Evelyn Heinze

Exposure to Inhalable, Respirable, and Ultrafine Particles in Welding Fume

This investigation aims to explore determinants of exposure to particle size-specific welding fume. Area sampling of ultrafine particles (UFP) was performed at 33 worksites in parallel with the collection of respirable particles. Personal sampling of respirable and inhalable particles was carried out in the breathing zone of 241 welders. Median mass concentrations were 2.48 mg m−3 for inhalable and 1.29 mg m−3 for respirable particles when excluding 26 users of powered air-purifying respirators (PAPRs). Mass concentrations were highest when flux-cored arc welding (FCAW) with gas was applied (median of inhalable particles: 11.6 mg m−3). Measurements of particles were frequently below the limit of detection (LOD), especially inside PAPRs or during tungsten inert gas welding (TIG). However, TIG generated a high number of small particles, including UFP. We imputed measurements <LOD from the regression equation with manganese to estimate determinants of the exposure to welding fume. Concentrations were mainly predicted by the welding process and were significantly higher when local exhaust ventilation (LEV) was inefficient or when welding was performed in confined spaces. Substitution of high-emission techniques like FCAW, efficient LEV, and using PAPRs where applicable can reduce exposure to welding fume. However, harmonizing the different exposure metrics for UFP (as particle counts) and for the respirable or inhalable fraction of the welding fume (expressed as their mass) remains challenging.

Levels and predictors of airborne and internal exposure to manganese and iron among welders

We investigated airborne and internal exposure to manganese (Mn) and iron (Fe) among welders. Personal sampling of welding fumes was carried out in 241 welders during a shift. Metals were determined by inductively coupled plasma mass spectrometry. Mn in blood (MnB) was analyzed by graphite furnace atom absorption spectrometry. Determinants of exposure levels were estimated with multiple regression models. Respirable Mn was measured with a median of 62 (inter-quartile range (IQR) 8.4–320) μg/m3 and correlated with Fe (r=0.92, 95% CI 0.90–0.94). Inhalable Mn was measured with similar concentrations (IQR 10–340 μg/m3). About 70% of the variance of Mn and Fe could be explained, mainly by the welding process. Ventilation decreased exposure to Fe and Mn significantly. Median concentrations of MnB and serum ferritin (SF) were 10.30 μg/l (IQR 8.33–13.15 μg/l) and 131 μg/l (IQR 76–240 μg/l), respectively. Few welders were presented with low iron stores, and MnB and SF were not correlated (r=0.07, 95% CI −0.05 to 0.20). Regression models revealed a significant association of the parent metal with MnB and SF, but a low fraction of variance was explained by exposure-related factors. Mn is mainly respirable in welding fumes. Airborne Mn and Fe influenced MnB and SF, respectively, in welders. This indicates an effect on the biological regulation of both metals. Mn and Fe were strongly correlated, whereas MnB and SF were not, likely due to higher iron stores among welders.

Levels and predictors of airborne and internal exposure to chromium and nickel among welders--results of the WELDOX study.

The objective of this analysis was to investigate levels and determinants of exposure to airborne and urinary chromium (Cr, CrU) and nickel (Ni, NiU) among 241 welders. Respirable and inhalable welding fume was collected during a shift, and the metal content was determined using inductively coupled plasma mass spectrometry. In post-shift urine, CrU and NiU were measured by means of graphite furnace atom absorption spectrometry, with resulting concentrations varying across a wide range. Due to a large fraction below the limits of quantitation we applied multiple imputations to the log-transformed exposure variables for the analysis of the data. Respirable Cr and Ni were about half of the concentrations of inhalable Cr and Ni, respectively. CrU and NiU were determined with medians of 1.2 μg/L (interquartile range <1.00; 3.61) and 2.9 μg/L (interquartile range <1.50; 5.97). Furthermore, Cr and Ni correlated in respirable welding fume (r=0.79, 95% CI 0.74-0.85) and urine (r=0.55, 95% CI 0.44-0.65). Regression models identified exposure-modulating variables in form of multiplicative factors and revealed slightly better model fits for Cr (R(2) respirable Cr 48%, CrU 55%) than for Ni (R(2) respirable Ni 42%, NiU 38%). The air concentrations were mainly predicted by the metal content in electrodes or base material in addition to the welding technique. Respirable Cr and Ni were good predictors for CrU and NiU, respectively. Exposure was higher when welding was performed in confined spaces or with inefficient ventilation, and lower in urine when respirators were used. In conclusion, statistical modelling allowed the evaluation of determinants of internal and external exposure to Cr and Ni in welders. Welding parameters were stronger predictors than workplace conditions. Airborne exposure was lowest inside respirators with supply of purified air.

Development of a 1-concentration-4-step dosimeter protocol for methacholine testing

Methacholine testing is an important diagnostic tool for asthma. Newly available dosimeter and software technology allows for simplification of the test. This study aimed to evaluate a single-concentration dosimeter protocol for methacholine testing by comparison with a multi-concentration dosimeter protocol similar to that recommended by the American Thoracic Society (ATS) (standard protocol). Fifty young subjects with high pretest probability for bronchial hyperresponsiveness underwent two challenges in randomized order within one week. The novel protocol used a Medic-Aid Sidestream nebulizer and a fixed methacholine concentration of 16mg/mL. Number and duration of nebulizations were matched to the last four doses of the standard protocol, and results were expressed cumulatively. The rank correlation between log slopes (n=50) was 0.86; that between log provocative doses (n=18), which differed at low values, was 0.58. When requiring a 20% fall in FEV(1) at any methacholine dose, 18 subjects were hyperresponsive and 28 normoresponsive in both tests (46/50 concordant). One subject was positive only with the standard, and 3 only with the novel protocol (Cohens kappa 83%). The novel protocol for methacholine testing yielded qualitative results similar to those of the ATS multi-concentration protocol, although there were quantitative differences at low doses. However, its design and handling may offer advantages for clinical practice.

DNA adducts and strand breaks in workers exposed to vapours and aerosols of bitumen: associations between exposure and effect

To study the associations between exposure to vapours and aerosols of bitumen and genotoxic effects, a cross-sectional and cross-shift study was conducted in 320 exposed workers and 118 non-exposed construction workers. Ambient air measurements were carried out to assess external exposure to vapours and aerosols of bitumen. Hydroxylated metabolites of naphthalene, phenanthrene and pyrene were measured in urine, whereas (+)-anti-benzo[a]pyrene-7,8-diol-9,10-epoxide ((+)-anti-BPDE), 8-oxo-7,8-dihydro-2′-deoxyguanosine (8oxodGuo) and DNA strand breaks were determined in blood. Significantly higher levels of 8-oxodGuo adducts and DNA strand breaks were found in both pre- and post-shift blood samples of exposed workers compared to those of the referents. No differences between exposed workers and referents were observed for (+)-anti-BPDE. Moreover, no positive associations between DNA damage and magnitude of airborne exposure to vapours and aerosols of bitumen could be observed in our study. Additionally, no relevant association between the urinary metabolites of PAH and the DNA damage in blood was observed. Overall, our results indicate increased oxidative DNA damage in workers exposed to vapours and aerosols of bitumen compared to non-exposed referents at the group level. However, increased DNA strand breaks in bitumen workers were still within the range of those found in non-exposed and healthy persons as reported earlier. Due to the lack of an association between oxidative DNA damage and exposure levels at the workplaces under study, the observed increase in genotoxic effects in bitumen workers cannot be attributed to vapours and aerosols of bitumen.

Cancer mortality in a surveillance cohort of German males formerly exposed to asbestos.

The objective of this analysis was the estimation of the cancer risks of asbestos and asbestosis in a surveillance cohort of high-exposed German workers. A group of 576 asbestos workers was selected for high-resolution computer tomography of the chest in 1993-1997. A mortality follow-up was conducted through 2007. Standardised mortality ratios (SMRs) were calculated and Poisson regression was performed to assess mesothelioma risks. A high risk was observed for pleural mesothelioma (SMR 28.10, 95% CI 15.73-46.36) that decreased after cessation of exposure (RR 0.1; 95% CI 0.0-0.6 for > or =30 vs. <30 years after last exposure). Asbestosis was a significant risk factor for mesothelioma (RR 6.0, 95% CI 2.4-14.7). Mesothelioma mortality was still in excess in former asbestos workers although decreasing after cessation of exposure. Fibrosis was associated with subsequent malignancy.

Levels and determinants of exposure to vapours and aerosols of bitumen.

Bitumen (referred to as asphalt in the United States) is a widely used construction material, and emissions from hot bitumen applications have been a long-standing health concern. One objective of the Human Bitumen Study was to identify potential determinants of the exposure to bitumen. The study population analysed comprised 259 male mastic asphalt workers recruited between 2003 and 2008. Personal air sampling in the workers’ breathing zone was carried out during the shift to measure exposure to vapours and aerosols of bitumen. The majority of workers were engaged in building construction, where exposure levels were lower than in tunnels but higher than at road construction sites. At building construction sites, exposure levels were influenced by the room size, the processing temperature of the mastic asphalt and the job task. The results show that protective measures should include a reduction in the processing temperature.

Implementation of Non-invasive Methods in the Diagnosis of Diisocyanate-Induced Asthma

Diisocyanate-induced asthma is difficult to diagnose since the immunopathological mechanisms and exposure determinants at the workplace are not well defined. The aim of this study was to evaluate the non-invasive methods of nasal lavage fluid (NALF) and induced sputum (IS) to enhance the diagnostic efficiency. Sixty-three diisocyanate-exposed workers with work-related shortness of breath underwent a standardized 4-steps-1-day-whole body exposure test with diisocyanates used at work up to 30 ppb. NALF and IS were collected before, 0.5, and 19 h after the end of exposure. Cellular composition and soluble inflammatory biomarkers were studied in the samples. In addition, ten controls with bronchial hyperresponsiveness, but without prior occupational diisocyanate exposure, were also examined. Twelve out of the 63 subjects (19 %) showed a significant asthmatic reaction (pulmonary responders) after challenge (FEV1 decrease >20 %). NALF samples did not demonstrate significant effects either on cellular composition or on mediator concentrations in the responders, non-responders, or controls at any time point. In contrast, in the IS samples of the pulmonary responders collected 19 h after challenge, the percentage of eosinophils was higher (p = 0.001) compared with baseline before challenge. Eosinophils were also increased 30 min and 19 h after challenge in IS samples of the responders compared with the non-responders or controls. In addition, 19 h after challenge the eosinophilic cationic protein (ECP) concentration was significantly higher in the responders than non-responders (p < 0.04) or controls (p < 0.002). In conclusion, positive asthmatic reactions to diisocyanates are accompanied by an influx of eosinophils into lower airways. Analysis of induced sputum should be implemented in the diagnostic procedure of diisocyanate-related airway diseases.

Allergic asthma after flour inhalation in subjects without occupational exposure to flours: an experimental pilot study.

ObjectiveCross-reactivity between grass pollen and grain flour allergens is well known, but their significance in apprentice bakers with primary sensitization to grass pollen is not known.MethodsTwenty-five subjects with mild asthma (most of them with hay fever), but without prior occupational flour exposure, underwent standardized experimental inhalation challenges with placebo and wheat and rye flours in randomized order on three consecutive days. Sensitization to flours and environmental allergens was assessed by skin prick tests and specific IgE antibodies in sera. IgE inhibition experiments were performed with wheat and rye flours as solid phases, and grass and tree pollen as inhibitors.ResultsFive subjects experienced a positive reaction after flour inhalation (responders), whereas 20 subjects did not show such a reaction (non-responders). All responders showed sensitizations to flours, whereas only 25% of the non-responders demonstrated the same sensitization. Specific IgE concentrations to flours, but also to grass and tree pollen, were higher in responders. Inhibition experiments demonstrated cross-reactivity between flours and grass or tree pollen, with higher inhibition rates in responders.ConclusionsSubjects with pronounced sensitizations to grass or tree pollen, but without prior occupational exposure to flours, may experience both sensitization and allergic asthmatic reactions to flours due to cross-reactive grass and tree pollen allergens.

Association Between Genetic Polymorphisms in Styrene-Metabolizing Enzymes and Biomarkers in Styrene-Exposed Workers∗

Single-nucleotide polymorphisms (SNP) in genes of styrene-metabolizing enzymes could modulate biomarker concentrations in blood or urine after exposure to styrene. Ten SNP were analyzed to study their influence on styrene-specific biomarkers in 89 workers of a fiber-reinforced plastic boat building factory. The internal styrene body burden was analyzed in post-shift blood and urine samples. External styrene exposure was measured by passive samplers. Spearman rank correlations between styrene exposure and biomarkers were calculated and distributions of biomarkers were checked for lognormality. Mixed linear models were applied to analyze the influence of genotypes and styrene exposure, on styrene in blood (Monday and Thursday post-shift) and on phenyglyoxylic acid (PGA; adjusted for day of measurement, Monday to Thursday) due to a lognormal distribution, smoking (current, not current), and use of respirators. Stratified analyzes for workers without and with different types of respirators were also performed. The models of both the subgroups revealed a significant influence dependent on the respirator type that workers used for inhalation protection. An influence of the external styrene concentration on the urinary PGA concentration was not observed. After implementation of the SNP into the model significant lower adjusted means of urinary PGA concentrations were found for GSTP1 105IleVal and CYP2E1 –71TT. For styrene levels in blood no significant effect was observed. A significant influence on styrene levels in blood was correlated with external styrene concentration only in workers without use of respirators. The effects of two SNP on urinary PGA decrease indicated a limited modulating SNP effect. The most effective prevention for styrene exposure was obtained with the wearing of respirators.