WorldWideScience

Sample records for program ntp toxicology

  1. 75 FR 57027 - National Toxicology Program (NTP); NTP Interagency Center for the Evaluation of Alternative...

    Science.gov (United States)

    2010-09-17

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

  2. 75 FR 32942 - National Toxicology Program (NTP); NTP Interagency Center for the Evaluation of Alternative...

    Science.gov (United States)

    2010-06-10

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

  3. 76 FR 8370 - National Toxicology Program (NTP); Office of Liaison, Policy and Review; Meeting of the NTP Board...

    Science.gov (United States)

    2011-02-14

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Toxicology Program (NTP); Office of Liaison... such as toxicology, pharmacology, pathology, biochemistry, epidemiology, risk assessment, carcinogenesis, mutagenesis, molecular biology, behavioral toxicology, neurotoxicology, immunotoxicology...

  4. 75 FR 64311 - National Toxicology Program (NTP); Office of Liaison, Policy and Review Meeting of the NTP Board...

    Science.gov (United States)

    2010-10-19

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Toxicology Program (NTP); Office of Liaison... preliminary study recommendations (see ``Request for Comments'' below). The NTP welcomes toxicology study... in toxicology that could be appropriately addressed through studies on the nominated substance(s...

  5. 75 FR 66766 - National Toxicology Program (NTP); Office of Liaison, Policy and Review; Meeting of the NTP Board...

    Science.gov (United States)

    2010-10-29

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Toxicology Program (NTP); Office of Liaison, Policy and Review; Meeting of the NTP Board of Scientific Counselors: Amended Notice AGENCY: National....gov ). Dated: October 21, 2010. John R. Bucher, Associate Director, National Toxicology Program. [FR...

  6. 75 FR 73085 - National Toxicology Program (NTP): Office of Liaison, Policy, and Review; Availability of Draft...

    Science.gov (United States)

    2010-11-29

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Toxicology Program (NTP): Office of Liaison... Materials The agenda topic is the peer review of the findings and conclusions of draft NTP TRs of toxicology.... Bucher, Associate Director, National Toxicology Program. [FR Doc. 2010-29945 Filed 11-26-10; 8:45 am...

  7. 76 FR 8741 - National Toxicology Program (NTP): Office of Liaison, Policy, and Review; Availability of Draft...

    Science.gov (United States)

    2011-02-15

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Toxicology Program (NTP): Office of Liaison... Materials The agenda topic is the peer review of the findings and conclusions of draft NTP TRs of toxicology... advisory committees. Dated: February 3, 2011. John R. Bucher, Associate Director, National Toxicology...

  8. 75 FR 21003 - National Toxicology Program (NTP); Office of Liaison, Policy and Review Meeting of the NTP Board...

    Science.gov (United States)

    2010-04-22

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Toxicology Program (NTP); Office of Liaison... toxicology study information from completed, ongoing, or anticipated studies, as well as information on... issues or topics in toxicology that could be appropriately addressed through studies on the nominated...

  9. 76 FR 71037 - Proposed National Toxicology Program (NTP) Review Process for the Report on Carcinogens: Request...

    Science.gov (United States)

    2011-11-16

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Proposed National Toxicology Program (NTP) Review Process...: Division of the National Toxicology Program (DNTP), National Institute of Environmental Health Sciences.... Bucher, Associate Director, National Toxicology Program. [FR Doc. 2011-29615 Filed 11-15-11; 8:45 am...

  10. 77 FR 22321 - National Toxicology Program (NTP) Interagency Center for the Evaluation of Alternative...

    Science.gov (United States)

    2012-04-13

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

  11. 75 FR 26757 - National Toxicology Program (NTP); Office of Liaison, Policy and Review; Meeting of the...

    Science.gov (United States)

    2010-05-12

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Toxicology Program (NTP); Office of Liaison, Policy and Review; Meeting of the Scientific Advisory Committee on Alternative Toxicological Methods... Director, National Toxicology Program. [FR Doc. 2010-11318 Filed 5-11-10; 8:45 am] BILLING CODE 4140-01-P ...

  12. 75 FR 25867 - National Toxicology Program (NTP) Interagency Center for the Evaluation of Alternative...

    Science.gov (United States)

    2010-05-10

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

  13. 76 FR 68461 - Meeting of the National Toxicology Program (NTP) Board of Scientific Counselors

    Science.gov (United States)

    2011-11-04

    ..., carcinogenesis, mutagenesis, molecular biology, behavioral toxicology, neurotoxicology, immunotoxicology... of diabetes and obesity ( http://ntp.niehs.nih.gov/go/36433 ) and on environmental enrichment in NTP...

  14. 75 FR 12244 - National Toxicology Program (NTP); Office of Liaison, Policy and Review; Meeting of the NTP Board...

    Science.gov (United States)

    2010-03-15

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Toxicology Program... authorities knowledgeable in fields such as toxicology, pharmacology, pathology, biochemistry, epidemiology, risk assessment, carcinogenesis, mutagenesis, molecular biology, behavioral toxicology, neurotoxicology...

  15. 77 FR 48995 - Draft National Toxicology Program (NTP) Monograph on Developmental Effects and Pregnancy Outcomes...

    Science.gov (United States)

    2012-08-15

    ... Program (NTP) Monograph on Developmental Effects and Pregnancy Outcomes Associated With Cancer... the panel completes its peer review of the draft monograph. Topic: Peer review of the draft NTP Monograph on Developmental Effects and Pregnancy Outcomes Associated with Cancer Chemotherapy Use during...

  16. National Toxicology Program

    Science.gov (United States)

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

  17. 76 FR 67200 - Proposed National Toxicology Program (NTP) Review Process for the Report on Carcinogens: Request...

    Science.gov (United States)

    2011-10-31

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health Proposed National Toxicology... Session AGENCY: Division of the National Toxicology Program (DNTP), National Institute of Environmental.... Bucher, Associate Director, National Toxicology Program. [FR Doc. 2011-28132 Filed 10-28-11; 8:45 am...

  18. 75 FR 2545 - National Toxicology Program (NTP); Center for the Evaluation of Risks to Human Reproduction...

    Science.gov (United States)

    2010-01-15

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

  19. 77 FR 1707 - National Toxicology Program (NTP) Final Process for Preparation of the Report on Carcinogens (RoC)

    Science.gov (United States)

    2012-01-11

    ... the RoC. The process is available on the NTP Web site ( http://ntp.niehs.nih.gov/go/rocprocess ) or by... Counselors public meeting (76 FR 68461) on December 15, 2011 ( http://ntp.niehs.nih.gov/go/9741 ). The NTP... Web site ( http://ntp.niehs.nih.gov/go/rocprocess ) or by contacting Dr. Lunn (see ADDRESSES...

  20. 75 FR 62845 - National Toxicology Program (NTP) Interagency Center for the Evaluation of Alternative...

    Science.gov (United States)

    2010-10-13

    ..., respectively. These one-day workshops will help participants gain a practical understanding of the theory and... have an opportunity to apply knowledge gained from the program using case studies in breakout group... Induced Eye Injuries (January 19, 2011) Welcome, Introduction, and Public Health Impact of Chemically...

  1. Development of novel whole-body exposure setups for rats providing high efficiency, National Toxicology Program (NTP) compatibility and well-characterized exposure

    Energy Technology Data Exchange (ETDEWEB)

    Kainz, Wolfgang [Food and Drug Administration (FDA), Center for Devices and Radiological Health (CDRH), 12725 Twinbrook Parkway, Rockville, MD 20852 (United States); Nikoloski, Neviana [IT' IS Foundation-The Foundation for Research on Information Technologies in Society, ETH Zurich, 8092 Zurich (Switzerland); Oesch, Walter [IT' IS Foundation-The Foundation for Research on Information Technologies in Society, ETH Zurich, 8092 Zurich (Switzerland); Berdinas-Torres, Veronica [IT' IS Foundation-The Foundation for Research on Information Technologies in Society, ETH Zurich, 8092 Zurich (Switzerland); Froehlich, Juerg [IT' IS Foundation-The Foundation for Research on Information Technologies in Society, ETH Zurich, 8092 Zurich (Switzerland); Neubauer, Georg [ARC Seibersdorf research GmbH, Kramergasse 1, A-1010 Vienna (Austria); Kuster, Niels [IT' IS Foundation-The Foundation for Research on Information Technologies in Society, ETH Zurich, 8092 Zurich (Switzerland)

    2006-10-21

    This paper presents the design, optimization, realization and verification of novel whole-body exposure setups for rats. The setups operating at 902 MHz and 1747 MHz provide highly efficient, National Toxicology Program (NTP) compatible and well-characterized exposures. They are compared to existing concepts of exposure setups with respect to efficiency, induced field uniformity, good laboratory practice (GLP) compatibility and cost. The novel exposure setup consists of a circular cascade of 17 sectorial waveguides excited by a novel loop antenna placed in the centre. The 70% overall efficiency of the exposure setup surpasses comparable values of existing setups. A field uniformity inside the phantom of more than 86% for the 1g cubical averaged specific absorption rate (SAR) within {+-}5 dB of the whole-body SAR (WB-SAR) was attained. The uniformity of the exposure inside the setup, defined as the variation of the WB-SAR between animals, was better than {+-}24%. Using only stainless steel, gold and polycarbonate in the vicinity of the animals ensured full GLP compatibility. The entire exposure system features fully automated computer controlled exposure and data monitoring, data storing and failure handling. Therefore, the proposed exposure system can be used to run blinded large scale, long-term exposure studies.

  2. 78 FR 24762 - National Toxicology Program Board of Scientific Counselors; Announcement of Meeting; Request for...

    Science.gov (United States)

    2013-04-26

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Toxicology Program... announces the next meeting of the National Toxicology Program (NTP) Board of Scientific Counselors (BSC... authorities knowledgeable in fields such as toxicology, pharmacology, pathology, biochemistry, epidemiology...

  3. 77 FR 60707 - National Toxicology Program Board of Scientific Counselors; Announcement of Meeting; Request for...

    Science.gov (United States)

    2012-10-04

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Toxicology Program... announces the next meeting of the National Toxicology Program (NTP) Board of Scientific Counselors (BSC... such as toxicology, pharmacology, pathology, biochemistry, epidemiology, risk assessment...

  4. 78 FR 45253 - National Toxicology Program Scientific Advisory Committee on Alternative Toxicological Methods...

    Science.gov (United States)

    2013-07-26

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

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

    Science.gov (United States)

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

    2013-01-01

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

  6. National toxicology program chemical nomination and selection process

    Energy Technology Data Exchange (ETDEWEB)

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

    1990-12-31

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

  7. 76 FR 55391 - Notice of Postponement of Release of Draft NTP Monograph on Potential Developmental Effects of...

    Science.gov (United States)

    2011-09-07

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Notice of Postponement of Release of Draft NTP Monograph... Review Draft Monograph AGENCY: Division of the National Toxicology Program (DNTP), National Institute of... NTP monograph and peer review panel meeting. SUMMARY: The NTP is postponing the release of the Draft...

  8. 76 FR 23323 - Meeting of the Scientific Advisory Committee on Alternative Toxicological Methods (SACATM)

    Science.gov (United States)

    2011-04-26

    ... the scientific validation and regulatory acceptance of toxicological and safety testing methods that... DEPARTMENT OF HEALTH AND HUMAN SERVICES Meeting of the Scientific Advisory Committee on Alternative Toxicological Methods (SACATM) AGENCY: National Toxicology Program (NTP), National Institute of...

  9. NTP-CERHR Expert Panel Report on the reproductive and developmental toxicity of hydroxyurea

    Science.gov (United States)

    The National Toxicology Program (NTP) and the National Institute of Environmental Health Sciences (NIEHS) established the NTP Center for the Evaluation of Risks to Human Reproduction (CERHR) in June 1998. The purpose of CERHR is to provide timely, unbiased, scientifically sound e...

  10. 75 FR 37443 - National Toxicology Program (NTP); NTP Interagency Center for the Evaluation of Alternative...

    Science.gov (United States)

    2010-06-29

    ... nonradioactive versions of the Local Lymph Node Assay (LLNA) for assessing allergic contact dermatitis (ACD) hazard potential of chemicals and products and expanded uses of the LLNA for pesticide formulations and... Authorization Act of 2000. The LLNA: 5-Bromo-2'-deoxyuridine-Enzyme- Linked Immunosorbent Assay (BrdU-ELISA) and...

  11. 76 FR 2388 - National Toxicology Program (NTP); NTP Interagency Center for the Evaluation of Alternative...

    Science.gov (United States)

    2011-01-13

    ... Nonradioactive Versions of the Murine Local Lymph Node Assay (LLNA) for Assessing Allergic Contact Dermatitis (ACD) Hazard Potential of Chemicals and Products, and Expanded Uses of the LLNA for Pesticide.... Federal agency responses to ICCVAM test method recommendations on two nonradioactive versions of the LLNA...

  12. 75 FR 25866 - National Toxicology Program (NTP); NTP Interagency Center for the Evaluation of Alternative...

    Science.gov (United States)

    2010-05-10

    ... available on the NICEATM-ICCVAM Web site at http://iccvam.niehs.nih.gov/methods/immunotox/rLLNA.htm and http... ICCVAM Test Method Evaluation Reports, which are available on the NICEATM-ICCVAM Web site at http://iccvam.niehs.nih.gov/methods/immunotox/LLNA-LD/TMER.htm and http://iccvam.niehs.nih.gov/methods/immunotox...

  13. 76 FR 61704 - Availability of Draft NTP Monograph on the Health Effects of Low-Level Lead; Request for Comments...

    Science.gov (United States)

    2011-10-05

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Availability of Draft NTP Monograph on the Health Effects... Monograph AGENCY: Division of the National Toxicology Program (DNTP), National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health. ACTION: Availability of Draft NTP Monograph...

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

    Science.gov (United States)

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

    2017-02-01

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

  15. Chemical Exacerbation of Light-induced Retinal Degeneration in F344/N Rats in National Toxicology Program Rodent Bioassays

    OpenAIRE

    Yamashita, Haruhiro; Hoenerhoff, Mark J.; Peddada, Shyamal D.; Sills, Robert C.; Pandiri, Arun R.

    2016-01-01

    Retinal degeneration due to chronic ambient light exposure is a common spontaneous age-related finding in albino rats, but it can also be related to exposures associated with environmental chemicals and drugs. Typically, light induced retinal degeneration has a central/hemispherical localization where as chemical induced retinal degeneration has a diffuse localization. This study was conducted to identify National Toxicology Program (NTP) rodent bioassays with treatment-related retinal degene...

  16. NTP Toxicology and Carcinogenesis Studies of 3,3'-Dimethoxybenzidine Dihydrochloride (CAS No. 20325-40-0) in F344/N Rats (Drinking Water Studies).

    Science.gov (United States)

    1990-01-01

    3,3'-Dimethoxybenzidine dihydrochloride is an off-white powder with a melting point of 274 degrees C. 3,3'-Dimethoxybenzidine is used principally as an intermediate in the production of commercial bisazobiphenyl dyes for coloring textiles, paper, plastic, rubber, and leather. In the synthesis of the bisazobiphenyl dyes, the amine groups of 3,3'-dimethoxybenzidine are chemically linked with other aromatic amines. A small quantity of 3,3'-dimethoxybenzidine is also used as an intermediate in the production of o-dianisidine diisocyanate, which is used in isocyanate-based adhesive systems and as a component of polyurethane elastomers. 3,3'-Dimethoxybenzidine dihydrochloride was evaluated in toxicity and carcinogenicity studies as part of the National Toxicology Program's Benzidine Dye Initiative. This Initiative was designed to evaluate the representative benzidine congeners and benzidine congener-derived and benzidine-derived dyes. 3,3'-Dimethoxybenzidine dihydrochloride was nominated for study because of the potential for human exposure during production of bisazobiphenyl dyes and because benzidine, a structurally related chemical, is a known human carcinogen. NTP Toxicology and Carcinogenesis studies were conducted by administering 3,3'-dimethoxybenzidine dihydrochloride (greater than 97.5% pure) in drinking water to groups of F344/N rats of each sex for 14 days, 13 weeks, 9 months, or 21-months. The 21-month studies were intended to last 24 months but were terminated early because of rapidly declining survival due to neoplasia. Studies were performed only in rats because similar studies are being performed in mice at the National Center for Toxicology Research. Genetic toxicology studies were conducted with Salmonella typhimurium, Chinese hamster over (CHO) cells, and Drosophila melanogaster. Fourteen-Day Studies: All rats receiving drinking water concentrations up to 4,500 ppm lived to the end of the studies. Rats that received water containing 4,500 ppm 3

  17. NTP-CERHR monograph on Soy Infant Formula.

    Science.gov (United States)

    2010-09-01

    Soy infant formula contains soy protein isolates and is fed to infants as a supplement to or replacement for human milk or cow milk. Soy protein isolates contains estrogenic isoflavones ("phytoestrogens") that occur naturally in some legumes, especially soybeans. Phytoestrogens are non-steroidal, estrogenic compounds. In plants, nearly all phytoestrogens are bound to sugar molecules and these phytoestrogen-sugar complexes are not generally considered hormonally active. Phytoestrogens are found in many food products in addition to soy infant formula, especially soy-based foods such as tofu, soy milk, and in some over-the-counter dietary supplements. Soy infant formula was selected for evaluation by the National Toxicology Program (NTP) because of the: (1)availability of large number of developmental toxicity studies in laboratory animals exposed to the isoflavones found in soy infant formula (namely, genistein) or other soy products, as well as a number of studies on human infants fed soy infant formula, (2)the availability of information on exposures in infants fed soy infant formula, and (3)public concern for effects on infant or child development. The NTP evaluation was conducted through its Center for the Evaluation of Risks to Human Reproduction (CERHR) and completed in September 2010. The results of this soy infant formula evaluation are published in an NTP Monograph. This document contains the NTP Brief on Soy Infant Formula, which presents NTP's opinion on the potential for exposure to soy infant formula to cause adverse developmental effects in humans. The NTP Monograph also contains an expert panel report prepared to assist the NTP in reaching conclusions on soy infant formula. The NTP concluded there is minimal concern for adverse effects on development in infants who consume soy infant formula. This level of concern represents a "2" on the five-level scale of concern used by the NTP that ranges from negligible concern ("1") to serious concern ("5"). This

  18. Appplication of a general fluid mechanics program to NTP system modeling

    International Nuclear Information System (INIS)

    Lee, S.K.

    1993-01-01

    An effort is currently underway at NASA and the Department of Energy (DOE) to develop an accurate model for predicting nuclear thermal propulsion (NTP) system performance. The objective of the effort is to develop several levels of computer programs which vary in detail and complexity according to user's needs. The current focus is on the Level 1 steady-state, parametric system model. This system model will combine a general fluid mechanics program, SAFSIM, with the ability to analyze turbines, pumps, nozzles, and reactor physics. SAFSIM (System Analysis Flow SIMulator) is a FORTRAN computer program that simulates integrated performance of systems involving fluid mechanics, heat transfer, and reactor dynamics. SAFSIM has the versatility to allow simulation of almost any system, including a nuclear reactor system. The focus of this paper is the validation of SAFSIM's capabilities as a base computational engine for a nuclear thermal propulsion system model. Validation is being accomplished by modeling of a nuclear engine test using SAFSIM and comparing the results to known experimental data

  19. NTP monograph on health effects of low-level lead.

    Science.gov (United States)

    2012-06-01

    Although reductions in lead (Pb) exposure for the U.S. population have resulted in lower blood Pb levels over time, epidemiological studies continue to provide evidence of health effects at lower and lower blood Pb levels. Low-level Pb was selected for evaluation by the National Toxicology Program (NTP) because of (1) the availability of a large number of epidemiological studies of Pb, (2) a nomination by the National Institute for Occupational Safety and Health for an assessment of Pb at lower levels of exposure, and (3) public concern for effects of Pb in children and adults. This evaluation summarizes the evidence in humans and presents conclusions on health effects in children and adults associated with low-level Pb exposure as indicated by less than 10 micrograms of Pb per deciliter of blood (Monograph on Health Effects of Low-Level Lead. The document and appendices are available at http://ntp.niehs.nih.gov/go/evals. This document provides background on Pb exposure and includes a review of the primary epidemiological literature for evidence that low-level Pb is associated with neurological, immunological, cardiovascular, renal, and/or reproductive and developmental effects. The NTP Monograph presents specific conclusions for each health effect area. Overall, the NTP concludes that there is sufficient evidence that blood Pb levels Monograph on November 17-18, 2011 (http://ntp.niehs.nih.gov/go/37090.

  20. 76 FR 51034 - Availability of Draft NTP Monograph on Potential Developmental Effects of Cancer Chemotherapy...

    Science.gov (United States)

    2011-08-17

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Availability of Draft NTP Monograph on Potential... Meeting To Peer Review Draft Monograph AGENCY: Division of the National Toxicology Program (DNTP...: Availability of Draft Monograph; Request for Comments; Announcement of a Peer Review Panel Meeting. SUMMARY...

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

    International Nuclear Information System (INIS)

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

    2005-01-01

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

  2. 75 FR 76995 - National Toxicology Program (NTP); Center for the Evaluation of Risks to Human Reproduction...

    Science.gov (United States)

    2010-12-10

    ... at the workshop. Registration to attend the workshop is closed; however, slides presented during the....O. Box 12233, MD K2-04, Research Triangle Park, NC 27709 (mail), 919-541-5021 (telephone), or thayer... (``Tox21'') high throughput screening initiative. Identify data gaps and areas for future evaluation...

  3. 75 FR 51815 - National Toxicology Program (NTP); Center for the Evaluation of Risks to Human Reproduction...

    Science.gov (United States)

    2010-08-23

    ... Exposure: Call for Information and Nomination of Scientific Experts AGENCY: National Institute of... and nomination of scientific experts. SUMMARY: CERHR is evaluating the scientific evidence regarding... information about current production levels, human exposure, use patterns, and environmental occurrence. This...

  4. 76 FR 28785 - Meeting of the National Toxicology Program (NTP) Board of Scientific Counselors

    Science.gov (United States)

    2011-05-18

    ..., biochemistry, epidemiology, risk assessment, carcinogenesis, mutagenesis, molecular biology, behavioral... Workshop: Role of Environmental Chemicals in the Development of Diabetes and Obesity Collaborative...

  5. NTP Toxicology and Carcinogenesis Studies of Molybdenum Trioxide (CAS No. 1313-27-5) in F344 Rats and B6C3F1 Mice (Inhalation Studies).

    Science.gov (United States)

    1997-04-01

    survival rate of male mice exposed to 30 mg/m(3) was marginally lower than that of the control group; survival rates of 10 and 100 mg/m(3) males and of all exposed groups of females were similar to those of the control groups. Mean body weights of exposed male mice were generally similar to those of the control group throughout the study. Mean body weights of exposed female mice were generally greater than those of the control group from week 11 until the end of the study. There was a significant exposure-dependent increase in blood molybdenum concentration in exposed mice. There were no toxicologically significant differences in bone density or curvature between control and exposed mice. Pathology Findings: The incidences of alveolar/bronchiolar carcinoma in all exposed groups of males were significantly greater than that in the control group. Incidences of alveolar/bronchiolar adenoma in females in the 30 and 100 mg/m(3) groups were significantly greater than that in the control group. Incidences of alveolar/bronchiolar adenoma or carcinoma (combined) in 10 and 30 mg/m(3) males and in 100 mg/m(3) females were significantly greater than those in the control groups and exceeded the historical control ranges for 2-year NTP inhalation studies. Incidences of metaplasia of the alveolar epithelium of minimal severity in the centriacinar region of the lung were significantly increased in all exposed groups of mice. The incidences of histiocyte cellular infiltration in all exposed groups of males were significantly greater than that in the control group. Incidences of hyaline degeneration of the respiratory epithelium of the nasal cavity in 100 mg/m(3) males and females and hyaline degeneration of the olfactory epithelium of the nasal cavity in 100 mg/m(3) females were significantly greater than those in the control groups. The incidences of squamous metaplasia of the epithelium lining the base of the epiglottis were significantly increased in all exposed groups of males and

  6. Chemical Carcinogenesis of the Gastrointestinal Tract in Rodents: An Overview with Emphasis on NTP Carcinogenesis Bioassays

    OpenAIRE

    Chandra, Sundeep A.; Nolan, Michael W.; Malarkey, David E.

    2009-01-01

    Cancers of the stomach and large intestine (LI) are the second and fourth leading causes of human cancer mortality. A review of the National Toxicology Program (NTP) database and the Carcinogenic Potency Database (CPDB) reveals that chemically induced neoplasms of the gastrointestinal tract (GIT) are relatively common. Within the GIT, epithelial tumors of the forestomach in mice and rats and LI of the rat are most common. Generally, there is a high species concordance for forestomach with at ...

  7. NTP comparison process

    Science.gov (United States)

    Corban, Robert

    The systems engineering process for the concept definition phase of the program involves requirements definition, system definition, and consistent concept definition. The requirements definition process involves obtaining a complete understanding of the system requirements based on customer needs, mission scenarios, and nuclear thermal propulsion (NTP) operating characteristics. A system functional analysis is performed to provide a comprehensive traceability and verification of top-level requirements down to detailed system specifications and provides significant insight into the measures of system effectiveness to be utilized in system evaluation. The second key element in the process is the definition of system concepts to meet the requirements. This part of the process involves engine system and reactor contractor teams to develop alternative NTP system concepts that can be evaluated against specific attributes, as well as a reference configuration against which to compare system benefits and merits. Quality function deployment (QFD), as an excellent tool within Total Quality Management (TQM) techniques, can provide the required structure and provide a link to the voice of the customer in establishing critical system qualities and their relationships. The third element of the process is the consistent performance comparison. The comparison process involves validating developed concept data and quantifying system merits through analysis, computer modeling, simulation, and rapid prototyping of the proposed high risk NTP subsystems. The maximum amount possible of quantitative data will be developed and/or validated to be utilized in the QFD evaluation matrix. If upon evaluation of a new concept or its associated subsystems determine to have substantial merit, those features will be incorporated into the reference configuration for subsequent system definition and comparison efforts.

  8. NTP Toxicology and Carcinogenesis Studies of Chloroprene (CAS No. 126-99-8) in F344/N Rats and B6C3F1 Mice (Inhalation Studies).

    Science.gov (United States)

    1998-09-01

    incidences of renal tubule hyperplasia in males exposed to 32 or 80 ppm were significantly greater than that in the chamber controls. Additional sections of kidney were examined from control and exposed males to verify these findings. The combined single- and step-section incidence of renal tubule adenoma in 80 ppm males and the combined incidences of renal tubule hyperplasia in all groups of exposed male mice were greater than those in the chamber controls. The incidences of olfactory epithelial atrophy, adenomatous hyperplasia, and metaplasia in 80 ppm males and females were significantly greater than those in the chamber controls. The incidences of hematopoietic proliferation of the spleen in 32 and 80 ppm males and in all groups of exposed females were significantly greater than those in the chamber controls. Genetic Toxicology: Chloroprene was not mutagenic in any of the tests performed by the NTP. No induction of mutations was noted in any of four strains of S. typhimurium in the presence or the absence of S9 metabolic activation enzymes, and no induction of sex-linked recessive lethal mutations was observed in germ cells of male D. melanogaster treated with chloroprene via feeding or injection. In male mice exposed to chloroprene by inhalation for 12 days over a 16-day period, no induction of chromosomal aberrations, sister chromatid exchanges, or micronucleated erythrocytes in bone marrow or peripheral blood occurred. Results of a second micronucleus assay in male and female mice after 13 weeks of exposure to chloroprene via inhalation were also negative. Conclusion: Under the conditions of these 2-year inhalation studies, there was clear evidence of carcinogenic activity of chloroprene in male F344/N rats based on increased incidences of neoplasms of the oral cavity; increased incidences of neoplasms of the thyroid gland, lung, and kidney were also attributed to chloroprene exposure. There was clear evidence of carcinogenic activity of chloroprene in female F344/N

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

    Science.gov (United States)

    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

  10. NTP Monograph: Developmental Effects and Pregnancy Outcomes Associated With Cancer Chemotherapy Use During Pregnancy.

    Science.gov (United States)

    2013-05-01

    The National Toxicology Program (NTP) Office of Health Assessment and Translation (OHAT) conducted an evaluation of the developmental effects and pregnancy outcomes associated with cancer chemotherapy use during pregnancy in humans. The final NTP monograph was completed in May 2013 (available at http:// ntp.niehs.nih.gov/go/36495). The incidence of cancer during pregnancy has been reported to occur from 17 to 100 per 100,000 pregnant women. Chemotherapy is a common treatment for cancer; however, most chemotherapy agents are classified as known or suspected human teratogens. Cancer chemotherapy use during pregnancy was selected for evaluation by the NTP because of the: (1) paucity of comprehensive reviews on the pregnancy outcomes following cancer chemotherapy use during pregnancy in humans, including the integration of the developmental animal toxicology literature with the observational studies in humans, and (2) growing public interest in the developmental effects of chemotherapy on offspring exposed to cancer chemotherapy during gestation due to the expected incidence of cancer diagnosed during pregnancy as women delay pregnancy to later ages. Of the approximately 110 cancer chemotherapeutic agents currently in use, the NTP monograph includes data on 56 agents used during 1,261 pregnancies for which pregnancy outcomes were documented. Overall, the NTP evaluation found that treatment with chemotherapy for cancer appeared to be associated with: (1) a higher rate of major malformations following exposure during the first trimester compared to exposure in the second and/or third trimester; (2) an increase the rate of stillbirth following exposure in the second and/ or third trimester; abnormally low levels of amniotic fluid (primarily attributable to Trastuzumab); and (3), also data are insufficient, impaired fetal growth and myelosuppression. Treatment with chemotherapy for cancer during pregnancy did not appear to increase spontaneous preterm birth, or impair

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

    Science.gov (United States)

    Masten, Lawrence W.

    1979-01-01

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

  12. NTP-CERHR Monograph on the Potential Human Reproductive and Developmental Effects of Di-n-Butyl Phthalate (DBP).

    Science.gov (United States)

    2003-04-01

    TThe National Toxicology Program (NTP) Center for the Evaluation of Risks to Human Reproduction (CERHR) conducted an evaluation of the potential for di-n-butyl phthalate (DBP) to cause adverse effects on reproduction and development in humans. DBP is one of 7 phthalate chemicals evaluated by the NTP CERHR Phthalates Expert Panel. These phthalates were selected for evaluation because of high production volume, extent of human exposures, use in children's products, and/or published evidence of reproductive or developmental toxicity. Unlike many phthalates, DBP is not currently used as a plasticizer in polyvinyl chloride plastics. DBP is a component of latex adhesives and is used in cosmetics and other personal care products, as a plasticizer in cellulose plastics, and as a solvent for dyes. The results of this evaluation on DBP are published in a NTP-CERHR monograph which includes: 1) the NTP Brief, 2) the Expert Panel Report on the Reproductive and Developmental Toxicity of Di-n-Butyl Phthalate, and 3) public comments received on the Expert Panel Report. As stated in the NTP Brief, the NTP reached the following conclusions regarding the possible effects of exposure to DBP on human development and reproduction. First, although DBP could possibly affect human reproduction and development if exposures are sufficiently high, the NTP concludes that there is negligible concern for reproductive toxicity in exposed adults. Second, the NTP concludes that there is minimal concern for developmental effects when pregnant women are exposed to DBP levels estimated by the panel (2-10 mug/kg body weight/day). There is no direct evidence that exposure of people to DBP adversely affects reproduction or development, but studies reviewed by the expert panel show that oral exposure to high doses of DBP (>/=100 mg/kg body weight/day) may adversely affect the prenatal and early postnatal development in rodents. Finally, based on exposure estimates in women of reproductive age, the NTP

  13. CEBS: a comprehensive annotated database of toxicological data

    Science.gov (United States)

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

    2017-01-01

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

  14. Toxicological benchmarks for wildlife. Environmental Restoration Program

    Energy Technology Data Exchange (ETDEWEB)

    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.

  15. NTP-CERHR monograph on the potential human reproductive and developmental effects of bisphenol A.

    Science.gov (United States)

    Shelby, Michael D

    2008-09-01

    The National Toxicology Program (NTP) Center for the Evaluation of Risks to Human Reproduction (CERHR) conducted an evaluation of the potential for bisphenol A to cause adverse effects on reproduction and development in humans. The CERHR Expert Panel on Bisphenol A completed its evaluation in August 2007. CERHR selected bisphenol A for evaluation because of the: widespread human exposure; public concern for possible health effects from human exposures; high production volume; evidence of reproductive and developmental toxicity in laboratory animal studies Bisphenol A (CAS RN: 80-05-7) is a high production volume chemical used primarily in the production of polycarbonate plastics and epoxy resins. Polycarbonate plastics are used in some food and drink containers; the resins are used as lacquers to coat metal products such as food cans, bottle tops, and water supply pipes. To a lesser extent bisphenol A is used in the production of polyester resins, polysulfone resins, polyacrylate resins, and flame retardants. In addition, bisphenol A is used in the processing of polyvinyl chloride plastic and in the recycling of thermal paper. Some polymers used in dental sealants and tooth coatings contain bisphenol A. The primary source of exposure to bisphenol A for most people is assumed to occur through the diet. While air, dust, and water (including skin contact during bathing and swimming) are other possible sources of exposure, bisphenol A in food and beverages accounts for the majority of daily human exposure. The highest estimated daily intakes of bisphenol A in the general population occur in infants and children. The results of this bisphenol A evaluation are published in an NTP-CERHR Monograph that includes the (1) NTP Brief and (2) Expert Panel Report on the Reproductive and Developmental Toxicity of Bisphenol A. Additional information related to the evaluation process, including the peer review report for the NTP Brief and public comments received on the draft NTP

  16. NTP Toxicology and Carcinogenesis Studies of Benzene (CAS No. 71-43-2) in F344/N Rats and B6C3F1 Mice (Gavage Studies).

    Science.gov (United States)

    1986-04-01

    Benzene ranks 16th in production volume for chemicals produced in the United States, with approximately 9.9 billion pounds being produced in 1984, 9.1 billion pounds in 1983, and 7.8 billion pounds in 1982. This simplest aromatic chemical in used in the synthesis of styrene (polystyrene plastics and synthetic rubber), phenol (phenolic resins), cyclohexane (nylon), aniline, maleic anhydride (polyester resins), alkylbenzenes (detergents), chlorobenzenes, and other products used in the production of drugs, dyes, insecticides, and plastics. Benzene, along with other light, high-octane aromatic hydrocarbons, such as toluene and xylenes, is a component of motor gasoline. Benzene is also used as a solvent, but for most applications, it has been replaced by less hazardous solvents. During the 17-week studies, groups of 10 or 15 male and female F344/N rats and B6C3F1 mice were gavaged 5 days per week with benzene in corn oil (5 ml/kg) at doses of 0 to 600 mg/kg. No benzene-related deaths occurred; in rats that received benzene, final mean body weights were 14%-22% lower compared with vehicle controls and in mice, slight dose-related reductions were observed (less than 10% differences). Doses for the 2-year studies were selected based on clinical observations (tremors in higher dosed mice), on clinical pathologic findings (lymphoid depletion in rats and leukopenia in mice), and on body weight effects. Two-year toxicology and carcinogenesis studies of benzene (greater than 99.7% pure) were conducted in groups of 50 F344/N rats and 50 B6C3F1 mice of each sex and for each dose. Doses of 0, 50, 100, or 200 mg/kg body weight benzene in corn oil (5 ml/kg) were administered by gavage to male rats, 5 days per week, for 103 weeks. Doses of 0, 25, 50, or 100 mg/kg benzene in corn oil were administered by gavage to female rats and to male and female mice for 103 weeks. Ten additional animals in each of the 16 groups were killed at 12 months and necropsies were performed. Hematologic

  17. The effect of study type on body weight and tumor incidence in B6C3F1 mice fed the NTP-2000 diet.

    Science.gov (United States)

    Marino, Dale J

    2012-07-01

    The B6C3F1 mouse is the standard mouse strain used in National Toxicology Program (NTP) carcinogenesis studies. Over time, increased liver tumorigenesis that was correlated with elevated body weights was noted in males and females. NTP therefore replaced the NIH-07 diet with the NTP-2000 diet and returned to group housing of females as lower body weights were noted in group housed mice. However, recent studies reported study-type differences in body weights at 3 months using the NTP-2000 diet with higher weights evident in drinking water and inhalation studies compared to feed studies. Therefore, body weight and tumor incidence data were collected for untreated control mice from all 2-year NTP feed (12), drinking water (8), water gavage (6) and inhalation (10) studies that used the NTP-2000 diet in order to assess the impact of study type on body weights and tumor incidences. Results show statistically significant elevated body weights and liver tumor incidences in males and females from drinking water, water gavage and inhalation studies compared to results from feed studies. Thus, the elevated body weights and liver tumorigenesis noted in mice using the NIH-07 diet were also evident using the NTP-2000 diet, which was introduced to address body weight elevations. Given the study-type dependent effects noted, these results emphasize the importance of carefully selecting historical control data for B6C3F1 mice. Moreover, because of the association between body weight and liver tumorigenesis, these results may have implications regarding dose-level selection for carcinogenicity studies involving B6C3F1 mice based on the maximum tolerated dose.

  18. NTP Radioisotopes SOC Ltd

    International Nuclear Information System (INIS)

    Letule, T.

    2017-01-01

    NTP Radioisotopes SOC Ltd, a wholly owned subsidiary of the South African Nuclear Energy Corporation (NECSA). Supplies around 20% of the world's medical radioisotopes used. NTP is a pioneer in the introduction and growth of nuclear medicine as in South Africa. Nuclear medicine is the medical specialty that involves the use of radioactive isotopes in the diagnosis and treatment of diseases. Nuclear medicine contributes to enhancing the lives of the society. There is a compelling need for nuclear medicine to be promoted and utilized in the rest of Africa, due to the increasing prevalence of cancer. Cancer is rapidly becoming a public health crisis in low-income and middle-income countries. In sub-Saharan Africa, patients often present with advanced disease

  19. NTP-CERHR monograph on the potential human reproductive and developmental effects of hydroxyurea.

    Science.gov (United States)

    2008-10-01

    The National Toxicology Program (NTP) Center for the Evaluation of Risks to Human Reproduction (CERHR) conducted an evaluation of the potential for hydroxyurea to cause adverse effects on reproduction and development in humans. Hydroxyurea is a drug used to treat cancer, sickle cell disease, and thalassemia. It is the only treatment for sickle cell disease in children, aside from blood transfusion and, in severe cases, hematopoietic stem cell transplantation. Hydroxyurea is FDA-approved for use in adults with sickle cell anemia to reduce the frequency of painful crises and the need for blood transfusions. Hydroxyurea may be given to children and adults with sickle cell disease for an extended period of time or for repeated cycles of therapy. Treatment with hydroxyurea is associated with known side effects such as cytotoxicity and myelosuppression, and hydroxyurea is genotoxic (can damage DNA). CERHR selected hydroxyurea for evaluation because of: its increasing use for treatment of sickle cell disease in children and adults, knowledge that it inhibits DNA synthesis and is cytotoxic, and published evidence of reproductive and developmental toxicity in rodents. The results of this evaluation are published in the NTP-CERHR Monograph on Hydroxyurea, which includes the NTP Brief and Expert Panel Report on the Reproductive and Developmental Toxicity of Hydroxyurea. Additional information related to the evaluation process, including public comments received on the draft NTP Brief and the final expert panel report, are available on the CERHR website (http:// cerhr.niehs.nih.gov/). See hydroxyurea under "CERHR Chemicals" on the homepage or go directly to http://cerhr.niehs.nih.gov/chemicals/hydroxyurea/hydroxyurea-eval.html). The NTP reached the following conclusions on the possible effects of exposure to hydroxyurea on human reproduction or development. The possible levels of concern, from lowest to highest, are negligible concern, minimal concern, some concern, concern

  20. Nuclear Thermal Propulsion (NTP) Development Activities at the NASA Marshall Space Flight Center - 2006 Accomplishments

    Science.gov (United States)

    Ballard, Richard O.

    2007-01-01

    In 2005-06, the Prometheus program funded a number of tasks at the NASA-Marshall Space Flight Center (MSFC) to support development of a Nuclear Thermal Propulsion (NTP) system for future manned exploration missions. These tasks include the following: 1. NTP Design Develop Test & Evaluate (DDT&E) Planning 2. NTP Mission & Systems Analysis / Stage Concepts & Engine Requirements 3. NTP Engine System Trade Space Analysis and Studies 4. NTP Engine Ground Test Facility Assessment 5. Non-Nuclear Environmental Simulator (NTREES) 6. Non-Nuclear Materials Fabrication & Evaluation 7. Multi-Physics TCA Modeling. This presentation is a overview of these tasks and their accomplishments

  1. Gasoline toxicology: overview of regulatory and product stewardship programs.

    Science.gov (United States)

    Swick, Derek; Jaques, Andrew; Walker, J C; Estreicher, Herb

    2014-11-01

    Significant efforts have been made to characterize the toxicological properties of gasoline. There have been both mandatory and voluntary toxicology testing programs to generate hazard characterization data for gasoline, the refinery process streams used to blend gasoline, and individual chemical constituents found in gasoline. The Clean Air Act (CAA) (Clean Air Act, 2012: § 7401, et seq.) is the primary tool for the U.S. Environmental Protection Agency (EPA) to regulate gasoline and this supplement presents the results of the Section 211(b) Alternative Tier 2 studies required for CAA Fuel and Fuel Additive registration. Gasoline blending streams have also been evaluated by EPA under the voluntary High Production Volume (HPV) Challenge Program through which the petroleum industry provide data on over 80 refinery streams used in gasoline. Product stewardship efforts by companies and associations such as the American Petroleum Institute (API), Conservation of Clean Air and Water Europe (CONCAWE), and the Petroleum Product Stewardship Council (PPSC) have contributed a significant amount of hazard characterization data on gasoline and related substances. The hazard of gasoline and anticipated exposure to gasoline vapor has been well characterized for risk assessment purposes. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  2. NTP-CERHR expert panel report on the developmental toxicity of soy infant formula.

    Science.gov (United States)

    McCarver, Gail; Bhatia, Jatinder; Chambers, Christina; Clarke, Robert; Etzel, Ruth; Foster, Warren; Hoyer, Patricia; Leeder, J Steven; Peters, Jeffrey M; Rissman, Emilie; Rybak, Michael; Sherman, Claire; Toppari, Jorma; Turner, Katie

    2011-10-01

    Soy infant formula contains soy protein isolates and is fed to infants as a supplement to or replacement for human milk or cow milk. Soy protein isolates contains estrogenic isoflavones (phytoestrogens) that occur naturally in some legumes, especially soybeans. Phytoestrogens are nonsteroidal, estrogenic compounds. In plants, nearly all phytoestrogens are bound to sugar molecules and these phytoestrogen-sugar complexes are not generally considered hormonally active. Phytoestrogens are found in many food products in addition to soy infant formula, especially soy-based foods such as tofu, soy milk, and in some over-the-counter dietary supplements. Soy infant formula was selected for National Toxicology Program (NTP) evaluation because of (1) the availability of large number of developmental toxicity studies in laboratory animals exposed to the isoflavones found in soy infant formula (namely, genistein) or other soy products, as well as few studies on human infants fed soy infant formula, (2) the availability of information on exposures in infants fed soy infant formula, and (3) public concern for effects on infant or child development. On October 2, 2008 (73 FR 57360), the NTP Center for the Evaluation of Risks to Human Reproduction (CERHR) announced its intention to conduct an updated review of soy infant formula to complete a previous evaluation that was initiated in 2005. Both the current and previous evaluations relied on expert panels to assist the NTP in developing its conclusions on the potential developmental effects associated with the use of soy infant formula, presented in the NTP Brief on Soy Infant Formula. The initial expert panel met on March 15 to 17, 2006, to reach conclusions on the potential developmental and reproductive toxicities of soy infant formula and its predominant isoflavone constituent genistein. The expert panel reports were released for public comment on May 5, 2006 (71 FR 28368). On November 8, 2006 (71 FR 65537), CERHR staff released

  3. Proceedings of the 2016 National Toxicology Program Satellite Symposium.

    Science.gov (United States)

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

    2017-01-01

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

  4. Proceedings of the 2015 National Toxicology Program Satellite Symposium.

    Science.gov (United States)

    Elmore, Susan A; Farman, Cindy A; Hailey, James R; Kovi, Ramesh C; Malarkey, David E; Morrison, James P; Neel, Jennifer; Pesavento, Patricia A; Porter, Brian F; Szabo, Kathleen A; Teixeira, Leandro B C; Quist, Erin M

    2016-06-01

    The 2015 Annual National Toxicology Program Satellite Symposium, entitled "Pathology Potpourri" was held in Minneapolis, Minnesota, at the American College of Veterinary Pathologists/American Society for Veterinary Clinical Pathology/Society of Toxicologic Pathology combined meeting. The goal of this symposium is to present and discuss diagnostic pathology challenges or nomenclature issues. Because of the combined meeting, both laboratory and domestic animal cases were presented. This article presents summaries of the speakers' talks, including challenging diagnostic cases 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 hepatocellular lesions, a proposed harmonized diagnostic approach to rat cardiomyopathy, crop milk in a bird, avian feeding accoutrement, heat exchanger in a tuna, metastasis of a tobacco carcinogen-induced pulmonary carcinoma, neurocytoma in a rat, pituicytoma in a rat, rodent mammary gland whole mounts, dog and rat alveolar macrophage ultrastructure, dog and rat pulmonary phospholipidosis, alveolar macrophage aggregation in a dog, degenerating yeast in a cat liver aspirate, myeloid leukemia in lymph node aspirates from a dog, Trypanosoma cruzi in a dog, solanum toxicity in a cow, bovine astrovirus, malignant microglial tumor, and nomenclature challenges from the Special Senses International Harmonization of Nomenclature and Diagnostic Criteria Organ Working Group. © The Author(s) 2016.

  5. 78 FR 54476 - Availability of Draft National Toxicology Program Technical Reports; Request for Comments; Notice...

    Science.gov (United States)

    2013-09-04

    ... glycidamide. The draft TRs should be available by September 20, 2013, at http://ntp.niehs.nih.gov/go/36051... attendance and comment. Information about the meeting and registration are available at http://ntp.niehs.nih... Time (EDT). Document Availability: Draft TRs should be available by September 20, 2013, at http://ntp...

  6. NTP-CERHR expert panel report on the reproductive anddevelopmental toxicity of hydroxyurea

    Energy Technology Data Exchange (ETDEWEB)

    Liebelt, E.L.; Balk, S.J.; Faber, W.; Fisher, J.W.; Hughes, C.L.; Lanzkron, S.M.; Lewis, K.M.; Marchetti, F.; Mehendale, H.M.; Rogers,J.M.; Shad, A.T.; Skalko, R.G.; Stanek, E.J.

    2007-01-01

    The National Toxicology Program (NTP) and the National Institute of Environmental Health Sciences (NIEHS) established the NTP Center for the Evaluation of Risks to Human Reproduction (CERHR) in June 1998. The purpose of CERHR is to provide timely, unbiased, scientifically sound evaluations of human and experimental evidence for adverse effects on reproduction and development caused by agents to which humans may be exposed. Hydroxyurea was selected for evaluation by a CERHR expert panel because of (1) its increasing use in the treatment of sickle cell disease in children and adults, (2) knowledge that it inhibits DNA synthesis and is cytotoxic, and (3) published evidence of its reproductive and developmental toxicity in rodents. Hydroxyurea is FDA-approved for reducing the frequency of painful crises and the need for blood transfusions in adults with sickle cell anemia who experience recurrent moderate-to-severe crises. Hydroxyurea is used in the treatment of cancer, sickle cell disease, and thalassemia. It is the only treatment for sickle cell disease aside from blood transfusion used in children. Hydroxyurea may be used in the treatment of children and adults with sickle cell disease for an extended period of time or for repeated cycles of therapy. Treatment with hydroxyurea may be associated with cytotoxic and myelosuppressive effects, and hydroxyurea is mutagenic.

  7. Integrated System Modeling for Nuclear Thermal Propulsion (NTP)

    Science.gov (United States)

    Ryan, Stephen W.; Borowski, Stanley K.

    2014-01-01

    Nuclear thermal propulsion (NTP) has long been identified as a key enabling technology for space exploration beyond LEO. From Wernher Von Braun's early concepts for crewed missions to the Moon and Mars to the current Mars Design Reference Architecture (DRA) 5.0 and recent lunar and asteroid mission studies, the high thrust and specific impulse of NTP opens up possibilities such as reusability that are just not feasible with competing approaches. Although NTP technology was proven in the Rover / NERVA projects in the early days of the space program, an integrated spacecraft using NTP has never been developed. Such a spacecraft presents a challenging multidisciplinary systems integration problem. The disciplines that must come together include not only nuclear propulsion and power, but also thermal management, power, structures, orbital dynamics, etc. Some of this integration logic was incorporated into a vehicle sizing code developed at NASA's Glenn Research Center (GRC) in the early 1990s called MOMMA, and later into an Excel-based tool called SIZER. Recently, a team at GRC has developed an open source framework for solving Multidisciplinary Design, Analysis and Optimization (MDAO) problems called OpenMDAO. A modeling approach is presented that builds on previous work in NTP vehicle sizing and mission analysis by making use of the OpenMDAO framework to enable modular and reconfigurable representations of various NTP vehicle configurations and mission scenarios. This approach is currently applied to vehicle sizing, but is extensible to optimization of vehicle and mission designs. The key features of the code will be discussed and examples of NTP transfer vehicles and candidate missions will be presented.

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

    International Nuclear Information System (INIS)

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

    1993-09-01

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

  9. Future NTP Development Synergy Leveraged from Current J-2X Engine Development

    Science.gov (United States)

    Ballard, Richard O.

    2008-01-01

    This paper is a discussion of how the many long-lead development elements required for the realization of a future nuclear thermal propulsion (NTP) system can be effectively leveraged from the ongoing work being conducted on the J-2X engine program for the Constellation Program. Development studies conducted to date for NTP forward planning have identified a number of technical areas that will require advancement to acceptable technology readiness levels (TRLs) before they can be utilized in NTP system development. These include high-temperature, high-area ratio nozzle extension; long-life, low-NPSP. turbomachinery; and low-boiloff propellant management; and a qualified nuclear fuel element. The current J-2X program is working many of these areas that can be leveraged to support NTP development in a highly compatible and synergistic fashion. In addition to supporting technical development, there are other programmatic issues being worked in the J-2X program that can be leveraged by a future NTP development program. These include compliance with recently-evolved space system requirements such as human-rating, fault tolerance and fracture control. These and other similar mandatory system requirements have been adopted by NASA and can result in a significant technical impact beyond elevation of the root technologies required by NTP. Finally, the exploitation of experience, methodologies, and procedures developed by the J-2X program in the areas of verification, qualification, certification, altitude simulation testing, and facility definition will be especially applicable to a future NTP system. The similarities in system mission (in-space propulsion) and operational environment (vacuum, zero-gee) between J-2X and NTP make this highly synergistic. Thus, it can be $hown that the collective benefit of leveraging experience and technologies developed during the J-2X program can result in significant savings in development cost and schedule for NTP.

  10. The U.S. National Library of Medicine's Toxicology and Environmental Health Information Program

    International Nuclear Information System (INIS)

    Wexler, Philip

    2004-01-01

    For nearly 40 years, the National Library of Medicine's (NLM) Toxicology and Environmental Health Information Program (TEHIP) has been a significant leader in organizing and providing public access to an extensive storehouse of toxicological information through its online databases. With the advent of the Internet, TEHIP has expanded its role to also serve as a pre-eminent portal to toxicological information worldwide. Its primary databases reside within the web-based TOXNET system, and include the scientifically peer-reviewed Hazardous Substances Data Bank (HSDB), the U.S. Environmental Protection Agency's Integrated Risk Information System (IRIS) and Toxics Release Inventory, the National Cancer Institute's Chemical Carcinogenesis Research Information System (CCRIS) and the TOXLINE file of over 3 million bibliographic references. TEHIP's ChemIDplus is an extensive chemical dictionary that extends beyond simple nomenclature to offer displays of molecular structures and links from particular chemicals to other databases containing more information. Specialty files in occupational safety and health, and household products have recently been added to TEHIP's suite of resources. Additional databases in risk assessment, drugs, toxicology education, and global resources, are under development. ''Special Topics'' pages lead users to structured summaries and links in areas such as arsenic, chemical warfare agents, biological warfare, and West Nile Virus. A database on alternatives to the use of live animals, a three-module toxicology tutor, and a glossary of terms in toxicology are among TEHIP's other information aids, as well an increasing commitment to serving consumers, as witnessed by the animated ToxTown program. Outside the sphere of TEHIP, NLM offers additional databases, such as PubMed, of significant value to toxicology researchers

  11. Preliminary investigations on a NTP cargo shuttle for earth to moon orbit payload transfer based on a particle bed reactor

    International Nuclear Information System (INIS)

    Raepsaet, X.; Proust, E.; Gervaise, F.; Baraer, L.; Naury, S.; Linet, F.L.

    1995-01-01

    MAPS, a 3-year study program on NTP has recently been launched at CEA following the conclusions of a preliminary scoping study of an NTP system for earth to moon orbit cargo shuttle missions. This paper presents the main results of this scoping study, and gives an outline of the MAPS program. (authors). 5 figs., 11 tabs., 7 refs

  12. Preliminary investigations on a NTP cargo shuttle for earth to moon orbit payload transfer based on a particle bed reactor

    Energy Technology Data Exchange (ETDEWEB)

    Raepsaet, X; Proust, E; Gervaise, F; Baraer, L; Naury, S; Linet, F L [CEA Centre d` Etudes de Saclay, 91 - Gif-sur-Yvette (France). Dept. de Mecanique et de Technologie; Bresson, C F; Coriolis, C.C. de; Bergeron, I T.A.; Bourquin, L V; Clech, L V; Devaux, L V; Chevillot, L V; Augier, E V [EAMEA, 50 - Cherbourg (France)

    1995-12-01

    MAPS, a 3-year study program on NTP has recently been launched at CEA following the conclusions of a preliminary scoping study of an NTP system for earth to moon orbit cargo shuttle missions. This paper presents the main results of this scoping study, and gives an outline of the MAPS program. (authors). 5 figs., 11 tabs., 7 refs.

  13. Wire core reactor for NTP

    International Nuclear Information System (INIS)

    Harty, R.B.

    1991-01-01

    The development of the wire core system for Nuclear Thermal Propulsion (NTP) that took place from 1963 to 1965 is discussed. A wire core consists of a fuel wire with spacer wires. It's an annular flow core having a central control rod. There are actually four of these, with beryllium solid reflectors on both ends and all the way around. Much of the information on the concept is given in viewgraph form. Viewgraphs are presented on design details of the wire core, the engine design, engine weight vs. thrust, a technique used to fabricate the wire fuel element, and axial temperature distribution

  14. NTP Toxicology and Carcinogenesis Studies of Barium Chloride Dihydrate (CAS No. 10326-27-9) in F344/N Rats and B6C3F1 Mice (Drinking Water Studies).

    Science.gov (United States)

    1994-01-01

    Barium chloride dihydrate, a white crystalline granule or powder, is used in pigments, aluminum refining, leather tanning and coloring, the manufacture of magnesium metal, ceramics, glass, and paper products, as a pesticide, and in medicine as a cardiac stimulant. Toxicology and carcinogenicity studies were conducted by administering barium chloride dihydrate (99% pure) in drinking water to F344/N rats and B6C3F1 mice for 15 days, 13 weeks, and 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, cultured Chinese hamster ovary cells, and mouse lymphoma cells. 15-DAY STUDY IN RATS: Groups of five males and five females received barium chloride dihydrate in the drinking water at concentrations of 0, 125, 250, 500, 1,000, or 2,000 ppm for 15 days, corresponding to average daily doses of 10, 15, 35, 60, or 110 mg barium/kg body weight to males and females. No chemical-related deaths, differences in final mean body weights, or clinical findings of toxicity were observed. Water consumption by male and female rats exposed to 2,000 ppm was slightly less (S16%) than controls during week 2. There were no significant differences in absolute or relative organ weights between exposed and control rats. No biologically significant differences in hematology, clinical chemistry, or neurobehavioral parameters occurred in rats. 15-DAY STUDY IN MICE: Groups of five males and five females received barium chloride dihydrate in the drinking water at concentrations of 0, 40, 80,173, 346, or 692 ppm for 15 days, corresponding to average daily doses of 5,10, 20, 40, or 70 mg barium/kg body weight to males and 5, 10, 15, 40, or 85 mg barium/kg body weight to females. No chemical-related deaths, differences in mean body weights or in water consumption, or clinical findings of toxicity were observed in mice. The relative liver weight of males receiving 692 ppm was significantly greater than that of the controls. The absolute and relative liver weights of females that

  15. Integrated NTP Vehicle Radiation Design

    Science.gov (United States)

    Caffrey, Jarvis; Rodriquez, Mitchell

    2018-01-01

    The development of a nuclear thermal propulsion stage requires consideration for radiation emitted from the nuclear reactor core. Applying shielding mass is an effective mitigating solution, but a better alternative is to incorporate some mitigation strategies into the propulsion stage and crew habitat. In this way, the required additional mass is minimized and the mass that must be applied may in some cases be able to serve multiple purposes. Strategies for crew compartment shielding are discussed that reduce dose from both engine and cosmic sources, and in some cases may also serve to reduce life support risks by permitting abundant water reserves. Early consideration for integrated mitigation solutions in a crewed nuclear thermal propulsion (NTP) vehicle will enable reduced radiation burden from both cosmic and nuclear sources, improved thrust-to-weight ratio or payload capacity by reducing 'dead mass' of shielding, and generally support a more robust risk posture for a NTP-powered Mars mission by permitting shorter trip times and increased water reserves

  16. Integrated NTP Vehicle Radiation Design

    Science.gov (United States)

    Caffrey, Jarvis A.; Rodriquez, Mitchell A.

    2018-01-01

    The development of a nuclear thermal propulsion stage requires consideration for radiation emitted from the nuclear reactor core. Applying shielding mass is an effective mitigating solution, but a better alternative is to incorporate some mitigation strategies into the propulsion stage and crew habitat. In this way, the required additional mass is minimized and the mass that must be applied may in some cases be able to serve multiple purposes. Strategies for crew compartment shielding are discussed that reduce dose from both engine and cosmic sources, and in some cases may also serve to reduce life support risks by permitting abundant water reserves. Early consideration for integrated mitigation solutions in a crewed nuclear thermal propulsion (NTP) vehicle will enable reduced radiation burden from both cosmic and nuclear sources, improved thrust-to-weight ratio or payload capacity by reducing 'dead mass' of shielding, and generally support a more robust risk posture for a NTP-powered Mars mission by permitting shorter trip times and increased water reserves.

  17. NTP Toxicology and Carcinogenesis of 1,2,3-Trichloropropane (CAS No. 96-18-4) in F344/N Rats and B6C3F1 Mice (Gavage Studies).

    Science.gov (United States)

    1993-08-01

    1,2,3-Trichloropropane is a colorless liquid used as a paint and varnish remover, solvent, and degreasing agent, and as a crosslinking agent in the synthesis of polysulfides and hexafluoropropylene. 1,2,3-Trichloropropane may be found as an impurity in certain nematocides and soil fumigants and as a contaminant of drinking and ground water. Studies on the toxic and carcinogenic effects of 1,2,3-trichloropropane were initiated because of the close structural relationship of this chemical to other short-chain halogenated compounds that were demonstrated to be carcinogenic in experimental animals, and because of the potential for human exposure. Toxicology and carcinogenicity studies were conducted by administering 1,2,3-trichloropropane (greater than 99% pure) in corn oil by gavage to groups of F344/N rats and B6C3FI mice for 17 weeks and 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium strains, mouse lymphoma cells, and Chinese hamster ovary cells. 17-Week Studies: Groups of 20 male and 20 female rats received 1,2,3-trichloropropane in corn oil by gavage at doses of 8, 16, 32, 63, 125, or 250 mg/kg body weight 5 days per week for up to 17 weeks; 30 male and 30 female rats received corn oil alone and served as controls. Animals were evaluated at 8 or 17 weeks. All rats in the 250 mg/kg groups died by week 5. One male and four female rats in the 125 mg/kg groups died during the study. The mean body weight gains and final mean body weights of males receiving 63 mg/kg and of males and females receiving 125 mg/kg were lower than those of the controls. Hematocrit values, hemoglobin concentrations, and erythrocyte counts decreased with dose in males and females. Serum alanine aminotransferase, aspartate aminotransferase, and sorbitol dehydrogenase activities were significantly increased in some female rats receiving 125 mg/kg. Serum pseudocholinesterase activity decreased with dose in females. Increases in kidney and liver weights were related

  18. NTP Toxicology and Carcinogenesis Studies of Dimethyl Methylphosphonate (CAS No. 756-79-6) in F344/N Rats and B6C3F1 Mice (Gavage Studies).

    Science.gov (United States)

    1987-11-01

    Dimethyl methylphosphonate (98% pure) is one of four chemicals nominated by the U.S. Army for toxicology and carcinogenesis studies because it was being considered for use to simulate the physical and spectroscopic (but not the biologic) properties of anticholinesterase (nerve) agents. Dimethyl methylphosphonate is also used as a flame retardant, a preignition additive for gasoline, an antifoam agent, a plasticizer and stabilizer, a textile conditioner and antistatic agent, and an additive for solvents and low-temperature hydraulic fluids. The United States produces 0.2-2 million pounds (91,000-910,000 kg) of per year. Gavage was chosen as the route of administration for all four candidate "simulants" to mimic potential exposure. Experimental Design: Dimethyl methylphosphonate was administered in corn oil by gavage to male and female F344/N rats and B6C3F1 mice in single-administration, 15-day, and 13-week studies to obtain toxicity data, to establish dose levels for the 2-year studies, and to identify target tissues. Additional studies were also performed to determine toxicity to the reproductive system of male F344/N rats and B6C3F1 mice and to study the potential for genetic damage in bacteria, mammalian cells, and Drosophila. Single-Administration Studies: In the single-administration studies, dimethyl methylphosphonate was given to rats and mice at doses up to 6,810 mg/kg body weight. No compound-related deaths were seen in male or female rats or male mice; two high dose female mice died. Rats exhibited inactivity, unsteady gait, and prostration after dosing; mice were inactive after dosing. Fifteen-Day Studies: Rats and mice received doses of 0, 1,250, 2,500, 5,000, 10,000, or 15,000 mg/kg dimethyl methylphosphonate per day. Compound-related deaths occurred in the three highest dose groups of rats and the two highest dose groups of mice. Rats receiving doses of 2,500 mg/kg or higher were inactive and at 5,000 or 10,000 mg/kg had an unsteady gait after dosing

  19. Automated toxicological screening reports of modified Agilent MSD Chemstation combined with Microsoft Visual Basic application programs.

    Science.gov (United States)

    Choe, Sanggil; Kim, Suncheun; Choi, Hyeyoung; Choi, Hwakyoung; Chung, Heesun; Hwang, Bangyeon

    2010-06-15

    Agilent GC-MS MSD Chemstation offers automated library search report for toxicological screening using total ion chromatogram (TIC) and mass spectroscopy in normal mode. Numerous peaks appear in the chromatogram of biological specimen such as blood or urine and often large migrating peaks obscure small target peaks, in addition, any target peaks of low abundance regularly give wrong library search result or low matching score. As a result, retention time and mass spectrum of all the peaks in the chromatogram have to be checked to see if they are relevant. These repeated actions are very tedious and time-consuming to toxicologists. MSD Chemstation software operates using a number of macro files which give commands and instructions on how to work on and extract data from the chromatogram and spectroscopy. These macro files are developed by the own compiler of the software. All the original macro files can be modified and new macro files can be added to the original software by users. To get more accurate results with more convenient method and to save time for data analysis, we developed new macro files for reports generation and inserted new menus in the Enhanced Data Analysis program. Toxicological screening reports generated by these new macro files are in text mode or graphic mode and these reports can be generated with three different automated subtraction options. Text reports have Brief mode and Full mode and graphic reports have the option with or without mass spectrum mode. Matched mass spectrum and matching score for detected compounds are printed in reports by modified library searching modules. We have also developed an independent application program named DrugMan. This program manages drug groups, lists and parameters that are in use in MSD Chemstation. The incorporation of DrugMan with modified macro modules provides a powerful tool for toxicological screening and save a lot of valuable time on toxicological work. (c) 2010 Elsevier Ireland Ltd. All

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

    Science.gov (United States)

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

    2009-05-01

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

  1. 75 FR 17333 - Addition of National Toxicology Program Carcinogens; Community Right-to-Know Toxic Chemical...

    Science.gov (United States)

    2010-04-06

    ... Business Information (CBI) or other information whose disclosure is restricted by statute. Do not submit... solvent recovery services on a contract or fee basis (previously classified under SIC 7389, Business... and female rats; and tumors of the forestomach and lung in male and female mice (NTP 1996). Two cohort...

  2. Aerobrake concepts for NTP systems study

    Science.gov (United States)

    Cruz, Manuel I.

    1992-01-01

    Design concepts are described for landing large spacecraft masses on the Mars surface in support of manned missions with interplanetary transportation using Nuclear Thermal Propulsion (NTP). Included are the mission and systems analyses, trade studies and sensitivity analyses, design analyses, technology assessment, and derived requirements to support this concept. The mission phases include the Mars de-orbit, entry, terminal descent, and terminal touchdown. The study focuses primarily on Mars surface delivery from orbit after Mars orbit insertion using an NTP. The requirements associated with delivery of logistical supplies, habitats, and other equipment on minimum energy Earth to Mars transfers are also addressed in a preliminary fashion.

  3. Ovarian toxicity and carcinogenicity in eight recent national toxicology program studies

    Energy Technology Data Exchange (ETDEWEB)

    Maronpot, R.R.

    1987-08-01

    Ovarian toxicity and/or carcinogenicity has been documented for at least eight chemicals recently tested in National Toxicity Program prechronic and chronic rodent studies. The chemicals that yielded treatment-related ovarian lesions were 1,3-butadiene, 4-vinylcyclohexene, vinylcylohexene deipoxide, nitrofurantoin, nitrofurazone, benzene, ..delta..-9-tetrahydrocannabinol, and tricresylphosphate. Typical nonneoplastic ovarian changes included hypoplasia, atrophy, follicular necrosis, and tubular hyperplasia. The most commonly observed treatment-related neoplasms were granulosa cell tumors and benign mixed tumors. A relationship between antecedent ovarian hypoplasia, atrophy, and hyperplasia and subsequent ovarian neoplasia is supported by some of these National Toxicology Program studies. Pathologic changes in other tissues such as the adrenal glands and uterus were associated with the treatment-related ovarian changes.

  4. dNTP deficiency induced by HU via inhibiting ribonucleotide reductase affects neural tube development

    International Nuclear Information System (INIS)

    Guan, Zhen; Wang, Xiuwei; Dong, Yanting; Xu, Lin; Zhu, Zhiqiang; Wang, Jianhua; Zhang, Ting; Niu, Bo

    2015-01-01

    Highlights: • Murine NTDs were successfully induced by means of hydroxyurea (HU). • The impairment of dNTP was induced via inhibition of ribonucleotide reductase. • dNTP deficiency induced by HU caused defective DNA synthesis and repair. • Abnormal apoptosis and proliferation induced by HU affected neural tube development. - Abstract: Exposure to environmental toxic chemicals in utero during the neural tube development period can cause developmental disorders. To evaluate the disruption of neural tube development programming, the murine neural tube defects (NTDs) model was induced by interrupting folate metabolism using methotrexate in our previous study. The present study aimed to examine the effects of dNTP deficiency induced by hydroxyurea (HU), a specific ribonucleotide reductase (RNR) inhibitor, during murine neural tube development. Pregnant C57BL/6J mice were intraperitoneally injected with various doses of HU on gestation day (GD) 7.5, and the embryos were checked on GD 11.5. RNR activity and deoxynucleoside triphosphate (dNTP) levels were measured in the optimal dose. Additionally, DNA damage was examined by comet analysis and terminal deoxynucleotidyl transferase mediated dUTP nick end-labeling (TUNEL) assay. Cellular behaviors in NTDs embryos were evaluated with phosphorylation of histone H3 (PH-3) and caspase-3 using immunohistochemistry and western blot analysis. The results showed that NTDs were observed mostly with HU treatment at an optimal dose of 225 mg/kg b/w. RNR activity was inhibited and dNTP levels were decreased in HU-treated embryos with NTDs. Additionally, increased DNA damage, decreased proliferation, and increased caspase-3 were significant in NTDs embryos compared to the controls. Results indicated that HU induced murine NTDs model by disturbing dNTP metabolism and further led to the abnormal cell balance between proliferation and apoptosis

  5. Fossil fuel toxicology

    International Nuclear Information System (INIS)

    Anon.

    1976-01-01

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

  6. Toxicology screen

    Science.gov (United States)

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

  7. Current Ground Test Options for Nuclear Thermal Propulsion (NTP)

    Science.gov (United States)

    Gerrish, Harold P., Jr.

    2014-01-01

    About 20 different NTP engines/ reactors were tested from 1959 to 1972 as part of the Rover and Nuclear Engine for Rocket Vehicle Application (NERVA) program. Most were tested in open air at test cell A or test cell C, at the Nevada Test Site (NTS). Even after serious engine breakdowns of the reactor (e.g., Phoebus 1A), the test cells were cleaned up for other engine tests. The engine test stand (ETS) was made for high altitude (approximately 1 psia) testing of an NTP engine with a flight configuration, but still had the exhaust released to open air. The Rover/NERVA program became aware of new environmental regulations which would prohibit the release of any significant quantity of radioactive particulates and noble gases into the open air. The nuclear furnace (NF-1) was the last reactor tested before the program was cancelled in 1973, but successfully demonstrated a scrubber concept on how to filter the NTP exhaust. The NF-1 was demonstrated in the summer of 1972. The NF-1 used a 44MW reactor and operated each run for approximately 90 minutes. The system cooled the hot hydrogen exhaust from the engine with a water spray before entering a particle filter. The exhaust then passed through a series of heat exchangers and water separators to help remove water from the exhaust and further reduce the exhaust temperatures. The exhaust was next prepared for the charcoal trap by passing through a dryer and effluent cooler to bring exhaust temperatures close to liquid nitrogen. At those low temperatures, most of the noble gases (e.g., Xe and Kr made from fission products) get captured in the charcoal trap. The filtered hydrogen is finally passed through a flare stack and released to the air. The concept was overall successful but did show a La plating on some surfaces and had multiple recommendations for improvement. The most recent detailed study on the NTP scrubber concept was performed by the ARES Corporation in 2006. The concept is based on a 50,000 lbf thrust engine

  8. Toxicology elements

    International Nuclear Information System (INIS)

    Viala, A.

    1998-01-01

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

  9. 42 CFR 493.937 - Toxicology.

    Science.gov (United States)

    2010-10-01

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

  10. Shoreline ecology program for Prince William Sound, Alaska, following the Exxon Valdez oil spill. Part 2: Chemistry and toxicology

    International Nuclear Information System (INIS)

    Boehm, P.D.; Page, D.S.; Gilfillan, E.S.; Stubblefield, W.A.; Harner, E.J.

    1995-01-01

    This paper describes chemical and toxicological results of a comprehensive shoreline ecology program that was designed to assess recovery in Prince William Sound following the Exxon Valdez oil spill of March 24, 1989. The program is an application of the sediment quality triad approach, combining chemical, toxicological, and biological measurements. The study was designed so that results could be extrapolated to the entire spill zone in the sound and projected forward in time. It combined one-time sampling of 64 randomly chosen study sites representing four major habitats and four oiling levels (including unoiled reference sites), with periodic sampling at 12 subjectively chosen fixed sites. Sediment samples--or when conditions required, filter-wipes from rock surfaces--were collected in each of three intertidal zones and from subtidal stations up to 30-m deep. Oil removal was generally quite rapid: by 1991 the concentration of oil spilled from the Exxon Valdez had been dramatically reduced on the majority of shorelines by both natural processes and cleanup efforts. Acute sediment toxicity from oil (as measured by standard toxicity tests) was virtually absent by 1990--91, except at a small number of isolated locations. The petroleum residues had degraded below the threshold of acute toxic effects. Measurable polycyclic aromatic hydrocarbon (PAH) levels are, in general, well below those conservatively associated with adverse effects, and biological recovery has been considerably more rapid than the removal of the last chemical remnants. 55 refs., 15 figs., 4 tabs

  11. Resource Guide to Careers in Toxicology, 3rd Edition.

    Science.gov (United States)

    Society of Toxicology, Reston, VA.

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

  12. A preliminary evaluation of the toxic equivalence factor (TEF) for 2,3,4,7,8-PCDF (4-PCDF) using data from the recent NTP dioxin bioassays

    Energy Technology Data Exchange (ETDEWEB)

    Budinsky, R.; Landenberger, B.; Fontaine, D. [The Dow Chemical Company (United States); Starr, T.B. [TBS Associates, Raleigh, NC (United States); Paustenbach, D. [ChemRisk (United States)

    2004-09-15

    PCDD/PCDF toxic equivalency factors (TEFs) are being routinely applied now in human cancer risk assessments for dioxin-like compounds despite the fact that until very recently only two congeners (1,2,3,6,7,8- and 1,2,3,7,8,9-hexachlorodibenzo-p-dioxin) other than 2,3,7,8-TCDD had been evaluated for carcinogenicity in a standard cancer bioassay. However, in December 2003, draft reports from the National Toxicology Program (NTP) cancer bioassays were made available for 2,3,7,8-TCDD, 4-PCDF, PCB 126, and a (presumably) equipotent mixture of these three compounds. These data provide important new information for evaluating the accuracy of TEFs in predicting the potential human cancer hazard for 4-PCDF and PCB126 alone and in combination with TCDD. We present herein results from a series of simple statistical tests demonstrating that the current TEF of 0.5 for 4-PCDF, when combined appropriately with the new TCDD bioassay data, fails to predict accurately the results from the new 4-PCDF bioassay.

  13. Green toxicology.

    Science.gov (United States)

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

    2014-01-01

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

  14. Forensic toxicology.

    Science.gov (United States)

    Davis, Gregory G

    2012-01-01

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

  15. NTP Toxicology and Carcinogenesis Studies of Xylenes (Mixed) (60% m-Xylene, 14% p-Xylene, 9% o-Xylene, and 17% Ethylbenzene) (CAS No. 1330-20-7) in F344/N Rats and B6C3F1 Mice (Gavage Studies).

    Science.gov (United States)

    1986-12-01

    The technical grade of xylenes (mixed) (hereafter termed xylenes) contains the three isomeric forms and ethylbenzene (percentage composition shown above). The annual production for 1985 was approximately 7.4 x 108 gallons. Xylenes is used as a solvent and a cleaning agent and as a degreaser and is a constituent of aviation and automobile fuels. Xylenes is also used in the production of benzoic acid, phthalate anhydride, and isophthalic and terephthalic acids as well as their dimethyl esters. Toxicology and carcinogenesis studies of xylenes were conducted in laboratory animals because a large number of workers are exposed and because the long- term effects of exposure to xylenes were not known. Exposure for the present studies was by gavage in corn oil. In single-administration studies, groups of five F344/N rats and B6C3F1 mice of each sex received 500, 1,000, 2,000, 4,000, or 6,000 mg/kg. Administration of xylenes caused deaths at 6,000 mg/kg in rats and mice of each sex and at 4,000 mg/kg in male rats. In rats, clinical signs observed within 24 hours of dosing at 4,000 mg/kg included prostration, muscular incoordination, and loss of hind limb movement; these effects continued through the second week of observation. Tremors, prone position, and slowed breathing were recorded for mice on day 3, but all mice appeared normal by the end of the 2- week observation period. In 14- day studies, groups of five rats of each sex were administered 0, 125, 250, 500, 1,000, or 2,000 mg/kg, and groups of five mice of each sex received 0, 250, 500, 1,000, 2,000, or 4,000 mg/kg. Chemical- related mortality occurred only at 2,000 mg/kg in rats and at 4,000 mg/kg in mice. Rats and mice exhibited shallow breathing and prostration within 48 hours following dosing at 2,000 mg/kg. These signs persisted until day 12 for rats, but no clinical signs were noted during the second week for mice. In 13- week studies, groups of 10 rats of each sex received 0, 62.5, 125, 250, 500, or 1,000 mg

  16. 77 FR 35395 - Draft Five-Year Plan (2013-2017) for the National Toxicology Program Interagency Center for the...

    Science.gov (United States)

    2012-06-13

    ... (ICCVAM) has developed a draft NICEATM-ICCVAM Five-Year Plan. The plan describes four core strategies to... innovations are driving transformative changes in toxicology and how safety testing is performed. The field of toxicology is evolving from a system based largely on animal testing toward one based on the integration of...

  17. NTP system definition and comparison process for SEI

    International Nuclear Information System (INIS)

    Corban, R.R.

    1993-01-01

    The concept definition, trade-offs, and ultimate selection of a nuclear thermal propulsion (NTP) system that will enable the Space Exploration Initiative (SEI) missions to Mars will require a rigorous systems engineering approach. A systems engineering process to provide a consistent comparison has been established to allow for evolving SEI mission requirements, level of concept definition and changing ''customer'' requirements, while continuing to improve the process as more data becomes available. All concepts will be evaluated against an established baseline NTP system to compare system benefits and merits. Establishing the evaluation criteria is extremely challenging and critical to the evaluation and selection process. Quality function deployment (QFD) will be utilized to provide structure and focus in obtaining the critical needs and attributes of the NTP system. System performance, cost, and risk analysis tools will be integrated into the process to provide the quantitative data required to allow for an informative decision on concept and technology decisions. This process will initiate the framework for design and development of a robust, reliable, cost effective NTP engine within NASA's philosophy for space systems to be developed ''faster, better, and cheaper.''

  18. NTP system definition and comparison process for SEI

    Science.gov (United States)

    Corban, Robert R.

    1993-01-01

    The concept definition, trade-offs, and ultimate selection of a nuclear thermal propulsion (NTP) system that will enable the Space Exploration Initiative (SEI) missions to Mars will require a rigorous systems engineering approach. A systems engineering process to provide a consistent comparison has been established to allow for evolving SEI mission requirements, level of concept definition and changing ``customer'' requirements, while continuing to improve the process as more data becomes available. All concepts will be evaluated against an established baseline NTP system to compare system benefits and merits. Establishing the evaluation criteria is extremely challenging and critical to the evaluation and selection process. Quality function deployment (QFD) will be utilized to provide structure and focus in obtaining the critical needs and attributes of the NTP system. System performance, cost, and risk analysis tools will be integrated into the process to provide the quantitative data required to allow for an informative decision on concept and technology decisions. This process will initiate the framework for design and development of a robust, reliable, cost effective NTP engine within NASA's philosophy for space systems to be developed ``faster, better, and cheaper.''

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

    Science.gov (United States)

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

    2017-05-25

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

  20. The Numerical Tokamak Project (NTP) simulation of turbulent transport in the core plasma: A grand challenge in plasma physics

    International Nuclear Information System (INIS)

    1993-12-01

    The long-range goal of the Numerical Tokamak Project (NTP) is the reliable prediction of tokamak performance using physics-based numerical tools describing tokamak physics. The NTP is accomplishing the development of the most advanced particle and extended fluid model's on massively parallel processing (MPP) environments as part of a multi-institutional, multi-disciplinary numerical study of tokamak core fluctuations. The NTP is a continuing focus of the Office of Fusion Energy's theory and computation program. Near-term HPCC work concentrates on developing a predictive numerical description of the core plasma transport in tokamaks driven by low-frequency collective fluctuations. This work addresses one of the greatest intellectual challenges to our understanding of the physics of tokamak performance and needs the most advanced computational resources to progress. We are conducting detailed comparisons of kinetic and fluid numerical models of tokamak turbulence. These comparisons are stimulating the improvement of each and the development of hybrid models which embody aspects of both. The combination of emerging massively parallel processing hardware and algorithmic improvements will result in an estimated 10**2--10**6 performance increase. Development of information processing and visualization tools is accelerating our comparison of computational models to one another, to experimental data, and to analytical theory, providing a bootstrap effect in our understanding of the target physics. The measure of success is the degree to which the experimentally observed scaling of fluctuation-driven transport may be predicted numerically. The NTP is advancing the HPCC Initiative through its state-of-the-art computational work. We are pushing the capability of high performance computing through our efforts which are strongly leveraged by OFE support

  1. TOXNET: Toxicology Data Network

    Science.gov (United States)

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

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

    Science.gov (United States)

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

    2012-06-01

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

  3. Space Toxicology

    Science.gov (United States)

    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.

  4. Animal toxicology

    Energy Technology Data Exchange (ETDEWEB)

    Amdur, M.

    1996-12-31

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

  5. A practice analysis of toxicology.

    Science.gov (United States)

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

    2016-12-01

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

  6. Forensic Toxicology: An Introduction.

    Science.gov (United States)

    Smith, Michael P; Bluth, Martin H

    2016-12-01

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

  7. Cells Lacking mtDNA Display Increased dNTP Pools upon DNA Damage

    DEFF Research Database (Denmark)

    Skovgaard, Tine; Rasmussen, Lene Juel; Munch-Petersen, Birgitte

    Imbalanced dNTP pools are highly mutagenic due to a deleterious effect on DNA polymerase fidelity. Mitochondrial DNA defects, including mutations and deletions, are commonly found in a wide variety of different cancer types. In order to further study the interconnection between dNTP pools...... and mitochondrial function we have examined the effect of DNA damage on dNTP pools in cells deficient of mtDNA. We show that DNA damage induced by UV irradiation, in a dose corresponding to LD50, induces an S phase delay in different human osteosarcoma cell lines. The UV pulse also has a destabilizing effect...... shows that normal mitochondrial function is prerequisite for retaining stable dNTP pools upon DNA damage. Therefore it is likely that mitochondrial deficiency defects may cause an increase in DNA mutations by disrupting dNTP pool balance....

  8. History of Japanese Society of Toxicology.

    Science.gov (United States)

    Satoh, Tetsuo

    2016-01-01

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

  9. Cornerstones of Toxicology.

    Science.gov (United States)

    Hayes, A Wallace; Dixon, Darlene

    2017-01-01

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

  10. Nuclear toxicology at CEA

    International Nuclear Information System (INIS)

    Giustranti, C.

    2001-01-01

    CEA (French commission of atomic energy) has launched a new program dedicated to the study of the transfer of heavy metals and some radionuclides from environment to living beings. The substances that will be studied, are those that are involved in research, medical activities, and in nuclear industry. It means iodine, technetium, trans-uranides (uranium and plutonium), fission products (iodine, cesium), carbon, cobalt, boron and beryllium. This program is composed of 2 axis: the first one concerns the bio-geo-chemical cycles that are involved in transfer and the second axis deals with the detoxication processes that appear in animal and man cells. This program will rely on the strong competencies of CEA in chemistry, radiochemistry, biology, physiology and toxicology. (A.C.)

  11. Toxicology Education Foundation

    Science.gov (United States)

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

  12. Environmental Toxicology Research Facility

    Data.gov (United States)

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

  13. Handbook of systems toxicology

    National Research Council Canada - National Science Library

    Casciano, Daniel A; Sahu, Saura C

    2011-01-01

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

  14. Green Toxicology – Application of predictive toxicology

    DEFF Research Database (Denmark)

    Vinggaard, Anne Marie; Wedebye, Eva Bay; Taxvig, Camilla

    2014-01-01

    safer chemicals and to identify problematic compounds already in use such as industrial compounds, drugs, pesticides and cosmetics, is required. Green toxicology is the application of predictive toxicology to the production of chemicals with the specific intent of improving their design for hazard...

  15. A particle bed reactor based NTP in the 112,500 N thrust class

    International Nuclear Information System (INIS)

    Ludewig, H.; Powell, J.R.; Lazareth, O.W. Jr.; Todosow, M.

    1993-01-01

    This paper discusses the application of a Particle Bed Reactor (PBR) to a 112,500 N thrust Nuclear Thermal Propulsion (NTP) Engine. The method of analysis is described, followed by a presentation of the results. It is concluded that the PBR would result in a very competitive NTP engine. In addition, due to the high power densities possible with a PBR, high thrust/weight ratios are possible. This conclusion can be used to satisfy a variety of mission goals

  16. A particle bed reactor based NTP in the 112,500 N thrust class

    Science.gov (United States)

    Ludewig, Hans; Powell, James R.; Lazareth, Otto W.; Todosow, Michael

    1993-01-01

    This paper discusses the application of a Particle Bed Reactor (PBR) to a 112,500 N thrust Nuclear Thermal Propulsion (NTP) Engine. The method of analysis is described, followed by a presentation of the results. It is concluded that the PBR would result in a very competitive NTP engine. In addition, due to the high power densities possible with a PBR, high thrust/weight ratios are possible. This conclusion can be used to satisfy a variety of mission goals.

  17. Information resources in toxicology--Italy

    International Nuclear Information System (INIS)

    Preziosi, Paolo; Dracos, Adriana; Marcello, Ida

    2003-01-01

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

  18. Toxicological benchmarks for screening contaminants of potential concern for effects on sediment-associated biota: 1994 Revision. Environmental Restoration Program

    International Nuclear Information System (INIS)

    Hull, R.N.; Suter, G.W. II

    1994-06-01

    Because a hazardous waste site may contain hundreds of chemicals, it is important to screen contaminants of potential concern for the ecological risk assessment. Often this screening is done as part of a Screening Assessment, the purpose of which is to evaluate the available data, identify data gaps, and screen contaminants of potential concern. Screening may be accomplished by using a set of toxicological benchmarks. These benchmarks are helpful in determining whether contaminants warrant further assessment or are at a level that requires no further attention. If a chemical concentration or the reported detection limit exceeds a proposed lower benchmark, more analysis is needed to determine the hazards posed by that chemical. If, however, the chemical concentration falls below the lower benchmark value, the chemical may be eliminated from further study. This report briefly describes three categories of approaches to the development of sediment quality benchmarks. These approaches are based on analytical chemistry, toxicity test and field survey data. A fourth integrative approach incorporates all three types of data. The equilibrium partitioning approach is recommended for screening nonpolar organic contaminants of concern in sediments. For inorganics, the National Oceanic and Atmospheric Administration has developed benchmarks that may be used for screening. There are supplemental benchmarks from the province of Ontario, the state of Wisconsin, and US Environmental Protection Agency Region V. Pore water analysis is recommended for polar organic compounds; comparisons are then made against water quality benchmarks. This report is an update of a prior report. It contains revised ER-L and ER-M values, the five EPA proposed sediment quality criteria, and benchmarks calculated for several nonionic organic chemicals using equilibrium partitioning

  19. On-line sources of toxicological information in Canada

    International Nuclear Information System (INIS)

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

    2003-01-01

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

  20. Reproductive and developmental toxicology

    National Research Council Canada - National Science Library

    Gupta, Ramesh C

    2011-01-01

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

  1. Interdependence of the kinetics of NTP hydrolysis and the stability of the RecA-ssDNA complex.

    Science.gov (United States)

    Katz, F S; Bryant, F R

    2001-09-18

    The ssDNA-dependent NTP hydrolysis activity of the RecA protein was examined using a series of dTn oligomers ranging in size from dT10 to dT2000 as the ssDNA effector. There were three distinct manifestations of the dTn-dependent NTP hydrolysis reaction, depending on the length of the dTn effector that was used. With longer dTn oligomers, NTP hydrolysis occurred with a turnover number of 20-25 min(-1) and the observed S0.5 value for the NTP was independent of the concentration of the dTn oligomer (DNA concentration-independent hydrolysis). With dTn oligomers of intermediate length, NTP hydrolysis still occurred with a turnover number of 20-25 min(-1), but the observed S0.5 for the NTP decreased with increasing dTn concentration until reaching a value similar to that obtained with the longer dTn oligomers (DNA concentration-dependent hydrolysis). With shorter dTn oligomers, the NTP hydrolysis activity was effectively eliminated. Although this general progression of kinetic behavior was observed for the three structurally related NTPs (dATP, ATP, and GTP), the dTn oligomer length at which DNA concentration-independent, DNA concentration-dependent, and no NTP hydrolysis was observed depended on the NTP being considered. For example, dATP (S0.5 = 35 microM) was hydrolyzed in the presence of dT20, whereas ATP (S0.5 = 70 microM) and GTP (S0.5 = 1200 microM) required at least dT50 and dT200 for hydrolysis, respectively. These results are discussed in terms of a kinetic model in which the stability of the RecA-ssDNA-NTP complex is dependent on the intrinsic S0.5 value of the NTP being hydrolyzed.

  2. A CHRONIC INHALATION STUDY OF METHYL BROMIDE TOXICITY IN B6C3F1 MICE. (FINAL REPORT TO THE NATIONAL TOXICOLOGY PROGRAM)

    Energy Technology Data Exchange (ETDEWEB)

    HABER, S.B.

    1987-06-26

    This report provides a detailed account of a two year chronic inhalation study of methyl bromide toxicity in B6C3Fl mice conducted for the National Toxicology Program. Mice were randomized into three dose groups (10, 33 and 100 ppm methyl bromide) and one control group (0 ppm) per sex and exposed 5 days/week, 6 hours/day, for a total of 103 weeks. Endpoints included body weight; clinical signs and mortality, and at 6, 15 and 24 months of exposure, animals were sacrificed for organ weights, hematology and histopathology. In addition, a subgroup of animals in each dosage group was monitored for neurobehavioral and neuropathological changes. After only 20 weeks of exposure, 48% of the males and 12% of the females in the 100 ppm group had died. Exposures were terminated in that group and the surviving mice were observed for the duration of the study. Exposure of B6C3Fl mice to methyl bromide, even for only 20 weeks, produced significant changes in growth rate, mortality, organ weights and neurobehavioral functioning. These changes occurred in both males and females, but were more pronounced in males.

  3. Toxicology ontology perspectives.

    Science.gov (United States)

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

    2012-01-01

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

  4. 77 FR 40358 - Meeting of the Scientific Advisory Committee on Alternative Toxicological Methods (SACATM)

    Science.gov (United States)

    2012-07-09

    ..., revised, and alternative safety testing methods with regulatory applicability and promotes the scientific... DEPARTMENT OF HEALTH AND HUMAN SERVICES Meeting of the Scientific Advisory Committee on Alternative Toxicological Methods (SACATM) AGENCY: Division of the National Toxicology Program (DNTP...

  5. SULEU NTP Core with Passive Reactivity Control and Enhanced Submersion Safety

    Energy Technology Data Exchange (ETDEWEB)

    Venneri, Paolo; Kim, Yong Hee [KAIST, Daejeon (Korea, Republic of); Eades, Michael J [The Ohio State University, Ohio (United States)

    2016-05-15

    In this summary, SULEU has been adapted to implement some of the latest developments of LEUNTP design efforts. These include the implementation of a rapid depletion burnable absorber to flatten the reactivity profile during operation and the addition of a lower axial reflector to help minimize the reactivity increase during the full submersion criticality accident. The purpose of this study is to show the state of current LEU-NTP designs in terms of resolving key issues such as minimizing control drum usage and resolving the full submersion criticality accident. Future work will include integrating the rapid depletion poison with other passive reactivity control devices (such as hydrogen density in the tie-tubes) and developing additional systems for mitigating the full submersion criticality accident. It is widely acknowledged that nuclear thermal propulsion (NTP) is an enabling technology for manned missions to Mars and other locations beyond low-Earth orbit. Without nuclear thermal propulsion, manned space travel will be severely limited by the propellant requirements of chemical propulsion and significantly longer travel times of electric propulsion. While the performance superiority of NTP is clear, its implementation has been to date unsuccessful due to the significant costs of development, implementation, and regulations associated with the heritage NTP designs. These new systems take heritage designs and experimental results and adapt them to use LEU fuel with minimum impact on the heritage system. This is done in order to ensure their continued relevance with existing NTP research efforts and enable their rapid implementation into existing NASA efforts for human Mars mission planning. Of the current baseline NTP designs being studied, this paper concerns itself with the improvement of the Superb Use of Low Enriched (SULEU) core.

  6. Evaluating a National Science and Technology Program Using the Human Capital and Relational Asset Perspectives

    Science.gov (United States)

    Hung, Chia-Liang; Chou, Jerome Chih-Lung; Roan, Hung-Wei

    2010-01-01

    The purpose of this research is to evaluate the performance of the National Science and Technology Program (NSTP) by targeting the Taiwan National Telecommunication Program (NTP) initiated in 1998. The Taiwan telecommunications industry has prospered, currently occupying key positions in global markets even though NTP seldom contributes positively…

  7. dNTP pool levels modulate mutator phenotypes of error-prone DNA polymerase ε variants.

    Science.gov (United States)

    Williams, Lindsey N; Marjavaara, Lisette; Knowels, Gary M; Schultz, Eric M; Fox, Edward J; Chabes, Andrei; Herr, Alan J

    2015-05-12

    Mutator phenotypes create genetic diversity that fuels tumor evolution. DNA polymerase (Pol) ε mediates leading strand DNA replication. Proofreading defects in this enzyme drive a number of human malignancies. Here, using budding yeast, we show that mutator variants of Pol ε depend on damage uninducible (Dun)1, an S-phase checkpoint kinase that maintains dNTP levels during a normal cell cycle and up-regulates dNTP synthesis upon checkpoint activation. Deletion of DUN1 (dun1Δ) suppresses the mutator phenotype of pol2-4 (encoding Pol ε proofreading deficiency) and is synthetically lethal with pol2-M644G (encoding altered Pol ε base selectivity). Although pol2-4 cells cycle normally, pol2-M644G cells progress slowly through S-phase. The pol2-M644G cells tolerate deletions of mediator of the replication checkpoint (MRC) 1 (mrc1Δ) and radiation sensitive (Rad) 9 (rad9Δ), which encode mediators of checkpoint responses to replication stress and DNA damage, respectively. The pol2-M644G mutator phenotype is partially suppressed by mrc1Δ but not rad9Δ; neither deletion suppresses the pol2-4 mutator phenotype. Thus, checkpoint activation augments the Dun1 effect on replication fidelity but is not required for it. Deletions of genes encoding key Dun1 targets that negatively regulate dNTP synthesis, suppress the dun1Δ pol2-M644G synthetic lethality and restore the mutator phenotype of pol2-4 in dun1Δ cells. DUN1 pol2-M644G cells have constitutively high dNTP levels, consistent with checkpoint activation. In contrast, pol2-4 and POL2 cells have similar dNTP levels, which decline in the absence of Dun1 and rise in the absence of the negative regulators of dNTP synthesis. Thus, dNTP pool levels correlate with Pol ε mutator severity, suggesting that treatments targeting dNTP pools could modulate mutator phenotypes for therapy.

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

    Science.gov (United States)

    Satoh, T

    2015-12-01

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

  9. Evidence-Based Toxicology.

    Science.gov (United States)

    Hoffmann, Sebastian; Hartung, Thomas; Stephens, Martin

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

  10. Agenda of behavioral toxicology

    Energy Technology Data Exchange (ETDEWEB)

    Weiss, B

    1978-01-01

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

  11. Toxicological benchmarks for wildlife: 1996 Revision

    International Nuclear Information System (INIS)

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

    1996-06-01

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

  12. Toxicological benchmarks for wildlife: 1996 Revision

    Energy Technology Data Exchange (ETDEWEB)

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

    1996-06-01

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

  13. Proper interpretation of chronic toxicity studies and their statistics: A critique of "Which level of evidence does the US National Toxicology Program provide? Statistical considerations using the Technical Report 578 on Ginkgo biloba as an example".

    Science.gov (United States)

    Kissling, Grace E; Haseman, Joseph K; Zeiger, Errol

    2015-09-02

    A recent article by Gaus (2014) demonstrates a serious misunderstanding of the NTP's statistical analysis and interpretation of rodent carcinogenicity data as reported in Technical Report 578 (Ginkgo biloba) (NTP, 2013), as well as a failure to acknowledge the abundant literature on false positive rates in rodent carcinogenicity studies. The NTP reported Ginkgo biloba extract to be carcinogenic in mice and rats. Gaus claims that, in this study, 4800 statistical comparisons were possible, and that 209 of them were statistically significant (p<0.05) compared with 240 (4800×0.05) expected by chance alone; thus, the carcinogenicity of Ginkgo biloba extract cannot be definitively established. However, his assumptions and calculations are flawed since he incorrectly assumes that the NTP uses no correction for multiple comparisons, and that significance tests for discrete data operate at exactly the nominal level. He also misrepresents the NTP's decision making process, overstates the number of statistical comparisons made, and ignores the fact that the mouse liver tumor effects were so striking (e.g., p<0.0000000000001) that it is virtually impossible that they could be false positive outcomes. Gaus' conclusion that such obvious responses merely "generate a hypothesis" rather than demonstrate a real carcinogenic effect has no scientific credibility. Moreover, his claims regarding the high frequency of false positive outcomes in carcinogenicity studies are misleading because of his methodological misconceptions and errors. Published by Elsevier Ireland Ltd.

  14. NTP-CERHR EXPERT PANEL REPORT ON THE REPRODUCTIVE AND DEVELOPMENTAL TOXICITY OF AMPHETAMINE AND METHAMPHETAMINE.

    Science.gov (United States)

    A manuscript describes the results of an expert panel meeting of the NTP Center for the Evaluation of Risks to Human Reproduction (CERHR). The purpose CERHR is to provide timely, unbiased, scientifically sound evaluations of human and experimental evidence for adverse effects ...

  15. The NTP-binding motif in cowpea mosaic virus B polyprotein is essential for viral replication

    NARCIS (Netherlands)

    Peters, S A; Verver, J; Nollen, E A; van Lent, J W; Wellink, J; van Kammen, A

    1994-01-01

    We have assessed the functional importance of the NTP-binding motif (NTBM) in the cowpea mosaic virus (CPMV) B-RNA-encoded 58K domain by changing two conserved amino acids within the consensus A and B sites (GKSRTGK500S and MDD545, respectively). Both Lys-500 to Thr and Asp-545 to Pro substitutions

  16. The ntp operon encoding the Na+V-ATPase of the thermophile Caloramator fervidus

    NARCIS (Netherlands)

    Ubbink-Kok, Trees; Nijland, Jeroen; Slotboom, Dirk-Jan; Lolkema, Juke S.

    2006-01-01

    The V-type ATPase of the thermophile Caloramator fervidus is an ATP-driven Na+ pump. The nucleotide sequence of the ntpFIKECGABD operon containing the structural genes coding for the nine subunits of the enzyme complex was determined. The identity of the proteins in two pairs of subunits (D, E and

  17. Metabonomics and toxicology.

    Science.gov (United States)

    Zhao, Liang; Hartung, Thomas

    2015-01-01

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

  18. Downloadable Computational Toxicology Data

    Science.gov (United States)

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

  19. Occupational medicine and toxicology

    Directory of Open Access Journals (Sweden)

    Fischer Axel

    2006-02-01

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

  20. Progress in computational toxicology.

    Science.gov (United States)

    Ekins, Sean

    2014-01-01

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

  1. In silico toxicology protocols.

    Science.gov (United States)

    Myatt, Glenn J; Ahlberg, Ernst; Akahori, Yumi; Allen, David; Amberg, Alexander; Anger, Lennart T; Aptula, Aynur; Auerbach, Scott; Beilke, Lisa; Bellion, Phillip; Benigni, Romualdo; Bercu, Joel; Booth, Ewan D; Bower, Dave; Brigo, Alessandro; Burden, Natalie; Cammerer, Zoryana; Cronin, Mark T D; Cross, Kevin P; Custer, Laura; Dettwiler, Magdalena; Dobo, Krista; Ford, Kevin A; Fortin, Marie C; Gad-McDonald, Samantha E; Gellatly, Nichola; Gervais, Véronique; Glover, Kyle P; Glowienke, Susanne; Van Gompel, Jacky; Gutsell, Steve; Hardy, Barry; Harvey, James S; Hillegass, Jedd; Honma, Masamitsu; Hsieh, Jui-Hua; Hsu, Chia-Wen; Hughes, Kathy; Johnson, Candice; Jolly, Robert; Jones, David; Kemper, Ray; Kenyon, Michelle O; Kim, Marlene T; Kruhlak, Naomi L; Kulkarni, Sunil A; Kümmerer, Klaus; Leavitt, Penny; Majer, Bernhard; Masten, Scott; Miller, Scott; Moser, Janet; Mumtaz, Moiz; Muster, Wolfgang; Neilson, Louise; Oprea, Tudor I; Patlewicz, Grace; Paulino, Alexandre; Lo Piparo, Elena; Powley, Mark; Quigley, Donald P; Reddy, M Vijayaraj; Richarz, Andrea-Nicole; Ruiz, Patricia; Schilter, Benoit; Serafimova, Rositsa; Simpson, Wendy; Stavitskaya, Lidiya; Stidl, Reinhard; Suarez-Rodriguez, Diana; Szabo, David T; Teasdale, Andrew; Trejo-Martin, Alejandra; Valentin, Jean-Pierre; Vuorinen, Anna; Wall, Brian A; Watts, Pete; White, Angela T; Wichard, Joerg; Witt, Kristine L; Woolley, Adam; Woolley, David; Zwickl, Craig; Hasselgren, Catrin

    2018-04-17

    The present publication surveys several applications of in silico (i.e., computational) toxicology approaches across different industries and institutions. It highlights the need to develop standardized protocols when conducting toxicity-related predictions. This contribution articulates the information needed for protocols to support in silico predictions for major toxicological endpoints of concern (e.g., genetic toxicity, carcinogenicity, acute toxicity, reproductive toxicity, developmental toxicity) across several industries and regulatory bodies. Such novel in silico toxicology (IST) protocols, when fully developed and implemented, will ensure in silico toxicological assessments are performed and evaluated in a consistent, reproducible, and well-documented manner across industries and regulatory bodies to support wider uptake and acceptance of the approaches. The development of IST protocols is an initiative developed through a collaboration among an international consortium to reflect the state-of-the-art in in silico toxicology for hazard identification and characterization. A general outline for describing the development of such protocols is included and it is based on in silico predictions and/or available experimental data for a defined series of relevant toxicological effects or mechanisms. The publication presents a novel approach for determining the reliability of in silico predictions alongside experimental data. In addition, we discuss how to determine the level of confidence in the assessment based on the relevance and reliability of the information. Copyright © 2018. Published by Elsevier Inc.

  2. Aerospace Toxicology and Microbiology

    Science.gov (United States)

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

    2007-01-01

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

  3. ACToR - Aggregated Computational Toxicology Resource

    International Nuclear Information System (INIS)

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

    2008-01-01

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

  4. Non-Thermal Plasma (NTP) session overview: Second International Symposium on Environmental Applications of Advanced Oxidation Technologies (AOTs)

    International Nuclear Information System (INIS)

    Rosocha, L.A.

    1996-01-01

    Advanced Oxidation Technologies (used in pollution control and treating hazardous wastes) has expanded from using hydroxyl radicals to treat organic compounds in water, to using reductive free radicals as well, and to application to pollutants in both gases and aqueous media. Non-Thermal Plasma (NTP) is created in a gas by an electrical discharge or energetic electron injection. Highly reactive species (O atoms, OH, N radicals, plasma electrons) react with entrained hazardous organic chemicals in the gas, converting them to CO2, H2O, etc. NTP can be used to simultaneously remove different kinds of pollutants (eg, VOCs, SOx, NOx in flue gases). This paper presents an overview of NTP technology for pollution control and hazardous waste treatment; it is intended as an introduction to the NTP session of the symposium

  5. Animal-free toxicology

    DEFF Research Database (Denmark)

    Knudsen, Lisbeth E

    2013-01-01

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

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

    Science.gov (United States)

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

  7. IRIS Toxicological Review of Tetrahydrofuran (THF) (Final Report)

    Science.gov (United States)

    EPA has released the Toxicological Review of Tetrahydrofuran: 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.

  8. Shuttle Lesson Learned - Toxicology

    Science.gov (United States)

    James, John T.

    2010-01-01

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

  9. Design Evolutuion of Hot Isotatic Press Cans for NTP Cermet Fuel Fabrication

    Science.gov (United States)

    Mireles, O. R.; Broadway, J.; Hickman, R.

    2014-01-01

    Nuclear Thermal Propulsion (NTP) is under consideration for potential use in deep space exploration missions due to desirable performance properties such as a high specific impulse (> 850 seconds). Tungsten (W)-60vol%UO2 cermet fuel elements are under development, with efforts emphasizing fabrication, performance testing and process optimization to meet NTP service life requirements [1]. Fuel elements incorporate design features that provide redundant protection from crack initiation, crack propagation potentially resulting in hot hydrogen (H2) reduction of UO2 kernels. Fuel erosion and fission product retention barriers include W coated UO2 fuel kernels, W clad internal flow channels and fuel element external W clad resulting in a fully encapsulated fuel element design as shown.

  10. Multidisciplinary Simulation of Graphite-Composite and Cermet Fuel Elements for NTP Point of Departure Designs

    Science.gov (United States)

    Stewart, Mark E.; Schnitzler, Bruce G.

    2015-01-01

    This paper compares the expected performance of two Nuclear Thermal Propulsion fuel types. High fidelity, fluid/thermal/structural + neutronic simulations help predict the performance of graphite-composite and cermet fuel types from point of departure engine designs from the Nuclear Thermal Propulsion project. Materials and nuclear reactivity issues are reviewed for each fuel type. Thermal/structural simulations predict thermal stresses in the fuel and thermal expansion mis-match stresses in the coatings. Fluid/thermal/structural/neutronic simulations provide predictions for full fuel elements. Although NTP engines will utilize many existing chemical engine components and technologies, nuclear fuel elements are a less developed engine component and introduce design uncertainty. Consequently, these fuel element simulations provide important insights into NTP engine performance.

  11. The development of a server NTP for a primary stallion of time and frequency

    International Nuclear Information System (INIS)

    Abid, Bilel; Dridi, Chaima

    2008-01-01

    Given the recent developments of the measure atomic time, the CNSTN proposes to realize a project that is the first of its kind in our country; this project is to develop a service atomic time - to build an atomic clock. Our objective in this project is to achieve the final task, so we prepared the final step is the release time from an analog signal and the developed an NTP server for a standard primary time and frequency sample. (author)

  12. DEAR Monte Carlo simulation versus experimental data in measurements with the DEAR NTP setup

    International Nuclear Information System (INIS)

    Bragadireanu, A.M.; Iliescu, M.; Petrascu, C.; Ponta, T.

    1999-01-01

    The DEAR NTP setup was installed in DAΦNE and is taking background data since February 1999. The goal of this work is to compare the measurements, in terms of charged particle hits (clusters), with the DEAR Monte Carlo simulation, taking into account the main effects due to which the particles are lost from circulating beams: Touschek effect and beam-gas interaction. To be mentioned that, during this period, no collisions between electrons and positrons have been achieved in the DEAR Interaction Point (IP) and consequently we don't have any experimental data concerning the hadronic background coming from φ-decays directly, or as secondary products of hadronic interactions. The NTP setup was shielded using lead and copper which gives a shielding factor of about 4. In parallel with the NTP setup, the signals from two scintillator slabs (150 x 80 x 2 mm) collected by 4 PMTs, positioned bellow the NTP setup and facing the IP, were digitized and counted using a National Instruments Timer/Counter Card. To compare experimental data with results of the Monte Carlo simulation we selected periods with only one circulating beam (electrons or positrons), in order to have a clean data set and we selected data files with CCD occupancy lower than 5%. As concerning the X-rays, the statistics was too poor to perform any quantitative comparison. The comparison between Monte Carlo, CCD data and kaon monitor data, for two beams are shown. It can be seen the agreement is fairly good and promising along the way of checking our routines which describes the experimental setup and the physical processes occurring in the accelerator environment. (authors)

  13. Toxicología Vegetal

    OpenAIRE

    García Fernández, Antonio Juan

    2010-01-01

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

  14. Suppression of the E. coli SOS response by dNTP pool changes.

    Science.gov (United States)

    Maslowska, Katarzyna H; Makiela-Dzbenska, Karolina; Fijalkowska, Iwona J; Schaaper, Roel M

    2015-04-30

    The Escherichia coli SOS system is a well-established model for the cellular response to DNA damage. Control of SOS depends largely on the RecA protein. When RecA is activated by single-stranded DNA in the presence of a nucleotide triphosphate cofactor, it mediates cleavage of the LexA repressor, leading to expression of the 30(+)-member SOS regulon. RecA activation generally requires the introduction of DNA damage. However, certain recA mutants, like recA730, bypass this requirement and display constitutive SOS expression as well as a spontaneous (SOS) mutator effect. Presently, we investigated the possible interaction between SOS and the cellular deoxynucleoside triphosphate (dNTP) pools. We found that dNTP pool changes caused by deficiencies in the ndk or dcd genes, encoding nucleoside diphosphate kinase and dCTP deaminase, respectively, had a strongly suppressive effect on constitutive SOS expression in recA730 strains. The suppression of the recA730 mutator effect was alleviated in a lexA-deficient background. Overall, the findings suggest a model in which the dNTP alterations in the ndk and dcd strains interfere with the activation of RecA, thereby preventing LexA cleavage and SOS induction. Published by Oxford University Press on behalf of Nucleic Acids Research 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  15. Oxidation behaviours of particulate matter emitted by a diesel engine equipped with a NTP device

    International Nuclear Information System (INIS)

    Gao, Jianbing; Ma, Chaochen; Xing, Shikai; Sun, Liwei

    2017-01-01

    Highlights: • Final oxidation temperatures increased for PM aggregation compared with raw PM. • Devolatilized PM aggregation exhibited similar oxidation rate constants. • DSC-based method is more accurate than TGA-based method. - Abstract: To resolve the regeneration problem of non-thermal plasma (NTP) reactor, the oxidation behaviours of diesel particulate matter (PM) were investigated. Oxidation kinetic parameters were calculated using Flynn-Wall-Ozawa (FWO) and Friedman-Reich-Levi (FRL) methods based on thermal gravimetric analyzer (TGA) and differential scanning calorimetry (DSC) results. The DSC-based method avoided the disadvantages of TGA-based method, and the oxidation kinetic parameters calculated using the two methods were compared. The results showed that the effect of plasma on the oxidation behaviours differed greatly for PM sampled at engine loads. The TGA profiles of PM aggregation (collected on the collection plate of NTP reactor) sampled at 60% and 100% engine loads were similar although they differed significantly for raw PM. Devolatilization of raw PM led the TGA profiles to shift slightly to lower temperature, however, the TGA curves shifted to higher temperature for PM aggregation and PM treated with plasma (PM escaping from NTP reactor). The oxidation rate constants of devolatilized PM aggregation sampled at different engine loads were almost the same. DSC-based method revealed the oxidation behaviours and kinetic parameters with more accuracy than TGA-based method.

  16. Toxicological aspects of water

    International Nuclear Information System (INIS)

    Garcia Puertas, P.

    1991-01-01

    Different toxicological aspects of water have been studied, remarking the activity of various chemical substances in the organism. These substances are divided in: trace metals (Sb, As, Cd, Zn, Cu, Cr, Fe, Mn, Hg, Ni, Pb, Se), other contaminants (CN-, polycyclic aromatic hydrocarbons, phenols, pesticides, detergents) and radioactivity. Finally, some considerations on this subject are made [es

  17. Nuclear Engine System Simulation (NESS). Volume 1: Program user's guide. Final Report

    International Nuclear Information System (INIS)

    Pelaccio, D.G.; Scheil, C.M.; Petrosky, L.J.

    1993-03-01

    A Nuclear Thermal Propulsion (NTP) engine system design analysis tool is required to support current and future Space Exploration Initiative (SEI) propulsion and vehicle design studies. Currently available NTP engine design models are those developed during the NERVA program in the 1960's and early 1970's and are highly unique to that design or are modifications of current liquid propulsion system design models. To date, NTP engine-based liquid design models lack integrated design of key NTP engine design features in the areas of reactor, shielding, multi-propellant capability, and multi-redundant pump feed fuel systems. Additionally, since the SEI effort is in the initial development stage, a robust, verified NTP analysis design tool could be of great use to the community. This effort developed an NTP engine system design analysis program (tool), known as the Nuclear Engine System Simulation (NESS) program, to support ongoing and future engine system and stage design study efforts. In this effort, Science Applications International Corporation's (SAIC) NTP version of the Expanded Liquid Engine Simulation (ELES) program was modified extensively to include Westinghouse Electric Corporation's near-term solid-core reactor design model. The ELES program has extensive capability to conduct preliminary system design analysis of liquid rocket systems and vehicles. The program is modular in nature and is versatile in terms of modeling state-of-the-art component and system options as discussed. The Westinghouse reactor design model, which was integrated in the NESS program, is based on the near-term solid-core ENABLER NTP reactor design concept. This program is now capable of accurately modeling (characterizing) a complete near-term solid-core NTP engine system in great detail, for a number of design options, in an efficient manner

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

    Science.gov (United States)

    Chung, Heesun; Choe, Sanggil

    2017-01-01

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

  19. Veterinary Forensic Toxicology.

    Science.gov (United States)

    Gwaltney-Brant, S M

    2016-09-01

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

  20. Toxicology of inorganic tin

    International Nuclear Information System (INIS)

    Burba, J.V.

    1982-01-01

    Tin(II) or stannous ion as a reducing agent is important in nuclear medicine because it is an essential component and common denominator for many in vivo radiodiagnostic agents, commonly called kits for the preparation of radiopharmaceuticals. This report is intended to alert nuclear medicine community regarding the wide range of biological effects that the stannous ion is capable of producing, and is a review of a large number of selected publications on the toxicological potential of tin(II)

  1. Operational Toxicology Research

    Science.gov (United States)

    2006-08-01

    techniques for perchlorate in water, groundwater, soil and biological matrices such as blood, urine, milk . thyroid and other tissues required for...toxicity when they are inhaled or ingested and they are irritating to the skin and mucus membranes (Committee on Toxicology, 1996). When compared to...the data collected. Develop analytical techniques for perchlorate in water, groundwater, soil, and biological matrices such as blood, urine, milk

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

    Science.gov (United States)

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

  3. Toxicological Benchmarks for Wildlife

    Energy Technology Data Exchange (ETDEWEB)

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

    1993-01-01

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

  4. Summary introduction to environmental toxicology

    International Nuclear Information System (INIS)

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

    1986-01-01

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

  5. High Throughput Transcriptomics @ USEPA (Toxicology ...

    Science.gov (United States)

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

  6. [Reform of Japan's NTP and its technical perspectives].

    Science.gov (United States)

    Mori, Toru

    2004-10-01

    and a new diagnostic of TB infection using whole-blood interferon-gamma determination (QuantiFERON). The quality of clinical diagnosis and monitoring of treatment should also be improved by introducing an external quality assurance system of commercial laboratory services. 2. Chemoprophylaxis. Although not explicitly defined in the new legislation, the expansion and improvement of chemoprophylaxis to cover anyone with any risk of clinical development of TB would have a tremendous effect in Japan, especially since 90% of patients who developed TB were infected tens of years ago. These technical innovations in diagnosis of TB infection will be very helpful. Development of new drug regimens for the preventive treatment is also badly needed. 3. Immunization. Prior to the amendment of the Law, the BCG vaccination of students entering primary and junior high schools has been already abandoned. In order to encourage the early primary vaccination for infants, the new Law will adopt the direct vaccination scheme in which babies will be given the BCG vaccine without tuberculin testing. This program will be implemented safely, only if it is given to young babies, e.g., less than one year old, as defined by the decree. It is essential to maintain the high level of vaccination coverage under the new program. The autonomy may encounter difficulty mobilizing client babies shortly after their birth (only one year, as compared with the current four years). To avoid the possible, though very rare, adverse health effects due to the vaccination of infected babies, careful questioning should be conducted regarding the risk of exposure to infection prior to vaccination. A ready course of treatment and examinations for abnormal reactions after vaccination (Koch's phenomenon) is also warranted. 4. Treatment and patient care: The revised Law clearly states the governmental responsibility for treating TB patients in close cooperation with a doctor. This is an important legal basis for the

  7. Historical perspectives on cadmium toxicology

    International Nuclear Information System (INIS)

    Nordberg, Gunnar F.

    2009-01-01

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

  8. ACToR-AGGREGATED COMPUTATIONAL TOXICOLOGY ...

    Science.gov (United States)

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

  9. Postmortem Biochemistry and Toxicology

    Directory of Open Access Journals (Sweden)

    Robert Flanagan

    2017-04-01

    Full Text Available The aim of postmortem biochemistry and toxicology is either to help establish the cause of death, or to gain information on events immediately before death. If self-poisoning is suspected, the diagnosis may be straightforward and all that could be required is confirmation of the agents involved. However, if the cause of death is not immediately obvious then suspicion of possible poisoning or of conditions such as alcoholic ketoacidosis is of course crucial. On the other hand, it may be important to investigate adherence to prescribed therapy, for example with anticonvulsants or antipsychotics, hence sensitive methods are required. Blood sampling (needle aspiration, peripheral vein, for example femoral, ideally after proximal ligation before opening the body minimizes the risk of sample contamination with, for example, gut contents or urine. Other specimens (stomach contents, urine, liver, vitreous humor may also be valuable and may be needed to corroborate unexpected or unusual findings in the absence of other evidence. The site of sampling should always be recorded. The availability of antemortem specimens should not necessarily preclude postmortem sampling. Appropriate sample preservation, transport, and storage are mandatory. Interpretation of analytical toxicology results must take into account what is known of the pharmacokinetics and toxicology of the agent(s in question, the circumstances under which death occurred including the mechanism of exposure, and other factors such as the stability of the analyte(s and the analytical methods used. It is important to realise that changes may occur in the composition of body fluids, even peripheral blood, after death. Such changes are likely to be greater after attempted resuscitation, and with centrally-acting drugs with large volumes of distribution given chronically, and may perhaps be minimised by prompt refrigeration of the body and performing the autopsy quickly.

  10. Toxicology of freshwater cyanobacteria.

    Science.gov (United States)

    Liyanage, H M; Arachchi, D N Magana; Abeysekara, T; Guneratne, L

    2016-07-02

    Many chemical contaminants in drinking water have been shown to cause adverse health effects in humans after prolonged exposure. Cyanobacteria are one of the most potent and diverse groups of photosynthetic prokaryotes. One key component of cyanobacterial success in the environment is the production of potent toxins as secondary metabolites, which have been responsible for numerous adverse health impacts in humans. Anthropogenic activities have led to the increase of eutrophication in freshwater bodies' worldwide, causing cyanobacterial blooms to become more frequent. The present article will discuss about harmful cyanobacteria and their toxicology with special references to microcystin, nodularin, and cylindrospermopsin.

  11. Pharmacogenetics and forensic toxicology.

    Science.gov (United States)

    Musshoff, Frank; Stamer, Ulrike M; Madea, Burkhard

    2010-12-15

    Large inter-individual variability in drug response and toxicity, as well as in drug concentrations after application of the same dosage, can be of genetic, physiological, pathophysiological, or environmental origin. Absorption, distribution and metabolism of a drug and interactions with its target often are determined by genetic differences. Pharmacokinetic and pharmacodynamic variations can appear at the level of drug metabolizing enzymes (e.g., the cytochrome P450 system), drug transporters, drug targets or other biomarker genes. Pharmacogenetics or toxicogenetics can therefore be relevant in forensic toxicology. This review presents relevant aspects together with some examples from daily routines. Copyright © 2010. Published by Elsevier Ireland Ltd.

  12. Nuclear Thermal Propulsion (NTP): A Proven, Growth Technology for Fast Transit Human Missions to Mars

    Science.gov (United States)

    Borowski, Stanley K.; McCurdy, David R.; Packard, Thomas W.

    2014-01-01

    The "fast conjunction" long surface stay mission option was selected for NASA's recent Mars Design Reference Architecture (DRA) 5.0 study because it provided adequate time at Mars (approx. 540 days) for the crew to explore the planet's geological diversity while also reducing the "1-way" transit times to and from Mars to approx. 6 months. Short transit times are desirable in order to reduce the debilitating physiological effects on the human body that can result from prolonged exposure to the zero-gravity (0-gE) and radiation environments of space. Recent measurements from the RAD detector attached to the Curiosity rover indicate that astronauts would receive a radiation dose of approx. 0.66 Sv (approx. 66 rem)-the limiting value established by NASA-during their 1-year journey in deep space. Proven nuclear thermal rocket (NTR) technology, with its high thrust and high specific impulse (Isp approx. 900 s), can cut 1-way transit times by as much as 50 percent by increasing the propellant capacity of the Mars transfer vehicle (MTV). No large technology scale-ups in engine size are required for these short transit missions either since the smallest engine tested during the Rover program-the 25 klbf "Pewee" engine is sufficient when used in a clustered arrangement of three to four engines. The "Copernicus" crewed MTV developed for DRA 5.0 is a 0-gE design consisting of three basic components: (1) the NTP stage (NTPS); (2) the crewed payload element; and (3) an integrated "saddle truss" and LH2 propellant drop tank assembly that connects the two elements. With a propellant capacity of approx. 190 t, Copernicus can support 1-way transit times ranging from approx. 150 to 220 days over the 15-year synodic cycle. The paper examines the impact on vehicle design of decreasing transit times for the 2033 mission opportunity. With a fourth "upgraded" SLS/HLV launch, an "in-line" LH2 tank element can be added to Copernicus allowing 1-way transit times of 130 days. To achieve 100

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-09-01

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

  14. Coincidence of needs in radiological and toxicological protection

    International Nuclear Information System (INIS)

    Osborne, R.V.

    1988-01-01

    Research needs for radiological protection and research programs that have evolved to meet these needs parallel closely those in the chemical toxicology field. The similarity of these needs is described as perceived from the radiological side. Further, the frame work for radiologically-related research, out lines of the research programs, and the development of the facilities at Chalk River Nuclear Labs were presented

  15. In silico toxicology for the pharmaceutical sciences

    International Nuclear Information System (INIS)

    Valerio, Luis G.

    2009-01-01

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

  16. Emerging approaches in predictive toxicology.

    Science.gov (United States)

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

    2014-12-01

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

  17. Mass Spectrometry Applications for Toxicology.

    Science.gov (United States)

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

    2016-12-01

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

  18. Mass Spectrometry Applications for Toxicology

    Science.gov (United States)

    Mbughuni, Michael M.; Jannetto, Paul J.

    2016-01-01

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

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

    International Nuclear Information System (INIS)

    Rojas, M.

    2005-01-01

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

  20. Effect of cell phone radiofrequency radiation on body temperature in rodents: Pilot studies of the National Toxicology Program's reverberation chamber exposure system.

    Science.gov (United States)

    Wyde, Michael E; Horn, Thomas L; Capstick, Myles H; Ladbury, John M; Koepke, Galen; Wilson, Perry F; Kissling, Grace E; Stout, Matthew D; Kuster, Niels; Melnick, Ronald L; Gauger, James; Bucher, John R; McCormick, David L

    2018-04-01

    Radiofrequency radiation (RFR) causes heating, which can lead to detrimental biological effects. To characterize the effects of RFR exposure on body temperature in relation to animal size and pregnancy, a series of short-term toxicity studies was conducted in a unique RFR exposure system. Young and old B6C3F1 mice and young, old, and pregnant Harlan Sprague-Dawley rats were exposed to Global System for Mobile Communication (GSM) or Code Division Multiple Access (CDMA) RFR (rats = 900 MHz, mice = 1,900 MHz) at specific absorption rates (SARs) up to 12 W/kg for approximately 9 h a day for 5 days. In general, fewer and less severe increases in body temperature were observed in young than in older rats. SAR-dependent increases in subcutaneous body temperatures were observed at exposures ≥6 W/kg in both modulations. Exposures of  ≥10 W/kg GSM or CDMA RFR induced excessive increases in body temperature, leading to mortality. There was also a significant increase in the number of resorptions in pregnant rats at 12 W/kg GSM RFR. In mice, only sporadic increases in body temperature were observed regardless of sex or age when exposed to GSM or CDMA RFR up to 12 W/kg. These results identified SARs at which measurable RFR-mediated thermal effects occur, and were used in the selection of exposures for subsequent toxicology and carcinogenicity studies. Bioelectromagnetics. 39:190-199, 2018. © 2018 The Authors. Bioelectromagnetics Published by Wiley Periodicals, Inc. © 2018 The Authors. Bioelectromagnetics Published by Wiley Periodicals, Inc.

  1. COMPUTATIONAL TOXICOLOGY-WHERE IS THE DATA? ...

    Science.gov (United States)

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

  2. Ninth Triennial Toxicology Salary Survey.

    Science.gov (United States)

    Gad, Shayne Cox; Sullivan, Dexter Wayne

    2016-01-01

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

  3. Nails in Forensic Toxicology: An Update.

    Science.gov (United States)

    Solimini, Renata; Minutillo, Adele; Kyriakou, Chrystalla; Pichini, Simona; Pacifici, Roberta; Busardo, Francesco Paolo

    2017-01-01

    The analysis of nails as a keratinized matrix to detect drugs or illicit substances has been increasingly used in forensic and clinical toxicology as a complementary test, especially for the specific characteristics of stably accumulating substances for long periods of time. This allows a retrospective investigation of chronic drug abuse, monitoring continuous drug or pharmaceutical use, reveal in utero drug exposure or environmental exposures. We herein review the recent literature investigating drug incorporation mechanisms and drug detection in nails for forensic toxicological purposes. Mechanisms of drug incorporation have not yet been fully elucidated. However, some research has lately contributed to a better understanding of how substances are incorporated into nails, suggesting three potential mechanisms of drug incorporation: contamination from sweat, incorporation from nail bed and incorporation from germinal matrix. In addition, numerous methods dealing with the determination of drugs of abuse, medications and alcohol biomarkers in nails have been reported in studies over the years. The latter methods could find application in clinical and forensic toxicology. The studies herein reviewed point out how important it is to standardize and harmonize the methodologies (either pre-analytical or analytical) for nails analysis and the optimization of sampling as well as the development of proficiency testing programs and the determination of cut-off values. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

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

  6. A Comparison of Materials Issues for Cermet and Graphite-Based NTP Fuels

    Science.gov (United States)

    Stewart, Mark E.; Schnitzler, Bruce G.

    2013-01-01

    This paper compares material issues for cermet and graphite fuel elements. In particular, two issues in NTP fuel element performance are considered here: ductile to brittle transition in relation to crack propagation, and orificing individual coolant channels in fuel elements. Their relevance to fuel element performance is supported by considering material properties, experimental data, and results from multidisciplinary fluid/thermal/structural simulations. Ductile to brittle transition results in a fuel element region prone to brittle fracture under stress, while outside this region, stresses lead to deformation and resilience under stress. Poor coolant distribution between fuel element channels can increase stresses in certain channels. NERVA fuel element experimental results are consistent with this interpretation. An understanding of these mechanisms will help interpret fuel element testing results.

  7. Controlador para un Reloj GPS de Referencia en el Protocolo NTP

    Science.gov (United States)

    Hauscarriaga, F.; Bareilles, F. A.

    The synchronization between computers in a local network plays a very important role on enviroments similar to IAR. Calculations for exact time are needed before, during and after an observation. For this purpose the IAR's GNU/Linux Software Development Team implemented a driver inside NTP protocol (an internet standard for time synchronization of computers) for a GPS receiver acquired a few years ago by IAR, which did not have support in such protocol. Today our Institute has a stable and reliable time base synchronized to atomic clocks on board GPS Satellites according to computers's synchronization standard, offering precise time services to all scientific community and particularly to the University of La Plata. FULL TEXT IN SPANISH

  8. A novel dNTP-limited PCR and HRM assay to detect Williams-Beuren syndrome.

    Science.gov (United States)

    Zhang, Lichen; Zhang, Xiaoqing; You, Guoling; Yu, Yongguo; Fu, Qihua

    2018-06-01

    Williams-Beuren syndrome (WBS) is caused by a microdeletion of chromosome arm 7q11.23. A rapid and inexpensive genotyping method to detect microdeletion on 7q11.23 needs to be developed for the diagnosis of WBS. This study describes the development of a new type of molecular diagnosis method to detect microdeletion on 7q11.23 based upon high-resolution melting (HRM). Four genes on 7q11.23 were selected as the target genes for the deletion genotyping. dNTP-limited duplex PCR was used to amplify the reference gene, CFTR, and one of the four genes respectively on 7q11.23. An HRM assay was performed on the PCR products, and the height ratio of the negative derivative peaks between the target gene and reference gene was employed to analyze the copy number variation of the target region. A new genotyping method for detecting 7q11.23 deletion was developed based upon dNTP-limited PCR and HRM, which cost only 96 min. Samples from 15 WBS patients and 12 healthy individuals were genotyped by this method in a blinded fashion, and the sensitivity and specificity was 100% (95% CI, 0.80-1, and 95% CI, 0.75-1, respectively) which was proved by CytoScan HD array. The HRM assay we developed is an rapid, inexpensive, and highly accurate method for genotyping 7q11.23 deletion. It is potentially useful in the clinical diagnosis of WBS. Copyright © 2018 Elsevier B.V. All rights reserved.

  9. Silencing of the pollen-specific gene NTP303 and its family members in tobacco affects in vivo pollen tube growth and results in male sterile plants.

    Science.gov (United States)

    de Groot, Peter; Weterings, Koen; de Been, Mark; Wittink, Floyd; Hulzink, Raymond; Custers, Jan; van Herpen, Marinus; Wullems, George

    2004-07-01

    In seed plants, successful fertilization requires correct regulation of pollen tube growth. At germination and during growth, the pollen tube interacts with tissues from the pistil while the pollen tube extends via tip growth. Despite the fact that much research has been devoted to the mechanisms regulating pollen tube growth, many aspects are currently unknown. Previously, we have isolated a pollen-specific gene from tobacco--NTP303--that probably functions during pollen tube growth. NTP303 is part of a family of five members. Its expression is regulated both at the transcriptional and at the translational level. While NTP303 transcripts accumulate to high levels between early bi-cellular and mature pollen stages, NTP303 protein is hardly detectable until germination and pollen tube growth. In order to elucidate the role and function of NTP303 in the pollen tube, we studied the effect of NTP303 gene silencing on pollen function. Therefore, we have transformed tobacco plants with NTP303 co-suppression and anti-sense gene constructs. In these plants, the kanamycin resistance trait--which was linked to the NTP303-silencing gene--was not transmitted through the male gametophyte. This indicated that lowering the transcript level of NTP303 and/or its family members interferes with pollen function. Because we could not find a readily distinguishable phenotype in pollen from the hemizygous anti-sense and co-suppression plants, we rescued the defective pollen to produce doubled haploid plants that were homozygous for the NTP303 anti-sense gene. We found that in pollen from these plants the transcript levels of all NTP303 family members were reduced. Although pollen and pollen tubes from these plants appeared completely normal in vitro, the pollen tubes showed slower growth rates in vivo and arrested in the style before they reached the ovary, so that fertilization failed. These data demonstrate that NTP303 and its family members are essential for normal pollen tube growth

  10. American College of Medical Toxicology

    Science.gov (United States)

    ... Publications Journal of Medical Toxicology About ACMT About Us History of ACMT ACMT Fact Sheet Strategic Plan ACMT ... Policies IJMT JMT Editorial Board About ACMT About Us History of ACMT ACMT Fact Sheet Strategic Plan ACMT ...

  11. Aggregated Computational Toxicology Resource (ACTOR)

    Data.gov (United States)

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

  12. Predictive toxicology in drug safety

    National Research Council Canada - National Science Library

    Xu, Jinghai J; Urban, Laszlo

    2011-01-01

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

  13. Aggregated Computational Toxicology Online Resource

    Data.gov (United States)

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

  14. Toxicology of Biodiesel Combustion products

    Science.gov (United States)

    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. ...

  15. Mass Spectrometry Applications for Toxicology

    OpenAIRE

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

    2016-01-01

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

  16. Behavioral assays in environmental toxicology

    Energy Technology Data Exchange (ETDEWEB)

    Weiss, B.

    1979-01-01

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

  17. IRIS Toxicological Review of Dichloromethane (Methylene ...

    Science.gov (United States)

    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 document presents background information and justification for the Intergrated Risk Information System (IRIS) Summary of the hazard and dose-response assessment of dichloromethane. IRIS Summaries may include oral reference dose (RfD) and inhalation reference concentration (RfC) values for chronic and other exposure durations, and a carcinogencity assessment. Internet/NCEA web site

  18. Ethanol Forensic Toxicology.

    Science.gov (United States)

    Perry, Paul J; Doroudgar, Shadi; Van Dyke, Priscilla

    2017-12-01

    Ethanol abuse can lead to negative consequences that oftentimes result in criminal charges and civil lawsuits. When an individual is suspected of driving under the influence, law enforcement agents can determine the extent of intoxication by measuring the blood alcohol concentration (BAC) and performing a standardized field sobriety test. The BAC is dependent on rates of absorption, distribution, and elimination, which are influenced mostly by the dose of ethanol ingested and rate of consumption. Other factors contributing to BAC are gender, body mass and composition, food effects, type of alcohol, and chronic alcohol exposure. Because of individual variability in ethanol pharmacology and toxicology, careful extrapolation and interpretation of the BAC is needed, to justify an arrest and assignment of criminal liability. This review provides a summary of the pharmacokinetic properties of ethanol and the clinical effects of acute intoxication as they relate to common forensic questions. Concerns regarding the extrapolation of BAC and the implications of impaired memory caused by alcohol-induced blackouts are discussed. © 2017 American Academy of Psychiatry and the Law.

  19. [Toxicologic blood emergency screening].

    Science.gov (United States)

    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.

  20. Toxicology of plutonium

    International Nuclear Information System (INIS)

    Bair, W.J.

    1974-01-01

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

  1. Developmental status of bioassays in genetic toxicology: a report of Phase II of the US Environmental Protection Agency Gene-Tox program

    Energy Technology Data Exchange (ETDEWEB)

    Brusick, D; Auletta, A

    1985-01-01

    The Gene-Tox Program was structured around two phases of genetic test data evaluation. The first phase consisted of 36 Work Group reports, each evaluating the results and performance of a specific bioassay. The second phase consisted of a plan to summarize the information provided by the Work Groups. The Gene-Tox Coordinating Committee was to be responsible for Phase II, and several subgroups were assigned specific goals in implementing this analysis. This report deals with Goal I which is to identify the developmental status of the individual bioassays reviewed by the Gene-Tox Work Groups in the first phase of the Program. 5 references, 6 tables.

  2. Calculating the Na⁺ translocating V-ATPase catalytic site affinity for substrate binding by homology modeled NtpA monomer using molecular dynamics/free energy calculation.

    Science.gov (United States)

    Muhammed, Zahed; Arai, Satoshi; Saijo, Shinya; Yamato, Ichiro; Murata, Takeshi; Suenaga, Atsushi

    2012-07-01

    Vacuolar ATPase (V-ATPase) of Enterococcus hirae is composed of a soluble catalytic domain (V₁; NtpA₃-B₃-D-G) and an integral membrane domain (V₀; NtpI-K₁₀) connected by a central and two peripheral stalks (NtpC, NtpD-G and NtpE-F). Recently nucleotide binding of catalytic NtpA monomer has been reported (Arai et al.). In the present study, we calculated the nucleotide binding affinity of NtpA by molecular dynamics (MD) simulation/free energy calculation using MM-GBSA approach based on homology modeled structure of NtpA monomer docked with ATP analogue, adenosine 5'-[β, γ-imido] triphosphate (AMP-PNP). The calculated binding free energies showed qualitatively good agreement with experimental data. The calculation was cross-validated further by the rigorous method, thermodynamic integration (TI) simulation. Finally, the interaction between NtpA and nucleotides at the atomic level was investigated by the analyses of components of free energy and the optimized model structures obtained from MD simulations, suggesting that electrostatic contribution is responsible for the difference in nucleotide binding to NtpA monomer. This is the first observation and suggestion to explain the difference of nucleotide binding properties in V-ATPase NtpA subunit, and our method can be a valuable primary step to predict nucleotide binding affinity to other subunits (NtpAB, NtpA₃B₃) and to explore subunit interactions and eventually may help to understand energy transduction mechanism of E. hirae V-ATPase. Copyright © 2012 Elsevier Inc. All rights reserved.

  3. Cancer and Toxicology Section

    International Nuclear Information System (INIS)

    Anon.

    1980-01-01

    The Cancer and Toxicology Section is concerned with the investigation of the mechanisms by which chemicals, radiation, and viruses cause the changes broadly identified as cancer. In addition, the study of mechanisms has been extended to include the nontumorigenic effects of various agents associated with fossil energy and fuels. Research in molecular genetics of carcinogenesis focuses largely on the transposon properties of the genomes of retroviruses. The transposon structure of the DNA genomes of endogenous murine N-tropic and B-tropic type C retroviruses is being elucidated, and their chromosomal location mapped in hamster-mouse cell hybrids. A model of the mechanism of retrovirus induction by radiation and chemicals is being developed, and experiments have established that compounds such as hydroxyurea act as inducer. There is the possibility that transposition of sequences of this endogenous virus may be linked to leukemogenesis. Research in regulation of gene expression aims at defining in molecular terms the mechanisms determining expression of specific genes, how these are regulated by hormones, and the events responsible for dysfunction of gene expression in cancer. In corollary work, a library of cloned cDNAs specific for products of genes of special interest to regulation is being developed. Improvement of reversed-phase chromatography as a means of isolating bacterial plasmids and restriction fragments of DNA is underway. Newly developed techniques permit the isolation of supercoiled plasmid DNA directly from bacterial extracts. The technology has been developed recently for the photosynthetic growth of the chemo-autotrophic organism Rhodospirillum rubrum and the enzyme ribulosebisphosphate carboxylase has been produced in quantity

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

    Science.gov (United States)

    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.

  5. The Manufacture of W-UO2 Fuel Elements for NTP Using the Hot Isostatic Pressing Consolidation Process

    Science.gov (United States)

    Broadway, Jeramie; Hickman, Robert; Mireles, Omar

    2012-01-01

    NTP is attractive for space exploration because: (1) Higher Isp than traditional chemical rockets (2)Shorter trip times (3) Reduced propellant mass (4) Increased payload. Lack of qualified fuel material is a key risk (cost, schedule, and performance). Development of stable fuel form is a critical path, long lead activity. Goals of this project are: Mature CERMET and Graphite based fuel materials and Develop and demonstrate critical technologies and capabilities.

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

    Science.gov (United States)

    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

  7. Toxicology study of senna (CAS No. 8013-11-4) in C57BL/6NTAC Mice and toxicology and carcinogenesis study of senna in genetically modified C3B6.129F1/Tac-Trp53tm1Brd haploinsufficient mice (Feed Studies).

    Science.gov (United States)

    2012-04-01

    Senna is used as a stimulant laxative in the management of constipation resulting from opioid use or when treatment with bulking or osmotic agents has failed. Increased use of senna was expected due to the removal of the stimulant laxatives danthron and phenolphthalein from the market. Senna was nominated for study by the Center for Drug Evaluation and Research, United States Food and Drug Administration (FDA) due to the wide use of laxative preparations, positive genotoxicity in vitro for some senna components or metabolites, and unknown carcinogenic potential. Because a 2-year rat study was ongoing by the manufacturer, the FDA requested that the NTP conduct a senna study in the p53(+/-) mouse. In this study, the potential for carcinogenic effects of senna was studied in the C3B6.129F1/Tac-Trp53tm1Brd N12 haploinsufficient (heterozygous F1 p53(+/-)) mouse model as an ongoing goal of the NTP to develop and test model systems for toxicology and carcinogenesis studies, especially those that can provide mechanistic information relative to understanding an agents mode of action. C57BL/6NTac mice were exposed to senna in feed for 5 weeks; heterozygous F1 p53(+/-) mice were exposed to senna in feed for 40 weeks. Genetic toxicology studies were conducted in Salmonella typhimurium, Escherichia coli, and mouse peripheral blood erythrocytes.

  8. Toxicological aspects of energy production

    International Nuclear Information System (INIS)

    Sanders, C.L.

    1986-01-01

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

  9. 2007 TOXICOLOGY AND RISK ASSESSMENT ...

    Science.gov (United States)

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

  10. Developmental and Reproductive Toxicology Database (DART)

    Data.gov (United States)

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

  11. IRIS Toxicological Review of Acrolein (2003 Final)

    Science.gov (United States)

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

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

    Science.gov (United States)

    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...

  13. 78 FR 77687 - Science Advisory Board to the National Center for Toxicological Research; Notice of Meeting

    Science.gov (United States)

    2013-12-24

    ... year. The SAB will be presented with an overview of the Division of Microbiology Subcommittee and the... National Toxicology Program of the National Institutes of Environmental Health Sciences on current and...

  14. Effect of NTP technology levels on engine sizing for a 2005 piloted Mars mission

    Science.gov (United States)

    Burr, Annette D.; Cross, Elden H.; Widman, Frederick W.; North, D. Michael

    1993-01-01

    Previous vehicle mass studies were performed for Mars launch windows in the 2010-2018 time frame. Within the last year, a study was performed to determine the effects of various Nuclear Thermal Propulsion (NTP) engine and mission parameters on Initial Mass in Low Earth Orbit (MLEO) for a piloted Mars mission during the 2005 opportunity. Particle Bed Reactor (PBR) and Enabler-type reactors were compared. Parameters evaluated included engine thrust, number of engines, number of Trans-Mars Injection (TMI) burns, engine thrust/weight, engine out capability, engine burn time, and Isp. Earth and Mars departure dates and outbound and return travel times were optimized for a 240-day total interplanetary transfer time (long-duration stay mission). Parameters which were seen to reduce IMLEO included a greater number of perigee burns, multiple engines, and higher Isp. Optimum engine thrust varied substantially depending on the configuration. Engine models developed jointly by Rocketdyne and Westinghouse within the last year formed the basis for the Enabler thrust optimization study.

  15. Effect of catalyst for the decomposition of VOCs in a NTP reactor

    International Nuclear Information System (INIS)

    Mohanty, Suchitra; Das, Smrutiprava; Paikaray, Rita; Sahoo, Gourishankar; Samantaray, Subrata

    2015-01-01

    Air pollution has become a major cause of human distress both directly and indirectly. VOCs are becoming the major air pollutants. So the decomposition of VOCs is present need of our society. Non-thermal plasma reactor (NTP) is proven to be effective for low concentration VOCs decomposition. For safe and effective application of DBD, optimization of treatment process requires different plasma parameter characterization. So electron temperature and electron density parameters of VOCs show the decomposition path ways. In this piece of work by taking the emission spectra and comparing the line intensity ratios, the electron temperature and density were determined. Also the decomposition rate in terms of the deposited products on the dielectric surface was studied. Decomposition rate increases in presence of catalyst as compared to the pure compound in presence of a carrier gas. Decomposition process was studied by UV-VIS, FTIR, OES Spectroscopic methods and by GCMS. Deposited products are analyzed by UV-VIS and FTIR spectroscopy. Plasma parameters like electron temperature, density are studied with OES. And gaseous products are studied by GCMS showing the peaks for the by products. (author)

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

    Science.gov (United States)

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

    2015-01-01

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

  17. 42 CFR 493.1213 - Condition: Toxicology.

    Science.gov (United States)

    2010-10-01

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

  18. Collaborative development of predictive toxicology applications.

    Science.gov (United States)

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

    2010-08-31

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

  19. Collaborative development of predictive toxicology applications

    Directory of Open Access Journals (Sweden)

    Hardy Barry

    2010-08-01

    Full Text Available Abstract 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

  20. Pulmonary toxicology of respirable particles

    International Nuclear Information System (INIS)

    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 that deal will radioactive particles. The last paper (Stannard) in the proceedings is an historical review of the field of inhalation toxicology and is not included in the analytics

  1. Surprises and omissions in toxicology

    Czech Academy of Sciences Publication Activity Database

    Rašková, H.; Zídek, Zdeněk

    2004-01-01

    Roč. 12, - (2004), S94-S96 ISSN 1210-7778. [Inderdisciplinary Czech-Slovak Toxicological Conference /8./. Praha, 03.09.2004-05.09.2004] Institutional research plan: CEZ:AV0Z5008914 Keywords : bacterial toxins Subject RIV: FR - Pharmacology ; Medidal Chemistry

  2. Regulatory issues in accreditation of toxicology laboratories.

    Science.gov (United States)

    Bissell, Michael G

    2012-09-01

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

  3. Functional dissection of the promoter of the pollen-specific gene NTP303 reveals a novel pollen-specific, and conserved cis-regulatory element.

    Science.gov (United States)

    Weterings, K; Schrauwen, J; Wullems, G; Twell, D

    1995-07-01

    Regulatory elements within the promoter of the pollen-specific NTP303 gene from tobacco were analysed by transient and stable expression analyses. Analysis of precisely targeted mutations showed that the NTP303 promoter is not regulated by any of the previously described pollen-specific cis-regulatory elements. However, two adjacent regions from -103 to -86 bp and from -86 to -59 bp were shown to contain sequences which positively regulated the NTP303 promoter. Both of these regions were capable of driving pollen-specific expression from a heterologous promoter, independent of orientation and in an additive manner. The boundaries of the minimal, functional NTP303 promoter were determined to lie within the region -86 to -51 bp. The sequence AAATGA localized from -94 to -89 bp was identified as a novel cis-acting element, of which the TGA triplet was shown to comprise an active part. This element was shown to be completely conserved in the similarly regulated promoter of the Bp 10 gene from Brassica napus encoding a homologue of the NTP303 gene.

  4. Systematic Review: Concept and Tool Development with Application in the Integrated Risk Information System (IRIS) Assessment Process

    Science.gov (United States)

    Systematic Review: Concept and tool development with application to the National Toxicology Program (NTP) and the Integrated Risk Information System (IRIS) Assessment Processes. There is growing interest within the environmental health community to incorporate systematic review m...

  5. Aristolochic Acids

    Science.gov (United States)

    ... a full list, see the FDA website at https: / / go. usa. gov/ xN66S. Contact the manufacturer or ... I go for more information? National Toxicology Program https: / / ntp. niehs. nih. gov/ go/ roc The Report ...

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

    Science.gov (United States)

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

    2017-08-01

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

  7. Modified Proofreading PCR for Detection of Point Mutations, Insertions and Deletions Using a ddNTP-Blocked Primer

    Science.gov (United States)

    Chen, Qianqian; Chen, Xiaoxiang; Zhang, Sichao; Lan, Ke; Lu, Jian; Zhang, Chiyu

    2015-01-01

    The development of simple, accurate, rapid and cost-effective technologies for mutation detection is crucial to the early diagnosis and prevention of numerous genetic diseases, pharmacogenetics, and drug resistance. Proofreading PCR (PR-PCR) was developed for mutation detection in 1998 but is rarely applied due to its low efficiency in allele discrimination. Here we developed a modified PR-PCR method using a ddNTP-blocked primer and a mixture of DNA polymerases with and without the 3'-5' proofreading function. The ddNTP-blocked primer exhibited the best blocking efficiency to avoid nonspecific primer extension while the mixture of a tiny amount of high-fidelity DNA polymerase with a routine amount of Taq DNA polymerase provided the best discrimination and amplification effects. The modified PR-PCR method is quite capable of detecting various mutation types, including point mutations and insertions/deletions (indels), and allows discrimination amplification when the mismatch is located within the last eight nucleotides from the 3'-end of the ddNTP-blocked primer. The modified PR-PCR has a sensitivity of 1-5 × 102 copies and a selectivity of 5 × 10-5 mutant among 107 copies of wild-type DNA. It showed a 100% accuracy rate in the detection of P72R germ-line mutation in the TP53 gene among 60 clinical blood samples, and a high potential to detect rifampin-resistant mutations at low frequency in Mycobacterium tuberculosis using an adaptor and a fusion-blocked primer. These results suggest that the modified PR-PCR technique is effective in detection of various mutations or polymorphisms as a simple, sensitive and promising approach. PMID:25915410

  8. Production and world-wide distribution of radioisotopes and allied products from NTP at Pelindaba, South Africa

    International Nuclear Information System (INIS)

    Louw, P.A.

    2001-01-01

    Nuclear Technology Products (NTP) a business division of the South African Nuclear Energy Corporation Ltd. (NECSA) is today a leading supplier of a range or radioisotope and supporting products to markets throughout the world. To achieve this status in the face of large technological, logistical and business barriers to entry has required the development of integrated and effective processes from a diverse and unconsolidated range of expertise and other resources. The various facilities and competencies established at NECSA over a period of 40 years had as their objective the accomplishment of strictly non-commercial strategic imperatives. Major emphasis was placed at Pelindaba on development of the capability to beneficiate the country's resources of uranium which are extracted as a by-product of gold mining. Fuel enrichment processes (using a method unique to NECSA) and nuclear fuel fabrication facilities were developed and commissioned during the period 1975 - 1990 and substantial quantities of enriched and depleted uranium material was produced. A small amount of locally produced, highly enriched fuel has been used to power the 20 MW SARARI -1 Research Reactor at Pelindaba which has been in operation since 1965. Major political and economic changes affecting South Africa gave rise, in the late 1980s, to the necessity for a fundamental strategic reorientation of NECSA. Over a period of time the fuel enrichment and fabrication programmes were terminated and ever greater emphasis was placed on development of businesses from established, diverse facilities and competencies with the objective of promoting increased financial independence and long term viability for the organisation. It was at this time that NTP the business responsible for production and marketing of radiation-based products at NECSA, was established. The various developments which facilitated the capacity of NTP to accede to its current position as a significant and growing provider of

  9. Studies on the immobilization of simulated HLW in NaTi2(PO4)3 (NTP) matrix

    International Nuclear Information System (INIS)

    Raja Madhavan, R.; Govindan Kutty, K.V.; Gandhi, A.S.

    2015-01-01

    Immobilization of high level nuclear waste (HLW) is a big challenge faced by the nuclear industry today. The HLW has to be contained and isolated from the biosphere for geological timescales. NZP family of compounds is very versatile monophasic hosts for HLW immobilization. Their crystal structure can accommodate nearly all the cations known to be present in HLW due to its open structure with voids of different size. In the present study a systematic investigation on NaTi 2 (PO 4 ) 3 belonging to the NZP family; as a potential host for HLW immobilization was carried out. A simulated HLW expected from Fast Breeder Test Reactor, India (FBTR) (150Gwd/T burnup, 1 year cooling) was used. Simulated NTP waste forms with 5, 10, 15 wt. % waste loading were prepared by employing a wet chemical method and characterized. Single phase simulated NTP waste forms with up to 5 wt.% waste loading could be prepared for samples sintered in air and above 5 wt.% waste loading, monazite phase is observed as a minor secondary phase. It was found that when sintering is done in Ar/10%H 2 , NTP matrix accepts up to 10 wt.% waste loading without formation of any second phase. From the SEM studies, it was observed that samples sintered in air as well as Ar/10%H 2 palladium segregated as a metal phase and uniformly distributed throughout the waste matrix. The elemental mapping revealed retention of some of the fission products like Ru, Mo, Cs that are volatile during sintering above 1173 K and are homogenously distributed in the matrix. (author)

  10. Toxicological effects of Kuwaiti oil fires

    Energy Technology Data Exchange (ETDEWEB)

    Engi, D.; Boozer, D.D.; Church, H.W.; Einfeld, W.; Gotway, C.A.; Spencer, F.W.; Zak, B.D. [Sandia National Labs., Albuquerque, NM (United States); Moore, P.W. [Tech. Reps., Inc., Albuquerque, NM (United States)

    1992-06-01

    The possibility of long-term smoke emissions (from 1 to 3 years) from burning Kuwaiti oil wells has increased concerns regarding personnel exposure and acute and chronic health effects. This document, which is the result of work done in the spring of 1991, addresses those concerns. Part 1 of this document describes follow-on efforts to the pre-war modeling studies of the toxicological hazards to exposed Kuwaiti populations. Part 2 describes a pollutant monitoring program that could be carried out in the summer of 1991 to measure real-time exposure levels and to obtain more detailed information about the pollutant source terms and meteorological conditions that are necessary inputs to model computations.

  11. Safety and Toxicology of Cannabinoids

    OpenAIRE

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

    2015-01-01

    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...

  12. 21 CFR 862.3200 - Clinical toxicology calibrator.

    Science.gov (United States)

    2010-04-01

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

  13. Postmortem aviation forensic toxicology: an overview.

    Science.gov (United States)

    Chaturvedi, Arvind K

    2010-05-01

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

  14. Pyrrolizidine Alkaloids: Chemistry, Pharmacology, Toxicology and Food Safety.

    Science.gov (United States)

    Moreira, Rute; Pereira, David M; Valentão, Patrícia; Andrade, Paula B

    2018-06-05

    Pyrrolizidine alkaloids (PA) are widely distributed in plants throughout the world, frequently in species relevant for human consumption. Apart from the toxicity that these molecules can cause in humans and livestock, PA are also known for their wide range of pharmacological properties, which can be exploited in drug discovery programs. In this work we review the current body of knowledge regarding the chemistry, toxicology, pharmacology and food safety of PA.

  15. Toxicological Analysis of Some Drugs of Abuse in Biological Samples

    OpenAIRE

    Anne Marie Ciobanu; Daniela Baconi; Cristian Bălălău; Carolina Negrei; Miriana Stan; Maria Bârcă

    2015-01-01

    Consumption of drugs of abuse is a scourge of modern world. Abuse, drug addiction and their consequences are one of the major current problems of European society because of the significant repercussions in individual, family, social and economic level. In this context, toxicological analysis of the drugs of abuse in biological samples is a useful tool for: diagnosis of drug addiction, checking an auto-response, mandatory screening in some treatment programs, identification of a substance ...

  16. Safety and Toxicology of Cannabinoids.

    Science.gov (United States)

    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.

  17. Delivering an Informational Hub for Data at the National Center for Computational Toxicology (ACS Spring Meeting) 7 of 7

    Science.gov (United States)

    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...

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

    Science.gov (United States)

    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...

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

    Science.gov (United States)

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

  20. The Emergence of Systematic Review in Toxicology.

    Science.gov (United States)

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

    2016-07-01

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

  1. 42 CFR 493.845 - Standard; Toxicology.

    Science.gov (United States)

    2010-10-01

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

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

    Science.gov (United States)

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

  3. A security analysis of version 2 of the Network Time Protocol (NTP): A report to the privacy and security research group

    Science.gov (United States)

    Bishop, Matt

    1991-01-01

    The Network Time Protocol is being used throughout the Internet to provide an accurate time service. The security requirements are examined of such a service, version 2 of the NTP protocol is analyzed to determine how well it meets these requirements, and improvements are suggested where appropriate.

  4. BROMOETHANE, CHLOROETHANE AND ETHYLENE OXIDE INDUCED UTERINE NEOPLASMS IN B6C3F1 MICE FROM 2-YEAR NTP INHALATION BIOASSAYS: PATHOLOGY AND INCIDENCE DATA REVISITED

    Science.gov (United States)

    SUMMARY: Chloroethane, bromoethane and etjulene oxide represent a unique set of three chemicals that induce endometrial neoplasms in the uterus of B6C3F1 mice following an inhalation route of exposure. The results of the NTP's chronic bioassays with these three compounds resu...

  5. Effect of Eimeria acervulina infection on cell-specific xanthine oxidase (XO) and inducible NO synthase (iNOS) activities and duodenal protein tyrosine nitration (NTp) in chickens

    Science.gov (United States)

    Intracellular generation of nitric oxide (NO) and superoxide anion (O¯2) during pro-inflammatory stress can result in the formation of 3'-nitrotyrosine proteins (NTp) that correlate with alteration in protein function and metabolic impairment. Our objective was to determine the cell-specific relati...

  6. Blood transcriptomics: applications in toxicology

    Science.gov (United States)

    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

  7. Evolution of toxicology information systems

    Energy Technology Data Exchange (ETDEWEB)

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

    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.

  8. Mind the Gap! A Journey towards Computational Toxicology.

    Science.gov (United States)

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

    2016-09-01

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

  9. Toxicological Analysis of Some Drugs of Abuse in Biological Samples

    Directory of Open Access Journals (Sweden)

    Anne Marie Ciobanu

    2015-10-01

    Full Text Available Consumption of drugs of abuse is a scourge of modern world. Abuse, drug addiction and their consequences are one of the major current problems of European society because of the significant repercussions in individual, family, social and economic level. In this context, toxicological analysis of the drugs of abuse in biological samples is a useful tool for: diagnosis of drug addiction, checking an auto-response, mandatory screening in some treatment programs, identification of a substance in the case of an overdose, determining compliance of the treatment. The present paper aims to address the needs of healthcare professionals involved in drugs addiction treatment through systematic presentation of information regarding their toxicological analysis. Basically, it is a tool that help you to select the suitable biological sample and the right collecting time, as well as the proper analysis technique, depending on the purpose of analysis, pharmacokinetic characteristics of the drugs of abuse, available equipment and staff expertise.

  10. Proceedings of the workshop on research needs in toxicology

    International Nuclear Information System (INIS)

    Myers, D.K.; Osborne, R.V.

    1988-05-01

    A workshop on the theme 'Research Needs in Toxicology' was held at the Chalk River laboratories in November 1987. A program in toxicological protection aims to develop a fundamental and unified understanding of the behaviour of toxic agents in the environment and workplace, and of the consequent effects on human health. This understanding is necessary so that risks from such agents can be assessed quantitatively and realistically. These assessments, together with consideration of economic and social factors, provide a sound basis for decisions made to safeguard health. Where are the gaps in our current knowledge and ability to make such assessments? What research is needed? In these workshop proceedings, a number of eminent toxicologists from Canada and the U.S.A. discuss these questions

  11. Toxicological profile for thorium. Draft report (Final)

    International Nuclear Information System (INIS)

    1990-10-01

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

  12. Toxicological profile for uranium. Final report

    International Nuclear Information System (INIS)

    1990-12-01

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

  13. Toxicological profile for radon. Final report

    International Nuclear Information System (INIS)

    1990-12-01

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

  14. Toxicological profile for plutonium. Final report

    International Nuclear Information System (INIS)

    1990-12-01

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

  15. Toxicological profile for radium. Final report

    International Nuclear Information System (INIS)

    1990-12-01

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

  16. Toxicology

    Science.gov (United States)

    Macewen, J. W.

    1973-01-01

    Oxygen toxicity is examined, including the effects of oxygen partial pressure variations on toxicity and oxygen effects on ozone and nitrogen dioxide toxicity. Toxicity of fuels and oxidizers, such as hydrazines, are reported. Carbon monoxide, spacecraft threshold limit values, emergency exposure limits, spacecraft contaminants, and water quality standards for space missions are briefly summarized.

  17. Early detection and monitoring of cartilage alteration in the experimental meniscectomised guinea pig model of osteoarthritis by 99mTc-NTP 15-5 scintigraphy

    International Nuclear Information System (INIS)

    Miot-Noirault, Elisabeth; Vidal, Aurelien; Bonafous, Jacques; Audin, Laurent; Madelmont, Jean-Claude; Moins, Nicole; Pastoureau, Philippe; Chomel, Agnes; Sarry, Laurent

    2007-01-01

    This study in the meniscectomised guinea pig aimed to demonstrate that the radiotracer 99m Tc-NTP 15-5 would have pathophysiological validity for in vivo osteoarthritis imaging. The specificity of 99m Tc-NTP 15-5 for cartilage was determined in healthy animals (n = 13), by tissue radioactivity counting, joint autoradiography and scintigraphy. 99m Tc-NTP 15-5 scintigraphy was performed at 20, 50, 80, 115, 130, 150 and 180 days after medial meniscectomy (n = 10 MNX) or sham operation (n = 5), and scintigraphic ratios (operated/contralateral) were calculated for femoral (F) and tibial (T) areas. F and T ratios were compared with those of 99m Tc-MDP bone scintigraphy. At the study end-point, autoradiographic analysis of joint 99m Tc-NTP 15-5 distribution and macroscopic scoring of cartilage integrity were performed. The high and specific accumulation of 99m Tc-NTP 15-5 in normal cartilage (about 5.5 ± 1.7 % of injected dose/g of tissue), which permitted joint imaging with high contrast, was affected by osteoarthritis. In the MNX group, 99m Tc-NTP 15-5 accumulation in cartilage within the operated joint, relative to the contralateral joint, was observed to change in the same animals as pathology progressed. Although F and T ratios were significantly higher in MNX (F = 1.7 ± 0.2; T = 1.6 ± 0.1) than in shams (F = 1.0 ± 0.1; T = 1.0 ± 0.1) at day 50, they were significantly lower in MNX (F = 0.6 ± 0.1; T = 0.7 ± 0.1) than in shams (F = 1.0 ± 0.1; T = 0.9 ± 0.1) at day 180. No change in 99m Tc-MDP uptake was observed over 6 months. Macroscopic analysis confirmed features of osteoarthritis only in MNX knees. These results in MNX guinea pigs provide additional support for the use of 99m Tc-NTP 15-5 for in vivo imaging of osteoarthritis. (orig.)

  18. Early detection and monitoring of cartilage alteration in the experimental meniscectomised guinea pig model of osteoarthritis by {sup 99m}Tc-NTP 15-5 scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Miot-Noirault, Elisabeth; Vidal, Aurelien; Bonafous, Jacques; Audin, Laurent; Madelmont, Jean-Claude; Moins, Nicole [UMR 484 INSERM, Rue Montalembert, BP 184, Clermont-Ferrand Cedex (France); Pastoureau, Philippe; Chomel, Agnes [Institut de Recherches Servier, Suresnes (France); Sarry, Laurent [ERI 14 INSERM - Faculte de Medecine, Clermont-Ferrand (France)

    2007-08-15

    This study in the meniscectomised guinea pig aimed to demonstrate that the radiotracer {sup 99m}Tc-NTP 15-5 would have pathophysiological validity for in vivo osteoarthritis imaging. The specificity of {sup 99m}Tc-NTP 15-5 for cartilage was determined in healthy animals (n = 13), by tissue radioactivity counting, joint autoradiography and scintigraphy. {sup 99m}Tc-NTP 15-5 scintigraphy was performed at 20, 50, 80, 115, 130, 150 and 180 days after medial meniscectomy (n = 10 MNX) or sham operation (n = 5), and scintigraphic ratios (operated/contralateral) were calculated for femoral (F) and tibial (T) areas. F and T ratios were compared with those of {sup 99m}Tc-MDP bone scintigraphy. At the study end-point, autoradiographic analysis of joint {sup 99m}Tc-NTP 15-5 distribution and macroscopic scoring of cartilage integrity were performed. The high and specific accumulation of {sup 99m}Tc-NTP 15-5 in normal cartilage (about 5.5 {+-} 1.7 % of injected dose/g of tissue), which permitted joint imaging with high contrast, was affected by osteoarthritis. In the MNX group, {sup 99m}Tc-NTP 15-5 accumulation in cartilage within the operated joint, relative to the contralateral joint, was observed to change in the same animals as pathology progressed. Although F and T ratios were significantly higher in MNX (F = 1.7 {+-} 0.2; T = 1.6 {+-} 0.1) than in shams (F = 1.0 {+-} 0.1; T = 1.0 {+-} 0.1) at day 50, they were significantly lower in MNX (F = 0.6 {+-} 0.1; T = 0.7 {+-} 0.1) than in shams (F = 1.0 {+-} 0.1; T = 0.9 {+-} 0.1) at day 180. No change in {sup 99m}Tc-MDP uptake was observed over 6 months. Macroscopic analysis confirmed features of osteoarthritis only in MNX knees. These results in MNX guinea pigs provide additional support for the use of {sup 99m}Tc-NTP 15-5 for in vivo imaging of osteoarthritis. (orig.)

  19. Investigation of independence in inter-animal tumor-type occurrences within the NTP rodent-bioassay database

    Energy Technology Data Exchange (ETDEWEB)

    Bogen, K.T. [Lawrence Livermore National Lab., CA (United States); Seilkop, S. [Analytical Sciences, Inc., Durham, NC (United States)

    1993-05-01

    Statistically significant elevation in tumor incidence at multiple histologically distinct sites is occasionally observed among rodent bioassays of chemically induced carcinogenesis. If such data are to be relied on (as they have, e.g., by the US EPA) for quantitative cancer potency assessment, their proper analysis requires a knowledge of the extent to which multiple tumor-type occurrences are independent or uncorrelated within individual bioassay animals. Although difficult to assess in a statistically rigorous fashion, a few significant associations among tumor-type occurrences in rodent bioassays have been reported. However, no comprehensive studies of animal-specific tumor-type occurrences at death or sacrifice have been conducted using the extensive set of available NTP rodent-bioassay data, on which most cancer-potency assessment for environmental chemicals is currently based. This report presents the results of such an analysis conducted on behalf of the National Research Council`s Committee on Risk Assessment for Hazardous Air Pollutants. Tumor-type associations among individual animals were examined for {approximately}2500 to 3000 control and {approximately}200 to 600 treated animals using pathology data from 62 B6C3F1 mouse studies and 61 F/344N rat studies obtained from a readily available subset of the NTP carcinogenesis bioassay database. No evidence was found for any large correlation in either the onset probability or the prevalence-at-death or sacrifice of any tumor-type pair investigated in control and treated rats and niece, although a few of the small correlations present were statistically significant. Tumor-type occurrences were in most cases nearly independent, and departures from independence, where they did occur, were small. This finding is qualified in that tumor-type onset correlations were measured only indirectly, given the limited nature of the data analyzed.

  20. Method Development in Forensic Toxicology.

    Science.gov (United States)

    Peters, Frank T; Wissenbach, Dirk K; Busardo, Francesco Paolo; Marchei, Emilia; Pichini, Simona

    2017-01-01

    In the field of forensic toxicology, the quality of analytical methods is of great importance to ensure the reliability of results and to avoid unjustified legal consequences. A key to high quality analytical methods is a thorough method development. The presented article will provide an overview on the process of developing methods for forensic applications. This includes the definition of the method's purpose (e.g. qualitative vs quantitative) and the analytes to be included, choosing an appropriate sample matrix, setting up separation and detection systems as well as establishing a versatile sample preparation. Method development is concluded by an optimization process after which the new method is subject to method validation. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  1. Testing of Binders Toxicological Effects

    Science.gov (United States)

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

    2017-11-01

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

  2. Predictive toxicology: the paths of the future

    International Nuclear Information System (INIS)

    Detilleux, Ph.; Vallier, L.; Legallais, C.; Leclerc, E.; Prot, J.M.; Choucha, L.; Baudoin, R.; Dufresne, M.; Gautier, A.; Carpentier, B.; Mansuy, D.; Pery, A.; Brochot, C.; Manivet, Ph.; Rabilloud, Th.; Spire, C.; Coumoul, X.; Junot, Ch.; Laprevote, O.; Le pape, A.; Le Guevel, R.; Tourneur, E.; Ben Mkaddem, S.; Chassin, C.; Aloulou, M.; Goujon, J.M.; Hertif, A.; Ouali, N.; Vimont, S.; Monteiro, R.; Rondeau, E.; Elbim, C.; Werts, C.; Vandewalle, A.; Ben Mkaddem, S.; Pedruzzi, E.; Coant, N.; Bens, M.; Cluzeaud, F.; Ogier-Denis, E.; Pongnimitprasert, N.; Babin-Chevaye, C.; Fay, M.; Bernard, M.; Dupuy, C.; Ei Benna, J.; Gougerot-Pocidale, M.A.; Braut-Boucher, F.; Pinton, Ph.; Lucioli, J.; Tsybulskyy, D.; Joly, B.; Laffitte, J.; Bourges-Abella, N.; Oswald, I.P.; Kolf-Clauw, M.; Pierre, St.; Bats, A.S.; Chevallier, A.; Bui, L.Ch.; Ambolet-Camoit, A.; Garlatti, M.; Aggerbeck, M.; Barouki, R.; Al Khansa, I.; Blanck, O.; Guillouzo, A.; Bars, R.; Rouas, C.; Bensoussan, H.; Suhard, D.; Tessier, C.; Grandcolas, L.; Pallardy, M.; Gueguen, Y.; Sparfel, L.; Pinel-Marie, M.L.; Boize, M.; Koscielny, S.; Desmots, S.; Pery, A.; Fardel, O.; Alvergnas, M.; Rouleau, A.; Lucchi, G.; Mantion, G.; Heyd, B.; Richert, L.; Ducoroy, P.; Martin, H.; Val, St.; Martinon, L.; Cachier, H.; Yahyaoui, A.; Marfaing, H.; Baeza-Squiban, A.; Martin-Chouly, C.; Bonvallet, M.; Morzadec, C.; Fardel, O.; Vernhet, L.; Baverel, G.; El Hage, M.; Nazaret, R.; Conjard-Duplany, A.; Ferrier, B.; Martin, G.; Legendre, A.; Desmots, S.; Lecomte, A.; Froment, P.; Habert, R.; Lemazurier, E.; Robinel, F.; Dupont, O.; Sanfins, E.; Dairou, J.; Chaffotte, A.F.; Busi, F.; Rodrigues Lima, F.; Dupret, J.M.; Mayati, A.; Le Ferrec, E.; Levoin, N.; Paris, H.; Uriac, Ph.; N'Diaye, M.; Lagadic-Gossmann, D.; Fardel, O.; Assemat, E.; Boublil, L.; Borot, M.C.; Marano, F.; Baeza-Squiban, A.; Martiny, V.Y.; Moroy, G.; Badel, A.; Miteva, M.A.; Hussain, S.; Ferecatu, I.; Borot, C.; Andreau, K.; Baeza-Squiban, A.; Marano, F.; Boland, S.; Leroux, M.; Zucchini-Pascal, N.; Peyre, L.; Rahmani, R.; Buron, N.; Porcedou, M.; Fromenty, B.; Borgne-Sanchez, A.; Rogue, A.; Spire, C.; Claude, N.; Guillouzo, A.

    2010-01-01

    Prevention of possible noxious effects in relation with the exposure to one or several chemical, physical or biological agents present in our domestic or professional environment is one of today's big public health stakes. Another stake is the better assessment of the risks linked with the use of health-care products. The efficacy and predictiveness of toxicology studies are directly related to the combination of alternate complementary methods and animal experiments (obtaining data from different species and with different models: in vitro, ex vivo and in vivo). Despite important efforts, the toxicological evaluation remains perfectible. The proceedings of this 2010 congress of the French Society of cell pharmaco-toxicology deal with recent advances, both scientific and technological, in 'predictive toxicology'. Four main topics are approached: cell and organ models, 'omics', in silico modeling, and new technologies (imaging, cell ships, high-speed processing). Among the different presentations, 3 abstracts present some recent advances in imaging techniques applied to toxicology studies. These are: 1 - first uses in toxicology of TOF-SIMS mass spectroscopy imaging (O. Laprevote, Paris-Descartes Univ. (FR)); 2 - Small animal imaging, a tool for predictive toxicology (A. Le Pape, CNRS Orleans (FR)); 3 - uranium localization at cell level using SIMS imaging technique (C. Rouas et al., IRSN Fontenay-aux-Roses (FR)). (J.S.)

  3. A primer on systematic reviews in toxicology.

    Science.gov (United States)

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

    2017-07-01

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

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

    Science.gov (United States)

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

  5. Principles and procedures in forensic toxicology.

    Science.gov (United States)

    Wyman, John F

    2012-09-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-10-31

    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

  7. Oleoresin Capsicum toxicology evaluation and hazard review

    Energy Technology Data Exchange (ETDEWEB)

    Archuleta, M.M.

    1995-10-01

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

  8. Techniques for Investigating Molecular Toxicology of Nanomaterials.

    Science.gov (United States)

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

    2016-06-01

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

  9. Space Toxicology: Human Health during Space Operations

    Science.gov (United States)

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

    2010-01-01

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

  10. Comparative BioInformatics and Computational Toxicology

    Science.gov (United States)

    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.

  11. Pulmonary toxicology of respirable particles. [Lead abstract

    Energy Technology Data Exchange (ETDEWEB)

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

    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)

  12. Environmental chemistry and toxicology of mercury

    National Research Council Canada - National Science Library

    Liu, Guangliang; Cai, Yong; O'Driscoll, Nelson J

    2012-01-01

    ... employed in recent studies. The coverage discusses the environmental behavior and toxicological effects of mercury on organisms, including humans, and provides case studies at the end of each chapter...

  13. IRIS Toxicological Review of Chloroform (Final Report)

    Science.gov (United States)

    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.

  14. Modern Instrumental Methods in Forensic Toxicology*

    Science.gov (United States)

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

    2009-01-01

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

  15. Integrative Systems Biology Applied to Toxicology

    DEFF Research Database (Denmark)

    Kongsbak, Kristine Grønning

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

  16. Fine Grained Tungsten Claddings for Cermet Based NTP Systems, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — In October 2011, NASA initiated the Nuclear Cryogenic Propulsion Stage (NCPS) program to evaluate the feasibility and affordability of Nuclear Thermal Propulsion...

  17. Fine Grained Tungsten Claddings for Cermet Based NTP Systems, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — In October 2011, NASA initiated the Nuclear Cryogenic Propulsion Stage (NCPS) program to evaluate the feasibility and affordability of Nuclear Thermal Propulsion...

  18. [Toxicological evaluation in the childhood].

    Science.gov (United States)

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

    2014-03-01

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

  19. Good Practices in Forensic Toxicology.

    Science.gov (United States)

    Drummer, Olaf H

    2017-01-01

    This manuscript provides an overview for analysts, medical and scientific investigators, and laboratory administrators, the range of factors that should be considered to implement best practice forensic toxicology. These include laboratory influence over the collection of specimens, their proper transport and chain-of-custody before arrival in the laboratory. In addition, the laboratory needs to ensure properly trained staff use suitably validated and documented analytical procedures that meet the intended purpose and type of case in an accredited or suitably quality oriented management system. To assist the investigating officers laboratory results require an interpretation over their possible significance when sufficient details are available over the circumstances of the case. This requires a thorough understanding of the various factors that influence concentrations of substances and ultimately their likely physiological effect. These include consideration of the route of ingestion, influence over chronicity of usage on tissue concentrations and tolerance, possible combined drug effects or likely adverse reactions and consideration of relevant genetic factors that may have influenced pharmacokinetic or pharmacodynamic response. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  20. Introduction: biomarkers in neurodevelopment toxicology

    Energy Technology Data Exchange (ETDEWEB)

    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.

  1. Defective mitochondrial respiration, altered dNTP pools and reduced AP endonuclease 1 activity in peripheral blood mononuclear cells of Alzheimer's disease patients

    DEFF Research Database (Denmark)

    Maynard, Scott; Hejl, Anne-Mette; Dinh, Tran Thuan Son

    2015-01-01

    AIMS: Accurate biomarkers for early diagnosis of Alzheimer's disease (AD) are badly needed. Recent reports suggest that dysfunctional mitochondria and DNA damage are associated with AD development. In this report, we measured various cellular parameters, related to mitochondrial bioenergetics...... as possible. We measured glycolysis and mitochondrial respiration fluxes using the Seahorse Bioscience flux analyzer, mitochondrial ROS production using flow cytometry, dNTP levels by way of a DNA polymerization assay, DNA strand breaks using the Fluorometric detection of Alkaline DNA Unwinding (FADU) assay...... on adjustments for gender and/or age. CONCLUSIONS: This study reveals impaired mitochondrial respiration, altered dNTP pools and reduced DNA repair activity in PBMCs of AD patients, thus suggesting that these biochemical activities may be useful as biomarkers for AD....

  2. Evaluating a national science and technology program using the human capital and relational asset perspectives.

    Science.gov (United States)

    Hung, Chia-Liang; Chou, Jerome Chih-Lung; Roan, Hung-Wei

    2010-11-01

    The purpose of this research is to evaluate the performance of the National Science and Technology Program (NSTP) by targeting the Taiwan National Telecommunication Program (NTP) initiated in 1998. The Taiwan telecommunications industry has prospered, currently occupying key positions in global markets even though NTP seldom contributes positively to patent citation performance. Hence, the authors of this study investigate the qualitative perspective of intellectual capital rather than quantitative technological indices. The current study focuses on both human capital and relational assets through surveys of 53 principal investigators of NTP projects and 63 industrial R&D managers of telecommunications corporations in the Taiwan market. Results show that NSTP member quality and the flow of employment are good indicators of human capital and that both perform better than the middle value in the case of Taiwan NTP. In addition, we find that industrial participants are more likely to share R&D resources than other academic researchers with higher intention of co-publishing, co-funding, and sharing equipment and facilities. The industrial NTP participants also have higher expectations regarding achieving advanced technology breakthroughs in contrast to non-NTP industrial interviewees. Moreover, industrial participants with greater industry-university cooperation intensity indeed obtain a particular advantage, that is, greater knowledge acquisition from other fields related to the effect of knowledge spillovers through the particular NSTP linkage. Accordingly, from the perspectives of human capital and relational assets, the authors conclude by articulating the importance of absorptive capacity resulting from good human capital and knowledge spillover contributed by relational assets within governmental technology policy and NSTP programming. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  3. Data governance in predictive toxicology: A review.

    Science.gov (United States)

    Fu, Xin; Wojak, Anna; Neagu, Daniel; Ridley, Mick; Travis, Kim

    2011-07-13

    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). 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. 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 identified as the new challenge in

  4. Data governance in predictive toxicology: A review

    Directory of Open Access Journals (Sweden)

    Fu Xin

    2011-07-01

    Full Text Available Abstract 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

  5. First realisation of a labelling kit of N.T.P. 15-5 ligand by {sup 99m}Tc in view of a clinical application in cartilage functional imaging; Premiere realisation d'une trousse de marquage du ligand NTP 15-5 par le 99mTc en vue d'une application clinique en imagerie fonctionnelle du cartilage

    Energy Technology Data Exchange (ETDEWEB)

    Miot-Noirault, E.; Cachin, F.; Vidal, A.; Auzeloux, P.; Chezal, J.M.; Gaumet, V.; Askienazy, S. [Inserm, EA4231, UMR 990, 63 - Clermont-Ferrand (France); Guenu, S. [UFR de pharmacie, laboratoire de chimie analytique, 63 - Clermont-Ferrand (France); Askienazy, S. [Laboratoires Cyclopharma, 63 - Saint-Beauzire (France)

    2010-07-01

    We are working on a SPECT tracer for functional imaging of articular cartilage, the {sup 99m}Tc-NTP 15-5. This molecule has its application in degenerative diseases of cartilage (arthrosis, arthritis and chondrosarcoma). Excellent reports of cartilage versus tissues fixing ratios are obtained in different animal models as well as human anatomical parts. For clinical application, we present the development of a labelling kit by the technetium of the ligand NTP 15-5. (N.C.)

  6. Incorporation of deoxyribonucleotides and ribonucleotides by a dNTP-binding cleft mutated reverse transcriptase in hepatitis B virus core particles

    International Nuclear Information System (INIS)

    Kim, Hee-Young; Kim, Hye-Young; Jung, Jaesung; Park, Sun; Shin, Ho-Joon; Kim, Kyongmin

    2008-01-01

    Our recent observation that hepatitis B virus (HBV) DNA polymerase (P) might initiate minus-strand DNA synthesis without primer [Kim et al., (2004) Virology 322, 22-30], raised a possibility that HBV P protein may have the potential to function as an RNA polymerase. Thus, we mutated Phe 436, a bulky amino acid with aromatic side chain, at the putative dNTP-binding cleft in reverse transcriptase (RT) domain of P protein to smaller amino acids (Gly or Val), and examined RNA polymerase activity. HBV core particles containing RT dNTP-binding cleft mutant P protein were able to incorporate 32 P-ribonucleotides, but not HBV core particles containing wild type (wt), priming-deficient mutant, or RT-deficient mutant P proteins. Since all the experiments were conducted with core particles isolated from transfected cells, our results indicate that the HBV RT mutant core particles containing RT dNTP-binding cleft mutant P protein could incorporate both deoxyribonucleotides and ribonucleotides in replicating systems

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

    Science.gov (United States)

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

    2017-07-01

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

  8. Systems Toxicology: Real World Applications and Opportunities

    Science.gov (United States)

    2017-01-01

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

  9. Non-precautionary aspects of toxicology

    International Nuclear Information System (INIS)

    Grandjean, Philippe

    2005-01-01

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

  10. Systems Toxicology: Real World Applications and Opportunities.

    Science.gov (United States)

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

    2017-04-17

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

  11. IRIS TOXICOLOGICAL REVIEW AND SUMMARY ...

    Science.gov (United States)

    The Draft Toxicological Review was developed to evaluate both the cancer and non cancer human health risks from environmental exposure to vinyl chloride. A reference concentration (RfC), and a reference dose (RfD) were developed based upon induction of liver cell polymorphism in a chronic dietary study utilizing Wistar rats. An RfC of 1E-1 mg/m3 and an RfD of 5E-3 mg/kg-d are recommended. On the basis of sufficient evidence for carcinogenicity in human epidemiology studies vinyl chloride is reaffirmed to be a known human carcinogen. Cancer potencies were derived for oral and inhalation exposure. An oral slope factor of 1.3 per (mg/kg-day) for continuous exposure during adulthood and 2.5 per (mg/kg-day) for continuous lifetime exposure from birth, based upon a chronic dietary study in female Wistar rats is recommended; an inhalation unit risk of 4.3 E-6 per (55g/m3) for continuous exposure during adulthood and 8.7 E-6 per (55g/m3) for continuous lifetime exposure from birth is also recommended, based upon exposure of male and female Sprague Dawley rats and Swiss mice, via inhalation, for a lifetime. A PBPK model was used in the derivation of the RfC, RfD, and cancer potency estimates. Its use is based on the assumption that equal tissue concentrations of reactive metabolite, chlorethylene oxide or chloracetaldehyde, at the critical target site will result in equivalent toxicity between species.

  12. IRIS Toxicological Review of Ethylene Glycol Mono Butyl Ether (Egbe) (Final Report)

    Science.gov (United States)

    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.

  13. IRIS Toxicological Review of Hydrogen Cyanide and Cyanide Salts (Final Report)

    Science.gov (United States)

    EPA has finalized the Toxicological Review of Hydrogen Cyanide and Cyanide Salts: 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. Mitochondrial-epigenetic crosstalk in environmental toxicology.

    Science.gov (United States)

    Weinhouse, Caren

    2017-11-01

    Crosstalk between the nuclear epigenome and mitochondria, both in normal physiological function and in responses to environmental toxicant exposures, is a developing sub-field of interest in environmental and molecular toxicology. The majority (∼99%) of mitochondrial proteins are encoded in the nuclear genome, so programmed communication among nuclear, cytoplasmic, and mitochondrial compartments is essential for maintaining cellular health. In this review, we will focus on correlative and mechanistic evidence for direct impacts of each system on the other, discuss demonstrated or potential crosstalk in the context of chemical insult, and highlight biological research questions for future study. We will first review the two main signaling systems: nuclear signaling to the mitochondria [anterograde signaling], best described in regulation of oxidative phosphorylation (OXPHOS) and mitochondrial biogenesis in response to environmental signals received by the nucleus, and mitochondrial signals to the nucleus [retrograde signaling]. Both signaling systems can communicate intracellular energy needs or a need to compensate for dysfunction to maintain homeostasis, but both can also relay inappropriate signals in the presence of dysfunction in either system and contribute to adverse health outcomes. We will first review these two signaling systems and highlight known or biologically feasible epigenetic contributions to both, then briefly discuss the emerging field of epigenetic regulation of the mitochondrial genome, and finally discuss putative "crosstalk phenotypes", including biological phenomena, such as caloric restriction, maintenance of stemness, and circadian rhythm, and states of disease or loss of function, such as cancer and aging, in which both the nuclear epigenome and mitochondria are strongly implicated. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Initiation of a medical toxicology consult service at a tertiary care children's hospital.

    Science.gov (United States)

    Wang, George Sam; Monte, Andrew; Hatten, Benjamin; Brent, Jeffrey; Buchanan, Jennie; Heard, Kennon J

    2015-05-01

    Currently, only 10% of board-certified medical toxicologists are pediatricians. Yet over half of poison center calls involve children toxicology consultation is not common at children's hospitals. In collaboration with executive staff from Department of Pediatrics and Emergency Medicine, regional poison center, and our toxicology fellowship, we established a toxicology consulting service at our tertiary-care children's hospital. There were 139 consultations, and the service generated 13 consultations in the first month; median of 11 consultations per month thereafter (range 8-16). The service increased pediatric cases seen by the fellowship program from 30 to 94. The transition to a consult service required a culture change. Historically, call center advice was the mainstay of consulting practice and the medical staff was not accustomed to the availability of bedside medical toxicology consultations. However, after promotion of the service and full attending and fellowship coverage, consultations increased. In collaboration with toxicologists from different departments, a consultation service can be rapidly established. The service filled a clinical need that was disproportionately utilized for high acuity patients, immediately utilized by the medical staff and provided a robust pediatric population for the toxicology fellowship.

  16. Triennial report 1981-83 of the Institute for Genetics and for Toxicology

    International Nuclear Information System (INIS)

    Hotz, G.

    1984-07-01

    The scientific activity of the Divisions of Genetics and of Toxicology of the Institute for Genetics and for Toxicology during the period January 1981 to December 1983 is described. In addition to reports on the various research topics this second 'Report' also gives an overview of the external scientific and teaching activities of the staff members during the period. In the field of radiation genetics most of the interest has been focussed on the mechanisms of gene repair, gene regulation and the molecular biology of tumor viruses in human and other mammalian cells. The main emphasis of the long term toxicology program has been on studies of radiotoxicology of the actinides and other heavy metals, especially in relation to chelation therapy and to the development of biochemical and physical methods for investigation of their metabolic behaviour. (orig.) [de

  17. Biennal Report 1979/80 of the Institute for Genetics and Toxicology

    International Nuclear Information System (INIS)

    Hotz, G.

    1981-07-01

    The research activities of the Genetics and the Toxicology Divisions of the Institute for Genetics and Toxicology of Fissile Materials during the period January 1979 to December 1980 are decribed. In addition to scientific reports on the various research topics the report gives an overview of the external scientific and teaching activities of the staff members during the review period. The main emphasis of the toxicology program has been on studies of the radiotoxicology of the actinides and other heavy metals, especially in relation to chelation therapy and to the development of biochemical and physical methods for investigation of their metabolic behaviour. In the field of radiation genetics most of the interest has been focussed on the mechanisms of gene repair, gene regulation and the molecular biology of tumor viruses. (orig.) [de

  18. Toxicology research projects directory, 1978. Monthly repts

    International Nuclear Information System (INIS)

    1978-01-01

    The Toxicology Research Projects Directory is a monthly publication of ongoing research projects in toxicology and related fields selected from the files of the Smithsonian Science Information Exchange (SSIE). Each issue lists toxicology-related research projects reported to SSIE during the one-month period preceding that issue. Each of the summaries is categorized by scientific discipline and assigned a unique identification number for cross-referencing from the Directory Indexes--Subject, Investigator, Performing Organization, Supporting Agency, and Master Grant Number. The thirteenth issue consists of Cumulative Indexes for the entire volume with referencing to projects in all of the previous twelve issues. The emphasis of the Directory is on the manifestations of the exposure of man and animals to toxic substances. Projects are classified by toxic agents, research orientation, and areas of environmental concern

  19. Prospects for applying synthetic biology to toxicology

    DEFF Research Database (Denmark)

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

    2017-01-01

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

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

    International Nuclear Information System (INIS)

    RITTMANN, P.D.

    1999-01-01

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

  1. Comptox Chemistry Dashboard: Web-Based Data Integration Hub for Environmental Chemistry and Toxicology Data (ACS Fall meeting 4 of 12)

    Science.gov (United States)

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

  2. Developmental toxicology: adequacy of current methods.

    Science.gov (United States)

    Peters, P W

    1998-01-01

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

  3. IRIS Toxicological Review of Trichloroethylene (TCE) ...

    Science.gov (United States)

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

  4. [Forensic toxicology, a growing scientific discipline].

    Science.gov (United States)

    Augsburger, Marc; Staub, Christian

    2008-07-02

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

  5. Risk assessment and toxicology databases for health effects assessment

    Energy Technology Data Exchange (ETDEWEB)

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

    1990-12-31

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

  6. 40 CFR 161.340 - Toxicology data requirements.

    Science.gov (United States)

    2010-07-01

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

  7. Accelerating the Development of 21st-Century Toxicology: Outcome of a Human Toxicology Project Consortium Workshop

    Science.gov (United States)

    Stephens, Martin L.; Barrow, Craig; Andersen, Melvin E.; Boekelheide, Kim; Carmichael, Paul L.; Holsapple, Michael P.; Lafranconi, Mark

    2012-01-01

    The U.S. National Research Council (NRC) report on “Toxicity Testing in the 21st century” calls for a fundamental shift in the way that chemicals are tested for human health effects and evaluated in risk assessments. The new approach would move toward in vitro methods, typically using human cells in a high-throughput context. The in vitro methods would be designed to detect significant perturbations to “toxicity pathways,” i.e., key biological pathways that, when sufficiently perturbed, lead to adverse health outcomes. To explore progress on the report’s implementation, the Human Toxicology Project Consortium hosted a workshop on 9–10 November 2010 in Washington, DC. The Consortium is a coalition of several corporations, a research institute, and a non-governmental organization dedicated to accelerating the implementation of 21st-century Toxicology as aligned with the NRC vision. The goal of the workshop was to identify practical and scientific ways to accelerate implementation of the NRC vision. The workshop format consisted of plenary presentations, breakout group discussions, and concluding commentaries. The program faculty was drawn from industry, academia, government, and public interest organizations. Most presentations summarized ongoing efforts to modernize toxicology testing and approaches, each with some overlap with the NRC vision. In light of these efforts, the workshop identified recommendations for accelerating implementation of the NRC vision, including greater strategic coordination and planning across projects (facilitated by a steering group), the development of projects that test the proof of concept for implementation of the NRC vision, and greater outreach and communication across stakeholder communities. PMID:21948868

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

    NARCIS (Netherlands)

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

    2005-01-01

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

  9. Towards a Fuzzy Expert System on Toxicological Data Quality Assessment.

    Science.gov (United States)

    Yang, Longzhi; Neagu, Daniel; Cronin, Mark T D; Hewitt, Mark; Enoch, Steven J; Madden, Judith C; Przybylak, Katarzyna

    2013-01-01

    Quality assessment (QA) requires high levels of domain-specific experience and knowledge. QA tasks for toxicological data are usually performed by human experts manually, although a number of quality evaluation schemes have been proposed in the literature. For instance, the most widely utilised Klimisch scheme1 defines four data quality categories in order to tag data instances with respect to their qualities; ToxRTool2 is an extension of the Klimisch approach aiming to increase the transparency and harmonisation of the approach. Note that the processes of QA in many other areas have been automatised by employing expert systems. Briefly, an expert system is a computer program that uses a knowledge base built upon human expertise, and an inference engine that mimics the reasoning processes of human experts to infer new statements from incoming data. In particular, expert systems have been extended to deal with the uncertainty of information by representing uncertain information (such as linguistic terms) as fuzzy sets under the framework of fuzzy set theory and performing inferences upon fuzzy sets according to fuzzy arithmetic. This paper presents an experimental fuzzy expert system for toxicological data QA which is developed on the basis of the Klimisch approach and the ToxRTool in an effort to illustrate the power of expert systems to toxicologists, and to examine if fuzzy expert systems are a viable solution for QA of toxicological data. Such direction still faces great difficulties due to the well-known common challenge of toxicological data QA that "five toxicologists may have six opinions". In the meantime, this challenge may offer an opportunity for expert systems because the construction and refinement of the knowledge base could be a converging process of different opinions which is of significant importance for regulatory policy making under the regulation of REACH, though a consensus may never be reached. Also, in order to facilitate the implementation

  10. Toxicological aspects of fuel and exhaust gas

    International Nuclear Information System (INIS)

    Avella, F.

    1993-01-01

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

  11. Evolution of Computational Toxicology-from Primitive ...

    Science.gov (United States)

    Presentation at the Health Canada seminar in Ottawa, ON, Canada on Nov. 15. 2016 Presentation at the Health Canada seminar in Ottawa, ON, Canada on Nov. 15. 2016 on the Evolution of Computational Toxicology-from Primitive Beginnings to Sophisticated Application

  12. Good cell culture practices &in vitro toxicology.

    Science.gov (United States)

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

    2017-12-01

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

  13. Research Models in Developmental Behavioral Toxicology.

    Science.gov (United States)

    Dietrich, Kim N.; Pearson, Douglas T.

    Developmental models currently used by child behavioral toxicologists and teratologists are inadequate to address current issues in these fields. Both child behavioral teratology and toxicology scientifically study the impact of exposure to toxic agents on behavior development: teratology focuses on prenatal exposure and postnatal behavior…

  14. A medical-toxicological view of tattooing

    DEFF Research Database (Denmark)

    Laux, Peter; Tralau, Tewes; Tentschert, Jutta

    2016-01-01

    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...

  15. Toxicodynetics: A new discipline in clinical toxicology.

    Science.gov (United States)

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

    2016-05-01

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

  16. Metabolomics in Toxicology and Preclinical Research

    Science.gov (United States)

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

    2013-01-01

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

  17. FISH PHYSIOLOGY, TOXICOLOGY, AND WATER QUALITY:

    Science.gov (United States)

    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...

  18. Toxicological requirements for risk assessment of shellfish ...

    African Journals Online (AJOL)

    There is increasing concern by consumers with regard to the health aspects and safety of foodstuffs. Most food additives and contaminants are controlled by regulatory authorities, with Acceptable Daily Intakes (ADIs) having been set on the basis of detailed acute short- and long-term toxicological studies. The situation with ...

  19. Phytochemical Screening, Antibacterial and Toxicological Activities ...

    African Journals Online (AJOL)

    The phytochemical screening, antibacterial and toxicological activities of extracts of the stem bark of Acacia senegal were investigated. The phytochemical analyses according to standard screening tests using conventional protocols revealed the presence of tannins, saponins and sterols in the stem bark of the plant.

  20. Toxicological perspectives of inhaled therapeutics and nanoparticles.

    Science.gov (United States)

    Hayes, Amanda J; Bakand, Shahnaz

    2014-07-01

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

  1. Collection of biological samples in forensic toxicology.

    Science.gov (United States)

    Dinis-Oliveira, R J; Carvalho, F; Duarte, J A; Remião, F; Marques, A; Santos, A; Magalhães, T

    2010-09-01

    Forensic toxicology is the study and practice of the application of toxicology to the purposes of the law. The relevance of any finding is determined, in the first instance, by the nature and integrity of the specimen(s) submitted for analysis. This means that there are several specific challenges to select and collect specimens for ante-mortem and post-mortem toxicology investigation. Post-mortem specimens may be numerous and can endow some special difficulties compared to clinical specimens, namely those resulting from autolytic and putrefactive changes. Storage stability is also an important issue to be considered during the pre-analytic phase, since its consideration should facilitate the assessment of sample quality and the analytical result obtained from that sample. The knowledge on degradation mechanisms and methods to increase storage stability may enable the forensic toxicologist to circumvent possible difficulties. Therefore, advantages and limitations of specimen preservation procedures are thoroughfully discussed in this review. Presently, harmonized protocols for sampling in suspected intoxications would have obvious utility. In the present article an overview is given on sampling procedures for routinely collected specimens as well as on alternative specimens that may provide additional information on the route and timing of exposure to a specific xenobiotic. Last, but not least, a discussion on possible bias that can influence the interpretation of toxicological results is provided. This comprehensive review article is intented as a significant help for forensic toxicologists to accomplish their frequently overwhelming mission.

  2. FISH PHYSIOLOGY, TOXICOLOGY, AND WATER QUALITY

    Science.gov (United States)

    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...

  3. Phytochemical analysis and toxicological evaluation of the ...

    African Journals Online (AJOL)

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

  4. The rat incisor in toxicologic pathology

    NARCIS (Netherlands)

    Kuijpers, M.H.M.; Kooij, A.J. van de; Slootweg, P.J.

    1996-01-01

    Microscopic examination of the incisors of rats and mice may reveal toxicologically significant changes. First, the incisor morphology reflects the nutritional status of the animal: fluctuations of mineral metabolism and vitamin availability are disclosed by the rodent incisors, because the incisors

  5. A prospective toxicology analysis in alcoholics

    DEFF Research Database (Denmark)

    Thomsen, Jørgen Lange; Simonsen, Kirsten Wiese; Felby, Søren

    1997-01-01

    A prospective and comprehensive investigation was done on 73 medico–legal autopsies in alcoholics. The results of the toxicology analyses are described. Alcohol intoxication was the cause of death in 8%, combined alcohol/drug intoxication in 15% and drugs alone in 19%. Alcoholic ketoacidosis...

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

    Science.gov (United States)

    Grandjean, P

    2015-12-01

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

  7. The Benefits of Nuclear Thermal Propulsion (NTP) in an Evolvable Mars Campaign

    Science.gov (United States)

    Borowski, Stanley K.; Mccurdy, David R.

    2014-01-01

    NTR: High thrust high specific impulse (2 x LOXLH2chemical) engine uses high power density fission reactor with enriched uranium fuel as thermal power source. Reactor heat is removed using H2propellant which is then exhausted to produce thrust. Conventional chemical engine LH2tanks, turbopumps, regenerative nozzles and radiation-cooled shirt extensions used --NTR is next evolutionary step in high performance liquid rocket engines During the Rover program, a common fuel element tie tube design was developed and used in the design of the 50 klbf Kiwi-B4E (1964), 75 klbf Phoebus-1B (1967), 250 klbf Phoebus-2A (June 1968), then back down to the 25 klbf Pewee engine (Nov-Dec 1968) NASA and DOE are using this same approach: design, build, ground then flight test a small engine using a common fuel element that is scalable to a larger 25 klbf thrust engine needed for human missions

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

    Science.gov (United States)

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

    2015-10-01

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

  9. Impact of online toxicology training on health professionals: the Global Educational Toxicology Uniting Project (GETUP).

    Science.gov (United States)

    Wong, Anselm; Vohra, Rais; Dawson, Andrew H; Stolbach, Andrew

    2017-11-01

    The Global Educational Toxicology Uniting Project (GETUP), supported by the American College of Medical Toxicology, links countries with and without toxicology services via distance education with the aim to improve education. Due to the lack of toxicology services in some countries there is a knowledge gap in the management of poisonings. We describe our experience with the worldwide delivery of an online introductory toxicology curriculum to emergency doctors and other health professionals treating poisoned patients. We delivered a 15-module introductory Internet-based toxicology curriculum to emergency doctors and health professionals, conducted from August to December 2016. This Internet-based curriculum was adapted from one used to teach emergency residents toxicology in the United States. Modules covered themes such as pharmaceutical (n = 8), toxidromes (n = 2) and agrochemicals (n = 5) poisoning. Participants completed pre-test and post-test multiple choice questions (MCQs) before and after completing the online module, respectively, throughout the course. We collected information on participant demographics, education and training, and perception of relevance of the curriculum. Participants gave feedback on the course and how it affected their practice. One hundred and thirty-six health professionals from 33 countries participated in the course: 98 emergency doctors/medical officers, 25 physicians, eight pharmacists/poisons information specialists, two toxicologists, two medical students and one nurse. Median age of participants was 34 years. Median number of years postgraduate was seven. Ninety (65%) had access to either a poisons information centre over the phone or toxicologist and 48 (35%) did not. All participants expected the course to help improve their knowledge. Overall median pre-module MCQ scores were 56% (95%CI: 38, 75%) compared to post-module MCQ scores median 89% (95% CI: 67, 100%) (p education to health professionals treating

  10. Isoquercitrin: Pharmacology, toxicology, and metabolism

    Czech Academy of Sciences Publication Activity Database

    Valentová, Kateřina; Vrba, J.; Bancířová, M.; Ulrichová, J.; Křen, Vladimír

    2014-01-01

    Roč. 68, JUN 2014 (2014), s. 267-282 ISSN 0278-6915 R&D Projects: GA ČR GPP301/12/P381; GA MŠk(CZ) LD13041; GA MŠk(CZ) 7E11011; GA ČR(CZ) GAP301/11/0767 Grant - others:GA ČR(CZ) GAP303/12/G163 Program:GA Institutional support: RVO:61388971 Keywords : Quercetin-3-glucoside * Quercetin-3-O-beta-D-glucopyranoside * Enzymatically modified isoquercitrin Subject RIV: CE - Biochemistry Impact factor: 2.895, year: 2014

  11. Nano-technology and nano-toxicology.

    Science.gov (United States)

    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.

  12. Avian models in teratology and developmental toxicology.

    Science.gov (United States)

    Smith, Susan M; Flentke, George R; Garic, Ana

    2012-01-01

    The avian embryo is a long-standing model for developmental biology research. It also has proven utility for toxicology research both in ovo and in explant culture. Like mammals, avian embryos have an allantois and their developmental pathways are highly conserved with those of mammals, thus avian models have biomedical relevance. Fertile eggs are inexpensive and the embryo develops rapidly, allowing for high-throughput. The chick genome is sequenced and significant molecular resources are available for study, including the ability for genetic manipulation. The absence of a placenta permits the direct study of an agent's embryotoxic effects. Here, we present protocols for using avian embryos in toxicology research, including egg husbandry and hatch, toxicant delivery, and assessment of proliferation, apoptosis, and cardiac structure and function.

  13. Systems Toxicology: The Future of Risk Assessment.

    Science.gov (United States)

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

    2015-01-01

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

  14. Regulated necrosis and its implications in toxicology.

    Science.gov (United States)

    Aki, Toshihiko; Funakoshi, Takeshi; Uemura, Koichi

    2015-07-03

    Recent research developments have revealed that caspase-dependent apoptosis is not the sole form of regulated cell death. Caspase-independent, but genetically regulated, forms of cell death include pyroptosis, necroptosis, parthanatos, and the recently discovered ferroptosis and autosis. Importantly, regulated necrosis can be modulated by small molecule inhibitors/activators, confirming the cell autonomous mechanism of these forms of cell death. The success of small molecule-mediated manipulation of regulated necrosis has produced great changes in the field of cell death research, and has also brought about significant changes in the fields of pharmacology as well as toxicology. In this review, we intend to summarize the modes of regulated cell death other than apoptosis, and discuss their implications in toxicology. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  15. [Interest of toxicological analysis for poisonings].

    Science.gov (United States)

    Mégarbane, Bruno; Baud, Frédéric J

    2008-04-30

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

  16. Toxicology of Nanomaterials: Permanent interactive learning

    Directory of Open Access Journals (Sweden)

    Castranova Vince

    2009-10-01

    Full Text Available Abstract Particle and Fibre Toxicology wants to play a decisive role in a time where particle research is challenged and driven by the developments and applications of nanomaterials. This aim is not merely quantitative in publishing a given number of papers on nanomaterials, but also qualitatively since the field of nanotoxicology is rapidly emerging and benchmarks for good science are needed. Since then a number of things have happened that merit further analysis. The interactive learning issue is best shown by report and communications on the toxicology of multi-wall carbon nanotubes (CNT. A special workshop on the CNT has now been organized twice in Nagano (Japan and this editorial contains a summary of the most important outcomes. Finally, we take the opportunity discuss some recent reports from the nanotech literature, and more specifically a Chinese study that claims severe consequences of nanoparticle exposure.

  17. Pharmacological and toxicological evaluation of Urtica dioica.

    Science.gov (United States)

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

    2013-02-01

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

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

    Science.gov (United States)

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

    2017-01-01

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

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

    International Nuclear Information System (INIS)

    Calabrese, Edward J.

    2005-01-01

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

  20. Nano-technology and nano-toxicology

    OpenAIRE

    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 ...

  1. The four cornerstones of Evolutionary Toxicology.

    Science.gov (United States)

    Bickham, John W

    2011-05-01

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

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

    OpenAIRE

    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...

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

    Science.gov (United States)

    EPA is conducting a peer review and public comment of the scientific basis supporting the human health hazard and dose-response assessment of 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.

  4. Loss of yeast peroxiredoxin Tsa1p induces genome instability through activation of the DNA damage checkpoint and elevation of dNTP levels.

    Directory of Open Access Journals (Sweden)

    Hei-Man Vincent Tang

    2009-10-01

    Full Text Available Peroxiredoxins are a family of antioxidant enzymes critically involved in cellular defense and signaling. Particularly, yeast peroxiredoxin Tsa1p is thought to play a role in the maintenance of genome integrity, but the underlying mechanism is not understood. In this study, we took a genetic approach to investigate the cause of genome instability in tsa1Delta cells. Strong genetic interactions of TSA1 with DNA damage checkpoint components DUN1, SML1, and CRT1 were found when mutant cells were analyzed for either sensitivity to DNA damage or rate of spontaneous base substitutions. An elevation in intracellular dNTP production was observed in tsa1Delta cells. This was associated with constitutive activation of the DNA damage checkpoint as indicated by phosphorylation of Rad9/Rad53p, reduced steady-state amount of Sml1p, and induction of RNR and HUG1 genes. In addition, defects in the DNA damage checkpoint did not modulate intracellular level of reactive oxygen species, but suppressed the mutator phenotype of tsa1Delta cells. On the contrary, overexpression of RNR1 exacerbated this phenotype by increasing dNTP levels. Taken together, our findings uncover a new role of TSA1 in preventing the overproduction of dNTPs, which is a root cause of genome instability.

  5. ICPP radiological and toxicological sabotage analysis

    International Nuclear Information System (INIS)

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

    1995-01-01

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

  6. Toxicological benchmarks for wildlife: 1994 Revision

    International Nuclear Information System (INIS)

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

    1994-09-01

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

  7. Toxicological benchmarks for wildlife: 1994 Revision

    Energy Technology Data Exchange (ETDEWEB)

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

    1994-09-01

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

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

    Science.gov (United States)

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

    2014-08-01

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

  9. Life-Time Dosimetric Assessment for Mice and Rats Exposed in Reverberation Chambers of the 2-Year NTP Cancer Bioassay Study on Cell Phone Radiation.

    Science.gov (United States)

    Gong, Yijian; Capstick, Myles; Kuehn, Sven; Wilson, Perry; Ladbury, John; Koepke, Galen; McCormick, David L; Melnick, Ronald L; Kuster, Niels

    2017-12-01

    In this paper, we present the detailed life-time dosimetry analysis for rodents exposed in the reverberation exposure system designed for the two-year cancer bioassay study conducted by the National Toxicology Program of the National Institute of Environmental Health Sciences. The study required the well-controlled and characterized exposure of individually housed, unrestrained mice at 1900 MHz and rats at 900 MHz, frequencies chosen to give best uniformity exposure of organs and tissues. The wbSAR, the peak spatial SAR and the organ specific SAR as well as the uncertainty and variation due to the exposure environment, differences in the growth rates, and animal posture were assessed. Compared to the wbSAR, the average exposure of the high-water-content tissues (blood, heart, lung) were higher by ~4 dB, while the low-loss tissues (bone and fat) were less by ~9 dB. The maximum uncertainty over the exposure period for the SAR was estimated to be <49% (k=2) for the rodents whereas the relative uncertainty between the group was <14% (k=1). The instantaneous variation (averaged over 1 min) was <13% (k=1), which is small compared to other long term exposure research projects. These detailed dosimetric results empowers comparison with other studies and provides a reference for studies of long-term biological effects of exposure of rodents to RF energy.

  10. The Weight of Evidence Does Not Support the Listing of Styrene as “Reasonably Anticipated to be a Human Carcinogen” in NTP's Twelfth Report on Carcinogens

    Science.gov (United States)

    Rhomberg, Lorenz R.; Goodman, Julie E.; Prueitt, Robyn L.

    2013-01-01

    Styrene was listed as “reasonably anticipated to be a human carcinogen” in the twelfth edition of the National Toxicology Program's Report on Carcinogens based on what we contend are erroneous findings of limited evidence of carcinogenicity in humans, sufficient evidence of carcinogenicity in experimental animals, and supporting mechanistic data. The epidemiology studies show no consistent increased incidence of, or mortality from, any type of cancer. In animal studies, increased incidence rates of mostly benign tumors have been observed only in certain strains of one species (mice) and at one tissue site (lung). The lack of concordance of tumor incidence and tumor type among animals (even within the same species) and humans indicates that there has been no particular cancer consistently observed among all available studies. The only plausible mechanism for styrene-induced carcinogenesis—a non-genotoxic mode of action that is specific to the mouse lung—is not relevant to humans. As a whole, the evidence does not support the characterization of styrene as “reasonably anticipated to be a human carcinogen,” and styrene should not be listed in the Report on Carcinogens. PMID:23335843

  11. Gordon Research Conference on Genetic Toxicology

    Energy Technology Data Exchange (ETDEWEB)

    Project Director Penelope Jeggo

    2003-02-15

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

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

    Science.gov (United States)

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

    2013-12-01

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

  13. Post-mortem toxicology in young sudden cardiac death victims

    DEFF Research Database (Denmark)

    Bjune, Thea; Risgaard, Bjarke; Kruckow, Line

    2017-01-01

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

  14. Advancing Risk Assessment through the Application of Systems Toxicology

    Science.gov (United States)

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

    2016-01-01

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

  15. New horizons in predictive toxicology: current status and application

    National Research Council Canada - National Science Library

    Wilson, A. G. E

    2012-01-01

    "In this comprehensive discussion of predictive toxicology and its applications, leading experts express their views on the technologies currently available and the potential for future developments...

  16. La toxicología en la Universidad de Sevilla

    OpenAIRE

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

    2010-01-01

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

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

    Science.gov (United States)

    Khan-Mayberry, Noreen N.; Sundaresan, Alemalu

    2009-01-01

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

  18. 77 FR 12836 - Draft Toxicological Review of Biphenyl: In Support of Summary Information on the Integrated Risk...

    Science.gov (United States)

    2012-03-02

    ... the draft human health assessment titled, ``Toxicological Review of Biphenyl: In Support of Summary... email: [email protected] . SUPPLEMENTARY INFORMATION: EPA's IRIS is a human health assessment... exposure to chemical substances found in the environment. Through the IRIS Program, EPA provides the...

  19. Application of toxicogenomics in hepatic systems toxicology for risk assessment: Acetaminophen as a case study

    NARCIS (Netherlands)

    Kienhuis, A.S.; Bessems, J.G.M.; Pennings, J.L.A.; Driessen, M.; Luijten, M.; Delft, van J.H.M.; Ven, van der L.T.M.

    2011-01-01

    Hepatic systems toxicology is the integrative analysis of toxicogenomic technologies, e.g., transcriptomics, proteomics, and metabolomics, in combination with traditional toxicology measures to improve the understanding of mechanisms of hepatotoxic action. Hepatic toxicology studies that have

  20. THE FUTURE OF TOXICOLOGY-PREDICTIVE TOXICOLOGY: AN EXPANDED VIEW OF CHEMICAL TOXICITY

    Science.gov (United States)

    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. Drug shortages: Implications for medical toxicology.

    Science.gov (United States)

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

    2015-07-01

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

  2. Toxicological Problems with the Redy System

    DEFF Research Database (Denmark)

    Broch Møller, B.; Bahnsen, M.; Solgaard, Per Bent

    1976-01-01

    be substituted by another antiseptic. Of special interest was the finding of a very high concentration of boron in the dialysate. It is suggested that this metal, which is a potentially toxic substance, may emanate from the patient. It is concluded that use of the REDY system carries no obvious toxicological......Dialysate from the REDY dialysis system was examined for toxic elements, special attention being paid to the content of zirconium and aluminium. Also investigated was the concentration of formaldehyde in the rinsing fluid of three consecutive washings. The amount of zirconium and aluminium found...

  3. Toxicological applications of neutron-activation analysis

    International Nuclear Information System (INIS)

    Cross, J.D.; Dale, I.M.; Smith, H.

    1975-01-01

    Thermal neutron-activation analysis is recognised as a useful tool for trace element studies in toxicology. This paper describes some recent applications of the technique to three elements when ingested by people in excess of normal intake Two of the elements (copper and chromium) are essential to life and one (bromine) is as yet unclassified. Three deaths were investiagted and trace element levels compared with normal levels from healthy subjects in the same geographical area who had died as a result of violence. (author)

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

    Science.gov (United States)

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

    2015-09-01

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

  5. Male Reproductive Toxicology: Environmental Exposures vs Reproductive Competence

    Science.gov (United States)

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

  6. Toxicological risks of selected flame-retardant chemicals

    National Research Council Canada - National Science Library

    2000-01-01

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

  7. IRIS Toxicological Review of Methanol (Noncancer) (Interagency Science Discussion Draft)

    Science.gov (United States)

    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...

  8. Recent developments in analytical toxicology : for better or for worse

    NARCIS (Netherlands)

    de Zeeuw, RA

    1998-01-01

    When considering the state of the art in toxicology from an analytical perspective, the key developments relate to three major areas. (1) Forensic horizon: Today forensic analysis has broadened its scope dramatically, to include workplace toxicology, drug abuse testing, drugs and driving, doping,

  9. Toxicological Risks of Selected Flame-Retardant Chemicals

    National Research Council Canada - National Science Library

    2000-01-01

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

  10. IRIS Toxicological Review of Trichloroethylene (Interagency Science Consultation Draft)

    Science.gov (United States)

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

  11. TOXICOLOGICAL RESEARCH INVOLVING HUMANS: ETHICAL AND REGULATORY CONSIDERATIONS

    Science.gov (United States)

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

  12. Toxicological and performance aspects of oxygenated motor vehicle fuels

    National Research Council Canada - National Science Library

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

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

  13. Toward the Rational Use of Exposure Information in Mixtures Toxicology

    Science.gov (United States)

    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...

  14. 75 FR 74053 - Availability of Final Toxicological Profiles

    Science.gov (United States)

    2010-11-30

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

  15. The Chemistry and Toxicology of Depleted Uranium

    Directory of Open Access Journals (Sweden)

    Sidney A. Katz

    2014-03-01

    Full Text Available Natural uranium is comprised of three radioactive isotopes: 238U, 235U, and 234U. Depleted uranium (DU is a byproduct of the processes for the enrichment of the naturally occurring 235U isotope. The world wide stock pile contains some 1½ million tons of depleted uranium. Some of it has been used to dilute weapons grade uranium (~90% 235U down to reactor grade uranium (~5% 235U, and some of it has been used for heavy tank armor and for the fabrication of armor-piercing bullets and missiles. Such weapons were used by the military in the Persian Gulf, the Balkans and elsewhere. The testing of depleted uranium weapons and their use in combat has resulted in environmental contamination and human exposure. Although the chemical and the toxicological behaviors of depleted uranium are essentially the same as those of natural uranium, the respective chemical forms and isotopic compositions in which they usually occur are different. The chemical and radiological toxicity of depleted uranium can injure biological systems. Normal functioning of the kidney, liver, lung, and heart can be adversely affected by depleted uranium intoxication. The focus of this review is on the chemical and toxicological properties of depleted and natural uranium and some of the possible consequences from long term, low dose exposure to depleted uranium in the environment.

  16. Space Toxicology Challenges and Ethical Considerations

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

  18. Integration of QSAR and in vitro toxicology.

    Science.gov (United States)

    Barratt, M D

    1998-01-01

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

  19. Web tools for predictive toxicology model building.

    Science.gov (United States)

    Jeliazkova, Nina

    2012-07-01

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

  20. PIXE applications to the toxicological field

    Energy Technology Data Exchange (ETDEWEB)

    Santos, C.E.I. dos; Dias, J.F.; Jobim, P.F.C.; Yoneama, M.L. [Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS (Brazil). Instituto de Fisica. Laboratorio de Implantacao Ionica; Andrade, V.M. [Universidade do Extremo Sul Catarinense, Criciuma, SC (Brazil). Laboratorio de Biologia Celular e Molecular; Amaral, L.; Silva, J. da [Universidade Luterana do Brasil, Canoas, RS (Brazil). Laboratorio de Toxicologia Generica

    2013-07-01

    Full text: Several studies have been carried out in order to investigate the toxicological properties of some chemical elements in different type of biological samples. lon beam techniques, in particular PIXE, have been successfully used to analyze the elemental composition of food, beverage, plants and animal tissues. In this context, the PIXE line of the lon Implantation Laboratory (Porto Alegre, Brazil) have been used in the last few years to study food and beverage processing and biological specimens exposed to contaminated environment. The aim of this study is to present some of our results using PIXE analysis applied to toxicological research field. For instance, a recent published research [1] investigated the genotoxic and mutagenic effects in tobacco farmers exposed to metal-based formulated pesticides. Levels of Mg, AI, CI, Zn, Cr and Br, elements associated with DNA damage, were higher in the blood samples of tobacco farmers exposed to pesticide than in the non-exposed group. The occupational genotoxicity among copper smelters was also investigated [2]. The elemental content of blood samples were analyzed by PIXE. DNA damage in the peripheral blood Iymphocytes of workers exposed to copper smelter was observed. However, no clear correlation was found between the metal content and DNA damage. [1] F. R. da Silva, J. da Silva, M. C. AlIgayer, C. F. Simon, J. F. Dias, C. E. I. dos Santos, M. Salvador, C. Branco, N. B. Schneider, V. Kahl, P. Rohr, K. Kvitko, J. Hazard. Mat., 225-226 (2012) 81-90. (author)

  1. PIXE applications to the toxicological field

    International Nuclear Information System (INIS)

    Santos, C.E.I. dos; Dias, J.F.; Jobim, P.F.C.; Yoneama, M.L.; Andrade, V.M.; Amaral, L.; Silva, J. da

    2013-01-01

    Full text: Several studies have been carried out in order to investigate the toxicological properties of some chemical elements in different type of biological samples. lon beam techniques, in particular PIXE, have been successfully used to analyze the elemental composition of food, beverage, plants and animal tissues. In this context, the PIXE line of the lon Implantation Laboratory (Porto Alegre, Brazil) have been used in the last few years to study food and beverage processing and biological specimens exposed to contaminated environment. The aim of this study is to present some of our results using PIXE analysis applied to toxicological research field. For instance, a recent published research [1] investigated the genotoxic and mutagenic effects in tobacco farmers exposed to metal-based formulated pesticides. Levels of Mg, AI, CI, Zn, Cr and Br, elements associated with DNA damage, were higher in the blood samples of tobacco farmers exposed to pesticide than in the non-exposed group. The occupational genotoxicity among copper smelters was also investigated [2]. The elemental content of blood samples were analyzed by PIXE. DNA damage in the peripheral blood Iymphocytes of workers exposed to copper smelter was observed. However, no clear correlation was found between the metal content and DNA damage. [1] F. R. da Silva, J. da Silva, M. C. AlIgayer, C. F. Simon, J. F. Dias, C. E. I. dos Santos, M. Salvador, C. Branco, N. B. Schneider, V. Kahl, P. Rohr, K. Kvitko, J. Hazard. Mat., 225-226 (2012) 81-90. (author)

  2. Regulatory toxicology in the twenty-first century: challenges, perspectives and possible solutions.

    Science.gov (United States)

    Tralau, Tewes; Oelgeschläger, Michael; Gürtler, Rainer; Heinemeyer, Gerhard; Herzler, Matthias; Höfer, Thomas; Itter, Heike; Kuhl, Thomas; Lange, Nikola; Lorenz, Nicole; Müller-Graf, Christine; Pabel, Ulrike; Pirow, Ralph; Ritz, Vera; Schafft, Helmut; Schneider, Heiko; Schulz, Thomas; Schumacher, David; Zellmer, Sebastian; Fleur-Böl, Gaby; Greiner, Matthias; Lahrssen-Wiederholt, Monika; Lampen, Alfonso; Luch, Andreas; Schönfelder, Gilbert; Solecki, Roland; Wittkowski, Reiner; Hensel, Andreas

    2015-06-01

    The advent of new testing systems and "omics"-technologies has left regulatory toxicology facing one of the biggest challenges for decades. That is the question whether and how these methods can be used for regulatory purposes. The new methods undoubtedly enable regulators to address important open questions of toxicology such as species-specific toxicity, mixture toxicity, low-dose effects, endocrine effects or nanotoxicology, while promising faster and more efficient toxicity testing with the use of less animals. Consequently, the respective assays, methods and testing strategies are subject of several research programs worldwide. On the other hand, the practical application of such tests for regulatory purposes is a matter of ongoing debate. This document summarizes key aspects of this debate in the light of the European "regulatory status quo", while elucidating new perspectives for regulatory toxicity testing.

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

    Science.gov (United States)

    Gerostamoulos, Dimitri; Beyer, Jochen

    2010-09-01

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

  4. NTP toxicology and carcinogensis studies of dipropylene glycol (CAS No. 25265-71-8) in F344/N rats and B6C3F1 mice (drinking water studies).

    Science.gov (United States)

    2004-06-01

    Dipropylene glycol is found in antifreeze, air fresheners, cosmetic products, solvents, and plastics. We studied the effects of dipropylene glycol on male and female rats and mice to identify potential or cancer-related hazards to humans. We gave groups of 50 male and female mice drinking water containing dipropylene glycol at concentrations of 10,000, 20,000, or 40,000 parts per million (corresponding to 1%, 2%, or 4%) for two years. Male and female rats received concentrations of 2,500, 10,000, or 40,000 parts per million. Other groups received untreated water and were the control group. Tissues from more than 40 sites were examined for every animal. The groups of animals receiving 40,000 ppm dipropylene glycol weighed less than the control animals. All the make rats receiving 40,000 ppm dipropylene glycol died before the end of the study, mainly because of kidney disease. All the other animal group survived as well as the controls. No increase in tumor rates were seen in any of the groups of rats or mice. We conclude that dipropylene glycol did not cause cancer in male or female rats or mice. Exposure to dipropylene glycol did increase the rate and severity of kidney nephropathy and inflammation of the liver and salivary gland in male rats and some atrophy of the epithelial tissue of the nose in male and female rats.

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

    Science.gov (United States)

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

    2011-01-01

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

  6. Titanium dioxide: inhalation toxicology and epidemiology.

    Science.gov (United States)

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

    2005-08-01

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

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

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

    2017-06-01

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

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

    Science.gov (United States)

    Barbosa, Fernando

    2017-01-01

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

    Science.gov (United States)

    Fujie, Tomoya; Hara, Takato; Kaji, Toshiyuki

    2016-01-01

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

  11. Recent developments in preclinical toxicological pathology

    International Nuclear Information System (INIS)

    Finch, John M.

    2005-01-01

    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

  12. Pharmacokinetics, pharmacodynamics and toxicology of theranostic nanoparticles

    Science.gov (United States)

    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.

  13. IRIS Toxicological Review of Tetrahydrofuran (THF) ...

    Science.gov (United States)

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

  14. Handbook of toxicology of chemical warfare agents

    CERN Document Server

    2010-01-01

    This groundbreaking book covers every aspect of deadly toxic chemicals used as weapons of mass destruction and employed in conflicts, warfare and terrorism. Including findings from experimental as well as clinical studies, this one-of-a-kind handbook is prepared in a very user- friendly format that can easily be followed by students, teachers and researchers, as well as lay people. Stand-alone chapters on individual chemicals and major topics allow the reader to easily access required information without searching through the entire book. This is the first book that offers in-depth coverage of individual toxicants, target organ toxicity, major incidents, toxic effects in humans, animals and wildlife, biosensors, biomarkers, on-site and laboratory analytical methods, decontamination and detoxification procedures, prophylactic, therapeutic and countermeasures, and the role of homeland security. Presents a comprehensive look at all aspects of chemical warfare toxicology in one reference work. This saves research...

  15. Applicability of Computational Systems Biology in Toxicology

    DEFF Research Database (Denmark)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2014-09-01

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

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

    Science.gov (United States)

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

    2013-01-01

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

  18. The Installation Restoration Program Toxicology Guide. Volume 5

    Science.gov (United States)

    1990-11-01

    therapeutic purposes or when acidic brews or drinks are made in galvanized vessels (5603). 74.2.5 Biological Monitoring Biological monitoring methods for zinc... therapeutic use of zinc supplements and from food contamination caused by the use of zinc galvanized containers. Symptoms develop within 24 hr and include...The fulvic acid fractions of horticultural peat and soil had overall conditional stability constants of 4.98 and 4.2-4.35, respectively. The overall

  19. The Installation Restoration Program Toxicology Guide. Volume 2

    Science.gov (United States)

    1987-05-01

    Periodic Table: fluorine , chlorine, bromine, iodine, and astatine. Fluorine is the most active of all chemical elements. 5/87 LIST OF ABBREVIATIONS...fire- retardant varnishes and as an aminizing agent for cotton fabric (901). 37.2 ENVIRONMENTAL FATE A1D EXPOSURE PATHWAYS 37.2.1 Transport in Soil...subject to packaging and labeling regulations. Directive on Paints, Varnishes . Printing Inks. Adhesives and Similar Product; (1334) Pentachlorophenol

  20. The Installation Restoration Program Toxicology Guide. Volume 1

    Science.gov (United States)

    1989-07-01

    injury, if present, is characterized by lower back pain, painful and decreased urination, edema and weight gain (17). Parkinsonism as a consequence of...As cited in 687) 692. Melamed, E.; Lavy, S. 1977. Parkinsonism associated with chronic inhalation of carbon tetrachloride. Lancet 1:1015. 693. Simler...Partyka, E.K. 1981. Chronic dysphagia and trigeminal anesthesia after trichloroethylene exposure. Ann. Int. Med. 95:710. 110. Manson, J.M.; Murphy

  1. The Installation Restoration Program Toxicology Guide. Volume 3

    Science.gov (United States)

    1987-06-01

    exchanges were observed in rat- kangaroo cells treated with p,p’-DDT at 10 Ug/mL/24 hours. The p,p’-isomer accounts for most ot thi toxicity attributed to...ity of degra..ative enzymes (2000,1991). In mammals, including man, DDT is metabolized by 2 pathways. It is convertud to a slight extent to DDE which...sympathetic discharge were observed to accompany the tremors and convulsions. These were thought to be due to changes in the metabolism of brain

  2. The Installation Restoration Program Toxicology Guide. Volume 2

    Science.gov (United States)

    1989-07-01

    15:1006-1014. Cumins 27-26 1,4-DICITLOROBBEJZENE 36. Mackay, D.; Patterson, S. IWI. Fugacity revisited. Enriron. Sci. TechnoL 16.654A-660A. 3X...and guinea pigs were exposed to vapor levels of 69 ppm for 93 seven-hour exposures, 5 days per week for 130 days. Only mild physiologic stress was

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

    National Research Council Canada - National Science Library

    Prince, Joseph

    1996-01-01

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

  4. The Installation Restoration Program Toxicology Guide. Volume 3

    Science.gov (United States)

    1989-07-01

    Cannon, C.; Bloom , A.D.; Nakamu~ra, F.; Ahmned, M.; Duk, S.; Rimpo, J.; Margolin, B~a; Resnickr. M.A; Anderson, B.; Zeiger, E. 1987. Chromosome...carbon compounds evaluated in the SCE test in vitro. Environ Mutage:. 9.401-410. 3846. Woodruff, R.& ; Mason, J.M.; Valencia , RL; Zi7nmering, S. 1984...0.2 ppm), bread, oranges and rum. This compound appears to be a r.ommon component of the diet although a total exposure from this source can not be

  5. The Installation Restoration Program Toxicology Guide. Volume 4

    Science.gov (United States)

    1989-07-01

    petechial hemorrhages. No gross malformations were seen. Injection of Vitamin B, improved the fetal survival rate from 37% to 70%. All newborns of dams...nced lethait,. conjunctivitis and tremors. ’The day following his last exposure to hydrazine he dev!oped fever , vomiting and diarrhea. He soon developed...hydazie.Arthrvlig and stiIfncss rash. fatigue and low grade fever developed in the technician, bit not the tW Hydrazinen vitro, blocked Igo production

  6. Translational toxicology: a developmental focus for integrated research strategies.

    Science.gov (United States)

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

    2013-09-30

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

  7. NTP Toxicity Study Report on the atmospheric characterization, particle size, chemical composition, and workplace exposure assessment of cellulose insulation (CELLULOSEINS).

    Science.gov (United States)

    Morgan, Daniel L

    2006-08-01

    application activities for longer periods of time. There was evidence of work-related eye and mucous membrane irritation among some workers, which were possibly caused by the additives present in CI, such as boric acid. There was little evidence of lower respiratory system health conditions associated with CI exposure. Based upon the results of the CI chemical characterization studies, the pulmonary toxicity study, and the worksite exposure assessment, the NTP concluded that additional studies of CI in laboratory animals are not warranted at this time. However, the animal pulmonary toxicity studies and worker health surveys focused on acute CI exposures and do not preclude the possibility of toxicity resulting from chronic exposure. Although exposure concentrations of respirable CI particulate matter were low, additional information is needed on the biodurability and reactivity of CI particles and fibers in the respiratory tract. CI should continue to be regarded as a nuisance dust, and workers should continue to wear protective masks to prevent inhalation exposure to CI dusts.

  8. [Development and Application of Metabonomics in Forensic Toxicology].

    Science.gov (United States)

    Yan, Hui; Shen, Min

    2015-06-01

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

  9. Application of Model Animals in the Study of Drug Toxicology

    Science.gov (United States)

    Song, Yagang; Miao, Mingsan

    2018-01-01

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

  10. Toxicología clínica comunitaria Community Clinical Toxicology

    Directory of Open Access Journals (Sweden)

    María Elena Leal

    2011-08-01

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

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

    International Nuclear Information System (INIS)

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

    1979-12-01

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

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

    International Nuclear Information System (INIS)

    Suter, Laura; Schroeder, Susanne; Meyer, Kirstin; Gautier, Jean-Charles; Amberg, Alexander; Wendt, Maria; Gmuender, Hans; Mally, Angela; Boitier, Eric; Ellinger-Ziegelbauer, Heidrun; Matheis, Katja; Pfannkuch, Friedlieb

    2011-01-01

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

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

    Science.gov (United States)

    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

  14. Using Toxicological Evidence from QSAR Models in Practice

    Science.gov (United States)

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

  15. Toxicological effects of spent engine oil from automechanic ...

    African Journals Online (AJOL)

    Toxicological effects of spent engine oil from automechanic workshops on the gills ... AFRICAN JOURNALS ONLINE (AJOL) · Journals · Advanced Search · USING ... Engine oil, a major lubricant in automobile engines is often discharged in its ...

  16. The minipig as a platform for new technologies in toxicology

    DEFF Research Database (Denmark)

    Forster, Roy; Ancian, Philippe; Fredholm, Merete

    2010-01-01

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

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

    Science.gov (United States)

    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 ...

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

    Science.gov (United States)

    Viette, Véronique; Hochstrasser, Denis; Fathi, Marc

    2012-01-01

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

  19. Metals in leafy vegetables grown in Addis Ababa and toxicological ...

    African Journals Online (AJOL)

    Metals in leafy vegetables grown in Addis Ababa and toxicological implications. ... the leafy vegetables is attributed to plant differences in tolerance to heavy metals. ... Treatment of industrial effluents and phyto-extraction of excess metals from ...

  20. Diversification in toxicology: man and environment. EUROTOX proceedings

    Energy Technology Data Exchange (ETDEWEB)

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

    1998-12-31

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

  1. Biochemical and toxicological studies of aqueous extract of ...

    African Journals Online (AJOL)

    Biochemical and toxicological studies of aqueous extract of Syzigium ... tract diseases and also used as food spices), on some biochemical indices, such as ... liver functions and blood parameters were studied in adult albino rats of both sexes.

  2. 75 FR 54889 - Development of Set 24 Toxicological Profiles

    Science.gov (United States)

    2010-09-09

    ... these documents will be available at the ATSDR Web site: http://www.atsdr.cdc.gov/toxpro2.html . Set 24... toxicological profiles for each substance included on the Priority List of Hazardous Substances ( http://www...

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

    Science.gov (United States)

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

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

    Science.gov (United States)

    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.

  5. Clinical toxicology of newer recreational drugs.

    Science.gov (United States)

    Hill, Simon L; Thomas, Simon H L

    2011-10-01

    Novel synthetic 'designer' drugs with stimulant, ecstasy-like (entactogenic) and/or hallucinogenic properties have become increasingly popular among recreational drug users in recent years. The substances used change frequently in response to market trends and legislative controls and it is an important challenge for poisons centres and clinical toxicologists to remain updated on the pharmacological and toxicological effects of these emerging agents. To review the available information on newer synthetic stimulant, entactogenic and hallucinogenic drugs, provide a framework for classification of these drugs based on chemical structure and describe their pharmacology and clinical toxicology. A comprehensive review of the published literature was performed using PUBMED and Medline databases, together with additional non-peer reviewed information sources, including books, media reports, government publications and internet resources, including drug user web forums. Novel synthetic stimulant, entactogenic or hallucinogenic designer drugs are increasingly available to users as demonstrated by user surveys, poisons centre calls, activity on internet drug forums, hospital attendance data and mortality data. Some population sub groups such as younger adults who attend dance music clubs are more likely to use these substances. The internet plays an important role in determining the awareness of and availability of these newer drugs of abuse. Most novel synthetic stimulant, entactogenic or hallucinogenic drugs of abuse can be classified according to chemical structure as piperazines (e.g. benzylpiperazine (BZP), trifluoromethylphenylpiperazine), phenethylamines (e.g. 2C or D-series of ring-substituted amfetamines, benzodifurans, cathinones, aminoindans), tryptamines (e.g. dimethyltryptamine, alpha-methyltryptamine, ethyltryptamine, 5-methoxy-alphamethyltryptamine) or piperidines and related substances (e.g. desoxypipradrol, diphenylprolinol). Alternatively classification may

  6. Principals Of Radiation Toxicology: Important Aspects.

    Science.gov (United States)

    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

  7. Analysis of Statistical Methods Currently used in Toxicology Journals.

    Science.gov (United States)

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

    2014-09-01

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

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

    Science.gov (United States)

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

    2017-01-01

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

  9. History of the Journal of the American College of Toxicology.

    Science.gov (United States)

    Christian, Mildred S

    2004-01-01

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

  10. Systems Toxicology: From Basic Research to Risk Assessment

    Science.gov (United States)

    2014-01-01

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

  11. Choosing the right laboratory: a review of clinical and forensic toxicology services for urine drug testing in pain management.

    Science.gov (United States)

    Reisfield, Gary M; Goldberger, Bruce A; Bertholf, Roger L

    2015-01-01

    Urine drug testing (UDT) services are provided by a variety of clinical, forensic, and reference/specialty laboratories. These UDT services differ based on the principal activity of the laboratory. Clinical laboratories provide testing primarily focused on medical care (eg, emergency care, inpatients, and outpatient clinics), whereas forensic laboratories perform toxicology tests related to postmortem and criminal investigations, and drug-free workplace programs. Some laboratories now provide UDT specifically designed for monitoring patients on chronic opioid therapy. Accreditation programs for clinical laboratories have existed for nearly half a century, and a federal certification program for drug-testing laboratories was established in the 1980s. Standards of practice for forensic toxicology services other than workplace drug testing have been established in recent years. However, no accreditation program currently exists for UDT in pain management, and this review considers several aspects of laboratory accreditation and certification relevant to toxicology services, with the intention to provide guidance to clinicians in their selection of the appropriate laboratory for UDT surveillance of their patients on opioid therapy.

  12. Analysis of volatile combustion products and a study of their toxicological effects.

    Science.gov (United States)

    Seader, J. D.; Einhorn, I. N.; Drake, W. O.; Mihlfeith, C. M.

    1972-01-01

    An experimental program was conducted to study the thermochemical, flammability and toxicological characteristics of uncoated and coated polyisocyanurate foams. The coatings used were fluorinated copolymer and an intumescent material. Combustion and pyrolysis gases were analyzed by gas chromatography and mass spectrometry. The LD-50 and LD-100 tests were performed on Sprague-Dawley rats housed in an environmental chamber. The isocyanurate foam, fluorinated-copolymer-coated foam, and the intumescent-coated foam were found to have excellent flammability and insulation characteristics, although smoke development was substantial.

  13. Zebrafish in Toxicology and Environmental Health.

    Science.gov (United States)

    Bambino, Kathryn; Chu, Jaime

    2017-01-01

    As manufacturing processes and development of new synthetic compounds increase to keep pace with the expanding global demand, environmental health, and the effects of toxicant exposure are emerging as critical public health concerns. Additionally, chemicals that naturally occur in the environment, such as metals, have profound effects on human and animal health. Many of these compounds are in the news: lead, arsenic, and endocrine disruptors such as bisphenol A have all been widely publicized as causing disease or damage to humans and wildlife in recent years. Despite the widespread appreciation that environmental toxins can be harmful, there is limited understanding of how many toxins cause disease. Zebrafish are at the forefront of toxicology research; this system has been widely used as a tool to detect toxins in water samples and to investigate the mechanisms of action of environmental toxins and their related diseases. The benefits of zebrafish for studying vertebrate development are equally useful for studying teratogens. Here, we review how zebrafish are being used both to detect the presence of some toxins as well as to identify how environmental exposures affect human health and disease. We focus on areas where zebrafish have been most effectively used in ecotoxicology and in environmental health, including investigation of exposures to endocrine disruptors, industrial waste byproducts, and arsenic. © 2017 Elsevier Inc. All rights reserved.

  14. Fluoride in groundwater: toxicological exposure and remedies.

    Science.gov (United States)

    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 (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. Botulinum Neurotoxins: Biology, Pharmacology, and Toxicology.

    Science.gov (United States)

    Pirazzini, Marco; Rossetto, Ornella; Eleopra, Roberto; Montecucco, Cesare

    2017-04-01

    The study of botulinum neurotoxins (BoNT) is rapidly progressing in many aspects. Novel BoNTs are being discovered owing to next generation sequencing, but their biologic and pharmacological properties remain largely unknown. The molecular structure of the large protein complexes that the toxin forms with accessory proteins, which are included in some BoNT type A1 and B1 pharmacological preparations, have been determined. By far the largest effort has been dedicated to the testing and validation of BoNTs as therapeutic agents in an ever increasing number of applications, including pain therapy. BoNT type A1 has been also exploited in a variety of cosmetic treatments, alone or in combination with other agents, and this specific market has reached the size of the one dedicated to the treatment of medical syndromes. The pharmacological properties and mode of action of BoNTs have shed light on general principles of neuronal transport and protein-protein interactions and are stimulating basic science studies. Moreover, the wide array of BoNTs discovered and to be discovered and the production of recombinant BoNTs endowed with specific properties suggest novel uses in therapeutics with increasing disease/symptom specifity. These recent developments are reviewed here to provide an updated picture of the biologic mechanism of action of BoNTs, of their increasing use in pharmacology and in cosmetics, and of their toxicology. Copyright © 2017 by The Author(s).

  16. Reproductive toxicological aspects of chromium in males

    International Nuclear Information System (INIS)

    Ernst, E.

    1994-01-01

    To expand our present understanding of the effects of chromium on male fertility a number of studies were designed to achieve this through the use of chromium intoxicated experimental animals and through investigation of sexual hormones and sperm quality in welders. Also in view of the lack of an experimental model for effects of noxious substance on the epididymal spermatozoa the main objectives of the series of studies reviewed here were: A. To establish a model for evaluation of epididymal sperm count and motility in the rat. B. To investigate and compare the effects of tri- and hexavalent chromium on epididymal spermatozoa. Further to describe the effects of low-dose long-time exposure of rats to the most toxicological interesting chromium oxidative state - hexavalent chromium. C. By the use of autoradiography and γ-countinuing to expand the present knowledge on the distribution of chromium in the body with special reference to the male reproductive organs. D. To describe the effects of exposure to hexavalent chromium in welding fume on levels of sexual hormones and semen parameters in welders. (EG)

  17. The in vitro toxicology of Swedish snus

    Science.gov (United States)

    Coggins, Christopher R. E.; Ballantyne, Mark; Curvall, Margareta; Rutqvist, Lars-Erik

    2012-01-01

    Three commercial brands of Swedish snus (SWS), an experimental SWS, and the 2S3 reference moist snuff were each tested in four in vitro toxicology assays. These assays were: Salmonella reverse mutation, mouse lymphoma, in vitro micronucleus, and cytotoxicity. Water extractions of each of the 5 products were tested using several different concentrations; the experimental SWS was also extracted using dimethyl sulfoxide (DMSO). Extraction procedures were verified by nicotine determinations. Results for SWS in the mutagenicity assays were broadly negative: there were occasional positive responses, but these were effectively at the highest concentration only (concentrations well above those suggested by regulatory guidelines), and were often associated with cytotoxicity. The 2S3 reference was unequivocally positive in one of the three conditions of the micronucleus assay (MNA), at the highest concentration only. Positive controls produced the expected responses in each assay. The SWS data are contrasted with data reported for combusted tobacco in the form of cigarettes, where strongly positive responses have been routinely reported for mutagenicity and cytotoxicity. These negative findings in a laboratory setting concur with the large amount of epidemiological data from Sweden, data showing that SWS are associated with considerably lower carcinogenic potential when compared with cigarettes. PMID:22400986

  18. Pharmacokinetics and toxicology of continuously infused nitroimidazoles

    International Nuclear Information System (INIS)

    Eifel, P.J.; Brown, J.M.

    1984-01-01

    The pharmacokinetics and toxicology of misonidazole (MISO) and SR-2508 given by continuous intraperitoneal infusion were studied in female C 3 H mice. The survival (time to death) of animals receiving continuous infusions of SR-2508 and MISO was compared and related to plasma concentration, rate of infusion and total amount of drug delivered. Brain and plasma concentrations were determined by HPLC. For SR-2508, plasma concentration was directly proportional to the infusion rate. However, as the infusion rate of MISO was doubled, the plasma concentration of MISO increased approximately 6-fold, reflecting a substantial increase in the apparent half-life. The brain/plasma concentration ratio in animals infused for up to 6 days with SR-2508 remained constant, at approximately 0.09. At plasma concentrations of 0.08-1.5 mM, animals receiving SR-2508 survived approximately 3 times as long as animals exposed to a comparable plasma concentration of MISO. Even at the lowest infusion rates employed in this study, the survival of mice receiving SR-2508 was much shorter than would have been predicted if the toxicity of these two drugs were solely related to the integral brain exposure. The low brain/plasma concentration ratio of SR-2508 was maintained throughout long continuous exposures

  19. Systems Toxicology of Male Reproductive Development ...

    Science.gov (United States)

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

  20. The Neuronal Transition Probability (NTP) Model for the Dynamic Progression of Non-REM Sleep EEG: The Role of the Suprachiasmatic Nucleus

    CERN Document Server

    Merica, H

    2011-01-01

    Little attention has gone into linking to its neuronal substrates the dynamic structure of non-rapid-eye-movement (NREM) sleep, defined as the pattern of time-course power in all frequency bands across an entire episode. Using the spectral power time-courses in the sleep electroencephalogram (EEG), we showed in the typical first episode, several moves towards-and-away from deep sleep, each having an identical pattern linking the major frequency bands beta, sigma and delta. The neuronal transition probability model (NTP) - in fitting the data well - successfully explained the pattern as resulting from stochastic transitions of the firing-rates of the thalamically-projecting brainstem-activating neurons, alternating between two steady dynamic-states (towards-and-away from deep sleep) each initiated by a so-far unidentified flip-flop. The aims here are to identify this flip-flop and to demonstrate that the model fits well all NREM episodes, not just the first. Using published data on suprachiasmatic nucleus (SCN...

  1. Study of the $K^{+}K^{-} \\pi^{+}\\pi^{-}\\pi^{0}$ final state in antiproton annihilation at rest in gaseous hydrogen at NTP with the OBELIX spectrometer

    CERN Document Server

    Nichitiu, F; Balestra, F; Bertin, A; Bonomi, G; Botta, E; Bressani, Tullio; Bruschi, M; Bussa, M P; Busso, L; Calvo, D; Capponi, M; Cerello, P G; Cicalò, C; Costa, S; D'Isep, D; De Castro, S; De Galco, A; Denisov, O; Donzella, A; Feliciello, A; Filippi, A; Filippini, V; Fontana, A; Galli, D; Garfagnini, R; Giacobbe, B; Gianotti, P; Gorchakov, O E; Grasso, A; Guaraldo, C; Iazzi, F; Lanaro, A; Lodi-Rizzini, E; Lucherini, V; Maggiora, A; Marcello, S; Marconi, U; Masoni, A; Massa, I; Mauro, S; Minetti, B; Mirfakhraee, N; Montagna, P; Panzarasa, A; Panzieri, D; Petrascu, C; Piccinini, M; Poli, M; Prakhov, S N; Puddu, G; Rosca, A; Rotondi, A; Rozhdestvensky, A M; Salvini, P; Semprini-Cesari, N; Spighi, R; Tessaro, S; Tosello, F; Tretyak, V I; Usai, G L; Vagnoni, V M; Vecchi, S; Venturelli, L; Villa, M; Vitale, A; Zenoni, A; Zoccoli, A

    2002-01-01

    A spin-parity analysis of a sample of pp to K/sup +/K/sup -/ pi /sup +/ pi /sup -/ pi /sup 0/ annihilation events taken at rest in gaseous H/sub 2/ at NTP is reported. The invariant mass spectrum of the K/sup +/K/sup -/ pi /sup 0/ system shows the presence of the E/t resonance pattern at 1.42 GeV. The analysis of this signal confirms the results obtained by the OBELIX Collaboration in previous works, namely: the existence of two pseudoscalar states at 1.413+or-0.002 and 1.460+or-0.012 GeV with widths 0.051+or-0.004 and 0.120+or-0.015 GeV, respectively. The pp system in the /sup 3/P/sub 1/ wave shows also a signal corresponding to the axial vector f/sub 1/ (1420) decaying to K*K with mass 1.420+or-0.003 GeV and width 0.061+or-0.005 GeV. A study of the incoherent phase space background shows that its origin is mostly due to the reflection of a resonant state in the K/sup +/K /sup -/ pi /sup +/ pi /sup -/ system. The isobar decomposition of this resonant state is mainly f/sub 0/(1370)( pi pi )/sub S/, its parame...

  2. DNA Polymerase Fidelity: Comparing Direct Competition of Right and Wrong dNTP Substrates with Steady State and Presteady State Kinetics†

    Science.gov (United States)

    Bertram, Jeffrey G.; Oertell, Keriann; Petruska, John; Goodman, Myron F.

    2009-01-01

    DNA polymerase fidelity is defined as the ratio of right (R) to wrong (W) nucleotide incorporations when dRTP and dWTP substrates compete at equal concentrations for primer extension at the same site in the polymerase-primer-template DNA complex. Typically, R incorporation is favored over W by 103 – 105, even in the absence of 3′-exonuclease proofreading. Straightforward in principal, a direct competition fidelity measurement is difficult to perform in practice because detection of a small amount of W is masked by a large amount of R. As an alternative, enzyme kinetics measurements to evaluate kcat/Km for R and W in separate reactions are widely used to measure polymerase fidelity indirectly, based on a steady-state derivation by Fersht. A systematic comparison between direct competition and kinetics has not been made until now. By separating R and W products using electrophoresis, we have successfully made accurate fidelity measurements for directly competing R and W dNTP substrates for 9 of the 12 natural base mispairs. We compare our direct competition results with steady state and presteady state kinetic measurements of fidelity at the same template site, using the proofreading-deficient mutant of Klenow Fragment (KF−) DNA polymerase. All the data are in quantitative agreement. PMID:20000359

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

    Science.gov (United States)

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

    2011-01-01

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

  4. 78 FR 12764 - Draft Office of Health Assessment and Translation Approach for Systematic Review and Evidence...

    Science.gov (United States)

    2013-02-25

    ... study will evaluate the association of bisphenol A (BPA) exposure with obesity and the other will... Health Assessments--February 2013; Request for Comments; Notice of a Meeting SUMMARY: The National Toxicology Program (NTP) requests public comments on the Draft Office of Health Assessment and Translation...

  5. The accuracy of extended histopathology to detect immunotoxic chemicals

    NARCIS (Netherlands)

    Germolec, D.R.; Kashon, M.; Nyska, A.; Kuper, C.F.; Portier, C.; Kommineni, C.; Johnson, K.A.; Luster, M.I.

    2004-01-01

    The accuracy of extended histopathology to detect immunotoxic chemicals in female B6C3F1 mice was evaluated under the auspices of the National Toxicology Program (NTP). A workgroup was formed consisting of four pathologists who conducted extended histopathological evaluation of lymphoid tissues

  6. Has Toxicity Testing Moved into the 21st Century? A Survey and Analysis of Perceptions in the Field of Toxicology.

    Science.gov (United States)

    Zaunbrecher, Virginia; Beryt, Elizabeth; Parodi, Daniela; Telesca, Donatello; Doherty, Joseph; Malloy, Timothy; Allard, Patrick

    2017-08-30

    Ten years ago, leaders in the field of toxicology called for a transformation of the discipline and a shift from primarily relying on traditional animal testing to incorporating advances in biotechnology and predictive methodologies into alternative testing strategies (ATS). Governmental agencies and academic and industry partners initiated programs to support such a transformation, but a decade later, the outcomes of these efforts are not well understood. We aimed to assess the use of ATS and the perceived barriers and drivers to their adoption by toxicologists and by others working in, or closely linked with, the field of toxicology. We surveyed 1,381 toxicologists and experts in associated fields regarding the viability and use of ATS and the perceived barriers and drivers of ATS for a range of applications. We performed ranking, hierarchical clustering, and correlation analyses of the survey data. Many respondents indicated that they were already using ATS, or believed that ATS were already viable approaches, for toxicological assessment of one or more end points in their primary area of interest or concern (26-86%, depending on the specific ATS/application pair). However, the proportions of respondents reporting use of ATS in the previous 12 mo were smaller (4.5-41%). Concern about regulatory acceptance was the most commonly cited factor inhibiting the adoption of ATS, and a variety of technical concerns were also cited as significant barriers to ATS viability. The factors most often cited as playing a significant role (currently or in the future) in driving the adoption of ATS were the need for expedited toxicology information, the need for reduced toxicity testing costs, demand by regulatory agencies, and ethical or moral concerns. Our findings indicate that the transformation of the field of toxicology is partly implemented, but significant barriers to acceptance and adoption remain. https://doi.org/10.1289/EHP1435.

  7. Tetrahydrocannabinols in clinical and forensic toxicology.

    Science.gov (United States)

    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.

  8. Perlite toxicology and epidemiology – a review

    Science.gov (United States)

    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

  9. Cross matching observations on toxicological and clinical data for the assessment of tolerability and safety of Ginkgo biloba leaf extract

    International Nuclear Information System (INIS)

    Heinonen, Tuula; Gaus, Wilhelm

    2015-01-01

    on G. biloba. We give an in depth analysis of the modes of action in animals and describe toxicological studies with regard to metabolism, pharmacokinetics, genotoxicity, as well as carcinogenicity (e.g., the Technical Report TR 578 of the US National Toxicology Program). In addition, 75 clinical trials with high methodological quality are summarized. They included a total of 7115 patients treated with G. biloba. Based on this extensive amount of information, the broad variety of investigations, and their accordance we conclude that G. biloba extract is well tolerated and safe for humans

  10. Computational toxicology: Its essential role in reducing drug attrition.

    Science.gov (United States)

    Naven, R T; Louise-May, S

    2015-12-01

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

  11. Pre implanted mouse embryos as model for uranium toxicology studies

    International Nuclear Information System (INIS)

    Kundt, Miriam S.

    2001-01-01

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

  12. Zebrafish neurotransmitter systems as potential pharmacological and toxicological targets.

    Science.gov (United States)

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

    2011-01-01

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

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

    Science.gov (United States)

    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.

  14. Exploring shared risks through public-private partnerships in public health programs: a mixed method.

    Science.gov (United States)

    Alonazi, Wadi B

    2017-06-12

    The natural assimilation of the process through which health partners sustain long-term relationships is a key issue in maintaining social well-being, reducing health risk factors, and sustaining public health programs. One global initiative in building effective healthcare systems is public-private partnerships (PPPs). This study elucidates the proposed key performance indicators initiated by the Ministry of Health of Saudi Arabia based on the projections of the government, known as Vision 2030, from the perspective of health risk factors. Through an inductive content analysis, this study assessed primary and secondary data in relation to the Saudi National Transformation Program (NTP). To identify the institutions that played a role in formulating the new Saudi Healthcare System, health policies, regulations, and reports published between 1996 and 2016 were categorized. After ranking the risk factors, the investigator selected 13 healthcare professionals in four focus group interviews to insightfully explore the challenges that the NTP faces from a health risk perspective. Thus, the study employed qualitative data gathered through focus group interviews with key figures as well as data extracted from written sources to identify distinct but interrelated partnerships practiced within risk management. A methodological overview of NTP priority and implementation offered practical guidance in the healthcare context. The five critical factors in maintaining successful and sustainable PPPs were (1) trustworthiness, (2) technological capability, (3) patient-centeredness, (4) competence, and (5) flexibility. Concession on primary and secondary healthcare services might be a good option based on the literature review and considering its popularity in other countries. A high outcome-based risk of PPPs was found as the most commonly shared perspective in risk management. Although the impact of the NTP rise has yet to be explored, its potential for challenging health

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

    DEFF Research Database (Denmark)

    Grandjean, P

    2015-01-01

    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...... 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...... 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...

  16. Molecular dynamics simulations and applications in computational toxicology and nanotoxicology.

    Science.gov (United States)

    Selvaraj, Chandrabose; Sakkiah, Sugunadevi; Tong, Weida; Hong, Huixiao

    2018-02-01

    Nanotoxicology studies toxicity of nanomaterials and has been widely applied in biomedical researches to explore toxicity of various biological systems. Investigating biological systems through in vivo and in vitro methods is expensive and time taking. Therefore, computational toxicology, a multi-discipline field that utilizes computational power and algorithms to examine toxicology of biological systems, has gained attractions to scientists. Molecular dynamics (MD) simulations of biomolecules such as proteins and DNA are popular for understanding of interactions between biological systems and chemicals in computational toxicology. In this paper, we review MD simulation methods, protocol for running MD simulations and their applications in studies of toxicity and nanotechnology. We also briefly summarize some popular software tools for execution of MD simulations. Published by Elsevier Ltd.

  17. Course constructions: A case-base of forensic toxicology.

    Science.gov (United States)

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

    2017-08-01

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

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

    Science.gov (United States)

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

  19. Structural constraints for proposed Fort Hancock low-level radioactive waste disposal site (NTP-S34), southern Hudspeth County, Texas

    International Nuclear Information System (INIS)

    Lemone, D.V.

    1989-01-01

    Structural complexities reduce the homogeneity necessary for a site characterization model to an unacceptable level for performance assessment for radioactive waste disposal sites. The proposed site lies between the northern, stable Diablo platform and the southern, mobile Mesozoic Chihuahua tectonic belt. Structural movement along this interface has been active for the past 14,000 years. In addition, the area lies along the northern margin of the Permian Marfa basin and the northeastern margin of the deeply faulted Hueco bolson segment of the late Cenozoic Rio Grande rift system. Recent seismic activity with extensive surface rupture in Quitman Canyon (30 mi southeast of the site) is also documented from the 1931 Valentine, Texas, earthquake (6.4 Richter scale). The site is underlain by either a thrust fault or the complex terminus of a Mesozoic thrust fault. This fault is a segment of the continuous thrust sheet extending from exposures in the Sierra Blanc area, 30 mi east (Devil Ridge fault), to the El Paso area west (Rio Grande fault). This segment of the Devil Ridge-Rio Grande thrust is documented by the Haymond Krupp No. 1 Thaxton wildcat drilled at Campogrande Mountain immediately south of the site. The recent rift fault scarp (Campo Grande) immediately south of the Thaxton well has a 17-mi surface trace and is, no doubt, related to the subsurface Clint fault to the west in the El Paso area. An additional complexity is the presence of a monoclinal flexure with a minimum of 900 ft of surface relief (2 mi northeast of NTP-S34). A 4.5-mi, east-west, down-to-the-south normal fault occurs near the top of the monocline with a small associated graben. These complexities seriously compromise the proposed Fort Hancock site

  20. Lewisite: its chemistry, toxicology, and biological effects.

    Science.gov (United States)

    Goldman, M; Dacre, J C

    1989-01-01

    routes for inducing teratogenicity is also problematical. Recently, Lewisite has been shown not to be teratogenic in either rats or rabbits. A monograph on arsenic, succinctly states that "no human epidemiological investigations have been conducted on the carcinogenicity of organic arsenic compounds" (WHO 1981). Indeed, the lack of such evidence eminating from epidemiological sources or from animal studies is resounding. At present, there is no evidence that Lewisite is either carcinogenic, mutagenic or teratogenic. A review of toxicological studies of other organic arsenicals has produced no evidence that they might be carcinogenic, mutagenic or teratogenic.

  1. Toxicological comments to the discussion about REACH.

    Science.gov (United States)

    Greim, Helmut; Arand, Michael; Autrup, Herman; Bolt, Hermann M; Bridges, James; Dybing, Erik; Glomot, Rémi; Foa, Vito; Schulte-Hermann, Rolf

    2006-03-01

    It is the ultimate goal of the intended REACH process (Registration, Evaluation and Authorization of Chemicals) of the European Union to identify substances of hazardous properties and to evaluate the risks of human and environmental exposure. During the last few months there has been a controversial discussion as to what extent in vitro studies and consideration of structure activity relationship provide sufficient information to waive repeated exposure studies. Industry as well as certain regulatory agencies or NGOs support this approach and propose that repeated dose studies may only be required beyond 100 t/a. From a toxicological point of view it has to be stressed that this discussion primarily considers the cost reduction and protection of animals, whereas protection of human health and the environment are secondary. In vitro studies only allow identification of specific hazardous properties which can be detected by the specific test system. Moreover, appropriate information on the dose response of adverse effects, identification of thresholds and NOELs that are essential for risk characterization cannot be obtained from these studies. Consequently, identification of all relevant hazardous properties and endpoints of adverse effects can only be determined in the intact animal by repeated dose studies such as 28-day or 90-day studies. In the absence of such information the hazard identification is incomplete and there is no basis for appropriate risk assessment of human exposure. Thus, any waiving of repeated dose studies in animals bears the probability of unforeseen effects in case of acute or continuous human exposure. From this the undersigning European Toxicologists conclude: 1. The intention of REACH is to identify hazardous properties in order that a reliable risk assessment can be made and measures taken to deal with chemicals posing a significant risk. 2. The recent debate has centered on ways in which the well established in vivo methods for risk

  2. Applications of scientific imaging in environmental toxicology

    Science.gov (United States)

    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

  3. Comparative analysis of perturbed molecular pathways identified in in vitro and in vivo toxicology studies

    NARCIS (Netherlands)

    Wiesinger, Martin; Mayer, Bernd; Jennings, Paul; Lukas, Arno

    The development of in vitro toxicological testing strategies are hampered by the difficulty in extrapolation to the intact organism. Academic toxicological literature contains a wealth of mechanistically rich information, especially arising from omic studies, which could potentially be utilized to

  4. Proceedings of the 30. Scientific symposium of industrial toxicology 2010

    International Nuclear Information System (INIS)

    Fargasova, A.; Jambrich, M.; Koprda, V.

    2010-06-01

    Scientific symposium deals with problems of industrial toxicology. The symposium proceeded in the following topics: (I) Relationships between chemical and biota; (II) Radioactivity in the environment, nuclear energy and renewable energy; (III) Accident risk and security industry, civil protection, crisis communication; (IV) Chemical toxicity, and monitoring of the work environment; (V) Chemicals in the environment and health; (VI) Contaminants in food, agricultural and animal products; (VI) Analytical methods in toxicology and environmental science; (VII) Biodegradable renewable raw materials and waste treatment. 27 lectures and 22 posters were presented there. Relevant papers for INIS scope are included.

  5. The DOE policy for protection against radiological and toxicological sabotage

    International Nuclear Information System (INIS)

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

    1995-01-01

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

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

    Science.gov (United States)

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

    2017-04-03

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

  7. In Silico Toxicology – Non-Testing Methods

    Science.gov (United States)

    Raunio, Hannu

    2011-01-01

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

  8. Programming

    International Nuclear Information System (INIS)

    Jackson, M.A.

    1982-01-01

    The programmer's task is often taken to be the construction of algorithms, expressed in hierarchical structures of procedures: this view underlies the majority of traditional programming languages, such as Fortran. A different view is appropriate to a wide class of problem, perhaps including some problems in High Energy Physics. The programmer's task is regarded as having three main stages: first, an explicit model is constructed of the reality with which the program is concerned; second, this model is elaborated to produce the required program outputs; third, the resulting program is transformed to run efficiently in the execution environment. The first two stages deal in network structures of sequential processes; only the third is concerned with procedure hierarchies. (orig.)

  9. Programming

    OpenAIRE

    Jackson, M A

    1982-01-01

    The programmer's task is often taken to be the construction of algorithms, expressed in hierarchical structures of procedures: this view underlies the majority of traditional programming languages, such as Fortran. A different view is appropriate to a wide class of problem, perhaps including some problems in High Energy Physics. The programmer's task is regarded as having three main stages: first, an explicit model is constructed of the reality with which the program is concerned; second, thi...

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

    Science.gov (United States)

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

    2011-01-01

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

  11. 77 FR 72858 - Toxicological Review of Inorganic Arsenic (Cancer and Noncancer Effects): In Support of Summary...

    Science.gov (United States)

    2012-12-06

    ... public stakeholder workshop to inform the development of a state of the science toxicological review of... arsenic (iAs) public stakeholder workshop is designed to inform the planning for EPA's toxicological... impact the toxicological review, and discuss approaches for dose-response. The ultimate goals of the...

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

    Science.gov (United States)

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

  13. Developing an effective toxicology/quality assurance partnership. Improving quality, compliance, and cooperation.

    Science.gov (United States)

    Usher, R W

    1995-12-01

    Toxicology and Quality Assurance (QA) at Eli Lilly and Company are well integrated, yet still independent organizations that are aligned with the same overall business objective: to efficiently deliver a high-quality product to the customer. One of the keys to success has been the implementation of a monitoring/metric and trend analysis program of key work processes that are central to the delivery of final product. Our metrics program indicates that the multiple changes that we have made have resulted in a higher quality product. This paper will discuss the practical changes we have made as a part of our Total Quality journey. This article is based solely on the authors' experiences while at Eli Lilly and Company.

  14. Phytochemical, toxicological and histo-pathological studies of some ...

    African Journals Online (AJOL)

    The plants therefore possess some important biological activities that could be harnessed and employed beneficially in the management of viral and bacterial infections. Keywords: Phytochemistry; toxicology; histo-pathology; rat; medicinal plants; Nigeria International Journal of Natural and Applied Sciences Vol. 2 (3) 2006: ...

  15. Measuring Impact of EPAs Computational Toxicology Research (BOSC)

    Science.gov (United States)

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

  16. Acute Toxicological Effects of Crude Oil On Haematological And ...

    African Journals Online (AJOL)

    The acute toxicological effects of Brass blend of crude oil on the haemoglobin concentration, and Liver functions in the Guinea pig were studied. 25 Guinea pigs divided into five animals per group were used for the study. They were divided into 5 groups. One group served as a control group, while the others received ...

  17. Magnesium 1993 Maternal-Fetal Toxicology. A Clinician's Guide ...

    African Journals Online (AJOL)

    I S I G I 0 I M I. Maternal-Fetal Toxicology. A Clinician's. Guide. 2nd edition. Ed. by Gideon Koren. Pp. 824 ... analysis is presented, and survival curve ideas for effects over time. Final chapters ... SPSS-PC+, SAS and Nanostat. Several important.

  18. Imaging mass spectrometry in drug development and toxicology.

    Science.gov (United States)

    Karlsson, Oskar; Hanrieder, Jörg

    2017-06-01

    During the last decades, imaging mass spectrometry has gained significant relevance in biomedical research. Recent advances in imaging mass spectrometry have paved the way for in situ studies on drug development, metabolism and toxicology. In contrast to whole-body autoradiography that images the localization of radiolabeled compounds, imaging mass spectrometry provides the possibility to simultaneously determine the discrete tissue distribution of the parent compound and its metabolites. In addition, imaging mass spectrometry features high molecular specificity and allows comprehensive, multiplexed detection and localization of hundreds of proteins, peptides and lipids directly in tissues. Toxicologists traditionally screen for adverse findings by histopathological examination. However, studies of the molecular and cellular processes underpinning toxicological and pathologic findings induced by candidate drugs or toxins are important to reach a mechanistic understanding and an effective risk assessment strategy. One of IMS strengths is the ability to directly overlay the molecular information from the mass spectrometric analysis with the tissue section and allow correlative comparisons of molecular and histologic information. Imaging mass spectrometry could therefore be a powerful tool for omics profiling of pharmacological/toxicological effects of drug candidates and toxicants in discrete tissue regions. The aim of the present review is to provide an overview of imaging mass spectrometry, with particular focus on MALDI imaging mass spectrometry, and its use in drug development and toxicology in general.

  19. A comprehensive toxicological evaluation of three adhesives using experimental cigarettes.

    Science.gov (United States)

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

    2013-01-01

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

  20. Manpower Development in Toxicology. EURO Reports and Studies, No. 9.

    Science.gov (United States)

    World Health Organization, Copenhagen (Denmark). Regional Office for Europe.

    This report addresses the widely held view that currently available literature in toxicology is inadequate in that there is a need to identify manpower deficiencies in this field and to suggest means to correct these deficiencies. It contains a list of specific recommendations including the organization of a working group, sponsored by the World…

  1. Systems Toxicology of Embryo Development (9th Copenhagen Workshop)

    Science.gov (United States)

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

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

    Science.gov (United States)

    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...

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

    Science.gov (United States)

    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...

  4. Solid-phase extraction procedures in systematic toxicological analysis

    NARCIS (Netherlands)

    Franke, J.P.; de Zeeuw, R.A

    1998-01-01

    In systematic toxicological analysis (STA) the substance(s) present is (are) not known at the start of the analysis. in such an undirected search the extraction procedure cannot be directed to a given substance but must be a general procedure where a compromise must be reached in that the substances

  5. Toxicological Effects of Cigarette Smoke on Some Biochemical ...

    African Journals Online (AJOL)

    It is believed that while normal people may suffer complications of active and passive cigarette smoking, diabetes patients may suffer more. This study therefore aimed at investigating the toxicological effects of cigarette smoke on some biochemical parameters of alloxan-induced diabetic rats. Adult male Wistar rats (n ...

  6. Recent trends in analytical procedures in forensic toxicology.

    Science.gov (United States)

    Van Bocxlaer, Jan F

    2005-12-01

    Forensic toxicology is a very demanding discipline,heavily dependent on good analytical techniques. That is why new trends appear continuously. In the past years. LC-MS has revolutionized target compound analysis and has become the trend, also in toxicology. In LC-MS screening analysis, things are less straightforward and several approaches exist. One promising approach based on accurate LC-MSTOF mass measurements and elemental formula based library searches is discussed. This way of screening has already proven its applicability but at the same time it became obvious that a single accurate mass measurement lacks some specificity when using large compound libraries. CE too is a reemerging approach. The increasingly polar and ionic molecules encountered make it a worthwhile addition to e.g. LC, as illustrated for the analysis of GHB. A third recent trend is the use of MALDI mass spectrometry for small molecules. It is promising for its ease-of-use and high throughput. Unfortunately, re-ports of disappointment but also accomplishment, e.g. the quantitative analysis of LSD as discussed here, alternate, and it remains to be seen whether MALDI really will establish itself. Indeed, not all new trends will prove themselves but the mere fact that many appear in the world of analytical toxicology nowadays is, in itself, encouraging for the future of (forensic) toxicology.

  7. Forensic toxicology in drug-facilitated sexual assault.

    Science.gov (United States)

    Dinis-Oliveira, Ricardo Jorge; Magalhães, Teresa

    2013-09-01

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

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

    African Journals Online (AJOL)

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

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

    International Nuclear Information System (INIS)

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

    1995-01-01

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

  10. Toxicological effect of consumption of extract of Jatropha ...

    African Journals Online (AJOL)

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

  11. Robust Bayesian Algorithm for Targeted Compound Screening in Forensic Toxicology

    NARCIS (Netherlands)

    Woldegebriel, M.; Gonsalves, J.; van Asten, A.; Vivó-Truyols, G.

    2016-01-01

    As part of forensic toxicological investigation of cases involving unexpected death of an individual, targeted or untargeted xenobiotic screening of post-mortem samples is normally conducted. To this end, liquid chromatography (LC) coupled to high-resolution mass spectrometry (MS) is typically

  12. Antidiabetic And Toxicological Evaluation Of Aqueous Ethanol Leaf ...

    African Journals Online (AJOL)

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

  13. Experimental designs and risk assessment in combination toxicology: Panel discussion

    NARCIS (Netherlands)

    Henschler, D.; Bolt, H.M.; Jonker, D.; Pieters, M.N.; Groten, J.P.

    1996-01-01

    Advancing our knowledge on the toxicology of combined exposures to chemicals and implementation of this knowledge in guidelines for health risk assessment of such combined exposures are necessities dictated by the simple fact that humans are continuously exposed to a multitude of chemicals. A

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

    Science.gov (United States)

    2009-10-01

    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

  15. Toxicology services in Libya: the present and the future

    African Journals Online (AJOL)

    and to revitalize the whole system. The aim is to provide a healthcare system centered around people's needs and expectations, up-to-date with the latest medical advances, and capable of meeting rising demands (1, 2). In Libya, there is no robust poison and toxicology service. This was evident during the 'methanol crisis'.

  16. Inhalation Toxicology Research Institute annual report, October 1, 1994--September 30, 1995

    International Nuclear Information System (INIS)

    Bice, D.E.; Hahn, F.F.; Hoover, M.D.; Neft, R.E.; Thornton-Manning, J.R.; Bradley, P.L.

    1995-12-01

    The mission of the Inhalation Toxicology Research Institute (ITRI) is to conduct basic and applied research to improve the understanding of the nature and magnitude of the human health impacts of inhaling airborne materials in the home, workplace, and general environment. Institute research programs have a strong basic science orientation with emphasis on the nature and behavior of airborne materials, the fundamental biology of the respiratory tract, the fate of inhaled materials and the mechanisms by which they cause disease, and the means by which data produced in the laboratory can be used to estimate risks to human health. Disorders of the respiratory tract continue to be a major health concern, and inhaled toxicants are thought to contribute substantially to respiratory morbidity. As the largest laboratory dedicated to the study of basic inhalation toxicology, ITRI provides a national resource of specialized facilities, personnel, and educational activities serving the needs of government, academia, and industry. Selected papers are indexed separately for inclusion in the Energy Science and Technology Database

  17. Inhalation Toxicology Research Institute annual report, October 1, 1994--September 30, 1995

    Energy Technology Data Exchange (ETDEWEB)

    Bice, D.E.; Hahn, F.F.; Hoover, M.D.; Neft, R.E.; Thornton-Manning, J.R.; Bradley, P.L. [eds.

    1995-12-01

    The mission of the Inhalation Toxicology Research Institute (ITRI) is to conduct basic and applied research to improve the understanding of the nature and magnitude of the human health impacts of inhaling airborne materials in the home, workplace, and general environment. Institute research programs have a strong basic science orientation with emphasis on the nature and behavior of airborne materials, the fundamental biology of the respiratory tract, the fate of inhaled materials and the mechanisms by which they cause disease, and the means by which data produced in the laboratory can be used to estimate risks to human health. Disorders of the respiratory tract continue to be a major health concern, and inhaled toxicants are thought to contribute substantially to respiratory morbidity. As the largest laboratory dedicated to the study of basic inhalation toxicology, ITRI provides a national resource of specialized facilities, personnel, and educational activities serving the needs of government, academia, and industry. Selected papers are indexed separately for inclusion in the Energy Science and Technology Database.

  18. Distance learning and toxicology: New horizons for Paracelsus

    International Nuclear Information System (INIS)

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

    2005-01-01

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

  19. Finding toxicological information: An approach for occupational health professionals

    Directory of Open Access Journals (Sweden)

    Franco Giuliano

    2008-08-01

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

  20. [The challenges of the ethics of personalism to clinical toxicology].

    Science.gov (United States)

    Brusiło, Jerzy

    2011-01-01

    The fields of philosophical anthropology and the ethics of personalism overlap in the area of many difficult personal situations involving clinical toxicology. These therapeutic situations need an integral, multidimensional, and personal approach for both the patient and the toxicologist. This means that man is treated not only as a physical (biological) being but also there is an appreciation for the mental sphere, which includes rational, emotional, and spiritual elements while not forgetting that the human person is also part of the human community. Studying such an individual's personal decision as suicide, we must realize that it's not just physiological or biochemical poisons but also includes the poisoning of the psyche, as well as poisoning relationships with loved ones (family), poisoning social relations (in school or the workplace) and poisoning the spirit, in other words, there is no meaning in life itself, nor the meaning of God's existence, nor the meaning of faith, hope and love. Not only is there a greater "variety of poisons" than before, they are much more extensive and deep. For example, we can name environmental pollution, industrial poisons, chemical waste, genetic modification, powerful medications, or even the toxic social environment of evil ideas, malicious manipulation of the human mind (destructive religious sects). In approaching the challenges of clinical toxicology, the doctor must not only be a specialist in chemistry, biochemistry and pharmacology. What then is of future of toxicology because of this human dimension (anthropological, ethical and spiritual) of this teaching? As today marks the occasion of the 45th anniversary of the Clinic of Toxicology CM UJ, should we shape the ethos of young doctors who want to deal with toxicology seriously?