IMMUNOTOXICITY OF 2,4-DIAMINOTOLUENE IN FEMALE B6C3F1 MICE

2,4-Diaminotoluene (DAT) has been demonstrated to be a potent carcinog en. The present studies were carried our to determine the toxic and im munotoxic potential of DAT. Mice exposed to DAT at 25-100 mg/kg per da y for 14 days by gavage showed a 42% increase in liver weight and a sl ight decrease in spleen weight, Histopathologic evaluation of selected organs showed the liver to be the major target with morphological cha nges which were dose dependent. The high dose (100 mg/kg) was associat ed with moderate centrilobular necrosis. No abnormal structure was not ed in the spleen, lungs, thymus, kidney or mesenteric lymph nodes. The liver toxicity was associated with an elevation in alanine aminotrans ferase activity. The only change noted in selected hematologic paramet ers was a 64% increase in peripheral blood leukocytes. Mice exposed to DAT showed a decreased IgM and IgG response to sheep erythrocytes. Th e decrease was not a function of a decreased number of B cells because the number of B cells increased dose dependently. Proliferative capac ity of immunocompetent cells was not impaired by exposure to DAT as me asured by the response to several mitogens. The delayed hypersensitivi ty response to keyhole limpet hemocyanin in mice exposed to DAT was in creased, Natural killer cell activity was decreased dose dependently a nd may represent a spleen cell pool shift because the number of B cell s increased in the presence of a decreasing spleen size. Serum C3 was suppressed at the high dose of DAT. Phagocytosis by splenic macrophage s, but not peritoneal macrophages, was inhibited by DAT exposure. DAT exposure for 14 days decreased host resistance to the bacteria, Strept ococcus pneumoniae and Listeria monocytogenes, while host resistance t o the pulmonary tumor model, B16F10, and the PYB6 fibrosarcoma was una ffected by DAT exposure. These data indicate that DAT is hepatotoxic a nd perturbs the differentiation and maturation of leukocytes.