Biomarkers of exposure to 1,3-butadiene as a basis for cancer risk assessment

1,3-Butadiene (BD) is carcinogenic in mice and rats, with mice being consid erably more sensitive than rats. Urine metabolites are 1,2-dihydroxybutyl m ercapturic acid (DHBMA) and a mixture of monohydroxy-3-butenyl mercapturic acids (MHBMA). The reactive metabolite 1,2-epoxy-3-butene forms 1- and 2-hy droxy-3-butenyl valine adducts in hemoglobin (MHBVal). The objectives of th e study were (1) to compare the suitability of MHBMA, DHBMA, and MHBVal as biomarkers for low levels of exposure to ED, and (2) to explore relative pa thways of metabolism of ED in humans for comparison with mice and rats, whi ch is important in relation to cancer risk assessment in man. Analytical me thods of measuring MHBMA, DHBMA, and MHBVal were modified and applied in 2 studies to workers engaged in the manufacture and use of ED. Airborne ED co ncentrations were assessed by personal air monitoring. MHBMA in urine was m ore sensitive for monitoring recent exposures to ED when compared to DHBMA and could measure 8-h time weighted average exposures as low as 0.13 ppm. R elatively high natural background levels in urine restricted the sensitivit y of DHBMA. The origin of this background is currently unknown. The measure ment of MHBVal adducts in hemoglobin was a sensitive method for monitoring cumulative exposures to ED at or above 0.35 ppm. Statistically significant relationships were found between urinary MHBMA and DHBMA concentrations, be tween either of these variables and 8-h airborne ED levels and between MHBV al adducts and average airborne ED levels over 60 days. The data on biomark ers demonstrated a much higher rate of hydrolytic metabolism of 1,2-epoxy-3 -butene in humans compared to mice and rats, which was reflected in a much higher DHBMA/(DHBMA + MHBMA) ratio and in much lower levels of MHBVal in hu mans. Assuming a genotoxic mechanism, the data of this study, coupled with other published data on DNA and hemoglobin binding in mice and rats, sugges t that the cancer risk for man from exposure to ED is expected to be less t han for the rat and much less than for the mouse.