory and elsewhere have demonstrated the potential application of blood gene expression profiling as a sensitive, mechanistically relevant and practical surrogate approach for the early detection of adverse health effects associated with exposure to toxic agents. The advantages of blood gene expression profiling as a surrogate approach to detect early target organ toxicity and the molecular mechanisms underlying the toxicity are illustrated and discussed using recent studies on hepatotoxicity and pulmonary toxicity. Furthermore, the important challenges this emerging field in toxicology faces are presented in this review article. PMID:23456664

  6. Toxicologic methods: controlled human exposures.

    PubMed Central

    Utell, M J; Frampton, M W

    2000-01-01

    The assessment of risk from exposure to environmental air pollutants is complex, and involves the disciplines of epidemiology, animal toxicology, and human inhalation studies. Controlled, quantitative studies of exposed humans help determine health-related effects that result from breathing the atmosphere. The major unique feature of the clinical study is the ability to select, control, and quantify pollutant exposures of subjects of known clinical status, and determine their effects under ideal experimental conditions. The choice of outcomes to be assessed in human clinical studies can be guided by both scientific and practical considerations, but the diversity of human responses and responsiveness must be considered. Subjects considered to be among the most susceptible include those with asthma, chronic obstructive lung disease, and cardiovascular disease. New experimental approaches include exposures to concentrated ambient air particles, diesel engine exhaust, combustion products from smoking machines, and experimental model particles. Future investigations of the health effects of air pollution will benefit from collaborative efforts among the disciplines of epidemiology, animal toxicology, and human clinical studies. PMID:10931779

  7. Nutritional toxicology: basic principles and actual problems.

    PubMed

    Hathcock, J N

    1990-01-01

    Nutritional toxicology is a specialty that combines the backgrounds and research approaches of nutrition and toxicology. Many problems of substantial importance to health and food safety involve interactions of nutrition process and requirement with the effects of toxicological impact. Solution of these problems requires research that meets the procedural and design criteria of experimental nutrition and these of experimental toxicology. The relationships may be described in three basic categories: (1) influence of nutrition on toxicities; (2) influence of toxicants on nutrition; and (3) toxicities of nutrients. Trypsin inhibitor research, an example of diet impacting on toxicological response, illustrates the necessity of controlling nutritional composition aspects that can confound the results. Prolonged acetaminophen administration provides an example of the effects of toxicants on nutritional requirement and function which could be important for persons with marginal sulphur amino acid intake.

  8. Systems Toxicology: Systematic Approach to Predict Toxicity.

    PubMed

    Kiani, Narsis A; Shang, Ming-Mei; Tegner, Jesper

    2016-01-01

    Drug discovery is complex and expensive. Numerous drug candidates fail late in clinical trials or even after being released to the market. These failures are not only due to commercial considerations and less optimal drug efficacies but, adverse reactions originating from toxic effects also constitute a major challenge. During the last two decades, significant advances have been made enabling the early prediction of toxic effects using in silico techniques. However, by design, these essentially statistical techniques have not taken the disease driving pathophysiological mechanisms into account. The complexity of such mechanisms in combination with their interactions with drugspecific properties and environmental and life-style related factors renders the task of predicting toxicity on a purely statistical basis which is an insurmountable challenge. In response to this situation, an interdisciplinary field has developed, referred to as systems toxicology, where the notion of a network is used to integrate and model different types of information to better predict drug toxicity. In this study, we briefly review the merits and limitations of such recent promising predictive approaches integrating molecular networks, chemical compound networks, and protein drug association networks.

  9. Nanoparticles: pharmacological and toxicological significance

    PubMed Central

    Medina, C; Santos-Martinez, M J; Radomski, A; Corrigan, O I; Radomski, M W

    2007-01-01

    Nanoparticles are tiny materials (<1000 nm in size) that have specific physicochemical properties different to bulk materials of the same composition and such properties make them very attractive for commercial and medical development. However, nanoparticles can act on living cells at the nanolevel resulting not only in biologically desirable, but also in undesirable effects. In contrast to many efforts aimed at exploiting desirable properties of nanoparticles for medicine, there are limited attempts to evaluate potentially undesirable effects of these particles when administered intentionally for medical purposes. Therefore, there is a pressing need for careful consideration of benefits and side effects of the use of nanoparticles in medicine. This review article aims at providing a balanced update of these exciting pharmacological and potentially toxicological developments. The classes of nanoparticles, the current status of nanoparticle use in pharmacology and therapeutics, the demonstrated and potential toxicity of nanoparticles will be discussed. PMID:17245366

  10. Historical perspectives on cadmium toxicology

    SciTech Connect

    Nordberg, Gunnar F.

    2009-08-01

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

  11. Principles and procedures in forensic toxicology.

    PubMed

    Wyman, John F

    2012-09-01

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

  12. Multiscale Toxicology- Building the Next Generation Tools for Toxicology

    SciTech Connect

    Retterer, S. T.; Holsapple, M. P.

    2013-10-31

    A Cooperative Research and Development Agreement (CRADA) was established between Battelle Memorial Institute (BMI), Pacific Northwest National Laboratory (PNNL), Oak Ridge National Laboratory (ORNL), Brookhaven National Laboratory (BNL), Lawrence Livermore National Laboratory (LLNL) with the goal of combining the analytical and synthetic strengths of the National Laboratories with BMI's expertise in basic and translational medical research to develop a collaborative pipeline and suite of high throughput and imaging technologies that could be used to provide a more comprehensive understanding of material and drug toxicology in humans. The Multi-Scale Toxicity Initiative (MSTI), consisting of the team members above, was established to coordinate cellular scale, high-throughput in vitro testing, computational modeling and whole animal in vivo toxicology studies between MSTI team members. Development of a common, well-characterized set of materials for testing was identified as a crucial need for the initiative. Two research tracks were established by BMI during the course of the CRADA. The first research track focused on the development of tools and techniques for understanding the toxicity of nanomaterials, specifically inorganic nanoparticles (NPs). ORNL"s work focused primarily on the synthesis, functionalization and characterization of a common set of NPs for dissemination to the participating laboratories. These particles were synthesized to retain the same surface characteristics and size, but to allow visualization using the variety of imaging technologies present across the team. Characterization included the quantitative analysis of physical and chemical properties of the materials as well as the preliminary assessment of NP toxicity using commercially available toxicity screens and emerging optical imaging strategies. Additional efforts examined the development of high-throughput microfluidic and imaging assays for measuring NP uptake, localization, and

  13. COMPUTATIONAL TOXICOLOGY: FRAMEWORK, PARTNERSHIPS, AND PROGRAM DEVELOPMENT

    EPA Science Inventory

    Computational toxicology is a new research initiative being developed within the Office of Research and Development (ORD) of the US Environmental Protection Agency (EPA). Operationally, it is defined as the application of mathematical and computer models together with molecular c...

  14. Space Toxicology: Human Health during Space Operations

    NASA Technical Reports Server (NTRS)

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

    2010-01-01

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

  15. MINING ENVIRONMENTAL TOXICOLOGY INFORMATION WEB RESOURCES

    EPA Science Inventory

    Environmental toxicology is the study of the ecological effects of anthropogenic substances released into the environment. It is a relatively diverse field addressing impacts to aquatic and terrestrial organisms and communities. The determination of potential risk associated with...

  16. Reproductive Toxicology: From Science to Public Policy

    EPA Science Inventory

    Male reproductive toxicology research substantially influences policies that protect men's health. US policy directs regulatory agencies to ensure environmental protection for vulnerable groups, including boys and men where factors like age- and sex-specific sensitivities are app...

  17. Comparative BioInformatics and Computational Toxicology

    EPA Science Inventory

    Reflecting the numerous changes in the field since the publication of the previous edition, this third edition of Developmental Toxicology focuses on the mechanisms of developmental toxicity and incorporates current technologies for testing in the risk assessment process.

  18. Pulmonary toxicology of respirable particles. [Lead abstract

    SciTech Connect

    Sanders, C.L.; Cross, F.T.; Dagle, G.E.; Mahaffey, J.A.

    1980-09-01

    Separate abstracts were prepared for the 44 papers presented in these proceedings. The last paper (Stannard) in the proceedings is an historical review of the field of inhalation toxicology and is not included in the analytics. (DS)

  19. IRIS Toxicological Review of Trichloroacetic Acid (TCA) ...

    EPA Pesticide Factsheets

    On September 24, 2009, the Toxicological Review of Trichloroacetic Acid (TCA) 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 before public release. In the new IRIS process, introduced by the EPA Administrator, all written comments on IRIS assessments submitted by other federal agencies and White House Offices will be made publicly available. Accordingly, interagency comments and the interagency science consultation draft of the IRIS Toxicological Review of Trichloroacetic Acid and the charge to external peer reviewers are posted on this site. The draft Toxicological Review of Trichloroacetic Acid provides scientific support and rationale for the hazard identification and dose-response assessment pertaining to chronic exposure to trichloroacetic acid.

  20. Techniques for Investigating Molecular Toxicology of Nanomaterials.

    PubMed

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

    2016-06-01

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

  1. Multiscale Toxicology - Building the Next Generation Tools for Toxicology

    SciTech Connect

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

    2012-09-01

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

  2. Modern Instrumental Methods in Forensic Toxicology*

    PubMed Central

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

    2009-01-01

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

  3. lazar: a modular predictive toxicology framework

    PubMed Central

    Maunz, Andreas; Gütlein, Martin; Rautenberg, Micha; Vorgrimmler, David; Gebele, Denis; Helma, Christoph

    2013-01-01

    lazar (lazy structure–activity relationships) is a modular framework for predictive toxicology. Similar to the read across procedure in toxicological risk assessment, lazar creates local QSAR (quantitative structure–activity relationship) models for each compound to be predicted. Model developers can choose between a large variety of algorithms for descriptor calculation and selection, chemical similarity indices, and model building. This paper presents a high level description of the lazar framework and discusses the performance of example classification and regression models. PMID:23761761

  4. IRIS Toxicological Review of Trichloroacetic Acid (TCA) ...

    EPA Pesticide Factsheets

    EPA is releasing the draft report, Toxicological Review of Trichloroacetic Acid (TCA), that was distributed to Federal agencies and White House Offices for comment during the Science Discussion step of the IRIS Assessment Development Process. Comments received from other Federal agencies and White House Offices are provided below with external peer review panel comments. The draft Toxicological Review of Trichloroacetic Acid provides scientific support and rationale for the hazard identification and dose-response assessment pertaining to chronic exposure to trichloroacetic acid.

  5. Integrating zebrafish toxicology and nanoscience for safer product development.

    PubMed

    Kim, Ki-Tae; Tanguay, Robert L

    2013-04-01

    The design, manufacture and application of safer products and manufacturing processes have been important goals over the last decade and will advance in the future under the umbrella of "Green Chemistry". In this review, we focus on the burgeoning diversity of new engineered nanomaterials (ENMs) and the prescient need for a nanotoxicology paradigm that quickly identifies potentially hazardous nanochemistries. Advances in predictive toxicological modeling in the developing zebrafish offer the most immediate translation to human hazard that is practically achievable with high throughput approaches. Translation in a vertebrate model that is also a low cost alternative to rodents for hazard prediction has been a desirable but elusive testing paradigm. The utility of zebrafish, if applied early in the ENM discovery pipeline, could greatly enhance efforts toward greener and more efficient nanoscience. Early pipeline detection of human and environmental health impacts will quickly inform decisions in the design and production of safer commercial ENMs.

  6. The State of the Art of the Zebrafish Model for Toxicology and Toxicologic Pathology Research—Advantages and Current Limitations

    PubMed Central

    Spitsbergen, Jan M.; Kent, Michael L.

    2007-01-01

    The zebrafish (Danio rerio) is now the pre-eminent vertebrate model system for clarification of the roles of specific genes and signaling pathways in development. The zebrafish genome will be completely sequenced within the next 1–2 years. Together with the substantial historical database regarding basic developmental biology, toxicology, and gene transfer, the rich foundation of molecular genetic and genomic data makes zebrafish a powerful model system for clarifying mechanisms in toxicity. In contrast to the highly advanced knowledge base on molecular developmental genetics in zebrafish, our database regarding infectious and noninfectious diseases and pathologic lesions in zebrafish lags far behind the information available on most other domestic mammalian and avian species, particularly rodents. Currently, minimal data are available regarding spontaneous neoplasm rates or spontaneous aging lesions in any of the commonly used wild-type or mutant lines of zebrafish. Therefore, to fully utilize the potential of zebrafish as an animal model for understanding human development, disease, and toxicology we must greatly advance our knowledge on zebrafish diseases and pathology. PMID:12597434

  7. A Synopsis of the "Influence of Epigenetics, Genetics, and Immunology" Session Part A at the 35th Annual Society of Toxicologic Pathology Symposium.

    PubMed

    Harrill, Alison H; Moggs, Jonathan G; Adkins, Karissa K; Augustin, Hellmut G; Johnson, Robert C; Leach, Michael W

    2017-01-01

    The overarching theme of the 2016 Society of Toxicology Pathology's Annual Symposium was "The Basis and Relevance of Variation in Toxicologic Responses." Session 4 focused on genetic variation as a potential source for variability in toxicologic responses within nonclinical toxicity studies and further explored how knowledge of genetic traits might enable targeted prospective and retrospective studies in drug development and human health risk assessment. In this session, the influence of both genetic sequence variation and epigenetic modifications on toxicologic responses and their implications for understanding risk were explored. In this overview, the presentations in this session will be summarized, with a goal of exploring the ramifications of genetic and epigenetic variability within and across species for toxicity studies and disseminating information regarding novel tools to harness this variability to advance understanding of toxicologic responses across populations.

  8. Regulatory forum opinion piece: differences between protein-based biologic products (biotherapeutics) and chemical entities (small molecules) of relevance to the toxicologic pathologist.

    PubMed

    Leach, Michael W

    2013-01-01

    With the advances in cell culture methodologies and molecular biology that have occurred over the past several decades, biologics have become as common as small molecules within the portfolios of the pharmaceutical industry. Toxicologic pathologists should be aware of some of the fundamental differences between small molecules and biologics. Effects are not always observed in studies following administration of biologics. When findings are observed, the toxicologic pathologist should initially determine whether the effect(s) are mediated (directly or indirectly) via the intended pharmacology, exaggerated pharmacology, an immune response, and/or off target effects. Following this determination, the toxicologic pathologist should provide an assessment regarding the relevance of the findings to the intended clinical population, usually humans. The toxicologic pathologist may also be asked to assess unusual species and models. Given their broad background in physiology and immunology, toxicologic pathologists are uniquely positioned to provide this input to drug development teams.

  9. Acetylcholinesterase Inhibitors: Pharmacology and Toxicology

    PubMed Central

    Čolović, Mirjana B; Krstić, Danijela Z; Lazarević-Pašti, Tamara D; Bondžić, Aleksandra M; Vasić, Vesna M

    2013-01-01

    Acetylcholinesterase is involved in the termination of impulse transmission by rapid hydrolysis of the neurotransmitter acetylcholine in numerous cholinergic pathways in the central and peripheral nervous systems. The enzyme inactivation, induced by various inhibitors, leads to acetylcholine accumulation, hyperstimulation of nicotinic and muscarinic receptors, and disrupted neurotransmission. Hence, acetylcholinesterase inhibitors, interacting with the enzyme as their primary target, are applied as relevant drugs and toxins. This review presents an overview of toxicology and pharmacology of reversible and irreversible acetylcholinesterase inactivating compounds. In the case of reversible inhibitors being commonly applied in neurodegenerative disorders treatment, special attention is paid to currently approved drugs (donepezil, rivastigmine and galantamine) in the pharmacotherapy of Alzheimer’s disease, and toxic carbamates used as pesticides. Subsequently, mechanism of irreversible acetylcholinesterase inhibition induced by organophosphorus compounds (insecticides and nerve agents), and their specific and nonspecific toxic effects are described, as well as irreversible inhibitors having pharmacological implementation. In addition, the pharmacological treatment of intoxication caused by organophosphates is presented, with emphasis on oxime reactivators of the inhibited enzyme activity administering as causal drugs after the poisoning. Besides, organophosphorus and carbamate insecticides can be detoxified in mammals through enzymatic hydrolysis before they reach targets in the nervous system. Carboxylesterases most effectively decompose carbamates, whereas the most successful route of organophosphates detoxification is their degradation by corresponding phosphotriesterases. PMID:24179466

  10. Introduction: biomarkers in neurodevelopment toxicology

    SciTech Connect

    Needleman, H.L.

    1987-10-01

    The search for markers of toxicant exposure and effect upon the development of organisms presents a set of challenges that differ in many ways from those encountered in the study of markers in reproduction or pregnancy. These latter two fields specify a relatively narrow set of organs or biological systems. The term development, on the other hand, can apply to any organ system, or to any set of phenomena that changes in an ordered way over time. For this reason the papers presented in the session on development were chosen to narrow the focus to neurodevelopmental markers, as such markers may be altered by neurotoxic exposure. In attempting to meet this task, the authors have been able to select a group of investigators who work at the leading edges of their respective fields of developmental neuroanatomy, neurotoxicology, neuroendocrinology, neuropsychology, and infant development. The notion that toxicants could affect behavior certainly is not new. Recent knowledge that behavioral aberrations can occur at exposures below those which produce organic changes, and that behavioral aberrations can occur at exposures below those which produce organic changes, and that behavioral observation might provide early markers of effect has given rise to two new fields: behavioral toxicology and behavioral teratology.

  11. [Toxicological evaluation in the childhood].

    PubMed

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

    2014-03-01

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

  12. New achievements in human cell toxicology: the 20th annual workshop on in vitro toxicology.

    PubMed

    Kolman, Ada

    2003-01-01

    The 20th Annual Workshop on In Vitro Toxicology (Oxford, UK, September 22-24, 2002) was convened as part of a European meeting entitled Human Cell Culture 2002. The meeting was arranged by the Scandinavian Society for Cell Toxicology (SSCT), the European Tissue Culture Society and the British Prostate Group. Two sessions, which are summarised in this report, were devoted to in vitro toxicology: Human Cell Toxicology and The SSCT Free Paper Session. Outstanding experts in the field of toxicology outlined contemporary approaches in toxicity testing in their lectures. Short oral presentations demonstrated a variety of in vitro model systems and methodologies, which can be useful for investigating human toxicity, as well as for studies on mechanisms of toxicity.

  13. Non-precautionary aspects of toxicology

    SciTech Connect

    Grandjean, Philippe . E-mail: pgrand@health.sdu.dk

    2005-09-01

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

  14. Various aspects of piscine toxicology

    PubMed Central

    Wlasow, Teresa; Demska-Zakes, Krystyna; Gomulka, Piotr; Jarmolowicz, Sylwia

    2010-01-01

    In opposition to toxicology of mammals piscine toxicology is closely connected with the conditions of external environment. The aquatic environment is necessary for embryonic development and after hatching during short or long-lasting larval period of most fish species. An aquatic environment is polluted by many industrial and agricultural wastes. Ammonia as a toxic and common compound in water have negative influence for aquaculture especially in intensive fish culture, recirculation system and hatchery facilities. Acute toxicity of ammonia was investigated in carp Cyprinus carpio L. and developmental stages of chub Squalius cephalus L. Changes in the peripheral blood characteristics and hemopoietic tissues of carp occurred after exposition to ammonia in acute tests and 3, 5 and 10 weeks sublethal concetration. The observed increase of the concentration of most amino acids in fish intoxicated with amonia suggests that the process reflects detoxication of ammonia which takes place both in the brain and muscles after 3 weeks of exposition. Phenol intoxication tests induced considerable unfavorable changes in the blood and dystrophic and necrobiotic lesions in tissues of fish leading to dysfunction both hemopoietic and reproductive processes. In study on fish reproduction disruptors the influence of oxygenated polycyclic hydrocarbons (17-β-estradiol, 4,7-dihydroxyisoflavone, 1,6-dihydroxynaphthalene and 1,5-dihydroxynaphthalene) and oxygenated monocyclic hydrocarbons (phenol, 4-n-heptylphenol, 4-n-buthylphenol, 4-sec-buthylphenol; 4-tert-buthylphenol) was assessed using histopathological methods. It was established that examined oxygenated aromatic hydrocarbons both natural (17-β-estradiol and 4,7-dihydroxyisoflavone) and synthetic can disrupt the differentiation of primary and secondary sex traits in pikeperch Sander lucioperca L. The chronic activity of these “biomimetics of estrogen” can lead to the disappearance of natural fish population. In vivo and in

  15. Clinical toxicology: clinical science to public health.

    PubMed

    Bateman, D N

    2005-11-01

    1. The aims of the present paper are to: (i) review progress in clinical toxicology over the past 40 years and to place it in the context of modern health care by describing its development; and (ii) illustrate the use of clinical toxicology data from Scotland, in particular, as a tool for informing clinical care and public health policy with respect to drugs. 2. A historical literature review was conducted with amalgamation and comparison of a series of published and unpublished clinical toxicology datasets from NPIS Edinburgh and other sources. 3. Clinical databases within poisons treatment centres offer an important method of collecting data on the clinical effects of drugs in overdose. These data can be used to increase knowledge on drug toxicity mechanisms that inform licensing decisions, contribute to evidence-based care and clinical management. Combination of this material with national morbidity datasets provides another valuable approach that can inform public health prevention strategies. 4. In conclusion, clinical toxicology datasets offer clinical pharmacologists a new study area. Clinical toxicology treatment units and poisons information services offer an important health resource.

  16. Innovations in testing strategies in reproductive toxicology.

    PubMed

    Piersma, Aldert H

    2013-01-01

    Toxicological hazard assessment currently finds itself at a crossroads where the existing classical test paradigm is challenged by a host of innovative approaches. Animal study protocols are being enhanced for additional parameters and improved for more efficient effect assessment with reduced animal numbers. Whilst existing testing paradigms have generally proven conservative for chemical safety assessment, novel alternative in silico and in vitro approaches and assays are being introduced that begin to elucidate molecular mechanisms of toxicity. Issues such as animal welfare, alternative assay validation, endocrine disruption, and the US-NAS report on toxicity testing in the twenty-first century have provided directionality to these developments. The reductionistic nature of individual alternative assays requires that they be combined in a testing strategy in order to provide a complete picture of the toxicological profile of a compound. One of the challenges of this innovative approach is the combined interpretation of assay results in terms of toxicologically relevant effects. Computational toxicology aims at providing that integration. In order to progress, we need to follow three steps: (1) Learn from past experience in animal studies and human diseases about critical end points and pathways of toxicity. (2) Design alternative assays for essential mechanisms of toxicity. (3) Build an integrative testing strategy tailored to human hazard assessment using a battery of available alternative tests for critical end points that provides optimal in silico and in vitro filters to upgrade toxicological hazard assessment to the mechanistic level.

  17. 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...

  18. 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...

  19. Comparison of toxicological and radiological aspects of K basins sludge

    SciTech Connect

    RITTMANN, P.D.

    1999-10-27

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

  20. 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.

  1. IRIS Toxicological Review of Acrylamide (External Review ...

    EPA Pesticide Factsheets

    EPA has conducted a peer review by EPA’s Science Advisory Board (SAB) of the scientific basis supporting the human health hazard and dose-response assessment of acrylamide that once finalized will appear on the Integrated Risk Information System (IRIS) database. Peer review is meant to ensure that the science is used credibly and appropriately in derivation of the dose-response assessments and toxicological characterization. The draft Toxicological Review of Acrylamide provides scientific support and rationale for the hazard identification and dose-response assessment pertaining to a chronic exposure to acrylamide.

  2. In silico toxicology - non-testing methods.

    PubMed

    Raunio, Hannu

    2011-01-01

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

  3. Toxicological benchmarks for wildlife: 1996 Revision

    SciTech Connect

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

    1996-06-01

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

  4. Behavioral Toxicological Studies of Pesticides in Laboratory Rats,

    DTIC Science & Technology

    Behavior, *Toxicology, *Pesticides, *Rats, Symposia, Laboratory tests, Toxicity, Insecticides, Exposure( General ), Dosage, Perception, Motor reactions, Learning, Military psychology , Military medicine

  5. Recent advances in toxicological testing of the stratum corneum.

    PubMed

    Piérard, G E; Piérard-Franchimont, C; Hermanns-Lê, T; Paquet, P

    2014-09-01

    α-Hydroxy acid (AHA) formulations are commonly used for skin chemical peelings. The primary target is the stratum corneum (SC). The aim of this study was to assess the effects of various glycolic acid concentrations and commercial phenolic acid formulations on the SC. Quantitative colorimetry of a corneoxenometry bioassay was used. The test procedure involved glycolic acid concentrations ranging from 3% to 70% in alcoholic solution. Exposure times were set for 1 min and 3 min. The bioassay showed consistent reactivity with a dose-effect relationship when using the selected low exposure times. In a similar procedure the aggressiveness of commercially available phenolic acid formulations was identified not using hazardous in vivo testing. Corneoxenometry appears useful for in vitro testing of AHA peeling agents during short exposure times.

  6. The use of comet assay in plant toxicology: recent advances

    PubMed Central

    Santos, Conceição L. V.; Pourrut, Bertrand; Ferreira de Oliveira, José M. P.

    2015-01-01

    The systematic study of genotoxicity in plants induced by contaminants and other stress agents has been hindered to date by the lack of reliable and robust biomarkers. The comet assay is a versatile and sensitive method for the evaluation of DNA damages and DNA repair capacity at single-cell level. Due to its simplicity and sensitivity, and the small number of cells required to obtain robust results, the use of plant comet assay has drastically increased in the last decade. For years its use was restricted to a few model species, e.g., Allium cepa, Nicotiana tabacum, Vicia faba, or Arabidopsis thaliana but this number largely increased in the last years. Plant comet assay has been used to study the genotoxic impact of radiation, chemicals including pesticides, phytocompounds, heavy metals, nanoparticles or contaminated complex matrices. Here we will review the most recent data on the use of this technique as a standard approach for studying the genotoxic effects of different stress conditions on plants. Also, we will discuss the integration of information provided by the comet assay with other DNA-damage indicators, and with cellular responses including oxidative stress, cell division or cell death. Finally, we will focus on putative relations between transcripts related with DNA damage pathways, DNA replication and repair, oxidative stress and cell cycle progression that have been identified in plant cells with comet assays demonstrating DNA damage. PMID:26175750

  7. 40 CFR 158.500 - Toxicology data requirements table.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES Toxicology § 158.500 Toxicology data requirements table... this section to determine the toxicology data requirements for a particular pesticide product. Notes... cholinesterase activity for certain pesticides, e.g., organophosphates and some carbamates. The route of...

  8. 40 CFR 158.500 - Toxicology data requirements table.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES Toxicology § 158.500 Toxicology data requirements table... this section to determine the toxicology data requirements for a particular pesticide product. Notes... cholinesterase activity for certain pesticides, e.g., organophosphates and some carbamates. The route of...

  9. 40 CFR 158.500 - Toxicology data requirements table.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES Toxicology § 158.500 Toxicology data requirements table... this section to determine the toxicology data requirements for a particular pesticide product. Notes... cholinesterase activity for certain pesticides, e.g., organophosphates and some carbamates. The route of...

  10. 40 CFR 158.500 - Toxicology data requirements table.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES Toxicology § 158.500 Toxicology data requirements table... this section to determine the toxicology data requirements for a particular pesticide product. Notes... cholinesterase activity for certain pesticides, e.g., organophosphates and some carbamates. The route of...

  11. 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... Systems § 862.3280 Clinical toxicology control material. (a) Identification. A clinical toxicology control... detect and monitor systematic deviations from accuracy resulting from reagent or instrument defects....

  12. Mammalian Toxicology Testing: Problem Definition Study. Part 3. Impact Of Future Changes Report.

    DTIC Science & Technology

    1981-03-01

    selected areas of the nervous system (brain, spinal cord or peripheral nerves) for pathological changes using contemporary morphological methods. Other...that affect the peripheral nervous system . Behavioral toxicology suffers from a lack of specificity and will require a larger data base before it is... nervous system have recently undergone a significant advancement through the use of fixation and epoxy embedding techniques with light microscopes for

  13. Delivering The Benefits of Chemical-Biological Integration in Computational Toxicology at the EPA (ACS Fall meeting)

    EPA Science Inventory

    Abstract: Researchers at the EPA’s National Center for Computational Toxicology integrate advances in biology, chemistry, and computer science to examine the toxicity of chemicals and help prioritize chemicals for further research based on potential human health risks. The intent...

  14. Reflections on the Origins and Evolution of Genetic Toxicology and the Environmental Mutagen Society

    SciTech Connect

    Wassom, John S.; Malling, Heinrich V.; Sankaranarayanan, K.; Lu, Po-Yung

    2010-01-01

    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 of 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

  15. 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.

  16. IRIS Toxicological Review of Chloroprene (Final Report)

    EPA Science Inventory

    The final Toxicological Review of Chloroprene provides scientific support and rationale for the hazard and dose-response assessment pertaining to chronic exposure to chloroprene. Chloroprene (C4H5Cl) is a volatile, flammable liquid used primarily in the manufacture of poly...

  17. IRIS Toxicological Review of Hexachloroethane (Final Report)

    EPA Science Inventory

    EPA has finalized the Toxicological Review of Hexachloroethane: in support of the Integrated Risk Information System (IRIS). Now final, this assessment may be used by EPA’s program and regional offices to inform decisions to protect human health.

  18. FISH PHYSIOLOGY, TOXICOLOGY, AND WATER QUALITY

    EPA Science Inventory

    Scientists from ten countries presented papers at the Fifth International Symposium on Fish Physiology, Toxicology, and Water Quality, which was held on the campus of the city University of Hong Kong on November 10-13, 1998. These Proceedings include 23 papers presented in sessi...

  19. FISH PHYSIOLOGY, TOXICOLOGY, AND WATER QUALITY:

    EPA Science Inventory

    Twenty-one participants from Europe, North America and China convened in Chongqing, China, October 12-14, 2005, for the Eighth International Symposium in Fish Physiology, Toxicology and Water Quality. The subject of the meeting was "Hypoxia in vertebrates: Comparisons of terrestr...

  20. IRIS TOXICOLOGICAL REVIEW OF PHOSGENE (2006 Final)

    EPA Science Inventory

    EPA is announcing 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 Quickview have also been added to the IRIS Database.

  1. Toxicologic Studies for Investigational New Drugs.

    DTIC Science & Technology

    This annual report presents the results of three toxicological studies on an investigational new drug completed from 15 September 1981 through 30...Investigational New Drug Applications for Phase I and early Phase II clinical studies. One drug (WR 6026-2HCl) has been tested for Walter Reed Army

  2. IRIS TOXICOLOGICAL REVIEW OF ACROLEIN (2003 Final)

    EPA Science Inventory

    EPA is announcing 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 Quickview have also been added to the IRIS Database.

  3. IRIS Toxicological Review of Vanadium Pentoxide ...

    EPA Pesticide Factsheets

    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 White House Offices before public release. In the new IRIS process (May 2009), introduced by the EPA Administrator, all written comments on IRIS assessments submitted by other federal agencies and White House Offices will be made publicly available. Accordingly, interagency comments and the interagency science consultation draft of the IRIS Toxicological Review of Vanadium Pentoxide and the charge to external peer reviewers are posted on this site. EPA is reassessing its IRIS toxicological review of vanadium pentoxide (CASRN 1314-62-1). This vanadium pentoxide reassessment consists of an oral reference dose (RfD), an inhalation reference concentration (RfC), an inhalation unit risk (IUR) and a cancer weight of evidence descriptor. This is the first assessment developing an RfC or IUR for this compound. This assessment is intended to provide human health data to support agency regulatory decisions.

  4. Toxicology of protein allergenicity: prediction and characterization.

    PubMed

    Kimber, I; Kerkvliet, N I; Taylor, S L; Astwood, J D; Sarlo, K; Dearman, R J

    1999-04-01

    The ability of exogenous proteins to cause respiratory and gastrointestinal allergy, and sometimes systemic anaphylactic reactions, is well known. What is not clear however, are the properties that confer on proteins the ability to induce allergic sensitization. With an expansion in the use of enzymes for industrial applications and consumer products, and a substantial and growing investment in the development of transgenic crop plants that express novel proteins introduced from other sources, the issue of protein allergenicity has assumed considerable toxicological significance. There is a need now for methods that will allow the accurate identification and characterization of potential protein allergens and for estimation of relative potency as a first step towards risk assessment. To address some of these issues, and to review progress that has been made in the toxicological investigation of respiratory and gastrointestinal allergy induced by proteins, a workshop, entitled the Toxicology of Protein Allergenicity: Prediction and Characterization, was convened at the 37th Annual Conference of the Society of Toxicology in Seattle, Washington (1998). The subject of protein allergenicity is considered here in the context of presentations made at that workshop.

  5. IRIS Toxicological Review of Pentachlorophenol (Final Report)

    EPA Science Inventory

    EPA has finalized the Toxicological Review of Pentachlorophenol: in support of the Integrated Risk Information System (IRIS). Now final, this assessment may be used by EPA’s program and regional offices to inform decisions to protect human health.

  6. IRIS Toxicological Review of Chloroform (Final Report)

    EPA Science Inventory

    EPA is announcing the release of the final report, Toxicological Review of Chloroform: in support of the Integrated Risk Information System (IRIS). The updated Summary for Chloroform and accompanying Quickview have also been added to the IRIS Database.

  7. IRIS Toxicological Review of Naphthalene (1998 Final)

    EPA Science Inventory

    EPA is announcing 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 Quickview have also been added to the IRIS Database.

  8. IRIS Toxicological Review of Biphenyl (Final Report)

    EPA Science Inventory

    EEPA has finalized the Toxicological Review of Biphenyl: in support of the Integrated Risk Information System (IRIS). Now final, this assessment may be used by EPA’s program and regional offices to inform decisions to protect human health.

  9. Exposure science and the U.S. EPA National Center for Computational Toxicology.

    PubMed

    Cohen Hubal, Elaine A; Richard, Ann M; Shah, Imran; Gallagher, Jane; Kavlock, Robert; Blancato, Jerry; Edwards, Stephen W

    2010-05-01

    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 integration of modern computing with molecular biology and chemistry will allow scientists to better prioritize data, inform decision makers on chemical risk assessments and understand a chemical's progression from the environment to the target tissue within an organism and ultimately to the key steps that trigger an adverse health effect. In this paper, several of the major research activities being sponsored by Environmental Protection Agency's National Center for Computational Toxicology are highlighted. Potential links between research in computational toxicology and human exposure science are identified. As with the traditional approaches for toxicity testing and hazard assessment, exposure science is required to inform design and interpretation of high-throughput assays. In addition, common themes inherent throughout National Center for Computational Toxicology research activities are highlighted for emphasis as exposure science advances into the 21st century.

  10. FutureTox II: In vitro Data and In Silico Models for Predictive Toxicology

    PubMed Central

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

    2015-01-01

    FutureTox II, a Society of Toxicology Contemporary Concepts in Toxicology workshop, was held in January, 2014. The meeting goals were to review and discuss the state of the science in toxicology in the context of implementing the NRC 21st century vision of predicting in vivo responses from in vitro and in silico data, and to define the goals for the future. Presentations and discussions were held on priority concerns such as predicting and modeling of metabolism, cell growth and differentiation, effects on sensitive subpopulations, and integrating data into risk assessment. Emerging trends in technologies such as stem cell-derived human cells, 3D organotypic culture models, mathematical modeling of cellular processes and morphogenesis, adverse outcome pathway development, and high-content imaging of in vivo systems were discussed. Although advances in moving towards an in vitro/in silico based risk assessment paradigm were apparent, knowledge gaps in these areas and limitations of technologies were identified. Specific recommendations were made for future directions and research needs in the areas of hepatotoxicity, cancer prediction, developmental toxicity, and regulatory toxicology. PMID:25628403

  11. Distance learning in toxicology: Australia's RMIT program

    SciTech Connect

    Ahokas, Jorma . E-mail: Jorma.ahokas@rmit.edu.au; Donohue, Diana; Rix, Colin; Wright, Paul

    2005-09-01

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

  12. Use of toxicological information in drug design.

    PubMed

    Matthews, E J; Benz, R D; Contrera, J F

    2000-12-01

    This paper is an extension of the keynote address and another talk at the Symposium on the Use of Toxiciological Information in Drug Design. The symposium was organized by American Chemical Society's Chemical Information Division at the 220th National Meeting of the American Chemical Society in Washington, DC, August 20-24, 2000. We outline an approach for meeting the scientific information needs of the U.S. Food and Drug Administration (FDA). Ready access to scientific information is critical to support safety-related regulatory decisions and is especially valuable in situations where available experimental information from in vivo/in vitro studies are inadequate or unavailable. This approach also has applications for lead selection in drug discovery. A pilot electronic toxicology/safety knowledge base and computational toxicology initiative is underway in the FDA Center for Drug Evaluation and Research (CDER) that may be a prototype for an FDA knowledge base. The objectives of this effort are: (i) to strengthen and broaden the scientific basis of regulatory decisions, (ii) to provide the Agency with an electronic scientific institutional memory, (iii) to create a scientific resource for regulatory and applied research, and (iv) to establish an internal Web-based support service that can provide decision support information for regulators that will facilitate the review process and improve consistency and uniformity. An essential component of this scientific knowledge base is the creation of a comprehensive electronic inventory of CDER-regulated substances that permit identification of clusters of substances having similar chemical, pharmacological or toxicological activities, and molecular structure/substructures. Furthermore, the inventory acts as a pointer and link to other databases and critical non-clinical and clinical pharmacology/toxicology studies and reviews in FDA archives. Clusters of related substances are identified through the use of: (i) an

  13. 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.

  14. 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.

  15. IRIS Toxicological Review of Inorganic Arsenic (Cancer) ...

    EPA Pesticide Factsheets

    On February 19, 2010, the draft IRIS Toxicological Review of Inorganic Arsenic (Cancer) external review draft document and the charge to external peer reviewers were released for public review and comment. The draft document and the charge to external peer reviewers were reviewed internally by EPA and by other federal agencies and White House Offices before public release. In the new IRIS process, introduced by the EPA Administrator, all written comments on IRIS assessments submitted by other federal agencies and White House Offices will be made publicly available. Accordingly, interagency comments and the interagency science consultation draft of the Toxicological Review of Inorganic Arsenic and the charge to external peer reviewers are posted on this site. This draft IRIS health assessment addresses only cancer human health effects that may result from chronic exposure to this chemical. An assessment of noncancer health effects of inorganic arsenic will be released for external peer review and public comment at a later date.

  16. [European Union funds and clinical toxicology].

    PubMed

    Wiszniewiecka, Monika; Cejrowski, Daniel; Sein Anand, Jacek

    2015-01-01

    Since 2014 we are heading the third programming period of help from European Union (EU). The new budget will run until 2020. From common resources of EU, 106 billion euro will reach Poland, of which about 82.3 billion to cohesion policy, levelling differences of regional development. Clinical toxicology centres will be able to apply for funding under the allocation for the health service. Polish health service very actively benefited from EU funds in previous programming periods, between 2004-2006, and 2007-2013. Thanks to grants from the EU, a large number of health centres were built or renovated. Unfortunately the needs of hospitals, which were underinvested for many years, exceeded available funds according to UE programmes. Except investment projects, also projects training of health professionals were executed. In the current programming period European Union will still support projects aimed at health service. Clinical toxicology centres should have a try of using this period to fulfil their plans.

  17. Nano-technology and nano-toxicology.

    PubMed

    Maynard, Robert L

    2012-01-01

    Rapid developments in nano-technology are likely to confer significant benefits on mankind. But, as with perhaps all new technologies, these benefits are likely to be accompanied by risks, perhaps by new risks. Nano-toxicology is developing in parallel with nano-technology and seeks to define the hazards and risks associated with nano-materials: only when risks have been identified they can be controlled. This article discusses the reasons for concern about the potential effects on health of exposure to nano-materials and relates these to the evidence of the effects on health of the ambient aerosol. A number of hypotheses are proposed and the dangers of adopting unsubstantiated hypotheses are stressed. Nano-toxicology presents many challenges and will need substantial financial support if it is to develop at a rate sufficient to cope with developments in nano-technology.

  18. Nano-technology and nano-toxicology

    PubMed Central

    Maynard, Robert L.

    2012-01-01

    Rapid developments in nano-technology are likely to confer significant benefits on mankind. But, as with perhaps all new technologies, these benefits are likely to be accompanied by risks, perhaps by new risks. Nano-toxicology is developing in parallel with nano-technology and seeks to define the hazards and risks associated with nano-materials: only when risks have been identified they can be controlled. This article discusses the reasons for concern about the potential effects on health of exposure to nano-materials and relates these to the evidence of the effects on health of the ambient aerosol. A number of hypotheses are proposed and the dangers of adopting unsubstantiated hypotheses are stressed. Nano-toxicology presents many challenges and will need substantial financial support if it is to develop at a rate sufficient to cope with developments in nano-technology. PMID:22662021

  19. Current developments in toxicological research on arsenic

    PubMed Central

    Bolt, Hermann M.

    2013-01-01

    There is a plethora of recent publications on all aspects relevant to the toxicology of arsenic (As). Over centuries exposures to arsenic continue to be a major public health problem in many countries. In particular, the occurrence of high As concentrations in groundwater of Southeast Asia receives now much attention. Therefore, arsenic is a high-priority matter for toxicological research. Key exposure to As are (traditional) medicines, combustion of As-rich coal, presence of As in groundwater, and pollution due to mining activities. As-induced cardiovascular disorders and carcinogenesis present themselves as a major research focus. The high priority of this issue is now recognized politically in a number of countries, research funds have been made available. Also experimental research on toxicokinetics and toxicodynamics and on modes of toxic action is moving very rapidly. The matter is of high regulatory concern, and effective preventive measures are required in a number of countries. PMID:27092031

  20. Toxicological Investigation of Radioactive Uranium in Seawater

    PubMed Central

    Bae, Jeong Mi; Kim, Jin

    2012-01-01

    Trace uranium detection measurement was performed using DNA immobilized on a graphite pencil electrode (DGE). The developed probe was connected to the portable handheld voltammetric systems used for seawater analysis. The sensitive voltammogram was obtained within only 30 s accumulation time, and the anodic stripping working range was attained at 100~800 μg/l U and 10~50 μg/l. The statistic relative standard deviation of 30.0 mg/l with the 15th stripping was 0.2115. Here, toxicological and analytical application was performed in the seawater survey in a contaminated power plant controlling water. The results were found to be applicable for real-time toxicological assay for trace control. PMID:24278591

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

    SciTech Connect

    Calabrese, Edward J. . E-mail: edwardc@schoolph.umass.edu

    2005-04-01

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

  2. Particle toxicology: from coal mining to nanotechnology.

    PubMed

    Borm, Paul J A

    2002-03-01

    Particle research has been historically closely connected to industrial activities or materials, such as coal, asbestos, man-made mineral fibers, and more recently ambient particulate matter (PM). It is the purpose of this review to combine insights and developments in particle toxicology with the historical context of exposure and organizations sponsoring such research in Europe. In supporting research on particle-induced respiratory effects and mechanisms, research programs of the European Community on Steel and Coal (ECSC) have played a tremendous role. Current particle research in Europe is dominated by PM, and funded by the World Health Organization (WHO), European Union Framework programs, and the Health Effects Institute (HEI). Differences between historical and current research in particle toxicology include the exposure concentrations, particle size, target populations, endpoints, and length of exposure. Inhaled particle effects are no longer confined to the lung, since particles are suggested to translocate to the blood while lung inflammation invokes systemic responses. Finally, the particle size and concentrations have both been reduced about 100-fold from 2-5 mg/m3 to 20-50 mg/m3 and from 1-2 microm to 20-100 nm (ultrafine) as domestic fuel burning has decreased and vehicle sources have increased and attention has moved from coal mining industry to general environment. There is, however, a further occupational link to nanotechnology, which continuously produces new materials in the ultrafine range. Although inhalation exposure is considered to be minimal in this technology, some particles are produced to be used for carrier purpose in medical applications. Based on our current knowledge of particle toxicology, it is highly desirable that toxicology and technology are linked in this extremely rapid developing area, to learn more about potential risks and also to develop knowledge on the role of surface and size in particle toxicity.

  3. Mycotoxins: occurrence, toxicology, and exposure assessment.

    PubMed

    Marin, S; Ramos, A J; Cano-Sancho, G; Sanchis, V

    2013-10-01

    Mycotoxins are abiotic hazards produced by certain fungi that can grow on a variety of crops. Consequently, their prevalence in plant raw materials may be relatively high. The concentration of mycotoxins in finished products is usually lower than in raw materials. In this review, occurrence and toxicology of the main mycotoxins are summarised. Furthermore, methodological approaches for exposure assessment are described. Existing exposure assessments, both through contamination and consumption data and biomarkers of exposure, for the main mycotoxins are also discussed.

  4. IRIS Toxicological Review of Trichloroacetic Acid (TCA) ...

    EPA Pesticide Factsheets

    EPA is conducting a peer review and public comment of the scientific basis supporting the human health hazard and dose-response assessment of Trichloroacetic acid (TCA) that when finalized will appear on the Integrated Risk Information System (IRIS) database. The draft Toxicological Review of trichloroacetic acid provides scientific support and rationale for the hazard and dose-response assessment pertaining to chronic exposure to trichloroacetic acid.

  5. Toxicological benchmarks for wildlife: 1994 Revision

    SciTech Connect

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

    1994-09-01

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

  6. Love Canal: environmental and toxicological studies

    SciTech Connect

    Kim, C.S.

    1981-01-01

    The New York State Department of Health has been involved at the Love Canal since 1978. The State has carried out numerous environmental and toxicological studies. The major purposes for these studies were to define how Love Canal contaminants might be escaping into the environment at large, what paths contaminant migration might take, and what toxicological effects Love Canal chemicals might have individually and together. Although underground contaminant migration was hypothesized along swales and underground utility bedding, these mechanisms have been proven not to be operative except for some migration along the utility bedding under Frontier Avenue. In general no underground migration has occurred outside the confines of the three city blocks that contain the Love Canal referred to as the ''first ring''. Studies have been confused by apparent burial of waste materials in areas proximate but not directly connected to the Love Canal. Migration of Love Canal leachate has occurred through storm sewers. Love Canal contaminants have reached creeks to the north and the Niagara River to the south through storm sewer transport. In spite of finding 2, 3, 7, 8 tetrachlorodibenzoparadioxin (TCDD), toxicological studies in situ and through exposure to volatile components in Love Canal soils do not indicate unusual toxicity. Animal studies continue in an attempt to determine the teratogenic and fetotoxic potential of Love Canal chemicals under different routes of exposure.

  7. IRIS Toxicological Review of Ammonia (Interagency Science ...

    EPA Pesticide Factsheets

    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 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. EPA is undertaking an 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.

  8. Biological markers of male reproductive toxicology

    SciTech Connect

    Ewing, L.L.; Mattison, D.R.

    1987-10-01

    Reproduction is a complex, stepwise series of processes that begins with gametogenesis, continues through gamete interaction, implantation, embryonic development, growth, parturition, and postnatal adaptation, and is completed with the development and sexual maturation of the newly formed organism. These reproductive processes do not take place in a chemically pristine environment, but rather in an environment increasingly contaminated with the products and by-products of the chemical age in which we live. Some environmental pollutants are known to be carcinogenic, mutagenic, or toxic to the reproductive system, but most have not been adequately tested for reproductive toxicity. Just as reproduction is complex, biological mechanisms underlying toxicology are similarly complex and involve absorption, distribution, metabolism (toxification and/or detoxification), excretion, and repair. The synthesis of these sciences into the relatively nascent science of reproductive toxicology includes teratology, pharmacology, epidemiology, and occupational and environmental health. Female reproductive function (especially pregnancy outcome) has historically been the focus of attention, but there is increasing interest in the effects of chemical exposure on male reproductive function. Several reports have documented the physiology, biochemistry, and toxicology of male mammalian reproduction, and evaluated susceptibility of the male to the effects of exogenous chemicals.

  9. ICPP radiological and toxicological sabotage analysis

    SciTech Connect

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

    1995-10-01

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

  10. A toxicological review of the propylene glycols.

    PubMed

    Fowles, Jeff R; Banton, Marcy I; Pottenger, Lynn H

    2013-04-01

    The toxicological profiles of monopropylene glycol (MPG), dipropylene glycol (DPG), tripropylene glycol (TPG) and polypropylene glycols (PPG; including tetra-rich oligomers) are collectively reviewed, and assessed considering regulatory toxicology endpoints. The review confirms a rich data set for these compounds, covering all of the major toxicological endpoints of interest. The metabolism of these compounds share common pathways, and a consistent profile of toxicity is observed. The common metabolism provides scientific justification for adopting a read-across approach to describing expected hazard potential from data gaps that may exist for specific oligomers. None of the glycols reviewed presented evidence of carcinogenic, mutagenic or reproductive/developmental toxicity potential to humans. The pathologies reported in some animal studies either occurred at doses that exceeded experimental guidelines, or involved mechanisms that are likely irrelevant to human physiology and therefore are not pertinent to the exposures experienced by consumers or workers. At very high chronic doses, MPG causes a transient, slight decrease in hemoglobin in dogs and at somewhat lower doses causes Heinz bodies to form in cats in the absence of any clinical signs of anemia. Some evidence for rare, idiosyncratic skin reactions exists for MPG. However, the larger data set indicates that these compounds have low sensitization potential in animal studies, and therefore are unlikely to represent human allergens. The existing safety evaluations of the FDA, USEPA, NTP and ATSDR for these compounds are consistent and point to the conclusion that the propylene glycols present a very low risk to human health.

  11. IRIS Toxicological Review of Thallium and Compounds ...

    EPA Pesticide Factsheets

    Thallium compounds are used in the semiconductor industry, the manufacture of optic lenses and low-melting glass, low-temperature thermometers, alloys, electronic devices, mercury lamps, fireworks, and imitation germs, and clinically as an imaging agent in the diagnosis of certain tumors. EPA's assessment of noncancer health effects and carcinogenic potential of thallium compounds was last prepared and added to the IRIS database between 1988 and 1990. The IRIS program is preparing an assessment that will incorporate current health effects information available for thallium and compounds, and current risk assessment methods. The IRIS assessment for thallium compounds will consist of a Toxicological Review and IRIS Summary. The Toxicological Review is a critical review of the physiochemical and toxicokinetic properties of a chemical, and its toxicity in humans and experimental systems. The assessment will present reference values for the noncancer effects of thallium compounds (RfD and Rfc), and a cancer assessment. The Toxicological Review and IRIS Summary have been subject to Agency review, Interagency review, and external scientific peer review. The final product will reflect the Agency opinion on the overall toxicity of thallium and compounds. EPA is undertaking an Integrated Risk Information System (IRIS) health assessment for thallium and compounds. IRIS is an EPA database containing Agency scientific positions on potential adverse human health effec

  12. Substance-tailored testing strategies in toxicology: an in silico methodology based on QSAR modeling of toxicological thresholds and Monte Carlo simulations of toxicological testing.

    PubMed

    Péry, Alexandre R R; Desmots, S; Mombelli, E

    2010-02-01

    The design of toxicological testing strategies aimed at identifying the toxic effects of chemicals without (or with a minimal) recourse to animal experimentation is an important issue for toxicological regulations and for industrial decision-making. This article describes an original approach which enables the design of substance-tailored testing strategies with a specified performance in terms of false-positive and false-negative rates. The outcome of toxicological testing is simulated in a different way than previously published articles on the topic. Indeed, toxicological outcomes are simulated not only as a function of the performance of toxicological tests but also as a function of the physico-chemical properties of chemicals. The required inputs for our approach are QSAR predictions for the LOAELs of the toxicological effect of interest and statistical distributions describing the relationship existing between in vivo LOAEL values and results from in vitro tests. Our methodology is able to correctly predict the performance of testing strategies designed to analyze the teratogenic effects of two chemicals: di(2-ethylhexyl)phthalate and Indomethacin. The proposed decision-support methodology can be adapted to any toxicological context as long as a statistical comparison between in vitro and in vivo results is possible and QSAR models for the toxicological effect of interest can be developed.

  13. Introduction to the Theme "New Methods and Novel Therapeutic Approaches in Pharmacology and Toxicology".

    PubMed

    Insel, Paul A; Amara, Susan G; Blaschke, Terrence F; Meyer, Urs A

    2017-01-06

    Major advances in scientific discovery and insights can result from the development and use of new techniques, as exemplified by the work of Solomon Snyder, who writes a prefatory article in this volume. The Editors have chosen "New Methods and Novel Therapeutic Approaches in Pharmacology and Toxicology" as the Theme for a number of articles in this volume. These include ones that review the development and use of new experimental tools and approaches (e.g., nanobodies and techniques to explore protein-protein interactions), new types of therapeutics (e.g., aptamers and antisense oligonucleotides), and systems pharmacology, which assembles (big) data derived from omics studies together with information regarding drugs and patients. The application of these new methods and therapeutic approaches has the potential to have a major impact on basic and clinical research in pharmacology and toxicology as well as on patient care.

  14. FutureTox: building the road for 21st century toxicology and risk assessment practices.

    PubMed

    Rowlands, J Craig; Sander, Miriam; Bus, James S

    2014-02-01

    This article reports on the outcome of FutureTox, a Society of Toxicology (SOT) Contemporary Concepts in Toxicology (CCT) workshop, whose goal was to address the challenges and opportunities associated with implementing 21st century technologies for toxicity testing, hazard identification, and risk assessment. One goal of the workshop was to facilitate an interactive multisector and discipline dialog. To this end, workshop invitees and participants included stakeholders from governmental and regulatory agencies, research institutes, academia, and the chemical and pharmaceutical industry in Europe and the United States. The workshop agenda was constructed to collectively review and discuss the state-of-the-science in these fields, better define the problems and challenges, outline their collective goals for the future, and identify areas of common agreement key to advancing these technologies into practice.

  15. Stem Cells, a New Generation Model for Predictive Nano Toxicological Assessment.

    PubMed

    Suma, Remya Nirmal; Mohanan, Parayanthala Valappil

    2015-01-01

    With the recent advancement in nanoscience and nanotechnology, there is a growing demand for assessment of the toxicological effects of nano materials to humans and other biological systems. And a predictive toxicology approach that uses in vitro screening assays in conjunction with in vivo study results are widely employed in nano safety evaluation. In recent years stem cells have gained wide attention in the scientific community owing to their potential benefits for various applications in health care systems. Stem cells are undifferentiated cells that have high replicative potential and multilineage differentiation capacity. And therefore, stem cells could be exploited for developing in vitro model systems to study nanomaterials interaction with the biological systems and a potential tool to predict toxicity in humans. The details provided in this article will give an overview of optimizing stem cell technology in predicting the toxicity of nano materials the essential features of the article.

  16. Cord Blood Cells for Developmental Toxicology and Environmental Health

    PubMed Central

    Il’yasova, Dora; Kloc, Noreen; Kinev, Alexander

    2015-01-01

    The Tox21 program initiated a shift in toxicology toward in vitro testing with a focus on the biological mechanisms responsible for toxicological response. We discuss the applications of these initiatives to developmental toxicology. Specifically, we briefly review current approaches that are widely used in developmental toxicology to demonstrate the gap in relevance to human populations. An important aspect of human relevance is the wide variability of cellular responses to toxicants. We discuss how this gap can be addressed by using cells isolated from umbilical cord blood, an entirely non-invasive source of fetal/newborn cells. Extension of toxicological testing to collections of human fetal/newborn cells would be useful for better understanding the effect of toxicants on fetal development in human populations. By presenting this perspective, we aim to initiate a discussion about the use of cord blood donor-specific cells to capture the variability of cellular toxicological responses during this vulnerable stage of human development. PMID:26697419

  17. In silico toxicology for the pharmaceutical sciences

    SciTech Connect

    Valerio, Luis G.

    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 of in silico approaches for the toxicological and pharmacological sciences. For pharmaceutical substances, this means active and impurity chemicals in the drug product may be screened using specialized software and databases designed to cover these substances through a chemical structure-based screening process and algorithm specific to a given software program. A major goal for use of these software programs is to enable industry scientists not only to enhance the discovery process but also to ensure the judicious use of in silico tools to support risk assessments of drug-induced toxicities and in safety evaluations. However, a great amount of applied research is still needed, and there are many limitations with these approaches which are described in this review. Currently, there is a wide range of endpoints available from predictive quantitative structure-activity relationship models driven by many different computational software programs and data sources, and this is only expected to grow. For example, there are models based on non-proprietary and/or proprietary information specific to assessing potential rodent carcinogenicity, in silico screens for ICH genetic toxicity assays, reproductive and developmental toxicity, theoretical

  18. National Toxicology Program: Annual plan for Fiscal Year 1991

    SciTech Connect

    Not Available

    1991-06-01

    The NTP Board of Scientific Counselors reviewed and reports on research programs of the NIEHS Experimental Toxicology Branch including both contract efforts and inhouse research and methods development activities for work groups in chemical disposition, general toxicology, toxicologic pathology, mutagenesis, and clinical pathology. The Board reviewed and approved seven concept proposals for collaborative studies having to do testing, methods development or validation activities in general or reproductive toxicology or germ cell mutagenesis. The Board also reviewed and made recommendations for further action on 13 chemicals nominated for NTP study.

  19. 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 ...

  20. 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...

  1. The toxicological properties of petroleum gases.

    PubMed

    McKee, Richard H; Herron, Deborah; Saperstein, Mark; Podhasky, Paula; Hoffman, Gary M; Roberts, Linda

    2014-01-01

    To characterize the toxicological hazards of petroleum gases, 90-day inhalation toxicity (Organization for Economic Cooperation and Development [OECD] 413) and developmental toxicity (OECD 414) tests were conducted with liquefied propane gas (LPG) at concentrations of 1000, 5000, or 10,000 ppm. A micronucleus test (OECD 474) of LPG was also conducted. No systemic or developmental effects were observed; the overall no observed adverse effect concentration (NOAEC) was 10,000 ppm. Further, there was no effect of LPG exposure at levels up to 10,000 ppm on micronucleus induction and no evidence of bone marrow toxicity. Other alkane gases (ethane, propane, n-butane, and isobutane) were then evaluated in combined repeated exposure studies with reproduction/development toxicity screening tests (OECD 422). There were no toxicologically important changes in parameters relating to systemic toxicity or neurotoxicity for any of these gases at concentrations ranging from 9000 to 16,000 ppm. There was no evidence of effects on developmental or reproductive toxicity in the studies of ethane, propane, or n-butane at the highest concentrations tested. However, there was a reduction in mating in the high-exposure group (9000 ppm) of the isobutane study, which although not significantly different was outside the range previously observed in the testing laboratory. Assuming the reduction in mating to have been toxicologically significant, the NOAEC for the isobutane reproductive toxicity screening test was 3000 ppm (7125 mg/m(3)). A method is proposed by which the toxicity of any of the 106 complex petroleum gas streams can be estimated from its composition.

  2. [Genetically modified organisms (GMO): toxicological aspects].

    PubMed

    Ludwicki, J K

    1998-01-01

    The genetically modified organisms (GMO) are one of the major public concerns partially due to the activity of the non-governmental organizations which believe that public opinion must be duly informed on what leaves the laboratories and enters the environment or is proposed as food. This article discusses some major toxicological and nutritional aspects of GMO designed as food for humans. The range of current use of GMOs, potential hazards for humans, safety assessment, allergenic concerns, and some aspects of the use of marker genes are discussed in regard to human safety. The need for relevant regulations is stressed.

  3. Selenium. Nutritional, toxicologic, and clinical aspects.

    PubMed Central

    Fan, A. M.; Kizer, K. W.

    1990-01-01

    Despite the recent findings of environmental contamination, selenium toxicosis in humans is exceedingly rare in the United States, with the few known cases resulting from industrial accidents and an episode involving the ingestion of superpotent selenium supplements. Chronic selenosis is essentially unheard of in this country because of the typical diversity of the American diet. Nonetheless, because of the growing public interest in selenium as a dietary supplement and the occurrence of environmental selenium contamination, medical practitioners should be familiar with the nutritional, toxicologic, and clinical aspects of this trace element. PMID:2219873

  4. Toxicology of sulfur in ruminants: review

    SciTech Connect

    Kandylis, K.

    1984-10-01

    This review deals with the toxicology of sulfur in ruminants including toxicity, neurotoxic effects, and mechanism of toxic action of hydrogen sulfide, clinical signs, and treatment. It will report effects of excessive intake of sulfur by ruminants on feed intake, animal performance, ruminal digestion and motility, rumination, and other physiological functions. Poisoning of animals with sulfur from industrial emissions (sulfur dioxide) also is discussed. Excessive quantities of dietary sulfur (above .3 to .4%) as sulfate or elemental sulfur may cause toxic effects and in extreme cases can be fatal. The means is discussed whereby consumption of excessive amounts of sulfur leads to toxic effects. 53 references, 1 table.

  5. 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

  6. The toxicological application of transcriptomics and epigenomics in zebrafish and other teleosts.

    PubMed

    Williams, Tim D; Mirbahai, Leda; Chipman, J Kevin

    2014-03-01

    Zebrafish (Danio rerio) is one of a number of teleost fish species frequently employed in toxicology. Toxico-genomics determines global transcriptomic responses to chemical exposures and can predict their effects. It has been applied successfully within aquatic toxicology to assist in chemical testing, determination of mechanisms and environmental monitoring. Moreover, the related field of toxico-epigenomics, that determines chemical-induced changes in DNA methylation, histone modifications and micro-RNA expression, is emerging as a valuable contribution to understanding mechanisms of both adaptive and adverse responses. Zebrafish has proven a useful and convenient model species for both transcriptomic and epigenetic toxicological studies. Despite zebrafish's dominance in other areas of fish biology, alternative fish species are used extensively in toxico-genomics. The main reason for this is that environmental monitoring generally focuses on species native to the region of interest. We are starting to see advances in the integration of high-throughput screening, omics techniques and bioinformatics together with more traditional indicator endpoints that are relevant to regulators. Integration of such approaches with high-throughput testing of zebrafish embryos, leading to the discovery of adverse outcome pathways, promises to make a major contribution to ensuring the safety of chemicals in the environment.

  7. The combined toxicological effects of titanium dioxide nanoparticles and bisphenol A on zebrafish embryos

    NASA Astrophysics Data System (ADS)

    Yan, Jun; Lin, Bencheng; Hu, Chuanlu; Zhang, Huashan; Lin, Zhiqing; Xi, Zhuge

    2014-08-01

    Environmental pollutants co-exist and exhibit interaction effects that are different from those associated with a single pollutant. As one of the more commonly manufactured nanomaterials, titanium dioxide nanoparticles (TiO2-NPs) are most likely to bind to other contaminants in water. In this paper, we aimed to study the combined toxicological effects of TiO2-NPs and bisphenol A (BPA) on organism. First, in vitro adsorption experiments were conducted to determine the adsorptive interaction between TiO2-NPs and BPA. Second, zebrafish embryo toxicity tests were performed to monitor for changes in the toxicological effects associated with the two chemicals. The study results demonstrated that adsorptive interactions exist between the two chemicals and increased toxicity effects which included an advanced toxicological effect time, decreased survival, increased morphological abnormalities, and delayed embryo hatching. Also, we suggest that the mode of combined action has a synergistic effect. Based on this, we postulate that concomitant exposure to TiO2-NPs and BPA increased BPA bioavailability and uptake into cells and organisms. Further studies are required to understand the mechanisms of interactions of this mixture.

  8. New challenges and innovation in forensic toxicology: focus on the "New Psychoactive Substances".

    PubMed

    Favretto, Donata; Pascali, Jennifer P; Tagliaro, Franco

    2013-04-26

    In the recent years, new molecules have appeared in the illicit market, claimed to contain "non-illegal" compounds, although exhibiting important psychoactive effects; this heterogeneous and rapidly evolving class of compounds are commonly known as "New Psychoactive Substances" or, less properly, "Smart Drugs" and are easily distributed through the e-commerce or in the so-called "Smart Shops". They include, among other, synthetic cannabinoids, cathinones and tryptamine analogs of psylocin. Whereas cases of intoxication and death have been reported, the phenomenon appears to be largely underestimated and is a matter of concern for Public Health. One of the major points of concern depends on the substantial ineffectiveness of the current methods of toxicological screening of biological samples to identify the new compounds entering the market. These limitations emphasize an urgent need to increase the screening capabilities of the toxicology laboratories, and to develop rapid, versatile yet specific assays able to identify new molecules. The most recent advances in mass spectrometry technology, introducing instruments capable of detecting hundreds of compounds at nanomolar concentrations, are expected to give a fundamental contribution to broaden the diagnostic spectrum of the toxicological screening to include not only all these continuously changing molecules but also their metabolites. In the present paper a critical overview of the opportunities, strengths and limitations of some of the newest analytical approaches is provided, with a particular attention to liquid phase separation techniques coupled to high accuracy, high resolution mass spectrometry.

  9. Toxicological effects of chlorpyrifos on growth, enzyme activity and chlorophyll a synthesis of freshwater microalgae.

    PubMed

    Chen, Shangchao; Chen, Mindong; Wang, Zhuang; Qiu, Weijian; Wang, Junfeng; Shen, Yafei; Wang, Yajun; Ge, Shun

    2016-07-01

    This paper aims to acquire the experimental data on the eco-toxicological effects of agricultural pollutants on the aquatic plants and the data can support the assessment of toxicity on the phytoplankton. The pesticide of Chlorpyrifos used as a good model to investigate its eco-toxicological effect on the different microalgae in freshwater. In order to address the pollutants derived from forestry and agricultural applications, freshwater microalgae were considered as a good sample to investigate the impact of pesticides such as Chlorpyrifos on aquatic life species. Two microalgae of Chlorella pyrenoidosa and Merismopedia sp. were employed to evaluate toxicity of Chlorpyrifos in short time and long time by means of measuring the growth inhibition rate, the redox system and the content of chlorophyll a, respectively. In this study, the results showed that EC50 values ranging from 7.63 to 19.64mg/L, indicating the Chlorpyrifos had a relatively limited to the growth of algae during the period of the acute toxicity experiment. Moreover, when two kinds of algae were exposed to a medium level of Chlorpyrifos, SOD and CAT activities were importantly advanced. Therefore, the growth rate and SOD and CAT activities can be highly recommended for the eco-toxicological assessment. In addition, chlorophyll a also could be used as a targeted parameter for assessing the eco-toxicity of Chlorpyrifos on both Chlorella pyrenoidosa and Merismopedia sp.

  10. In Vitro Developmental Toxicology Screens: A Report on the Progress of the Methodology and Future Applications.

    PubMed

    Zhang, Cindy; Ball, Jonathan; Panzica-Kelly, Julie; Augustine-Rauch, Karen

    2016-04-18

    There has been increasing focus on generation and assessment of in vitro developmental toxicology models for assessing teratogenic liability of chemicals. The driver for this focus has been to find reliable in vitro assays that will reduce or replace the use of in vivo tests for assessing teratogenicity. Such efforts may be eventually applied in testing pharmaceutical agents where a developmental toxicology assay or battery of assays may be incorporated into regulatory testing to replace one of the two species currently used in teratogenic assessment. Such assays may be eventually applied in testing a broader spectrum of chemicals, supporting efforts aligned with Tox21 strategies and responding to REACH legislation. This review describes the developmental toxicology assays that are of focus in these assessments: rodent whole embryo culture, zebrafish embryo assays, and embryonic stem cell assays. Progress on assay development as well as future directions of how these assays are envisioned to be applied for broader safety testing of chemicals are discussed. Altogether, the developmental model systems described in this review provide rich biological systems that can be utilized in better understanding teratogenic mechanisms of action of chemotypes and are promising in providing proactive safety assessment related to developmental toxicity. Continual advancements in refining/optimizing these in vitro assays are anticipated to provide a robust data set to provide thoughtful assessment of how whole animal teratogenicity evaluations can be reduced/refined in the future.

  11. The combined toxicological effects of titanium dioxide nanoparticles and bisphenol A on zebrafish embryos

    PubMed Central

    2014-01-01

    Environmental pollutants co-exist and exhibit interaction effects that are different from those associated with a single pollutant. As one of the more commonly manufactured nanomaterials, titanium dioxide nanoparticles (TiO2-NPs) are most likely to bind to other contaminants in water. In this paper, we aimed to study the combined toxicological effects of TiO2-NPs and bisphenol A (BPA) on organism. First, in vitro adsorption experiments were conducted to determine the adsorptive interaction between TiO2-NPs and BPA. Second, zebrafish embryo toxicity tests were performed to monitor for changes in the toxicological effects associated with the two chemicals. The study results demonstrated that adsorptive interactions exist between the two chemicals and increased toxicity effects which included an advanced toxicological effect time, decreased survival, increased morphological abnormalities, and delayed embryo hatching. Also, we suggest that the mode of combined action has a synergistic effect. Based on this, we postulate that concomitant exposure to TiO2-NPs and BPA increased BPA bioavailability and uptake into cells and organisms. Further studies are required to understand the mechanisms of interactions of this mixture. PMID:25177222

  12. 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...

  13. 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...

  14. 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...

  15. [The hygiene and toxicology of fertilizers at the present stage].

    PubMed

    Prodanchuk, N G; Mudryĭ, I V

    2007-01-01

    The paper touches upon the topical aspects of the hygiene and toxicology of fertilizers and their state sanitary-and-epidemiological examination at the present stage. It also considers guidelines for the toxicological-and-hygienic evaluation when state trials are carried out.

  16. 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...

  17. 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...

  18. 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...

  19. 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...

  20. ACToR: Aggregated Computational Toxicology Resource (T)

    EPA Science Inventory

    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 ...

  1. 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...

  2. 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...

  3. 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...

  4. 76 FR 23600 - Availability of Draft Toxicological Profile

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-27

    ... HUMAN SERVICES Agency for Toxic Substances and Disease Registry Availability of Draft Toxicological Profile AGENCY: Agency for Toxic Substances and Disease Registry (ATSDR), Department of Health and Human... Toxicology and Environmental Medicine, Agency for Toxic Substances and Disease Registry, Mailstop F- 62,...

  5. 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...

  6. 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....

  7. 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...

  8. 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...

  9. 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 ...

  10. 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...

  11. 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

  12. Behavioral Screening for Toxicology | Science Inventory | US ...

    EPA Pesticide Factsheets

    Screening for behavioral toxicity, or neurotoxicity, has been in use for decades; however, only in the past 20 years has this become a standard practice in toxicology. Current screening batteries, such as the functional observational battery (FOB), are derived from protocols used in pharmacology, toxicology, and psychology. Although there is a range of protocols in use today, all focus on detailed observations and specific tests of reflexes and responses. Several neurological functions are typically assessed, including autonomic, neuromuscular, and sensory, as well as levels of activity and excitability. The tests have been shown to be valid in detecting expected effects of known neurotoxicants, and reliable and reproducible whn compared across laboratories. Regardless of the specific protocol used, proper conduct and statistical analyses of the data are critical. Interpretation is based on the information from individual end points as well as the profile, or pattern, of effects observed. As long as continual refinements are made, behavioral screening methods will continue to be important tools with which to protect human health in the future.autonomic function; behavior; behavioral phenotypes; behavioral toxicity; excitability; functional observational battery ; motor activity; mouse; neuromuscular function; positive controls; rat; screening battery ; sensory function Screening for behavioral toxicity, or neurotoxicity, has been in use for decades; how

  13. IRIS Toxicological Review of Ammonia (Revised External ...

    EPA Pesticide Factsheets

    In August 2013, EPA submitted a revised draft IRIS assessment of ammonia to the agency's Science Advisory Board (SAB) and posted this draft on the IRIS website. EPA had previously released a draft of the assessment for public comment, held a public meeting about the draft, and then revised it based on the comments received. The SAB CAAC-Ammonia panel will review this draft assessment. Details about the meeting dates, times, and location are available via the Federal Register Notice posted on March 25, 2014. The SAB provided information on how the public can participate in the external peer review meetings, as well as instructions about how to provide comments to the SAB in the notice. Additional information on the SAB review of ammonia is on the SAB website. Report Information: The Toxicological Review of Ammonia was originally released for a 60-day public comment period on June 8, 2012. [Federal Register Notice Jun 8, 2012] EPA revised the toxicological review in response to the public comments received. EPA has released the revised external review draft ammonia assessment and the SAB CAAC is conducting a peer review of the scientific basis supporting the assessment that will appear in the Integrated Risk Information System (IRIS) database. Information regarding the peer review can be found at the SAB review of ammonia website. EPA is undertaking an Integrated Risk Information System (IRIS) health assessment for ammonia. IRIS is an EPA database cont

  14. IRIS Toxicological Review of Ammonia Noncancer Inhalation ...

    EPA Pesticide Factsheets

    In September 2016, EPA finalized the IRIS assessment of Ammonia (Noncancer Inhalation). The Toxicological Review was reviewed internally by EPA and by other federal agencies and White House Offices before public release in June 2016. Consistent with the May 2009 IRIS assessment development process, all written comments on IRIS assessments submitted by other federal agencies and White House Offices are made publicly available. Accordingly, interagency comments and the interagency science discussion materials provided to other agencies, including interagency review drafts of the IRIS Toxicological Review of Ammonia (Noncancer Inhalation) are posted on this site. Note: No major science comments were received on the Interagency Science Discussion Draft. EPA is undertaking an 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.

  15. Toxicological properties of fenugreek (Trigonella foenum graecum).

    PubMed

    Ouzir, Mounir; El Bairi, Khalid; Amzazi, Saaïd

    2016-10-01

    Fenugreek (Trigonella foenum graecum), used as traditional medicine and natural additive food, has been shown to exert significant antiatherogenic, antidiabetic, antianorexic, antioxidant, anticarcinogenic, antihyperlipidemic, galactogogue and anti-inflammatory effects in several human and animal models. Besides, several medicinal pharmaceutical and nutraceutical properties, fenugreek have toxic effects as well. The aim of this review is discuss the cumulative evidence, which suggests that consumption of fenugreek induced some serious toxicological side effects. In this review, many teratogenic effects of fenugreek, from congenital malformations to death, were reported in human, rodent, rabbit, and chick. Moreover, results obtained in rats, mice and rabbits show a testicular toxicity and anti-fertility effects in male associated with oxidative stress and DNA damage, as well as anti-fertility, antiimplantation and abortifacient activity in females related to saponin compound of fenugreek which suggest that fenugreek is not recommended for use during pregnancy. Indeed, the consumption of fenugreek should be avoided for persons having peanut and chickpeas allergy because of possible cross-reactivity as well as chronic asthma. Accumulating evidence suggest also that fenugreek may have neurodevelopmental, neurobehavioral and neuropathological side effects. It is suggested that future studies would be conducted to identify molecular and cellular mechanisms underlying the fenugreek toxicological properties.

  16. The preclinical toxicology of salmeterol hydroxynaphthoate.

    PubMed

    Owen, K; Beck, S L; Damment, S J P

    2010-05-01

    An extensive toxicology programme on salmeterol hydroxynaphthoate (Serevent), a marketed long-acting beta(2)-adrenoceptor agonist, has been carried out. The studies evaluated both the local (respiratory tract) and systemic tolerance to single and repeated dosing, effects on all stages of reproduction, as well as the genotoxic and oncogenic potential. High acute doses were well tolerated and caused no specific target organ toxicity. In repeat dose studies, animals tolerated salmeterol very well both locally and systemically. No significant effects on the respiratory tract of dogs were seen and only minor laryngeal changes, typical of those occurring with many inhaled medicines, were noted in rats. The high systemic concentrations achieved resulted in a number of changes that are considered to be the result of excessive and prolonged beta( 2)-adrenoceptor stimulation. These included tachycardia, skeletal muscle hypertrophy and minor haematological and blood biochemical changes in general toxicity studies, foetal effects in rabbit organogenesis studies and increased incidences of smooth muscle tumours of the mesovarium in the rat and of the uterus in the mouse oncogenicity studies. Salmeterol showed no evidence of any genotoxic potential. Results of the extensive toxicology programme provide good assurance of the safety for the inhaled use of salmeterol in patients; this has ben confirmed by many years of clinical experience during its development and marketing.

  17. IRIS Toxicological Review and Summary Documents for ...

    EPA Pesticide Factsheets

    Carbon tetrachloride is a volatile haloalkane with a wide range of industrial and chemical applications. It is produced commercially from chlorination of a variety of low molecular weight hydrocarbons such as carbon disulfide, methanol, methane, propane, and ethylene dichloride. It is also produced by thermal chlorination in the production of tetrachloroethylene. Major uses of carbon tetrachloride have been in the recovery of tin from tin plating waste, in formulation of petrol additives and refrigerants, in metal degreasing and agricultural fumigants, in chlorination of organic compounds, in the production of semiconductors, in the reduction of fire hazard, as a solvent for rubber cement, and as a catalyst in polymer technology. Its production has been decreasing and it is no longer permitted in products intended for home use. Despite this ban, carbon tetrachloride has been detected at 314 hazardous waste sites. EPA's assessment of noncancer health effects and carcinogenic potential of carbon tetrachloride was last prepared and added to the IRIS database in 1991. The IRIS program is preparing an assessment that will incorporate health effects information available for carbon tetrachloride, and current risk assessment methods. The IRIS assessment for carbon tetrachloride will consist of a Toxicological Review and IRIS Summary. The Toxicological Review is a critical review of the physiochemical and toxicokinetic properties of a chemical, and its toxicity

  18. Clinical pharmacology and toxicology of dichloroacetate.

    PubMed

    Stacpoole, P W; Henderson, G N; Yan, Z; James, M O

    1998-08-01

    Dichloroacetate (DCA) is a xenobiotic of interest to both environmental toxicologists and clinicians. The chemical is a product of water chlorination and of the metabolism of various drugs and industrial chemicals. Its accumulation in groundwater and at certain Superfund sites is considered a potential health hazard. However, concern about DCA toxicity is predicated mainly on data obtained in inbred rodent strains administered DCA at doses thousands of times higher than those to which humans are usually exposed. In these animals, chronic administration of DCA induces hepatotoxicity and neoplasia. Ironically, the DCA doses used in animal toxicology experiments are very similar to those used clinically for the chronic or acute treatment of several acquired or hereditary metabolic or cardiovascular diseases. As a medicinal, DCA is generally well tolerated and stimulates the activity of the mitochondrial pyruvate dehydrogenase enzyme complex, resulting in increased oxidation of glucose and lactate and an amelioration of lactic acidosis. By this mechanism, the drug may also enhance cellular energy metabolism. DCA is dehalogenated in vivo to monochloroacetate and glyoxylate, from which it can be further catabolized to glycolate, glycine, oxalate, and carbon dioxide. It remains to be determined whether important differences in its metabolism and toxicology exist in humans between environmentally and clinically relevant doses.

  19. Toxicological Effects of Fullerenes on Caenorhabditis elegans

    NASA Astrophysics Data System (ADS)

    Schomaker, Justin; Snook, Renee; Howell, Carina

    2014-03-01

    The nematode species Caenorhabditis elegans is a useful genetic model organism due to its simplicity and the substantial molecular, genetic, and developmental knowledge about the species. In this study, this species was used to test the toxicological effects of C60 fullerene nanoparticles. In previous studies using rats, a solution of C60 fullerenes in olive oil proved to extend the life of the subjects. The purpose of this experiment was to subject C. elegans to varying concentrations of C60 fullerenes and observe their toxicological effects. Initial findings indicate a link between fullerene exposure and enlargement of the vulva as well as the formation of a small nodule at the base of the tail in some individuals. While the fullerenes are not lethally toxic in C. elegans, results will be presented that pertain to changes in life span and progeny of the nematodes exposed to varying concentrations of fullerenes as well as the mechanisms of toxicity. High magnification imaging via SEM and/or AFM will be used to characterize the fullerene nanoparticles. Testing the toxicity of fullerenes in a wide variety of organisms will lead to a more complete understanding of the effects of fullerenes on living organisms to ultimately understand their effects in humans. This work was supported by National Science Foundation grants DUE-1058829, DMR-0923047, DUE-0806660 and Lock Haven FPDC grants.

  20. 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.

  1. Toxicological profile for polycyclic aromatic hydrocarbons. Final report

    SciTech Connect

    Not Available

    1990-12-01

    The ATSDR Toxicological Profile for Polycyclic Aromatic Hydrocarbons (PAHs): Acenaphthene, Acenaphthylene, Anthracene, Benzo(a)anthracene, Benzo(a)pyrene, Benzo(b)fluoranthene, Benzo(g,h,i)perylene, Benzo(k)fluoranthene, Chrysene, Dibenzo(a,h)anthracene, Fluoranthene, Fluorene, Indeno(1,2,3-cd)pyrene, Phenanthrene, Pyrene is intended to characterize succinctly the toxicological and health effects information for the substance. It identifies and reviews the key literature that describes the substance's toxicological properties. Other literature is presented but described in less detail. The profile begins with a public health statement, which describes in nontechnical language the substance's relevant toxicological properties. The adequacy of information to determine the substance's health effects is described. Research gaps in nontoxic and health effects information are described. Research gaps that are of significance to the protection of public health will be identified in a separate effort. The focus of the document is on health and toxicological information.

  2. The Aggregate Exposure Pathway (AEP): A conceptual framework for advancing exposure science research and applications

    EPA Science Inventory

    Historically, risk assessment has relied upon toxicological data to obtain hazard-based reference levels, which are subsequently compared to exposure estimates to determine whether an unacceptable risk to public health may exist. Recent advances in analytical methods, biomarker ...

  3. Applying evolutionary genetics to developmental toxicology and risk assessment.

    PubMed

    Leung, Maxwell C K; Procter, Andrew C; Goldstone, Jared V; Foox, Jonathan; DeSalle, Robert; Mattingly, Carolyn J; Siddall, Mark E; Timme-Laragy, Alicia R

    2017-03-04

    Evolutionary thinking continues to challenge our views on health and disease. Yet, there is a communication gap between evolutionary biologists and toxicologists in recognizing the connections among developmental pathways, high-throughput screening, and birth defects in humans. To increase our capability in identifying potential developmental toxicants in humans, we propose to apply evolutionary genetics to improve the experimental design and data interpretation with various in vitro and whole-organism models. We review five molecular systems of stress response and update 18 consensual cell-cell signaling pathways that are the hallmark for early development, organogenesis, and differentiation; and revisit the principles of teratology in light of recent advances in high-throughput screening, big data techniques, and systems toxicology. Multiscale systems modeling plays an integral role in the evolutionary approach to cross-species extrapolation. Phylogenetic analysis and comparative bioinformatics are both valuable tools in identifying and validating the molecular initiating events that account for adverse developmental outcomes in humans. The discordance of susceptibility between test species and humans (ontogeny) reflects their differences in evolutionary history (phylogeny). This synthesis not only can lead to novel applications in developmental toxicity and risk assessment, but also can pave the way for applying an evo-devo perspective to the study of developmental origins of health and disease.

  4. Silver nanoparticles: synthesis, properties, toxicology, applications and perspectives

    NASA Astrophysics Data System (ADS)

    Tran, Quang Huy; Quy Nguyen, Van; Le, Anh-Tuan

    2013-09-01

    In recent years the outbreak of re-emerging and emerging infectious diseases has been a significant burden on global economies and public health. The growth of population and urbanization along with poor water supply and environmental hygiene are the main reasons for the increase in outbreak of infectious pathogens. Transmission of infectious pathogens to the community has caused outbreaks of diseases such as influenza (A/H5N1), diarrhea (Escherichia coli), cholera (Vibrio cholera), etc throughout the world. The comprehensive treatments of environments containing infectious pathogens using advanced disinfectant nanomaterials have been proposed for prevention of the outbreaks. Among these nanomaterials, silver nanoparticles (Ag-NPs) with unique properties of high antimicrobial activity have attracted much interest from scientists and technologists to develop nanosilver-based disinfectant products. This article aims to review the synthesis routes and antimicrobial effects of Ag-NPs against various pathogens including bacteria, fungi and virus. Toxicology considerations of Ag-NPs to humans and ecology are discussed in detail. Some current applications of Ag-NPs in water-, air- and surface- disinfection are described. Finally, future prospects of Ag-NPs for treatment and prevention of currently emerging infections are discussed.

  5. High-throughput cellular microarray platforms: applications in drug discovery, toxicology and stem cell research

    PubMed Central

    Fernandes, Tiago G.; Diogo, Maria Margarida; Clark, Douglas S.; Dordick, Jonathan S.; Cabral, Joaquim M.S.

    2017-01-01

    Cellular microarrays are powerful experimental tools for high-throughput screening of large numbers of test samples. Miniaturization increases assay throughput while reducing reagent consumption and the number of cells required, making these systems attractive for a wide range of assays in drug discovery, toxicology, stem cell research and potentially therapy. Here, we provide an overview of the emerging technologies that can be used to generate cellular microarrays, and we highlight recent significant advances in the field. This emerging and multidisciplinary approach offers new opportunities for the design and control of stem cells in tissue engineering and cellular therapies and promises to expedite drug discovery in the biotechnology and pharmaceutical industries. PMID:19398140

  6. Commemorating Toxicology at the National Institute of Environmental Health Sciences on the Occasion of Its 50th Anniversary

    PubMed Central

    Bucher, John R.; Birnbaum, Linda S.

    2016-01-01

    Summary: In 1978, the National Toxicology Program (NTP) was established and headquartered at the National Institute of Environmental Health Sciences (NIEHS) in Research Triangle Park, North Carolina. On the occasion of the 50th Anniversary of the NIEHS, this article documents some of the historical and current NTP programs and scientific advances that have been made possible through this long-standing relationship. PMID:27801649

  7. Computational Toxicology as Implemented by the U.S. EPA: Providing High Throughput Decision Support Tools for Screening and Assessing Chemical Exposure, Hazard and Risk

    EPA Science Inventory

    Computational toxicology is the application of mathematical and computer models to help assess chemical hazards and risks to human health and the environment. Supported by advances in informatics, high-throughput screening (HTS) technologies, and systems biology, the U.S. Environ...

  8. Risk, Uncertainty and Precaution in Science: The Threshold of the Toxicological Concern Approach in Food Toxicology.

    PubMed

    Bschir, Karim

    2017-04-01

    Environmental risk assessment is often affected by severe uncertainty. The frequently invoked precautionary principle helps to guide risk assessment and decision-making in the face of scientific uncertainty. In many contexts, however, uncertainties play a role not only in the application of scientific models but also in their development. Building on recent literature in the philosophy of science, this paper argues that precaution should be exercised at the stage when tools for risk assessment are developed as well as when they are used to inform decision-making. The relevance and consequences of this claim are discussed in the context of the threshold of the toxicological concern approach in food toxicology. I conclude that the approach does not meet the standards of an epistemic version of the precautionary principle.

  9. Toxicology of metals and metalloids: Promising issues for future studies in environmental health and toxicology.

    PubMed

    Barbosa, Fernando

    2017-02-17

    The function and behavior of chemical elements in ecosystems and in human health probably comprise one of the most studied issues and a theme of great interest and fascination in science. Hot topics are emerging on an annual basis in this field. Bearing this in mind, some promising themes to explore in the field of metals and metalloids in the environment and in toxicology are highlighted and briefly discussed herein.

  10. [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.

  11. Public health partnerships in medical toxicology education and practice.

    PubMed

    Schier, Joshua G; Rubin, Carol; Schwartz, Michael D; Thomas, Jerry D; Geller, Robert J; Morgan, Brent W; McGeehin, Michael A; Frumkin, Howard

    2010-06-01

    In December 2002, the medical toxicology sub-board, which consists of representatives from emergency medicine, preventive medicine, and pediatrics, released revised core content for medical toxicology, aiming to better meet the academic challenges imposed by the continually expanding knowledge base of medical toxicology. These challenges included the addition of relatively new areas of interest in medical toxicology, including population health, while simultaneously ensuring that a structural framework existed to accommodate future areas of interest. There is no evidence readily available to assess how well the educational curricula of existing fellowship programs are meeting these needs. In an effort to address this, the authors describe a medical toxicology fellowship program that consists of a partnership among the Emory University School of Medicine, the Georgia Poison Control Center, and the CDC, as well as the results of a reorganization of its academic curriculum that occurred in 2006. To the best of the authors' knowledge, this is the first published report describing such a curriculum redesign. Suggestions and potential resources proposed as enhancements for the public health-associated education of medical toxicology fellows are discussed. The authors also seek to initiate a discussion among programs about how to optimally meet the new challenges developed by the medical toxicology sub-board.

  12. Biosynthesis and Toxicological Effects of Patulin

    PubMed Central

    Puel, Olivier; Galtier, Pierre; Oswald, Isabelle P.

    2010-01-01

    Patulin is a toxic chemical contaminant produced by several species of mold, especially within Aspergillus, Penicillium and Byssochlamys. It is the most common mycotoxin found in apples and apple-derived products such as juice, cider, compotes and other food intended for young children. Exposure to this mycotoxin is associated with immunological, neurological and gastrointestinal outcomes. Assessment of the health risks due to patulin consumption by humans has led many countries to regulate the quantity in food. A full understanding of the molecular genetics of patulin biosynthesis is incomplete, unlike other regulated mycotoxins (aflatoxins, trichothecenes and fumonisins), although the chemical structures of patulin precursors are now known. The biosynthetic pathway consists of approximately 10 steps, as suggested by biochemical studies. Recently, a cluster of 15 genes involved in patulin biosynthesis was reported, containing characterized enzymes, a regulation factor and transporter genes. This review includes information on the current understanding of the mechanisms of patulin toxinogenesis and summarizes its toxicological effects. PMID:22069602

  13. Recent developments in preclinical toxicological pathology

    SciTech Connect

    Finch, John M. . E-mail: john.finch@eur.crl

    2005-09-01

    In the late nineteenth century, microscopists developed a quaint method for examining the fine structure of biological specimens: paraffin embedding and staining with hematoxylin and eosin. This ancient technology is here to stay for the foreseeable future, because it can and does reveal the truth about biological processes. However, the role of pathology is developing with ever greater worldwide interaction between pathologists, and better communication and agreeing of international standards. Furthermore, recent techniques including immunohistochemistry, electron microscopy and image analysis complement the traditional tried and tested tools. There is also in toxicologic pathology a willingness to use pathology methods and skills in new contexts, drug discovery in particular. But even in these days of genetic modification, proteomics and high throughput screening, pathologists continue to rely on dyes extracted from a Central American logwood used in Mexico before the Spanish invasion in 1520.

  14. Nature's chemicals and synthetic chemicals: comparative toxicology.

    PubMed Central

    Ames, B N; Profet, M; Gold, L S

    1990-01-01

    The toxicology of synthetic chemicals is compared to that of natural chemicals, which represent the vast bulk of the chemicals to which humans are exposed. It is argued that animals have a broad array of inducible general defenses to combat the changing array of toxic chemicals in plant food (nature's pesticides) and that these defenses are effective against both natural and synthetic toxins. Synthetic toxins such as dioxin are compared to natural chemicals, such as indole carbinol (in broccoli) and ethanol. Trade-offs between synthetic and natural pesticides are discussed. The finding that in high-dose tests, a high proportion of both natural and synthetic chemicals are carcinogens, mutagens, teratogens, and clastogens (30-50% for each group) undermines current regulatory efforts to protect public health from synthetic chemicals based on these tests. PMID:2217211

  15. Amanita muscaria: chemistry, biology, toxicology, and ethnomycology.

    PubMed

    Michelot, Didier; Melendez-Howell, Leda Maria

    2003-02-01

    The fly agaric is a remarkable mushroom in many respects; these are its bearing, history, chemical components and the poisoning that it provokes when consumed. The 'pantherina' poisoning syndrome is characterized by central nervous system dysfunction. The main species responsible are Amanita muscaria and A. pantherina (Amanitaceae); however, some other species of the genus have been suspected for similar actions. Ibotenic acid and muscimol are the active components, and probably, some other substances detected in the latter species participate in the psychotropic effects. The use of the mushroom started in ancient times and is connected with mysticism. Current knowledge on the chemistry, toxicology, and biology relating to this mushroom is reviewed, together with distinctive features concerning this unique species.

  16. The use of kestrels in toxicology

    USGS Publications Warehouse

    Wiemeyer, Stanley N.; Lincer, J.L.; Bird, David M.; Bowen, Reed

    1987-01-01

    Various species of kestrels have become important bioindicators of environmental quality and test species for comparative toxicology in captivity. At least 7 species of kestrels have been used to document the presence of environmental contamination primarily organochlorines and metals, in at least 15 countries. Captive kestrels have been used in studies involving a wide variety of environmental contaminants and toxicants examining: bioaccumulation; lethal toxicity using acute, chronic, and secondary exposures; effects on reproduction, eggshell thickness, and related enzyme systems; and effects on a wide variety of physiological and biochemical parameters. Field studies have examined the response of kestrels to exposure to insecticides. Kestrels should continue to play a vital role as a bioindicator and raptorial 'white mouse', especially because of their relationship to other falconiformes, several of which have been shown to be extremely sensitive to environmental changes.

  17. IRIS Toxicological Review of Vanadium Pentoxide (External ...

    EPA Pesticide Factsheets

    This vanadium pentoxide reassessment consists of an oral reference dose (RfD), an inhalation reference concentration (RfC), an inhalation unit risk (IUR) and a cancer weight of evidence descriptor. This is the first assessment developing an RfC or IUR for this compound. This assessment is intended to provide human health data to support agency regulatory decisions. EPA is reassessing its IRIS toxicological review of vanadium pentoxide (CASRN 1314-62-1). This vanadium pentoxide reassessment consists of an oral reference dose (RfD), an inhalation reference concentration (RfC), an inhalation unit risk (IUR) and a cancer weight of evidence descriptor. This is the first assessment developing an RfC or IUR for this compound. This assessment is intended to provide human health data to support agency regulatory decisions.

  18. Toxicological implications of extended space flights

    NASA Technical Reports Server (NTRS)

    Weiss, Bernard; Utell, Mark; Morrow, Paul

    1992-01-01

    This paper draws attention to the needs and mechanisms for shielding crewmembers on long-duration space flights from hazards related to chemical toxicants. Specific attention is given to existing data on sources of impaired performance, namely, neurotoxicants, respiratory infections, pulmonary function. The behavioral effects associated with long-term exposure to volatile organic solvents can impair crucial functional parameters of space flight and mission objectives. Respiratory infections contribute to performance decrements of up to 20 percent, and pulmonary function can be impaired by contaminants such as ozone leading to reduced performance. It is concluded that these and other sources of toxicologically induced performance reductions be studied since they impinge on vehicle design and mission objectives.

  19. Nature's chemicals and synthetic chemicals: Comparative toxicology

    SciTech Connect

    Ames, B.N.; Profet, M.; Gold, L.S. )

    1990-10-01

    The toxicology of synthetic chemicals is compared to that of natural chemicals, which represent the vast bulk of the chemicals to which humans are exposed. It is argued that animals have a broad array of inducible general defenses to combat the changing array of toxic chemicals in plant food (nature's pesticides) and that these defenses are effective against both natural and synthetic toxins. Synthetic toxins such as dioxin are compared to natural chemicals, such as indole carbinol (in broccoli) and ethanol. Trade-offs between synthetic and natural pesticides are discussed. The finding that in high-dose tests, a high proportion of both natural and synthetic chemicals are carcinogens, mutagens, teratogens, and clastogens (30-50{percent} for each group) undermines current regulatory efforts to protect public health from synthetic chemicals based on these tests.

  20. Toxicological benchmarks for wildlife. Environmental Restoration Program

    SciTech Connect

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

    1993-09-01

    This report presents toxicological benchmarks for assessment of effects of 55 chemicals on six representative mammalian wildlife species (short-tailed shrew, white-footed mouse, cottontail ink, red fox, and whitetail deer) and eight avian wildlife species (American robin, woodcock, wild turkey, belted kingfisher, great blue heron, barred owl, Cooper`s hawk, and redtailed hawk) (scientific names are presented in Appendix C). These species were chosen because they are widely distributed and provide a representative range of body sizes and diets. The chemicals are some of those that occur at United States Department of Energy (DOE) waste sites. The benchmarks presented in this report are values believed to be nonhazardous for the listed wildlife species.

  1. Blood purification in toxicology: nephrology's ugly duckling.

    PubMed

    Ghannoum, Marc; Nolin, Thomas D; Lavergne, Valery; Hoffman, Robert S

    2011-05-01

    Contrary to popular opinion, application of extracorporeal therapies for poisonings predates their use for ESRD. Despite this observation, the science of blood purification in toxicology remains desperately stagnant today. In fact, much of our current knowledge is derived from George Schreiner's 1958 review. Original publications are almost exclusively composed of case reports and case series, from which good inference is impossible. Until randomized controlled trials become available, the medical community would be well served by a group mandated to systematically review available literature, extract relevant information, provide recommendations based on current evidence, and propose research initiatives. The EXtracorporeal TReatments In Poisoning workgroup, formed by several international experts in different medical fields and represented by over 20 societies, now has this mission.

  2. Wind of Change Challenges Toxicological Regulators

    PubMed Central

    Tralau, Tewes; Riebeling, Christian; Pirow, Ralph; Oelgeschläger, Michael; Seiler, Andrea; Liebsch, Manfred

    2012-01-01

    Background: In biomedical research, the past two decades have seen the advent of in vitro model systems based on stem cells, humanized cell lines, and engineered organotypic tissues, as well as numerous cellular assays based on primarily established tumor-derived cell lines and their genetically modified derivatives. Objective: There are high hopes that these systems might replace the need for animal testing in regulatory toxicology. However, despite increasing pressure in recent years to reduce animal testing, regulators are still reluctant to adopt in vitro approaches on a large scale. It thus seems appropriate to consider how we could realistically perform regulatory toxicity testing using in vitro assays only. Discussion and Conclusion: Here, we suggest an in vitro–only approach for regulatory testing that will benefit consumers, industry, and regulators alike. PMID:22871563

  3. 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.

  4. Toxicological criterion of the heroin poisoning.

    PubMed

    Shigeev, S

    2007-01-01

    The paper presents toxicological characteristics of 198 cases of acute parenteral heroin intoxication, analyzes the clinically encountered range of blood and urinary concentrations of its metabolites. The principal causes of death are elucidated in victims of heroin poisoning at the hospital stage. Where there is a relationship of death probability to the detection of morphine in the victims' biological fluids is considered; its blood and urinary concentrations are determined, which undoubtedly suggests the occurrence of poisoning-related death. It has been established that death from poisoning by heroin may occur in the whole range of its detectable concentrations. There is no doubt that the blood morphine concentrations of at least 2.0 microg/ml should be considered to be fatal.

  5. Pharmacokinetics, pharmacodynamics and toxicology of theranostic nanoparticles

    NASA Astrophysics Data System (ADS)

    Kang, Homan; Mintri, Shrutika; Menon, Archita Venugopal; Lee, Hea Yeon; Choi, Hak Soo; Kim, Jonghan

    2015-11-01

    Nanoparticles (NPs) are considered a promising tool in both diagnosis and therapeutics. Theranostic NPs possess the combined properties of targeted imaging and drug delivery within a single entity. While the categorization of theranostic NPs is based on their structure and composition, the pharmacokinetics of NPs are significantly influenced by the physicochemical properties of theranostic NPs as well as the routes of administration. Consequently, altered pharmacokinetics modify the pharmacodynamic efficacy and toxicity of NPs. Although theranostic NPs hold great promise in nanomedicine and biomedical applications, a lack of understanding persists on the mechanisms of the biodistribution and adverse effects of NPs. To better understand the diagnostic and therapeutic functions of NPs, this review discusses the factors that influence the pharmacokinetics, pharmacodynamics and toxicology of theranostic NPs, along with several strategies for developing novel diagnostic and therapeutic modalities.

  6. Aquatic toxicology: past, present, and prospects.

    PubMed Central

    Pritchard, J B

    1993-01-01

    Aquatic organisms have played important roles as early warning and monitoring systems for pollutant burdens in our environment. However, they have significant potential to do even more, just as they have in basic biology where preparations like the squid axon have been essential tools in establishing physiological and biochemical mechanisms. This review provides a brief summary of the history of aquatic toxicology, focusing on the nature of aquatic contaminants, the levels of contamination in our waters, and the origins of these agents. It considers the features of the aquatic environment that determine the availability of xenobiotics to aquatic life and the fate of foreign chemicals within the organism. Finally, toxic effects are considered with primary emphasis on the potential of aquatic models to facilitate identification of the underlying mechanisms of toxicity. PMID:8354173

  7. 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.

  8. 77 FR 20022 - Substances To Be Evaluated for Set 26 Toxicological Profiles

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-03

    ... Set 26 toxicological profile development. ATSDR's Division of Toxicology and Human Health Sciences... submitting comments. Mail: Division of Toxicology and Human Health Sciences (proposed), 1600 Clifton Rd. NE... Toxicology and Human Health Sciences (proposed), 1600 Clifton Rd. NE., MS F-62, Atlanta, Georgia 30333,...

  9. National toxicology program chemical nomination and selection process

    SciTech Connect

    Selkirk, J.K.

    1990-12-31

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

  10. Lessons from Toxicology: Developing a 21st-Century Paradigm for Medical Research

    PubMed Central

    Austin, Christopher P.; Balapure, Anil K.; Birnbaum, Linda S.; Bucher, John R.; Fentem, Julia; Fitzpatrick, Suzanne C.; Fowle, John R.; Kavlock, Robert J.; Kitano, Hiroaki; Lidbury, Brett A.; Muotri, Alysson R.; Peng, Shuang-Qing; Sakharov, Dmitry; Seidle, Troy; Trez, Thales; Tonevitsky, Alexander; van de Stolpe, Anja; Whelan, Maurice; Willett, Catherine

    2015-01-01

    Summary Biomedical developments in the 21st century provide an unprecedented opportunity to gain a dynamic systems-level and human-specific understanding of the causes and pathophysiologies of disease. This understanding is a vital need, in view of continuing failures in health research, drug discovery, and clinical translation. The full potential of advanced approaches may not be achieved within a 20th-century conceptual framework dominated by animal models. Novel technologies are being integrated into environmental health research and are also applicable to disease research, but these advances need a new medical research and drug discovery paradigm to gain maximal benefits. We suggest a new conceptual framework that repurposes the 21st-century transition underway in toxicology. Human disease should be conceived as resulting from integrated extrinsic and intrinsic causes, with research focused on modern human-specific models to understand disease pathways at multiple biological levels that are analogous to adverse outcome pathways in toxicology. Systems biology tools should be used to integrate and interpret data about disease causation and pathophysiology. Such an approach promises progress in overcoming the current roadblocks to understanding human disease and successful drug discovery and translation. A discourse should begin now to identify and consider the many challenges and questions that need to be solved. PMID:26523530

  11. Comparative Toxicology of Libby Amphibole and Naturally Occurring Asbestos

    EPA Science Inventory

    Summary sentence: Comparative toxicology of Libby amphibole (LA) and site-specific naturally occurring asbestos (NOA) provides new insights on physical properties influencing health effects and mechanisms of asbestos-induced inflammation, fibrosis, and tumorigenesis.Introduction/...

  12. NEW PUBLIC DATA AND INTERNET RESOURCES IMPACTING PREDICTIVE TOXICOLOGY.

    EPA Science Inventory

    High-throughput screening (HTS) technologies, along with efforts to improve public access to chemical toxicity information resources and to systematize older toxicity studies, have the potential to significantly improve predictive capabilities in toxicology.

  13. 75 FR 54889 - Development of Set 24 Toxicological Profiles

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-09

    ... ATSDR Web site: http://www.atsdr.cdc.gov/toxpro2.html . Set 24 Toxicological Profiles The following... included on the Priority List of Hazardous Substances ( http://www.atsdr.cdc.gov/cercla/07list.html )....

  14. Using Toxicological Evidence from QSAR Models in Practice

    EPA Science Inventory

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

  15. Space toxicology: protecting human health during space operations.

    PubMed

    Khan-Mayberry, Noreen; James, John T; Tyl, Rochelle; Lam, Chiu-wing

    2011-02-01

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

  16. 75 FR 74053 - Availability of Final Toxicological Profiles

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-30

    ... available through the U.S. Department of Commerce, National Technical Information Service (NTIS), 5285 Port... as determined by NTIS. Twenty-first Set Toxicological profile NTIS order No. CAS No. 1. Boron...

  17. Linking Mass Spectrometry with Toxicology for Emerging Water Contaminants

    EPA Science Inventory

    This overview presentation will discuss the benefits of combining mass spectrometry with toxicology. These benefits will be described for 3 main areas: (1) Toxicity assays used to test new environmental contaminants previously identified using mass spectrometry, such that furth...

  18. Caenorhabditis elegans: An Emerging Model in Biomedical and Environmental Toxicology

    PubMed Central

    Leung, Maxwell C. K.; Williams, Phillip L.; Benedetto, Alexandre; Au, Catherine; Helmcke, Kirsten J.; Aschner, Michael; Meyer, Joel N.

    2008-01-01

    The nematode Caenorhabditis elegans has emerged as an important animal model in various fields including neurobiology, developmental biology, and genetics. Characteristics of this animal model that have contributed to its success include its genetic manipulability, invariant and fully described developmental program, well-characterized genome, ease of maintenance, short and prolific life cycle, and small body size. These same features have led to an increasing use of C. elegans in toxicology, both for mechanistic studies and high-throughput screening approaches. We describe some of the research that has been carried out in the areas of neurotoxicology, genetic toxicology, and environmental toxicology, as well as high-throughput experiments with C. elegans including genome-wide screening for molecular targets of toxicity and rapid toxicity assessment for new chemicals. We argue for an increased role for C. elegans in complementing other model systems in toxicological research. PMID:18566021

  19. IRIS Toxicological Review of Trichloroethylene (Interagency Science Discussion Draft)

    EPA Science Inventory

    EPA is releasing the draft report, Toxicological Review of Trichloroethylene, that was distributed to Federal agencies and White House Offices for comment during the Science Discussion step of the IRIS Assessment Development Process. Comments received from other Federal agencies ...

  20. 75 FR 52535 - Availability of Draft Toxicological Profile

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-26

    ..., ATSDR, in cooperation with the National Toxicology Program (NTP), may plan a program of research designed to determine these health effects. Although a number of key studies for this substance...

  1. Toxicology and risk assessment information resources for librarians.

    PubMed

    Stirling, D A

    2000-01-01

    Many librarians work with toxicologists and risk assessors seeking information about chemicals and hazardous substances of concern to human health and the environment. Therefore, this article reviews reliable, accurate, readily accessible, and user-friendly sources of toxicological and risk assessment information. A summary and description of pertinent toxicological data, literature, and profile sources is presented. The majority of the resources are available online; however, descriptions of several important print sources are included.

  2. [Methods of toxicologic evaluation--possibilities and limits].

    PubMed

    Strubelt, O

    1990-06-01

    Toxicological knowledge is founded on observation in humans consisting of casuistic presentations and epidemiologic research and on animal experiments. The possibilities and limitations of these sources of knowledge are presented with special reference to the problems of the dose and of toxic interactions. The limitations of toxicological knowledge primarily result from the impossibility to prove "no action". Therefore, it is not possible to prove the absolute safety of a substance but only the acceptability by assessing its advantages and risks.

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

    EPA Pesticide Factsheets

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

  4. Principals Of Radiation Toxicology: Important Aspects.

    NASA Astrophysics Data System (ADS)

    Popov, Dmitri; Maliev, Slava; Jones, Jeffrey

    “All things are poison, and nothing is without poison; only the dose permits something not to be poisonous.” Paracelsus Key Words: Radiation Toxins (RT), Radiation Toxicants (RTc), Radiation Poisons (RP), Radiation Exposure (RE), Radiation Toxicology is the science about radiation poisons. [D.Popov et al. 2012,J.Zhou et al. 2007,] Radiation Toxins is a specific proteins with high enzymatic activity produced by living irradiated mammals. [D.Popov et al. 2012,] Radiation Toxicants is a substances that produce radiomimetics effects, adverse biological effects which specific for radiation. [D.Popov et al. 2012,] Radiation Toxic agent is specific proteins that can produce pathological biological effects specific for physical form of radiation.[D.Popov et al. 1990,2012,V. Maliev 2007] Different Toxic Substances isolated from cells or from blood or lymph circulation. [Kudriashov I. et al. 1970, D.Popov et al. 1990,2012,V. Maliev et al. 2007,] Radiation Toxins may affects many organs or specific organ, tissue, specific group of cells. [Kudriashov I. et al. 1970, D.Popov et al. 1990,2012,V. Maliev et al. 2007] For example: Radiation Toxins could induce collective toxic clinical states to include: systemic inflammatory response syndrome (SIRS),toxic multiple organ injury (TMOI), toxic multiple organ dysfunction syndromes (TMODS),and finally, toxic multiple organ failure (TMOF). [T. Azizova et al. 2005, Konchalovsky et al., 2005, D. Popov et al 2012] However, Radiation Toxins could induce specific injury of organs or tissue and induce Acute Radiation Syndromes such as Acute Radiation Cerebrovascular Syndrome, Acute Radiation Cardiovascular Syndrome, Acute Radiation Hematopoietic Syndrome, Acute Radiation GastroIntestinal Syndrome. [ D.Popov et al. 1990, 2012, V. Maliev et al. 2007] Radiation Toxins correlates with Radiation Exposure and the dose-response relationship is a fundamental and essential concept in classic Toxicology and Radiation Toxicology.[ D.Popov et al

  5. Toxicology as a nanoscience? – Disciplinary identities reconsidered

    PubMed Central

    Kurath, Monika; Maasen, Sabine

    2006-01-01

    Toxicology is about to establish itself as a leading scientific discipline in addressing potential health effects of materials on the nanosize level. Entering into a cutting-edge field, has an impact on identity-building processes within the involved academic fields. In our study, we analyzed the ways in which the entry into the field of nanosciences impacts on the formation of disciplinary identities. Using the methods of qualitative interviews with particle toxicologists in Germany, Holland, Switzerland and the USA, we could demonstrate that currently, toxicology finds itself in a transitional phase. The development of its disciplinary identity is not yet clear. Nearly all of our interview partners stressed the necessity of repositioning toxicology. However, they each suggested different approaches. While one part is already propagandizing the establishment of a new discipline – 'nanotoxicology'- others are more reserved and are demanding a clear separation of traditional and new research areas. In phases of disciplinary new-orientation, research communities do not act consistently. Rather, they establish diverse options. By expanding its disciplinary boundaries, participating in new research fields, while continuing its previous research, and only vaguely defining its topics, toxicology is feeling its way into the new fields without giving up its present self-conception. However, the toxicological research community is also discussing a new disciplinary identity. Within this, toxicology could develop from an auxiliary into a constitutive position, and take over a basic role in the cognitive, institutional and social framing of the nanosciences. PMID:16646961

  6. Methylglyoxal in living organisms: chemistry, biochemistry, toxicology and biological implications.

    PubMed

    Kalapos, M P

    1999-11-22

    Despite the growing interest towards methylglyoxal and glyoxalases their real role in metabolic network is still obscure. In the light of developments several reviews have been published in this field mainly dealing with only a narrow segment of this research area. In this article a trial is made to present a comprehensive overview of methylglyoxal research, extending discussion from chemistry to biological implications by reviewing some important characteristics of methylglyoxal metabolism and toxicity in a wide variety of species, and emphasizing the action of methylglyoxal on energy production, free radical generation and cell killing. Special attention is paid to the discussion of alpha-oxoaldehyde production in the environment as a potential risk factor and to the possible role of this a-dicarbonyl in diseases. Concerning the interaction of methylglyoxal with biological macromolecules (DNA, RNA, proteins) an earlier review (Kalapos, Toxicology Letters, 73, 1994, 3-24) means a supplementation to this paper, thus hoping the avoidance of unnecessary bombast. The paper arrives at the conclusion that since the early stage of evolution the function of methylglyoxalase pathway has been related to carbohydrate metabolism, but its significance has been changed over the thousands of years. Namely, at the beginning of evolution methylglyoxalase path was essential for the reductive citric acid cycle as an anaplerotic route, while in the extant metabolism it concerns with the detoxification of methylglyoxal and plays some regulatory role in triose-phosphate household. As there is a tight junction between methylglyoxal and carbohydrate metabolism its pathological role in the events of the development of diabetic complications emerges in a natural manner and further progress is hoped in this field. In contrast, significant advancement cannot be expected in relation to cancer research.

  7. Numerical descriptors for the characterization of chiral compounds and their applications in modeling biological and toxicological activities.

    PubMed

    Natarajan, Ramanathan; Basak, Subhash C

    2011-01-01

    Due to the advancement in chiral synthesis and separation technology and the new regulatory policies for chiral pharmaceuticals several manufacturers are replacing the previously marketed racemate chemicals with single enantiomeric products, the so called chiral switch. Though 25% of agrochemicals are chiral in nature, most of them are sold as racemates or enantiomer enriched products. Chiral pesticides and some of the pharmaceuticals reach the human food chain as pollutants. Stereoisomers (enantiomers and diastereoisomers) not only differ from one another in their medicinal effects, but also in their phramacokinectic (adsorption, distribution, biotransformation and excretion) profiles and toxicological properties. Several recent attempts have been reported in the literature on developing mathematical models to predict the properties of chiral molecules from structure and such methods utilized numerical characterization. A comparison of different mathematical approaches on the numerical characterization of molecules with chiral center(s) and a brief background on the importance of stereochemistry in pharmacology, agrochemistry and environmental toxicology is presented.

  8. Current Understanding of Perfluoroalkyl Acid Toxicology ...

    EPA Pesticide Factsheets

    The perfluoroalkyl acids (PFAAs) are a family of organic chemicals consisting of a perfluorinated carbon backbone (4-14 carbons in length) and an anionic head group (sulfonate, carboxylate or phosphonate). These compounds have excellent surface-tension reducing properties and have numerous industrial and consumer applications. However, they are chemically stable, persistent in the environment, ubiquitously distributed, and present in humans and wildlife. Two issues must be considered regarding PFAA toxicology: pharmacokinetics and potency of the chemicals. The rates of PFAA clearance and their body burden accumulation are dependent on carbon-chain length and animal species. In general, the serum half-life of PFAAs increases with chain length in both rodents and humans, but the estimates in humans are markedly higher than those in laboratory animals. Recent studies with laboratory animal models have indicated a number of toxic effects of PFAAs, including tumor induction, hepatotoxicity, developmental toxicity, immunotoxicity, neurotoxicity and endocrine disruption. The modes of PFAA actions are not well understood, but are thought to involve, in part, activation of nuclear receptor signals (such as peroxisome proliferator-activated receptor-a, PPARa). Based on PPARa activation, potency of PFAAs increases with carbon-chain length, carboxylates are stronger than sulfonates, and mouse receptor is more reactive than human receptor. Adverse effects of perfluorophospho

  9. Oleoresin Capsicum toxicology evaluation and hazard review

    SciTech Connect

    Archuleta, M.M.

    1995-10-01

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

  10. A medical-toxicological view of tattooing.

    PubMed

    Laux, Peter; Tralau, Tewes; Tentschert, Jutta; Blume, Annegret; Al Dahouk, Sascha; Bäumler, Wolfgang; Bernstein, Eric; Bocca, Beatrice; Alimonti, Alessandro; Colebrook, Helen; de Cuyper, Christa; Dähne, Lars; Hauri, Urs; Howard, Paul C; Janssen, Paul; Katz, Linda; Klitzman, Bruce; Kluger, Nicolas; Krutak, Lars; Platzek, Thomas; Scott-Lang, Victoria; Serup, Jørgen; Teubner, Wera; Schreiver, Ines; Wilkniß, Elena; Luch, Andreas

    2016-01-23

    Long perceived as a form of exotic self-expression in some social fringe groups, tattoos have left their maverick image behind and become mainstream, particularly for young people. Historically, tattoo-related health and safety regulations have focused on rules of hygiene and prevention of infections. Meanwhile, the increasing popularity of tattooing has led to the development of many new colours, allowing tattoos to be more spectacular than ever before. However, little is known about the toxicological risks of the ingredients used. For risk assessment, safe intradermal application of these pigments needs data for toxicity and biokinetics and increased knowledge about the removal of tattoos. Other concerns are the potential for phototoxicity, substance migration, and the possible metabolic conversion of tattoo ink ingredients into toxic substances. Similar considerations apply to cleavage products that are formed during laser-assisted tattoo removal. In this Review, we summarise the issues of concern, putting them into context, and provide perspectives for the assessment of the acute and chronic health effects associated with tattooing.

  11. Toxicologic aspects of voodoo in Haiti.

    PubMed

    Craan, A G

    1988-12-01

    Voodoo is a folk religion that emerged from the interaction of West African ethnotheologies with European Christian rituals. Haitian Voodoo priests control two major practices which might be of interest to toxicologists: healing and poisoning. Intoxications arising from therapeutic activities pertaining to this cult are of the same kind as those encountered in the practice of Modern Medicine. Remedies used in Voodoo originate generally from plants, as do most prescription drugs; however, the poisons are extracted from both plant and animal tissues, then administered to intended victims as a means of punishment established by a clandestine justice system. The present paper reviews recent attempts at analyzing some of the most lethal Voodoo poisons which appear to induce catalepsy. Although tetrodotoxin was singled out as the probable active ingredient, chromatographic analyses of such poisons as well as the presence of yet unidentified neurotoxicants in Caribbean fish and amphibians familiar to Voodoo practitioners suggest otherwise. To gain more insight into this problem, it is proposed that chemical analyses and toxicological studies be carried out on each ingredient individually, then on combinations of ingredients contained in these Voodoo potions. Such a strategy could help discriminate between active and inactive components and focus on the real toxic elements.

  12. Organic N-chloramines: chemistry and toxicology.

    PubMed

    Scully, F E; Bempong, M A

    1982-12-01

    The stability of aqueous solutions of organic N-chloramines, suspected of contaminating chlorinated water, has been studied. Two factors influence the decomposition of solutions of N-chloropiperidine and N-chlorodiethylamine: a spontaneous decomposition and photodecomposition. Since solutions of these compounds are relatively long-lived, a need for an analytical method for their identification is discussed. A new method is described which involves reaction of organic N-chloramines with arenesulfinic acid salts. The method gives high yields of stable arenesulfonamides. Several toxicological studies of N-chloropiperidine are described. The compound is mutagenic by Ames assay in Salmonella typhimurium strain TA 100 and does not require metabolic activation as indicated in a total body fluids analysis using C57BL/J6 mice. N-Chloropiperidine was subjected to a modified in vitro cell transformation assay using diploid fibroblast cells from Syrian hamster fetuses. A maximum number of foci of 4 per dish was observed at a seeding of 5 X 10(3) cells/60 mm dish. Under similar conditions, MNNG-induced foci ranged from 4 to 7 per dish.

  13. The toxicology of indium tin oxide.

    PubMed

    Bomhard, Ernst M

    2016-07-01

    Indium tin oxide (ITO) is a technologically important semiconductor. An increasing number of cases of severe lung effects (characterized by pulmonary alveolar proteinosis and/or interstitial fibrosis) in ITO-exposed workers warrants a review of the toxicological hazards. Short- and long-term inhalation studies in rats and mice revealed persistent alveolar proteinosis, inflammation and fibrosis in the lungs down to concentrations as low as 0.01mg/m(3). In rats, the incidences of bronchiolo-alveolar adenomas and carcinomas were significantly increased at all concentrations. In mice, ITO was not carcinogenic. A few bronchiolo-alveolar adenomas occurring after repeated intratracheal instillation of ITO to hamsters have to be interpreted as treatment-related. In vitro and in vivo studies on the formation of reactive oxygen species suggest epigenetic effects as cause of the lung tumor development. Repeated intratracheal instillation of ITO to hamsters slightly affected the male sexual organs, which might be interpreted as a secondary effect of the lung damage. Epidemiological and medical surveillance studies, serum/blood indium levels in workers as well as data on the exposure to airborne indium concentrations indicate a need for measures to reduce exposure at ITO workplaces.

  14. Role of toxicological interactions in lung injury

    SciTech Connect

    Witschi, H.P.; Hakkinen, P.J.

    1984-04-01

    Interactions between two or more toxic agents can produce lung damage by chemical-chemical interactions, chemical-receptor interactions or by modification, by a first agent, of the cell and tissue response to a second agent. Interactions may occur by simultaneous exposure and if exposure to two agents is separated in time. Chemical-chemical interactions have been mostly studied in the toxicology of air pollutants, where it was shown that the untoward effect of certain oxidants may be enhanced in the presence of other aerosols. Interactions at the receptor site have been found in isolated perfused lung experiments. Oxygen tolerance may be an example, when pre-exposure to one concentration of oxygen mitigates later exposure to 100% oxygen by modifying cellular and enzymatic composition of the lung. Damage of the alveolar zone by the antioxidant butylated hydroxytoluene (BHT) can be greatly enhanced by subsequent exposure to oxygen concentration which, otherwise, would have little if any demonstrable effect. The synergistic interaction between BHT and oxygen results in a resulting interstitial pulmonary fibrosis. Acute or chronic lung disease may then be caused not only by one agent, but very likely in many instances by the interaction of several agents. 121 references.

  15. Review of the toxicology of styrene.

    PubMed

    Bond, J A

    1989-01-01

    Styrene is used in the production of plastics and resins, which include polystyrene resins, acrylonitrile-butadiene-styrene resins, styrene-acrylonitrile resins, styrene-butadiene copolymer resins, styrene-butadiene rubber, and unsaturated polyester resins. In 1985, styrene ranked in the top ten of synthetic organic chemicals produced in the U.S. This review focuses on various aspects of styrene toxicology including acute and chronic toxicity, carcinogenicity, genotoxicity, pharmacokinetics, effects on hepatic and extrahepatic xenobiotic-metabolizing enzymes, pharmacokinetic modeling, and covalent interactions with macromolecules. There appear to be many similarities between the toxicity and metabolism of styrene in rodents and humans. Needed areas of future research on styrene include studies on the molecular dosimetry of styrene in terms of both hemoglobin and DNA adducts. The results of such research should improve our ability to assess the relationship between exposure to styrene and surrogate measures of "effective dose", thereby improving our ability to estimate the effects of low-level human exposures.

  16. Liver cell models in in vitro toxicology.

    PubMed Central

    Guillouzo, A

    1998-01-01

    In vitro liver preparations are increasingly used for the study of hepatotoxicity of chemicals. In recent years their actual advantages and limitations have been better defined. The cell models, slices, and mainly primary hepatocyte cultures, appear to be the most powerful in vitro systems, as liver-specific functions and responsiveness to inducers are retained either for a few days or several weeks depending on culture conditions. Maintenance of phase I and phase II xenobiotic metabolizing enzyme activities allows various chemical investigations to be performed, including determination of kinetic parameters, metabolic profile, interspecies comparison, inhibition and induction effects, and drug-drug interactions. In vitro liver cell models also have various applications in toxicology: screening of cytotoxic and genotoxic compounds, evaluation of chemoprotective agents, and determination of characteristic liver lesions and associated biochemical mechanisms induced by toxic compounds. Extrapolation of the results to the in vivo situation remains a matter of debate. Presently, the most convincing applications of liver cell models are the studies on different aspects of metabolism and mechanisms of toxicity. For the future, there is a need for better culture conditions and differentiated hepatocyte cell lines to overcome the limited availability of human liver tissues. In addition, strategies for in vitro analysis of potentially toxic chemicals must be better defined. PMID:9599700

  17. Systems Toxicology of Male Reproductive Development ...

    EPA Pesticide Factsheets

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

  18. Toxicologic interactions between ozone and bacterial endotoxin

    SciTech Connect

    Peavy, D.L.; Fairchild, E.J. II

    1987-02-01

    The effects of acute exposure of mice to bacterial lipopolysaccharide (LPS), the endotoxin of gram negative microorganisms, and ozone (O3) have been investigated. Intraperitoneal (ip) administration of 5 mg/kg LPS to CD-1 mice followed by exposure to 15 ppm O3 for 1.5 hr produced synergistic effects as measured by pulmonary edemagenesis and lethality assays. In contrast, ip administration of 0.1-1.6 mg/kg LPS to CD-1 mice over 5 consecutive days, a dose regimen resulting in LPS tolerance, protected against a lethal challenge of 20 ppm O3 for 3 hr. A statistically significant increase in catalase and glutathione peroxidase activity was measured in homogenates of lungs obtained from CD-1 mice receiving a tolerance-inducing regimen of LPS. These results demonstrate that two, distinct toxicologic interactions can occur between O3 and bacterial LPS. Synergism between these agents could explain, in part, the increased susceptibility of O3-exposed animals to respiratory infection with gram negative microorganisms. Protection resulting from LPS-induced increases in pulmonary antioxidant activity provides additional evidence that O3 and, possibly, LPS mediate their toxicity through oxidative mechanisms.

  19. Aquaculture: Environmental, toxicological, and health issues.

    PubMed

    Cole, David W; Cole, Richard; Gaydos, Steven J; Gray, Jon; Hyland, Greg; Jacques, Mark L; Powell-Dunford, Nicole; Sawhney, Charu; Au, William W

    2009-07-01

    Aquaculture is one of the fastest growing food-producing sectors, supplying approximately 40% of the world's fish food. Besides such benefit to the society, the industry does have its problems. There are occupational hazards and safety concerns in the aquaculture industry. Some practices have caused environmental degradation. Public perception to farmed fish is that they are "cleaner" than comparable wild fish. However, some farmed fish have much higher body burden of natural and man-made toxic substances, e.g. antibiotics, pesticides, and persistent organic pollutants, than wild fish. These contaminants in fish can pose health concerns to unsuspecting consumers, in particular pregnant or nursing women. Regulations and international oversight for the aquaculture industry are extremely complex, with several agencies regulating aquaculture practices, including site selection, pollution control, water quality, feed supply, and food safety. Since the toxicological, environmental, and health concerns of aquaculture have not been adequately reviewed recently, we are providing an updated review of the topic. Specifically, concerns and recommendations for improving the aquaculture industry, and for protection of the environment and the consumers will be concisely presented.

  20. A SYSTEMS BIOLOGY APPROACH TO DEVELOPMENTAL TOXICOLOGY

    EPA Science Inventory

    Abstract
    Recent advances in developmental biology have yielded detailed models of gene regulatory networks (GRNs) involved in cell specification and other processes in embryonic differentiation. Such networks form the bedrock on which a systems biology approach to developme...

  1. Toxicological and ecotoxicological properties of gas-to-liquid (GTL) products. 1. Mammalian toxicology.

    PubMed

    Boogaard, Peter J; Carrillo, Juan-Carlos; Roberts, Linda G; Whale, Graham F

    2017-02-01

    Gas-to-liquid (GTL) products are synthetic hydrocarbons produced from natural gas using a Fischer-Tropsch process. This process yields a synthetic crude oil that consists of saturated hydrocarbons, primarily linear alkanes, with increasing amounts of branched (methyl-groups) alkanes as the chains get longer. In addition, small amounts of cycloalkanes (branched cyclopentanes and cyclohexanes) may be formed as the polymerization reaction prolongs. This synthetic crude can subsequently be refined to a range of products very similar to petroleum refining. However, in contrast to their petroleum-derived analogs, GTL products are essentially free of unsaturated or aromatic constituents and also no sulfur-, oxygen-, or nitrogen-containing constituents are present. From a regulatory perspective, GTL products are new substances which require extensive testing to assess their hazardous properties. As a consequence, a wide range of GTL products, covering the entire portfolio of GTL products, have been tested over the past few years in a wide variety of toxicological studies, including reproductive and prenatal development toxicity studies. This review provides an overview of the hazardous properties of the various GTL products. In general, the data collected on GTL products provide strong proof that they exert minimal health effects. In addition, these data provide supporting evidence for what is known on the mechanisms of mammalian toxicology of their petroleum-derived analogs. In the few cases where adverse effects were found for the GTL substances, these were usually less severe than the adverse effects observed with their petroleum-derived analogs.

  2. Summary of chemically induced pulmonary lesions in the National Toxicology Program (NTP) toxicology and carcinogenesis studies.

    PubMed

    Dixon, Darlene; Herbert, Ronald A; Kissling, Grace E; Brix, Amy E; Miller, Rodney A; Maronpot, Robert R

    2008-04-01

    The lung is the second most common target site of neoplasia of chemicals tested by the National Toxicology Program (NTP). Of all peer-reviewed NTP studies to date (N = 545), a total of sixty-four chemicals in sixty-six reports produced significant site-specific neoplasia in the lungs of rats and/or mice. Of the studies associated with lung tumor induction, approximately 35% were inhalation and 35% were gavage studies, with dosed-feed, dosed-water, topical, intraperitoneal, or in utero routes of chemical administration accounting for 18%, 6%, 3%, 1%, and 1% of the studies, respectively. The most commonly induced lung tumors were alveolar/bronchiolar (A/B) adenoma and/or carcinoma for both species. The most frequently observed nonneoplastic lesions included hyperplasia and inflammation in both species. The liver was the most common primary site of origin of metastatic lesions to the lungs of mice; however, skin was most often the primary site of origin of metastatic lesions to the lungs of rats. In summary, A/B adenoma and carcinoma were the most frequently diagnosed chemically induced tumors in the lungs of both rats and mice in the NTP toxicology and carcinogenesis bioassays, and hyperplasia and inflammation were the most common nonneoplastic changes observed.

  3. The New Toxicology of Sophisticated Materials: Nanotoxicology and Beyond

    PubMed Central

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

    2011-01-01

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

  4. Latin America's present and future challenges in toxicology education

    SciTech Connect

    Rojas, M. . E-mail: martini@telcel.net.ve

    2005-09-01

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

  5. Evidence from Toxicology: The Most Essential Science for Prevention

    PubMed Central

    Mandrioli, Daniele; Silbergeld, Ellen Kovner

    2015-01-01

    Background The most essential goal of medicine and public health is to prevent harm (primum non nocere). This goal is only fully achieved with primary prevention, which requires us to identify and prevent harms prior to human exposure through research and testing that does not involve human subjects. For that reason, public health policies place considerable reliance on nonhuman toxicological studies. However, toxicology as a field has often not produced efficient and timely evidence for decision making in public health. In response to this, the U.S. National Research Council called for the adoption of evidence-based methods and systematic reviews in regulatory decision making. The U.S. Environmental Protection Agency (EPA), the Food and Drug Administration (FDA), and the European Food Safety Agency (EFSA) have recently endorsed these methods in their assessments of safety and risk. Objectives In this commentary we summarize challenges and problems in current practices in toxicology as applied to decision making. We compare these practices with the principles and methods utilized in evidence-based medicine and health care, with emphasis on the record of the Cochrane Collaboration. Discussion We propose a stepwise strategy to support the development, validation, and application of evidence-based toxicology (EBT). We discuss current progresses in this field produced by the Office of Health Assessment and Translation (OHAT) of the National Toxicology Program and the Navigation Guide works. We propose that adherence to the Cochrane principles is a fundamental prerequisite for the development and implementation of EBT. Conclusion The adoption of evidence-based principles and methods will enhance the validity, transparency, efficiency, and acceptance of toxicological evidence, with benefits in terms of reducing delays and costs for all stakeholders (researchers, consumers, regulators, and industry). Citation Mandrioli D, Silbergeld EK. 2016. Evidence from toxicology: the

  6. The new toxicology of sophisticated materials: nanotoxicology and beyond.

    PubMed

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

    2011-03-01

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

  7. The role of the toxicologic pathologist in the post-genomic era(#).

    PubMed

    Maronpot, Robert R

    2013-06-01

    molecular biologists. In this present era newly emerging DVM and MD scientists enter the work arena with a PhD in pathology often based on some aspect of molecular biology or molecular pathology research. In molecular biology, the almost daily technological advances require one's complete dedication to remain at the cutting edge of the science. Similarly, the practice of toxicologic pathology, like other morphological disciplines, is based largely on experience and requires dedicated daily examination of pathology material to maintain a well-trained eye capable of distilling specific information from stained tissue slides - a dedicated effort that cannot be well done as an intermezzo between other tasks. It is a rare individual that has true expertise in both molecular biology and pathology. In this genomic era, the newly emerging DVM-PhD or MD-PhD pathologist enters a marketplace without many job opportunities in contrast to the pre-genomic era. Many face an identity crisis needing to decide to become a competent pathologist or, alternatively, to become a competent molecular biologist. At the same time, more PhD molecular biologists without training in pathology are members of the research teams working in drug development and toxicology. How best can the toxicologic pathologist interact in the contemporary team approach in drug development, toxicology research and safety testing? Based on their biomedical training, toxicologic pathologists are in an ideal position to link data from the emerging technologies with their knowledge of pathobiology and toxicology. To enable this linkage and obtain the synergy it provides, the bench-level, slide-reading expert pathologist will need to have some basic understanding and appreciation of molecular biology methods and tools. On the other hand, it is not likely that the typical molecular biologist could competently evaluate and diagnose stained tissue slides from a toxicology study or a cancer bioassay. The post-genomic era: The post

  8. Poison control centers in developing countries and Asia's need for toxicology education

    SciTech Connect

    Makalinao, Irma R. . E-mail: docirma@mydestiny.net; Awang, Rahmat

    2005-09-01

    Poison control centers (PCCs) in developing countries have been set up in response to the challenge of decreasing mortality and morbidity from poisoning. The services range from poison information to actual clinical treatment mostly of acute cases. Lately, PCCs have expanded from their traditional role to one that actively engages in community health studies, toxicovigilance along with treatment of chronic poisoning. Recognizing that types of poisoning and specific needs may vary from country to country, toxicology education that addresses these unique regional issues has become more necessary. Toxicology education, both formal and informal, exists in various stages of development in Asia. Clearly, there are gaps that need to be addressed especially in areas where there are no poison centers or where strengthening is necessary. Collaboration between PCCs in developing countries can help augment available resources including human, analytical and technical expertise. The critical mass of trained toxicologists will fill in the demand for clinical and regulatory specialists and educators as well. This paper highlights the experiences and resources available to the Philippine and Malaysian poison centers and the strengths generated by networking and collaboration. The role of Asia Pacific Association of Medical Toxicology (APAMT) as the Science NGO representative to the Intergovernmental Forum on Chemical Safety (IFCS) forum standing committee in promoting chemical safety at the regional level will be discussed. The 'Clearinghouse on the Sound Management of Chemicals', a platform for engaging multi-stakeholder and interdisciplinary partnerships, will be described as a possible model for capacity building to advance chemical safety through education and training not only in developing countries in Asia but globally as well.

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

    SciTech Connect

    Lock, Edward A.; 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. 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

  10. Fraud, errors and gamesmanship in experimental toxicology.

    PubMed

    Purchase, Iain F H

    2004-09-30

    We expect moral behaviour from scientists. Morality implies being a good person and being good at one's profession. The general view appears to be that the vast majority of scientists aim to achieve these high standards. Science prides itself on the 'self-correcting' mechanism in the scientific method, namely the requirement to reproduce findings before they are taken seriously. However, when findings are related to the adverse effects of chemicals there are several features that make this less effective than in some other fields of science. First, is the perception that everyone is exposed to chemicals and observations about chemical danger are immediately applicable to many people. Second, it is often easy to summarize adverse findings in attention-getting headlines seen by the lay public before the slow process of replication and interpretation has time to work. Third, most regulatory toxicology studies on a particular compound are only done once to minimise cost and the use of animals. Finally, the question posed about chemicals--are they safe?--is easy to ask but more difficult to test with appropriate studies. Fabrication of data in regulatory studies was found to occur in several contract laboratories in the 1960s and this lead directly to the introduction of Good Laboratory Practice regulations. Now studies submitted for regulatory purposes must comply with GLP regulations and this has virtually eliminated flawed studies due to fraudulent or careless behaviour. It is possible to discern different ways in which the expected standards have not been met. The first is in the intention of the work. Thus reports that the Roodeplaats Research Laboratory in South Africa was seeking to identify toxins that would kill without trace is an example where the intention is unacceptable. The second is in the conduct of the studies. Here the examples of William McBride and Michael Briggs who falsified data are pertinent. The example of the retraction of reports on the

  11. Toxicological Properties of the Organophosphorus Insecticide Dimethoate

    PubMed Central

    Sanderson, D. M.; Edson, E. F.

    1964-01-01

    The results are presented of extensive toxicological studies on the systemic organophosphate insecticide dimethoate, and compared with published results from other laboratories. It behaves as a typical indirect anticholinesterase, by conversion in the liver to at least four short-lived active metabolites, whose hydrolysis products are rapidly excreted, mainly in the urine. The acute oral toxicity of dimethoate is low in mammals but higher in avians. Dermal absorption is notably slow and dermal toxicity correspondingly low. Cumulative dosing of rats and guinea-pigs gave no cholinesterase inhibition at 0·7 and 4 mg./kg./day respectively. Dietary feeding to growing rats caused no cholinesterase inhibition at 0·5 mg./kg./day and no other effect at 10 times this dose. The main plant metabolite is identical with one formed in the liver, and comparative feeding tests with normal dimethoate and that partly metabolized in vegetation showed that residue analysis determined total hazard. Tests on humans, some with 32P-labelled material, confirmed that metabolism and urinary excretion are very rapid, that skin absorption is very slow, and that at least 2·5 mg., and probably up to 18 mg., could be ingested daily for at least three weeks without cholinesterase inhibition or other effects. Vapour hazards proved negligible. Oral toxicity was not potentiated by any of 17 other insecticides. The earliest detectable effect of dimethoate poisoning was always erythrocyte cholinesterase inhibition. Symptoms of poisoning could be effectively treated by atropine but not by oxime therapy. No known cases of occupational poisoning have occurred during five years' commercial usage of dimethoate. PMID:14106136

  12. Tetrahydrocannabinols in clinical and forensic toxicology.

    PubMed

    Kochanowski, Maciej; Kała, Maria

    2005-01-01

    Cannabinoids are the natural constituents of marihuana (cannabis). The main of them are delta9-tetrahydrocannabinol (9THC)--psychoactive agent, cannabinol (CBN) and cannabidiol (CBD). Cannabis is administered either by smoking or orally. 9THC potency and duration of action as well as its and two of its major metabolites concentrations in organism highly depend on the route of administration. A single active dose of 9THC is estimated on 520 mg. 9THC is rapidly metabolised. It is hydroxylated to an active metabolite, I1 -hydroxy-delta9-tetrahydro-cannabinol (11-OH-THC), then oxidised to an inactive 11-nor-9-carboxy-delta9-tetrahydrocannabinol (THCCOOH), which is conjugated with glucuronic acid and predominantly excreted in the urine. The maximum psychological effect persists for 4-6 h after administration despite of very low 9THC blood concentrations. 9THC plasma concentration declined to values of 2-3 ng/ml during 3-4 h after smoking. Such a low concentration of the active compound in human organism create a demand for use of sensitive analytical methods for detection and determination of 9THC and its metabolites. The most effective techniques for 9THC and related compounds determination in biological material are chromatographic ones (gas and liquid) with mass spectrometric detection and different ionization modes. 9THC and its two metabolites (11-OH-THC and THCCOOH) are present in blood and hair, 9THC in saliva, and THCCOOH in urine. 9THC and related compounds are determined in autopsy material, although deaths by overdose of cannabis are exceptionally rare. Fatalities happen most often after intravenous injection of hashish oil. 9THC and its metabolites determination in different biological materials gives the basis for a wide interpretation of analytical results for clinical and forensic toxicology purposes.

  13. Perlite toxicology and epidemiology – a review

    PubMed Central

    Niebo, Ron; McConnell, Ernest E.

    2014-01-01

    Perlite is a generic name for an amorphous volcanic alumina–silicate rock that expands by a factor of 4–20 when rapidly heated to 1400–1800 °F (760–980 °C). Both the ore and the expanded product have extensive and widespread commercial applications. Limited data on the toxicology of perlite in animal studies indicate that the LD50 (oral ingestion) is more than 10 g/kg and, from a chronic inhalation study in guinea pigs and rats, that the NOAEL for the inhalation pathway is 226 mg/m3. Health surveillance studies of workers in US perlite mines and expansion plants (including some workers exposed to levels greater than prevailing occupational exposure limits (OELs) conducted over 20 years indicate that the respiratory health of workers is not adversely affected. Studies in Turkish mines and expanding plants had generally similar results, but are more difficult to interpret because of high smoking rates in these populations. A recent mortality study of permanent residents of the island of Milos (Greece) exposed to various mining dusts (including perlite) resulted in non-significant increases in standard mortality ratios for pneumonia and chronic obstructive pulmonary disease (COPD), whereas a companion morbidity study revealed elevated odds ratios for allergic rhinitis, pneumonia, and COPD when compared to another industrial area of Greece. Residents were exposed to other mining dusts and other possible causes or contributing factors and no ambient monitoring data were presented so it is not possible to use this study for risk calculations of perlite-exposed populations. Perlite is regulated as a “nuisance dust” in most countries. PMID:24601903

  14. Fluoride in groundwater: toxicological exposure and remedies.

    PubMed

    Jha, S K; Singh, R K; Damodaran, T; Mishra, V K; Sharma, D K; Rai, Deepak

    2013-01-01

    Fluoride is a chemical element that is found most frequently in groundwater and has become one of the most important toxicological environmental hazards globally. The occurrence of fluoride in groundwater is due to weathering and leaching of fluoride-bearing minerals from rocks and sediments. Fluoride when ingested in small quantities (<0.5 mg/L) is beneficial in promoting dental health by reducing dental caries, whereas higher concentrations (>1.5 mg/L) may cause fluorosis. It is estimated that about 200 million people, from among 25 nations the world over, may suffer from fluorosis and the causes have been ascribed to fluoride contamination in groundwater including India. High fluoride occurrence in groundwaters is expected from sodium bicarbonate-type water, which is calcium deficient. The alkalinity of water also helps in mobilizing fluoride from fluorite (CaF2). Fluoride exposure in humans is related to (1) fluoride concentration in drinking water, (2) duration of consumption, and (3) climate of the area. In hotter climates where water consumption is greater, exposure doses of fluoride need to be modified based on mean fluoride intake. Various cost-effective and simple procedures for water defluoridation techniques are already known, but the benefits of such techniques have not reached the rural affected population due to limitations. Therefore, there is a need to develop workable strategies to provide fluoride-safe drinking water to rural communities. The study investigated the geochemistry and occurrence of fluoride and its contamination in groundwater, human exposure, various adverse health effects, and possible remedial measures from fluoride toxicity effects.

  15. Lupinus mutabilis: Composition, Uses, Toxicology, and Debittering.

    PubMed

    Carvajal-Larenas, F E; Linnemann, A R; Nout, M J R; Koziol, M; van Boekel, M A J S

    2016-07-03

    Lupinus mutabilis has protein (32.0-52.6 g/100 g dry weight) and lipid (13.0-24.6 g/100 g dry weight) contents similar to soya bean (Glycine max). The Ω3, Ω6, and Ω9 contents are 1.9-3.0, 26.5-39.6, and 41.2-56.2 g/100 g lipid, respectively. Lupins can be used to fortify the protein content of pasta, bread, biscuits, salads, hamburgers, sausages, and can substitute milk and soya bean. Specific lupin protein concentrates or isolates display protein solubility (>90%), water-absorption capacity (4.5 g/g dry weight), oil-absorption capacity (3.98 g/g), emulsifying capacity (2000 mL of oil/g), emulsifying stability (100%, 60 hours), foaming capacity (2083%), foaming stability (78.8%, 36 hours), and least gelation concentration (6%), which are of industrial interest. Lupins contain bitter alkaloids. Preliminary studies on their toxicity suggest as lethal acute dose for infants and children 10 mg/kg bw and for adults 25 mg/kg bw. However, alkaloids can also have medical use for their hypocholesterolemic, antiarrhythmic, and immunosuppressive activity. Bitter lupins can be detoxified by biological, chemical, or aqueous processes. The shortest debittering process requires one hour. This review presents the nutritional composition of lupins, their uses (as food, medicine, and functional protein isolates), toxicology, and debittering process scenarios. It critically evaluates the data, infers conclusions, and makes suggestions for future research.

  16. Perlite toxicology and epidemiology--a review.

    PubMed

    Maxim, L Daniel; Niebo, Ron; McConnell, Ernest E

    2014-04-01

    Perlite is a generic name for an amorphous volcanic alumina-silicate rock that expands by a factor of 4-20 when rapidly heated to 1400-1800 °F (760-980 °C). Both the ore and the expanded product have extensive and widespread commercial applications. Limited data on the toxicology of perlite in animal studies indicate that the LD₅₀ (oral ingestion) is more than 10 g/kg and, from a chronic inhalation study in guinea pigs and rats, that the NOAEL for the inhalation pathway is 226 mg/m³. Health surveillance studies of workers in US perlite mines and expansion plants (including some workers exposed to levels greater than prevailing occupational exposure limits (OELs) conducted over 20 years indicate that the respiratory health of workers is not adversely affected. Studies in Turkish mines and expanding plants had generally similar results, but are more difficult to interpret because of high smoking rates in these populations. A recent mortality study of permanent residents of the island of Milos (Greece) exposed to various mining dusts (including perlite) resulted in non-significant increases in standard mortality ratios for pneumonia and chronic obstructive pulmonary disease (COPD), whereas a companion morbidity study revealed elevated odds ratios for allergic rhinitis, pneumonia, and COPD when compared to another industrial area of Greece. Residents were exposed to other mining dusts and other possible causes or contributing factors and no ambient monitoring data were presented so it is not possible to use this study for risk calculations of perlite-exposed populations. Perlite is regulated as a "nuisance dust" in most countries.

  17. Pharmacological and toxicological properties of Nigella sativa.

    PubMed

    Ali, B H; Blunden, Gerald

    2003-04-01

    The seeds of Nigella sativa Linn. (Ranunculaceae), commonly known as black seed or black cumin, are used in folk (herbal) medicine all over the world for the treatment and prevention of a number of diseases and conditions that include asthma, diarrhoea and dyslipidaemia. This article reviews the main reports of the pharmacological and toxicological properties of N. sativa and its constituents. The seeds contain both fixed and essential oils, proteins, alkaloids and saponin. Much of the biological activity of the seeds has been shown to be due to thymoquinone, the major component of the essential oil, but which is also present in the fi ed oil. The pharmacological actions of the crude extracts of the seeds (and some of its active constituents, e.g. volatile oil and thymoquinone) that have been reported include protection against nephrotoxicity and hepatotoxicity induced by either disease or chemicals. The seeds/oil have antiinflammatory, analgesic, antipyretic, antimicrobial and antineoplastic activity. The oil decreases blood pressure and increases respiration. Treatment of rats with the seed extract for up to 12 weeks has been reported to induce changes in the haemogram that include an increase in both the packed cell volume (PCV) and haemoglobin (Hb), and a decrease in plasma concentrations of cholesterol, triglycerides and glucose. The seeds are characterized by a very low degree of toxicity. Two cases of contact dermatitis in two individuals have been reported following topical use. Administration of either the seed extract or its oil has been shown not to induce significant adverse effects on liver or kidney functions. It would appear that the beneficial effects of the use of the seeds and thymoquinone might be related to their cytoprotective and antioxidant actions, and to their effect on some mediators of inflammation.

  18. Toxicology of Marine Mammals: New Developments and Opportunities.

    PubMed

    Weijs, Liesbeth; Zaccaroni, Annalisa

    2016-01-01

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

  19. Role of chronic toxicology studies in revealing new toxicities.

    PubMed

    Galijatovic-Idrizbegovic, Alema; Miller, Judith E; Cornell, Wendy D; Butler, James A; Wollenberg, Gordon K; Sistare, Frank D; DeGeorge, Joseph J

    2016-12-01

    Chronic (>3 months) preclinical toxicology studies are conducted to support the safe conduct of clinical trials exceeding 3 months in duration. We have conducted a review of 32 chronic toxicology studies in non-rodents (22 studies in dogs and 10 in non-human primates) and 27 chronic toxicology studies in rats dosed with Merck compounds to determine the frequency at which additional target organ toxicities are observed in chronic toxicology studies as compared to subchronic studies of 3 months in duration. Our review shows that majority of the findings are observed in the subchronic studies since additional target organs were not observed in 24 chronic non rodent studies and in 21 chronic rodent studies. However, 6 studies in non rodents and 6 studies in rodents yielded new findings that were not seen in studies of 3-month or shorter duration. For 3 compounds the new safety findings did contribute to termination of clinical development plans. Although the incidence of compound termination associated with chronic toxicology study observations is low (∼10%), the observations made in these studies can be important for evaluating human safety risk.

  20. Chemical Mixtures: Considering the Evolution of Toxicology and Chemical Assessment

    PubMed Central

    Monosson, Emily

    2005-01-01

    The assessment of chemical mixtures is a complex topic for toxicologists, regulators, and the public. In this article the linkage between the science of toxicology and the needs of governmental regulatory agencies in the United States is explored through an overview of environmental regulations enacted over the past century and a brief history of modern toxicology. One of the goals of this overview is to encourage both regulators and scientists to consider the benefits and limitations of this science–regulatory relationship as they tackle existing issues such as chemical mixtures. It is clear that a) over the past 100 years chemical regulation and toxicologic research, have in large part, shared a common emphasis on characterization and regulation of individual chemicals. But chemical mixtures have been, and continue to be, evaluated at hazardous waste sites around the United States. For this reason the current U.S. Environmental Protection Agency guidelines for chemical mixtures assessment are also reviewed. These guidelines highlight the current practice of mixtures assessment, which relies primarily on the existing single-chemical database. It is also clear that b) the science and assessment of chemical mixtures are moving forward through the combined efforts of regulatory agencies and scientists from a broad range of disciplines, including toxicology. Because toxicology is at this exciting crossroads, particular attention should be paid to the forces (e.g., public demands, regulatory needs, funding, academic interests) that both promote and limit the growth of this expanding discipline. PMID:15811826

  1. Toxicological challenges to microbial bioethanol production and strategies for improved tolerance.

    PubMed

    Akinosho, Hannah; Rydzak, Thomas; Borole, Abhijeet; Ragauskas, Arthur; Close, Dan

    2015-12-01

    Bioethanol production output has increased steadily over the last two decades and is now beginning to become competitive with traditional liquid transportation fuels due to advances in engineering, the identification of new production host organisms, and the development of novel biodesign strategies. A significant portion of these efforts has been dedicated to mitigating the toxicological challenges encountered across the bioethanol production process. From the release of potentially cytotoxic or inhibitory compounds from input feedstocks, through the metabolic co-synthesis of ethanol and potentially detrimental byproducts, and to the potential cytotoxicity of ethanol itself, each stage of bioethanol production requires the application of genetic or engineering controls that ensure the host organisms remain healthy and productive to meet the necessary economies required for large scale production. In addition, as production levels continue to increase, there is an escalating focus on the detoxification of the resulting waste streams to minimize their environmental impact. This review will present the major toxicological challenges encountered throughout each stage of the bioethanol production process and the commonly employed strategies for reducing or eliminating potential toxic effects.

  2. Impact of computational structure-based predictive toxicology in drug discovery.

    PubMed

    Mohan, Chethampadi Gopi

    2011-06-01

    Computational tools for predicting toxicity have been envisioned to have the potential to broadly impact up on the attrition rate of compounds in pre-clinical drug discovery and development. An integrated approach of computer-assisted, predictive, and physico-chemical properties of a compound, along with its in vitro and in vivo analysis, needs to be routinely exercised in the lead identification and lead optimization processes. Starting with a good lead can save a lot of money and it can significantly reduce the entire drug discovery process. The journey towards triple R's- reduce, replace and refine, further proves to be successful in predicting adverse drug reactions in patients (or animals) enrolled in clinical trials. However, the impact of predictive toxicity analysis was modest and relatively narrow in scope, due to the limited domain knowledge in this field. It is important to note that advances within medical science and newer approaches in drug development will require predictive toxicology applications to be viable. The field of computational toxicology has been heading in a direction more relevant to human diseases by reducing the adverse drug reactions. Therefore, efforts must be directed to integrating these tools relevant to the goal of preventing undesired toxicity in pre-clinical trials followed by different phases of clinical trials.

  3. Decavanadate Toxicology and Pharmacological Activities: V10 or V1, Both or None?

    PubMed

    Aureliano, M

    2016-01-01

    This review covers recent advances in the understanding of decavanadate toxicology and pharmacological applications. Toxicological in vivo studies point out that V10 induces several changes in several oxidative stress parameters, different from the ones observed for vanadate (V1). In in vitro studies with mitochondria, a particularly potent V10 effect, in comparison with V1, was observed in the mitochondrial depolarization (IC50 = 40 nM) and oxygen consumption (99 nM). It is suggested that mitochondrial membrane depolarization is a key event in decavanadate induction of necrotic cardiomyocytes death. Furthermore, only decavanadate species and not V1 potently inhibited myosin ATPase activity stimulated by actin (IC50 = 0.75 μM) whereas exhibiting lower inhibition activities for Ca(2+)-ATPase activity (15 μM) and actin polymerization (17 μM). Because both calcium pump and actin decavanadate interactions lead to its stabilization, it is likely that V10 interacts at specific locations with these proteins that protect against hydrolysis but, on the other hand, it may induce V10 reduction to oxidovanadium(IV). Putting it all together, it is suggested that the pharmacological applications of V10 species and compounds whose mechanism of action is still to be clarified might involve besides V10 and V1 also vanadium(IV) species.

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

    PubMed

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

    2016-05-01

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

  5. Decavanadate Toxicology and Pharmacological Activities: V10 or V1, Both or None?

    PubMed Central

    Aureliano, M.

    2016-01-01

    This review covers recent advances in the understanding of decavanadate toxicology and pharmacological applications. Toxicological in vivo studies point out that V10 induces several changes in several oxidative stress parameters, different from the ones observed for vanadate (V1). In in vitro studies with mitochondria, a particularly potent V10 effect, in comparison with V1, was observed in the mitochondrial depolarization (IC50 = 40 nM) and oxygen consumption (99 nM). It is suggested that mitochondrial membrane depolarization is a key event in decavanadate induction of necrotic cardiomyocytes death. Furthermore, only decavanadate species and not V1 potently inhibited myosin ATPase activity stimulated by actin (IC50 = 0.75 μM) whereas exhibiting lower inhibition activities for Ca2+-ATPase activity (15 μM) and actin polymerization (17 μM). Because both calcium pump and actin decavanadate interactions lead to its stabilization, it is likely that V10 interacts at specific locations with these proteins that protect against hydrolysis but, on the other hand, it may induce V10 reduction to oxidovanadium(IV). Putting it all together, it is suggested that the pharmacological applications of V10 species and compounds whose mechanism of action is still to be clarified might involve besides V10 and V1 also vanadium(IV) species. PMID:26904166

  6. Toxicological challenges to microbial bioethanol production and strategies for improved tolerance

    DOE PAGES

    Akinsho, Hannah; Rydzak, Thomas; Borole, Abhijeet P.; ...

    2015-09-30

    Bioethanol production output has increased steadily over the last two decades and is now beginning to become competitive with traditional liquid transportation fuels due to advances in engineering, the identification of new production host organisms, and the development of novel biodesign strategies. A significant portion of these efforts has been dedicated to mitigating the toxicological challenges encountered across the bioethanol production process. From the release of potentially cytotoxic or inhibitory compounds from input feedstocks, through the metabolic co-synthesis of ethanol and potentially detrimental byproducts, and to the potential cytotoxicity of ethanol itself, each stage of bioethanol production requires the applicationmore » of genetic or engineering controls that ensure the host organisms remain healthy and productive to meet the necessary economies required for large scale production. In addition, as production levels continue to increase, there is an escalating focus on the detoxification of the resulting waste streams to minimize their environmental impact. Thus, this review will present the major toxicological challenges encountered throughout each stage of the bioethanol production process and the commonly employed strategies for reducing or eliminating potential toxic effects.« less

  7. Toxicological challenges to microbial bioethanol production and strategies for improved tolerance

    SciTech Connect

    Akinsho, Hannah; Rydzak, Thomas; Borole, Abhijeet P.; Ragauskas, Arthur; Close, Dan

    2015-09-30

    Bioethanol production output has increased steadily over the last two decades and is now beginning to become competitive with traditional liquid transportation fuels due to advances in engineering, the identification of new production host organisms, and the development of novel biodesign strategies. A significant portion of these efforts has been dedicated to mitigating the toxicological challenges encountered across the bioethanol production process. From the release of potentially cytotoxic or inhibitory compounds from input feedstocks, through the metabolic co-synthesis of ethanol and potentially detrimental byproducts, and to the potential cytotoxicity of ethanol itself, each stage of bioethanol production requires the application of genetic or engineering controls that ensure the host organisms remain healthy and productive to meet the necessary economies required for large scale production. In addition, as production levels continue to increase, there is an escalating focus on the detoxification of the resulting waste streams to minimize their environmental impact. Thus, this review will present the major toxicological challenges encountered throughout each stage of the bioethanol production process and the commonly employed strategies for reducing or eliminating potential toxic effects.

  8. Mechanistic modeling of pesticide exposure: The missing keystone of honey bee toxicology.

    PubMed

    Sponsler, Douglas B; Johnson, Reed M

    2017-04-01

    The role of pesticides in recent honey bee losses is controversial, partly because field studies often fail to detect effects predicted by laboratory studies. This dissonance highlights a critical gap in the field of honey bee toxicology: there exists little mechanistic understanding of the patterns and processes of exposure that link honey bees to pesticides in their environment. The authors submit that 2 key processes underlie honey bee pesticide exposure: 1) the acquisition of pesticide by foraging bees, and 2) the in-hive distribution of pesticide returned by foragers. The acquisition of pesticide by foraging bees must be understood as the spatiotemporal intersection between environmental contamination and honey bee foraging activity. This implies that exposure is distributional, not discrete, and that a subset of foragers may acquire harmful doses of pesticide while the mean colony exposure would appear safe. The in-hive distribution of pesticide is a complex process driven principally by food transfer interactions between colony members, and this process differs importantly between pollen and nectar. High priority should be placed on applying the extensive literature on honey bee biology to the development of more rigorously mechanistic models of honey bee pesticide exposure. In combination with mechanistic effects modeling, mechanistic exposure modeling has the potential to integrate the field of honey bee toxicology, advancing both risk assessment and basic research. Environ Toxicol Chem 2017;36:871-881. © 2016 SETAC.

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

    EPA Pesticide Factsheets

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

  10. Thresholds as a unifying theme in regulatory toxicology.

    PubMed

    Cheeseman, M A

    2005-10-01

    The scientific basis for the US Food and Drug Administration (FDA) threshold of regulation is discussed in relation to its toxicological testing recommendations for food contact substances and the existing methods it employs for exposure estimation. A case is made that the FDA's threshold of regulation is a natural extension of its toxicity testing regime. The genetic toxicity tests recommended in the exposure-based toxicological testing framework for food contact substances are examined regarding their ability to predict positively carcinogens of varying potency. In addition, the computational toxicology program MULTICASE v. 3.1 is also examined for its ability to predict positively carcinogens of varying potency. It is concluded that MULTICASE can provide equivalent results to genetic toxicity tests at the lowest dietary concentrations.

  11. Juvenile Toxicology: Relevance and Challenges for Toxicologists and Pathologists

    PubMed Central

    Remick, Amera K.; Catlin, Natasha R.; Quist, Erin M.; Steinbach, Thomas J.; Dixon, Darlene

    2015-01-01

    The Society of Toxicologic Pathology (STP) Education Committee and the STP Reproductive Special Interest Group held a North Carolina regional meeting entitled, “Juvenile Toxicology: Relevance and Challenges for Toxicologists and Pathologists” on March 13, 2015, at the National Institute of Environmental Health Sciences/National Toxicology Program in Research Triangle Park, North Carolina. The purpose of this regional meeting was to familiarize attendees with the topic of juvenile toxicity testing and discuss its relevance to clinical pediatric medicine, regulatory perspectives, challenges of appropriate study design confronted by toxicologists, and challenges of histopathologic examination and interpretation of juvenile tissues faced by pathologists. The 1-day meeting was a success with over 60 attendees representing industry, government, research organizations, and academia. PMID:26220944

  12. Systems toxicology: modelling biomarkers of glutathione homeostasis and paracetamol metabolism.

    PubMed

    Stahl, Simone H; Yates, James W; Nicholls, Andrew W; Kenna, J Gerry; Coen, Muireann; Ortega, Fernando; Nicholson, Jeremy K; Wilson, Ian D

    2015-08-01

    One aim of systems toxicology is to deliver mechanistic, mathematically rigorous, models integrating biochemical and pharmacological processes that result in toxicity to enhance the assessment of the risk posed to humans by drugs and other xenobiotics. The benefits of such 'in silico' models would be in enabling the rapid and robust prediction of the effects of compounds over a range of exposures, improving in vitro-in vivo correlations and the translation from preclinical species to humans. Systems toxicology models of organ toxicities that result in high attrition rates during drug discovery and development, or post-marketing withdrawals (e.g., drug-induced liver injury (DILI)) should facilitate the discovery of safe new drugs. Here, systems toxicology as applied to the effects of paracetamol (acetaminophen, N-acetyl-para-aminophenol (APAP)) is used to exemplify the potential of the approach.

  13. IRIS Toxicological Review of Cerium Oxide and Cerium ...

    EPA Pesticide Factsheets

    On September 29, 2009, the IRIS Summary and Toxicological Review of Cerium Oxide and Cerium Compounds was finalized and loaded onto the IRIS database. The Toxicological Review of Cerium Oxide and Cerium Compounds was reviewed internally by EPA, by other federal agencies and White House Offices, by expert external peer reviewers, and by the public. In the new IRIS process, introduced by the EPA Administrator, all written comments on IRIS assessments submitted by other federal agencies and White House Offices will be made publicly available. Accordingly, interagency comments and the interagency draft of the Cerium Oxide and Cerium Compounds IRIS assessment are posted on this site. The draft Toxicological Review of Cerium Oxide and Cerium Compounds provides scientific support and rationale for the hazard identification and dose-response assessment pertaining to chronic exposure to cerium oxide and cerium compounds.

  14. 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...

  15. 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...

  16. 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)

  17. 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...

  18. 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...

  19. Preparation and characterization of "Libby Amphibole" toxicological testing material

    USGS Publications Warehouse

    Lowers, Heather; Wilson, Stephen A.; Hoefen, Todd M.; Benzel, William M.; Meeker, Gregory P.

    2012-01-01

    The U.S. Environmental Protection Agency (USEPA) began work in Libby, Mont. in 1999 when an Emergency Response Team was sent to investigate local concern and media reports regarding asbestos-contaminated vermiculite. Since that time, the site has been granted Superfund status and site remediation to a safe level of asbestos has been ongoing. The amphibole asbestos from the Vermiculite Mountain vermiculite deposit near Libby, Mont. (Libby amphibole) is unusual in the sense that it is currently not classified as one of the regulated six asbestos minerals—chrysotile (a serpentine mineral) and the amphibole minerals amosite (asbestiform cummingtonite-grunerite), crocidolite (asbestiform riebeckite), asbestiform anthophyllite, asbestiform tremolite, and asbestiform actinolite. The amphiboles from the Vermiculite Mountain vermiculite deposit, primarily winchite and richterite, are related to tremolite and in the past have been referred to as sodium-rich tremolite or soda tremolite (Larsen, 1942; Boettcher, 1966; Wylie and Verkouteren, 2000; Gunter and others, 2003; Meeker and others, 2003). The public health issues in Libby, Mont. have brought to light many of the inconsistencies in the literature regarding fiber characteristics, nomenclature, and toxicology. To better understand the toxicological characteristics of the Libby amphibole, investigators require a sufficient quantity of material representing the range of fibrous amphiboles present in the vicinity of Vermiculite Mountain to use in toxicology studies. The material collected in 2000 (Meeker and others, 2003) has been exhausted and a second collection and preparation effort, funded by the USEPA, was conducted in 2007. Both the 2000 (LA2000) and 2007 (LA2007) materials were generated to support research needs identified by the USEPA and the National Toxicology Program, and new in-vivo and in-vitro toxicology studies are underway. This Open-File Report describes the process of preparation and summarizes the

  20. Applications of scientific imaging in environmental toxicology

    NASA Astrophysics Data System (ADS)

    El-Demerdash, Aref M.

    The national goals of clean air, clean water, and healthy ecosystems are a few of the primary forces that drive the need for better environmental monitoring. As we approach the end of the 1990s, the environmental questions at regional to global scales are being redefined and refined in the light of developments in environmental understanding and technological capability. Research in the use of scientific imaging data for the study of the environment is urgently needed in order to explore the possibilities of utilizing emerging new technologies. The objective of this research proposal is to demonstrate the usability of a wealth of new technology made available in the last decade to providing a better understanding of environmental problems. Research is focused in two imaging techniques macro and micro imaging. Several examples of applications of scientific imaging in research in the field of environmental toxicology were presented. This was achieved on two scales, micro and macro imaging. On the micro level four specific examples were covered. First, the effect of utilizing scanning electron microscopy as an imaging tool in enhancing taxa identification when studying diatoms was presented. Second, scanning electron microscopy combined with energy dispersive x-ray analyzer were demonstrated as a valuable and effective tool for identifying and analyzing household dust samples. Third, electronic autoradiography combined with FT-IR microscopy were used to study the distribution pattern of [14C]-Malathion in rats as a result of dermal exposure. The results of the autoradiography made on skin sections of the application site revealed the presence of [ 14C]-activity in the first region of the skin. These results were evidenced by FT-IR microscopy. The obtained results suggest that the penetration of Malathion into the skin and other tissues is vehicle and dose dependent. The results also suggest the use of FT-IR microscopy imaging for monitoring the disposition of

  1. In Silico Toxicology – Non-Testing Methods

    PubMed Central

    Raunio, Hannu

    2011-01-01

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

  2. IRIS Toxicological Review of Ethyl Tertiary Butyl Ether (ETBE) ...

    EPA Pesticide Factsheets

    The IRIS Toxicological Review of Ethyl Tertiary Butyl Ether (ETBE) was released for external peer review in April 2017. EPA’s Science Advisory Board’s (SAB) Chemical Assessment Advisory Committee (CAAC) will conduct a peer review of the scientific basis supporting the ETBE assessment and release a final report of their review. Information regarding the peer review can be found on the SAB website. EPA is conducting an Integrated Risk Information System (IRIS) health assessment for Ethyl Tertiary Butyl Ether (ETBE). The outcome of this project is a Toxicological Review and IRIS Summary for ETBE that will be entered into the IRIS database.

  3. Mammalian Toxicology Testing: Problem Definition Study. Capability Modules.

    DTIC Science & Technology

    1981-04-01

    AD-A112 9 LIFE SYSTEMS INC CLEVELAND OH F/S 6/90 MAM4ALIAN TOXICO.OY TESTING $ PROBLLM DEFINITION STUDY. CAPABL--ETC(U) APR t R A WYNVEEN, R V ALBAN...11111 .25 1-4 1.6 *fl*Ifl- ii, MICROCOPY RESOLUTION TEST CHART NATIONAL BURLAU OF STANDARDS 1963 A AD LSI TR-47-191 MAMMALIAN TOXICOLOGY TESTING : PROBLEM...REPORT & PERIOD COVEREDw MAMMALIAN TOXICOLOGY TESTING : PROBLEM Supporting Document DEFINITION STUDY, CAPABILITY MODULES 15 December 1980-5 April 1981

  4. Application of the programmable calculator in reporting emergency toxicology data.

    PubMed

    Samuels, R W

    1977-12-01

    The use of a programmable calculator in reporting the results of emergency toxicology analyses by personnel who do not routinely perform such analyses has eliminated the problems previously encountered due to unfamiliarity with a particular test or tests. The program that is used alerts the physician to those drugs that could possibly interfere in the screening tests used for emergency toxicology analyses and, in addition, provides him or her with an updated listing of popular street and recreational drugs and drugs of abuse in this area in the event that one of these is not detectable in the screening procedure.

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

    SciTech Connect

    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.

  6. Career advancement opportunities and the ACVP/STP Coalition.

    PubMed

    Cockerell, Gary

    2014-07-01

    A new service to facilitate career advancement opportunities has been implemented by the American College of Veterinary Pathologists (ACVP)/Society of Toxicologic Pathology (STP) Coalition for Veterinary Pathology Fellows. This service will allow rapid communication of these opportunities between veterinary pathologists in academia, industry, and government, and will be useful to trainees as well as established pathologists.

  7. 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...

  8. 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...

  9. Animal experiments scrutinised: systematic reviews demonstrate poor human clinical and toxicological utility.

    PubMed

    Knight, Andrew

    2007-01-01

    The assumption that animal models are reasonably predictive of human outcomes provides the basis for their widespread use in toxicity testing and in biomedical research aimed at developing cures for human diseases. To investigate the validity of this assumption, the comprehensive "Scopus" biomedical bibliographic databases were searched for published systematic reviews of the human clinical or toxicological utility of animal experiments. Of 20 reviews examining clinical utility, authors concluded that the animal models were substantially consistent with or useful in advancing clinical outcomes in only two cases, and the conclusion in one case was contentious. Included were reviews of the clinical utility of experiments expected by ethics committees to lead to medical advances, of highly-cited experiments published in major journals, and of chimpanzee experiments - the species most likely to be predictive of human outcomes. Seven additional reviews failed to clearly demonstrate utility in predicting human toxicological outcomes such as carcinogenicity and teratogenicity. Consequently, animal data may not generally be assumed to be substantially useful for these purposes. Possible causes include interspecies differences, the distortion of experimental outcomes arising from experimental environments and protocols, and the poor methodological quality of many animal experiments evident in at least 11 reviews. No reviews existed in which a majority of animal experiments were of good quality. While the latter problems might be minimised with concerted effort, given their widespread nature, the interspecies limitations are likely to be technically and theoretically impossible to overcome. Yet, unlike non-animal models, animal models are not normally subjected to formal scientific validation. Instead of simply assuming they are predictive of human outcomes, the consistent application of formal validation studies to all test models is clearly warranted, regardless of their

  10. Radiological/toxicological sabotage assessments at the Savannah River Site

    SciTech Connect

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

    1995-11-01

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

  11. IRIS Toxicological Review of Libby Amphibole Asbestos (Final Report)

    EPA Science Inventory

    EPA has finalized the, Toxicological Review of Libby Amphibole Asbestos: in support of the Integrated Risk Information System (IRIS). Now final, this assessment may be used by EPA’s program and regional offices to inform decisions to protect human health.

  12. IRIS Toxicological Review of Chloroprene (Interagency Science Discussion Draft)

    EPA Science Inventory

    EPA is releasing the draft report, Toxicological Review of Chloroprene, that was distributed to Federal agencies and White House Offices for comment during the Science Discussion step of the IRIS Assessment Development Process. Co...

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

    EPA Science Inventory

    EPA has finalized the Toxicological Review of Trichloroacetic Acid: in support of the Integrated Risk Information System (IRIS). Now final, this assessment may be used by EPA’s program and regional offices to inform decisions to protect human health.

  14. IRIS Toxicological Review for Carbon Tetrachloride (Interagency Science Discussion Draft)

    EPA Science Inventory

    EPA released the draft report,Toxicological Review for Carbon Tetrachloride(Interagency Science Discussion Draft), that was distributed to Federal agencies and White House Offices for comment during the Science Discussion step of the IRIS Assessment Development Process. Co...

  15. SYMPOSIUM IN ITALY: FISH PHYSIOLOGY, TOXICOLOGY, AND WATER QUALITY

    EPA Science Inventory

    Scientists from Europe, North America and South America convened in Capri, Italy, April 24-28, 2006 for the Ninth International Symposium on Fish Physiology, Toxicology, and Water Quality. The subject of the meeting was Eutrophication: The toxic effects of ammonia, nitrite and th...

  16. IRIS Toxicological Review of Biphenyl (Interagency Science Discussion Draft)

    EPA Science Inventory

    EPA is releasing the draft report, Toxicological Review of Biphenyl, that was distributed to other federal agencies and the Executive Office of the President for comment during Interagency Science Discussion (IASD) (Step 6b) of the IRIS assessment development process. Interagenc...

  17. IRIS Toxicological Review of 2-Methylnaphthalene (2003, Final)

    EPA Science Inventory

    EPA is announcing 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 Quickview have also been added to the IRIS Database.

  18. IRIS Toxicological Review of Carbon Tetrachloride (Final Report)

    EPA Science Inventory

    EPA has finalized the Toxicological Review of Carbon Tetrachloride: in support of the Integrated Risk Information System (IRIS). Now final, this assessment may be used by EPA’s program and regional offices to inform decisions to protect human health.

  19. A UNIFYING CONCEPT FOR ASSESSING TOXICOLOGICAL INTERACTIONS: CHANGES IN SLOPE

    EPA Science Inventory

    Robust statistical methods are important to the evaluation of interactions among chemicals in a mixture. However, different concepts of interaction as applied to the statistical analysis of chemical mixture toxicology data or as used in environmental risk assessment often can ap...

  20. IRIS Toxicological Review for Acrylamide (Interagency Science Discussion Draft)

    EPA Science Inventory

    EPA is releasing the draft report, Toxicological Review for Acrylamide, that was distributed to Federal agencies and White House Offices for comment during the Science Discussion step of the IRIS Assessment Development Process<...

  1. Computational Toxicology - A State of the Science Mini Review

    EPA Science Inventory

    This mini-review is based on presentations and discussions at the International Science Forum on Computational Toxicology that was sponsored by the Office of Research and Development of the US Environmental Protection Agency and held in Research Triangle Park, NC on May 21-23, 20...

  2. IRIS Toxicological Review of Methanol (External Review Draft; December 2009)

    EPA Science Inventory

    NOTE: The IRIS Toxicological Review of Methanol (external review draft; December 2009) was released for public comment and external peer review in January 2010 (Federal Register Not...

  3. IRIS Toxicological Review of Dichloromethane (Methylene Chloride) (Final Report)

    EPA Science Inventory

    EPA has finalized the Toxicological Review of Dichloromethane (Methylene Chloride): In support of the Integrated Risk Information System (IRIS). Now final, this assessment may be used by EPA’s program and regional offices to inform decisions to protect human health. This ...

  4. INTEGRATING EPIDEMIOLOGY AND TOXICOLOGY IN NEUROTOXICITY RISK ASSESSMENT.

    EPA Science Inventory

    This manuscript provides an overview of the use of data from toxicology and epidemiology studies for neurotoxicity risk assessment. Parameters such as the use of subjects, study designs, exposures, and measured outcomes are compared and contrasted. The main concern for use of d...

  5. IRIS Toxicological Review of Trimethylbenzenes (Interagency Science Discussion Draft)

    EPA Science Inventory

    In September 2016, EPA finalized the IRIS assessment of Trimethylbenzenes. The Toxicological Review was reviewed internally by EPA and by other federal agencies and White House Offices before public release in June 2016. Consistent with the May 2009 IRIS assessment development pr...

  6. IRIS Toxicological Review of Mirex (2003 External Review Draft)

    EPA Science Inventory

    EPA is providing for public information a draft Toxicological Review, draft IRIS Summary, and charge to external peer reviewers for EPA's Health Assessment of Mirex. These documents are provided for public viewing during an external scientific peer review period. While EPA is not...

  7. The startle response and toxicology: Methods, use and interpretation.

    EPA Science Inventory

    The startle response (SR) is a sensory-evoked motor reflex that has been used successfully in toxicology for decades. Advantages of this procedure include: rapidly objective measurement of a defined neural circuit, measurement of habituation of the response, and a high potential ...

  8. Wiki-based Data Management to Support Systems Toxicology*

    EPA Science Inventory

    As the field of toxicology relies more heavily on systems approaches for mode of action discovery, evaluation, and modeling, the need for integrated data management is greater than ever. To meet these needs, we developed a flexible data management system that assists scientists ...

  9. IRIS Toxicological Review of 1,4-Dioxane (Final Report)

    EPA Science Inventory

    The final Toxicological Review of 1,4-dioxane provides scientific support and rationale for the hazard and dose-response assessment pertaining to chronic exposure to 1,4-dioxane. Human health risk concerns for 1,4-dioxane are primarily related to exposure from drinking, ground, ...

  10. IRIS Toxicological Review of Decabromodiphenyl Ether (Final Report)

    EPA Science Inventory

    EPA is announcing 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 Quickview have also been added to the IRIS Data...

  11. 75 FR 71132 - Availability of Draft Toxicological Profiles

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-22

    ... HUMAN SERVICES Agency for Toxic Substances and Disease Registry Availability of Draft Toxicological Profiles AGENCY: Agency for Toxic Substances and Disease Registry (ATSDR), Department of Health and Human... Medicine, Agency for Toxic Substances and Disease Registry, Mailstop F-62, 1600 Clifton Road, NE.,...

  12. IRIS Toxicological Review of Pentachlorophenol (Interagency Science Discussion Draft)

    EPA Science Inventory

    EPA is releasing the draft report, Toxicological Review of Pentachlorophenol, that was distributed to Federal agencies and White House Offices for comment during the Science Discussion step of the IRIS Assessment Development Pr...

  13. 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...

  14. CUMULATIVE RISK ASSESSMENT: GETTING FROM TOXICOLOGY TO QUANTITATIVE ANALYSIS

    EPA Science Inventory

    INTRODUCTION: GETTING FROM TOXICOLOGY TO QUANTITATIVE ANALYSIS FOR CUMULATIVE RISK

    Hugh A. Barton1 and Carey N. Pope2
    1US EPA, Office of Research and Development, National Health and Environmental Effects Research Laboratory, Research Triangle Park, NC
    2Department of...

  15. IRIS TOXICOLOGICAL REVIEW OF METHYL ETHYL KETONE (2003 Final)

    EPA Science Inventory

    EPA is announcing 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 Quickview have also been added to the IRIS Database.

  16. The need for a paradigm shift in toxicology xx.

    EPA Science Inventory

    This manuscript briefly reviews the impact of the NAS report “Toxicity Testing in the 21st Century: A Vision and A Strategy” and it’s potential impact on the field of toxicology. ). This report provides a strategic and tactical framework for attaining the goals of deter...

  17. MODELING CHEMICAL FATE AND METABOLISM FOR COMPUTATIONAL TOXICOLOGY

    EPA Science Inventory

    The goal of ORD's Computational Toxicology initiative is to develop the science for EPA to prioritize toxicity-testing requirements for chemicals subject to regulation. Many toxic effects, however, result from metabolism of parent chemicals to form metabolites that are much more...

  18. 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...

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

    EPA Pesticide Factsheets

    On August 21, 2013, the draft Toxicological Review of Benzo[a]pyrene and the draft charge to external peer reviewers were released for public review and comment. 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 Benzo[a]pyrene and the charge to external peer reviewers, are posted on this site. EPA is undertaking an update of the Integrated Risk Information System (IRIS) health assessment for benzo[a]pyrene (BaP). The outcome of this project is an updated Toxicological Review and IRIS Summary for BaP that will be entered into the IRIS database.

  20. [The toxicological aspects of poisonings by psilocybine-containing mushrooms].

    PubMed

    Babakhanian, R V; Bushuev, E S; Kazankov, S P; Kostyrko, T A

    1997-01-01

    Cases involving the investigation of psylocybin-containing mushrooms became more frequent in forensic chemical and criminological expert evaluation in recent years. The authors present the data on the main chemical factors contained in these mushrooms, on the mechanism of their toxic effect, clinical picture of poisoning, and methods of chemical and toxicological analysis.

  1. Adverse outcome pathways (AOPs): A framework to support predictive toxicology

    EPA Science Inventory

    High throughput and in silico methods are providing the regulatory toxicology community with capacity to rapidly and cost effectively generate data concerning a chemical’s ability to initiate one or more biological perturbations that may culminate in an adverse ecological o...

  2. Wiki-Based Data Management to Support Systems Toxicology

    EPA Science Inventory

    As the field of toxicology relies more heavily on systems approaches for mode of action discovery, evaluation, and modeling, the need for integrated data management is greater than ever. To meet these needs, we have developed a flexible system that assists individual or multiple...

  3. IRIS Toxicological Review of Tetrahydrofuran (THF) (Interagency Science Discussion Draft)

    EPA Science Inventory

    EPA is releasing the draft report, Toxicological Review of Tetrahydrofuran, that was distributed to Federal agencies and White House Offices for comment during the Science Discussion step of the IRIS Assessment Development Proc...

  4. New Toxico-Cheminformatics & Computational Toxicology Initiatives At EPA

    EPA Science Inventory

    EPA’s National Center for Computational Toxicology is building capabilities to support a new paradigm for toxicity screening and prediction. The DSSTox project is improving public access to quality structure-annotated chemical toxicity information in less summarized forms than tr...

  5. IRIS Toxicological Review of Thallium and Compounds (Final Report)

    EPA Science Inventory

    EPA has finalized the Toxicological Review of Thallium and Compounds: in support of the Integrated Risk Information System (IRIS). Now final, this assessment may be used by EPA’s program and regional offices to inform decisions to protect human health.

  6. IRIS TOXICOLOGICAL REVIEW OF TETRACHLOROETHYLENE (PERCHLOROETHYLENE) (INTERAGENCY SCIENCE DISCUSSION DRAFT)

    EPA Science Inventory

    EPA is releasing the draft report, Toxicological Review of Tetrachloroethylene (Perchloroethylene), that was distributed to Federal agencies and White House Offices for comment during the Science Discussion step of the IRIS Assessment...

  7. IRIS Toxicological Review of Vinyl Chloride (Final Report, 2000)

    EPA Science Inventory

    EPA is announcing the release of the final report, Toxicological Review of Vinyl Chloride: in support of the Integrated Risk Information System (IRIS). The updated Summary for Vinyl Chloride and accompanying Quickview have also been added to the IRIS Database.

  8. E-submission chronic toxicology study supplemental files

    EPA Pesticide Factsheets

    The formats and instructions in these documents are designed to be used as an example or guide for registrants to format electronic files for submission of animal toxicology data to OPP for review in support of registration and reevaluation of pesticides.

  9. A FRAMEWORK FOR A COMPUTATIONAL TOXICOLOGY RESEARCH PROGRAM IN ORD

    EPA Science Inventory

    "A Framework for a Computational Toxicology Research Program in ORD" was drafted by a Technical Writing Team having representatives from all of ORD's Laboratories and Centers. The document describes a framework for the development of an program within ORD to utilize approaches d...

  10. IRIS Toxicological Review for Dichloromethane (Methylene Chloride) (Final Report)

    EPA Science Inventory

    EPA has finalized the Toxicological Review of Dichloromethane (Methylene Chloride): In support of the Integrated Risk Information System (IRIS). Now final, this assessment may be used by EPA’s program and regional offices to inform decisions to protect human health. This ...

  11. Toxicological Review of Cyanobacterial Toxins: Cylindrospermopsin (External Review Draft)

    EPA Science Inventory

    The National Center for Environmental Assessment has prepared the Toxicological Reviews of Cyanobacterial Toxins: Anatoxin-a, Cylindrospermopsin and Microcystins (LR, RR, YR and LA) as a series of dose-response assessments to support the health assessment of unregulated contamina...

  12. IRIS Toxicological Review of Ethylene Glycol Mono Butyl ...

    EPA Pesticide Factsheets

    EPA has finalized the Toxicological Review of Ethylene Glycol Mono Butyl Ether: in support of the Integrated Risk Information System (IRIS). Now final, this assessment may be used by EPA’s program and regional offices to inform decisions to protect human health. N/A

  13. IRIS Toxicological Review of Pentabromodiphenyl Ether (Final Report)

    EPA Science Inventory

    The purpose of this Toxicological Review is to provide scientific support and rationale for the hazard and dose-response assessment in IRIS pertaining to chronic exposure to 2,2',4,4',5-pentabromodiphenyl ether. It is not intended to be a comprehensive treatise on the chemical...

  14. History of toxicology and allied sciences: a bibliographic review and guide to suggested readings.

    PubMed

    Stirling, Dale A

    2006-01-01

    With roots extending to antiquity, toxicology is a profession that recognizes that the past is often prologue to the present. In that spirit, this article provides a comprehensive bibliographic overview of writings on the history of toxicology and allied sciences. These writings pertain to the evolution of toxicology, its various methods, concepts, and theories; as well as pioneers of the profession and the growth of professional toxicological organizations. It is not an exhaustive survey, but provides a thorough accounting of literature pertaining to the history of toxicology.

  15. Characterization of the toxicological hazards of hydrocarbon solvents.

    PubMed

    Mckee, Richard H; Adenuga, M David; Carrillo, Juan-Carlos

    2015-04-01

    Hydrocarbon solvents are liquid hydrocarbon fractions derived from petroleum processing streams, containing only carbon and hydrogen atoms, with carbon numbers ranging from approximately C5-C20 and boiling between approximately 35-370°C. Many of the hydrocarbon solvents have complex and variable compositions with constituents of 4 types, alkanes (normal paraffins, isoparaffins, and cycloparaffins) and aromatics (primarily alkylated one- and two-ring species). Because of the compositional complexity, hydrocarbon solvents are now identified by a nomenclature ("the naming convention") that describes them in terms of physical/chemical properties and compositional elements. Despite the compositional complexity, most hydrocarbon solvent constituents have similar toxicological properties, and the overall toxicological hazards can be characterized in generic terms. To facilitate hazard characterization, the solvents were divided into 9 groups (categories) of substances with similar physical and chemical properties. Hydrocarbon solvents can cause chemical pneumonitis if aspirated into the lung, and those that are volatile can cause acute CNS effects and/or ocular and respiratory irritation at exposure levels exceeding occupational recommendations. Otherwise, there are few toxicologically important effects. The exceptions, n-hexane and naphthalene, have unique toxicological properties, and those solvents containing constituents for which classification is required under the Globally Harmonized System (GHS) are differentiated by the substance names. Toxicological information from studies of representative substances was used to fulfill REACH registration requirements and to satisfy the needs of the OECD High Production Volume (HPV) initiative. As shown in the examples provided, the hazard characterization data can be used for hazard classification and for occupational exposure limit recommendations.

  16. Pest toxicology: the primary mechanisms of pesticide action.

    PubMed

    Casida, John E

    2009-04-01

    Pesticides are used to control pests before they harm us or our crops. They are selective toxicants in the form and manner used. Pesticides must be effective without human or crop injury. They must also be safe relative to human and environmental toxicology. The study of how the pesticide works on the pest is referred to here as pest toxicology. About 700 pesticides, including insecticides, herbicides, and fungicides, act on perhaps 95 biochemical targets in pest insects, weeds, and destructive fungi. Current insecticides act primarily on four nerve targets, i.e., acetylcholinesterase, the voltage-gated chloride channel, the acetylcholine receptor, and the gamma-aminobutyric acid receptor, systems which are present in animals but not plants. Herbicides act mostly on plant specific pathways by blocking photosynthesis, carotenoid synthesis, or aromatic and branched chain amino acid synthesis essential in plants but not mammals. Many fungicides block ergosterol (the fungal sterol) or tubulin biosynthesis or cytochrome c reductase, while others disrupt basic cellular functions. A major limiting factor in the continuing use of almost all pesticides is the selection of strains not only resistant to the selecting or pressuring compounds but also cross-resistant to other pesticides acting at the same target. One approach to reinstating control is to shift from compounds with the resistant target site or mode of action to another set which have a sensitive target. This type of pesticide management led to the formation of Resistance Action Committees for insecticides, herbicides, and fungicides with very knowledgable experts to define resistance groups, which are in fact listings of primary target sites in pest toxicology. Continued success in pest and pesticide management requires an understanding of comparative biochemistry and molecular toxicology considering pests, people, and crops. Defining and applying the principles of pest toxicology are critical to food production

  17. Toxicology of chemical mixtures: experimental approaches, underlying concepts, and some results.

    PubMed

    Yang, R S; Hong, H L; Boorman, G A

    1989-12-01

    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, there is yet 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 city 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 2 years at the NTP, encompassing general toxicology, immunotoxicology, developmental and reproductive toxicology, biochemical toxicology, myelotoxicology, genetic toxicology, neurobehavioral toxicology, and hepato- and renal toxicology.

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

    SciTech Connect

    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 city 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.

  19. THE ATHENS LAB'S ROLE IN EPA'S COMPUTATIONAL TOXICOLOGY PROGRAM WITH AN EMPHASIS ON METABOLOMICS AS A DIAGNOSTIC TOOL FOR TOXICOLOGY

    EPA Science Inventory

    This presentation gives a brief introduction to EPA's computational toxicology program and the Athens Lab's role in it. The talk also covered a brief introduction to metabolomics; advantages/disadvanage of metabolomics for toxicity assessment; goals of the EPA Athens metabolomics...

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

    SciTech Connect

    Gulumian, Mary . E-mail: mary.gulumian@nioh.nhls.co.za; 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.

  1. The placenta in toxicology. Part IV: Battery of toxicological test systems based on human placenta.

    PubMed

    Göhner, Claudia; Svensson-Arvelund, Judit; Pfarrer, Christiane; Häger, Jan-Dirk; Faas, Marijke; Ernerudh, Jan; Cline, J Mark; Dixon, Darlene; Buse, Eberhard; Markert, Udo R

    2014-01-01

    This review summarizes the potential and also some limitations of using human placentas, or placental cells and structures for toxicology testing. The placenta contains a wide spectrum of cell types and tissues, such as trophoblast cells, immune cells, fibroblasts, stem cells, endothelial cells, vessels, glands, membranes, and many others. It may be expected that in many cases the relevance of results obtained from human placenta will be higher than those from animal models due to species specificity of metabolism and placental structure. For practical and economical reasons, we propose to apply a battery of sequential experiments for analysis of potential toxicants. This should start with using cell lines, followed by testing placenta tissue explants and isolated placenta cells, and finally by application of single and dual side ex vivo placenta perfusion. With each of these steps, the relative workload increases while the number of feasible repeats decreases. Simultaneously, the predictive power enhances by increasing similarity with in vivo human conditions. Toxic effects may be detected by performing proliferation, vitality and cell death assays, analysis of protein and hormone expression, immunohistochemistry or testing functionality of signaling pathways, gene expression, transport mechanisms, and so on. When toxic effects appear at any step, the subsequent assays may be cancelled. Such a system may be useful to reduce costs and increase specificity in testing questionable toxicants. Nonetheless, it requires further standardization and end point definitions for better comparability of results from different toxicants and to estimate the respective in vivo translatability and predictive value.

  2. Systematic reviews of animal experiments demonstrate poor human clinical and toxicological utility.

    PubMed

    Knight, Andrew

    2007-12-01

    The assumption that animal models are reasonably predictive of human outcomes provides the basis for their widespread use in toxicity testing and in biomedical research aimed at developing cures for human diseases. To investigate the validity of this assumption, the comprehensive Scopus biomedical bibliographic databases were searched for published systematic reviews of the human clinical or toxicological utility of animal experiments. In 20 reviews in which clinical utility was examined, the authors concluded that animal models were either significantly useful in contributing to the development of clinical interventions, or were substantially consistent with clinical outcomes, in only two cases, one of which was contentious. These included reviews of the clinical utility of experiments expected by ethics committees to lead to medical advances, of highly-cited experiments published in major journals, and of chimpanzee experiments--those involving the species considered most likely to be predictive of human outcomes. Seven additional reviews failed to clearly demonstrate utility in predicting human toxicological outcomes, such as carcinogenicity and teratogenicity. Consequently, animal data may not generally be assumed to be substantially useful for these purposes. Possible causes include interspecies differences, the distortion of outcomes arising from experimental environments and protocols, and the poor methodological quality of many animal experiments, which was evident in at least 11 reviews. No reviews existed in which the majority of animal experiments were of good methodological quality. Whilst the effects of some of these problems might be minimised with concerted effort (given their widespread prevalence), the limitations resulting from interspecies differences are likely to be technically and theoretically impossible to overcome. Non-animal models are generally required to pass formal scientific validation prior to their regulatory acceptance. In contrast

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

    PubMed

    Kavlock, Robert; Dix, David

    2010-02-01

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

  4. Toxicological effects of pyrethroids on non-target aquatic insects.

    PubMed

    Antwi, Frank B; Reddy, Gadi V P

    2015-11-01

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

  5. 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.

  6. IRIS Toxicological Review of Ethyl Tertiary Butyl Ether (Etbe) ...

    EPA Pesticide Factsheets

    In September 2016, the U.S. Environmental Protection Agency's (USEPA) released the draft Integrated Risk Information System (IRIS) Toxicological Review of Ethyl Tertiary Butyl Ether (ETBE). Consistent with the 2013 IRIS Enhancements, draft IRIS assessments are released prior to external peer review for a 60-day public comment period and discussed at an upcoming public science meeting. Accordingly, the toxicological review, supplementary information, and other materials pertaining to this draft assessment are posted on this site. This material is being released for public viewing and comment prior to a public meeting, providing an opportunity for the IRIS Program to engage in early discussions with stakeholders and the public on data that may be used to identify adverse health effects and characterize exposure-response relationships.

  7. IRIS Toxicological Review of Benzo[a]pyrene (External ...

    EPA Pesticide Factsheets

    The IRIS Toxicological Review of Benzo[a]pyrene was released for external peer review in September 2014. The EPA’s Science Advisory Board’s (SAB) Chemical Assessment Advisory Committee (CAAC) conducted a peer review of the scientific basis supporting the benzo[a]pyrene assessment and released a final report of their review in April 2016. Information regarding the peer review can be found at the SAB's website. 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.

  8. 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.

  9. Salvia divinorum: toxicological aspects and analysis in human biological specimens.

    PubMed

    Margalho, Cláudia; Corte-Real, Francisco; López-Rivadulla, Manuel; Gallardo, Eugenia

    2016-07-01

    The identification and quantitation of the main psychoactive component of Salvia divinorum (salvinorin A) in biological specimens are crucial in forensic and clinical toxicology. Despite all the efforts made, its uncontrolled abuse has increased quickly, exposing its users' health to serious risks both in the short and long term. The use of alternative biological matrices in toxicological analyzes can be advantageous as complementary postmortem samples, or in situations when neither blood nor urine can be collected; they may be useful tools in those determinations, providing important information about prior exposure. The aim of this article is to present a brief summary of legal aspects of Salvia divinorum and salvinorin A, including the methods used for the determination of the latter in biological matrices.

  10. Toxicology of antimicrobial nanoparticles for prosthetic devices

    PubMed Central

    Nuñez-Anita, Rosa Elvira; Acosta-Torres, Laura Susana; Vilar-Pineda, Jorge; Martínez-Espinosa, Juan Carlos; de la Fuente-Hernández, Javier; Castaño, Víctor Manuel

    2014-01-01

    Advances in nanotechnology are producing an accelerated proliferation of new nanomaterial composites that are likely to become an important source of engineered health-related products. Nanoparticles with antifungal effects are of great interest in the formulation of microbicidal materials. Fungi are found as innocuous commensals and colonize various habitats in and on humans, especially the skin and mucosa. As growth on surfaces is a natural part of the Candida spp. lifestyle, one can expect that Candida organisms colonize prosthetic devices, such as dentures. Macromolecular systems, due to their properties, allow efficient use of these materials in various fields, including the creation of reinforced nanoparticle polymers with antimicrobial activity. This review briefly summarizes the results of studies conducted during the past decade and especially in the last few years focused on the toxicity of different antimicrobial polymers and factors influencing their activities, as well as the main applications of antimicrobial polymers in dentistry. The present study addresses aspects that are often overlooked in nanotoxicology studies, such as careful time-dependent characterization of agglomeration and ion release. PMID:25187703

  11. Toxicological evaluation of lactase derived from recombinant Pichia pastoris.

    PubMed

    Zou, Shiying; He, Xiaoyun; Liu, Yifei; Chen, Delong; Luo, Yunbo; Huang, Kunlun; Zhang, Wei; Xu, Wentao

    2014-01-01

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

  12. Application of DNA Profiling in Resolving Aviation Forensic Toxicology Issues

    DTIC Science & Technology

    2009-10-01

    mislabeled. The low number of the accident cases requiring DNA profiling suggests that the sample- submitting agencies take extensive precautionary measures ...muscle,.spleen,.and.vitreous.fluid Toxicological Findings Pilot: Carboxyhemoglobin .20% Cyanide.1 .80.µg/mL.in.blood Diphenhydramine.0 .030.µg/mL.in.blood...Diphenhydramine.present.in.liver Copilot: Carboxyhemoglobin .25% Cyanide.2 .07.µg/mL.in.blood Diphenhydramine.0 .036.µg/mL.in.blood

  13. 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

  14. IRIS Toxicological Review of Urea (External Review Draft) ...

    EPA Pesticide Factsheets

    EPA conducted a peer review and public comment of the scientific basis of a draft report supporting the human health hazard and dose-response assessment of Urea that when finalized will appear on the Integrated Risk Information System (IRIS) database. The draft Toxicological Review of Urea provides scientific support and rationale for the hazard and dose-response assessment pertaining to chronic exposure to Urea.

  15. Behavior as a common focus of toxicology and nutrition

    SciTech Connect

    Weiss, B.

    1980-01-01

    Behavior as an index of toxicity parallels its role as an index of nutritional impairment, just as toxicology and nutrition share other common themes. Intersections among the three disciplines arise because foodstuffs serve as one of the major routes of toxic exposure and also because food elements modify toxicity. With this perspective, the safety of our food supply is examined in the contexts of essential nutrients, toxins, toxic metals, manufactured contaminants, self-administered toxicants, and food additives.

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

    PubMed

    Bozinovska, C

    2013-01-01

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

  17. IRIS Toxicological Review of Cerium Oxide and Cerium ...

    EPA Pesticide Factsheets

    EPA conducted a peer review of the scientific basis supporting the human health hazard and dose-response assessment of cerium oxide and cerium compounds that will appear on the Integrated Risk Information System (IRIS) database. The draft Toxicological Review of cerium oxide and cerium compounds provides scientific support and rationale for the hazard and dose-response assessment pertaining to chronic exposure to cerium oxide and cerium compounds.

  18. IRIS Toxicological Review of Beryllium and Compounds (2008 ...

    EPA Pesticide Factsheets

    EPA is conducting a peer review and public comment of the scientific basis supporting the human health hazard and dose-response assessment of Beryllium that when finalized will appear on the Integrated Risk Information System (IRIS) database. An IRIS Toxicological Review of Beryllium and Compounds was published in 1988 and reassessed in 1998. The current draft (2007) only focuses on the cancer assessment and does not re-evaluate posted reference doses or reference concentrations.

  19. Current trends in safety testing and toxicological research

    NASA Astrophysics Data System (ADS)

    Zbinden, G.

    1982-06-01

    The paper reviews current concepts of toxicological evaluation of new drugs and other chemicals. Instead of completing a predetermined check-list toxicologists now consider the potential adverse effects of the substances under actual conditions of use. They then design experimental models which have a high probability to predict the toxic effects. Moreover, the enhanced susceptibilities of special risk populations is more and more taken into consideration.

  20. Toxicological Evaluation of Lactase Derived from Recombinant Pichia pastoris

    PubMed Central

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

    2014-01-01

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

  1. Computational derivation of structural alerts from large toxicology data sets.

    PubMed

    Ahlberg, Ernst; Carlsson, Lars; Boyer, Scott

    2014-10-27

    Structural alerts have been one of the backbones of computational toxicology and have applications in many areas including cosmetic, environmental, and pharmaceutical toxicology. The development of structural alerts has always involved a manual analysis of existing data related to a relevant end point followed by the determination of substructures that appear to be related to a specific outcome. The substructures are then analyzed for their utility in posterior validation studies, which at times have stretched over years or even decades. With higher throughput methods now being employed in many areas of toxicology, data sets are growing at an unprecedented rate. This growth has made manual analysis of data sets impractical in many cases. This report outlines a fully automatic method that highlights significant substructures for toxicologically important data sets. The method identifies important substructures by computationally breaking chemical structures into fragments and analyzing those fragments for their contribution to the given activity by the calculation of a p-value and a substructure accuracy. The method is intended to aid the expert in locating and analyzing alerts by automatic retrieval of alerts or by enhancing existing alerts. The method has been applied to a data set of AMES mutagenicity results and compared to the substructures generated by manual curation of this same data set as well as another computationally based substructure identification method. The results show that this method can retrieve significant substructures quickly, that the substructures are comparable and in some cases superior to those derived from manual curation, that the substructures found covers all previously known substructures, and that they can be used to make reasonably accurate predictions of AMES activity.

  2. IRIS Toxicological Review of Ethyl Tertiary Butyl Ether (Etbe) ...

    EPA Pesticide Factsheets

    EPA is conducting a peer review and public comment of the scientific basis supporting the human health hazard and dose-response assessment of ethyl tertiary butyl ether (ETBE) that when finalized will appear on the Integrated Risk Information System (IRIS) database. The draft Toxicological Review of Ethyl Tertiary Butyl Ether provides scientific support and rationale for the hazard and dose-response assessment pertaining to chronic exposure to ethyl tertiary butyl ether.

  3. A Review of the Toxicology of Halogenated Fire Extinguishing Agents

    DTIC Science & Technology

    1974-11-01

    coronary reserve limited by atherosclerosis and who may be either suffering from intermittent bouts of angina pectoris , or be potential candidates for...and angina pectoris has not been demonstrated in the laboratory the pharmacologic-toxicologic basis has been established by these studies and warrants...anginal attacks in the near future. Furthermore, angina is known to be aggravated by any factor that increases myocardial oxygen demand such as

  4. The Installation Restoration Program Toxicology Guide. Volume 5

    DTIC Science & Technology

    1990-11-01

    the technical monitor was Major Michael L . Shelley (AAMRL/THB, WPAFB, OH). The program managers for the updated version volumes 1 through 4 of the...Toxicology Guide were Jeffrey W. Fisher, Ph.D., (AAMRLTHA, WPAFB, OH) and Major Michael L . Shelley. Program managers for volume 5 (metals) were Lt. Col...in soil. L Liter(s) lb Pound(s) LC. The concentration required to kill 50% of test individuals. LCD, Lowest reported lethal concentration. AB-8

  5. Toxicology profiles of chemical and radiological contaminants at Hanford

    SciTech Connect

    Harper, B.L.; Strenge, D.L.; Stenner, R.D.; Maughan, A.D.; Jarvis, M.K.

    1995-07-01

    This document summarizes toxicology information required under Section 3.3 (Toxicity Assessment) of HSRAM, and can also be used to develop the short toxicology profiles required in site assessments (described in HSRAM, Section 3.3.5). Toxicology information is used in the dose-response step of the risk assessment process. The dose-response assessment describes the quantitative relationship between the amount of exposure to a substance and the extent of toxic injury or disease. Data are derived from animal studies or, less frequently, from studies in exposed human populations. The risks of a substance cannot be ascertained with any degree of confidence unless dose-response relations are quantified. This document summarizes dose-response information available from the US Environmental Protection Agency (EPA). The contaminants selected for inclusion in this document represent most of the contaminants found at Hanford (both radiological and chemical), based on sampling and analysis performed during site investigations, and historical information on waste disposal practices at the Hanford Site.

  6. IRIS Toxicological Review of Ethyl Tertiary Butyl Ether (Etbe) ...

    EPA Pesticide Factsheets

    In September 2016, EPA released the draft IRIS Toxicological Review of Ethyl Tertiary Butyl Ether (ETBE) for public comment and discussion. The draft assessment was reviewed internally by EPA and by other federal agencies and White House Offices before public release. Consistent with the May 2009 IRIS assessment development process, all written comments on IRIS assessments submitted by other federal agencies and White House Offices are made publicly available. Accordingly, interagency comments and the interagency science consultation materials provided to other agencies, including interagency review drafts of the IRIS Toxicological Review of Ethyl Tertiary Butyl Ether are posted on this site. EPA is undertaking an new health assessment for ethyl tertiary butyl ether (ETBE) for the Integrated Risk Information System (IRIS). The outcome of this project will be a Toxicological Review and IRIS Summary of ETBE that will be entered on the IRIS database. 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 process, i.e., hazard identification and dose-response evaluation. IRIS assessments are used nationally and internationally in combination with specific situational exposure assessment infor

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

    EPA Pesticide Factsheets

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

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

    EPA Pesticide Factsheets

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

  9. Selecting the best design for nonstandard toxicology experiments.

    PubMed

    Webb, Jennifer M; Smucker, Byran J; Bailer, A John

    2014-10-01

    Although many experiments in environmental toxicology use standard statistical experimental designs, there are situations that arise where no such standard design is natural or applicable because of logistical constraints. For example, the layout of a laboratory may suggest that each shelf serve as a block, with the number of experimental units per shelf either greater than or less than the number of treatments in a way that precludes the use of a typical block design. In such cases, an effective and powerful alternative is to employ optimal experimental design principles, a strategy that produces designs with precise statistical estimates. Here, a D-optimal design was generated for an experiment in environmental toxicology that has 2 factors, 16 treatments, and constraints similar to those described above. After initial consideration of a randomized complete block design and an intuitive cyclic design, it was decided to compare a D-optimal design and a slightly more complicated version of the cyclic design. Simulations were conducted generating random responses under a variety of scenarios that reflect conditions motivated by a similar toxicology study, and the designs were evaluated via D-efficiency as well as by a power analysis. The cyclic design performed well compared to the D-optimal design.

  10. The Use of Accelerator Mass Spectrometry in Human Health and Molecular Toxicology

    PubMed Central

    Enright, Heather A.; Malfatti, Michael A.; Zimmermann, Maike; Ognibene, Ted; Henderson, Paul; Turteltaub, Kenneth W.

    2016-01-01

    Accelerator Mass Spectrometry (AMS) has been adopted as a powerful bio-analytical method for human studies in the areas of pharmacology and toxicology. The exquisite sensitivity (10−18 mol) of AMS has facilitated studies of toxins and drugs at environmentally and physiologically relevant concentrations in humans. Such studies include: risk assessment of environmental toxicants, drug candidate selection, absolute bioavailability determination, and more recently, assessment of drug-target binding as a biomarker of response to chemotherapy. Combining AMS with complementary capabilities such as high performance liquid chromatography (HPLC) can maximize data within a single experiment and provide additional insight when assessing drugs and toxins, such as metabolic profiling. Recent advances in the AMS technology at Lawrence Livermore National Laboratory have allowed for direct coupling of AMS with complementary capabilities such as HPLC via a liquid sample moving wire interface, offering greater sensitivity compared to graphite-based analysis therefore, enabling the use of lower 14C and chemical doses, which are imperative for clinical testing. The aim of this review is to highlight the recent efforts in human studies using AMS, including technological advancements and discussion of the continued promise of AMS for innovative clinical based research. PMID:27726383

  11. Structured Development and Promotion of a Research Field: Hormesis in Biology, Toxicology, and Environmental Regulatory Science.

    PubMed

    Mushak, Paul; Elliott, Kevin C

    2015-12-01

    The ability of powerful and well-funded interest groups to steer scientific research in ways that advance their goals has become a significant social concern. This steering ability is increasingly being recognized in the peer-reviewed scientific literature and in findings of deliberative scientific bodies. This paper provides a case study that illustrates some of the major strategies that can be used to structure and advance a controversial research field. It focuses on hormesis, described as a type of dose-response relationship in toxicology and biology showing low-dose stimulation but high-dose inhibition, or the reverse. Hormesis proponents tout its significance, arguing that substances toxic at high doses and beneficial at lower doses should be regulated less stringently. We identify five strategies employed by hormesis proponents to foster its acceptance: (1) creating institutions focused on supporting hormesis; (2) developing terminology, study designs, and data interpretations that cast it in a favorable light; (3) using bibliometric techniques and surveys to attract attention; (4) aggressively advocating for the phenomenon and challenging critics; and (5) working with outside interest groups to apply the hormesis phenomenon in the economic and political spheres. We also suggest a number of oversight strategies that can be implemented to help promote credible and socially responsible research in cases like this one.

  12. Use of Accelerator Mass Spectrometry in Human Health and Molecular Toxicology.

    PubMed

    Enright, Heather A; Malfatti, Michael A; Zimmermann, Maike; Ognibene, Ted; Henderson, Paul; Turteltaub, Kenneth W

    2016-12-19

    Accelerator mass spectrometry (AMS) has been adopted as a powerful bioanalytical method for human studies in the areas of pharmacology and toxicology. The exquisite sensitivity (10(-18) mol) of AMS has facilitated studies of toxins and drugs at environmentally and physiologically relevant concentrations in humans. Such studies include risk assessment of environmental toxicants, drug candidate selection, absolute bioavailability determination, and more recently, assessment of drug-target binding as a biomarker of response to chemotherapy. Combining AMS with complementary capabilities such as high performance liquid chromatography (HPLC) can maximize data within a single experiment and provide additional insight when assessing drugs and toxins, such as metabolic profiling. Recent advances in the AMS technology at Lawrence Livermore National Laboratory have allowed for direct coupling of AMS with complementary capabilities such as HPLC via a liquid sample moving wire interface, offering greater sensitivity compared to that of graphite-based analysis, therefore enabling the use of lower (14)C and chemical doses, which are imperative for clinical testing. The aim of this review is to highlight the recent efforts in human studies using AMS, including technological advancements and discussion of the continued promise of AMS for innovative clinical based research.

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

    PubMed

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

    2016-03-01

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

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

    PubMed

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

    2015-04-01

    Clays and clay minerals are widely used in many facets of our society. This review addresses the main clays of each phyllosilicate groups, namely, kaolinite, montmorillonite (Mt) and sepiolite, placing special emphasis on Mt and kaolinite, which are the clays that are more frequently used in food packaging, one of the applications that are currently exhibiting higher development. The improvements in the composite materials obtained from clays and polymeric matrices are remarkable and well known, but the potential toxicological effects of unmodified or modified clay minerals and derived nanocomposites are currently being investigated with increased interest. In this sense, this work focused on a review of the published reports related to the analysis of the toxicological profile of commercial and novel modified clays and derived nanocomposites. An exhaustive review of the main in vitro and in vivo toxicological studies, antimicrobial activity assessments, and the human and environmental impacts of clays and derived nanocomposites was performed. From the analysis of the scientific literature different conclusions can be derived. Thus, in vitro studies suggest that clays in general induce cytotoxicity (with dependence on the clay, concentration, experimental system, etc.) with different underlying mechanisms such as necrosis/apoptosis, oxidative stress or genotoxicity. However, most of in vivo experiments performed in rodents showed no clear evidences of systemic toxicity even at doses of 5000mg/kg. Regarding to humans, pulmonary exposure is the most frequent, and although clays are usually mixed with other minerals, they have been reported to induce pneumoconiosis per se. Oral exposure is also common both intentionally and unintentionally. Although they do not show a high toxicity through this pathway, toxic effects could be induced due to the increased or reduced exposure to mineral elements. Finally, there are few studies about the effects of clay minerals on

  15. "You Can't Always Get What You Want" - Linearity as the Golden Ratio of Toxicology.

    PubMed

    Bast, Aalt; Hanekamp, Jaap C

    2014-12-01

    Referring to the Golden Ratio (i.e. expressed in the Fibonacci sequence) in nature and art, we conclude that toxicology knows its own Golden Ration, namely linearity. The latter seems imposed on pharmaco-toxicological processes that in fact show far more complexity than simple linearity could hope to elucidate. Understanding physiological and pharmaco-toxicological processes as primarily linear is challenged in this contribution based on very straightforward principles and examples.

  16. 75 FR 26757 - National Toxicology Program (NTP); Office of Liaison, Policy and Review; Meeting of the...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-12

    ...); Office of Liaison, Policy and Review; Meeting of the Scientific Advisory Committee on Alternative Toxicological Methods (SACATM) AGENCY: National Institute of Environmental Health Sciences [[Page 26758

  17. 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

  18. Toxicological assessment of Ricinus communis Linn root extracts.

    PubMed

    Ilavarasan, Raju; Mallika, Moni; Venkataraman, Subramanian

    2011-03-01

    Ricinus communis Linn (Euphorbiaceae) plant parts are claimed to be used as carminative, asthma, bronchitis, leprosy, anti-inflammatory, cathartic, and aphrodisiac. The toxicological study was carried out in the root part of the plant. The collected root was extracted with methanol and water. The extracts were vacuum-dried to yield the respective aqueous (AE) and methanol (ME) extracts. Toxicological assessment sought to determine the safety of Ricinus communis root extracts. The extracts were evaluated in the acute toxicity study (OECD-423 guidelines) and 90 days repeated dose toxicological assessment in Wistar albino rats. The acute oral toxicity of the aqueous (AE) and methanol (ME) extracts did not produce any toxic symptoms or mortality at the dose level of 2000 mg/kg in rats. In the 90 days (sub-chronic toxicity) repeated dose toxicity study the extracts (AE and ME) were administered 1000 mg/kg daily through oral route. The sub-chronic toxicity study demonstrated no significant changes in body weight, food, and water intake. Hematology parameters RBC, WBC, DLC, Hb, blood clotting time, and the biochemical parameters glucose, blood urea nitrogen, creatinine, total cholesterol, total protein, total bilirubin AST, ALT, and ALP were estimated. Histopathology observation of the major vital organs (liver, kidney, heart, spleen, lungs, ovary, testis, and brain) were tested. The hematology, biochemical and histopathology evaluations did not show any adverse effects in any of the organs tested. These results demonstrate the non-toxic nature of the root extracts AE and ME can be used for long-term usage in clinical practice.

  19. Acute Poisoning During Pregnancy: Observations from the Toxicology Investigators Consortium.

    PubMed

    Zelner, Irene; Matlow, Jeremy; Hutson, Janine R; Wax, Paul; Koren, Gideon; Brent, Jeffrey; Finkelstein, Yaron

    2015-09-01

    Acute poisonings during pregnancy pose a particular challenge to health care providers because of the potential for an immediate life threat or possible life-long implications for both the mother and fetus, including teratogenicity of the poison or its antidote. We describe recent consequential exposures among pregnant women in the USA. We identified all poisoning cases involving pregnant women that were catalogued by the medical toxicology services across the 37 sites of the Toxicology Investigators Consortium (ToxIC) Registry of the American College of Medical Toxicology between January 2010 and December 2012. Of 17,529 exposure cases reported in the ToxIC Registry, 103 (0.6 %) involved pregnant women, 80 % of whom were symptomatic and about a quarter displayed a specific toxidrome. The majority of cases (n = 53; 51.5 %) involved intentional exposures, most commonly to pharmaceutical agents, followed by unintentional pharmaceutical exposures (10 %) and withdrawal syndromes (9 %). Non-opioid analgesics were the most common class of agents encountered (31 %), followed by sedative-hypnotics/muscle relaxants (18 %), opioids (17 %), anti-convulsants (10 %), and anti-depressants (10 %). Over a third of cases involved exposure to multiple substances, and 32 % involved exposure to more than one drug class. The most commonly administered antidotes were N-acetylcysteine (23 %), sodium bicarbonate (10 %), flumazenil (4 %), and physostigmine (4 %). About half of acute poisoning cases among pregnant women presenting for emergency care involved intentional exposures, mostly with over-the-counter analgesics and psychoactive medications. Clinicians should be cognizant of the unique circumstances, maternal and fetal risks, and management principles of the acutely poisoned pregnant woman.

  20. Risk assessment and toxicology databases for health effects assessment

    SciTech Connect

    Lu, P.Y.; Wassom, J.S.

    1990-12-31

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

  1. Cichorium intybus: Traditional Uses, Phytochemistry, Pharmacology, and Toxicology

    PubMed Central

    Street, Renée A.

    2013-01-01

    The genus Cichorium (Asteraceae) is made up of six species with major geographical presence in Europe and Asia. Cichorium intybus, commonly known as chicory, is well known as a coffee substitute but is also widely used medicinally to treat various ailments ranging from wounds to diabetes. Although this plant has a rich history of use in folklore, many of its constituents have not been explored for their pharmacological potential. Toxicological data on C. intybus is currently limited. This review focuses on the economic and culturally important medicinal uses of C. intybus. Traditional uses, scientific validation, and phytochemical composition are discussed in detail. PMID:24379887

  2. Functional toxicology: a new approach to detect biologically active xenobiotics.

    PubMed Central

    McLachlan, J A

    1993-01-01

    The pervasiveness of chemicals in the environment with estrogenic activity and other biological functions recommends the development of new approaches to monitor and study them. Chemicals can be screened for activity in vitro using a panel of human or animal cells that have been transfected with a specific receptor and reporter gene; for example, the estrogen receptor. By using a variety of different receptors, the screening of xenobiotics for biological functions can be broad. Chemicals could then be classified by their function in vitro which, in some cases, may be a useful guide for toxicological studies. Images Figure 1. PMID:8119246

  3. IRIS Toxicological Review of Benzo[a]pyrene (Public ...

    EPA Pesticide Factsheets

    EPA is developing an Integrated Risk Information System (IRIS) assessment of benzo[a]pyrene and has released the draft assessment for public comment and external peer review. When final, the assessment will appear on the IRIS database. 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.

  4. 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

  5. IRIS Toxicological Review of Ethylene Glycol Mono-Butyl ...

    EPA Pesticide Factsheets

    EPA released the draft report, Toxicological Review for Ethylene Glycol Mono-Butyl Ether , that was distributed to Federal agencies and White House Offices for comment during the Science Discussion step of the IRIS Assessment Development Process. Comments received from other Federal agencies and White House Offices are provided below with external peer review panel comments. EPA is conducting a peer review of the scientific basis supporting the human health hazard and dose-response assessment of EGBE that will appear on the Integrated Risk Information System (IRIS) database.

  6. Data quality in predictive toxicology: reproducibility of rodent carcinogenicity experiments.

    PubMed Central

    Gottmann, E; Kramer, S; Pfahringer, B; Helma, C

    2001-01-01

    We compared 121 replicate rodent carcinogenicity assays from the two parts (National Cancer Institute/National Toxicology Program and literature) of the Carcinogenic Potency Database (CPDB) to estimate the reliability of these experiments. We estimated a concordance of 57% between the overall rodent carcinogenicity classifications from both sources. This value did not improve substantially when additional biologic information (species, sex, strain, target organs) was considered. These results indicate that rodent carcinogenicity assays are much less reproducible than previously expected, an effect that should be considered in the development of structure-activity relationship models and the risk assessment process. PMID:11401763

  7. A review on pharmacology and toxicology of Elephantopus scaber Linn.

    PubMed

    Hiradeve, Sachin M; Rangari, Vinod D

    2014-01-01

    Elephantopus scaber Linn., family Asteraceae, is a small herb found in the Neotropics, Europe, Asia, Africa and Australia. The parts of this plant have been used traditionally for the treatment of number of diseases in many countries. The plant has been extensively screened for anticancer activity. Sesquiterpene lactones such as deoxyelephantopin, isodeoxyelephantopin, scabertopin and isoscabertopin. have been found to be prominent anticancer constituents. Many other biological activities such as antimicrobial, hepatoprotective, antioxidant, antidiabetic, anti-inflammatory, analgesic, antiasthamatic, antiplatelet and wound healing ability have been reported in various research articles. This review has been envisaged with an intention to provide the scientific information about the pharmacological and toxicological profile of E. scaber.

  8. 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

    2017-02-09

    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

  9. 77 FR 35395 - Draft Five-Year Plan (2013-2017) for the National Toxicology Program Interagency Center for the...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-13

    ... alternative test methods and strategies. NICEATM and ICCVAM work collaboratively to evaluate new and improved... for the Evaluation of Alternative Toxicological Methods and the Interagency Coordinating Committee on the Validation of Alternative Methods AGENCY: Division of National Toxicology Program (DNTP),...

  10. 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.

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

    EPA Science Inventory

    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...

  12. Toxicology testing in fatally injured workers: a review of five years of Iowa FACE cases.

    PubMed

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

    2013-11-14

    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.

  13. 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...

  14. 40 CFR 158.230 - Experimental use permit data requirements for toxicology.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... product; PAIRA=Pure active ingredient radio-labeled; TGAI=Technical grade of the active ingredient. (c... Experimental use permit data requirements for toxicology. All toxicology data, as described in paragraph (c) of.... The following test notes apply to the data requirements in the table to paragraph (c) of this...

  15. IRIS Toxicological Review of Tert-Butyl Alcohol (Tert-Butanol) (Interagency Science Consultation Draft)

    EPA Science Inventory

    On April 29, 2016, the Toxicological Review of tert-Butyl Alcohol (tert-Butanol) (Public Comment Draft) was released for public comment. The draft Toxicological Review and charge were reviewed internally by EPA and by other federal agencies and the Executive Office ...

  16. Implications of gender differences for human health risk assessment and toxicology

    EPA Science Inventory

    This paper from The Human Health working group of SGOMSEC 16 examines a broad range of issues on gender effects in toxicology. Gender differences in toxicology begin at the gamete and embryo stage, continuing through development and maturation and into old age. Sex influences exp...

  17. A Directory of Information Resources in the United States, General Toxicology.

    ERIC Educational Resources Information Center

    Library of Congress, Washington, DC. National Referral Center for Science and Technology.

    Listed are institutions and organizations which can serve as information sources on toxicology. Each entry gives the toxicology-related interests of the institution, holdings (of publications), publications of the institution, and information services provided. Poison control centers are listed separately as an appendix. Other appendices list some…

  18. IRIS Toxicological Review of Benzo[a]pyrene (Interagency Science Consultation Draft)

    EPA Science Inventory

    On August 21, 2013, the draft Toxicological Review of Benzo[a]pyrene and the draft charge to external peer reviewers were released for public review and comment. The Toxicological Review and charge were reviewed internally by EPA and by other federal agencies and White House Offi...

  19. IRIS Toxicological Review of 1,4-Dioxane (with Inhalation Update) (Interagency Science Discussion Draft)

    EPA Science Inventory

    On September 9, 2011, the Toxicological Review of 1,4-Dioxane (inhalation) (External Review Draft) was posted for external peer review and public comment. Subsequently, the Toxicological Review and IRIS Summary were reviewed internally by EPA and by other federal agencies and Exe...

  20. 78 FR 4147 - Notice of Development of Set 26 Toxicological Profiles

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-18

    ... HUMAN SERVICES Agency for Toxic Substances and Disease Registry Notice of Development of Set 26... and Human Services (HHS). ACTION: Notice. SUMMARY: This notice announces the development of Set 26.../toxprofiles/index.asp . Set 26 Toxicological Profiles The following toxicological profiles are now...