Urinary butadiene diepoxide: a potential biomarker of blood diepoxide

The carcinogenicity of 1,3-butadiene (BD) varies greatly in the rodent species in which 2-year bioassay studies were completed. This raises the question of whether the risk of BD exposure in humans is more like that of the sensitive species, the mouse, or more like that of the resistant species, the rat. Numerous studies have indicated that one reason for the species differences in response to BD is that the blood and tissues of BD-exposed mice contain high levels of both the mono- and the diepoxide metabolite, while the tissue and blood of exposed rats contain very little of the diepoxide. The diepoxide is far more mutagenic than the monoepoxide, and so it is reasonable that the diepoxide plays a major role in tumor induction in the mouse. If the diepoxide is the primary carcinogen, the presence of the diepoxide in the blood of exposed individuals should be an indicator of risk from BD exposure. In this study, we report that the diepoxide is sufficiently stable to be excreted into the urine of exposed rodents and that the urinary levels of the diepoxide reflect the relative levels of the compound in the blood of the two species. The conclusion is that urinary diepoxide should be investigated as a potential biomarker of the formation of the diepoxide in humans exposed to BD.