Short Term Toxicity of Nitrous Oxide on the Immune, Hemopoietic, and Endocrine Systems in CD-1 Mice

Abstract

Occupational exposures to subanesthetic levels of N2O have been documented to result in suppressed proliferative cell activities. Male CD-1 mice were exposed to 0, 50, 500, and 5000 ppm of N2O for 6 hr/day, 5 days/week for 2 or 13 weeks. Tritiated-thymidine ([3H]-TdR) uptake was measured in CD-1 splenic lymphocytes cultured with and without mitogens and in a mixed lymphocyte culture (MLC). Antibody-mediated immunocompetency was determined for sheep red blood cell (SRBC)-sensitized animals by plaque forming cell (PFC) assay and serum anti-SRBC antibody (Ab) titer. Deoxyuridine suppression tests (dUrdST) were performed on bone marrow cells. There was significantly decreased splenic lymphocyte uptake of [3H]-TdR by cells cultured with mitogenic substances and in MLC following 2–week exposures to 5000 ppm. After 13–week exposures the animals' splenic lymphocytes showed increased [3H]-TdR uptake following high N2O dosing in both the mitogen-induced blastogenesis and MLC assays. Compared to control animals, the 5000 ppm exposure group had significantly depressed PFC activity and circulating anti-SRBC Ab levels following the 13-week N2O exposures, and all 13-week exposure groups demonstrated decreased liver weights and leukopenia. Bone marrow activity at these dosing levels was depressed in a dose-dependent fashion following 13-week gas exposures.