LOCAL VERSUS SYSTEMIC IMMUNOTOXICITY OF ISOBUTYL NITRITE FOLLOWING SUBCHRONIC INHALATION EXPOSURE OF FEMALE B6C3F1 MICE

Female B6C3F1 mice were exposed to isobutyl nitrite (IBN) by inhalatio n at 0, 37.5, 75, or 150 ppm for 6 hr per day, 5 days per week for 15 weeks. The potential of this compound to induce immunotoxicity was ass essed during the 3rd, 13th, 14th, and 15th week of exposure and after 2 weeks of recovery following the 15 weeks of exposure. Both systemic and lung immune functions were examined, including body and lymphoid o rgan weights, pulmonary macrophage function and host defense, expressi on of splenic lymphocyte cell-surface markers, natural killer cell fun ction, mixed lymphocyte reaction, and induction of specific antibody t o a T-cell-dependent antigen. There was a dose-related suppression of T-cell-dependent antibody-forming cell responses in the spleen followi ng IBN exposure; however, other measures of T-cell and nonspecific imm unity were not significantly affected. A dose-related increase of H2O2 production by alveolar macrophages was present after 12 but not after 68 exposures to IBN. In contrast, pulmonary host defense mechanisms a gainst Klebsiella pneumoniae were unaffected. These results suggest th at in the absence of changes in host resistance, IBN may have selectiv e and partially reversible effects on the immune system. (C) 1995 soci ety of Toxicology