Development and Validation of Methods for Applying Pharmacokinetic Data in RiskAssessment. Volume 5. Vinyl Chloride

摘要

Physiologically-based pharmacokinetic (PBPK) modeling was used as a tool toexamine the behavior of vinyl chloride (VC) in mammalian systems. Previously proposed VC models were reviewed and evaluated for applicability to risk assessment issues. Alternative VC models were proposed and evaluated. These alternative models incorporated glutathione involvement in VC toxicity. This volume consists of two parts. Models for rats were examined and model results compared to experimental results available in the literature and to closed chamber (gas uptake) studies. Alternative models are presented and also compared to the experimental data. Part 2 contains some preliminary results documenting progress toward the extension of a rat model to other species, mice and hamsters. Strain-specific results are presented for those species and for rats. That work is based on additional gas uptake studies conducted at WPAFB which included measurement of hepatic glutathione levels in exposed and unexposed animals.