Urinary metabolites and haemoglobin adducts as biomarkers of exposure to 1,3-butadiene: a basis for 1,3-butadiene cancer risk assessment.

Since 1,3-butadiene (BD) is a suspected human carcinogen, exposure to BD should be minimised and controlled. This study aimed at comparing the suitability of biomarkers for low levels of exposure to BD, and at exploration of the relative pathways of human metabolism of BD for comparison with experimental animals. Potentially sensitive biomarkers for BD are its urinary metabolites 1,2-dihydroxybutyl mercapturic acid (DHBMA, also referred to as MI) and 1- and 2-monohydroxy-3-butenyl mercapturic acid (MHBMA, also referred to as MII) and its haemoglobin (Hb) adducts 1- and 2-hydroxy-3-butenyl valine (MHBVal). In two field studies in BD-workers, airborne BD, MHBMA, DHBMA and MHBVal were determined. MHBMA proved more sensitive than DHBMA for monitoring recent exposures to BD and could measure 8-h time weighted average exposures as low as 0.13 ppm (0.29 mg/m(3)). The sensitivity of DHBMA was restricted by relatively high natural background levels in urine, of which the origin is currently unknown. MHBVal proved a sensitive method for monitoring cumulative exposures to BD at or above 0.35 ppm (0.77 mg/m(3)). Statistically significant relationships were found between either MHBMA or DHBMA and 8-h airborne BD levels, and between MHBVal adducts and average airborne BD levels over 60 days. The data showed a much higher rate of hydrolytic metabolism of BD in humans compared to animals, which was reflected in a much higher DHBMA/(MHBMA+DHBMA) ratio, and in much lower levels of MHBVal in humans, confirming in vitro results. Assuming a genotoxic mechanism, the data of this study coupled with our recent data on DNA and Hb binding in rodents, suggest that the cancer risk for humans from exposure to BD will be less than for the rat, and much less than for the mouse.