Metabolic Disposition Study of Chlorinated Hydrocarbons in Rats and Mice

Abstract

Chlorinated hydrocarbons found in a bioassay to be carcinogenic to B6C3F1 mice and Osborne-Mendel rats (1,2-dichloroethane), carcinogenic only to mice (1,1,2-trichloroethane, 1,1,2,2,-tetrachloroethane, hexachloroethane, trichloroethylene and tetrachloroethylene) and noncarcinogenic to either species (1,1-dichloroethane and 1,1,1-trichloroethane) were used to investigate the biochemical bases for tumorigenesis. Studies were conducted after chronic oral dosing of adult mice and rats with the MTD [maximum tolerated dose] and 1/4 MTD of each compound. The extent to which the compounds were metabolized in 48 h, hepatic protein binding, and urinary metabolite patterns were examined. Metabolism of the compounds (mmoles per kg body weight) was 1.7- to 10-fold greater in mice than in rats. Hepatic protein binding (nanomole equivalents bound to 1 mg of liver protein) was 1.2- to 8.3-fold higher in mice than in rats except for 1,2-dichloroethane and 1,1,1-trichloroethane. The noncarcinogens 1,1,-dichloroethane and 1,1,1-trichloroethane, exhibited 2- to 18-fold more binding in mice than did the carcinogens 1,2-dhchloroethane and 1,1,2-trichloroethane. Urinary metabolite patterns of the compounds were similar in both species. The biochemical parameters measured provided no clue to differentiate the carcinogens from the noncarcinogens.