Studies on the Carcinogenicity of Pentachloroethane in Rats and Mice

Studies on the Carcinogenicity of Pentachloroethane in Ratsand Mice. Mennear, J.H., Haseman, J.K., Sullivan, D.J., Bernal,E. and Hildebrandt, P.K. (1982). Fundam. Appl. Toxicol. 2:82–87.The carcinogenicity of chronically administered (41 to 103 weeks)technical-grade pentachloroethane (PCE) was assessed in groupsof 50 male and female Fischer 344 rats and B6C3F₁ mice. Themajor contaminant in the PCE sample used for the chronic studywas hexachloroethane (4.2%). Prechronic studies (two and 13weeks repeated dose) employing gavage doses of from 5.0 to 1000mg/kg/day of PCE failed to reveal specific target organ toxicityin these species. In the absence of treatment-related pathologicalchanges during the prechronic tests, the doses for the chronicstudies were set on the basis of survival and body weight gainsduring the 13-week repeated dose study. During the chronic studiesdose levels of 75 and 150 mg/kg for rats and 250 and 500 mg/kgfor mice were administered, by gavage, five days per week. Thesurvival of high-dose rats (both sexes) was significantly reducedas compared to the survival of control animals and that of thelow-dose males was slightly, but not significantly, reduced.Although the administration of PCE to rats did not increasethe incidence of primary tumors, it did produce a significantdose-related increase in the incidence of chronic renal inflammationamong males. The survival times of all treated groups of micewere significantly shortened by PCE administration. Despitethis reduced survival time, the incidence of hepato-cellularcarcinoma was significantly increased in all treated groups.With the exception of a dose-related increase in the incidenceof hepatocellular adenoma among females, there were no othersignificant increases in primary tumor incidence in mice. Neitherrenal lesions in rats nor hepatocellular carcinoma in mice wereconsidered to be adequate explanations for the decreased survivals.Complete histopathological examinations failed to reveal thecause of decreased survival. The results of the study show thattechnical-grade PCE, like numerous other chlorinated ethanes,is an hepato-carcinogen for B6C3F₁ mice. This interpretationfor PCE per se, however, must be tempered because the majorcontaminant, hexachloroethane, has been shown to produce hepatocellularcarcinoma in mice. While the results obtained in rats suggesta species difference in susceptibility, the reduced survivalin this species may have contributed to the absence of a carcinogeniceffect.