Role of decomposition products in sodium methyldithiocarbamate-induced immunotoxicity

Sodium methyldithiocarbamate (SMD) is a widely used agricultural agent that causes immunological changes in B6C3F1 mice. The most prominent effects of SMD include a decrease in thymus weight and percentage of CD4+CD8+ thymocytes, an increase in spleen weight, an increase in the percentage of neutrophils in the blood, a decrease in the percentage of lymphocytes in the blood, and a decrease in natural killer (NK) cell activity in the spleen. The mechanism by which SMD causes these changes is unknown, and the relative importance of the parent compound and its decomposition products is not known. In addition, it is not known if these effects are unique to mice, or if other mammals are affected similarly. This prompted the present investigation of the major decomposition product of SMD, methylisothiocyanate (MITC), and two minor products, methylamine and carbon disulfide, in mice. Equimolar dosages of methylamine and carbon disulfide caused minimal immunological changes, and these changes were not characteristic of those noted for SMD. In contrast, MITC significantly decreased thymus weight and cellularity and changed peripheral white blood cell populations in a manner similar to that noted for an equimolar dosage of SMD. However, MITC did not significantly affect NK cell activity or increase spleen weight. Thus, MITC is probably responsible for some of the immunological changes noted in SMD-treated mice. The remaining changes are not produced by MITC, methylamine, or carbon disulfide. Thus, it is likely that the parent compound or a synergistic action of the parent compound with one or more of the decomposition products is responsible for these remaining changes (increased spleen weight and decreased splenic NK cell activity). Data are also presented that indicate that SMD-induced thymic atrophy occurs in rats as well as mice and that the dosage required to decrease thymus weight by 50% is lower for rats than for mice. Investigations of other mammals are needed to indicate SMD's potential as a human immunotoxicant and to compare the role of MITC in the immunotoxic effects of SMD in different species.