Interspecies Extrapolations of Halocarbon Respiratory and Tissue Kinetics: Applications to Predicting Toxicity in Different Species.
Annual rept. no. 1, 15 Jul 1991-14 Jul 1992,
GEORGIA UNIV ATHENS DEPT OF PHARMACOLOGY AND TOXICOLOGY
Pagination or Media Count:
A series of experiments have been conducted to provide a pharmacokinetic data base for interspecies comparisons and for formulation and validation of physiologically-based pharmacokinetic models. The basic experimental design has involved giving equal doses of halocarbons to the rat and the dog, two species of widely different size. 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. The respiratory elimination of TCE and systemic uptake of TCE and PCE has been measured in rats. 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, and PCE and TET in dogs. A neurobehavioral operant testing system has been set up and a protocol established 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. The direct measurements of halocarbon concentrations in exhaled breath and tissues have provided an extensive data base that will be used to formulate and validate the physiologically-based pharmacokinetic PBPK models for exposure to halocarbons. Physiologically based pharmacokinetic models, interspecies extrapolations, halocarbons, neurobehavioral measurements, operant testing, central nervous system depression toxico-dynamic model.
- TEST AND EVALUATION
- DATA BASES
- EXPERIMENTAL DESIGN
- PHYSICOCHEMICAL PROPERTIES
- NERVOUS SYSTEM
- ADIPOSE TISSUE
- LABORATORY ANIMALS
- CENTRAL NERVOUS SYSTEM
- Anatomy and Physiology
- Medicine and Medical Research