Hemoglobin adduct based molecular dosimetry of 1,3-butadiene

1195 1,3-Butadiene (BD) is an important contaminant in the environment. BD is present for example in car exhausts and cigarette smoke. It is widely used in the plastic industry. Some epidemiological studies have indicated that BD may pose a cancer risk to workers exposed to it. It is a carcinogenic compound in animal tests with a significant species difference in sensitivity to get malignant tumors. BD is metabolized to electrophilic epoxides which may react with nucleophilic sites in cellular macromolecules. The formed adducts can be used to estimate the molecular dose of the reactive metabolites. We have been working with the method which allow us to measure the adducts formed from the three epoxymetabolites, butadienemonoepoxide (BMO), butadienediolepoxide (THB) and butadienediepoxide (DEB). The method is based on the analysis of tryptic peptide fragments of the globin protein in red blood cells. Analysis was performed using HPLC/MS/MS techniques. The usefulness of the method was tested by analysing mouse blood samples. Animals were exposed to 62,5, 625 and 1300 ppm of BD for 10 days. Model peptide fragments were synthezised, isolated by HPLC and their identity was confirmed by mass spectrometric methods. Adducts derived from BMO were detected on animals exposed to 62.5, 625 and 1300 ppm BD. THB adducts were also detected in all exposure levels. DEB adducts were not detected. A dose responce was seen in BMO adducts, however the level of THB adducts decreased if the exposure level was increased. We report a method which has a potential use in human monitoring and which presumable allow the assessment of a long term low exposure. The Finnish Work Environment Fund is acknowledged for financial support.