Effect of oral dosing vehicles on the acute hepatotoxicity of carbon tetrachloride in rats

Abstract

Although carbon tetrachloride (CCl 4) is of concern as a drinking water contaminant, it has been necessary in most oral toxicity studies to give CCl 4 in an oil vehicle due to its limited water solbility. The primary objective of our study was to assess the influence of dosing vehicles on the acute hepatotoxicity of CCl 4. Fasted 200- to 230-g rats were generally found to be more susceptible to CCl 4 hepatotoxicity than fasted 300- to 330-g rats. A time-course study revealed that corn oil did not delay the onset or time of maximal liver injury by an oral 100 mg/kg dose of CCl 4, but did reduce the extent of injury relative to that when the chemical was given undiluted or as an aqueous emulsion. Fasted 200- to 230-g male Sprague-Dawley rats were given 0, 10, 25, 50, 100, 250, 500, or 1000 mg CCl 4/kg body wt by gavage: in corn oil; as an aqueous emulsion; as the undiluted chemical; and in the 10 and 25 mg/kg doses only, in water. Blood and liver samples were taken 24 hr after dosing for measurement of serum and microsomal enzymes. Pathological examination of liver samples was also conducted. Dose-dependent increases in serum enzyme levels and pathological changes and dose-dependent decreases in microsomal P450 and glucose-6-phosphatase activity were observed in each vehicle group. Both the 10 and 25 mg/kg oral doses of CCl 4 in water caused significant elevations in serum enzymes and hepatic centrolobular vacuolation. The study revealed that acute hepatotoxicity was less pronounced at each dosage level in rats given CCl 4 in corn oil than in other vehicle groups. These findings demonstrate that dosing vehicles can significantly influence the acute hepatotoxicity of CCl 4 in rats and are a cause for additional consideration and review of the practice of routinely using vegetable oils as a diluent in studies of volatile organic compound (VOC) toxicity. The use of aqueous Emulphor emulsions appears more appropriate in acute toxicity studies of VOC drinking water contaminants such as CCl 4, in that the emulsion did not substantially alter the toxicity of CCl 4 from that of undiluted CCl 4 or CCl 4 ingested in water.