Metabolites of the PAH diol epoxide pathway and other urinary biomarkers of phenanthrene and pyrene in workers with and without exposure to bitumen fumes.

PURPOSE: This study investigates the diol epoxide pathway of phenanthrene (PHE) together with phenolic metabolites of PHE and pyrene (PYR) in workers with and without exposure to bitumen fumes. METHODS: The metabolite concentrations were determined in urine samples collected from 91 mastic asphalt workers and 42 construction workers as reference group before and after shift. During shift, vapours and aerosols of bitumen were measured according to a German protocol in the workers' breathing zone. RESULTS: The median concentration of vapours and aerosols of bitumen in mastic asphalt workers was 6.3 mg/m3. Metabolite concentrations were highest in post-shift urines of smokers with bitumen exposure and showed an increase during shift. The Spearman correlations between the creatinine-adjusted concentrations of metabolites and vapours and aerosols of bitumen in non-smokers were weak (e.g. sum of Di-OH-PYR: 0.28) or negligible (e.g. 1,2-PHE-diol: 0.08; PHE-tetrol: 0.12). Metabolites from the diol epoxide pathway of PHE were excreted in higher concentrations than phenolic metabolites (post-shift, non-smoking asphalt workers: 1,2-PHE-diol 2.59 µg/g crea vs. sum of all OH-PHE 1.87 µg/g crea). 1,2-PHE-diol was weakly correlated with PHE-tetrol (Spearman coefficient 0.30), an endpoint of the diol epoxide pathway. By contrast, we found a close correlation between the sum of 1,6-DiOH-PYR and 1,8-DiOH-PYR with 1-OH-PYR (Spearman coefficient 0.76). CONCLUSIONS: Most urinary PAH metabolites were higher after shift in bitumen-exposed workers, although the association with bitumen was weak or negligible likely due to the small PAH content. The additional metabolites of PHE and PYR complete the picture of the complex metabolic pathways. Nevertheless, none of the PAH metabolites can be considered to be a specific biomarker for bitumen exposure.

Airborne exposure to inhalable hexavalent chromium in welders and other occupations: Estimates from the German MEGA database.

This study aimed to estimate occupational exposure to inhalable hexavalent chromium (Cr(VI)) using the exposure database MEGA. The database has been compiling Cr(VI) concentrations and ancillary data about measurements at German workplaces. We analysed 3659 personal measurements of inhalable Cr(VI) collected between 1994 and 2009. Cr(VI) was determined spectrophotometrically at 540 nm after reaction with diphenylcarbazide. We assigned the measurements to pre-defined at-risk occupations using the information provided about the workplaces. Two-thirds of the measurements were below the limit of quantification (LOQ) and multiply imputed according to the distribution above LOQ. The 75th percentile value was 5.2 µg/m(3) and the 95th percentile was 57.2 µg/m(3). We predicted the geometric mean for 2h sampling in the year 2000, and the time trend of Cr(VI) exposure in these settings with and without adjustment for the duration of measurements. The largest dataset was available for welding (N = 1898), which could be further detailed according to technique. The geometric means were above 5 µg/m(3) in the following situations: spray painting, shielded metal arc welding, and flux-cored arc welding if applied to stainless steel. The geometric means were between 1 µg/m(3) and 5 µg/m(3) for gas metal arc welding of stainless steel, cutting, hard-chromium plating, metal spraying and in the chemical chromium industry. The exposure profiles described here are useful for epidemiologic and industrial health purposes. Exposure to Cr(VI) varies not only between occupations, but also within occupations as shown for welders. In epidemiologic studies, it would be desirable to collect exposure-specific information in addition to the job title.

Oxidatively damaged guanosine in white blood cells and in urine of welders: associations with exposure to welding fumes and body iron stores.

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 2.35/10(6) 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 < 0.0001) and higher 8-oxoGuo concentrations for respirable iron >1,000 µg/m(3) compared to ≤57 µg/m(3). 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.

Influence of welding fume on systemic iron status.

Iron is the major metal found in welding fumes, and although it is an essential trace element, its overload causes toxicity due to Fenton reactions. To avoid oxidative damage, excess iron is bound to ferritin, and as a result, serum ferritin (SF) is a recognized biomarker for iron stores, with high concentrations linked to inflammation and potentially also cancer. However, little is known about iron overload in welders. Within this study, we assessed the iron status and quantitative associations between airborne iron, body iron stores, and iron homeostasis in 192 welders not wearing dust masks. Welders were equipped with personal samplers in order to determine the levels of respirable iron in the breathing zone during a working shift. SF, prohepcidin and other markers of iron status were determined in blood samples collected after shift. The impact of iron exposure and other factors on SF and prohepcidin were estimated using multiple regression models. Our results indicate that respirable iron is a significant predictor of SF and prohepcidin. Concentrations of SF varied according to the welding technique and respiratory protection used, with a median of 103 µg l(-1) in tungsten inert gas welders, 125 µg l(-1) in those wearing air-purifying respirators, and 161 µg l(-1) in other welders. Compared to welders with low iron stores (SF < 25 µg l(-1)), those with excess body iron (SF ≥ 400 µg l(-1)) worked under a higher median concentration of airborne iron (60 µg m(-3) versus 148 µg m(-3)). Even though air concentrations of respirable iron and manganese were highly correlated, and low iron stores have been reported to increase manganese uptake in the gastrointestinal tract, no correlation was seen between SF and manganese in blood. In conclusion, monitoring SF may be a reasonable method for health surveillance of welders. Respiratory protection with air-purifying respirators can decrease iron exposure and avoid chronically higher SF in welders working with high-emission technologies.

Reduction in welding fume and metal exposure of stainless steel welders: an example from the WELDOX study.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

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.

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

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/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.

Air sampling and determination of vapours and aerosols of bitumen and polycyclic aromatic hydrocarbons in the Human Bitumen Study.

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.

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.

Occupational exposure to polycyclic aromatic hydrocarbons and DNA damage by industry: a nationwide study in Germany.

Exposure to polycyclic aromatic hydrocarbons (PAH) and DNA damage were analyzed in coke oven (n = 37), refractory (n = 96), graphite electrode (n = 26), and converter workers (n = 12), whereas construction workers (n = 48) served as referents. PAH exposure was assessed by personal air sampling during shift and biological monitoring in urine post shift (1-hydroxypyrene, 1-OHP and 1-, 2 + 9-, 3-, 4-hydroxyphenanthrenes, SigmaOHPHE). DNA damage was measured by 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) and DNA strand breaks in blood post shift. Median 1-OHP and SigmaOHPHE were highest in converter workers (13.5 and 37.2 microg/g crea). The industrial setting contributed to the metabolite concentrations rather than the air-borne concentration alone. Other routes of uptake, probably dermal, influenced associations between air-borne concentrations and levels of PAH metabolites in urine making biomonitoring results preferred parameters to assess exposure to PAH. DNA damage in terms of 8-oxo-dGuo and DNA strand breaks was higher in exposed workers compared to referents ranking highest for graphite-electrode production. The type of industry contributed to genotoxic DNA damage and DNA damage was not unequivocally associated to PAH on the individual level most likely due to potential contributions of co-exposures.

Chromated metal products may be hazardous to patients with chromate allergy.

BACKGROUND: Hidden allergen exposure may contribute to persistence and relapse of chromate dermatitis. According to case reports, chromated metal products, such as screws, fittings, etc., may be relevant allergen sources for patients sensitized to chromate. OBJECTIVES: To examine concomitant patch test reactivity to potassium dichromate 0.5% petrolatum (pet.) and three different types of chromated metal rings. PATIENTS/METHODS: Patients with proven or suspected chromate allergy were patch tested with potassium dichromate 0.5% pet. and three different types of chromated metal rings (yellow, olive, and black). Hexavalent chromium Cr(VI) release from the patch tested rings was chemically analysed. RESULTS: Ninety-five patients were tested: 49/95 (52%) reacted to potassium dichromate and 25/95 (26%) reacted to black chromated rings. Reactions to chromated rings exclusively occurred in patients reacting to potassium dichromate. Of 20 patients with a strong reaction to potassium dichromate, 14 reacted to black chromated rings. These were shown to have a high Cr(VI) release. Only two patients reacted to the other chromated rings, which had a very low Cr(VI) release. CONCLUSIONS: Handling chromated metal products must be regarded a hazard to chromate-sensitive patients, in particular those with a strong sensitization.

Biological monitoring as a useful tool for the detection of a coal-tar contamination in bitumen-exposed workers.

In our research project entitled "Chemical irritative and/or genotoxic effect of fumes of bitumen under high processing temperatures on the airways," 73 mastic asphalt workers exposed to fumes of bitumen and 49 construction nonexposed workers were analyzed and compared with respect to polycyclic aromatic hydrocarbons (PAHs) exposure and exposure-related health effects. In order to assess the internal exposure the monohydroxylated metabolites of pyrene, 1- hydroxypyrene (1-OHP), and phenanthrene, 1-, 2- and 9-, and 3- and 4-hydroxyphenanthrene (OHPH) were determined in pre- and post-shift urinary samples. Significantly higher concentrations 1-OHP and OHPH were detected in the post-shift urine samples of 7 mastic asphalt workers working on the same construction site compared to the reference workers and all other 66 mastic asphalt workers. The adjusted mean OHPH in the reference, 66 mastic worker, and 7 worker subgroups was 1022, 1544, and 12919 ng/g creatinine (crn) respectively, indicating a marked rise in the 7 worker subgroup. In addition, there was a more than 12-fold increase of PAH metabolites from pre- to post-shift in these 7 workers, whereas in the other mastic asphalt workers there was only a twofold rise in PAH-metabolite concentration between pre- and post-shift values. The analysis of a drilling core from the construction site of the seven workers led to the detection of the source for this marked PAH exposure during the working shift as being coal tar plates, which were, without knowledge of the workers and coordinators, the underground material of the mastic asphalt layer. The evaluation of the stationary workplace concentration showed enhanced levels of phenanthrene, pyrene, fluorene, anthracene, and acenaphthene during working shifts at the construction site of these seven workers. Our study shows that biological monitoring is also a useful tool for the detection of unrecognized sources with high PAH concentrations.

Irritative effects of fumes and aerosols of bitumen on the airways: results of a cross-shift study.

Possible health hazards of fumes and aerosols of bitumen are in discussion, and data on their adverse effects on human airways under current exposure conditions are limited. To assess the irritative effects of exposure to fumes and aerosols of bitumen on the airways, a cross-sectional cross-shift study was conducted including external and internal exposure measurements, spirometry and especially non-invasive methods like nasal lavage collection and induction of sputum in order to identify and evaluate more precisely inflammatory process in the upper and lower airways. The cross-shift study comprised 74 mastic asphalt workers who were exposed to fumes and aerosols of bitumen and 49 construction workers without this exposure as reference group. Questionnaire, spirometry, ambient monitoring and urinary analysis were performed. Humoral and cellular parameters were measured in nasal lavage fluid (NALF) and induced sputum. For data analysis, a mixed linear model was performed on the different outcomes with exposure group, time of measurement (pre-, post-shift), current smoking, German nationality and age as fixed factors and subjects as random factor. Based on personal exposure measurements during shift, mastic asphalt workers were classified into a low (< or =10 mg/m(3); n = 46) and a high (>10 mg/m(3); n = 28) exposure group. High exposure was accompanied by significant higher urinary post-shift concentrations of 1-hydroxypyrene and the sum of hydroxyphenanthrenes. Acute respiratory symptoms were reported more frequently in the high exposure group after shift. Significant cross-shift declines in lung function parameters (forced expiratory volume in 1 s [FEV(1) (% predicted)] and forced vital capacity [FVC (% predicted)]) were measured in mastic asphalt workers. Pre-shift FEV(1) (% predicted) and FVC (% predicted) were higher in the low exposure group. In pre- and post-shift NALF samples, interleukin (IL)-1beta-, IL-8- and total protein concentrations were lower in the low exposure group compared to the reference and the high exposure group. Pre- and post-shift neutrophil percentages in both nasal and sputum samples were also lower in the low exposure group. Significantly higher pre- and post-shift sputum concentrations of IL-8, IL-6, nitrogen oxide (NO) derivatives and total protein were detected especially in highly exposed workers. Irritative effects of exposure to fumes and aerosols of bitumen on the upper and lower airways were apparent, especially in mastic asphalt workers with exposure above 10 mg/m(3).

Assessment of DNA damage in WBCs of workers occupationally exposed to fumes and aerosols of bitumen.

We conducted a cross-shift study with 66 bitumen-exposed mastic asphalt workers and 49 construction workers without exposure to bitumen. Exposure was assessed using personal monitoring of airborne bitumen exposure, urinary 1-hydroxypyrene (1-OHP), and the sum of 1-, 2 + 9-,3-,4-hydroxyphenanthrene (OHPH). Genotoxic effects in WBC were determined with nonspecific DNA adduct levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) and the formation of DNA strand breaks and alkali-labile sites. Concentration of fumes and aerosols of bitumen correlated significantly with the concentrations of 1-OHP and OHPH after shift (r(s) = 0.27; P = 0.03 and r(s) = 0.55; P < 0.0001, respectively). Bitumen-exposed workers had more DNA strand breaks than the reference group (P < 0.0001) at both time points and a significant correlation with 1-OHP and OHPH in the postshift urines (r(s) = 0.32; P = 0.001 and r(s) = 0.27; P = 0.004, respectively). Paradoxically, we measured higher levels of DNA strand breaks, although not significant, in both study groups before shift. 8-OxodGuo adduct levels did not correlate with DNA strand breaks. Further, 8-oxodGuo levels were associated neither with personal exposure to bitumen nor with urinary metabolite concentrations. Significantly more DNA adducts were observed after shift not only in bitumen-exposed workers but also in the reference group. Only low-exposed workers had significantly elevated 8-oxodGuo adduct levels before as well as after shift (P = 0.0002 and P = 0.02, respectively). Our results show that exposure to fumes and aerosols of bitumen may contribute to an increased DNA damage assessed with strand breaks.