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

Background: 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. Methods: 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. Results: 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. Conclusions: 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

Outcome of Occupational Latex Allergy—Work Ability and Quality of Life

OBJECTIVE: The quality of life (QOL) and work ability of health care workers allergic to natural rubber latex (NRL) were assessed after implementation of regulations on powder-free NRL gloves in Germany. METHODS: 196 HCW with reported NRL allergy answered a questionnaire (response rate 58%) containing the Work Ability Index (WAI), Mini Asthma Quality of Life Questionnaire (MiniAQLQ), and Dermatology Life Quality Index (DLQI). RESULTS: 63.2% still had NRL-related symptoms during the last 6 month. However on a scale from 0 to 10, the intensity of NRL-related symptoms decreased from 8.5 before to 2.3 after implementation of regulations on powder-free NRL gloves. A higher number of subjects were able to avoid NRL in the private than in the work environment (85% vs. 61%). NRL-related symptoms decreased and WAI increased with successful avoidance of NRL at workplace (b = 0.23, p = 0.003). QOL was only little affected by NRL allergy (mean: MiniAQLQ = 6.0; DLQI = 4.1). CONCLUSIONS: Although there was improvement after implementation of powder-free NRL gloves, there is still a considerable number of HCW with NRL-related symptoms. Further investigations on latex avoidance and the cause of persisiting allergic symptoms in HCW with NRL allergy are therefore needed

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

Abstract Background 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. Methods 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. Results 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. Conclusions 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.</p

Cross-Sectional Study on Respiratory Morbidity in Workers After Exposure to Synthetic Amorphous Silica at Five German Production Plants Exposure Assessment and Exposure Estimates

Objectives: Synthetic amorphous silicas (SASs) are nanostructured polymorphs of silicon dioxide. We compared two different exposure assessments. Methods: This study estimated cumulative exposure to inhalable SAS dust in 484 male workers from five German SAS-producing plants. Two procedures (P1 and P2) were applied. P1 was based on an expert assessment. P2 was a multiple exposure assessment (15 scenarios) anchored by a recent measurement series (1375 personal measurements of inhalable SAS dust concentration) and used expert assessments. Results: Cumulative exposure estimates for P1 averaged 56.9 mg/m(3).yrs (range, 0.1 to 419); for a selected P2 scenario, the mean was 31.8 mg/m(3).yrs (range, 0.4 to 480), (P < 0.0001). Averages varied between the 15 P2-scenarios from 12.6 to 109.6 mg/m(3).yrs. Different time trends for SAS concentrations were observed. Conclusions: Both approaches suffer from considerable uncertainties that need to be considered in epidemiological studies

Cross-Sectional Study on Nonmalignant Respiratory Morbidity due to Exposure to Synthetic Amorphous Silica

Objectives: The aim of this study was to assess the health impact of chronic exposure to synthetic amorphous silica (SAS) on nonmalignant respiratory morbidity. Methods: We used multiple linear and logistic regression models and Monte Carlo multimodel analyses of two exposure scenarios to evaluate the effect of cumulative exposure to inhalable SAS dust on symptoms, spirometry, and chest films in 462 male workers from five German SAS-producing plants. Results: Exposure to SAS was associated with a reduction in forced vital capacity (FVC) in one of the two exposure scenarios but had no effect on forced expiratory volume in 1 second (FEV1) or FEV1/FVC in either exposure scenario. Monte Carlo analysis indicated a decline in FVC of -11mL per 10 mg/m(3)-years exposure (-6 to -0.4). Chest films showed no evidence of pneumoconiosis. Conclusion: This study provides limited evidence of minor dose-related effects of chronic exposure to SAS on lung function

Multivariate linear regression analyses for factors influencing WAI (adjusted for gender and age); currently employed participants (n = 136¹).

<p>The following factors had no influence on the WAI: level of most intensive complaints ever, level of complaints in the year of the claim, NRL-avoidance in the private environment, asthma in the 6 months before the survey, period of filing the claim to the survey.</p>1<p>differing n due to missing values.</p

Occupational status, NRL avoidance, NRL-related symptoms, work ability, QOL.

1<p>participants working in the same or a comparable occupation.</p>2<p>participants with NRL-related respiratory symptoms at the time of filing the claim.</p>3<p>participants with NRL-related cutaneous symptoms at the time of filing the claim.</p