Skip to main content
Log in

Biomarkers of exposure in Monday morning urine samples as a long-term measure of exposure to aromatic diisocyanates

  • Original Article
  • Published:
International Archives of Occupational and Environmental Health Aims and scope Submit manuscript

Abstract

Purpose

Exposure to diisocyanates is a known occupational hazard. One method for monitoring occupational exposure is by analyzing biomarkers in hydrolyzed urine and plasma. The half-life of the biomarkers in plasma is about 3 weeks, and the urinary elimination is divided into one fast (hours) and one slow phases (weeks). Polymorphism in glutathione S-transferase enzymes (GST) is earlier shown to modify the metabolism. The aim of the study was to assess whether biomarkers of exposure in urine collected after two non-exposed days correlate with levels in plasma and whether they can be used as a measure for long-term exposure to aromatic diisocyanates and further whether polymorphisms in GST influenced the correlations.

Methods

Biomarkers of exposure was analyzed in urine and blood samples collected from 24 workers, exposed to at least one of toluene-, methylenediphenyl- or naphthalene diisocyanate, on a Monday morning after at least two unexposed days. Moreover, genotype was determined for 19 of the workers.

Results

The corresponding specific gravity-adjusted biomarkers in urine and plasma levels for the different diisocyanates correlated well (r between 0.689 and 0.988). When taking all samples together, the correlation coefficient was 0.926. Polymorphism in the GSTM1 genotype seemed to modify the association.

Conclusion

Urine collected after two unexposed days can possibly be used as long-term biomarker of exposure for aromatic diisocyanates.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Altman DG (1991) Diagnostics test. In: Practical statistics for medical research. London, Chapman and Hall, pp 414–419

  • Bakerly ND, Moore VC, Vellore AD, Jaakkola MS, Robertson AS, Burge PS (2008) Fifteen-year trends in occupational asthma: data from the Shield surveillance scheme. Occup Med 58:169–174

    Article  Google Scholar 

  • Boeniger MF, Lowry LK, Rosenberg J (1993) Interpretation of urine results used to assess chemical exposure with emphasis on creatinine adjustment: a review. Am Ind Hyg Assoc J 54:615–627

    Article  CAS  Google Scholar 

  • Broberg K, Tinnerberg H, Axmon A, Warholm M, Rannug A, Littorin M (2008) Influence of genetic factors on toluene diisocyanate-related symptoms. Environ Health 7:15

    Article  CAS  Google Scholar 

  • Broberg K, Littorin M, Axmon A, Jönsson BAG, Sennbro CJ, Tinnerberg H, Warholm M, Rannug A (2010) The GSTP1 Ile 105 val polymorphism modifies the metabolism of toluene diisocyanate (TDI). Pharmacogenet Genom 20:104–111

    Article  CAS  Google Scholar 

  • Brorson T, Skarping G, Sangö C (1991) Biological monitoring of isocyanates and related amines—Part IV: 2,4- and 2,6-toluenediamine in plasma and urine after test-chamber exposure of humans to 2,4- and 2,6-toluene diisocyanate. Int Arch Occup Environ Health 63:253–259

    Article  CAS  Google Scholar 

  • Budnik LT, Nowak D, Merger R, Lemiere C, Baur X (2011) Elimination kinetics of diisocyanates after specific inhalative challenges in humans: mass spectrometry analysis, as a basis for biomonitoring strategies. J Occup Med Toxicol 6:9

    Article  CAS  Google Scholar 

  • Dalene M, Skarping G, Lind P (1997) 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 58:587–591

    Article  CAS  Google Scholar 

  • Day BW, Jin R, Basalyga DM, Kramarik JA, Karol MH (1997) Formation, solvolysis, and transcarbamoylation reactions of bis(s-glutathionyl) adducts of 2,4- and 2,6-diisocyanatotoluene. Chem Res Toxicol 10:424–431

    Article  CAS  Google Scholar 

  • Henriks-Eckerman ML, Välimää J, Rosenberg CK, Peltonen K, Engström K (2002) Exposure to airborne isocyanates and other thermal degradation products at polyurethane-processing workplaces. J Environ Monit 4:717–721

    Article  CAS  Google Scholar 

  • Johannesson G, Sennbro CJ, Willix P, Lindh CH, Jönsson BAG (2004) Identification and characterization of adducts between serum albumin and MDI in human plasma. Arch Toxicol 78:378–383

    Article  CAS  Google Scholar 

  • Kääriä K, Hirvonen A, Norppa H, Piirilä P, Vainio H, Rosenberg C (2001a) Exposure to 2,4- and 2,6-toluene diisocyanate (TDI) during production of flexible foam: determination of airborne TDI and urinary 2,4- and 2,6-toluenediamine (TDA). Analyst 126:1025–1031

    Article  CAS  Google Scholar 

  • Kääriä K, Hirvonen A, Norppa H, Piirilä P, Vainio H, Rosenberg C (2001b) Exposure to 4,4′-methylenediphenyl diisocyanate (MDI) during moulding of rigid polyurethane foam: determination of airborne MDI and urinary methylene dianiline (MDA). Analyst 126:476–479

    Article  Google Scholar 

  • Lantz RC, Lemus R, Lange RW, Karol MH (2001) Rapid reduction of intracellular glutathione in human bronchial epithelial cells exposed to occupational levels of toluene diisocyanate. Toxicol Sci 60:348–355

    Article  CAS  Google Scholar 

  • Lind P, Dalene M, Skarping G (1996) Biomarkers of toluene diisocyanate and thermal degradation products of polyurethane, with special reference to the sample preparation. Anal Chim Acta 333:277–283

    Article  CAS  Google Scholar 

  • Lind P, Dalene M, Lindström V, Grubb A, Skarping G (1997a) Albumin adducts in plasma from workers exposed to toluene diisocyanate. Analyst 122:151–154

    Article  CAS  Google Scholar 

  • Lind P, Dalene M, Tinnerberg H, Skarping G (1997b) Biomarkers in hydrolysed urine, plasma and erythrocytes among workers exposed to thermal degradation products from toluene diisocyanate foam. Analyst 122:51–56

    Article  CAS  Google Scholar 

  • Littorin M, Rylander L, Skarping G, Dalene M, Welinder H, Strömberg U, Skerfving S (2000) Exposure biomarkers and risk of gluing and heating of polyurethane: a cross sectional study of respiratory symptoms. Occup Environ Med 57:396–405

    Article  CAS  Google Scholar 

  • Littorin M, Axmon A, Broberg K, Sennbro CJ, Tinnerberg H (2007) Eye and airway symptoms in low occupational exposure to toluene diisocyanate. Scand J Work Environ Health 33:280–285

    Article  CAS  Google Scholar 

  • Liu Y, Berode M, Stowe MH, Holm CT, Walsh FX, Slade MD, Boeniger MF, Redlich CA (2004) Urinary hexamethylene diamine to assess respiratory exposure to hexamethylene diisocyanate aerosol. Int J Occup Environ Health 10:262–271

    Article  CAS  Google Scholar 

  • Maitre A, Berode M, Perdrix A, Romazini S, Savolainen H (1993) Biological monitoring of occupational exposure to toluene diisocyanate. Int Arch Occup Environ Health 65:97–100

    Article  CAS  Google Scholar 

  • Maitre A, Berode M, Perdrix A, Stoklov M, Mallion JM, Savolainen H (1996) Urinary hexamethylene diamine as an indicator of occupational exposure to hexamethylene diisocyanate. Int Arch Occup Environ Health 69:65–68

    Article  CAS  Google Scholar 

  • Mapp CE, Fryer AA, De Marzo N, Pozzato V, Padoan M, Boschetto P, Strange RC, Hemmingsen A, Spiteri MA (2002) Glutathione S-transferase GSTP1 is a susceptibility gene for occupational asthma induced by isocyanates. J Allergy Clin Immunol 109:867–872

    Article  CAS  Google Scholar 

  • Nielsen J, Welinder H, Ottosson H, Bensryd I, Venge P, Skerfving S (1994) Nasal challenge shows pathogenetic relevance of specific IgE serum antibodies for nasal symptoms caused by hexahydrophthalic anhydride. Clin Exp Allergy 24:440–449

    Article  CAS  Google Scholar 

  • Piirilä P, Wikman H, Luukkonen R, Kääriä K, Rosenberg C, Nordman H, Norppa H, Vainio H, Hirvonen A (2001) Glutathione S-transferase genotypes and allergic responses to diisocyanate exposure. Pharmacogen 11:437–445

    Article  Google Scholar 

  • Rosenberg C, Savolainen H (1986) Determination of occupational exposure to toluene diisocyanate by biological monitoring. J Chromatogr 367:385–392

    Article  CAS  Google Scholar 

  • Rosqvist S, Nielsen J, Welinder H, Rylander L, Lindh CH, Jönsson BA (2003) Exposure-response relationships for hexahydrophtalic and methylhexahydrophtalic anhydrides with total plasma protein adducts as biomarkers. Scand J Work Environ Health 29:297–303

    Article  CAS  Google Scholar 

  • Sabbioni G, Gu Q, Vanimireddy LR (2012) Determination of isocyanate specific albumin-adducts in workers exposed to toluene diisocyanates. Biomarkers 17:150–159

    Article  CAS  Google Scholar 

  • Sennbro CJ, Lindh CH, Tinnerberg H, Gustavsson C, Littorin M, Welinder H, Jönsson BAG (2003) Development, validation and characterization of an analytical method for quantification of hydrolysable urinary metabolites and plasma protein adducts of 2,4- and 2,6-toluene diisocyanate, 1,5-naphthalene diisocyanate and 4,4′-methylenediphenyl diisocyanate. Biomarkers 8:204–217

    Article  CAS  Google Scholar 

  • Sennbro CJ, Lindh CH, Tinnerberg H, Welinder H, Littorin M, Jönsson BAG (2004) Biological monitoring of exposure to toluene diisocyanate. Scand J Work Environ Health 30:371–378

    Article  CAS  Google Scholar 

  • Sennbro CJ, Littorin M, Tinnerberg H, Jönsson BAG (2005) Upper reference limits for biomarkers of exposure to aromatic diisocyanates. Int Arch Occup Environ Health 78:541–546

    Article  CAS  Google Scholar 

  • Sennbro CJ, Lindh C, Mattsson C, Jönsson BAG, Tinnerberg H (2006) Biological monitoring of exposure to 1,5-naphthalene diisocyanate and 4,4′-methylenediphenyl diisocyanate. Int Arch Occup Environ Health 79:647–653

    Article  CAS  Google Scholar 

  • SWEA Swedish work environment authority (2011) AFS 2011:18 Occupational exposure limit values. Stockholm, Sweden (in Swedish)

  • Swensson Å, Holmquist CE, Lundgren KD (1955) Injury to the respiratory tract by isocyanates used in making lacquers. Br J Industr Med 12:50–53

    CAS  Google Scholar 

  • Tinnerberg H, Skarping G, Dalene M, Hagmar L (1995) Test chamber exposure of humans to 1,6-hexamethylene diisocyanate and isophorone diisocyanate. Int Arch Occup Environ Health 67:367–374

    Article  CAS  Google Scholar 

  • Törnqvist M, Fred C, Haglund J, Helleberg H, Paulsson B, Rydberg P (2002) Protein adducts: quantitative and qualitative aspects of their formation, analysis and application. J Chromatogr B 778:279–308

    Article  Google Scholar 

Download references

Acknowledgments

Financial support for this work was obtained from the Swedish Council for Work Life and Social Research. The authors also thank Mr. Christian Mattsson, Ms. Eva Assarsson and Mrs. Karin Paulsson for skillful technical and medical assistance and the workers in the study for invaluable participation.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Håkan Tinnerberg.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tinnerberg, H., Broberg, K., Lindh, C.H. et al. Biomarkers of exposure in Monday morning urine samples as a long-term measure of exposure to aromatic diisocyanates. Int Arch Occup Environ Health 87, 365–372 (2014). https://doi.org/10.1007/s00420-013-0872-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00420-013-0872-y

Keywords

Navigation