of Work: This project is intended to increase our understanding of the use and application of mathematical and statistical models in toxicology and biochemistry and to implement these mathematical models to aid in explaining current research findings. The research effort explores a diverse range of biological areas, including carcinogenesis, pharmacology, developmental biology, neurology, immunology and endocrinology. Major accomplishments include (1) evaluation of the risks from exposure to pwer-line frequency electric and magnetic fields (2) the derivation of methods for the analysis of carcinogenicity data including data on papillomas, carcinomas and maintaining tissue size (3) new stochastic models of carcinogenesis (4) methods were developed for linking PBPK models, premalignant lesion data, cell labelling data and tumor incidence data (5) models for mortality/morbidity in urban areas are being validated in a Japanese population (6) exposure assessment models have been developed (7) built and experimentally validated a mathematical model describing the estrus cycle in rats and menstrual cycle in women (8) developed methods for evaluating the adequacy of benchmark doses, (9) continued to aid in the scientific improvement of risk assessment methods through the application of sound science to key environmental issues such as exposure to TCDD, aflatoxins and endocrine disruptors. - risk assessment dioxin magnetic fields biomathematics toxicokinetics cancer modeling dose-response

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Intramural Research (Z01)
Project #
1Z01ES048002-12
Application #
6289968
Study Section
Special Emphasis Panel (CBRA)
Project Start
Project End
Budget Start
Budget End
Support Year
12
Fiscal Year
1999
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code
Portier, C (2009) 4 Toxicological decision-making on hazards and risks - status quo and way forward: 4.1 current concepts and schemes of science-driven toxicological decision-making - an overview. Hum Exp Toxicol 28:123-5
Prause, Andrea S; Stoffel, Michael H; Portier, Christopher J et al. (2009) Expression and function of 5-HT7 receptors in smooth muscle preparations from equine duodenum, ileum, and pelvic flexure. Res Vet Sci 87:292-9
Schmitz, A; Portier, C J; Thormann, W et al. (2008) Stereoselective biotransformation of ketamine in equine liver and lung microsomes. J Vet Pharmacol Ther 31:446-55
Gohlke, Julia M; Griffith, William C; Faustman, Elaine M (2008) Computational models of ethanol-induced neurodevelopmental toxicity across species: Implications for risk assessment. Birth Defects Res B Dev Reprod Toxicol 83:1-11
Pfeiffer, Julia B R; Mevissen, Meike; Steiner, Adrian et al. (2007) In vitro effects of bethanechol on specimens of intestinal smooth muscle obtained from the duodenum and jejunum of healthy dairy cows. Am J Vet Res 68:313-22
Barton, Hugh A; Chiu, Weihsueh A; Woodrow Setzer, R et al. (2007) Characterizing uncertainty and variability in physiologically based pharmacokinetic models: state of the science and needs for research and implementation. Toxicol Sci 99:395-402
Gohlke, Julia M; Portier, Christopher J (2007) The forest for the trees: a systems approach to human health research. Environ Health Perspect 115:1261-3
Smith, Marjo V; Miller, Chris R; Kohn, Michael et al. (2007) Absolute estimation of initial concentrations of amplicon in a real-time RT-PCR process. BMC Bioinformatics 8:409
Knobloch, M; Portier, C J; Levionnois, O L et al. (2006) Antinociceptive effects, metabolism and disposition of ketamine in ponies under target-controlled drug infusion. Toxicol Appl Pharmacol 216:373-86
Becker, Richard A; Borgert, Christopher J; Webb, Simon et al. (2006) Report of an ISRTP workshop: progress and barriers to incorporating alternative toxicological methods in the U.S. Regul Toxicol Pharmacol 46:18-22

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