IMMUNOTOXICITY OF MONO-NITROTOLUENES IN FEMALE B6C3F1 MICE .1. PARA-NITROTOLUENE

para-Nitrotoluene (p-nitrotoluene) is used primarily as an intermediat e in the production of various dyes, explosives, pharmaceuticals, and in the production of rubber and agricultural products. Previous invest igations indicated that p-nitrotoluene was mutagenic in the Ames Test and that other mono-substituted nitrotoluenes bound covalently to hepa tic macromolecules. The objective of these studies was to evaluate the potential immunotoxicity of p-nitrotoluene in mice exposed by the ora l route. Mice exposed to p-nitrotoluene (200-600 mg/kg) daily for 14 d ays showed modest dose-dependent increases in liver and spleen weights . The livers of mice exposed subchronically to 400 and 600 mg/kg showe d a mild to moderate swelling of the hepatocytes adjacent to the centr al veins; this swelling appeared to be reversible and there was no evi dence of necrosis. The proportion of monocytes in blood was decreased in mice treated with p-nitrotoluene or toluene. Serum chemistries, bon e marrow cellularity and the number of CFU-M and CFU-GM were unaffecte d. Immunologic investigations showed p-nitrotoluene suppressed the IgM response to sRBC and the DHR response to KLH. There was a 24% decreas e in the percentage of CD4+ T lymphocytes in the spleen. There was no dose-dependent alteration of peritoneal macrophage numbers or differen tial count, unstimulated natural killer cell activity, response to B c ell mitogen LPS, C3 activity or interferon levels. Exposure of mice to p-nitrotoluene decreased resistance to Listeria monocytogenes but not to Streptococcus pneumoniae, Plasmodium yoelii or the B16F10 melanoma , and increased resistance to the PYB6 tumor. These studies indicated that the immune system is an important target for toxicity of p-nitrot oluene. The decreased host resistance to L. monocytogenes can be attri buted to the decrease in T lymphocytes and to a decreased delayed hype rsensitivity response to KLH.