Dithiocarbamates as potential confounders in butadiene epidemiology

Hematopoietic neoplasms associated with occupational exposure to 1,3-butadiene (BD) have been the subject of controversy. This has largely been due to the inconsistent results of epidemiology studies that have reported alternatively no or weak associations between exposure to BD and hematopoietic neoplasms. Moreover, the specificity of association of BD exposure with individual leukemia types remains unclear. In addition, a distinct difference in the pattern of leukemia risk has been observed between workers employed in BD monomer production and those involved in styrene-butadiene rubber (SBR) production: with no increase in leukemia risk observed for exposure to BD monomer alone. These observations are consistent with an increase in leukemia risk associated with the SBR process but not BD monomer and suggest the possibility that the increase may be the result of exposure to confounding factors previously not considered. In this regard, evidence is accumulating to suggest that SBR studies may be confounded by the presence of an important class of biologically active chemicals employed in the rubber industry, dithiocarbamates. The hematotoxicity and immunotoxicity of dithiocarbamates have been implicated in a wide range of clinical, animal and molecular studies, and an extremely high concordance exists between the risk of developing leukemia in SBR production and opportunity for exposure to this class of agents. Based on these findings additional studies on the epidemiology, carcinogenesis and molecular biology of dithiocarbamates are clearly warranted.