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© 1991 Oxford University Press

other

Immunotoxicologic Assessment of Subacute Exposure of Rats to Carbon Tetrachloride with Comparison to Hepatotoxicity and Nephrotoxicity1

RALPH J. SMIALOWICZ, JANE ELLEN SIMMONS, ROBERT W. LUEBKE and JOHN W. ALLIS

Health Effects Research Laboratory, U S. Environmental Protection Agency Research Triangle Park, North Carolina 27711

Received September 28, 1990; accepted February 18, 1991

Immunotoxicologic Assessment of Subacute Exposure of Rats to Carbon 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 carbon tetrachloride (CCI4) were evaluated in young adult (8-9 weeks old) male Fischer 344 rats dosed by gavage with CCI4 for 10 consecutive days at 0, 5, 10, 20 or 40 mg/kg/day. Two days following the last treatment rats were evaluated for alterations in immune function by monitoring the following; body and lymphoid organ weights; mitogen and mixed leukocyte reaction lymphoproliferative responses; natural killer cell activity; and cytotoxic T lymphocyte responses. A separate group of similarly dosed rats was immunized with sheep red blood cells (SRBQ on Day 9 of dosing, and the primary antibody response was assessed 4 days later. Hepatic and renal toxicity were assessed 2 days after the last treatment by monitoring organ weights, serum indicators of hepatic and renal damage, and hepatic cytochrome P450 levels, as well as by histological evaluation. Significant increases in relative liver weights were observed in rats dosed at 40 mg/kg/day. Histologically, these livers displayed mild to moderate vacuolar degeneration and minimal to mild hepatocellular necrosis. In addition, serum levels of aspartate aminotransferase and alanine aminotransferase were elevated at this dosage, as well as at 20 mg/kg/day. There were no renal effects observed at these dosages of CCU. In addition, no consistent alterations were observed in the immune parameters examined in these same animals nor in the rats immunized with SRBC. Furthermore, there was no difference in the antibody response to SRBC in another set of rats dosed at 40, 80, or 160 mg/kg/day CCI4. These results indicate that CCU is not immunotoxic in the rat at dosages that produce overt hepatotoxicity.


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