{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T03:34:24Z","timestamp":1791862464021,"version":"4.3.4"},"reference-count":70,"publisher":"Wiley","issue":"1-2","license":[{"start":{"date-parts":[[2025,2,24]],"date-time":"2025-02-24T00:00:00Z","timestamp":1740355200000},"content-version":"vor","delay-in-days":54,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Environ and Mol Mutagen"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Formaldehyde (FA) is a highly reactive aldehyde that is regarded as an inhalation hazard and human carcinogen. Herein, we report a follow\u2010up study evaluating the effects of exposure duration on the toxicity and mutagenicity of FA using a human in\u00a0vitro air\u2010liquid\u2010interface (ALI) airway tissue model. Previously we exposed ALI cultures to 7.5, 15 and 30\u2010ppm FA fumes 4\u2009h\/day for 5\u2009days; currently, we have increased the exposure duration of cultures exposed to 7.5 and 15\u2009ppm FA to 5\u2009days\/week for 4\u2009weeks, followed by a 28\u2010day recovery. Due to its toxicity, cultures exposed to 30\u2009ppm FA were treated for 5\u2009days, followed by the recovery. Tissue responses were evaluated following the treatment and recovery. DNA damage was measured using the Comet\u2010Chip assay after 3\u2009days of exposure, and mutagenesis was evaluated by duplex sequencing following the recovery. The toxicity detected following the 4\u2010week exposure was similar to that seen previously with the 5\u2010day exposures: both 7.5 and 15\u2009ppm FA induced moderate decreases in tissue integrity, FANCD2 DNA\u2010repair enzyme expression and IL\u20106 release, and moderate increases in IL\u20101RA release. Effects on cell proliferation, ciliary function and tissue structure were minimal. Additionally, neither the 4\u2010week exposure to 7.5 and 15\u2009ppm FA nor the 5\u2010day exposure to 30\u2009ppm FA induced DNA damage or mutations. Using this experimental design, exposure of human ALI airway cultures to FA fumes does not produce genotoxicity or mutagenicity, even when exposures are conducted over a 28\u2010day period.<\/jats:p>","DOI":"10.1002\/em.70000","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T09:01:13Z","timestamp":1741683673000},"page":"6-21","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Characterizing the Pulmonary Toxicity and Potential Mutagenicity of Formaldehyde Fumes in a Human Bronchial Epithelial Tissue Model"],"prefix":"10.1002","volume":"66","author":[{"given":"Yuan","family":"Le","sequence":"first","affiliation":[{"name":"Division of Genetic and Molecular Toxicology, National Center for Toxicological Research US Food and Drug Administration  Jefferson Arkansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baiping","family":"Ren","sequence":"additional","affiliation":[{"name":"Division of Genetic and Molecular Toxicology, National Center for Toxicological Research US Food and Drug Administration  Jefferson Arkansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Levan","family":"Muskhelishvili","sequence":"additional","affiliation":[{"name":"Toxicologic Pathology Associates  Jefferson Arkansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly","family":"Davis","sequence":"additional","affiliation":[{"name":"Toxicologic Pathology Associates  Jefferson Arkansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiying","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Genetic and Molecular Toxicology, National Center for Toxicological Research US Food and Drug Administration  Jefferson Arkansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Gwinn","sequence":"additional","affiliation":[{"name":"Division of Translational Toxicology National Institute of Environmental Health Sciences  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego","family":"Rua","sequence":"additional","affiliation":[{"name":"Division of Biology, Chemistry, and Materials Science, Office of Science and Engineering Laboratories, Center for Devices and Radiological Heath US Food and Drug Administration  Silver Spring Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert H.","family":"Heflich","sequence":"additional","affiliation":[{"name":"Division of Genetic and Molecular Toxicology, National Center for Toxicological Research US Food and Drug Administration  Jefferson Arkansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuefei","family":"Cao","sequence":"additional","affiliation":[{"name":"Division of Genetic and Molecular Toxicology, National Center for Toxicological Research US Food and Drug Administration  Jefferson Arkansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,2,24]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1359-6101(02)00020-5"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2014.11.008"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djp096"},{"issue":"10","key":"e_1_2_7_5_1","first-page":"4736","article-title":"Loss of Tumorigenicity With Simultaneous Changes in Radiosensitivity and Photosensitivity During In\u00a0Vitro Growth of L5178Y Murine Lymphoma Cells","volume":"43","author":"Beer J. 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