Interactions, in rats, between CC14-induced liver cirrhosis and chronic treatment with the organochlorine insecticide chlordane*

Rats were exposed to gaseous carbon tetrachloride, twice weekly over a period of 10 weeks, to induce hepatic cirrhosis. Simultaneously some animals were fed chlordane twice weekly to give a dose rate of 0.1 mg/kg/day. Half the animals in each group were sacrificed at 10 weeks, the remaining animals received a further 10 weeks exposure to chlordane. Progress of the disease was monitored by weekly measurements of serum-glutamate pyruvate transaminase and alkaline phosphatase concentrations. At 10 weeks and 20 weeks livers were removed from sacrificed animals and micropathological examinations were made. Liver lipid, microsomal protein, cytochrome P 450 content, and, where applicable, tissue content of oxychlordane, the stable metabolite of chlordane, were determined. After 10 weeks of treatment animals which had received the dual treatment, CCl 4 and chlordane, showed a significant loss of microsomal protein and liver lipid compared to the controls. After 20 weeks these animals showed significant differences (p 450 content. Their histopathological appearance was also different to that of the controls. A high negative correlation (r = −0.8) was found between the degree of necrosis and oxychlordane content of livers treated animals. Continued exposure to chlordane after cessation of exposure to CCl 4 apparently promotes a more rapid return to the normal functional state of the liver.