Pharmacokinetics of tetrachloroethylene

Abstract

A physiological pharmacokinetic model is developed to describe the pharmacokinetics of tetrachloroethylene (PCE) in mice, rats, and humans. The body is divided into four tissue compartments (vessel-rich, muscle, slowly perfused fat, and liver) connected by the arterial and venous blood flow pathways. The physiological parameters of the model are blood flow rates, cardiac output, tissue volumes, ventilation rate, and tissue/air and blood/air partition coefficients. Metabolism is assumed to occur only in the liver compartment and is described by a combination of a linear metabolic component and a Michaelis-Menten component. The metabolic parameters for PCE were determined by fitting model predictions to species-specific empirical data. Comparison of model results with independent empirical data on inhalation and gavage exposures in mice, rats, and humans demonstrates that the physiological pharmacokinetic model can be used to determine the time course of PCE in these species. We show that human metabolic parameters can be predicted by scaling rat metabolic parameters as a function of body weight, whereas scaling of the metabolic parameters of mice overestimates human metabolism.