IMMUNOTOXICITY OF NITROBENZENE IN FEMALE B6C3F1 MICE

Nitrobenzene (NBZ) is primarily employed as an oxidizing agent in the synthesis of analine and benzene compounds. It produces myelotoxic eff ects and effects on erythrocytes in both animal models and man. Report ed hepatosplenomegaly and effects on the bone marrow are indicators th at NBZ may be immunotoxic. In these studies, female B6C3F1 mice were e xposed to 30, 100 and 300 mg/kg of NBZ in corn oil by gavage for 14 co nsecutive days. To assess the immunotoxic potential of NBZ, body and o rgan weights were determined and selected immunologic and host resista nce responses were studied. In these studies, the liver and spleen app eared to be the primary target organs. Both liver and spleen weights w ere dose dependently increased. Gross histopathologic examinations rev ealed significant changes in the spleen, consisting of severe congesti on of the red pulp areas with erythrocytes and reticulocytes. Serum ch emistry profiles showed increases in alanine aminotransferase and aspa rtate aminotransferase activities, indicating liver toxicity. Hematolo gic studies showed a decrease in erythrocyte number and a concomitant increase in mean corpuscular hemoglobin and mean corpuscular volume. A dose-dependent increase in peripheral reticulocytes was also seen. DN A synthesis was enhanced, as was the number of formed elements and the number of monocyte/granulocyte stem cells in the bone marrow of treat ed mice. IgM responses were decreased and the phagocytic activity of m acrophages in the liver was dose dependently increased with a concomit ant decrease in the activities in the spleen and lung. Other immunolog ical parameters examined were unchanged. Host resistance to microbial or viral infection was not markedly altered by NBZ; however, there wer e trends towards increased susceptibility where T-cell function contri butes to host defense. These data indicate that NBZ-induced hemolysis and liver injury are linked to the observed alterations in bone marrow activity.