Skip to main content
NCBI home page
Occupational and Environmental Medicine logoLink to Occupational and Environmental Medicine
. 2000 Jun;57(6):396–405. doi: 10.1136/oem.57.6.396

Exposure biomarkers and risk from gluing and heating of polyurethane: a cross sectional study of respiratory symptoms

M Littorin 1, L Rylander 1, G Skarping 1, M Dalene 1, H Welinder 1, U Stromberg 1, S Skerfving 1
PMCID: PMC1739970  PMID: 10810129

Abstract

OBJECTIVES—To define the relation between exposure to polyurethane (PUR) glue, biomarkers of exposure and effect, and work related symptoms that occur at least once a week.
METHODS—In a cross sectional study, 152 workers and 14 clerks in a factory with exposure to sprayed and heated PUR glue containing 4,4'-diphenylmethane (MDI) or 1,6-hexamethylene (HDI) di-isocyanate were examined with gas chromatography-mass spectrometry (GC-MS) for metabolites of MDI in plasma (P-MDX) and urine (U-MDX), 2,4- and 2,6-toluene di-isocyanate (TDI; P-TDX, U-TDX) and HDI in plasma and urine, specific serum IgG (S-IgG-MDI, S-IgG-HDI, and S-IgG-TDI, respectively) and IgE (S-IgE-MDI). Work related symptoms of the eyes and airways (nose or lower airways, or both), and lung function were also evaluated.
RESULTS—P-MDX was detected in 65% of the workers, U-TDX in 47%, HDX in none. Three per cent were positive for S-IgE-MDI, 33% for S-IgG-MDI, 32% for S-IgG-TDI, and 12% for S-IgG-HDI. A few clerks had metabolites, and some had antibodies. Most metabolites and immunoglobulins were slightly correlated—for example, P-MDX v S-IgG-MDI: rs=0.21. Workers who heated glue had increased P-MDX (odds ratio (OR)=12 for a value above the median) and S-IgG-MDI (OR=3.7), sprayers P-2,4-TDX (OR=6.2) and P-2,6-TDX (OR=16). Twenty six per cent of the workers had work related symptoms of the airways, 21% from the nose, 11% from the lower airways. Spraying of glue increased the risk of work related symptoms and slightly decreased lung function. U-MDX was associated with work related symptoms from the airways (OR=3.7) and P-2,6-TDX with work related symptoms from the lower airways (OR=6.6). S-IgG-MDI was related to work related symptoms from the airways (OR=2.6).
CONCLUSIONS—There were relations between exposures to sprayed and heated PUR glue based on MDI and HDI, concentrations of metabolites of MDI and TDI in plasma and urine, specific IgG serum antibodies against MDI, TDI, and HDI, and work related symptoms.


Keywords: isocyanate; metabolites; antibodies

Full Text

The Full Text of this article is available as a PDF (162.2 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Akbar-Khanzadeh F., Rivas R. D. Exposure to isocyanates and organic solvents, and pulmonary-function changes in workers in a polyurethane molding process. J Occup Environ Med. 1996 Dec;38(12):1205–1212. doi: 10.1097/00043764-199612000-00005. [DOI] [PubMed] [Google Scholar]
  2. Baur X., Marek W., Ammon J., Czuppon A. B., Marczynski B., Raulf-Heimsoth M., Roemmelt H., Fruhmann G. Respiratory and other hazards of isocyanates. Int Arch Occup Environ Health. 1994;66(3):141–152. doi: 10.1007/BF00380772. [DOI] [PubMed] [Google Scholar]
  3. Bernstein J. A. Overview of diisocyanate occupational asthma. Toxicology. 1996 Jul 17;111(1-3):181–189. doi: 10.1016/0300-483x(96)03375-6. [DOI] [PubMed] [Google Scholar]
  4. Berode M. Detoxification of an aliphatic amine by N-acetylation: experimental and clinical studies. Biochem Int. 1991 Jul;24(5):947–950. [PubMed] [Google Scholar]
  5. Bignon J. S., Aron Y., Ju L. Y., Kopferschmitt M. C., Garnier R., Mapp C., Fabbri L. M., Pauli G., Lockhart A., Charron D. HLA class II alleles in isocyanate-induced asthma. Am J Respir Crit Care Med. 1994 Jan;149(1):71–75. doi: 10.1164/ajrccm.149.1.8111601. [DOI] [PubMed] [Google Scholar]
  6. Brorson T., Skarping G., Nielsen J. Biological monitoring of isocyanates and related amines. II. Test chamber exposure of humans to 1,6-hexamethylene diisocyanate (HDI). Int Arch Occup Environ Health. 1990;62(5):385–389. doi: 10.1007/BF00381369. [DOI] [PubMed] [Google Scholar]
  7. Cartier A., Grammer L., Malo J. L., Lagier F., Ghezzo H., Harris K., Patterson R. Specific serum antibodies against isocyanates: association with occupational asthma. J Allergy Clin Immunol. 1989 Oct;84(4 Pt 1):507–514. doi: 10.1016/0091-6749(89)90364-3. [DOI] [PubMed] [Google Scholar]
  8. 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):165–169. doi: 10.1007/BF00381626. [DOI] [PubMed] [Google Scholar]
  9. 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 Aug;58(8):587–591. doi: 10.1080/15428119791012522. [DOI] [PubMed] [Google Scholar]
  10. FUCHS S., VALADE P. Etude clinique et expérimentale sur quelques cas d'intoxication par le desmodur T (diisocyanate de toluylène 1-2-4 et 1-2-6). Arch Mal Prof. 1951;12(2):191–196. [PubMed] [Google Scholar]
  11. Hagmar L., Nielsen J., Skerfving S. Clinical features and epidemiology of occupational obstructive respiratory disease caused by small molecular weight organic chemicals. Monogr Allergy. 1987;21:42–58. [PubMed] [Google Scholar]
  12. Jakobsson K., Kronholm-Diab K., Rylander L., Hagmar L. Airway symptoms and lung function in pipelayers exposed to thermal degradation products from MDI-based polyurethane. Occup Environ Med. 1997 Dec;54(12):873–879. doi: 10.1136/oem.54.12.873. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Keskinen H., Tupasela O., Tiikkainen U., Nordman H. Experiences of specific IgE in asthma due to diisocyanates. Clin Allergy. 1988 Nov;18(6):597–604. doi: 10.1111/j.1365-2222.1988.tb02911.x. [DOI] [PubMed] [Google Scholar]
  14. Lind P., Dalene M., Tinnerberg H., Skarping G. Biomarkers in hydrolysed urine, plasma and erythrocytes among workers exposed to thermal degradation products from toluene diisocyanate foam. Analyst. 1997 Jan;122(1):51–56. doi: 10.1039/a606148f. [DOI] [PubMed] [Google Scholar]
  15. Liss G. M., Bernstein D. I., Moller D. R., Gallagher J. S., Stephenson R. L., Bernstein I. L. Pulmonary and immunologic evaluation of foundry workers exposed to methylene diphenyldiisocyanate (MDI). J Allergy Clin Immunol. 1988 Jul;82(1):55–61. doi: 10.1016/0091-6749(88)90051-6. [DOI] [PubMed] [Google Scholar]
  16. Littorin M., Truedsson L., Welinder H., Skarping G., Mårtensson U., Sjöholm A. G. Acute respiratory disorder, rhinoconjunctivitis and fever associated with the pyrolysis of polyurethane derived from diphenylmethane diisocyanate. Scand J Work Environ Health. 1994 Jun;20(3):216–222. doi: 10.5271/sjweh.1405. [DOI] [PubMed] [Google Scholar]
  17. Malo J. L., Ouimet G., Cartier A., Levitz D., Zeiss C. R. Combined alveolitis and asthma due to hexamethylene diisocyanate (HDI), with demonstration of crossed respiratory and immunologic reactivities to diphenylmethane diisocyanate (MDI). J Allergy Clin Immunol. 1983 Oct;72(4):413–419. doi: 10.1016/0091-6749(83)90508-0. [DOI] [PubMed] [Google Scholar]
  18. Maître A., Berode M., Perdrix A., Romazini S., Savolainen H. Biological monitoring of occupational exposure to toluene diisocyanate. Int Arch Occup Environ Health. 1993;65(2):97–100. doi: 10.1007/BF00405726. [DOI] [PubMed] [Google Scholar]
  19. Maître A., Berode M., Perdrix A., Stoklov M., Mallion J. M., Savolainen H. Urinary hexane diamine as an indicator of occupational exposure to hexamethylene diisocyanate. Int Arch Occup Environ Health. 1996;69(1):65–68. doi: 10.1007/BF02630741. [DOI] [PubMed] [Google Scholar]
  20. Nielsen J., Welinder H., Schütz A., Skerfving S. Specific serum antibodies against phthalic anhydride in occupationally exposed subjects. J Allergy Clin Immunol. 1988 Jul;82(1):126–133. doi: 10.1016/0091-6749(88)90062-0. [DOI] [PubMed] [Google Scholar]
  21. Raulf-Heimsoth M., Baur X. Pathomechanisms and pathophysiology of isocyanate-induced diseases--summary of present knowledge. Am J Ind Med. 1998 Aug;34(2):137–143. doi: 10.1002/(sici)1097-0274(199808)34:2<137::aid-ajim6>3.0.co;2-u. [DOI] [PubMed] [Google Scholar]
  22. Rosenberg C., Savolainen H. Determination of occupational exposure to toluene diisocyanate by biological monitoring. J Chromatogr. 1986 Oct 3;367(2):385–392. doi: 10.1016/s0021-9673(00)94859-3. [DOI] [PubMed] [Google Scholar]
  23. Schütze 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 Mar;16(3):573–582. doi: 10.1093/carcin/16.3.573. [DOI] [PubMed] [Google Scholar]
  24. Sepai O., Henschler D., Sabbioni G. Albumin adducts, hemoglobin adducts and urinary metabolites in workers exposed to 4,4'-methylenediphenyl diisocyanate. Carcinogenesis. 1995 Oct;16(10):2583–2587. doi: 10.1093/carcin/16.10.2583. [DOI] [PubMed] [Google Scholar]
  25. Skarping G., Dalene M., Littorin M. 4,4'-Methylenedianiline in hydrolysed serum and urine from a worker exposed to thermal degradation products of methylene diphenyl diisocyanate elastomers. Int Arch Occup Environ Health. 1995;67(2):73–77. doi: 10.1007/BF00572229. [DOI] [PubMed] [Google Scholar]
  26. Skarping G., Dalene M., Svensson B. G., Littorin M., Akesson B., Welinder H., Skerfving S. Biomarkers of exposure, antibodies, and respiratory symptoms in workers heating polyurethane glue. Occup Environ Med. 1996 Mar;53(3):180–187. doi: 10.1136/oem.53.3.180. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Tanser A. R., Bourke M. P., Blandford A. G. Isocyanate asthma: respiratory symptoms caused by diphenyl-methane di-isocyanate. Thorax. 1973 Sep;28(5):596–600. doi: 10.1136/thx.28.5.596. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Tee R. D., Cullinan P., Welch J., Burge P. S., Newman-Taylor A. J. Specific IgE to isocyanates: a useful diagnostic role in occupational asthma. J Allergy Clin Immunol. 1998 May;101(5):709–715. doi: 10.1016/S0091-6749(98)70181-2. [DOI] [PubMed] [Google Scholar]
  29. 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):367–374. doi: 10.1007/BF00381050. [DOI] [PubMed] [Google Scholar]
  30. Tinnerberg H., Spanne M., Dalene M., Skarping G. Determination of complex mixtures of airborne isocyanates and amines. Part 3. Methylenediphenyl diisocyanate, methylenediphenylamino isocyanate and methylenediphenyldiamine and structural analogues after thermal degradation of polyurethane. Analyst. 1997 Mar;122(3):275–278. doi: 10.1039/a607564i. [DOI] [PubMed] [Google Scholar]
  31. Tse K. S., Johnson A., Chan H., Chan-Yeung M. A study of serum antibody activity in workers with occupational exposure to diphenylmethane diisocyanate. Allergy. 1985 Jul;40(5):314–320. doi: 10.1111/j.1398-9995.1985.tb00242.x. [DOI] [PubMed] [Google Scholar]
  32. Vandenplas O., Malo J. L., Saetta M., Mapp C. E., Fabbri L. M. Occupational asthma and extrinsic alveolitis due to isocyanates: current status and perspectives. Br J Ind Med. 1993 Mar;50(3):213–228. doi: 10.1136/oem.50.3.213. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Wass U., Belin L. Immunologic specificity of isocyanate-induced IgE antibodies in serum from 10 sensitized workers. J Allergy Clin Immunol. 1989 Jan;83(1):126–135. doi: 10.1016/0091-6749(89)90487-9. [DOI] [PubMed] [Google Scholar]
  34. Welinder H., Nielsen J., Bensryd I., Skerfving S. IgG antibodies against polyisocyanates in car painters. Clin Allergy. 1988 Jan;18(1):85–93. doi: 10.1111/j.1365-2222.1988.tb02847.x. [DOI] [PubMed] [Google Scholar]
  35. White W. G., Morris M. J., Sugden E., Zapata E. Isocyanate-induced asthma in a car factory. Lancet. 1980 Apr 5;1(8171):756–760. doi: 10.1016/s0140-6736(80)91247-7. [DOI] [PubMed] [Google Scholar]
  36. Woellner R. C., Hall S., Greaves I., Schoenwetter W. F. Epidemic of asthma in a wood products plant using methylene diphenyl diisocyanate. Am J Ind Med. 1997 Jan;31(1):56–63. doi: 10.1002/(sici)1097-0274(199701)31:1<56::aid-ajim9>3.0.co;2-v. [DOI] [PubMed] [Google Scholar]
  37. Zammit-Tabona M., Sherkin M., Kijek K., Chan H., Chan-Yeung M. Asthma caused by diphenylmethane diisocyanate in foundry workers. Clinical, bronchial provocation, and immunologic studies. Am Rev Respir Dis. 1983 Aug;128(2):226–230. doi: 10.1164/arrd.1983.128.2.226. [DOI] [PubMed] [Google Scholar]

Articles from Occupational and Environmental Medicine are provided here courtesy of BMJ Publishing Group

RESOURCES