Project Summary (2000-2006)

This project is designed to develop a fundamental understanding of the influence of route of exposure on the total body burden and internal target tissue dosimetry of commonly encountered Superfund contaminants. Particular chemicals of concern include trichloroethylene, perchloroethylene, 1,1-dichloroethylene, vinyl chloride, toluene, xylene, benzene, diethylbenzene isomers, and chloroform. Researchers are extending existing physiologically-based pharmacokinetic (PBPK) models to describe brain dosimetry following exposures, thereby enhancing the ability to extrapolate animal studies accurately to relevant human exposure scenarios and improve hazard and risk assessments. Exposure assessment studies are being 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. These data will be coupled with PBPK modeling to determine the uptake kinetics and brain dosimetry. Results will be directly applicable to companion research projects within this Superfund program focused on development of biomarkers of susceptibility and response in potentially exposed populations.