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The malignant mesothelioma is a rare malignancy and mainly caused by occupational exposure to asbestos. German cancer registries are providing a national database to investigate temporal and regional patterns of mesothelioma incidence. These may be of interest for healthcare planning and for surveillance programs aiming at the formerly exposed workforce. We analyzed population-based incidence data of malignant mesothelioma by site, type, sex, age, as well as district and state of patient’s residence. Age-standardized incidence rates (AIRs40+) were calculated according to the European standard population truncated to the age of 40 years and older. We present rates at national, state, and district level and trends of incidence of northern states of Germany. In total, 7,547 malignant mesotheliomas were reported to German cancer registries diagnosed between 2009 and 2013—90% located to the pleura. On average, 1,198 men and 312 women were affected each year. We estimated AIR40+ of 4.77 in 100,000 German men and 0.98 in 100,000 German women. Regional clusters were predominantly located to the seaports of West Germany. The highest regional AIR40+ was 20 per 100,000 men. Corresponding rates in northeast Germany were between 2 and 4 per 100,000 men. Regional clusters of high incidence indicate districts with former shipyards and steel industry, but predominantly in the western part of Germany. The West-to-East difference corresponds to patterns of mortality. Twenty years after banning asbestos in Germany, Bremen and Hamburg are presenting the highest mesothelioma incidence but show steadily decreasing trends.

Objectives Exposure to hexavalent chromium (Cr(VI)) has been primarily studied in chromate production. Here, we measured personal exposure to respirable Cr(VI) together with airborne and urinary Cr and Ni in welders to explore levels and associations between various measures of exposure. Methods Shift concentrations of Cr(VI), Cr, and Ni were measured in respirable welding fumes in 50 men who used either gas metal arc welding (GMAW) (n = 24) or tungsten inert gas welding (TIG) (n = 19) as their major technique. Cr and Ni were determined in pre- and post-shift urine samples. Concentrations below the limit of quantification (LOQ) were multiply imputed. Spearman correlation coefficients (rs) were calculated with 95% confidence intervals (CIs) to explore associations between the exposure variables, and regression models were applied to estimate the effect of the parent metal on the urinary concentration. Results Regarding the respirable Cr(VI), 62% of the measurements were below the LOQ, the 75th percentile was 0.50 µg m-3, and 8 out of 50 (16%) welders exceeded 1 µg m-3. The highest shift concentration that occurred as a result of shielded metal arc welding (SMAW) was 180 µg m-3. The Cr(VI) content in total Cr ranged from 4 to 82% (median 20%), although the concentration correlated with total Cr (rs 0.55, 95% CI 0.46; 0.64). The correlation between Cr(VI) and Ni was weaker (rs 0.42, 95% CI 0.34; 0.51) than that between total Cr and Ni in welding fumes (rs 0.83, 95% CI 0.74; 0.92). Both Cr(VI) and total Cr influenced the urinary Cr concentrations in post-shift samples (P = 0.0008 and P ≤ 0.0001, respectively). The airborne shift exposure was a weaker determinant than the Cr content in pre-shift urine samples, which strongly correlated with post-shift urinary Cr (rs 0.78, 95% CI 0.69; 0.87). Conclusions The Cr(VI) content in total Cr varied considerably in welding fumes. The majority of welders using GMAW or TIG presented with shift concentrations of respirable Cr(VI) below 1 µg m-3. However, very high Cr(VI) concentrations may occur, for example in SMAW. The urinary concentration of total Cr, cannot be used to precisely determine the shift concentration of respirable Cr(VI) in welders.

The International Agency for Research on Cancer considers the carcinogenicity of welding fume of priority for re-evaluation. Genotoxic effects in experimental animals are still inconclusive. Here, we investigated the association of personal exposure to metals in respirable welding fumes during a working shift with oxidatively damaged guanosine in DNA of white blood cells (WBC) and in postshift urine samples from 238 welders. Medians of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodGuo) were 2.35/106 dGuo in DNA of WBC and 4.33 µg/g creatinine in urine. The median of 8-oxo-7,8-dihydroguanosine (8-oxoGuo) was 7.03 µg/g creatinine in urine. The extent of both urinary parameters was higher in welders applying techniques with high particle emission rates to stainless steel than in tungsten inert gas welders (8-oxodGuo: 9.96 vs. 4.49 µg/L, 8-oxoGuo: 15.7 vs. 7.7 µg/L), but this apparent difference diminished after creatinine adjustment. We applied random intercept models to estimate the influence of airborne and systemic exposure to metals on oxidatively damaged guanosine in WBC and urine together with covariates. We observed a highly significant nonlinear association of urinary 8-oxoGuo with serum ferritin (P 1,000 µg/m3 compared to ≤57 µg/m3. Similar effects were found for manganese. Airborne chromium but not nickel was associated with all oxidatively modified guanosine measures, whereas urinary chromium as well as nickel showed associations with urinary modified guanosines. In summary, oxidatively damaged urinary guanosine was associated with airborne and systemic exposure to metals in welders and showed a strong relation to body iron stores. Electronic supplementary material The online version of this article (doi:10.1007/s00204-014-1319-2) contains supplementary material, which is available to authorized users.

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 range1.00; 3.61) and 2.9 μg/L (interquartile range1.50; 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.

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/m(3) and correlated with Fe (r=0.92, 95% CI 0.90-0.94). Inhalable Mn was measured with similar concentrations (IQR 10-340 μg/m(3)). 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.

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.

The chemical complexity of emissions from bitumen applications is a challenge in the assessment of exposure. Personal sampling of vapours and aerosols of bitumen was organized in 320 bitumen-exposed workers and 69 non-exposed construction workers during 2001-2008. Area sampling was conducted at 44 construction sites. Area and personal sampling of vapours and aerosols of bitumen showed similar concentrations between 5 and 10 mg/m(3), while area sampling yielded higher concentrations above the former occupational exposure limit (OEL) of 10 mg/m(3). The median concentration of personal bitumen exposure was 3.46 mg/m(3) (inter-quartile range 1.80-5.90 mg/m(3)). Only few workers were exposed above the former OEL. The specificity of the method measuring C-H stretch vibration is limited. This accounts for a median background level of 0.20 mg/m³ in non-exposed workers which is likely due to ubiquitous aliphatic hydrocarbons. Further, area measurements of polycyclic aromatic hydrocarbons (PAHs) were taken at 25 construction sites. U.S. EPA PAHs were determined with GC/MS, with the result of a median concentration of 2.47 μg/m(3) at 15 mastic asphalt worksites associated with vapours and aerosols of bitumen, with a Spearman correlation coefficient of 0.45 (95% CI -0.13 to 0.78). PAH exposure at mastic-asphalt works was higher than at reference worksites (median 0.21 μg/m(3)), but about one order of magnitude lower compared to coke-oven works. For a comparison of concentrations of vapours and aerosols of bitumen and PAHs in asphalt works, differences in sampling and analytical methods must to be taken into account.

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.

Powdered latex gloves or latex gloves with high allergen content are forbidden in Germany since 1998. It was the aim of this study to test the hypothesis that nationwide preventive measures enable health care workers with latex allergy to work without health risks about 10 years afterwards.Ninety-one health care workers who had been reported to the accident insurance between 1996 and 2004 for occupational latex allergy were examined in 2007. The survey included a questionnaire, a physical examination, spirometry, methacholine testing, skin prick testing and serum IgE measurements to latex and environmental allergens.Recent work-related possibly allergic symptoms were reported by 32 subjects (35%), among them 18 subjects (20%) with symptoms of the eyes, nose or airways. Current sensitization to latex was detected in 61 subjects (67%), and 60 subjects (66%) were atopic. Eleven subjects (12%) showed mild airway obstruction, and 27 subjects (30%) were considered hyperresponsive to methacholine. Whereas overall recent symptoms of the eyes, nose or airways were associated with current latex sensitization (OR 4.5; 95% CI 1.3-16.2), this was not the case for objective outcome parameters (spirometry, bronchial hyperresponsiveness).Although most subjects had only mild disease, ongoing work-related symptoms of the eyes, nose or airways in a substantial number of subjects with latex allergy suggest the need for further secondary preventive measures in German healthcare.

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 foror =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.

Objectives Some epidemiological and animal data indicate that night work might increase the risk for breast cancer. We have investigated the risk in a German population-based case–control study known as GENICA (gene environment interaction and breast cancer). Methods The GENICA study involved interviews to assess shift work information in 857 breast cancer cases and 892 controls. We estimated risks of employment status and night shift characteristics using conditional logistic regression models, adjusting for potential confounders. Resampling and bootstrapping were applied to adjust the risk estimates for a potential selection bias. Results Among 1749 women, 56 cases and 57 controls worked in night shifts for ≥1 year, usually in the healthcare sector (63.0% of controls). Female night workers were more frequently nulliparous and low-educated than day workers (28.6% versus 17.8% and 12.3% versus 9.2%, respectively). Fewer women in night work had ever used post-menopausal hormone therapy (35.7% versus 51.9%). An elevated breast cancer risk was not associated with having ever done shift or night work when compared to women employed in day work only [odds ratio (OR) 0.96, 95% confidence interval (95% CI) 0.67–1.38 and OR 0.91, 95% CI 0.55–1.49, respectively). Women who reported >807 night shifts, the third quartile of the distribution among controls, experienced a breast cancer risk of 1.73 (95% CI 0.71–4.22). Night work for ≥20 years was associated with an OR of 2.48 (95% CI 0.62–9.99) based on 12 cases and 5 controls. Conclusions Long-term night work was associated with a modestly, but not significantly, increased breast cancer risk, while having ever done night work was not. The precision of the results was limited by a low prevalence of night work in this study population.

Summary 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 (Cohen's 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.

Methacholine testing is one of the standard tools for the diagnosis of mild asthma, but there is little information about optimal outcome measures. In this study a total of 395 college students were tested by the ATS dosimeter protocol for methacholine testing, with minor modification. Body plethysmography and spirometry were measured after each inhalation step. The end-of-test-criteria were (i) decrease in forced expiratory volume in 1 s (FEV1) of ≥ 20 % and (ii) doubling of specific airway resistance and its increase to ≥ 2.0 kPa∙s. The results were expressed by receiver operating characteristic (ROC) plots using questionnaire answers as a reference. The areas under the ROC curves were iteratively calculated for a wide range of thresholds for both measures. We found that ROC plots showed maximal sensitivities of about 0.5–0.6 for FEV1 and about 0.7 for specific airway conductance (sGt), with similar specificities of about 0.7–0.8 taking questions with the known high specificity as references. Accordingly, larger maximal areas under the ROC curve were observed for body plethysmography, but the differences were small. A decrease in FEV1 of about 15 % and a decrease of sGt of about 60 % showed the largest areas under the ROC curves. In conclusion, body plethysmography yielded better sensitivity than spirometry, with similar specificity. However, replacing the common spirometric criterium for a positive test (20 % decrease in FEV1 from baseline) by the optimal body plethysmographic criterium would result in an increase of false positive tests from about 4 to 8 % in healthy young adults.

The role of genetic variants and environmental factors in breast cancer etiology has been intensively studied in the last decades. Gene-environment interactions are now increasingly being investigated to gain more insights into the development of breast cancer, specific subtypes, and therapeutics. Recently, night shift work that involves circadian disruption has gained rising interest as a potential non-genetic breast cancer risk factor. Here, we analyzed genetic polymorphisms in genes of cellular clocks, melatonin biosynthesis and signaling and their association with breast cancer as well as gene-gene and gene-night work interactions in a German case-control study on breast cancer.GENICA is a population-based case-control study on breast cancer conducted in the Greater Region of Bonn. Associations between seven polymorphisms in circadian genes (CLOCK, NPAS2, ARTNL, PER2 and CRY2), genes of melatonin biosynthesis and signaling (AANAT and MTNR1B) and breast cancer were analyzed with conditional logistic regression models, adjusted for potential confounders for 1022 cases and 1014 controls. Detailed shift-work information was documented for 857 breast cancer cases and 892 controls. Gene-gene and gene-shiftwork interactions were analyzed using model-based multifactor dimensionality reduction (mbMDR).For combined heterozygotes and rare homozygotes a slightly elevated breast cancer risk was found for rs8150 in gene AANAT (OR 1.17; 95% CI 1.01-1.36), and a reduced risk for rs3816358 in gene ARNTL (OR 0.82; 95% CI 0.69-0.97) in the complete study population. In the subgroup of shift workers, rare homozygotes for rs10462028 in the CLOCK gene had an elevated risk of breast cancer (OR for AA vs. GG: 3.53; 95% CI 1.09-11.42). Shift work and CLOCK gene interactions were observed in the two-way interaction analysis. In addition, gene-shiftwork interactions were detected for MTNR1B with NPAS2 and ARNTL.In conclusion, the results of our population-based case-control study support a putative role of the CLOCK gene in the development of breast cancer in shift workers. In addition, higher order interaction analyses suggest a potential relevance of MTNR1B with the key transcriptional factor NPAS2 with ARNTL. Hence, in the context of circadian disruption, multivariable models should be preferred that consider a wide range of polymorphisms, e.g. that may influence chronotype or light sensitivity. The investigation of these interactions in larger studies is needed.

» Ermittlung der individuellen kumulativen Lebenszeitexposition [mg/m3 x Jahre] durch Gewichtung der Tatigkeitsdauer » Korperliche Untersuchung » Spirometrie (Master Scope, Jaeger, Hoechberg); FEV1, FVC, FEV1/FVC und MEF25, Sollwert-Empfehlungen der Global Lung Initiative (GLI), Sollgrenzwert < 5. Zentil » Spirometrische Defi nition der COPD nach GOLD; FEV1/FVC < 70% und FEV1 ≥ 80% Soll (GOLD-1), FEV1 50% 80% Soll (GOLD-2), FEV1 30% 50% Soll (GOLD-3), FEV1 ≤ 30% Soll (GOLD-4). » Statistik: SAS Version 9.2 (SAS Institut, USA); multiple lineare Regressionsanalyse.

A 62-year-old female sausage packer reported progressive work-related asthma, rhinitis and contact urticaria after contact to dry sausages refined by moulds. Whereas skin prick tests with commercial mould extracts were negative, the patient showed weak skin sensitization to a cultivated mould sample from a dry sausage. Specific immunoglobulin E antibodies to various moulds were demonstrated by ImmunoCAP and antibodies to the cultivated mould sample were demonstrated by enzyme allergosorbent test. The mould was identified by pheno- and genotyping as Penicillium camemberti. Five atopic controls did not show sensitization with the same tests. Crossreactivity of P. camemberti and Penicillium notatum was shown by enzyme allergosorbent inhibition tests. Although no challenge tests were considered due to the patient’s airway obstruction, a diagnosis of allergic occupational asthma was made. We conclude that immunoglobulin E-mediated allergic occupational asthma due to moulds may occur in dry sausage packers.

The association between exposure to welding fume and chronic obstructive pulmonary disease (COPD) has been insufficiently clarified. In this study we assessed the influence of exposure to welding fume on lung function parameters. We investigated forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC, and expiratory flow rates in 219 welders. We measured current exposure to respirable particles and estimated a worker’s lifetime exposure considering welding techniques, working conditions and protective measures at current and former workplaces. Multiple regression models were applied to estimate the influence of exposure to welding fume, age, and smoking on lung function. We additionally investigated the duration of working as a welder and the predominant welding technique. The findings were that age- and smoking-adjusted lung function parameters showed no decline with increasing duration, current exposure level, and lifetime exposure to welding fume. However, 15 % of the welders had FEV1/FVC below the lower limit of normal, but we could not substantiate the presence of an association with the measures of exposure. Adverse effects of cigarette smoking were confirmed. In conclusion, the study did not support the notion of a possible detrimental effect of exposure to welding fume on lung function in welders.

Inhalative challenges are important in the diagnosis of occupational asthma due to diisocyanates. As existing protocols are time-consuming and costly, it was the aim of this study to develop a short duration whole body exposure protocol. Ninety three subjects with suspected occupational diisocyanate-induced asthma and verified current or previous occupational exposure to diisocyanates and ten control subjects without diisocyanate exposure but with bronchial hyperresponsiveness were investigated. After baseline examination on the first day, subjects underwent a standardized whole body multiple-steps-1-day challenge with exposures of up to four times 30 min to concentrations of 5, 10, 20, and 30 ppb of the dominant diisocyanate used at work on the second day. Common spirometric and body plethysmographic parameters were used as positivity criteria. Overall, 14 subjects demonstrated a positive diisocyanate challenge, 19 were considered doubtful, and 60 were negative. All controls had negative challenges. Positive reactions occurred during the challenge (n = 10) or during follow-up (n = 4). Eight subjects showed >40 % fall of FEV1. These severe reactions occurred after 5 ppb (n = 2) or 10 ppb (n = 3), while isolated late reactions after 2 h of follow-up were not observed. Multivariate analysis showed an association between a positive challenge and both the degree of previous occupational exposure and the presence of baseline bronchial hyperresponsiveness. In summary, the proposed 4-steps-1-day diisocyanate challenge protocol induced pronounced bronchial reactions in a small number of subjects. As these reactions were more likely to occur after low concentrations, it is recommended to shift the initial concentration/dose step to lower exposures.

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.

In a plant where flux-cored arc welding was applied to stainless steel, we investigated changes in airborne and internal metal exposure following improvements of exhaust ventilation and respiratory protection.Twelve welders were examined at a time in 2008 and in 2011 after improving health protection. Seven welders were enrolled in both surveys. Exposure measurement was performed by personal sampling of respirable welding fume inside the welding helmets during one work shift. Urine and blood samples were taken after the shift. Chromium (Cr), nickel (Ni), and manganese (Mn) were determined in air and biological samples.The geometric mean of respirable particles could be reduced from 4.1 mg/m(3) in 2008-0.5 mg/m(3) in 2011. Exposure to airborne metal compounds was also strongly reduced (Mn: 399 vs. 6.8 μg/m(3); Cr: 187 vs. 6.3 μg/m(3); Ni: 76 vs. 2.8 μg/m(3)), with the most striking reduction inside helmets with purified air supply. Area sampling revealed several concentrations above established or proposed exposure limits. Urinary metal concentrations were also reduced, but to a lesser extent (Cr: 14.8 vs. 4.5 μg/L; Ni: 7.9 vs. 3.1 μg/L). Although biologically regulated, the mean Mn concentration in blood declined from 12.8 to 8.9 μg/L.This intervention study demonstrated a distinct reduction in the exposure of welders using improved exhaust ventilation and welding helmets with purified air supply in the daily routine. Data from area sampling and biomonitoring indicated that the area background level may add considerably to the internal exposure.

Non-invasive methods to assess inflammation of lower airways are induced sputum (IS), exhaled nitric oxide (eNO), and exhaled breath condensate (EBC). Here we focused on the assessment of airway inflammation with a panel of non-invasive methods in health care workers (HCWs) with suspected latex allergy with and without current allergic respiratory symptoms about 10 years after the latex ban in German health care facilities. Seventy-seven non-smoking subjects were examined by skin prick test and specific IgE measurements, eNO, IS, and EBC. Sensitivity, specificity, and positive and negative predicted values for relevant biomarkers were calculated using current asthma symptoms as the gold standard. Twenty-nine subjects (38%) reported ongoing asthmatic symptoms (AS). In these subjects the EBC concentrations of nitrogen oxides (NOx; p=0.027) and leukotriene B4 (p=0.025) were significantly higher than in subjects without AS. In addition, in the subjects with AS the numbers of eosinophils (p=0.015) and the concentrations of IL-5 (p= 0.021) in IS samples were significantly higher than in the subjects without AS. A good correlation between several inflammatory markers in IS was detected. The maximum Youden Index was reached for IS total eosinophils ≥3.5·104 with a test efficiency of 0.72. In conclusion, non-invasive inflammatory monitoring with EBC and IS may assist the diagnosis of allergic asthma. Self-reported current asthmatic symptoms were reflected by eosinophilic inflammation and the best parameter to support the asthma diagnosis is a total number of eosinophils ≥3.5·104 in IS.

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

We investigated the micronucleus frequencies in peripheral blood lymphocytes of 225 mastic asphalt workers (age 17–62 years) and 69 non-bitumen-exposed road construction workers (age 18–64 years) in Germany before and after the working shift. Median shift exposure to vapours and aerosols of bitumen of exposed workers was 3.0 mg/m³. Micronuclei (MN) were determined with a standard method using cytochalasin B. Median MN frequency was 6.0 (interquartile range (IQR) 4.0–8.5) MN/1,000 binucleated lymphocytes (MN/1,000 BNC) in exposed workers and 6.0 (IQR 4.0–8.3) MN/1,000 BNC in non-exposed workers before shift. After shift, we observed 6.5 (IQR 4.4–9.3) MN/1,000 BNC in exposed workers and 6.5 (IQR 4.0–9.0) MN/1,000 BNC in non-exposed workers. Regression models were applied with the log-transformed MN frequency as the dependent variable in order to estimate the effects of exposure to vapours and aerosols of bitumen and of potential confounders. Age was the strongest predictor of MN formation in both exposed workers and referents. Our data suggest that MN formation was not associated with concentration of vapours and aerosols of bitumen during shift at the individual level. Although similar MN frequencies were observed in both groups, the modelling of factors potentially influencing MN frequency revealed a weak group difference in the post-shift model. We conclude that this small difference cannot be judged to be a relevant mutagenic effect of exposure to vapours and aerosols of bitumen, also with regard to the lack of adjustment for multiple testing and the lack of a group effect in the original data.

Data concerning the influence of sequence variants of metabolizing enzymes on the effect modulation of current exposure to vapors and aerosols of bitumen in humans are limited. To assess the influence of 18 single-nucleotide polymorphisms (SNP) in genes coding for enzymes involved in polycyclic aromatic hydrocarbon (PAH) and amine metabolism regarding their impact on urinary markers 1-hydroxpyrene (1-OHP) and the sum of 1-, 2+9-, 3-, 4-hydroxyphenanthrene (OHPHE). Based on personal ambient monitoring data for bitumen emissions, 218 German workers exposed to vapors and aerosols of bitumen during a shift and 96 German roadside construction workers without exposure to bitumen but with similar working tasks were studied. SNP determination based on DNA aliquots isolated from blood samples by real-time PCR or direct sequencing. The impact of sequence variants on the urinary levels of 1-OHP and sum of OHPHE was estimated with mixed linear models, adjusted for age, creatinine, exposure, smoking, SNP, and time of measurement. In the mixed linear model, an increasing metabolite level of OHPHE was only slightly modulated by the CC variant of the cytochrome P450 SNP CYP1A1 3801T>C (rs4646903; P = 0.051). In contrast, GSTM1 carriers showed a significant (P= 0.046) and double-mutated variants of three NAT2-specific SNP (NAT2*341CC, P = 0.06; NAT2*481TT, P = 0.06; NAT2*803GG, P = 0.042) displayed a decreasing influence on OHPHE levels. None of the SNP studied showed a significant effect on 1-OHP. The modulating SNP effects on OHPHE in the adjusted model were less pronounced when compared with the effects observed in a recent study with 170 workers occupationally exposed to PAH in German industries. This may be due to the much lower PAH exposure in the Human Bitumen Study.

Emission levels of vapours and aerosols of bitumen are different when processing rolled asphalt compared to mastic asphalt, with working temperatures up to 180 and 250°C, respectively. During the Human Bitumen Study, we examined six workers handling rolled asphalt and mastic asphalt in two consecutive weeks at the same construction site in a tunnel. In addition to the determination of exposure to bitumen and polycyclic aromatic hydrocarbons (PAH) during shift, we examined urinary PAH metabolites, irritative and genotoxic effects before and after shift. Median personal shift concentration of vapours and aerosols of bitumen was 1.8 (range 0.9-2.4) mg/m(3) during the application of rolled asphalt and 7.9 (range 4.9-11.9) mg/m(3) when mastic asphalt was applied. Area measurement of vapours and aerosols of bitumen revealed higher concentrations than the personal measurements for mastic asphalt (mastic asphalt: 34.9 mg/m(3); rolled asphalt: 1.8 mg/m(3)). Processing mastic asphalt was associated also with higher PAH concentrations. Urinary 1-hydroxypyrene and the sum of 1-, 2+ 9-, 3- and 4-hydroxyphenanthrene increased slightly during shift without clear difference between mastic and rolled asphalt application. However, the post-shift urinary PAH-metabolite concentrations did not reflect the different PAH exposure during mastic and rolled asphalt application. Individual workers could be identified by their spirometry results indicating that these data reflect more chronic than acute effects. In most cases, an increase of 8-oxodGuo adducts was observed during shift that was independent of the asphalt application. 8-oxodGuo and (+)-anti-BPDE-DNA adducts were higher than in exposed workers of the Human Bitumen Study independent of the asphalt application. The DNA-strand breaks were considerably higher pre-shift and decreased during shift. In this study, mastic asphalt application led to significantly higher exposure to vapours and aerosols of bitumen, as well as to airborne PAH, compared to rolled asphalt application. Nevertheless, no differences in the excretion of urinary PAH metabolites, lung function impairment and genotoxic markers were detected. However, higher levels of genotoxicity markers on both examination days compared with the results of the Human Bitumen Study may indicate a possible influence of the specific tunnel setting.

Cross-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. Twenty-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. Five 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. Subjects 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.

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.

Die Internationale Krebsagentur (International Agency for Research on Cancer, IARC) stufte im Jahre 2007 Nachtschichtarbeit, die mit zirkadianen Storungen einhergeht, in die Kategorie 2A (wahrscheinlich krebserzeugend) ein (Straif et al. 2007). In epidemiologischen Studien beruhen die Angaben zu Schichtarbeit in der Regel auf Eigenangaben der Probanden. GENICA ist eine bevolkerungsbezogene Fall-Kontroll-Studie mit 1143 inzidenten Brustkrebsfallen und 1155 Kontrollen aus der Region Bonn. In einer Nacherhebung im Rahmen der Erfassung von Hormonpraparaten wurden alle erreichbaren Frauen telefonisch zu Schichtarbeit befragt (857 Mammakarzinom-Patientinnen und 892 Kontrollen). Dabei wurde erfasst, in welchem Zeitraum die Frauen in Wechsel-oder Nachtschicht tatig waren. Nach der Einstufung von Nachtschichtarbeit durch die IARC wurden weiterhin von 223 Schichtarbeiterinnen detaillierte Angaben zu Schichtsystemen, Beschaftigungsverhaltnissen, Tatigkeiten, Dauer und Uhrzeiten erfasst. Die Reliabilitat der Angaben zu Nacht- und Wechselschicht in den nachfolgenden Befragungen wurde mit Kappa Statistik und logistischer Regression untersucht. Risikoschatzungen wurden mit logistischer Regression bedingt nach Alter und unter Berucksichtigung von Confoundern durchgefuhrt, wobei ein moglicher Einfluss einer Selektionsverzerrung durch die verschiedenen Interviews mit Bootstrapping-Verfahren untersucht wurde. Insgesamt kann Schichtarbeit zuverlassig berichtet werden. Auch bei variierenden Definitionen von Nachtarbeit ergeben sich nur wenige Umklassifizierungen. Die Komplexitat der Schichtsysteme erfordert jedoch ein geeignetes Erhebungsinstrument, um die relevanten Einflussfaktoren untersuchen zu konnen.

Objectives The aim of this analysis was to explore exposure to welding fumes and potential influencing factors of the airborne concentrations. Methods Personal sampling of welding fumes was carried out in 241 welders. Ninety respirable dust measurements were below the limits of detection (LOD). Therefore, we applied Tobit regression and imputations of values below LOD according to the log-normal distributions of the data ≥LOD with maximum likelihood estimation. We estimated regression coefficients for the welding processes, protective measures, and other factors. Results Main determinant of the concentrations was the type of welding process. The use of flux-cored wire in gas metal arc welding was estimated to increase the concentration in comparison with gas metal arc welding with solid wire (GMAW) by a factor of 2.20 (95% CI 1.58 to 3.06) using Tobit regression and by 2.36 (95% CI 1.51 to 3.69) using imputation. Tungsten inert gas welding was associated with 0.15 fold lower levels than with GMAW in both models. Dust extraction reduced the concentrations, whereas welding in confined space increased exposure levels with significant effects in both approaches. Conclusions Exposure to respirable welding fumes was frequently found below LOD. Two different approaches to deal with data

Fumes of bitumen contain small amounts of polycyclic aromatic hydrocarbons (PAH). Some of them are known to be carcinogenic. Therefore a possible genotoxic risk from exposure of workers during hot application of bitumen in mastic asphalt laying is under discussion. In order to address this question we investigated the micronucleus (MN) frequencies in lymphocytes of mastic asphalt workers and reference persons not exposed to bitumen.