Abstract
BackgroundIsocyanates 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.MethodsA 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.ResultsAfter 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.ConclusionsThe 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.
Highlights
Isocyanates are some of the leading occupational causes of respiratory disorders, predominantly asthma
A period of at least three days without known occupational exposure was kept in each case prior to the investigation. 30 subjects (25%) of the study group showed positive specific inhalation challenge (SIC) results, 42 subjects (35%) showed bronchial hyperresponsiveness (NSBHR) as evaluated by methacholine challenge testing, according to the centers definition. 17 subjects (14%) had specific IgE antibodies to the particular isocyanate
It is known that the respective industrial products represent a mixture of 2,4- and 2,6-TDA which is used at the majority of workplaces
Summary
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. Isocyanates, which are characterized by the highly reactive N = C = O groups, are one of the most frequent causes of occupational asthma and can elicit hypersensitivity pneumonitis and accelerated lung function loss [3,4,5,6,7]. Clinical diagnosis and the differential identification of isocyanates as the cause of work-related disorders are often difficult because of multiple exposures (i.e. to HDI and to MDI/TDI during spray painting) [1,3,7]. Exposure monitoring may recognize risk factors for disease development and help to prevent the onset or aggravation of disease. A reliable measurement system of incidental exposure would benefit bystanders and members of the general public, as well
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