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1.
  • Alhamdow, Ayman, et al. (author)
  • DNA-methylation of the cancer-related genes F2RL3 and AHRR is associated with occupational exposure to polycyclic aromatic hydrocarbons
  • 2018
  • In: Carcinogenesis. - : Oxford University Press. - 0143-3334 .- 1460-2180. ; 39:7, s. 869-878
  • Journal article (peer-reviewed)abstract
    • Some polycyclic aromatic hydrocarbons (PAH) are known carcinogens and workplace PAH exposure may increase the risk of cancer. Monitoring early cancer-related changes can indicate whether the exposure is carcinogenic. Here, we enrolled 151 chimney sweeps, 152 controls, and 19 creosote-exposed male workers from Sweden. We measured urinary PAH metabolites using LC/MS/MS, the cancer-related markers telomere length (TL) and mitochondrial DNA copy number (mtDNAcn) using qPCR, and DNA methylation of lung cancer-related genes F2RL3 and AHRR using pyrosequencing. The median 1-hydroxypyrene (PAH metabolite) concentrations were highest in creosote-exposed workers (8.0 μg/g creatinine) followed by chimney sweeps (0.34 μg/g creatinine) and controls (0.05 μg/g creatinine). TL and mtDNAcn did not differ between study groups. Chimney sweeps and creosote-exposed workers had significantly lower methylation of AHRR CpG site cg05575921 (88.1% and 84.9%, respectively) than controls (90%). Creosote-exposed workers (73.3%), but not chimney sweeps (76.6%) had lower methylation of F2RL3 cg03636183 than controls (76.7%). Linear regression analyses showed that chimney sweeps had lower AHRR cg05575921 methylation (B=-2.04; P<0.057, adjusted for smoking and age) and lower average AHRR methylation (B=-2.05; P<0.035), and non-smoking chimney sweeps had lower average F2RL3 methylation (B=-0.81; P<0.042, adjusted for age) compared with controls. These cancer-related markers were not associated with urinary concentrations of PAH metabolites. In conclusion, although we found no associations with PAH metabolites in urine (short-term exposure), our results suggest dose-response relationship between PAH exposure and DNA hypomethylation of lung cancer-related loci. These findings indicate that further protective measures should be taken to reduce PAH exposure.
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2.
  • Landberg, Hanna, et al. (author)
  • Comparison and Evaluation of Multiple Users' Usage of the Exposure and Risk Tool : Stoffenmanager 5.1
  • 2015
  • In: Annals of Occupational Hygiene. - : Oxford University Press (OUP). - 0003-4878 .- 1475-3162. ; 59:7, s. 821-835
  • Journal article (peer-reviewed)abstract
    • Stoffenmanager is an exposure and risk assessment tool that has a control banding part, with risk bands as outcome and a quantitative exposure assessment part, with the 90th percentile of the predicted exposure as a default outcome. The main aim of the study was to investigate whether multiple users of Stoffenmanager came to the same result when modelling the same scenarios. Other aims were to investigate the differences between outcomes of the control banding part with the measured risk quota and to evaluate the conservatism of the tool by testing whether the 90th percentiles are above the measured median exposures. We investigated airborne exposures at companies in four different types of industry: wood, printing, metal foundry, and spray painting. Three scenarios were modelled and measured, when possible, at each company. When modelled, 13 users visited each company on the same occasion creating individual assessments. Consensus assessments were also modelled for each scenario by six occupational hygienists. The multiple users' outcomes were often spread over two risk bands in the control banding part, and the differences in the quantitative exposure outcomes for the highest and lowest assessments per scenario varied between a factor 2 and 100. Four parameters were difficult for the users to assess and had a large impact on the outcome: type of task, breathing zone, personal protection, and control measures. Only two scenarios had a higher measured risk quota than predicted by the control banding part, also two scenarios had slightly higher measured median exposure value than modelled consensus in the quantitative exposure assessment part. Hence, the variability between users was large but the model performed well.
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3.
  • Landberg, Hanna E, et al. (author)
  • A Study of the Validity of Two Exposure Assessment Tools : Stoffenmanager and the Advanced REACH Tool
  • 2017
  • In: Annals of Work Exposures and Health. - : Oxford University Press. - 2398-7308 .- 2398-7316. ; 61:5, s. 575-588
  • Journal article (peer-reviewed)abstract
    • The use of exposure modelling tools for estimating chemical airborne exposure has increased since the European Union's REACH legislation for safe use of industrial chemicals came into force. Two tools that European Chemicals Agency recommends are Stoffenmanager® and the Advanced REACH Tool (ART). The aim of this study was to investigate the validity of these two exposure modelling tools by comparing the lack of agreement between estimated and measured exposure. We examined the airborne chemical exposure at companies in seven different types of industries: wood, printing, foundry, spray painting, flour milling, chemical industry, and plastic moulding industry. The inhalable exposure of liquids or powders at two to three situations at each company was modelled with both tools and measured. To study the validity of the tools, the mean differences and precisions (lack of agreement) of exposures from both situations handling liquids and powders were calculated by using the 50th percentile outcome of the tools and the geometric mean of the measured exposure (all data were ln transformed). For Stoffenmanager, the mean difference and precision of the situations concerning liquids were 0.22 ± 1.0 and for powders -0.024 ± 0.66. It was also shown that Stoffenmanager overestimated low exposures and underestimated high exposures. Stoffenmanager showed higher agreement with the measured exposure in the wood and flour mill industries than in foundry and the plastic moulding industry. For ART, the mean difference and precision of liquids were -0.55 ± 0.88 and for powders -1.4 ± 1.6. ART showed lower agreement with the measured exposure in the wood industry.
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4.
  • Landberg, Hanna E., et al. (author)
  • Evaluation of risk assessment approaches of occupational chemical exposures based on models in comparison with measurements
  • 2018
  • In: Safety Science. - : Elsevier. - 0925-7535 .- 1879-1042. ; 109, s. 412-420
  • Journal article (peer-reviewed)abstract
    • Risk assessments of chemicals in work places are needed to protect workers' health and safety. Several different strategies can be used for conducting risk assessments. The aim of this study was to investigate approaches to risk assessment of chemicals based on exposure assessment models relative to occupational exposure limits values (OELs) and derived no-effect levels (DNELs) and in comparison with measurements relative to OELs. A second aim was to evaluate the modelled recommended outcome and compare it with measurements of exposure. In this study, 29 situations were assessed with ECETOC TRA, Stoffenmanager (R) 5.1 and ART. Personal exposure measurements were also performed. The percentage of measured exposure exceeding the recommended output was calculated to investigate the level of conservatism. All the modelled exposures were compared with OELs and DNELs where possible, and the GM of the measured exposure was compared with OELs (risk quotas). For ECETOC TRA, 31% of measured exposure exceeded modelled exposure. For Stoffenmanager (R) it was 17% and for ART and ART B it was 3% and 0% respectively. Hence, according to our data, ECETOC TRA is the least conservative. An investigation of the risk quotas showed that ECETOC TRA had 4 false safe situations, meaning the risk was low when the model was used but was high when measurements were used. This may lead to underestimating risks. All models had an elevated proportion, ECETOC TRA and ART the highest, of false unsafe situations meaning the risk was low when measurements were used but high when models were used.
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5.
  • Landberg, Hanna, et al. (author)
  • Evaluating the Risk Assessment Approach of the REACH Legislation : A Case Study
  • 2019
  • In: Annals of Work Exposures and Health. - : Oxford University Press. - 2398-7308 .- 2398-7316. ; 63:1, s. 68-76
  • Journal article (peer-reviewed)abstract
    • Risk assessments based on occupational exposure to chemicals have increased since REACH (European regulation on Registration, Evaluation, Authorization, and restriction of Chemicals) came into force. The European Chemicals Agency (ECHA) recommends that chemical exposure could be calculated using exposure models and that parameters used to calculate the exposure scenario (ES) should be communicated in extended safety data sheets (e-SDS) as workplace instructions which downstream users are obligated to follow. We aimed to evaluate REACH's risk assessment approach using the Stoffenmanager((R)) 6.1, the Advanced REACH Tool 1.5 (ART), and the European Centre for Ecotoxicology and Toxicology of Chemicals' targeted risk assessment (ECETOC TRA 3.1) exposure models. We observed 239 scenarios in three companies handling chemicals using 45 e-SDS. Risk characterization ratios (RCRs) were calculated by dividing estimated exposures by derived no-effect levels (DNELs). Observed RCRs were much lower than registered RCRs, indicating lower exposures. However, about 12% of the observed ES still had RCRs > 1, after adjustment for control measures and personal protections described in the ES, when using Stoffenmanager((R)). The ES with observed RCRs > 1 were the same by Stoffenmanager((R)) and ART, but not by ECETOC TRA. Stoffenmanager and ART identified 25 adjusted scenarios with RCR > 1, while ECETOC TRA gave RCR < 1 for the same scenarios. The ES with RCR > 1 were significantly associated to chemicals with higher vapour pressure and lower DNELs than ES with RCR < 1 by Stoffenmanager((R)). The correlations between observed and registered RCRs were lower than those between RCRs calculated from the different models themselves; ECETOC TRA had the lowest correlation with the registered ES. These results put in question the generic ES recommended under the REACH legislation. Downstream users may get better estimates by assessing their own ES, especially for chemicals with low DNELs and high vapour pressure.
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6.
  • Alhamdow, Ayman, et al. (author)
  • Cancer-related proteins in serum are altered in workers occupationally exposed to polycyclic aromatic hydrocarbons : a cross-sectional study
  • 2019
  • In: Carcinogenesis. - : Oxford University Press (OUP). - 0143-3334 .- 1460-2180. ; 40:6, s. 771-781
  • Journal article (peer-reviewed)abstract
    • Exposure to some polycyclic aromatic hydrocarbons (PAH) increases the risk of cancer and is common, particularly for workers in occupations such as chimney sweeping. In exposed workers, screening of early cancer-related markers provides important information to identify individuals at risk. Here, we aimed to elucidate the associations between PAH exposure and serum levels of cancer-related proteins in 118 chimney sweeps and 126 occupationally unexposed controls, all non-smoking males from Sweden. Monoydroxylated metabolites of pyrene, phenanthrene, benzo[a]pyrene, and benzo[a]anthracene were measured in urine using LC/MS/MS and 90 cancer-related proteins were measured in serum using a Proximity Extension Assay. Linear regression analysis adjusted for age, BMI, and false discovery rate (FDR) identified 17 serum proteins that were differentially expressed (16 upregulated and 1 downregulated) in chimney sweeps compared with controls (FDR<0.05). Concentrations of the peptidase kallikrein 13 (KLK13) showed significant positive associations with urinary concentrations of the PAH metabolites 3-hydroxybenzo[a]pyrene (B, 95%CI: 0.042, 0.008-0.076) and 3-hydroxybenzo[a]anthracene (B, 95%CI: 0.068, 0.002-0.134). Moreover, dose-response relationships were observed between KLK13 and 3-hydroxybenzo[a]pyrene (trend test P=0.027) and 3-hydroxybenzo[a]anthracene (P=0.035). Pathway and gene ontology analyses showed that cell movement, cell adhesion, and cell migration were the predominant molecular functions associated with the top differentially expressed proteins. In conclusion, we found a number of putative cancer-related proteins differentially expressed in workers exposed to PAH. This warrants effective measure to reduce PAH exposure among workers as well as further investigation to confirm these findings.
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7.
  • Alhamdow, Ayman, et al. (author)
  • Cardiovascular Disease-Related Serum Proteins in Workers Occupationally Exposed to Polycyclic Aromatic Hydrocarbons
  • 2019
  • In: Toxicological Sciences. - : Oxford University Press (OUP). - 1096-6080 .- 1096-0929. ; 171:1, s. 235-246
  • Journal article (peer-reviewed)abstract
    • Chimney sweeps have higher incidence and mortality of cardiovascular disease (CVD), likely related to their exposure to polycyclic aromatic hydrocarbons (PAH). In order to identify underlying mechanisms of PAH-related CVD, we here investigated whether PAH exposure was associated with levels of putative CVD-related proteins in serum among currently working chimney sweeps. We enrolled 116 chimney sweeps and 125 unexposed controls, all nonsmoking male workers from Sweden. We measured monohydroxylated PAH metabolites in urine by liquid chromatography coupled to tandem mass spectrometry and a panel of 85 proteins in serum using proximity extension assay. Linear regression analysis adjusted for age and body mass index showed that 25 proteins were differentially expressed between chimney sweeps and the controls (p <. 05, adjusted for false discovery rate). Of the 25 proteins, follistatin (FS), prointerleukin-16 (IL-16), and heat shock protein beta-1 (HSP 27) showed positive associations with the monohydroxylated metabolites of PAH in a dose-response manner (p <. 05). Pathway and gene ontology analyses demonstrated that the differentially expressed proteins were mainly involved in inflammatory response and immunological functions, such as leukocyte migration, cell movement of leukocytes, and adhesion of immune cells. In conclusion, we found a number of putative CVD-related proteins differentially expressed, between PAH-exposed and unexposed individuals, and mainly involved in inflammation and immune function. Our data warrant protective measures to reduce PAH exposure and longitudinal investigations of the protein profile in chimney sweeps and other occupational groups exposed to PAH.
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8.
  • Alhamdow, Ayman, et al. (author)
  • Chimney sweeps in Sweden : a questionnaire-based assessment of long-term changes in work conditions, and current eye and airway symptoms
  • 2017
  • In: International Archives of Occupational and Environmental Health. - : Springer Science and Business Media LLC. - 0340-0131 .- 1432-1246. ; 90:2, s. 207-216
  • Journal article (peer-reviewed)abstract
    • Objectives: To explore chimney sweeping work tasks, chimney sweeps’ use of protective equipment, and type of fuel used by clients, over time. Further, to assess work-relatedness of current eye and airway symptoms. Methods: In a cross-sectional study in 2011, male Swedish chimney sweeps (n = 483; age 21–69 years) answered a questionnaire about their occupational history and eye and airway symptoms. Results: Between 1960 and 2010, black-soot-sweeping in private homes was the major task, although it decreased during the time period, for chimney sweeps. Between 1975 and 2010, the use of petroleum oil decreased, whereas the use of pellets and wood increased. Also, the use of gloves and masks increased significantly. Black-soot-sweeping in industry was associated with work-related eye symptoms (prevalence odds ratio POR = 3.76, 95% CI: 1.72–8.24, for every 10% increment of working time, adjusted for age and tobacco smoking). Chimney sweeps also had slightly higher prevalence of cough with increasing black-soot-sweeping (POR = 1.06, 95% CI: 0.99–1.13 for every 10% increment, further adjusted for the use of mask), and the association was more pronounced, although nonsignificant, for black-soot-sweeping in industry (adjusted POR = 1.26, 95% CI: 0.98–1.61). Conclusions: Chimney sweeping tasks and use of protective equipment as well as type of fuel used by the clients changed significantly over the last 35 years, which may have changed chimney sweeps’ exposure to soot. Still, chimney sweeps in Sweden have black-soot-sweeping-related eye and airway symptoms.
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9.
  • Alhamdow, Ayman, et al. (author)
  • Early markers of cardiovascular disease are associated with occupational exposure to polycyclic aromatic hydrocarbons
  • 2017
  • In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7:1
  • Journal article (peer-reviewed)abstract
    • Occupational exposure to soot, rich in polycyclic aromatic hydrocarbons (PAH), has been associated with increased risk of cardiovascular disease (CVD). However, our knowledge about PAH exposure and early markers of CVD remains limited. In this cross-sectional study of 151 chimney sweeps and 152 controls, we investigated occupational exposure to PAH and early markers of CVD. Blood pressure (BP) (chimney sweeps only), urinary PAH metabolites and serum biomarkers were measured (C-reactive protein, homocysteine, gamma-glutamyltransferase, cholesterol, HDL, LDL, and triglycerides). Chimney sweeps had up to 7 times higher concentrations of PAH metabolites in urine than controls (P < 0.001): Median concentrations (adjusted for specific gravity) for 1-hydroxypyrene, 2-hydroxyphenanthrene, 3-hydroxybenzo[a]pyrene, and 3-hydroxybenzo[a]anthracene were 0.56 μg/L, 0.78 μg/L, 4.75 ng/L, and 6.28 ng/L, respectively. Compared with controls, chimney sweeps had increased homocysteine, cholesterol, and HDL (β = 3.4 μmol/L, 0.43 mmol/L, and 0.13 mmol/L, respectively, P ≤ 0.003, adjusted for age, BMI, and smoking). In chimney sweeps, PAH metabolites correlated positively with the percentage of soot sweeping (P < 0.001). 2-hydroxyphenanthrene, 3-hydroxybenzo[a]pyrene, and 3-hydroxybenzo[a]anthracene were positively associated with diastolic BP (P < 0.044, adjusted for age, BMI, and smoking). PAH exposure among chimney sweeps resulted in elevated levels of markers for CVD risk. These findings stress the need to reduce occupational exposure to PAH.
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10.
  • Broström, Julia M., et al. (author)
  • Toluene diisocyanate exposure and autotaxin–lysophosphatidic acid signalling
  • 2018
  • In: Toxicology and Applied Pharmacology. - : Elsevier BV. - 0041-008X .- 1096-0333. ; 355, s. 43-51
  • Journal article (peer-reviewed)abstract
    • Toluene diisocyanate (TDI) is a reactive chemical used in manufacturing plastics. TDI exposure adversely affects workers' health, causing occupational asthma, but individuals differ in susceptibility. We recently suggested a role for signalling mediated by the enzyme autotaxin (ATX) and its product, lysophosphatidic acid (LPA), in TDI toxicity. Here we genotyped 118 TDI-exposed workers for six single-nucleotide polymorphisms (SNPs) in genes encoding proteins implicated in ATX–LPA signalling: purinergic receptor P2X7 (P2RX7), C–C motif chemokine ligand 2 (CCL2), interleukin 1β (IL1B), and caveolin 1 (CAV1). Two P2RX7 SNPs (rs208294 and rs2230911) significantly modified the associations between a biomarker of TDI exposure (urinary 2,4-toluene diamine) and plasma LPA; two IL1B SNPs (rs16944 and rs1143634) did not. CAV1 rs3807989 modified the associations, but the effect was not statistically significant (p = 0.05–0.09). In vitro, TDI-exposed bronchial epithelial cells (16HBE14o-) rapidly released ATX and IL-1β. P2X7 inhibitors attenuated both responses, but confocal microscopy showed non-overlapping localizations of ATX and IL-1β, and down-regulation of CAV1 inhibited the ATX response but not the IL-1β response. This study indicates that P2X7 is pivotal for TDI-induced ATX–LPA signalling, which was modified by genetic variation in P2RX7. Furthermore, our data suggest that the TDI-induced ATX and IL-1β responses occur independently.
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11.
  • Broström, Julia, et al. (author)
  • Toluene diisocyanate: Induction of the autotaxin-lysophosphatidic acid axis and its association with airways symptoms.
  • 2015
  • In: Toxicology and Applied Pharmacology. - : Elsevier BV. - 1096-0333 .- 0041-008X. ; 287:3, s. 222-231
  • Journal article (peer-reviewed)abstract
    • Diisocyanates are industrial chemicals which have a wide range of applications in developed and developing countries. They are notorious lung toxicants and respiratory sensitizers. However, the mechanisms behind their adverse effects are not adequately characterized. Autotaxin (ATX) is an enzyme producing lysophosphatidic acid (LPA), and the ATX-LPA axis has been implicated in lung related inflammatory conditions and diseases, including allergic asthma, but not to toxicity of environmental low-molecular-weight chemicals. We investigated effects of toluene diisocyanate (TDI) on ATX induction in human lung epithelial cell models, and we correlated LPA-levels in plasma to biomarkers of TDI exposure in urine collected from workers exposed to <5ppb (parts per billion). Information on workers' symptoms was collected through interviews. One nanomolar TDI robustly induced ATX release within 10min in vitro. A P2X7- and P2X4-dependent microvesicle formation was implicated in a rapid ATX release and a subsequent protein synthesis. Co-localization between purinergic receptors and ATX was documented by immunofluorescence and confocal microscopy. The release was modulated by monocyte chemoattractant protein-1 (MCP-1) and by extracellular ATP. In workers, we found a dose-response relationship between TDI exposure biomarkers in urine and LPA levels in plasma. Among symptomatic workers reporting "sneezing", the LPA levels were higher than among non-symptomatic workers. This is the first report indicating induction of the ATX-LPA axis by an environmental low-molecular-weight chemical, and our data suggest a role for the ATX-LPA axis in TDI toxicity.
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12.
  • Hamada, Haneen, et al. (author)
  • Assessment of dermal uptake of diphenylmethane-4,4'-diisocyanate using tape stripping and biological monitoring
  • 2018
  • In: EJD. European journal of dermatology. - : John Libbey Publishing. - 1167-1122 .- 1952-4013. ; 28:2, s. 143-148
  • Journal article (peer-reviewed)abstract
    • Very little is known about the dermal uptake of isocyanates, and dermal exposure to isocyanates has been discussed as a factor involved in the induction of respiratory diseases. To investigate the dermal uptake of diphenylmethane-4,4'-diisocyanate (4,4'-MDI). Four volunteers were dermally exposed to 10, 25, 49 and 50 mg 4,4'-MDI, respectively, for eight hours. The exposed areas were tape stripped. Urine and blood were biologically monitored for 48 hours. Tape strips, plasma, and urine were analysed by liquid chromatography-mass spectrometry. In total, 35-70% of the applied dose of 4,4'-MDI was absorbed by the skin. Very low fractions of applied dose were found in the tape strips. The 4,4'-MDA concentration in plasma and urine was low, but peaked in urine at 10-14 hours and plasma at 8-32 hours after exposure. 4,4'-MDI is readily absorbed by human skin. Only small fractions of 4,4'-MDI remain as such in the superficial skin layers. The amounts found in blood and urine were only small fractions of the total applied doses which indicates that very small amounts of 4,4'-MDI penetrate the skin and reach the blood stream. The dermal uptake and distribution of 4,4'-MDI is much slower compared to that associated with airway uptake. Our data strongly indicate that formation of 4,4'-MDA from 4,4'-MDI upon reacting with water in the skin can only occur to a very limited extent.
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14.
  • Hedmer, Maria, et al. (author)
  • Diesel Exhaust Exposure Assessment Among Tunnel Construction Workers—Correlations Between Nitrogen Dioxide, Respirable Elemental Carbon, and Particle Number
  • 2017
  • In: Annals of Work Exposures and Health. - : Oxford University Press (OUP). - 2398-7308 .- 2398-7316. ; 61:5, s. 539-553
  • Journal article (peer-reviewed)abstract
    • Objectives: Occupational exposure to diesel exhaust is common due the widespread use of dieselpowered combustion engines. Diesel exhaust is chemically complex and consists of thousands of compounds present as gases and particulate matter. Both nitrogen dioxide (NO2) and elemental carbon(EC) have been used as markers for diesel exhaust exposure. Currently EC is regarded as the best surrogate of diesel exhaust. The objective was to quantify the occupational exposure to diesel exhaust in underground tunnel construction work using a multi-metric approach, and to investigate the correlations between NO2, respirable EC, respirable organic carbon (OC), respirable total carbon(TC), respirable dust (RD), and particle number. Also, the use of NO2 as a proxy for diesel exhaust was evaluated, how much of the variability in the diesel exhaust exposure was attributed to within and between individual factors and if there was a difference between expert and self-administered measurements of NO2. Methods: The personal exposure to diesel exhaust was assessed by expert supervised measurements of NO2, EC, OC, TC, RD and particle number in the breathing zones of underground tunnel workers. Stationary sampling of NO2, EC, OC, TC, RD, size-fractioned mass concentration, and particle number were conducted. The personal and stationary measurements were conducted on threeoccasions simultaneously. The workers measured their exposure by repeated self-administered measurements of NO2. The self-administered measurements were performed twice for each worker with at least one month lag between the samplings. Results: In the simultaneous sampling of diesel exhaust, the geometric mean (GM) concentration of NO2 and respirable EC were 72 μg m−3 (10th–90th percentile 34–140 μg m−3) and 2.6 μg m−3 (10th–90th percentile 1.6–7.3 μg m−3), respectively. The GM for OC and TC was 28 μg m−3 (10th–90th percentile 20–42 μg m−3) and 31 μg m−3 (10th–90th percentile 20–50 μg m−3), respectively. The GM for RD and particle number was 180 μg m−3 (10th–90th percentile 20–530 μg m−3) and 47 900 cm−3 (10th–90th percentile (27 500–94 100 cm−3), respectively. A significant correlation was found between NO2 and respirable EC [Spearman’s correlation r = 0.53 (P = 0.05)]. The within-worker variability of NO2 was 45.5% and the between-worker variability was 54.5%. The self-administered measured concentrations of NO2 (GM 70 μg m−3) did not statistically differ from the NO2 concentrations measured by an expert (P > 0.35).Conclusion: The diesel exhaust exposure in tunnel construction work was low. A significant correlation between NO2 and EC was observed. This indicates that NO2 could be used as a proxy for diesel exhaust in tunnel work if diesel exhaust is the only source of NO2 and if the ratio between EC and NO2 is known and constant. Passive sampling of NO2 is much easier and cheaper to perform compared with active sampling of EC. It is possible to utilize self-administered NO2 measurements in extreme and inaccessible work environments. This study adds support to continued use of NO2 as an exposure marker in combination with EC for diesel exhaust exposure. In tunnel construction work, the variability in the diesel exhaust exposure was high both between- and within-workers.
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16.
  • Hossain, Bakhtiar, et al. (author)
  • Exposure to welding fumes is associated with hypomethylation of the F2RL3 gene: a cardiovascular disease marker.
  • 2015
  • In: Occupational and Environmental Medicine. - : BMJ. - 1470-7926 .- 1351-0711. ; 72:12, s. 845-851
  • Journal article (peer-reviewed)abstract
    • Welders are at risk for cardiovascular disease. Recent studies linked tobacco smoke exposure to hypomethylation of the F2RL3 (coagulation factor II (thrombin) receptor-like 3) gene, a marker for cardiovascular disease prognosis and mortality. However, whether welding fumes cause hypomethylation of F2RL3 remains unknown.
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17.
  • Jönsson, Lena S, et al. (author)
  • The ordinary work environment increases symptoms from eyes and airways in mild steel welders.
  • 2015
  • In: International Archives of Occupational and Environmental Health. - : Springer Science and Business Media LLC. - 1432-1246 .- 0340-0131. ; 88:8, s. 1131-1140
  • Journal article (peer-reviewed)abstract
    • We aimed to follow diary-registered symptoms from eyes and airways in mild steel welders and relate them to different exposure measures. Furthermore, we would clarify the influence of possible effect modifiers.
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18.
  • Li, Huiqi, et al. (author)
  • A Cross-Sectional Study of the Cardiovascular Effects of Welding Fumes.
  • 2015
  • In: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 10:7
  • Journal article (peer-reviewed)abstract
    • OBJECTIVES: Occupational exposure to particulate air pollution has been associated with an increased risk of cardiovascular disease. However, the risk to welders working today remains unclear. We aimed to elucidate the cardiovascular effects of exposure to welding fumes. METHODS: In a cross-sectional study, structured interviews and biological sampling were conducted for 101 welders and 127 controls (all non-smoking males) from southern Sweden. Personal breathing zone sampling of respirable dust was performed. Blood pressure (BP) and endothelial function (using peripheral arterial tonometry) were measured. Plasma and serum samples were collected from peripheral blood for measurement of C-reactive protein, low-density lipoprotein, homocysteine, serum amyloid A, and cytokines. RESULTS: Welders were exposed to 10-fold higher levels of particles than controls. Welders had significantly higher BP compared to controls, an average of 5 mm Hg higher systolic and diastolic BP (P≤0.001). IL-8 was 3.4 ng/L higher in welders (P=0.010). Years working as a welder were significantly associated with increased BP (β=0.35, 95%CI 0.13 - 0.58, P=0.0024 for systolic BP; β=0.32, 95%CI 0.16 - 0.48, P<0.001 for diastolic BP, adjusted for BMI) but exposure to respirable dust was not associated with BP. No clear associations occurred between welding and endothelial function, or other effect markers. CONCLUSIONS: A modest increase in BP was found among welders compared to controls suggesting that low-to-moderate exposure to welding fumes remains a risk factor for cardiovascular disease.
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19.
  • Li, Huiqi, et al. (author)
  • Oxidative stress, telomere shortening, and DNA methylation in relation to low-to-moderate occupational exposure to welding fumes.
  • 2015
  • In: Environmental and Molecular Mutagenesis. - : Wiley. - 1098-2280 .- 0893-6692. ; 56:8, s. 684-693
  • Journal article (peer-reviewed)abstract
    • Evidence suggests that exposure to welding fumes is a risk factor for lung cancer. We examined relationships between low-to-moderate occupational exposure to particles from welding fumes and cancer-related biomarkers for oxidative stress, changes in telomere length, and alterations in DNA methylation. We enrolled 101 welders and 127 controls (all currently nonsmoking men) from southern Sweden. We performed personal sampling of respirable dust and measured 8-oxodG concentrations in urine using a simplified liquid chromatography tandem mass spectrometry method. Telomere length in peripheral blood was measured by quantitative polymerase chain reaction. Methylation status of 10 tumor suppressor genes was determined by methylation-sensitive high-resolution melting analysis. All analyses were adjusted for age, body mass index, previous smoking, passive smoking, current residence, and wood burning stove/boiler at home. Welders were exposed to respirable dust at 1.2 mg/m(3) (standard deviation, 3.3 mg/m(3) ; range, 0.1-19.3), whereas control exposures did not exceed 0.1 mg/m(3) (P < 0.001). Welders and controls did not differ in 8-oxodG levels (β = 1.2, P = 0.17) or relative telomere length (β = -0.053, P = 0.083) in adjusted models. Welders showed higher probability of adenomatous polyposis coli (APC) methylation in the unadjusted model (odds ratio = 14, P = 0.014), but this was not significant in the fully adjusted model (P = 0.052). Every working year as a welder was associated with 0.0066 units shorter telomeres (95% confidence interval -0.013 to -0.00053, P = 0.033). Although there were no clear associations between concentrations of respirable dust and the biomarkers, there were modest signs of associations between oxidative stress, telomere alterations, DNA methylation, and occupational exposure to low-to-moderate levels of particles. Environ. Mol. Mutagen., 2015. © 2015 Wiley Periodicals, Inc.
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20.
  • Ludvigsson, Linus, et al. (author)
  • Carbon Nanotube Emissions from Arc Discharge Production: Classification of Particle Types with Electron Microscopy and Comparison with Direct Reading Techniques.
  • 2016
  • In: Annals of Occupational Hygiene. - : Oxford University Press (OUP). - 1475-3162 .- 0003-4878. ; 60:4, s. 493-512
  • Journal article (peer-reviewed)abstract
    • Introduction: An increased production and use of carbon nanotubes (CNTs) is occurring worldwide. In parallel, a growing concern is emerging on the adverse effects the unintentional inhalation of CNTs can have on humans. There is currently a debate regarding which exposure metrics and measurement strategies are the most relevant to investigate workplace exposures to CNTs. This study investigated workplace CNT emissions using a combination of time-integrated filter sampling for scanning electron microscopy (SEM) and direct reading aerosol instruments (DRIs). Material and Methods: Field measurements were performed during small-scale manufacturing of multiwalled carbon nanotubes using the arc discharge technique. Measurements with highly time- and size-resolved DRI techniques were carried out both in the emission and background (far-field) zones. Novel classifications and counting criteria were set up for the SEM method. Three classes of CNT-containing particles were defined: type 1: particles with aspect ratio length:width >3:1 (fibrous particles); type 2: particles without fibre characteristics but with high CNT content; and type 3: particles with visible embedded CNTs. Results: Offline sampling using SEM showed emissions of CNT-containing particles in 5 out of 11 work tasks. The particles were classified into the three classes, of which type 1, fibrous CNT particles contributed 37%. The concentration of all CNT-containing particles and the occurrence of the particle classes varied strongly between work tasks. Based on the emission measurements, it was assessed that more than 85% of the exposure originated from open handling of CNT powder during the Sieving, mechanical work-up, and packaging work task. The DRI measurements provided complementary information, which combined with SEM provided information on: (i) the background adjusted emission concentration from each work task in different particle size ranges, (ii) identification of the key procedures in each work task that lead to emission peaks, (iii) identification of emission events that affect the background, thereby leading to far-field exposure risks for workers other than the operator of the work task, and (iv) the fraction of particles emitted from each source that contains CNTs. Conclusions: There is an urgent need for a standardized/harmonized method for electron microscopy (EM) analysis of CNTs. The SEM method developed in this study can form the basis for such a harmonized protocol for the counting of CNTs. The size-resolved DRI techniques are commonly not specific enough to selective analysis of CNT-containing particles and thus cannot yet replace offline time-integrated filter sampling followed by SEM. A combination of EM and DRI techniques offers the most complete characterization of workplace emissions of CNTs today.
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21.
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22.
  • Nilsson, Patrik T., et al. (author)
  • Emissions into the air from bitumen and rubber bitumen - Implications for asphalt workers' exposure
  • 2018
  • In: Annals of Work Exposures and Health. - : Oxford University Press (OUP). - 2398-7308 .- 2398-7316. ; 62:7, s. 828-839
  • Journal article (peer-reviewed)abstract
    • The risk among asphalt workers of developing adverse health effects may increase due to their occupational exposure. One area of special concern arises when rubber granules are mixed into bitumen to enhance asphalt properties. This research characterizes and compares bitumen and rubber bitumen regarding the emissions of and workers' exposure to particulates, polycyclic aromatic hydrocarbons (PAHs) and benzothiazole. A laboratory and a field study were carried out. In the laboratory, two types of bitumen, one with and one without rubber, were heated up to two temperatures (140°C and 160°C). The concentrations and chemical compositions of the emissions were determined. In the field at asphalt work sites, both emissions and worker exposure measurements were performed. The methods applied included direct-reading sampling techniques next to the asphalt work area and personal sampling techniques on asphalt workers. The exposure measurements on asphalt workers for respirable dust, total dust, particle number and mass, and total PAH concentrations showed similar concentrations when both standard and rubber bitumen were used. The asphalt-surfacing machine operators were the workers with the highest observed exposure followed by the screed operators and roller drivers. Both laboratory and field measurements showed higher concentrations of benzothiazole when rubber bitumen was used, up to 7.5 times higher in the laboratory. The levels of naphthalene, benzo(a)pyrene, and total particles were lower for both types compared with the Swedish occupational exposure limits, 8-h time weighted average concentrations. Benzo(a)pyrene exceeded however the health-based guideline value given by the WHO for both types of bitumen. The study concludes that several air pollutants such as benzothiazole and PAHs are emitted into the air during asphalt work, but it is not evident if exposure to rubber bitumen possesses a higher risk than exposure to standard bitumen in terms of asphalt worker exposure.
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23.
  • Wahlberg, K., et al. (author)
  • Filaggrin variations are associated with PAH metabolites in urine and DNA alterations in blood
  • 2019
  • In: Environmental Research. - : Elsevier BV. - 0013-9351 .- 1096-0953. ; 177
  • Journal article (peer-reviewed)abstract
    • Dermal chemical exposure is common in many professions. The filaggrin protein is important for the skin barrier and variations in the filaggrin gene (FLG) may influence the uptake of chemicals via the skin, and consequently, the degree of systemic effects. The aim of this study was to investigate, in chimney sweeps with occupational exposure to polycyclic aromatic hydrocarbons (PAH) from soot, the influence of variation in FLG on internal PAH dose and DNA alterations, including epigenetic, previously linked to cancer and cardiovascular disease. We used TaqMan PCR to genotype 151 chimney sweeps and 152 controls for four FLG null variants (R501X, R2447X, S3247X and 2282del4) which cause impaired skin barrier, and FLG copy number variation (12th repeat, CNV12) which potentially is beneficial for the skin barrier. The internal dose of PAH was represented by urinary PAH metabolites (e.g. 1-hydroxypyrene and 3-hydroxybenzo[a]pyrene) that we measured by LC-MS/MS. We measured epigenetic alterations (methylation of AHRR and F2RL3) in blood by pyrosequencing; and DNA alterations (telomere length and mitochondrial DNA copy number) by real-time PCR. Hypomethylation of AHRR or F2RL3 is a risk factor for lung cancer and shorter telomere length a risk factor for cardiovascular disease. The frequencies of FLG null were 8.6 and 11.8% (p = 0.35), and CNV12 27.8 and 19.7% (p = 0.09) in chimney sweeps and controls, respectively. We found that among chimney sweeps working predominately with soot sweeping (high PAH exposure), CNV12 carriers had lower concentrations of PAH metabolites in urine compared with non-carriers (median 1-hydroxypyrene = 0.37 vs 0.86 μg/g creatinine respectively; p = 0.025 by linear regression models adjusted for age, BMI and smoking) compared to sweeps not carrying CNV12. Further, FLG null was associated with approximately 2.5% higher methylation of F2RL3 (cg03636183, p = 0.019 after adjustment for exposure group, age, BMI and smoking). FLG null was associated with approximately 7% shorter telomere length (p = 0.015, adjusted model). Our results suggest that FLG variations may influence the dose of PAH in highly exposed workers, possibly via dermal uptake. It also suggests that FLG variation may influence the degree of (epi)genotoxicity in the body. FLG variation is common in the working population and should be considered in risk assessment. © 2019
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24.
  • Xu, Yiyi, et al. (author)
  • Exposure, respiratory symptoms, lung function and inflammation response of road-paving asphalt workers
  • 2018
  • In: Occupational and Environmental Medicine. - : BMJ. - 1351-0711 .- 1470-7926. ; 75:7, s. 494-500
  • Journal article (peer-reviewed)abstract
    • Background Controversy exists as to the health effects of exposure to asphalt and crumb rubber modified (CRM) asphalt, which contains recycled rubber tyres. Objective To assess exposures and effects on airway symptoms, lung function and inflammation biomarkers in conventional and CRM asphalt road pavers. Methods 116 conventional asphalt workers, 51 CRM asphalt workers and 100 controls were investigated. A repeated-measures analysis included 31 workers paving with both types of asphalt. Exposure to dust, nitrosamines, benzothiazole and polycyclic aromatic hydrocarbon (PAH) was measured in worksites. Self-reported symptoms, spirometry test and blood sampling were conducted prework and postwork. Symptoms were further collected during off-season for asphalt paving. Results Dust, PAHs and nitrosamine exposure was highly varied, without difference between conventional and CRM asphalt workers. Benzothiazole was higher in CRM asphalt workers (p<0.001). Higher proportions of asphalt workers than controls reported eye symptoms with onset in the current job. Decreased lung function from preworking to postworking was found in CRM asphalt workers and controls. Preworking interleukin-8 was higher in CRM asphalt workers than in the controls, followed by a decrement after 4days of working. No differences in any studied effects were found between conventional and CRM asphalt paving. Conclusion CRM asphalt workers are exposed to higher benzothiazole. Further studies are needed to identify the source of nitrosamines in conventional asphalt. Mild decrease in lung function in CRM asphalt workers and work-related eye symptoms in both asphalt workers were observed. However, our study did not find strong evidence for severe respiratory symptoms and inflammation response among asphalt workers.
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25.
  • Xu, Yiyi, et al. (author)
  • Occupational exposure to particles and mitochondrial DNA : Relevance for blood pressure
  • 2017
  • In: Environmental Health: A Global Access Science Source. - : Springer Science and Business Media LLC. - 1476-069X. ; 16:1
  • Journal article (peer-reviewed)abstract
    • Background: Particle exposure is a risk factor for cardiovascular diseases. Mitochondrial DNA (mtDNA) is a primary target for oxidative stress generated by particle exposure. We aimed to elucidate the effects of occupational exposure to particle-containing welding fumes on different biomarkers of mtDNA function, and in turn, explore if they modify the association between particle exposure and cardiovascular response, measured as blood pressure. Methods: We investigated 101 welders and 127 controls (all non-smoking males) from southern Sweden. Personal sampling of the welders’ exposure to respirable dust was performed during work hours (average sampling time: 6.8 h; range: 2.4-8.6 h) and blood pressure was measured once for each subject. We measured relative mtDNA copy number by quantitative PCR and methylation of the mitochondrial regulatory region D-loop and the tRNA encoding gene MT-TF by bisulfite-pyrosequencing. We calculated the relative number of unmethylated D-loop and MT-TF as markers of mtDNA function to explore the modification of mtDNA on the association between particle exposure and blood pressure. General linear models were used for statistical analyses. Results: Welders had higher mtDNA copy number (β = 0.11, p = 0.003) and lower DNA methylation of D-loop (β = −1.4, p = 0.002) and MT-TF (β = −1.5, p = 0.004) than controls. Higher mtDNA copy number was weakly associated with higher personal respirable dust exposure among welders with exposure level above 0.7 mg/m3 (β = 0.037, p = 0.054). MtDNA function modified the effect of welding fumes on blood pressure: welders with low mtDNA function had higher blood pressure than controls, while no such difference was found in the group with high mtDNA function. Conclusion: Increased mtDNA copy number and decreased D-loop and MT-TF methylation were associated with particle-containing welding fumes exposure, indicating exposure-related oxidative stress. The modification of mtDNA function on exposure-associated increase in blood pressure may represent a mitochondria-environment interaction.
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