title: Hemoglobin adducts of epoxybutene in workers occupationally exposed to 1,3-butadiene.
abstract: 1,3-Butadiene (BD) is an important chemical widely used in the synthetic rubber industry. Hemoglobin adducts of two of its reactive metabolites have been already investigated as possible parameters for exposure assessment. In this study hemoglobin adducts of epoxybutene (EB) were analyzed in blood samples from 17 workers in a BD monomer production unit and 19 controls in a heat production unit of a petrochemical plant near Prague, Czech Republic. BD exposure was determined by personal air sampling. The median level of exposure was 440 microg/m3 (range < 11-17 mg/m3) for the exposed workers and < 6 microg/m3 (< 5-150 microg/m3) for the controls. The adduct N-(2-hydroxy-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 with high background levels, especially in the negative ion chemical ionization (NCI) mode. In the present study a limit of detection of 0.2 pmol/g globin was achieved by using 400 mg globin, a variation in extraction solvents, an additional purification step and a widely extended GC temperature program. The median hemoglobin adduct level of the Czech BD monomer production workers (0.7 pmol/g globin; n = 17) was significantly higher than that of the controls (0.2 pmol/g globin; n = 19; P<0.05). Smoking controls showed higher hemoglobin adduct levels than nonsmoking controls (P<0.1) and significantly higher BD exposure levels (P<0.01).
authors.affiliation: Department of Toxicology, University of Würzburg, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Begemann
authors.forename: R J
authors.initials: RJ
authors.lastname: Srám
authors.forename: H G
authors.initials: HG
authors.lastname: Neumann
mesh_terms: D000395:Air Pollutants, Occupational / Q000009:adverse effects*; D002070:Butadienes / Q000008:administration & dosage / Q000009:adverse effects*; D002273:Carcinogens / Q000008:administration & dosage / Q000009:adverse effects*; D004784:Environmental Monitoring / Q000379:methods; D004852:Epoxy Compounds / Q000378:metabolism*; D008401:Gas Chromatography-Mass Spectrometry; D006454:Hemoglobins / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D019570:Inhalation Exposure; D016273:Occupational Exposure; D012907:Smoking / Q000097:blood
chemical_list: D000395:Air Pollutants, Occupational; D002070:Butadienes; D002273:Carcinogens; D004852:Epoxy Compounds; D006454:Hemoglobins; C024370:3,4-epoxy-1-butene; C031763:1,3-butadiene