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

Lygia T Budnik1*, Dennis Nowak2, Rolf Merget3, Catherine Lemiere4 and Xaver Baur1

Author Affiliations

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, 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'Hôpital du Sacré-Coeur de Montréal, Montréal, Canada

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Journal of Occupational Medicine and Toxicology 2011, 6:9  doi:10.1186/1745-6673-6-9

Published: 29 March 2011



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.


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.


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.


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.

isocyanates; biomonitoring; biological monitoring; exposure assessment, occupational asthma; hypersensitivity pneumonitis; specific inhalation challenge