Cancer-related changes and low-to-moderate exposure to welding fumes: A longitudinal study.
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ABSTRACT: Objective
This study tested for an association between early cancer-related biomarkers and low-to-moderate exposure to fumes from welding mild steel.Methods
Male, non-smoking participants from southern Sweden were recruited and examined (N=338, 171 welders and 167 controls); of these, 78 welders and 96 controls were examined on two occasions six years apart. Exposure to welding fumes was evaluated by measuring respirable dust, welding years, and cumulative exposure. DNA methylation of CpG sites within the cancer-related genes AHRR, F2RL3, and B3GNTL1 was measured by pyrosequencing and relative mitochondrial DNA copy number and telomere length were measured by qPCR in whole-blood samples. Multivariate models were used for longitudinal analysis.Results
Median exposure to respirable dust was 0.7 mg/m3 at both timepoints, adjusted for use of personal protective equipment. Compared with controls, welders showed a significant decrease over time in DNA methylation of B3GNTL1 CpG1 and CpG4 [adjusted for age, body mass index, and smoking: β=-0.66, standard error (SE)=0.28; β=-0.48, SE=0.24, respectively]. In addition, exposure to respirable dust and cumulative exposure was associated with a decrease in methylation of F2RL3 CpG2 among all welders (adjusted β=-0.67, SE=0.23 and β=-0.03, SE=0.02, respectively). No significant associations were found for AHRR, mitochondrial DNA copy number, or telomere length.Conclusion
Low-to-moderate exposure to welding fumes was associated with a small effect on selected early epigenetic biomarkers of cancer. The direction of the methylation pattern (lower methylation of specific CpG sites) indicates early lung cancer-related changes associated with mild steel welding.
SUBMITTER: Dauter UM
PROVIDER: S-EPMC8729166 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description: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.
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Project description:Background & aimsInhalation of welding fume may cause pulmonary disease known as welder's lung. At our centre we came across a number of welders with systemic iron overload and prolonged occupational history and we aimed at characterizing this novel clinical form of iron overload.MethodsAfter exclusion of other known causes of iron overload, 20 welders were fully evaluated for working history, hepatic, metabolic and iron status. MRI iron assessment was performed in 19 patients and liver biopsy in 12. We included 40 HFE-HH patients and 24 healthy controls for comparison.Results75% of patients showed lung HRCT alterations; 90% had s-FERR > 1000 ng/mL and 60% had TSAT > 45%. Liver iron overload was mild in 8 and moderate-severe in 12. The median iron removed was 7.8 g. Welders showed significantly lower TSAT and higher SIS and SIS/TIS ratio than HFE-HH patients. Serum hepcidin was significantly higher in welders than in HFE-HH patients and healthy controls. At liver biopsy, 50% showed liver fibrosis that was mild in four, and moderate-severe in two. Liver staging correlated with liver iron overload.ConclusionsWelders with prolonged fume exposure can develop severe liver iron overload. The mechanism of liver iron accumulation is quite different to that of HFE-HH suggesting that reticuloendothelial cells may be the initial site of deposition. We recommend routine measurement of serum iron indices in welders to provide adequate diagnosis and therapy, and the inclusion of prolonged welding fume exposure in the list of acquired causes of hyperferritinemia and iron overload.
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Project description:BackgroundOccupational welding fumes contain varieties of toxic metal particles and may affect cardiovascular system like the Particulate Matters (PM). Few studies have focused on the effects of toxic metals on the hemodynamic balance; however, the reporting results were not consistent. This study aimed to investigate the association between toxic metals exposure (Chromium (Cr), Manganese (Mn) and Lead (Pb)) and blood hemostatic parameters status after a 3-week exposure cessation among workers exposed to welding fumes.MethodologyStructured interviews and biological samplings were conducted for 86 male workers without a history of Anemia and Cardiovascular diseases (CVDs) and working in a confined space to construct crude oil tanks. Metal levels of Cr, Mn and Pb in urine were measured during the working days using Inductively Coupled Plasma Mass Spectrometer (ICP-MS) method. The concentrations of hemostatic proteins in blood (White blood cell counts (WBC), Lymphocytes, Monocyte, Eosinophil, Neutrophil, Hematocrit (Hct) were assessed after a 3 weeks exposure cessation. Workers were divided into groups based on occupation type (welder group and non-welder group), and based on metal levels (high and low exposure groups) for comparison. Linear regression models were used to explore the association between metal exposure and multiple blood hemostatic parameters adjusted for age, Body Mass Index (BMI), and smoking status.ResultsUrine Mn and Cr level of the welder group was significantly higher than the non-welder group (Mn: 0.96 VS 0.22 ug/g creatinine, p < 0.001; Cr: 0.63 VS 0.22 ug/g creatinine, p < 0.01). The mean value of Hct in the welder group was 44.58 ± 2.84 vol%, significantly higher than the non-welder group (43.07 ± 3.31 vol%, p = 0.026). The median value of WBC in the high Mn-exposed group (6.93 ± 1.59 X 106 Cell/ml) was significantly lower than the low Mn-exposed group (7.90 ± 2.13 X 106 Cell/ml, p = 0.018). The linear regression analyses showed that there was a significantly negative association between log transformed WBC value and the Mn exposure groups (high and low) after adjusting for age, BMI, and smoking status (β = - 0.049, p = 0.045), but no significant result was found between WBC and occupation types (welder and non-welder) (p > 0.05). Multiple linear regression analysis also showed positive association between Hct and occupational types (welder and non-welders) (β = 0.014, p = 0.055). The other hemostatic parameters were not different from controls when divided by occupation type or metal level groups.ConclusionsOur results showed that welders were exposed to about 3 to 4 times higher Mn and Cr concentrations than non-welders. Moreover, one third of the non-welders were exposed to high-exposure groups of Mn and Cr metals. Regression models revealed a significant association of the WBC counts with the Mn exposure group. Therefore, we infer that Mn exposure may play a significant role on the blood hemostatic parameters of workers in the confined space. Hazard identification for non-welders should also be conducted in the confined space.
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Project description: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 r S = 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.
| S-EPMC7485227 | biostudies-literature
Project description:BackgroundWelders 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.MethodsWe investigated 101 welders (median span of working as a welder: 7 years) and 127 unexposed controls (non-welders with no obvious exposure to respirable dust at work), age range 23-60 years, all currently non-smoking, in Sweden. The participants were interviewed about their work history, lifestyle factors and diseases. Personal sampling of respirable dust was performed for the welders. DNA methylation of F2RL3 in blood was assessed by pyrosequencing of four CpG sites, CpG_2 (corresponds to cg03636183) to CpG_5, in F2RL3. Multivariable linear regression analysis was used to assess the association between exposure to welding fumes and F2RL3 methylation.ResultsWelders had 2.6% lower methylation of CpG_5 than controls (p<0.001). Higher concentrations of measured respirable dust among the welders were associated with hypomethylation of CpG_2, CpG_4 and CpG_5 (β=-0.49 to -1.4, p<0.012); p<0.029 adjusted for age, previous smoking, passive smoking, education, current residence and respirator use. Increasing the number of years working as a welder was associated with hypomethylation of CpG_4 (linear regression analysis, β=-0.11, p=0.039, adjusted for previous smoking). Previous tobacco smokers had 1.5-4.7% (p<0.014) lower methylation of 3 of the 4 CpG sites in F2RL3 (CpG_2, CpG_4 and CpG_5) compared to never-smokers. A non-significant lower risk of cardiovascular disease with more methylation was observed for all CpG sites.ConclusionsWelding fumes exposure and previous smoking were associated with F2RL3 hypomethylation. This finding links low-to-moderate exposure to welding fumes to adverse effects on the cardiovascular system, and suggests a potential mechanistic pathway for this link, via epigenetic effects on F2RL3 expression.
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Project description: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.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.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.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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Project description:Zinc- and copper-containing welding fumes can cause systemic inflammation after exposure in humans. Recent ex vivo studies have shown that the observed inflammation originates from exposed immune cells. In vitro studies identified the soluble fraction of metal particles as the main effectors. Isolated perfused mouse lungs (IPLs) were perfused and ventilated for 270 min. Lungs were instilled with saline solution (control), welding fume particle suspension (WFs) or the soluble fraction of the welding fumes (SF-WFs). Bronchoalveolar lavage fluid (BALF) and perfusate samples were analyzed for cytokine levels and lung tissue mRNA expression levels were analyzed via RT-PCR. All lungs instilled with WFs did not complete the experiments due to a fatal reduction in tidal volume. Accordingly, IL-6 and MPO levels were significantly higher in BALF of WF lungs compared to the control. IL-6 and MPO mRNA expression levels were also increased for WFs. Lungs instilled with SF-WFs only showed mild reactions in tidal volume, with BALF and mRNA expression levels not significantly differing from the control. Zinc- and copper-containing welding fume particles adversely affect IPLs when instilled, as evidenced by the fatal loss in tidal volume and increased cytokine expression and secretion. The effects are mainly caused by the particles, not by the soluble fraction.
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