{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T09:06:31Z","timestamp":1779267991948,"version":"3.51.4"},"reference-count":38,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T00:00:00Z","timestamp":1771804800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T00:00:00Z","timestamp":1771804800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Risk Analysis"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>In parallel with the evolution of epidemiological evidence over nearly two decades, various advisory and regulatory groups in Europe and the United States have conducted several hazard assessments on inhalation exposure to formaldehyde and risk of leukemia. All of the hazard assessments addressed all or the myeloid leukemias (MLs) combined, and none focused on the acute type, etiologically distinct and shown to have a chemical cause (e.g., benzene). However, conclusions regarding formaldehyde as a human leukemogen have been conflicting, although largely based on the same modest body of evidence. As there are no known animal models for formaldehyde and leukemia (any type), good evidence that formaldehyde cannot reach the bone marrow, and no demonstrated mechanism whereby formaldehyde induces leukemia, the hazard assessment ultimately rests on about ten epidemiological studies and their interpretation. Beginning in 2009 with the International Agency for Research on Cancer (IARC), followed by other groups in the United States and Europe, formaldehyde has been classified as causing human ML. On the other hand, the EU Scientific Committee on Occupational Exposure Limits (SCOEL) and the European Chemicals Agency (ECHA) concluded that formaldehyde unlikely causes ML. Multiple classifications of formaldehyde as leukemogenic were motivated by claims of \u201cnew studies,\u201d including Beane Freeman et\u00a0al., Hauptmann et\u00a0al., and Zhang et\u00a0al. Closer evaluation of these reveals no increased occurrence of ML in Beane Freeman et\u00a0al. and several important criticisms in the others that limit their value for classifying formaldehyde. Nevertheless, the hazard assessments summarized here varied with some observing consistent positive findings and some others\u2014including recent meta\u2010analyses\u2014finding no association. That similar hazard assessment approaches applied to the same modest collection of epidemiological studies can lead to different\u2014and even conflicting\u2014causal conclusions is problematic. One might reasonably conclude that the research methods for evaluating epidemiological data are unreliable, leading to non\u2010replicable and sometimes unexplained findings and conclusions. Assuming that frameworks for critical review and synthesis of epidemiological evidence are reasonably valid\u2014and faithfully followed\u2014it remains possible that they are methodologically inadequate, inadvertently increasing the potential for subjective elements to be incorporated and allowed to influence interpretations and conclusions. A serious international effort to develop robust and replicable hazard assessment methods based on epidemiological evidence and promote universal adoption is overdue.<\/jats:p>","DOI":"10.1111\/risa.70198","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T23:09:13Z","timestamp":1773011353000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Formaldehyde and Myeloid Leukemia: Diverging Tracks of Human Health Science and Regulation"],"prefix":"10.1111","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9700-8679","authenticated-orcid":false,"given":"Kenneth A.","family":"Mundt","sequence":"first","affiliation":[{"name":"Department of Biostatistics and Epidemiology University of Massachusetts Amherst Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9457-3234","authenticated-orcid":false,"given":"William J.","family":"Thompson","sequence":"additional","affiliation":[{"name":"Independent Epidemiology Consultant  Hume Missouri USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,2,23]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1080\/10408444.2016.1211987"},{"key":"e_1_2_7_3_1","unstructured":"ANSES.2018.Opinion on the Revision of ANSES's Reference Values for Formaldehyde: Occupational Exposure Limits (OELs) Derived No\u2010Effect Levels (DNELs) for Professionals Toxicity Reference Values (TRVs) and Indoor Air Quality Guidelines (IAQGs).ANSES.https:\/\/www.anses.fr\/en\/system\/files\/AIR2017SA0041EN.pdf."},{"key":"e_1_2_7_4_1","unstructured":"ANSES.2020.Methodological Guide for the Development of Expertise With a View to Creating or Modifying Tables of Occupational Diseases or Recommendations to Regional Committees for the Recognition of Occupational Diseases.ANSES."},{"key":"e_1_2_7_5_1","unstructured":"ANSES.2023.Expertise Pertaining to Myeloid Leukaemia in Connection With Occupational Exposure to Formaldehyde in View of Creating an Occupational Disease Table or Drafting Recommendations for CRRMPs. (Request 2021\u2010SA\u20100031).ANSES."},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djp096"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajim.1066"},{"key":"e_1_2_7_8_1","unstructured":"Bolt H. M. G.Johnson G. D.Nielsen D.Papameletiou andC. L.Klein.2016.SCOEL\/REC\/125 Formaldehyde Recommendation from the Scientific Committee on Occupational Exposure Limits.Publications Office of the European Union."},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/JOM.0000000000000466"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwu049"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yrtph.2010.08.013"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1080\/10408444.2024.2337435"},{"key":"e_1_2_7_13_1","unstructured":"ECHA (European Chemicals Agency).2019.Substance Evaluation Conclusion as Required by REACH Article 48 and Evaluation Report for Formaldehyde CAS No. 50\u201000\u20100 (EC No. 200\u2010001\u20108). Evaluating Member State: France. Co\u2010Evaluating Member State: The Netherlands. 07 June 2019.ECHA."},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.3109\/10408444.2013.818618"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djp416"},{"key":"e_1_2_7_16_1","unstructured":"IARC.2012.IARC Monographs on the Evaluation of Carcinogenic Risks to Humans.A Review of Human Carcinogens Part F: Chemical Agents and Related Occupations.World Health Organization (WHO); International Agency for Research on Cancer."},{"key":"e_1_2_7_17_1","unstructured":"IARC.1982.IARC Monographs on the Evaluation of the Carcinogenic Risks to Humans.Some Industrial Chemicals and Dyestuffs.World Health Organization; International Agency for Research on Cancer."},{"key":"e_1_2_7_18_1","unstructured":"IARC.1987.IARC Monographs on the Evaluation of the Carcinogenic Risks to Humans.Overall Evaluations of Carcinogenicity: An Updating of IARC Monographs Volumes 1 to 42. Supplement 7.World Health Organization; International Agency for Research on Cancer."},{"key":"e_1_2_7_19_1","unstructured":"IARC IARC Monographs on the Evaluation of the Carcinogenic Risks to Humans.1995.Wood Dust and Formaldehyde.World Health Organization; International Agency for Research on Cancer."},{"key":"e_1_2_7_20_1","unstructured":"IARC IARC Monographs on the Evaluation of the Carcinogenic Risks to Humans.2006.Formaldehyde 2\u2010Butoxyethanol and 1\u2010Tert\u2010Butoxypropan\u20102\u2010ol.World Health Organization (WHO); International Agency for Research on Cancer."},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gloepi.2024.100143"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gloepi.2022.100093"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajim.22199"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885\u2010021\u201007908\u20103"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1080\/10408444.2017.1301878"},{"key":"e_1_2_7_26_1","volume-title":"Review of the Environmental Protection Agency's Draft IRIS Assessment of Formaldehyde","author":"NRC (National Research Council)","year":"2011"},{"key":"e_1_2_7_27_1","volume-title":"Review of the Formaldehyde Assessment in the National Toxicology Program 12th Report on Carcinogens","author":"NRC (National Research Council)","year":"2014"},{"key":"e_1_2_7_28_1","volume-title":"Report on Carcinogens","author":"NTP (National Toxicology Program)","year":"2011"},{"key":"e_1_2_7_29_1","volume-title":"Report on Carcinogens","author":"NTP (National Toxicology Program)","year":"2021"},{"key":"e_1_2_7_30_1","unstructured":"RAC (Risk Assessment Committee).2012.Opinion Proposing Harmonised Classification and Labelling at EU Level of Formaldehyde.European Chemicals Agency.https:\/\/echa.europa.eu\/registry\u2010of\u2010clh\u2010intentions\u2010until\u2010outcome\/\u2010\/dislist\/details\/0b0236e180a13be9."},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1158\/1055\u20109965.EPI\u201010\u20100155"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.5271\/sjweh.3436"},{"key":"e_1_2_7_33_1","unstructured":"UK Health Security Agency Guidance (UK HSA).2024.Formaldehyde: Toxicological Overview.UK HAS.https:\/\/www.gov.uk\/government\/publications\/formaldehyde\u2010properties\u2010incident\u2010management\u2010and\u2010toxicology\/formaldehyde\u2010toxicological\u2010overview."},{"key":"e_1_2_7_34_1","unstructured":"US EPA OCSPP.2024.Human Health Risk Assessment for Formaldehyde. 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