Hexavalent chromium still a concern in Sweden - Evidence from a cross-sectional study within the SafeChrom project.

OBJECTIVES: Hexavalent chromium (Cr(VI)) is classified as a human carcinogen. Occupational Cr(VI) exposure can occur during different work processes, but the current exposure to Cr(VI) at Swedish workplaces is unknown. METHODS: This cross-sectional study (SafeChrom) recruited non-smoking men and women from 14 companies with potential Cr(VI) exposure (n = 113) and controls from 6 companies without Cr(VI) exposure (n = 72). Inhalable Cr(VI) was measured by personal air sampling (outside of respiratory protection) in exposed workers. Total Cr was measured in urine (pre- and post-shift, density-adjusted) and red blood cells (RBC) (reflecting Cr(VI)) in exposed workers and controls. The Bayesian tool Expostats was used to assess risk and evaluate occupational exposure limit (OEL) compliance. RESULTS: The exposed workers performed processing of metal products, steel production, welding, plating, and various chemical processes. The geometric mean concentration of inhalable Cr(VI) in exposed workers was 0.15 µg/m3 (95% confidence interval: 0.11-0.21). Eight of the 113 exposed workers (7%) exceeded the Swedish OEL of 5 µg/m3, and the Bayesian analysis estimated the share of OEL exceedances up to 19.6% for stainless steel welders. Median post-shift urinary (0.60 µg/L, 5th-95th percentile 0.10-3.20) and RBC concentrations (0.73 µg/L, 0.51-2.33) of Cr were significantly higher in the exposed group compared with the controls (urinary 0.10 µg/L, 0.06-0.56 and RBC 0.53 µg/L, 0.42-0.72). Inhalable Cr(VI) correlated with urinary Cr (rS = 0.64) and RBC-Cr (rS = 0.53). Workers within steel production showed the highest concentrations of inhalable, urinary and RBC Cr. Workers with inferred non-acceptable local exhaustion ventilation showed significantly higher inhalable Cr(VI), urinary and RBC Cr concentrations compared with those with inferred acceptable ventilation. Furthermore, workers with inferred correct use of respiratory protection were exposed to significantly higher concentrations of Cr(VI) in air and had higher levels of Cr in urine and RBC than those assessed with incorrect or no use. Based on the Swedish job-exposure-matrix, approximately 17 900 workers were estimated to be occupationally exposed to Cr(VI) today. CONCLUSIONS: Our study demonstrates that some workers in Sweden are exposed to high levels of the non-threshold carcinogen Cr(VI). Employers and workers seem aware of Cr(VI) exposure, but more efficient exposure control strategies are required. National strategies aligned with the European strategies are needed in order to eliminate this cause of occupational cancer.

Sensitive methods for assessment of lung health in welders and controls.

BACKGROUND: Welders are exposed to gas and particle emissions that can cause severe lung disease, such as chronic obstructive pulmonary disease (COPD), a leading cause of mortality and morbidity worldwide. It is difficult to detect COPD early and therefore mitigating measures may be delayed. The aim of this study was to investigate lung health in welders and evaluate new sensitive methods with potential to assess early onset pulmonary changes in occupational settings. METHODS: This study assessed the lung health and symptoms in active welders (n = 28) and controls (n = 17). Lung measurements were performed with standard spirometry and new methods: airspace dimension assessment (AiDA), oscillometry, blood serum biomarkers (club cell secretory protein 16, surfactant protein D, matrix metalloproteinases, fibroblast, hepatocyte growth factor, interleukins), and one urine biomarker (desmosine). RESULTS: According to spirometry measurements, all participants had normal lung function. However, prevalence of cough was significantly higher among welders compared with controls and lung changes were found in welders with the novel methods. Welders had significantly higher respiratory system resistance assessed with oscillometry, serum levels of metalloproteinases 9 and hepatocyte growth factor, compared with controls. Airspace dimensions were on average higher among welders compared with controls, but the difference was not significant. The number of welding years correlated with decreased respiratory system reactance and increased serum levels of matrix metalloproteinases 9, interleukin 6, and hepatocyte growth factor. Airspace dimension assessment indices were correlated with increasing levels of inflammatory markers and matrix metalloproteinases. CONCLUSIONS: This study indicated the potential to use new and more sensitive methods for identification of changes in lungs when standard spirometry failed to do so.

Effects of cleaning spray use on eyes, airways, and ergonomic load.

BACKGROUND: Cleaning workers are exposed to chemicals and high physical workload, commonly resulting in airway problems and pain. In this study the response in the upper airways and the physical workload following airborne and ergonomic exposure of cleaning spray was investigated. METHODS: A survey was answered by professional cleaning workers to investigate their use of cleaning sprays and the perceived effects on eyes, airways and musculoskeletal pain. A human chamber exposure study was then conducted with 11 professional cleaning workers and 8 non-professional cleaning workers to investigate the airborne exposure, acute effects on eyes and airways, and physical load during cleaning with sprays, foam application and microfiber cloths premoistened with water. All cleaning products used were bleach, chlorine, and ammonia free. The medical assessment included eye and airway parameters, inflammatory markers in blood and nasal lavage, as well as technical recordings of the physical workload. RESULTS: A high frequency of spray use (77%) was found among the 225 professional cleaning workers that answered the survey. Based on the survey, there was an eight times higher risk (p < 0.001) of self-experienced symptoms (including symptoms in the nose, eyes and throat, coughing or difficulty breathing) when they used sprays compared to when they cleaned with other methods. During the chamber study, when switching from spray to foam, the airborne particle and volatile organic compound (VOC) concentrations showed a decrease by 7 and 2.5 times, respectively. For the whole group, the peak nasal inspiratory flow decreased (-10.9 L/min, p = 0.01) during spray use compared to using only water-premoistened microfiber cloths. These effects were lower during foam use (-4.7 L/min, p = 0.19). The technical recordings showed a high physical workload regardless of cleaning with spray or with water. CONCLUSION: Switching from a spraying to a foaming nozzle decreases the exposure of both airborne particles and VOCs, and thereby reduces eye and airway effects, and does not increase the ergonomic load. If the use of cleaning products tested in this study, i.e. bleach, chlorine, and ammonia free, cannot be avoided, foam application is preferable to spray application to improve the occupational environment.

Nickel penetration into stratum corneum in FLG null carriers-A human experimental study.

BACKGROUND: The filaggrin gene (FLG) plays a role in skin diseases, with the skin barrier function being impaired in FLG null carriers. The role of FLG status in relation to nickel penetration into the skin remains unclear. OBJECTIVES: To elucidate the association between FLG status and nickel penetration into stratum corneum (SC) in individuals without self-reported history of nickel allergy. METHODS: Forty participants (23 FLG wt and 17 FLG null) were exposed to a nickel solution (80 µg/cm2 ) which was applied onto 2 × 2 cm on their left forearm. After 4 h, the area was tape-stripped with 10 consecutive tapes. Nickel in each tape was quantified using inductively coupled plasma mass spectrometry. RESULTS: The average recovered nickel dose was 35%-48%. A tendency towards lower recovery was seen in FLG null carriers compared to FLG wt carriers, and lower recovery in those with history of skin and/or respiratory symptoms compared to those without such history. This was however not statistically significant. CONCLUSION: FLG null carriers had less nickel recovered by tape strips compared with FLG wt carriers and, compared with individuals without a history of skin and/or respiratory symptoms, indicating higher nickel penetration into SC for FLG null carriers, but further studies are needed.

Underground emissions and miners' personal exposure to diesel and renewable diesel exhaust in a Swedish iron ore mine.

PURPOSE: Underground diesel exhaust exposure is an occupational health risk. It is not known how recent intensified emission legislation and use of renewable fuels have reduced or altered occupational exposures. We characterized these effects on multipollutant personal exposure to diesel exhaust and underground ambient air concentrations in an underground iron ore mine. METHODS: Full-shift personal sampling (12 workers) of elemental carbon (EC), nitrogen dioxide (NO2), polycyclic aromatic hydrocarbons (PAHs), and equivalent black carbon (eBC) was performed. The study used and validated eBC as an online proxy for occupational exposure to EC. Ambient air sampling of these pollutants and particle number size distribution and concentration were performed in the vicinity of the workers. Urine samples (27 workers) were collected after 8 h exposure and analyzed for PAH metabolites and effect biomarkers (8-oxodG for DNA oxidative damage, 4-HNE-MA for lipid peroxidation, 3-HPMA for acrolein). RESULTS: The personal exposures (geometric mean; GM) of the participating miners were 7 µg EC m-3 and 153 µg NO2 m-3, which are below the EU occupational exposure limits. However, exposures up to 94 µg EC m-3 and 1200 µg NO2 m-3 were observed. There was a tendency that the operators of vehicles complying with sharpened emission legislation had lower exposure of EC. eBC and NO2 correlated with EC, R = 0.94 and R = 0.66, respectively. No correlation was found between EC and the sum of 16 priority PAHs (GM 1790 ng m-3). Ratios between personal exposures and ambient concentrations were similar and close to 1 for EC and NO2, but significantly higher for PAHs. Semi-volatile PAHs may not be effectively reduced by the aftertreatment systems, and ambient area sampling did not predict the personal airborne PAHs exposure well, neither did the slightly elevated concentration of urinary PAH metabolites correlate with airborne PAH exposure. CONCLUSION: Miners' exposures to EC and NO2 were lower than those in older studies indicating the effect of sharpened emission legislation and new technologies. Using modern vehicles with diesel particulate filter (DPF) may have contributed to the lower ambient underground PM concentration and exposures. The semi-volatile behavior of the PAHs might have led to inefficient removal in the engines aftertreatment systems and delayed removal by the workplace ventilation system due to partitioning to indoor surfaces. The results indicate that secondary emissions can be an important source of gaseous PAH exposure in the mine.

Lung function and self-rated symptoms in healthy volunteers after exposure to hydrotreated vegetable oil (HVO) exhaust with and without particles.

BACKGROUND: Diesel engine exhaust causes adverse health effects. Meanwhile, the impact of renewable diesel exhaust, such as hydrotreated vegetable oil (HVO), on human health is less known. Nineteen healthy volunteers were exposed to HVO exhaust for 3 h in a chamber with a double-blind, randomized setup. Exposure scenarios comprised of HVO exhaust from two modern non-road vehicles with 1) no aftertreatment system ('HVOPM+NOx' PM1: 93 µg m-3, EC: 54 µg m-3, NO: 3.4 ppm, NO2: 0.6 ppm), 2) an aftertreatment system containing a diesel oxidation catalyst and a diesel particulate filter ('HVONOx' PM1: ~ 1 µg m-3, NO: 2.0 ppm, NO2: 0.7 ppm) and 3) filtered air (FA) as control. The exposure concentrations were in line with current EU occupational exposure limits (OELs) of NO, NO2, formaldehyde, polycyclic aromatic hydrocarbons (PAHs), and the future OEL (2023) of elemental carbon (EC). The effect on nasal patency, pulmonary function, and self-rated symptoms were assessed. Calculated predicted lung deposition of HVO exhaust particles was compared to data from an earlier diesel exhaust study. RESULTS: The average total respiratory tract deposition of PM1 during HVOPM+NOx was 27 µg h-1. The estimated deposition fraction of HVO PM1 was 40-50% higher compared to diesel exhaust PM1 from an older vehicle (earlier study), due to smaller particle sizes of the HVOPM+NOx exhaust. Compared to FA, exposure to HVOPM+NOx and HVONOx caused higher incidence of self-reported symptoms (78%, 63%, respectively, vs. 28% for FA, p < 0.03). Especially, exposure to HVOPM+NOx showed 40-50% higher eye and throat irritation symptoms. Compared to FA, a decrement in nasal patency was found for the HVONOx exposures (- 18.1, 95% CI: - 27.3 to - 8.8 L min-1, p < 0.001), and for the HVOPM+NOx (- 7.4 (- 15.6 to 0.8) L min-1, p = 0.08). Overall, no clinically significant change was indicated in the pulmonary function tests (spirometry, peak expiratory flow, forced oscillation technique). CONCLUSION: Short-term exposure to HVO exhaust concentrations corresponding to EU OELs for one workday did not cause adverse pulmonary function changes in healthy subjects. However, an increase in self-rated mild irritation symptoms, and mild decrease in nasal patency after both HVO exposures, may indicate irritative effects from exposure to HVO exhaust from modern non-road vehicles, with and without aftertreatment systems.

Biomarkers after Controlled Inhalation Exposure to Exhaust from Hydrogenated Vegetable Oil (HVO).

Hydrogenated vegetable oil (HVO) is a renewable diesel fuel used to replace petroleum diesel. The organic compounds in HVO are poorly characterized; therefore, toxicological properties could be different from petroleum diesel exhaust. The aim of this study was to evaluate the exposure and effective biomarkers in 18 individuals after short-term (3 h) exposure to HVO exhaust and petroleum diesel exhaust fumes. Liquid chromatography tandem mass spectrometry was used to analyze urinary biomarkers. A proximity extension assay was used for the measurement of inflammatory proteins in plasma samples. Short-term (3 h) exposure to HVO exhaust (PM1 ~1 µg/m3 and ~90 µg/m3 for vehicles with and without exhaust aftertreatment systems, respectively) did not increase any exposure biomarker, whereas petroleum diesel exhaust (PM1 ~300 µg/m3) increased urinary 4-MHA, a biomarker for p-xylene. HVO exhaust from the vehicle without exhaust aftertreatment system increased urinary 4-HNE-MA, a biomarker for lipid peroxidation, from 64 ng/mL urine (before exposure) to 141 ng/mL (24 h after exposure, p < 0.001). There was no differential expression of plasma inflammatory proteins between the HVO exhaust and control exposure group. In conclusion, short-term exposure to low concentrations of HVO exhaust did not increase urinary exposure biomarkers, but caused a slight increase in lipid peroxidation associated with the particle fraction.

Evaluation of 92 cardiovascular proteins in dried blood spots collected under field-conditions: Off-the-shelf affinity-based multiplexed assays work well, allowing for simplified sample collection.

Workplace-collected blood spots deposited on filter paper were analysed with multiplexed affinity-based protein assays and found to be suitable for proteomics analysis. The protein extension assay (PEA) was used to characterize 92 proteins using 1.2 mm punches in repeated samples collected from 20 workers. Overall, 97.8% of the samples and 91.3% of the analysed proteins passed quality control. Both within and between spot correlations using six replicates from the same individual were above 0.99, suggesting that comparable levels are obtained from multiple punches from the same spot and from consecutive spots. Protein levels from dried blood and wet serum from the same individuals were compared and the majority of the analysed proteins were found to be significantly correlated. These results open up for simplified sample collection of blood in field conditions for proteomic analysis, but also highlight that not all proteins can be robustly measured from dried whole blood.

Filaggrin Polymorphisms and the Uptake of Chemicals through the Skin-A Human Experimental Study.

BACKGROUND: The filaggrin protein is important for skin barrier structure and function. Loss-of-function (null) mutations in the filaggrin gene FLG may increase dermal absorption of chemicals. OBJECTIVE: The objective of the study was to clarify if dermal absorption of chemicals differs depending on FLG genotype. METHOD: We performed a quantitative real-time polymerase chain reaction (qPCR)-based genetic screen for loss-of-function mutations (FLG null) in 432 volunteers from the general population in southern Sweden and identified 28 FLG null carriers. In a dermal exposure experiment, we exposed 23 FLG null and 31 wild-type (wt) carriers to three organic compounds common in the environment: the polycyclic aromatic hydrocarbon pyrene, the pesticide pyrimethanil, and the ultraviolet-light absorber oxybenzone. We then used liquid-chromatography mass-spectrometry to measure the concentrations of these chemicals or their metabolites in the subjects' urine over 48 h following exposure. Furthermore, we used long-range PCR to measure FLG repeat copy number variants (CNV), and we performed population toxicokinetic analysis. RESULTS: Lag times for the uptake and dermal absorption rate of the chemicals differed significantly between FLG null and wt carriers with low (20-22 repeats) and high FLG CNV (23-24 repeats). We found a dose-dependent effect on chemical absorption with increasing lag times by increasing CNV for both pyrimethanil and pyrene, and decreasing area under the urinary excretion rate curve (AUC(0-40h)) with increasing CNV for pyrimethanil. FLG null carriers excreted 18% and 110% more metabolite (estimated by AUC(0-40h)) for pyrimethanil than wt carriers with low and high CNV, respectively. CONCLUSION: We conclude that FLG genotype influences the dermal absorption of some common chemicals. Overall, FLG null carriers were the most susceptible, with the shortest lag time and highest rate constants for skin absorption, and higher fractions of the applied dose excreted. Furthermore, our results indicate that low FLG CNV resulted in increased dermal absorption of chemicals. https://doi.org/10.1289/EHP7310.

Effect of welding fumes on the cardiovascular system: a six-year longitudinal study.

Objective This study investigated whether low-to-moderate exposure to welding fumes is associated with adverse effects on the cardiovascular system. Methods To test this, we performed a longitudinal analysis of 78 mild steel welders and 96 controls; these subjects were examined twice, six years apart (ie, timepoints 1 and 2). All subjects (male and non-smoking at recruitment) completed questionnaires describing their health, work history, and lifestyle. We measured their blood pressure, endothelial function (by EndoPAT), and risk markers for cardiovascular disease [low-density lioprotein (LDL), homocysteine, C-reactive protein]. Exposure to welding fumes was assessed from the responses to questionnaires and measurements of respirable dust in their breathing zones adjusted for use of respiratory protection equipment. Linear mixed-effect regression models were used for the longitudinal analysis. Results Median respirable dust concentrations, adjusted for respirable protection, of the welders were 0.7 (5-95 percentile range 0.2-4.2) and 0.5 (0.1-1.9) mg/m 3at timepoints 1 and 2, respectively. Over the six-year period, welders showed a statistically significant increase in systolic [5.11 mm Hg, 95% confidence interval (CI) 1.92-8.31] and diastolic (3.12 mm Hg, 95% CI 0.74-5.5) blood pressure compared with controls (multi-variable adjusted mixed effect models). Diastolic blood pressure increased non-significantly by 0.22 mm Hg (95% CI -0.02-0.45) with every additional year of welding work. No consistent significant associations were found between exposure and endothelial function, LDL, homocysteine, or C-reactive protein. Conclusion Exposure to welding fumes at low-to-moderate levels is associated with increased blood pressure, suggesting that reducing the occupational exposure limit (2.5 mg/m 3for inorganic respirable dust in Sweden) is needed to protect cardiovascular health of workers.

Exposure to Mild Steel Welding and Changes in Serum Proteins With Putative Neurological Function-A Longitudinal Study.

Welders are exposed to high levels of metal particles, consisting mainly of iron and manganese (Mn) oxide. Metal particles, especially those containing Mn can be neurotoxic. In this exploratory study, we evaluated associations between welding and expression of 87 putative neurology-related proteins in serum in a longitudinal approach. The study cohort from southern Sweden included welders working with mild steel (n = 56) and controls (n = 67), all male and non-smoking, which were sampled at two timepoints (T1, T2) 6-year apart. Observed associations in the longitudinal analysis (linear mixed models) were further evaluated (linear regression models) in another cross-sectional sample which included welders (n = 102) and controls (n = 89) who were sampled only once (T1 or T2). The median respirable dust levels for welders after adjusting for respiratory protection was at T1 0.6 (5-95 percentile: 0.2-4.2) and at T2 0.5 (0.1-1.8) mg/m3. The adjusted median respirable Mn concentration was at T2 0.049 mg/m3 (0.003-0.314) with a Spearman correlation between adjusted respirable dust and respirable Mn of rS = 0.88. We identified five neurology-related proteins that were differentially expressed in welders vs. controls in the longitudinal sample, of which one (nicotinamide/nicotinic acid mononucleotide adenylyltransferase 1; NMNAT1) was also differentially expressed in the cross-sectional sample. NMNAT1, an axon-protective protein linked to Alzheimers disease, was upregulated in welders compared with controls but no associations were discerned with degree of exposure (welders only: years welding, respirable dust, cumulative exposure). However, we identified five additional proteins that were associated with years welding (GCSF, EFNA4, CTSS, CLM6, VWC2; welders only) both in the longitudinal and in the cross-sectional samples. We also observed several neurology-related proteins that were associated with age and BMI. Our study indicates that low-to-moderate exposure to welding fumes is associated with changes in circulating levels of neurology-related proteins.

Mild steel welding is associated with alterations in circulating levels of cancer-related proteins.

Welding fumes were recently classified as carcinogenic to humans and worldwide millions work as welders or perform welding operations. The purpose of this study was to identify new biomarkers of welding-induced carcinogenesis. We evaluated a panel of 91 putative cancer-related proteins in serum in a cohort of welders working with mild steel (n = 77) and controls (n = 94) from southern Sweden sampled on two occasions 6-year apart using a longitudinal analysis (linear mixed models). The significant results from the longitudinal analysis were tested for reproducibility in welders (n = 88) and controls (n = 69) sampled once during the same sampling period as timepoint 1 or timepoint 2 (linear regression models), i.e., in a cross-sectional setting. The models were adjusted for age, body-mass index, and use of snus. All study participants were non-smokers at recruitment. Exposure to welding fumes was assessed using questionnaires and respirable dust measurement in the breathing zone that was adjusted for personal respiratory protection equipment. The median respirable dust in welders was 0.7 (0.2-4.2) and 0.5 (0.1-1.9) mg/m3 at the first and second timepoints, respectively. We identified 14 cancer-related proteins that were differentially expressed in welders versus controls in the longitudinal analysis, out of which three were also differentially expressed in the cross-sectional analysis (cross-sectional group). Namely, syndecan 1 (SDC1), folate receptor 1 (FOLR1), and secreted protein acidic and cysteine rich (SPARC) were downregulated, in welders compared with controls. In addition, FOLR1 was negatively associated with years welding. Disease and function analysis indicated that the top proteins are related to lung cancer as well as cell invasion and migration. Our study indicates that moderate exposure to welding fumes is associated with changes in circulating levels of putative cancer-related proteins, out of which FOLR1 showed a clear dose-response relationship. It is, however, unclear to which extent these changes are adaptive or potential early biomarkers of cancer.

Acute respiratory effects and biomarkers of inflammation due to welding-derived nanoparticle aggregates.

PURPOSE: Welders are exposed to airborne particles from the welding environment and often develop symptoms work-related from the airways. A large fraction of the particles from welding are in the nano-size range. In this study we investigate if the welders' airways are affected by exposure to particles derived from gas metal arc welding in mild steel in levels corresponding to a normal welding day. METHOD: In an exposure chamber, 11 welders with and 10 welders without work-related symptoms from the lower airways and 11 non-welders without symptoms, were exposed to welding fumes (1 mg/m3) and to filtered air, respectively, in a double-blind manner. Symptoms from eyes and upper and lower airways and lung function were registered. Blood and nasal lavage (NL) were sampled before, immediately after and the morning after exposure for analysis of markers of oxidative stress. Exhaled breath condensate (EBC) for analysis of leukotriene B4 (LT-B4) was sampled before, during and immediately after exposure. RESULTS: No adverse effects of welding exposure were found regarding symptoms and lung function. However, EBC LT-B4 decreased significantly in all participants after welding exposure compared to filtered air. NL IL-6 increased immediately after exposure in the two non-symptomatic groups and blood neutrophils tended to increase in the symptomatic welder group. The morning after, neutrophils and serum IL-8 had decreased in all three groups after welding exposure. Remarkably, the symptomatic welder group had a tenfold higher level of EBC LT-B4 compared to the two groups without symptoms. CONCLUSION: Despite no clinical adverse effects at welding, changes in inflammatory markers may indicate subclinical effects even at exposure below the present Swedish threshold limit (8 h TWA respirable dust).