| 1. |
- Broberg, Karin, et al.
(författare)
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Metodutveckling för blodprovstagning på filterpapper
- 2022
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Blodprov för metallanalyser tas vanligtvis via prov av venblod från armvecket. Detta är dock eninvasiv metod och provtagningen måste utföras av medicinskt utbildad personal. Ett sätt att erhållablod med en mindre invasiv metod och som ger betydligt mindre blodvolym är att genom ett stick ifingret droppa kapillärblod på ett filterpapper som får torka. Ytterligare fördelar med dennaprovtagningsmetod är att det blir möjligt med ”självprovtagning” och att för en mindre kostnad kanblod samlas in från fler personer.Vi genomförde ett utvecklingsprojekt för att ta fram en metod för att samla in och mäta metallernakadmium, kvicksilver och bly i torkat blod (blodspottar på filterpapper) erhållet via självprovtagninggenom stick i fingret.Vi tog fram en sur tvättmetod för att tvätta bort metaller (bakgrundshalter) i filterpapper innan dekan användas för provtagning. Vi utvecklade en enkel men effektiv alkalisk urlakningsmetod avmetaller i blodspottarna. Vi tog fram ett självprovtagningskit för blodspottar samt instruktionsvideodesignat för att minimera kontaminering av metaller i omgivningsmiljön. Vi jämfördevenblodsprovtagning med självprovstagning för 17 försökspersoner och fann överensstämmelseframförallt för bly. Vi gjorde en inter-laboratoriejämförelse för mätning av metaller i blodspottar frånfem personer och fann överensstämmelse för kvicksilver och bly.Studien visar att det är möjligt att mäta toxiska metaller i små volymer från blodspottar erhållna viasjälvprovtagning. Emellertid skilde sig halterna i venblod och i blodspottar för vissa personer ochframförallt för kadmium. Det beror troligen på att blodspottarna kan kontamineras vid utstansningmed de stansverktyg som finns att köpa på marknaden. Ytterligare metodutveckling via framtagningav adekvat stansverktyg rekommenderas för att kunna mäta kadmium i blodspottar samt att däreftertesta metoden i HÄMI-projekt.
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| 2. |
- Engström, Karin, et al.
(författare)
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Evaluation of the impact of genetic polymorphisms in glutathione-related genes on the association between methylmercury or n-3 polyunsaturated long chain fatty acids and risk of myocardial infarction : a case-control study
- 2011
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Ingår i: Environmental Health. - : BioMed Central (BMC). - 1476-069X. ; 10:33
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Tidskriftsartikel (refereegranskat)abstract
- Background: The n-3 polyunsaturated fatty acids eicosapentaenoic acid and docosahexaenoic acid, which are present in fish, are protective against myocardial infarction. However, fish also contains methylmercury, which influences the risk of myocardial infarction, possibly by generating oxidative stress. Methylmercury is metabolized by conjugation to glutathione, which facilitates elimination. Glutathione is also an antioxidant. Individuals with certain polymorphisms in glutathione-related genes may tolerate higher exposures to methylmercury, due to faster metabolism and elimination and/or better glutathione-associated antioxidative capacity. They would thus benefit more from the protective agents in fish, such as eicosapentaenoic+docosahexaenoic acid and selenium. The objective for this study was to elucidate whether genetic polymorphisms in glutathione-related genes modify the association between eicosapentaenoic+docosahexaenoic acid or methylmercury and risk of first ever myocardial infarction. Methods: Polymorphisms in glutathione-synthesizing (glutamyl-cysteine ligase catalytic subunit, GCLC and glutamyl-cysteine ligase modifier subunit, GCLM) or glutathione-conjugating (glutathione S-transferase P, GSTP1) genes were genotyped in 1027 individuals from northern Sweden (458 cases of first-ever myocardial infarction and 569 matched controls). The impact of these polymorphisms on the association between erythrocyte-mercury (proxy for methylmercury) and risk of myocardial infarction, as well as between plasma eicosapentaenoic+docosahexaenoic acid and risk of myocardial infarction, was evaluated by conditional logistic regression. The effect of erythrocyte-selenium on risk of myocardial infarction was also taken into consideration. Results: There were no strong genetic modifying effects on the association between plasma eicosapentaenoic+docosahexaenoic acid or erythrocyte-mercury and risk of myocardial infarction risk. When eicosapentaenoic+docosahexaenoic acid or erythrocyte-mercury were divided into tertiles, individuals with GCLM-588 TT genotype displayed a lower risk relative to the CC genotype in all but one tertile; in most tertiles the odds ratio was around 0.5 for TT. However, there were few TT carriers and the results were not statistically significant. The results were similar when taking plasma eicosapentaenoic+docosahexaenoic acid, erythrocyte-selenium and erythrocyte-mercury into account simultaneously. Conclusions: No statistically significant genetic modifying effects were seen for the association between plasma eicosapentaenoic+docosahexaenoic acid or erythrocyte-mercury and risk of myocardial infarction. Still, our results indicate that the relatively rare GCLM-588 TT genotype may have an impact, but a larger study is necessary for confirmation.
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| 3. |
- Engström, Karin, et al.
(författare)
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Genetic variation in glutathione-related genes and body burden of methylmercury
- 2008
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Ingår i: Journal of Environmental Health Perspectives. - Research Triangle Park, N.C. : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 116:6, s. 734-739
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Exposure to toxic methylmercury (MeHg) through fish consumption is a large problem worldwide, and it has led to governmental recommendations of reduced fish consumption and blacklisting of mercury-contaminated fish. The elimination kinetics of MeHg varies greatly among individuals. Knowledge about the reasons for such variation is of importance for improving the risk assessment for MeHg. One possible explanation is hereditary differences in MeHg metabolism. MeHg is eliminated from the body as a glutathione (GSH) conjugate. OBJECTIVES: We conducted this study to assess the influence of polymorphisms in GSH-synthesizing [glutamyl-cysteine ligase modifier subunit (GCLM-588) and glutamyl-cysteine ligase catalytic subunit (GCLC-129)] or GSH-conjugating [glutathione S-transferase pi 1 (GSTP1-105 and GSTP1-114)] genes on MeHg retention. METHODS: Based on information obtained from questionnaires, 292 subjects from northern Sweden had a high consumption of fish (lean/fat fish two to three times per week or more). We measured total Hg in erythrocytes (Ery-Hg) and long-chain n-3 polyunsaturated fatty acids in plasma (P-PUFA; an exposure marker for fish intake). RESULTS: The GSTP1 genotype modified Ery-Hg; effects were seen for GSTP1-105 and -114 separately, and combining them resulted in stronger effects. We found evidence of effect modification: individuals with zero or one variant allele demonstrated a steeper regression slope for Ery-Hg (p = 0.038) compared with individuals with two or more variant alleles. The GCLM-588 genotype also influenced Ery-Hg (p = 0.035): Individuals with the GCLM-588 TT genotype demonstrated the highest Ery-Hg, but we saw no evidence of effect modification with increasing P-PUFA. CONCLUSIONS: These results suggest a role of GSH-related polymorphisms in MeHg metabolism.
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| 4. |
- Gliga, Anda R., et al.
(författare)
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Exposure to Mild Steel Welding and Changes in Serum Proteins With Putative Neurological Function—A Longitudinal Study
- 2020
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Ingår i: Frontiers in Public Health. - : Frontiers Media SA. - 2296-2565. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Welders are exposed to high levels of metal particles, consisting mainly of iron and manganese (Mn) oxide. Metal particles, especially those containing Mn can be neurotoxic. In this exploratory study, we evaluated associations between welding and expression of 87 putative neurology-related proteins in serum in a longitudinal approach. The study cohort from southern Sweden included welders working with mild steel (n = 56) and controls (n = 67), all male and non-smoking, which were sampled at two timepoints (T1, T2) 6-year apart. Observed associations in the longitudinal analysis (linear mixed models) were further evaluated (linear regression models) in another cross-sectional sample which included welders (n = 102) and controls (n = 89) who were sampled only once (T1 or T2). The median respirable dust levels for welders after adjusting for respiratory protection was at T1 0.6 (5–95 percentile: 0.2–4.2) and at T2 0.5 (0.1–1.8) mg/m3. The adjusted median respirable Mn concentration was at T2 0.049 mg/m3 (0.003–0.314) with a Spearman correlation between adjusted respirable dust and respirable Mn of rS = 0.88. We identified five neurology-related proteins that were differentially expressed in welders vs. controls in the longitudinal sample, of which one (nicotinamide/nicotinic acid mononucleotide adenylyltransferase 1; NMNAT1) was also differentially expressed in the cross-sectional sample. NMNAT1, an axon-protective protein linked to Alzheimers disease, was upregulated in welders compared with controls but no associations were discerned with degree of exposure (welders only: years welding, respirable dust, cumulative exposure). However, we identified five additional proteins that were associated with years welding (GCSF, EFNA4, CTSS, CLM6, VWC2; welders only) both in the longitudinal and in the cross-sectional samples. We also observed several neurology-related proteins that were associated with age and BMI. Our study indicates that low-to-moderate exposure to welding fumes is associated with changes in circulating levels of neurology-related proteins.
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| 5. |
- Harari, Raul, et al.
(författare)
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Exposure and toxic effects of elemental mercury in gold-mining activities in Ecuador
- 2012
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Ingår i: Toxicology Letters. - : Elsevier BV. - 1879-3169 .- 0378-4274. ; 213:1, s. 75-82
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Tidskriftsartikel (refereegranskat)abstract
- Traditional gold mining, using metallic mercury (Hg-0) to form gold amalgam, followed by burning to remove the Hg-0, is widely used in South America, Africa and Asia. The gold is sold to merchants who burn it again to eliminate remaining Hg-0. In Ecuador, 200 gold miners, 37 gold merchants and 72 referents were studied. The median Hg concentrations in urine (U-Hg) were 3.3 (range 0.23-170), 37 (3.2-420), and 1.6 (0.2-13) mu g/g creatinine, respectively, and in whole blood (B-Hg) were 5.2, 30, and 5.0 mu g/L, respectively. Biomarker concentrations among merchants were statistically significantly higher than among miners and referents; also the miners differed from the referents. Burning of gold amalgam among miners was intermittent; U-Hg decreased in the burning-free period. In computerized neuromotor examinations, B-Hg and U-Hg concentrations were associated with increases in the centre frequency of the tremor, as well as in reaction time and postural stability. Retention of Hg (B-Hg), and the elimination rate (U-Hg) appears to be modified by polymorphism in a gene of an enzyme in the glutathione synthesis (GCLM), but there were no significant genetic modifications for the associations between exposure and neurotoxicity. Thus, the gold merchants have a much higher exposure and risk than the miners, in whom the exposure varies over time. The metabolism of Hg is modified by genetic traits. The present exposure to Hg had limited neurotoxic effects. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
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| 6. |
- Jiang, Zheshun, et al.
(författare)
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Circulating lung-cancer-related non-coding RNAs are associated with occupational exposure to hexavalent chromium - A cross-sectional study within the SafeChrom project
- 2024
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Ingår i: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 190
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Tidskriftsartikel (refereegranskat)abstract
- Background: Hexavalent chromium (Cr(VI)) is classified as a group 1 human carcinogen and increases the risk of lung cancer. Non-coding RNAs (ncRNAs) have key regulatory roles in lung cancer, but less is known about their relation to Cr(VI) exposure.Objectives: We aimed to 1) measure the expression of lung cancer-related circulating ncRNAs in exposed workers and controls; 2) assess associations between ncRNAs expression and Cr concentrations in red blood cells (RBC) and urine; and 3) evaluate correlations between the ncRNAs.Methods: The study included 111 Cr(VI) exposed workers and 72 controls recruited from the SafeChrom project. Cr concentrations were measured in RBC (biomarker of long-term exposure) and urine (biomarker of short-term exposure) samples. Long ncRNA (lncRNA) and microRNA (miRNA) were extracted from plasma followed by deoxyribonuclease treatment, complementary DNA synthesis, and quantitative real-time polymerase chain reaction using target-specific assays for three lncRNAs (H19, MALAT1, NORAD), and four miRNAs (miR-142-3p, miR-15b-5p, miR-3940-5p, miR-451a).Results: Expression levels of lncRNAs MALAT1 and NORAD, and all four miRNAs, were significantly lower in Cr (VI) exposed workers compared with controls, and correlated significantly with RBC-Cr concentrations (rS = -0.16 to -0.38). H19 was non-significantly increased in exposed workers but significantly correlated with miR142-3p (rS = -0.33) and miR-15b-5p (rS = -0.30), and NORAD was significantly positively correlated with all four miRNAs (rS = 0.17 to 0.46). In multivariate regression models adjusting for confounders, expressions of lncRNAs MALAT1 and NORAD and all miRNAs were still significantly lower in the exposed group compared with controls, and the expression decreased with increasing RBC-Cr concentrations. Conclusions: Cr(VI) exposure was inversely and in a dose-response manner associated with the expression of circulating non-coding RNA, which suggests ncRNAs as potential biomarkers for Cr(VI)-induced toxicity.
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| 7. |
- Jiang, Zheshun, et al.
(författare)
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Hexavalent chromium still a concern in Sweden : Evidence from a cross-sectional study within the SafeChrom project
- 2024
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Ingår i: International journal of hygiene and environmental health. - : Elsevier. - 1438-4639 .- 1618-131X. ; 256
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesHexavalent chromium (Cr(VI)) is classified as a human carcinogen. Occupational Cr(VI) exposure can occur during different work processes, but the current exposure to Cr(VI) at Swedish workplaces is unknown.MethodsThis cross-sectional study (SafeChrom) recruited non-smoking men and women from 14 companies with potential Cr(VI) exposure (n = 113) and controls from 6 companies without Cr(VI) exposure (n = 72). Inhalable Cr(VI) was measured by personal air sampling (outside of respiratory protection) in exposed workers. Total Cr was measured in urine (pre- and post-shift, density-adjusted) and red blood cells (RBC) (reflecting Cr(VI)) in exposed workers and controls. The Bayesian tool Expostats was used to assess risk and evaluate occupational exposure limit (OEL) compliance.ResultsThe exposed workers performed processing of metal products, steel production, welding, plating, and various chemical processes. The geometric mean concentration of inhalable Cr(VI) in exposed workers was 0.15 μg/m3 (95% confidence interval: 0.11–0.21). Eight of the 113 exposed workers (7%) exceeded the Swedish OEL of 5 μg/m3, and the Bayesian analysis estimated the share of OEL exceedances up to 19.6% for stainless steel welders. Median post-shift urinary (0.60 μg/L, 5th-95th percentile 0.10–3.20) and RBC concentrations (0.73 μg/L, 0.51–2.33) of Cr were significantly higher in the exposed group compared with the controls (urinary 0.10 μg/L, 0.06–0.56 and RBC 0.53 μg/L, 0.42–0.72). Inhalable Cr(VI) correlated with urinary Cr (rS = 0.64) and RBC-Cr (rS = 0.53). Workers within steel production showed the highest concentrations of inhalable, urinary and RBC Cr. Workers with inferred non-acceptable local exhaustion ventilation showed significantly higher inhalable Cr(VI), urinary and RBC Cr concentrations compared with those with inferred acceptable ventilation. Furthermore, workers with inferred correct use of respiratory protection were exposed to significantly higher concentrations of Cr(VI) in air and had higher levels of Cr in urine and RBC than those assessed with incorrect or no use. Based on the Swedish job-exposure-matrix, approximately 17 900 workers were estimated to be occupationally exposed to Cr(VI) today.ConclusionsOur study demonstrates that some workers in Sweden are exposed to high levels of the non-threshold carcinogen Cr(VI). Employers and workers seem aware of Cr(VI) exposure, but more efficient exposure control strategies are required. National strategies aligned with the European strategies are needed in order to eliminate this cause of occupational cancer.
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| 8. |
- Jiang, Zheshun, et al.
(författare)
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O-193 THE SAFECHROM PROJECT - CIRCULATING LUNG-CANCER-RELATED NON-CODING RNAS ARE ASSOCIATED WITH OCCUPATIONAL EXPOSURE TO HEXAVALENT CHROMIUM
- 2024
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Ingår i: Occupational Medicine. - 0962-7480. ; 74:Suppl 1, s. 378-379
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Hexavalent chromium, Cr(VI), is classified as a Group 1 human carcinogen and causes lung cancer. This study was to investigate associations between occupational exposure to Cr(VI) and lung cancer-related non-coding RNAs.The study included 111 Cr(VI) exposed workers and 72 controls in Sweden, 91.4\smokers. Cr concentration in red blood cells (RBC-Cr) was measured. MicroRNA (miRNA) and long non-coding RNA (lncRNA) were extracted from plasma followed by DNAse treatment, cDNA synthesis, and qPCR using target-specific assays for four miRNAs (miR-142-3p, miR-15b-5p, miR-3940-5p, miR-451a), and three lncRNAs (H19, MALAT1, NORAD).Median RBC-Cr concentrations were significantly higher in the exposed group (0.73 µg/L, 5-95\.51-2.33) compared with controls (0.53 µg/L, 0.42-0.72). Plasma relative expression levels of all miRNAs, MALAT1 and NORAD were significantly lower in the exposed workers compared with controls. In the exposed group, significant negative correlations (rS=-0.19 - -0.27) were found between RBC-Cr and miR-142-3p, miR-15b-5p, miR-451a and NORAD. NORAD correlated with miR-142-3p (rS=0.34) and miR-15b-5p (rS=0.28). In multivariate regression models adjusting for confounders, expression of the miRNAs, MALAT1 and NORAD was still significantly lower in the exposed group compared with controls, and the expression decreased with increasing RBC-Cr.Cr(VI) exposure was associated in a dose-response manner with differential expression of circulating non-coding RNAs in exposed workers, which suggests non-coding RNAs as potential toxicological biomarkers for Cr(VI). Relations between miRNAs and lncRNAs suggest that they participate in the same lncRNA-miRNA-mRNA regulatory axes, which may play important roles in Cr(VI) carcinogenesis.Occupational Cr(VI) exposure may impact circulating lung-cancer-related non-coding RNAs expression.
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| 9. |
- Jiang, Zheshun, et al.
(författare)
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P-205 THE SAFECHROM PROJECT - EVIDENCE FROM A CROSS-SECTIONAL STUDY SHOWS THAT HEXAVALENT CHROMIUM IS STILL A CONCERN IN SWEDEN
- 2024
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Ingår i: Occupational Medicine. - 0962-7480. ; 74:Suppl 1, s. 291-292
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Hexavalent chromium Cr(VI) is a human carcinogen, but the current exposure to Cr(VI) at Swedish workplaces is unknown.Recruitment of 113 workers with potential Cr(VI) exposure and 72 controls was combined with measurements of inhalable Cr(VI) (only exposed workers) and total Cr in urine and red blood cells (RBC), Bayesian analysis of occupational exposure limit (OEL) compliance was used, as well as the Swedish job-exposure-matrix.Exposed workers performed processing of metal products, steel production, welding, and plating. The geometric mean concentration of inhalable Cr(VI) in exposed workers was 0.15 μg/m3. Eight workers (7\ exceeded the Swedish OEL (5 μg/m3), and the share of OEL exceedances was estimated to be up to 19.6\ and RBC-Cr were significantly higher in exposed workers compared with controls. Workers with inferred non-acceptable local exhaustion ventilation showed significantly higher inhalable Cr(VI), urine- and RBC-Cr than those with acceptable ventilation. Workers with inferred correct use of respiratory protection had higher inhalable Cr(VI), and, paradoxically, higher urine- and RBC-Cr concentrations than workers with incorrect use. We estimate that ~17 900 Swedish workers are occupationally exposed to Cr(VI) today.Our study showed that although most air measurements were relatively low, 7\ and particularly stainless steel workers are at risk for exceeding the OEL. The existing protective measures implemented at workplaces are still inadequate and insufficient.Some workers in Sweden are exposed to high levels of the non-threshold carcinogen Cr(VI). National strategies aligned with European strategies are needed to eliminate occupational cancer.
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| 10. |
- Kippler, Maria, et al.
(författare)
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Biomonitorering av kadmium i urin hos svenska kvinnor
- 2024
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Exponering för låga halter av kadmium via kosten kan ge upphov till benskörhet, ökad risk för frakturer samt hjärtkärlsjukdom. Kvinnor utgör en riskgrupp. Syftet med studien vara var att jämföra halter av kadmium i urin hos svenska icke-rökande kvinnor i åldern 50–59 år boende i olika delar av landet samt att relatera kadmiumhalterna i urin till kända exponeringskällor. Medianhalten av kadmium i urin bland de undersökta kvinnorna (N=130) var 0,21 μg/g kreatinin respektive 0,20 μg/L (justerat för densitet). Åtta procent av kvinnorna hade en kadmiumhalt som överskred 0,5 μg/g kreatinin och 3 % av kvinnorna hade en halt som överskred 1 μg/g kreatinin och som visat skadlig påverkan på skelettet respektive njurarna. Kvinnor bosatta i Västerbotten och Norrbotten hade lägre kadmiumhalter i urin än kvinnor i Skåne, Stockholm och Västra Götaland. Kvinnor som var födda i ett land utanför Europa hade högre kadmiumhalter i urin än kvinnor födda i Europa. Med avseende på olika typer av livsmedel så hade kvinnor som sällan åt kött och bröd högre kadmiumhalter i urin. Likaså hade kvinnor med högre intag av baljväxter högre kadmiumhalter än kvinnor som rapporterade att de aldrig åt baljväxter. Vi fann inga signifikanta samband med andra typer av livsmedel, kosttillskott, eller källor till dricksvatten. Vi fann geografiska, etniska och kost-relaterade skillnader i kadmiumhalter i urin hos icke-rökande medelålders kvinnor i Sverige. Åtta procent av kvinnorna överskred den kadmiumhalt i urin som har kopplats till skador på skelettet. Vid jämförelse med kadmiumhalterna i urin från den föregående undersökningen 2018–2019 bland icke-rökande kvinnor i åldern 50–59 år så fanns det ingen indikation på att exponeringen har minskat över tid. Därför rekommenderas en fortsatt biomonitorering av kadmiumhalterna i känsliga grupper och insatser för att minska kadmiumexponering i befolkningen är nödvändiga.
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