COMPARISON OF BIOCHEMICAL ALTERATIONS ELICITED IN LIVERS FROM RATS TREATED WITH CARBON TETRACHLORIDE, CHLOROFORM, 1,2,2-TRICHLOROETHANE AND 1,1,1-TRICHLOROETHANE

Chlorinated hydrocarbons differ in their capacity to produce liver damage. The comparative effects of carbon tetrachloride (CCl4), chloroform, 1,1,1trichloroethane and 1,1,2-trichloroethane were studied in rats. CCl4 produced the highest increase in hepatic triglycerides and also produced elevated levels at the lowest dose (0.03 ml/kg). Chloroform was intermediate in producing elevated liver triglyceride levels; with 1,1,2-trichloroethane, enhanced triglyceride levels were demonstrated only at near-lethal dosages. No enhanced hepatic triglyceride level was demonstrated with 1,1,1-trichloroethane. Significant dose-related decreases in glucose 6-phosphatase activity were demonstrated with doses of 0.3 ml/kg of CCl4 or greater. With the other chlorinated hydrocarbons, no decrease in hepatic glucose 6-phosphatase activity was detected. When the hydrocarbons were added directly to liver homogenates, only those incubations containing CCl4 exhibited increased lipid peroxidation (enhanced thiobarbituric acid reactants). In vivo, evidence of lipid peroxidation (diene conjugates) in the liver was obtained 15 min after CCl4 treatment; this effect reached its peak at 30 min. Enhanced diene conjugates were detected with doses of 0.3 ml/kg of CCl4 or greater. However, with the other three hydrocarbons, no increase in diene conjugates was detected. Thus, this study shows that while the temporal relationships of CCl4-induced hepatotoxicity are compatible with the lipid peroxidation hypothesis, the dosage relationship is weaker. Also the lack of qualitative similarity in the results obtained with chloroform is disturbing. © 1969.