Oral Toxicity of Carbon Tetrachioride: Acute, Subacute, and Subchronic Studies in Rats |
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Authors: | BRUCKNER, J. V. MACKENZIE, W. F. MURALIDHARA, S. LUTHRA, R. KYLE, G. M. ACOSTA, D. |
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Abstract: | Oral Toxicity of Carbon Tetrachloide: Acute, Subacute, and SubchronicStudies in Rats. BRUCKNER, J. V., MACKENZIE, W. F., MURALIDHARA,S., LUTHRA, R., KYLE, G. M., AND ACOSTA, D. (1986). Fundam.Appl. Toxicol. 6, 1634. This investigation was conductedto characterize the acute, subacute, and subchronic toxic potencyof ingested carbon tetrachloride (CCl4) In the first acute andsubacute toxicity study, male Sprague-Dawley rats of 300350g were gavaged with 0, 20, 40, or 80 mg CCl4/kg once daily for5 consecutive days, rested for 2 days, and dosed once dailyfor 4 additional days. Rats of 200250 g were gavagedwith 0, 20, 80, or 160 mg CCl4/kg according to the same dosageregimen in the second acute and subacute study. In the firstand second studies one group of rats at each dosage level wassacrificed for clinical chemistry and histopathological evaluationat 24 hr, 4 days, and 11 days after initiation of dosing. Single20- and 40-mg/kg doses had no apparent toxic effect at 24 hr,although 80 mg/kg caused mild hepatic centrilobular vacuolizationand significant increases in some serum enzyme levels. In general,there was progressively severe hepatic injury at each dosagelevel over the 11-day period. CCl4 was more hepatotoxic to the200250-g rats than to the 300350-g rats. In thesubchronic study, rats initially 200250 g were gavaged5 times weekly for 12 weeks with 0, 1, 10, or 33 mg CCl4/kgBody weight and clinical chemistry indices were monitored duringthe 12 weeks of dosing and 2 weeks after cessation of dosing,A dose of 1 mg/kg had no apparent adverse effect; 10 mg/kg producedslight, but statistically significant increases in sorbitoldehydrogenase activity and mild hepatic centrilobular vacuolization;33 mg/kg caused marked hepatotoxicity. Serum enzyme levels remainedelevated during the 12-week dosing period, but returned towardnormal within 13 days of cessation of CCl4 exposure. Microscopicexamination of livers of the 33-mg/kg rats revealed cirrhosis,characterized by bile duct proliferation, fibrosis, lobulardistortion, parenchymal regeneration, hyperplastic nodules,and single-cell necrosis. The fibrosis was not reversed withinthe 13-day recovery period. |
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