| 1. |
- Alhamdow, Ayman, et al.
(författare)
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DNA-methylation of the cancer-related genes F2RL3 and AHRR is associated with occupational exposure to polycyclic aromatic hydrocarbons
- 2018
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Ingår i: Carcinogenesis. - : Oxford University Press. - 0143-3334 .- 1460-2180. ; 39:7, s. 869-878
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Tidskriftsartikel (refereegranskat)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. |
- Hagenbjörk-Gustafsson, Annika, et al.
(författare)
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Determinants of personal exposure to some carcinogenic substances and nitrogen dioxide among the general population in five Swedish cities
- 2014
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Ingår i: Journal of Exposure Science and Environmental Epidemiology. - : Springer Science and Business Media LLC. - 1559-0631 .- 1559-064X. ; 24:4, s. 437-443
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Tidskriftsartikel (refereegranskat)abstract
- Environmental levels of airborne carcinogenic and related substances are comparatively better known than individual exposure and its determinants. We report on a personal monitoring program involving five Swedish urban populations. The aim of the program was to investigate personal exposure to benzene, 1,3-butadiene, formaldehyde, and nitrogen dioxide (NO2). The measurements were performed among 40 inhabitants during seven consecutive days, in one urban area each year, during 2000-2008. The estimated population exposure levels were 1.95 mu g/m(3) for benzene, 0.56 mu g/m(3) for 1,3-butadiene, 19.4 mu g/m(3) for formaldehyde, and 14.1,mu g/m(3) for NO2. Statistical analysis using a mixed-effects model revealed that time spent in traffic and time outdoors contributed to benzene and 1,3- butadiene exposure. For benzene, refueling a car was an additional determinant influencing the exposure level. Smoking or environmental tobacco smoke were significant determinants of exposure to NO2, benzene, and 1, 3-butadiene. Those with a gas stove had higher NO2 exposure. Living in a single-family house increased the exposure to formaldehyde significantly. In a variance component model, the between-subject variance dominated for 1,3-butadiene and formaldehyde, whereas the between-city variance dominated for NO2. For benzene, the between-subject and between-cities variances were similar.
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| 3. |
- Landberg, Hanna, et al.
(författare)
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Comparison and Evaluation of Multiple Users' Usage of the Exposure and Risk Tool : Stoffenmanager 5.1
- 2015
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Ingår i: Annals of Occupational Hygiene. - : Oxford University Press (OUP). - 0003-4878 .- 1475-3162. ; 59:7, s. 821-835
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Tidskriftsartikel (refereegranskat)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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| 4. |
- Landberg, Hanna E, et al.
(författare)
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A Study of the Validity of Two Exposure Assessment Tools : Stoffenmanager and the Advanced REACH Tool
- 2017
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Ingår i: Annals of Work Exposures and Health. - : Oxford University Press. - 2398-7308 .- 2398-7316. ; 61:5, s. 575-588
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Tidskriftsartikel (refereegranskat)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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| 5. |
- Landberg, Hanna E., et al.
(författare)
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Evaluation of risk assessment approaches of occupational chemical exposures based on models in comparison with measurements
- 2018
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Ingår i: Safety Science. - : Elsevier. - 0925-7535 .- 1879-1042. ; 109, s. 412-420
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Tidskriftsartikel (refereegranskat)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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| 6. |
- Landberg, Hanna, et al.
(författare)
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Evaluating the Risk Assessment Approach of the REACH Legislation : A Case Study
- 2019
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Ingår i: Annals of Work Exposures and Health. - : Oxford University Press. - 2398-7308 .- 2398-7316. ; 63:1, s. 68-76
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Tidskriftsartikel (refereegranskat)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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| 7. |
- Albin, Maria, et al.
(författare)
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Cytogenetic and morphologic subgroups of myelodysplastic syndromes in relation to occupational and hobby exposures.
- 2003
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Ingår i: Scandinavian Journal of Work, Environment and Health. - 0355-3140. ; 29:5, s. 378-387
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: This study investigated the association between occupational and hobby exposure and the risk of myelodysplastic syndromes (MDS) while focusing on differential patterns of clonal chromosome aberrations and morphologic subgroups. METHODS: A case-referent study was conducted with 330 MDS patients investigated cytogenetically in 1976-1993 (cases) and matched referents. Telephone interviews with either the person or a next-of-kin were used. The participation rate of the cases and referents was 85% and 60%, respectively. Information was obtained from the next-of-kin more often for the cases (88%) than for the referents (26%). Occupational hygienists assessed the exposure using interview data on worktasks and hobbies. Associations with disease risk were evaluated for 10 exposures with a logistic regression analysis. RESULTS: The investigated exposures were generally not associated with cytogenetically abnormal MDS. Effect estimates for specific cytogenetic or morphologic subgroups were generally imprecise. Occupational exposure to extremely low-frequency magnetic fields (EMF) was associated with MDS with a normal karyotype [odds ratio (OR) 2.0, 95% confidence interval (95% CI) 1.0-4.0]. The exposure-response association was consistent for intensity but inconclusive for duration. A decreased risk was observed for MDS, irrespective of karyotypic pattern, among farmers and farmhands (OR 0.53, 95% CI 0.35-0.81). CONCLUSIONS: Cytogenetically abnormal MDS was generally not associated with occupational or hobby exposure to known or suspected genotoxic agents. However, exposure prevalences and intensities were low for several agents. An association was suggested between occupational exposure to EMF and MDS with a normal karyotype. Biases due to differential information quality and selective participation cannot be ruled out.
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| 8. |
- Alhamdow, Ayman, et al.
(författare)
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Cancer-related proteins in serum are altered in workers occupationally exposed to polycyclic aromatic hydrocarbons : a cross-sectional study
- 2019
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Ingår i: Carcinogenesis. - : Oxford University Press (OUP). - 0143-3334 .- 1460-2180. ; 40:6, s. 771-781
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Tidskriftsartikel (refereegranskat)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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| 9. |
- Alhamdow, Ayman, et al.
(författare)
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Cardiovascular Disease-Related Serum Proteins in Workers Occupationally Exposed to Polycyclic Aromatic Hydrocarbons
- 2019
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Ingår i: Toxicological Sciences. - : Oxford University Press (OUP). - 1096-6080 .- 1096-0929. ; 171:1, s. 235-246
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Tidskriftsartikel (refereegranskat)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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| 10. |
- Alhamdow, Ayman, et al.
(författare)
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Chimney sweeps in Sweden : a questionnaire-based assessment of long-term changes in work conditions, and current eye and airway symptoms
- 2017
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Ingår i: International Archives of Occupational and Environmental Health. - : Springer Science and Business Media LLC. - 0340-0131 .- 1432-1246. ; 90:2, s. 207-216
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Tidskriftsartikel (refereegranskat)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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| 11. |
- Alhamdow, Ayman, et al.
(författare)
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Early markers of cardiovascular disease are associated with occupational exposure to polycyclic aromatic hydrocarbons
- 2017
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7:1
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Tidskriftsartikel (refereegranskat)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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| 12. |
- Alhamdow, Ayman, et al.
(författare)
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Fluorene exposure among PAH-exposed workers is associated with epigenetic markers related to lung cancer
- 2020
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Ingår i: Occupational and Environmental Medicine. - : BMJ. - 1351-0711 .- 1470-7926. ; 77:7, s. 488-495
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Exposure to high-molecular-weight polycyclic aromatic hydrocarbons (PAHs) may cause cancer in chimney sweeps and creosote-exposed workers, however, knowledge about exposure to low-molecular-weight PAHs in relation to cancer risk is limited. In this study, we aimed to investigate occupational exposure to the low-molecular-weight PAHs phenanthrene and fluorene in relation to different cancer biomarkers. Methods We recruited 151 chimney sweeps, 19 creosote-exposed workers and 152 unexposed workers (controls), all men. We measured monohydroxylated metabolites of phenanthrene and fluorene in urine using liquid chromatography coupled to tandem mass spectrometry. We measured, in peripheral blood, the cancer biomarkers telomere length and mitochondrial DNA copy number using quantitative PCR; and DNA methylation ofF2RL3andAHRRusing pyrosequencing. Results Median PAH metabolite concentrations were higher among chimney sweeps (up to 3 times) and creosote-exposed workers (up to 353 times), compared with controls (p<0.001; adjusted for age and smoking). n-ary sumation OH-fluorene (sum of 2-hydroxyfluorene and 3-hydroxyfluorene) showed inverse associations with percentage DNA methylation ofF2RL3andAHRRin chimney sweeps (B (95% CI)=-2.7 (-3.9 to -1.5) forF2RL3_cg03636183, and -7.1 (-9.6 to -4.7) forAHRR_cg05575921: adjusted for age and smoking), but not in creosote-exposed workers. In addition, n-ary sumation OH-fluorene showed a 42% mediation effect on the inverse association between being a chimney sweep and DNA methylation ofAHRRCpG2. Conclusions Chimney sweeps and creosote-exposed workers were occupationally exposed to low-molecular-weight PAHs. Increasing fluorene exposure, among chimney sweeps, was associated with lower DNA methylation ofF2RL3andAHRR, markers for increased lung cancer risk. These findings warrant further investigation of fluorene exposure and toxicity.
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| 13. |
- Almstrand, Ann-Charlotte, et al.
(författare)
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An explorative study on respiratory health among operators working in polymer additive manufacturing
- 2023
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Ingår i: Frontiers in Public Health. - : Frontiers Media S.A.. - 2296-2565. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Additive manufacturing (AM), or 3D printing, is a growing industry involving a wide range of different techniques and materials. The potential toxicological effects of emissions produced in the process, involving both ultrafine particles and volatile organic compounds (VOCs), are unclear, and there are concerns regarding possible health implications among AM operators.The objective of this study was to screen the presence of respiratory health effects among people working with liquid, powdered, or filament plastic materials in AM. MethodsIn total, 18 subjects working with different additive manufacturing techniques and production of filament with polymer feedstock and 20 controls participated in the study. Study subjects filled out a questionnaire and underwent blood and urine sampling, spirometry, impulse oscillometry (IOS), exhaled NO test (FeNO), and collection of particles in exhaled air (PEx), and the exposure was assessed. Analysis of exhaled particles included lung surfactant components such as surfactant protein A (SP-A) and phosphatidylcholines. SP-A and albumin were determined using ELISA. Using reversed-phase liquid chromatography and targeted mass spectrometry, the relative abundance of 15 species of phosphatidylcholine (PC) was determined in exhaled particles. The results were evaluated by univariate and multivariate statistical analyses (principal component analysis). ResultsExposure and emission measurements in AM settings revealed a large variation in particle and VOC concentrations as well as the composition of VOCs, depending on the AM technique and feedstock. Levels of FeNO, IOS, and spirometry parameters were within clinical reference values for all AM operators. There was a difference in the relative abundance of saturated, notably dipalmitoylphosphatidylcholine (PC16:0_16:0), and unsaturated lung surfactant lipids in exhaled particles between controls and AM operators. ConclusionThere were no statistically significant differences between AM operators and controls for the different health examinations, which may be due to the low number of participants. However, the observed difference in the PC lipid profile in exhaled particles indicates a possible impact of the exposure and could be used as possible early biomarkers of adverse effects in the airways.
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| 14. |
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| 15. |
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| 16. |
- Bergendorf, Ulf, et al.
(författare)
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Cancerframkallande ämnen i tätortsluft –Personlig exponering ochbakgrundsmätningar i Malmö 2008
- 2010
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Den allmänna befolkningens personliga exponering i Malmö för några cancerframkallandeämnen undersöktes under perioden september-december 2008. Totalt 61 mätningargenomfördes på 41 slumpmässigt utvalda individer med personburna passiva provtagare förbensen, 1,3-butadien, formaldehyd, samt kvävedioxid, i sjudygnsperioder. Upprepademätningar gjordes på 20 personer. Parallellt med de personburna mätningarna utfördesstationära mätningar på två platser i Malmö, en på Rådhustaket, som anses representeraMalmös urbana bakgrund, samt en i gatunivå på Dalaplan.Utöver detta utfördes även pumpad tvådygnsprovtagning av partiklar (PM2.5) ochpolyaromatiska kolväten (PAH) stationärt inomhus i vardagsrum samt vid den urbanabakgrundsstationen. PAH-mätningarna presenteras nedan som nivåer av bens(a)pyren.Deltagarfrekvensen var 63 %. Medianresultat från studien i Malmö presenteras i nedanståendetabell:Ämne Personburnamätningar/vardagsrumsmätningarUtomhusmätningarRådhustaket DalaplanBensen(μg/m3)1,0 0,65 1,11,3-Butadien(μg/m3)0,31 0,05 0,12Formaldehyd(μg/m3)12 3,4 3,0Kvävedioxid(μg/m3)15 20 28Bens(a)pyren(pg/m3) 14 24 -PM2.5(μg/m3) 5,8 5,3 -Denpersonliga exponeringen för bensen korrelerade med halten av butadien, inga andraämnen korrelerade med varandra.Den personliga exponeringen för bensen och butadien korrelerade med både egen rökning ochpassiv rökning. Det fanns också samband mellan butadien och tid i egen bostad.Kvävedioxidhalterna korrelerade till innehav av gasspis. Bens(a)pyren mätt i urban bakgrundkorrelerade med både PM2.5 och summa PAH. För inomhusmätningarna korrelerade summaPAH med både PM2.5 och bens(a)pyren.Det fanns inga korrelationer mellan de parallella bakgrundsmätningarna och medelhalter avde personburna exponeringarna för något av de studerade ämnena.Vid en jämförelse med 2003 års mätning har de personburna halterna av bensen och butadiensjunkit signifikant. För kvävedioxid visar denna undersökning att de stationärabakgrundshalterna har sjunkit tydligt vilket också konfirmeras med mätningar genomförda avMalmö kommun, medan de personburna nivåerna ligger på samma nivåer.Denna studie är en del i Naturvårdsverkets hälsorelaterade miljöövervakning, luft, ochfinansieras av Naturvårdsverket. Liknande undersökning har tidigare genomförts i Malmö2003 och i Göteborg, Stockholm, Umeå och Lindesberg mellan 2000 och 2007.
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| 17. |
- Björk, Jonas, et al.
(författare)
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Are occupational, hobby, or lifestyle exposures associated with Philadelphia chromosome positive chronic myeloid leukaemia?
- 2001
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Ingår i: Occupational and Environmental Medicine. - : BMJ. - 1470-7926 .- 1351-0711. ; 58:11, s. 722-727
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To investigate a broad range of occupational, hobby, and lifestyle exposures, suggested as risk factors for Philadelphia chromosome positive (Ph+) chronic myeloid leukaemia (CML). METHODS: A case-control study, comprising 255 Ph+CML patients from southern Sweden and matched controls, was conducted. Individual data on work tasks, hobbies, and lifestyle exposures were obtained by telephone interviews. Occupational hygienists assessed occupational and hobby exposures for each subject individually. Also, occupational titles were obtained from national registries, and group level exposure-that is, the exposure proportion for each occupational title-was assessed with a job exposure matrix. The effects of 11 exposures using individual data and two exposures using group data (organic solvents and animal dust) were estimated. RESULTS: For the individual data on organic solvents, an effect was found for moderate or high intensity of exposure (odds ratio (OR) 3.4, 95% confidence interval (95% CI) 1.1 to 11) and for long duration (15-20 years) of exposure (OR 2.1, 95% CI 1.1 to 4.0). By contrast, the group data showed no association (OR 0.69, 95% CI 0.27 to 1.8; moderate or high intensity versus no exposure). For extremely low frequency electromagnetic fields (EMFs), only individual data were available. An association with long occupational exposure to EMFs was found (OR 2.3, 95% CI 1.2 to 4.5). However, no effect of EMF intensity was indicated. No significant effects of benzene, gasoline or diesel, or tobacco smoking were found. OR estimates below unity were suggested for personal use of hair dye and for agricultural exposures. CONCLUSIONS: Associations between exposure to organic solvents and EMFs, and Ph+CML were indicated but were not entirely consistent.
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| 21. |
- Broberg Palmgren, Karin, et al.
(författare)
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Influence of genetic factors on toluene diisocyanate-related symptoms: evidence from a cross-sectional study
- 2008
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Ingår i: Environmental Health. - 1476-069X. ; 7:15
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Tidskriftsartikel (refereegranskat)abstract
- Background: Toluene diisocyanate (TDI) is a highly reactive compound used in the production of, e. g., polyurethane foams and paints. TDI is known to cause respiratory symptoms and diseases. Because TDI causes symptoms in only a fraction of exposed workers, genetic factors may play a key role in disease susceptibility. Methods: Workers (N = 132) exposed to TDI and a non-exposed group ( N = 114) were analyzed for genotype (metabolising genes: CYP1A1*2A, CYP1A1*2B, GSTM1*O, GSTM3*B, GSTP1 1105V, GSTP1 A114V, GSTT1*O, MPO -463, NAT1*3, *4, *10, *11, *14, *15, NAT2*5, *6, *7, SULT1A1 R213H; immune-related genes: CCL5 -403, HLA-DQB1* 05, TNF-308, TNF-863) and symptoms of the eyes, upper and lower airways ( based on structured interviews). Results: For three polymorphisms: CYP1A1*2A, CYP1A1*2B, and TNF -308 there was a pattern consistent with interaction between genotype and TDI exposure status for the majority of symptoms investigated, although it did reach statistical significance only for some symptoms: among TDI-exposed workers, the CYP1A1 variant carriers had increased risk (CYP1A1*2A and eye symptoms: variant carriers OR 2.0 95% CI 0.68-6.1, p-value for interaction 0.048; CYP1A1*2B and wheeze: IV carriers OR = 12, 1.4-110, p-value for interaction 0.057). TDI-exposed individuals with TNF-308 A were protected against the majority of symptoms, but it did not reach statistical significance. In the non-exposed group, however, TNF -308 A carriers showed higher risk of the majority of symptoms ( eye symptoms: variant carriers OR = 2.8, 1.1-7.1, p-value for interaction 0.12; dry cough OR = 2.2, 0.69-7.2, p-value for interaction 0.036). Individuals with SULT1A1 213H had reduced risk both in the exposed and non-exposed groups. Other polymorphisms, showed associations to certain symptoms: among TDI-exposed, NAT1*10 carriers had a higher risk of eye symptoms and CCL5 -403 AG+AA as well as HLA-DQB1 *05 carriers displayed increased risk of symptoms of the lower airways. GSTM1, GSTM3 and GSTP1 only displayed effects on symptoms of the lower airways in the non-exposed group. Conclusion: Specific gene-TDI interactions for symptoms of the eyes and lower airways appear to exist. The results suggest different mechanisms for TDI- and non- TDI-related symptoms of the eyes and lower airways.
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| 22. |
- Broberg Palmgren, Karin, et al.
(författare)
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The GSTP1 Ile105 Val polymorphism modifies the metabolism of toluene di-isocyanate.
- 2010
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Ingår i: Pharmacogenetics & Genomics. - 1744-6872 .- 1744-6880. ; 20:2, s. 104-111
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Toluene di-isocyanate (TDI) is widely used in the production of polyurethane foams and paints. As TDI causes respiratory disease in only a fraction of exposed workers, genetic factors may play a key role in disease susceptibility. Polymorphisms in TDI metabolising genes may affect elimination kinetics, resulting in differences in body retention, and in its turn differences in adverse effects. OBJECTIVES: To analyze how genotype modifies the associations between (i) TDI in air (2,4-TDI and 2,6-TDI) and its metabolites toluene diamine (TDA; 2,4-TDA and 2,6-TDA) in hydrolyzed urine; and (ii) 2,4-TDA and 2,6-TDA in hydrolyzed plasma and 2,4-TDA and 2,6-TDA in urine. METHODS: Workers exposed to TDI were analyzed for 2,4-TDI and 2,6-TDI in air (N=70), 2,4-TDA and 2,6-TDA in hydrolyzed urine (N=124) and in plasma (N=128), and genotype: CYP1A1*2A, CYP1A1*2B, GSTA1-52, GSTM1O, GSTM3B, GSTP1 I105V, GSTP1 A114V, GSTT1O, MPO-463, NAT1*3, *4, *10, *11, *14, *15, NAT2*5, *6, *7, and SULT1A1 R213H. RESULTS: GSTP1 105 strongly modified the relationship between 2,4-TDA in plasma and in urine: ValVal carriers had about twice as steep regression slope than IleIle carriers. A similar pattern was found for 2,6-TDA. CYP1A1*2A, GSTM1, GSTP1, GSTT1, and MPO possibly influenced the relationship between TDA in plasma and urine. CONCLUSION: Our results show, for the first time, genetic modification on the human TDI metabolism. The findings suggest that GSTP1 genotype should be considered when evaluating biomarkers of TDI exposure in urine and plasma. Moreover, the results support earlier findings of GSTP1 105 Val as protective against TDI-related asthma.
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| 23. |
- Broström, Julia M., et al.
(författare)
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Toluene diisocyanate exposure and autotaxin–lysophosphatidic acid signalling
- 2018
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Ingår i: Toxicology and Applied Pharmacology. - : Elsevier BV. - 0041-008X .- 1096-0333. ; 355, s. 43-51
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Tidskriftsartikel (refereegranskat)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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| 24. |
- Broström, Julia, et al.
(författare)
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Toluene diisocyanate: Induction of the autotaxin-lysophosphatidic acid axis and its association with airways symptoms.
- 2015
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Ingår i: Toxicology and Applied Pharmacology. - : Elsevier BV. - 1096-0333 .- 0041-008X. ; 287:3, s. 222-231
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Tidskriftsartikel (refereegranskat)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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| 25. |
- Friman, Katarina, et al.
(författare)
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Cancerframkallande ämnen i tätortsluft Malmö 2003
- 2004
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Den allmänna befolkningens personliga exponering i Malmö för några cancerframkallande ämnen undersöktes under perioden oktober-november 2003. Totalt 60 mätningar genomfördes på slumpmässigt utvalda individer med personburna passiva provtagare för bensen, 1,3-butadien, formaldehyd, acetaldehyd, samt kvävedioxid, i sjudygnsperioder. Samtidigt med de personburna mätningarna utfördes stationära mätningar på två platser i Malmö, en på Miljöförvaltningens tak, som anses representera Malmös urbana bakgrundshalter, samt en i gatunivå på Södervärn, som är ett trafikbelastat busstorg. Utöver detta utfördes även pumpad provtagning av polyaromatiska kolväten (PAH) i tredygnsmätningar stationärt utomhus. Hos tio av deltagarna mättes PAH stationärt i sovrummet under 24 timmar. PAH-mätningar utfördes även hos tio personer från personalen på Yrkes- och miljömedicinska kliniken i Lund och Miljöförvaltningen i Malmö både personburet och stationärt i sovrummet. PAH-mätningarna presenteras som nivåer av bens(a)pyren. Studier med liknande upplägg har tidigare genomförts i Göteborg (2000), Umeå (2001), samt Stockholm (2002/2003).Deltagarfrekvensen var endast 43 %. Bortfallet orsakade en snedfördelning, vilket gav en överrepresentation av personer bosatta i de centrala delarna av Malmö.Medianresultat från studien i Malmö presenteras i nedanstående tabell.ÄmnePersonburna mätningarStationära mätningarμg/m3μg/m3 Miljöförvaltningens takSödervärnBensen1.71.02.01,3-Butadien0.60.10.2Formaldehyd1633Acetaldehyd1001Kvävedioxid142542Bens(a)pyren ng/m30.170.070.13Den personliga exponeringen för bensen korrelerar med om man är rökare och hur ofta man tankar eller hanterar bensin. De uppmätta koncentrationerna av 1,3-butadien var mer än sex gånger högre för rökare än icke-rökare och i genomsnitt hade deltagare som eldat med ved under provtagningen 50 procent högre butadienexponering än deltagare som inte vedeldat. Studien visade att huvudexponeringen av formaldehyd och acetaldehyd sker från emissioner inomhus. I båda fallen var exponeringen större i enfamiljshus än i flerfamiljshus. Kvävedioxid är i sig inte cancerframkallande, men mättes som indikator på trafikrelaterade luftföroreningar. Kvävedioxidhalterna korrelerade inte till vistelse i specifika miljöer och ej heller till övriga ämnen, varken personburet eller stationärt. För de personburna passiva mätningarna var inomindividvariabiliteten en liten del av den totala variabiliteten. Det förelåg en stark korrelation mellan personburna mätningar av bens(a)pyren och parallella stationära mätningar i hemmet.
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