Accession Number : ADA311291

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

Descriptive Note : Final technical rept. 15 Jul 91-14 Nov 95,

Corporate Author : GEORGIA UNIV RESEARCH FOUNDATION INC ATHENS

Personal Author(s) : Dallas, Cham E. ; Burckner, J. V. ; Gallo, J. M. ; Tackett, R. L. ; Reigle, T.

PDF Url : ADA311291

Report Date : 27 MAY 1996

Pagination or Media Count : 353

Abstract : 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 evaluating the toxicokinetics 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, TRI and TCE in mice and PCE and TET in dogs. For neurobehavioral studies, an operant testing system and rotorod system have 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 and mice. Neurobehavioral depression was compared with uptake of PCE and TRI in the brain and blood of rats, and with TRI in mice. The regional brain distribution of TRI was evaluated in mice and rats following inhalation exposure. This data was compared to the regional brain distribution of cyclic GMP resulting from TRI inhalation. The toxicokinetics of inhaled TCE was also evaluated in different brain regions in rats, and compared to the various isoforms of glutathione s-transferase in the brain.

Descriptors :   *TISSUES(BIOLOGY), *TOXICITY, *RESPIRATORY SYSTEM, *PHARMACOKINETICS, *EXPERIMENTAL PSYCHOLOGY, DATA BASES, BRAIN, RATS, CHEMICALS, TEST EQUIPMENT, TARGETS, SAMPLING, LUNG, VOLATILITY, KINETICS, MUSCLES, MUSCULOSKELETAL SYSTEM, EXPOSURE(PHYSIOLOGY), PHYSICOCHEMICAL PROPERTIES, MICE, LIVER, HALOGENATED HYDROCARBONS, CONCENTRATION(CHEMISTRY), CENTRAL NERVOUS SYSTEM, BLOOD, DOGS, ORAL INTAKE, TRICHLOROETHYLENE, ORGANS(ANATOMY), TRICHLOROETHANES, EXTRAPOLATION, INHALATION, GLUTATHIONE, ADIPOSE TISSUE, HALOCARBON PLASTICS.

Subject Categories : Psychology
      Medicine and Medical Research
      Pharmacology

Distribution Statement : APPROVED FOR PUBLIC RELEASE