Validation and Application of Pharmacokinetic Models for Interspecies Extrapolations in Toxicity Risk Assessments of Volatile Organics.

摘要

Direct measurements of perchloroethylene (PER), trichloroethylene (TCE), trichloroethane (TRI) and dichloroethylene (DCE) were made in the blood and exhaled breath of rats during and following inhalation exposures. The pharmacokinetics of these four halocarbons were also investigated following oral administration. An accurate assay for measuring volatile halogenated hydrocarbons in a variety of body tissues was developed and demonstrated for PER, TCE, TRI, and tetrachloroethane (TET). The tissue concentration-time profiles and bioavailability for PER and TET were determined in liver, kidney, brain, fat, lung, heart, and muscle tissues following oral and intraarterial administrations in rats. Interspecies comparisons of the pharmacokinetics of PER and TET were made following oral and intraarterial administrations in two species: Sprague-Dawley rats and Beagle dogs. Neurobehavioral determinations were conducted in rats following inhalation exposures, single oral bolus administration, and gastric infusion of PER.