Immunotoxicological Characteristics of Sodium Methyldithiocarbamate

This study was conducted to assess immunotoxicological effects and selected general toxicological effects of sodium methyldithiocarbamate (SMD). Initially, the compound was administered orally to female B6C3F1 mice at 300 mg/kg/day for 3, 5, 10, or 14 days. Body, liver, kidney, spleen, and thymus weights were measured. Selected hematological and bone marrow parameters were examined. Flow cytometric analysis was used to assess changes in lymphocyte subpopulations in the thyrnus and spleen, and production of antibody-forming cells in vitro was measured. Major effects included decreased thymus weight at all time points; increased spleen weight after 10 or 14 days of exposure, increased bone marrow cellularity after 10 or 14 days of exposure, significant decreases in mature lymphocyte subpopulations which were greater in the thymus than in the spleen, relatively selective depletion of the major subpopulation of thy mocytes (CD4+CD8+ and decreased body weight. Overall patterns of changes were consistent with the conclusion that SMD rapidly depletes most CD4+CD8+ thymocytes, more slowly depletes a smaller number of mature lymphocytes in the thymus and spleen, and induces compensatory and/or detoxication mechanisms after 10–14 days of exposure. Subsequent experiments were done to assess selected immune function parameters. SMD at 50–300 mg/kg/day for 7 days caused substantial, dose-dependent suppression of NK cell activity. No suppression of antibody production in vivo or splenocyte responses to mitogens or allogeneic lymphocytes in vitro was detected. NK cell activity, thymus weight, and CD4+CD8+ thymocyte numbers were suppressed by dermal administration of SMD. These results indicate that NK cell activity is significantly decreased by SMD, but mature T and B lymphocytes which survive treatment are generally not significantly impaired with regard to the functions tested. In several experiments, immunological parameters were significantly suppressed in the absence of a significant decrease in body weight, suggesting that most of the effects of SMD on the immune system are not secondary to generalized toxicity.