The research in this proposal to provide a fundamental understanding of the influence of route of reexposure on the total body burden and internal target tissue dosimetry of commonly encountered. Superfund contaminants, including trichloroethylene, perchloroethylene, 1,1- dichloroethylene, vinyl chloride, toluene, xylene, benzene, diethylbenzene isomers, and chloroform. Furthermore, since this research will involved extension of existing physiologically based pharmacokinetic models to describe the brain dosimetry following exposures, this effort will enhance the ability to accurately extrapolate animal studies to relevant human exposure scenarios and improve hazard and risk assessments. Exposure assessment studies will be conducted with human volunteers using a novel real-time breath analysis system to determine the uptake of any of the nine potential contaminants of study from tap water by each of three routes: inhalation, ingestion, and dermal contact. This data will be coupled with physiologically based pharmacokinetic (PBPK) modeling to determine the uptake kinetics and brain dosimetry. The resultant data from these comprehensive research projects within this Superfund program focused on development of biomarkers of susceptibility and response in potentially exposed populations. The specific research objectives are: 1. To generate physiologically based pharmacokinetic models to describe target organ dosimetry by route exposure. 2. To use the models to predict human dosimetry under environmentally relevant exposure conditions at characterized field study locations. 3. To conduct field studies to provide actual exposure assessments and target organ dose estimates by each route of exposure.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Hazardous Substances Basic Research Grants Program (NIEHS) (P42)
Project #
5P42ES010338-03
Application #
6577804
Study Section
Special Emphasis Panel (ZES1)
Project Start
2002-04-01
Project End
2003-03-31
Budget Start
Budget End
Support Year
3
Fiscal Year
2002
Total Cost
$100,818
Indirect Cost
Name
Oregon Health and Science University
Department
Type
DUNS #
009584210
City
Portland
State
OR
Country
United States
Zip Code
97239
Kisby, Glen E; Moore, Holly; Spencer, Peter S (2013) Animal models of brain maldevelopment induced by cycad plant genotoxins. Birth Defects Res C Embryo Today 99:247-55
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Sabalowsky, Andrew R; Semprini, Lewis (2010) Trichloroethene and cis-1,2-dichloroethene concentration-dependent toxicity model simulates anaerobic dechlorination at high concentrations. II: continuous flow and attached growth reactors. Biotechnol Bioeng 107:540-9
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