Interspecies Extrapolations of Halocarbon Respiratory and Tissue Kinetics: Applications to Predicting Toxicity in Different Species.
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.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 27, 1996
- Accession Number
- ADA311291
Entities
People
- Cham E. Dallas
- J. M. Gallo
- J. V. Burckner
- R. L. Tackett
- T. Reigle
Organizations
- University of Georgia Research Foundation