{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T23:55:49Z","timestamp":1787961349206,"version":"build-2784847793"},"reference-count":53,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2020,11,2]],"date-time":"2020-11-02T00:00:00Z","timestamp":1604275200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","award":["R01 ES019188"],"award-info":[{"award-number":["R01 ES019188"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","award":["P30 ES000002"],"award-info":[{"award-number":["P30 ES000002"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>Studies of occupational metal exposures and amyotrophic lateral sclerosis (ALS) have focused primarily on known neurotoxicants, including lead, mercury, selenium, and cadmium. However, these exposures are often co-occurring with other lesser studied metals. We conducted a population-based case-control study with the aim of assessing associations between occupational chromium, iron, and nickel exposures and risk of ALS. We identified ALS cases in Denmark from 1982 through 2013 from the Danish National Patient Registry and matched them to 100 controls based on birth year and sex. Cumulative metal exposures were estimated using job exposure matrices applied to occupational history from the Danish Pension Fund. Although mutually adjusted odds of ALS were higher in men with chromium exposures in the third quartile (aOR = 1.24; 95% CI 0.91, 1.69) and fourth quartile (aOR = 1.19; 95% CI: 0.80, 1.76) compared to those with no exposure, differences did not reach statistical significance. We also observed higher odds of ALS in women with nickel exposures in the third quartile (aOR = 2.21; 95% CI: 1.14, 4.28), but not for the fourth quartile (aOR = 0.61; 95% CI: 0.23, 1.64). Our findings do not suggest associations between occupational exposures to these metals and ALS. However, unavoidable non-differential misclassification from the use of JEMs may have masked truly increased risk.<\/jats:p>","DOI":"10.3390\/ijerph17218086","type":"journal-article","created":{"date-parts":[[2020,11,2]],"date-time":"2020-11-02T19:51:31Z","timestamp":1604346691000},"page":"8086","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Study of Occupational Chromium, Iron, and Nickel Exposure and Amyotrophic Lateral Sclerosis in Denmark"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3929-9540","authenticated-orcid":false,"given":"Aisha S.","family":"Dickerson","sequence":"first","affiliation":[{"name":"Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johnni","family":"Hansen","sequence":"additional","affiliation":[{"name":"Danish Cancer Society Research Center, 2100 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ole","family":"Gredal","sequence":"additional","affiliation":[{"name":"National Rehabilitation Center for Neuromuscular Disorders, 8000 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc G.","family":"Weisskopf","sequence":"additional","affiliation":[{"name":"Departments Epidemiology of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1056\/NEJMra1603471","article-title":"Amyotrophic Lateral Sclerosis","volume":"377","author":"Brown","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2031","DOI":"10.1016\/S0140-6736(07)60944-1","article-title":"Amyotrophic lateral sclerosis","volume":"369","author":"Mitchell","year":"2007","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"17071","DOI":"10.1038\/nrdp.2017.71","article-title":"Amyotrophic lateral sclerosis","volume":"3","author":"Hardiman","year":"2017","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1136\/oemed-2018-105110","article-title":"Study of occupation and amyotrophic lateral sclerosis in a Danish cohort","volume":"75","author":"Dickerson","year":"2018","journal-title":"Occup. Environ. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1016\/j.ncl.2015.07.009","article-title":"Potential Environmental Factors in Amyotrophic Lateral Sclerosis","volume":"33","author":"Oskarsson","year":"2015","journal-title":"Neurol. Clin."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.toxlet.2020.04.019","article-title":"Assessment of occupational exposure to stainless steel welding fumes\u2014A human biomonitoring study","volume":"329","author":"Stanislawska","year":"2020","journal-title":"Toxicol. Lett."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/S1470-2045(09)70134-2","article-title":"A review of human carcinogens\u2014Part C: Metals, arsenic, dusts, and fibres","volume":"10","author":"Straif","year":"2009","journal-title":"Lancet Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Su, T.-Y., Pan, C.-H., Hsu, Y.-T., and Lai, C.-H. (2019). Effects of Heavy Metal Exposure on Shipyard Welders: A Cautionary Note for 8-Hydroxy-2\u2019-Deoxyguanosine. Int. J. Environ. Res. Public Health, 16.","DOI":"10.3390\/ijerph16234813"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.envint.2018.11.055","article-title":"Urinary metals and metal mixtures and oxidative stress biomarkers in an adult population from Spain: The Hortega Study","volume":"123","author":"Tormos","year":"2019","journal-title":"Environ. Int."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1021\/tx900338d","article-title":"Risks of Copper and Iron Toxicity during Aging in Humans","volume":"23","author":"Brewer","year":"2010","journal-title":"Chem. Res. Toxicol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1038\/nrn1537","article-title":"Iron, brain ageing and neurodegenerative disorders","volume":"5","author":"Zecca","year":"2004","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Aschner, M., and Costa, L.G. (2017). Neurotoxicity of Metal Mixtures. Neurotoxicity of Metals, Springer International Publishing.","DOI":"10.1007\/978-3-319-60189-2"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/S0300-483X(02)00378-5","article-title":"Cytotoxicity and oxidative mechanisms of different forms of chromium","volume":"180","author":"Bagchi","year":"2002","journal-title":"Toxicology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1016\/j.chemosphere.2018.03.062","article-title":"Interactions between chromium(III) and iron(III), molybdenum(III) or nickel(II): Cytotoxicity, genotoxicity and mutagenicity studies","volume":"201","author":"Terpilowska","year":"2018","journal-title":"Chemosphere"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1093\/aje\/kwi343","article-title":"Prospective Study of Occupation and Amyotrophic Lateral Sclerosis Mortality","volume":"162","author":"Cragg","year":"2005","journal-title":"Am. J. Epidemiol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Filippini, T., Tesauro, M., Fiore, M., Malagoli, C., Consonni, M., Violi, F., Iacuzio, L., Arcolin, E., Conti, G.O., and Cristaldi, A. (2020). Environmental and Occupational Risk Factors of Amyotrophic Lateral Sclerosis: A Population-Based Case-Control Study. Int. J. Environ. Res. Public Health, 17.","DOI":"10.3390\/ijerph17082882"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Dickerson, A.S. (2020). Comment on: Filippini, T.; Tesauro, M.; Fiore, M.; Malagoli, C.; Consonni, M.; Violi, F.; Iacuzio, L.; Arcolin, E.; Oliveri Conti, G.; Cristaldi, A.; Zuccarello, P.; Zucchi, E.; Mazzini, L.; Pisano, F.; Gagliardi, I.; Patti, F.; Mandrioli, J.; Ferrante, M.; Vinceti, M. Environmental and Occupational Risk Factors of Amyotrophic Lateral Sclerosis: A Population-Based Case-Control Study. Int. J. Environ. Res. Public Health 2020, 17, 2882. Int. J. Environ. Res. Public Health, 17.","DOI":"10.3390\/ijerph17186490"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1136\/oemed-2016-103700","article-title":"Occupational exposures and the risk of amyotrophic lateral sclerosis","volume":"74","author":"Peters","year":"2017","journal-title":"Occup. Environ. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.jocn.2017.08.035","article-title":"Military service and the risk of amyotrophic lateral sclerosis: A meta-analysis","volume":"45","author":"Tai","year":"2017","journal-title":"J. Clin. Neurosci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1097\/EDE.0000000000000376","article-title":"Military Service and Amyotrophic Lateral Sclerosis in a Population-based Cohort","volume":"26","author":"Weisskopf","year":"2015","journal-title":"Epidemiology"},{"key":"ref_21","first-page":"7","article-title":"Amyotrophic lateral sclerosis and environmental factors","volume":"31","author":"Bozzoni","year":"2016","journal-title":"Funct. Neurol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"302","DOI":"10.3109\/17482960802455416","article-title":"Exposure to chemicals and metals and risk of amyotrophic lateral sclerosis: A systematic review","volume":"10","author":"Sutedja","year":"2009","journal-title":"Amyotroph. Lateral Scler."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1159\/000443146","article-title":"Environmental Risk Factors and Amyotrophic Lateral Sclerosis: An Umbrella Review and Critical Assessment of Current Evidence from Systematic Reviews and Meta-Analyses of Observational Studies","volume":"46","author":"Belbasis","year":"2016","journal-title":"Neuroepidemiology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1136\/oemed-2016-103780","article-title":"Occupational exposure and amyotrophic lateral sclerosis in a prospective cohort","volume":"74","author":"Koeman","year":"2017","journal-title":"Occup. Environ. Med."},{"key":"ref_25","first-page":"87","article-title":"Lead, cadmium, and selenium in the blood of patients with sporadic amyotrophic lateral sclerosis","volume":"18","author":"Vinceti","year":"1997","journal-title":"Neurol. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1136\/oemed-2018-105469","article-title":"Population-based study of amyotrophic lateral sclerosis and occupational lead exposure in Denmark","volume":"76","author":"Dickerson","year":"2019","journal-title":"Occup. Environ. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.neuro.2016.06.015","article-title":"Identification of risk factors associated with onset and progression of amyotrophic lateral sclerosis using systematic review and meta-analysis","volume":"61","author":"Wang","year":"2017","journal-title":"Neurotoxicology"},{"key":"ref_28","first-page":"279","article-title":"Possible involvement of overexposure to environmental selenium in the etiology of amyotrophic lateral sclerosis: A short review","volume":"46","author":"Vinceti","year":"2010","journal-title":"Ann. Ist. Super Sanit\u00e0"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"449","DOI":"10.2147\/CLEP.S91125","article-title":"The Danish National Patient Registry: A review of content, data quality, and research potential","volume":"7","author":"Schmidt","year":"2015","journal-title":"Clin. Epidemiol."},{"key":"ref_30","first-page":"441","article-title":"The Danish Civil Registration System. A cohort of eight million persons","volume":"53","author":"Pedersen","year":"2006","journal-title":"Dan. Med Bull."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1177\/1403494810394716","article-title":"The Supplementary Pension Fund Register","volume":"39","author":"Hansen","year":"2011","journal-title":"Scand. J. Public Health"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1080\/02841860902718747","article-title":"Construction of job-exposure matrices for the Nordic Occupational Cancer Study (NOCCA)","volume":"48","author":"Kauppinen","year":"2009","journal-title":"Acta Oncol."},{"key":"ref_33","first-page":"380","article-title":"Use of the Finnish Information System on Occupational Exposure (FINJEM) in Epidemiologic, Surveillance, and Other Applications","volume":"58","author":"Kauppinen","year":"2014","journal-title":"Ann. Occup. Hyg."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1007\/s40572-017-0156-x","article-title":"The Healthy Worker Survivor Effect: Target Parameters and Target Populations","volume":"4","author":"Brown","year":"2017","journal-title":"Curr. Environ. Health Rep."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1097\/EDE.0000000000000217","article-title":"Evolving Methods for Inference in the Presence of Healthy Worker Survivor Bias","volume":"26","author":"Buckley","year":"2015","journal-title":"Epidemiology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"317","DOI":"10.5271\/sjweh.737","article-title":"Attenuation of exposure-response curves in occupational cohort studies at high exposure levels","volume":"29","author":"Stayner","year":"2003","journal-title":"Scand. J. Work. Environ. Health"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1097\/EDE.0000000000000365","article-title":"Occupational Exposure to Electric Shocks and Magnetic Fields and Amyotrophic Lateral Sclerosis in Sweden","volume":"26","author":"Fischer","year":"2015","journal-title":"Epidemiology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1097\/01.EDE.0000078446.76859.c9","article-title":"Neurodegenerative Diseases in Welders and Other Workers Exposed to High Levels of Magnetic Fields","volume":"14","author":"Gustavsson","year":"2003","journal-title":"Epidemiology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1097\/01.EDE.0000071409.23291.7b","article-title":"Occupational Magnetic Field Exposure and Neurodegenerative Disease","volume":"14","author":"Feychting","year":"2003","journal-title":"Epidemiology"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Gunnarsson, L.-G., and Bodin, L. (2019). Occupational Exposures and Neurodegenerative Diseases\u2014A Systematic Literature Review and Meta-Analyses. Int. J. Environ. Res. Public Health, 16.","DOI":"10.3390\/ijerph16030337"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1038\/jes.2014.39","article-title":"Case-control study of occupational exposure to electric shocks and magnetic fields and mortality from amyotrophic lateral sclerosis in the US, 1991\u20131999","volume":"25","author":"Vergara","year":"2015","journal-title":"J. Expo. Sci. Environ. Epidemiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/S0361-9230(01)00455-5","article-title":"Mechanisms by which metals promote events connected to neurodegenerative diseases","volume":"55","author":"Campbell","year":"2001","journal-title":"Brain Res. Bull."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/S1367-5931(99)00073-3","article-title":"Metals and neuroscience","volume":"4","author":"Bush","year":"2000","journal-title":"Curr. Opin. Chem. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/S1367-5931(99)80035-0","article-title":"Redox metals and neu rodegenerative disease","volume":"3","author":"Sayre","year":"1999","journal-title":"Curr. Opin. Chem. Biol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Salama, A.A.A., Hegazy, R., and Hassan, A. (2016). Intranasal Chromium Induces Acute Brain and Lung Injuries in Rats: Assessment of Different Potential Hazardous Effects of Environmental and Occupational Exposure to Chromium and Introduction of a Novel Pharmacological and Toxicological Animal Model. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0168688"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.tox.2017.10.006","article-title":"Molecular mechanisms of nickel induced neurotoxicity and chemoprevention","volume":"392","author":"Song","year":"2017","journal-title":"Toxicology"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Saito, M., Arakaki, R., Yamada, A., Tsunematsu, T., Kudo, Y., and Ishimaru, N. (2016). Molecular Mechanisms of Nickel Allergy. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17020202"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"246","DOI":"10.2174\/156652411795243450","article-title":"The Role of Immune and Inflammatory Mechanisms in ALS","volume":"11","author":"McCombe","year":"2011","journal-title":"Curr. Mol. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1159\/000072925","article-title":"Occupational Exposure to Metals and Solvents and the Risk of Motor Neuron Disease","volume":"22","author":"Gait","year":"2003","journal-title":"Neuroepidemiology"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1159\/000095552","article-title":"Amyotrophic Lateral Sclerosis and Exposure to Environmental Toxins: An Australian Case-Control Study","volume":"27","author":"Morahan","year":"2006","journal-title":"Neuroepidemiology"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"361","DOI":"10.3109\/17482960802382313","article-title":"An exploratory case-control study on spinal and bulbar forms of amyotrophic lateral sclerosis in the province of Rome","volume":"10","author":"Binazzi","year":"2009","journal-title":"Amyotroph. Lateral Scler."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1111\/j.1468-1331.2012.03769.x","article-title":"Exposure to environmental toxins and the risk of sporadic motor neuron disease: An expanded Australian case-control study","volume":"19","author":"Pamphlett","year":"2012","journal-title":"Eur. J. Neurol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1093\/oxfordjournals.aje.a009070","article-title":"Occupational exposures and amyotrophic lateral sclerosis. A population-based case-control study","volume":"145","author":"McGuire","year":"1997","journal-title":"Am. J. Epidemiol."}],"container-title":["International Journal of Environmental Research and Public Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-4601\/17\/21\/8086\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:28:21Z","timestamp":1760178501000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-4601\/17\/21\/8086"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,2]]},"references-count":53,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2020,11]]}},"alternative-id":["ijerph17218086"],"URL":"https:\/\/doi.org\/10.3390\/ijerph17218086","relation":{},"ISSN":["1660-4601"],"issn-type":[{"value":"1660-4601","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,2]]}}}