Biomarkers for assessing occupational exposures to 1,3-butadiene

The overall objective of this study was to evaluate a continuum of biomarke rs in blood and urine for their sensitivities as indicators of low level oc cupational exposures to 1,3 butadiene (BD). The study design was largely cr oss-sectional, with biological samples collected within a short timeframe. Personal 8-h BD exposure measures were made on several occasions over a 60- day period for each potentially exposed worker in order provide maximum acc uracy for this independent variable and to accommodate the different expres sion intervals of the several biomarkers. Co-exposures to styrene, toluene and benzene were also measured. The study included 24 BD monomer production workers (mean BD exposure =0.642 mg/m(3)), 34 polymerization workers (mean BD exposure =1.794 mg/ml) and 25 controls (mean BD exposure =0.023 mg/m(3) ). The several biomarkers were measured by a consortium of investigators at different locations in the US and Europe. These biomarkers included: (1) m etabolic genotypes (CYP2E1. EH, GST M1, GST T1, ADH2, ADH3), determined in Prague and Burlington. VT; (2) urinary M1 and M2 metabolites (1,2-dihydroxy -4-[N-acetylcysteinyl]-butane and 1-hydroxy-2-[N-acetyleysteinyl]-3-butene, respectively), determined in Albuquerque, NM and Leiden; (3) hemoglobin ad ducts (N-[2-dihydroxy-3-butenyl]valine = HBVal and N-[2,3,4-trihydroxybutyl ]valine = THBVal), determined in Amsterdam and Chapel Hill, NC, respectivel y; (4) HPRT mutations determined by autoradiographic assay in Galveston, TX , with slides re-read in Burlington, VT; (6) hypoxanthine-guanine phosphori bosyltransferase (HPRT) mutations determined by cloning assay in Leiden wit h mutational spectra characterized in Burlington, VT; (7) sister chromatid exchanges and chromosome aberrations determined by standard methods and FIS H analysis in Prague. Urinary M1 and M2 metabolites and HBVal and THBVal he moglobin adducts were all significantly correlated with BD exposure levels, with adducts being the most highly associated. No significant relationship s were observed between BD exposures and HPRT mutations or any of the cytog enetic endpoints, regardless of method of assay. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.