Pharmacokinetic/Mechanism-Based Analysis of the Carcinogenic Risk of Perchloroethylene

摘要

The implications of existing pharmacokinetic information for the human carcinogenic risk of perchloroethylene were explored using physiologically based pharmacokinetic modeling. The models used were easily implemented on the Apple MacIntosh microcomputer based systems dynamics modeling system (STELLA) and could be used by relatively inexperienced people, facilitating understanding of effects of changes in model structure and parameters. Human models incorporated a realistic diurnal pattern of change in breathing rates and blood flows to tissues allowing different assumptions for activity during waking hours and timing of exposure relative to activity and sleep. Regression analysis of data from other compounds was used to determine human tissue partition coefficients for perchloroethylene (127184). The models reproduced human, rat, and mouse data on metabolite output. Comparison with published human data on breath concentrations indicated possible loss from an unknown route, perhaps skin. Data from gavage studies were integrated with inhalation data.