Elimination kinetics of diisocyanates after specific inhalative challenges in humans: mass spectrometry analysis, as a basis for biomonitoring strategies

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• 作者：Lygia T Budnik (1)
  Dennis Nowak (2)
  Rolf Merget (3)
  Catherine Lemiere (4)
  Xaver Baur (1)
  
• 关键词：isocyanates ; biomonitoring ; biological monitoring ; exposure assessment ; occupational asthma ; hypersensitivity pneumonitis ; specific inhalation challenge
• 刊名：Journal of Occupational Medicine and Toxicology
• 出版年：2011
• 出版时间：December 2011
• 年：2011
• 卷：6
• 期：1
• 全文大小：690KB
• 参考文献：1. Malo JL, Ghezzo H, Elie R: Occupational asthma caused by isocyanates: patterns of asthmatic reactions to increasing day-to-day doses. / Am J Respir Crit Care Med 1999,159(6):1879-883.
  2. Pronk A, Preller L, Raulf-Heimsoth M, Jonkers IC, Lammers JW, Wouters IM, Doekes G, Wisnewski AV, Heederik D: Respiratory symptoms, sensitization, and exposure response relationships in spray painters exposed to isocyanates. / Am J Respir Crit Care Med 2007,176(11):1090-097. CrossRef
  3. Mapp CE: "Occupational asthma": a matter of concern. / Eur Respir J 1994,7(1):1. CrossRef
  4. Baur X, Wieners D, Marczynski B: Late asthmatic reaction caused by naphthylene-1,5 diisocyanate. / Scand J Work Environ Health 2000,26(1):78-0.
  5. Malo JL, Lemiere C, Desjardins A, Cartier A: Prevalence and intensity of rhinoconjunctivitis in subjects with occupational asthma. / Eur Respir J 1997,10(7):1513-515. CrossRef
  6. Merget R, Marczynski B, Chen Z, Remberger K, Raulf-Heimsoth M, Willrot PO, Baur X: Haemorrhagic hypersensitivity pneumonitis due to naphthylene-1,5-diisocyanate. / Eur Respir J 2002,19(2):377-80. CrossRef
  7. Dykewicz MS: Occupational asthma: current concepts in pathogenesis, diagnosis, and management. / J Allergy Clin Immunol 2009,123(3):519-28. quiz 529-30 CrossRef
  8. Redlich CA, Herrick CA: Lung/skin connections in occupational lung disease. / Curr Opin Allergy Clin Immunol 2008,8(2):115-19. CrossRef
  9. Boulet LP, Lemiere C, Gautrin D, Cartier A: New insights into occupational asthma. / Curr Opin Allergy Clin Immunol 2007,7(1):96-01.
  10. Baur X: Evidence for allergic reactions in isocyanate asthma. / J Allergy Clin Immunol 2007,119(3):757-58. author reply 758 CrossRef
  11. Monso E, Cloutier Y, Lesage J, Perreault G, Malo JL: What is the respiratory retention of inhaled hexamethylene di-isocyanate? / Eur Respir J 2000,16(4):729-30. CrossRef
  12. Karlsson D, Dahlin J, Skarping G, Dalene M: Determination of isocyanates, aminoisocyanates and amines in air formed during the thermal degradation of polyurethane. / J Environ Monit 2002,4(2):216-22. CrossRef
  13. Rosenberg C, Nikkila K, Henriks-Eckerman ML, Peltonen K, Engstrorm K: Biological monitoring of aromatic diisocyanates in workers exposed to thermal degradation products of polyurethanes. / J Environ Monit 2002,4(5):711-16. CrossRef
  14. Sepai O, Henschler D, Sabbioni G: Albumin adducts, hemoglobin adducts and urinary metabolites in workers exposed to 4,4'-methylenediphenyl diisocyanate. / Carcinogenesis 1995,16(10):2583-587. CrossRef
  15. Sabbioni G, Wesp H, Lewalter J, Rumler R: Determination of isocyanate biomarkers in construction site workers. / Biomarkers 2007,12(5):468-83. CrossRef
  16. Creely KS, Hughson GW, Cocker J, Jones K: Assessing isocyanate exposures in polyurethane industry sectors using biological and air monitoring methods. / Ann Occup Hyg 2006,50(6):609-21. CrossRef
  17. Pronk A, Yu F, Vlaanderen J, Tielemans E, Preller L, Bobeldijk I, Deddens JA, Latza U, Baur X, Heederik D: Dermal, inhalation, and internal exposure to 1,6-HDI and its oligomers in car body repair shop workers and industrial spray painters. / Occup Environ Med 2006,63(9):624-31. CrossRef
  18. Lemiere C, Bai T, Balter M, Bayliff C, Becker A, Boulet LP, Bowie D, Cartier A, Cave A, Chapman K, / et al.: Adult Asthma Consensus Guidelines update 2003. / Can Respir J 2004,11(Suppl A):9A-18A.
  19. Baur X, Marek W, Ammon J, Czuppon AB, Marczynski B, Raulf-Heimsoth M, Roemmelt H, Fruhmann G: Respiratory and other hazards of isocyanates. / Int Arch Occup Environ Health 1994,66(3):141-52. CrossRef
  20. Schutze D, Sepai O, Lewalter J, Miksche L, Henschler D, Sabbioni G: Biomonitoring of workers exposed to 4,4'-methylenedianiline or 4,4'-methylenediphenyl diisocyanate. / Carcinogenesis 1995,16(3):573-82. CrossRef
  21. Bolognesi C, Baur X, Marczynski B, Norppa H, Sepai O, Sabbioni G: Carcinogenic risk of toluene diisocyanate and 4,4'-methylenediphenyl diisocyanate: epidemiological and experimental evidence. / Crit Rev Toxicol 2001,31(6):737-72. CrossRef
  22. Tinnerberg H, Mattsson C: Usage of air monitoring and biomarkers of isocyanate exposure to assess the effect of a control intervention. / Ann Occup Hyg 2008,52(3):187-94. CrossRef
  23. Skarping G, Brorson T, Sango C: Biological monitoring of isocyanates and related amines. III. Test chamber exposure of humans to toluene diisocyanate. / Int Arch Occup Environ Health 1991,63(2):83-8. CrossRef
  24. Brorson T, Skarping G, Sango C: Biological monitoring of isocyanates and related amines. IV. 2,4- and 2,6-toluenediamine in hydrolysed plasma and urine after test-chamber exposure of humans to 2,4- and 2,6-toluene diisocyanate. / Int Arch Occup Environ Health 1991,63(4):253-59. CrossRef
  25. Rosenberg C, Savolainen H: Determination in urine of diisocyanate-derived amines from occupational exposure by gas chromatography-mass fragmentography. / Analyst 1986,111(9):1069-071. CrossRef
  26. Kaaria K, Hirvonen A, Norppa H, Piirila P, Vainio H, Rosenberg C: Exposure to 4,4'-methylenediphenyl diisocyanate (MDI) during moulding of rigid polyurethane foam: determination of airborne MDI and urinary 4,4'-methylenedianiline (MDA). / Analyst 2001,126(4):476-79. CrossRef
  27. Brorson T, Skarping G, Sandstrom JF, Stenberg M: Biological monitoring of isocyanates and related amines. I. Determination of 1,6-hexamethylene diamine (HDA) in hydrolysed human urine after oral administration of HDA. / Int Arch Occup Environ Health 1990,62(1):79-4. CrossRef
  28. Sakai T, Morita Y, Roh J, Kim H, Kim Y: Improvement in the GC-MS method for determining urinary toluene-diamine and its application to the biological monitoring of workers exposed to toluene-diisocyanate. / Int Arch Occup Environ Health 2005,78(6):459-66. CrossRef
  29. Kennedy AL, Stock MF, Alarie Y, Brown WE: Uptake and distribution of 14C during and following inhalation exposure to radioactive toluene diisocyanate. / Toxicol Appl Pharmacol 1989,100(2):280-92. CrossRef
  30. Littorin M, Truedsson L, Welinder H, Skarping G, Martensson U, Sjoholm AG: Acute respiratory disorder, rhinoconjunctivitis and fever associated with the pyrolysis of polyurethane derived from diphenylmethane diisocyanate. / Scand J Work Environ Health 1994,20(3):216-22.
  31. Lind P, Dalene M, Skarping G, Hagmar L: Toxicokinetics of 2,4- and 2,6-toluenediamine in hydrolysed urine and plasma after occupational exposure to 2,4- and 2,6- toluene diisocyanate. / Occup Environ Med 1996,53(2):94-9. CrossRef
  32. Dalene M, Skarping G, Lind P: Workers exposed to thermal degradation products of TDI- and MDI-based polyurethane: biomonitoring of 2,4-TDA, 2,6-TDA, and 4,4'-MDA in hydrolyzed urine and plasma. / Am Ind Hyg Assoc J 1997,58(8):587-91.
  33. Dalene M, Jakobsson K, Rannug A, Skarping G, Hagmar L: MDA in plasma as a biomarker of exposure to pyrolysed MDI-based polyurethane: correlations with estimated cumulative dose and genotype for N-acetylation. / Int Arch Occup Environ Health 1996,68(3):165-69. CrossRef
  34. Tinnerberg H, Skarping G, Dalene M, Hagmar L: Test chamber exposure of humans to 1,6-hexamethylene diisocyanate and isophorone diisocyanate. / Int Arch Occup Environ Health 1995,67(6):367-74. CrossRef
  35. Slatter JG, Rashed MS, Pearson PG, Han DH, Baillie TA: Biotransformation of methyl isocyanate in the rat. Evidence for glutathione conjugation as a major pathway of metabolism and implications for isocyanate-mediated toxicities. / Chem Res Toxicol 1991,4(2):157-61. CrossRef
  36. Baur X, Budnik LT: [New data on occupational exposure to isocyanates]. / Pneumologie 2009,63(11):656-61. CrossRef
  
• 作者单位：Lygia T Budnik (1)
  Dennis Nowak (2)
  Rolf Merget (3)
  Catherine Lemiere (4)
  Xaver Baur (1)
  
  1. Institute for Occupational Medicine and Maritime Medicine (ZfAM), University Medical Center, Hamburg-Eppendorf, Hamburg, Germany
  2. Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, Ludwig-Maximillian-University Munich, Bochum, Germany
  3. Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr-University (IPA), Bochum, Germany
  4. University de Montréal, Departement of Medicine, Centre de recherche de l’H?pital du Sacré-Coeur de Montréal, Montréal, Canada
  

文摘

Background Isocyanates are some of the leading occupational causes of respiratory disorders, predominantly asthma. Adequate exposure monitoring may recognize risk factors and help to prevent the onset or aggravation of these aliments. Though, the biomonitoring appears to be most suitable for exposure assessment, the sampling time is critical, however. In order to settle the optimal time point for the sample collection in a practical biomonitoring approach, we aimed to measure the elimination of isocyanate urine metabolites. Methods A simple biomonitoring method enabling detection of all major diamine metabolites, from mono-, poly- and diisocyanates in one analytical step, has been established. Urine samples from 121 patients undergoing inhalative challenge tests with diisocyanates for diagnostic reasons were separated by gas chromatography and analyzed with mass spectrometry (GC-MS) at various time points (0-24 h) after the onset of exposure. Results After controlled exposures to different concentrations of diisocyanates (496 ± 102 ppb-min or 1560 ± 420 ppb-min) the elimination kinetics (of respective isocyanate diamine metabolites) revealed differences between aliphatic and aromatic isocyanates (the latter exhibiting a slower elimination) and a dose-response relationship. No significant differences were observed, however, when the elimination time patterns for individual isocyanates were compared, in respect of either low or high exposure or in relation to the presence or absence of prior immunological sensitization. Conclusions The detection of isocyanate metabolites in hydrolyzed urine with the help of gas chromatography combined with mass spectrometric detection system appears to be the most suitable, reliable and sensitive method to monitor possible isocyanate uptake by an individual. Additionally, the information on elimination kinetic patterns must be factored into estimates of isocyanate uptake before it is possible for biomonitoring to provide realistic assessments of isocyanate exposure. The pathophysiological elimination of 1,6-hexamethylene diamine, 2,4-diamine toluene, 2,6-diamine toluene, 1,5-naphthalene diamine, 4,4'-diphenylmethane diamine and isophorone diamines (as respective metabolites of: 1,6-hexamethylene diisocyanate, 2,4-toluene diisocyanate and 2,6 toluene diisocyanate, 1,5-naphthalene diisocyanate, 4,4'-diphenylmethane diisocyanate and isophorone diisocyanates) differs between individual isocyanates' diamines.