EFFECT OF ORAL DOSING VEHICLES ON THE SUBCHRONIC HEPATOTOXICITY OF CARBON-TETRACHLORIDE IN THE RAT

Previous studies in this laboratory have shown that corn oil delayed and prolonged the gastrointestinal absorption of carbon tetrachloride (CCl4) and reduced its acute hepatotoxicity in rats. The objective of the present study was to extend the duration of ingestion of CCl4 to assess vehicle effects on the subchronic oral toxicity of CCl4. Male Harlan Sprague-Dawley rats were given doses of 0, 25, or 100 mg CCl4/kg body weight by gavage in either corn oil or a 1% Emulphor aqueous emulsion 5 times a week for 13 wk. Blood was collected at 4, 8, and 13 wk for measurement of serum enzymes. Liver samples were also taken at 13 wk for measurement of triglyceride and microsomal enzyme levels, as well as for histopathological examination. Serum enzyme levels peaked at 8 wk in the high-dose groups, but not until 13 wk in the low-dose animals. Effects of CCl4 on serum and microsomal enzymes were of similar magnitude in the two vehicle groups. A comprehensive histopathological examination revealed no qualitative or quantitative differences between the corn oil and aqueous vehicle groups in hepatic lesions. Although CCl4 and chloroform have been reported by other investigators to be more hepatotoxic to mice when given for 90 d in corn oil, current findings indicate that corn oil does not significantly alter the subchronic hepatotoxicity of CCl4 in rats from that when the halocarbon is given in an aqueous medium.