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) A comprehensive, biologically based mathematical model was developed for the rat estrus cycle (2) A model was developed which describes the important factors for priming hepatocytes to enter the G1 phase of the cell cycle (3) Methods were developed for the backcalculation of exposures in an occupational cohort (4) An NTP study, designed around a PBPK model, of transgenic animals exposed to 2,3,7,8-TCDD was analyzed using a two-stage and a three-stage model (5) A biologically-based model was developed for developmental toxicity (6) Data on morbidity for the city of Tokyo from 1980 to 1994 were analyzed to determine the effects of daily temperatures and air pollutant concentrations (NO2, O3 and PM10) on heat stress and related diseases (7) The impact of polymorphisms on the estimation of risks in a general population were explored (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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Intramural Research (Z01)
Project #
1Z01ES048002-13
Application #
6432309
Study Section
(CBRA)
Project Start
Project End
Budget Start
Budget End
Support Year
13
Fiscal Year
2000
Total Cost
Indirect Cost
Name
U.S. National Inst of Environ Hlth Scis
Department
Type
DUNS #
City
State
Country
United States
Zip Code
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
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
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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