Immunotoxicologic assessment of subacute exposure of rats to carbon tetrachloride with comparison to hepatotoxicity and nephrotoxicity.
The immunotoxicity, hepatotoxicity, and nephrotoxicity of subacute exposure to carbon tetrachloride (CCl4) were evaluated in young adult (8-9 weeks old) male Fischer 344 rats dosed by gavage with CCl4 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 (SRBC) 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 CCl4. 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 CCl4. These results indicate that CCl4 is not immunotoxic in the rat at dosages that produce overt hepatotoxicity.
Smialowicz
R J
RJ
Health Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711.
Simmons
J E
JE
Luebke
R W
RW
Allis
J W
JW
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002252:Carbon Tetrachloride Poisoning / Q000276:immunology* / Q000473:pathology; D056486:Chemical and Drug Induced Liver Injury / Q000276:immunology* / Q000473:pathology; D007107:Immune System / Q000187:drug effects*; D007674:Kidney Diseases / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology; D007694:Killer Cells, Natural / Q000187:drug effects; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D011920:Rats, Inbred WF; D012756:Sheep / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects