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 sh ould be minimised and controlled. This study aimed at comparing the suitabi lity of biomarkers for low levels of exposure to BD, and at exploration of the relative pathways of human metabolism of BD for comparison with experim ental animals. Potentially sensitive biomarkers for BD are its urinary meta bolites 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 vali ne (MHBVal). In two field studies in BD-workers, airborne BD, MHBMA, DHBMA and MHBVal were determined. MHBMA proved more sensitive than DHBMA for moni toring recent exposures to BD and could measure 8-h time weighted average e xposures as low as 0.13 ppm (0.29 mg/m(3)). The sensitivity of DHBMA was re stricted by relatively high natural background levels in urine, of which th e origin is currently unknown. MHBVal proved a sensitive method for monitor ing cumulative exposures to BD at or above 0.35 ppm (0.77 mg/m(3)). Statist ically significant relationships were found between either MHBMA or DHBMA a nd 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 me tabolism 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 da ta of this study coupled with our recent data on DNA and Hb binding in rode nts, suggest that the cancer risk for humans from exposure to BD will be le ss than for the rat, and much less than for the mouse. (C) 2001 Elsevier Sc ience Ireland Ltd. All rights reserved.