title: Albumin adducts, hemoglobin adducts and urinary metabolites in workers exposed to 4,4'-methylenediphenyl diisocyanate.
abstract: 4,4'-Methylenediphenyl diisocyanate (MDI) is the most widely used isocyanate in the manufacture of polyurethanes. MDI has been implicated as one of the major causes of occupational asthma. Hydrolysis of MDI can yield 4,4'-methylenedianiline (MDA), which is a suspected human carcinogen. Thus the need to monitor occupational exposure to MDI is of great significance. The use of air monitors alone has been found to be insufficient and there is a need for sensitive markers of recent and long-term exposure. We obtained biological samples from a group of 20 workers exposed to MDI vapor during the manufacture of polyurethane products. The air levels of MDI in the factory were measured using personal, work room and work station monitors. In most cases the levels were below detection limits. The blood and urine samples were analyzed for the presence of adducts and metabolites using GC-MS methods. Urinary base-extractable metabolites were found above control levels in 15 of the 20 workers and ranged from 0.035 to 0.83 pmol MDA/ml. The level of the acetylated metabolite N'-acetyl-4,4'-methylenedianiline (AcMDA) ranged from 0.13 to 7.61 pmol/ml. The amount of MDA released after acid hydrolysis was on average 6.5 times higher than the amount of free MDA and AcMDA present in urine. MDA was detected as a hemoglobin (Hb) adduct in all of the 20 subjects. The level ranged from 70 to 710 fmol/g Hb. In one individual the Hb adduct of AcMDA was detected. This is the first time a Hb adduct of AcMDA has been detected after occupational exposure to MDI. This is a further piece of evidence for the biological availability of the suspected human carcinogen MDA from in vivo hydrolysis of MDI. Plasma albumin conjugates of MDI can cause the onset of respiratory disorders in both man and animal models. Thus we investigated the presence of plasma protein adducts. The plasma MDA levels ranged from 0.25 to 5.4 pmol/ml. Up to 120 fmol/mg were found to be covalently bound to albumin.
authors.affiliation: Institut für Pharmakologie und Toxikologie, Universität Würzburg, Germany.
authors.forename: O
authors.initials: O
authors.lastname: Sepai
authors.forename: D
authors.initials: D
authors.lastname: Henschler
authors.forename: G
authors.initials: G
authors.lastname: Sabbioni
mesh_terms: D000107:Acetylation; D000328:Adult; D000485:Allergens / Q000097:blood / Q000378:metabolism* / Q000652:urine; D001711:Biotransformation; D002273:Carcinogens; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D017953:Isocyanates / Q000097:blood / Q000378:metabolism* / Q000652:urine; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure; D012709:Serum Albumin / Q000378:metabolism*; D001559:Benzhydryl Compounds
chemical_list: D000485:Allergens; D002273:Carcinogens; D006454:Hemoglobins; D017953:Isocyanates; D012709:Serum Albumin; C005969:4,4'-diphenylmethane diisocyanate; D001559:Benzhydryl Compounds