In Vivoandin VitroStudies of Perchloroethylene Metabolism for Physiologically Based Pharmacokinetic Modeling in Rats, Mice, and Humans

Autor: Reitz, Richard H., Gargas, Michael L., Mendrala, Alan L., Schumann, Alan M.
Zdroj: Toxicology and Applied Pharmacology; February 1996, Vol. 136 Issue: 2 p289-306, 18p
Abstrakt: In vivoexperiments in rats and mice andin vitroexperiments in rats, mice, and humans have been used to develop and validate a “2nd generation” physiologically based pharmacokinetic (PBPK) model for perchloroethylene (PERC). The refined PBPK model should be useful in the preparation of carcinogenic risk assessment based on amounts of PERC metabolites formed in the livers of rodents and humans according to procedures developed by EPA. A sensitivity analysis of the PBPK model revealed that the most significant uncertainties in this process (other than the choice of the appropriate dose/response model based on mechanism of action of PERC) were in the techniques used to estimate rates of PERC metabolism in humans.In vitrostudies with human tissues reported help define what some have called the range of “equally reasonable alternatives” for estimating human risk.
Databáze: Supplemental Index