Interspecies Extrapolations of Halocarbon Respiratory and Tissue Kinetics:Applications to Predicting Toxicity in Different Species

摘要

A series of experiments have been conducted to provide a pharmacokinetic database for interspecies comparisons and for formulation and validation of physiologically-based pharmacokinetic models. The basic experimental design has involved giving equal doses of halocarbons in different species, including mice, rats, and dogs. Perchloroethylene (PCE), tetrachloroethane (TET), trichloroethylene (TCE), and trichloroethane (TRI) have been employed as test chemicals, in order to evaluate the relative importance of the physicochemical property of volatility on the kinetics and toxicity of halocarbons. In order to determine the dose received in target organs and other tissues, serial samples of brain, liver, kidney, lung, heart, skeletal muscle, and adipose tissue have been taken and analyzed for halocarbon content after administration of PCE, TET, and TRI in rats, PCE and TET in dogs, and TRI in mice. For neurobehavioral studies, an operant testing system has been employed for monitoring the central nervous system effects of halocarbons. Neurobehavioral studies have been conducted following oral and inhalation exposure to PCE, and from inhalation exposure to TRI in rats.