Urinary butadiene diepoxide: a potential biomarker of blood diepoxide

The carcinogenicity of 1,3-butadiene (BD) varies greatly in the rodent spec ies in which 2-year bioassay studies were completed. This raises the questi on of whether the risk of ED exposure in humans is more like that of the se nsitive species, the mouse, or more like that of the resistant species, the rat. Numerous studies have indicated that one reason for the species diffe rences in response to ED is that the blood and tissues of ED-exposed mice c ontain high levels of both the mono- and the diepoxide metabolite, while th e tissue and blood of exposed rats contain very little of the diepoxide. Th e diepoxide is far more mutagenic than the monoepoxide, and so it is reason able 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 ED exposure. In this study, we report that the diepoxide is sufficiently stabl e to be excreted into the urine of exposed rodents and that the urinary lev els of the diepoxide reflect the relative levels of the compound in the blo od of the two species. The conclusion is that urinary diepoxide should be i nvestigated as a potential biomarker of the formation of the diepoxide in h umans exposed to ED. (C) 2001 Elsevier Science Ireland Ltd. All rights rese rved.