Immunotoxicologic Assessment of Subacute Exposure of Rats to Carbon Tetrachloride with Comparison to Hepatotoxicity and Nephrotoxicity

Immunotoxicologic Assessment of Subacute Exposure of Rats toCarbon Tetrachloride with Comparison to Hepatotoxicity and Nephrotoxicity.SMIALOWICZ, R.J., SIMMONS, J. E., LUEBKE, R. W., AND ALLIS,J. W. (1991). Fundam. Appl. Toxicol 17, 186-196. The immunotoxicity,hepatotoxicity, and nephrotoxicity of subacute exposure to carbontetrachloride (CCI4) were evaluated in young adult (8-9 weeksold) male Fischer 344 rats dosed by gavage with CCI4 for 10consecutive days at 0, 5, 10, 20 or 40 mg/kg/day. Two days followingthe last treatment rats were evaluated for alterations in immunefunction by monitoring the following; body and lymphoid organweights; mitogen and mixed leukocyte reaction lymphoproliferativeresponses; natural killer cell activity; and cytotoxic T lymphocyteresponses. A separate group of similarly dosed rats was immunizedwith sheep red blood cells (SRBQ on Day 9 of dosing, and theprimary antibody response was assessed 4 days later. Hepaticand renal toxicity were assessed 2 days after the last treatmentby monitoring organ weights, serum indicators of hepatic andrenal damage, and hepatic cytochrome P450 levels, as well asby histological evaluation. Significant increases in relativeliver weights were observed in rats dosed at 40 mg/kg/day. Histologically,these livers displayed mild to moderate vacuolar degenerationand minimal to mild hepatocellular necrosis. In addition, serumlevels of aspartate aminotransferase and alanine aminotransferasewere elevated at this dosage, as well as at 20 mg/kg/day. Therewere no renal effects observed at these dosages of CCU. In addition,no consistent alterations were observed in the immune parametersexamined in these same animals nor in the rats immunized withSRBC. Furthermore, there was no difference in the antibody responseto SRBC in another set of rats dosed at 40, 80, or 160 mg/kg/dayCCI⁴. These results indicate that CCU is not immunotoxic inthe rat at dosages that produce overt hepatotoxicity.