Hemoglobin adducts of epoxybutene in workers occupationally exposed to 1,3-butadiene

1,3-Butadiene (BD) is an important chemical widely used in the synthetic ru bber industry. Hemoglobin adducts of two of its reactive metabolites have b een already investigated as possible parameters for exposure assessment. In this study hemoglobin adducts of epoxybutene (EB) were analyzed in blood s amples from 17 workers in a ED monomer production unit and 19 controls in a heat production unit of a petrochemical plant near Prague, Czech Republic. ED exposure was determined by personal air sampling. The median level of e xposure was 440 mug/m(3) (range < 11-17 mg/m(3)) for the exposed workers an d < 6 mug/m(3) (< 5-150 <mu>g/m(3)) for the controls. The adduct N-(2-hydro xy-3-butenyl)valine (HBVal) formed by the reaction of the N-terminal valine of globin with carbon-1 of EB was measured. The N-alkylated amino acid was analyzed by gas chromatography/mass spectrometry (GC/MS) after degradation by the modified Edman procedure. Using published methods problems arose wi th high background levels, especially in the negative ion chemical ionizati on (NCI) mode. In the present study a limit of detection of 0.2 pmol/g glob in was achieved by using 400 mg globin, a variation in extraction solvents, an additional purification step and a widely extended GC temperature progr am. The median hemoglobin adduct level of the Czech ED monomer production w orkers (0.7 pmol/g globin; n = 17) was significantly higher than that of th e controls (0.2 pmol/g globin; n = 19; P < 0.05). Smoking controls showed h igher hemoglobin adduct levels than nonsmoking controls (P<0.1) and signifi cantly higher ED exposure levels (P<0.01).