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Development, validation and characterization of an analytical method for the 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

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Summary, in English

Occupational exposure to diisocyanates within the plastic industry causes irritation and disorders in the airway. The aim of this study was to develop, validate and characterize a method for the determination of 2,4-toluenediamine (2,4-TDA), 2,6-toluenediamine (2,6-TDA), 1,5-diaminonaphthalene (1,5-NDA) and 4,4'-methylenedianiline (4,4'-MDA) in hydrolysed urine and plasma, and to study the correlation between the plasma and urinary levels of these potential biomarkers of 2,4-toluene diisocyanate (2,4-TDI), 2,6-toluene diisocyanate (2,6-TDI), 1,5-naphthalene diisocyanate (1,5-NDI) and 4,4'-methylenediphenyl diisocyanate (4,4'-MDI), respectively. Samples were hydrolysed with 0.3 M NaOH at 100degreesC for 24 h. The diamines were extracted, derivatized with pentafluoropropionic acid anhydride, and quantified by selected ion monitoring on gas chromatography-mass spectrometry. The repeatability and reproducibility of the method were 7-18% and 7-19%, respectively. Dialysis experiments showed that the metabolites of 2,4-TDI, 2,6-TDI, 1,5-NDI and 4,4'-MDI in plasma were exclusively protein adducts. No free diamines were found in urine, indicating that all diisocyanate-related metabolites were in a conjugated form. For each diisocyanate-related biomarker, there were strongly significant correlations (p < 0.001) between individual levels of metabolites in plasma and urine, with Spearman's rank correlation coefficient (r(s)) values of 0.74-0.90. The methods presented here will be valuable for the development of biological monitoring methods for diisocyanates.

Publishing year

2003

Language

English

Pages

204-217

Publication/Series

Biomarkers

Volume

8

Issue

3-4

Document type

Journal article

Publisher

Taylor & Francis

Topic

  • Environmental Health and Occupational Health

Keywords

  • diisocyanates
  • biological markers
  • gas chromatography-mass spectrometry
  • protein adducts

Status

Published

ISBN/ISSN/Other

  • ISSN: 1366-5804