{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T10:17:15Z","timestamp":1787825835931,"version":"build-2784847793"},"reference-count":37,"publisher":"Wiley","issue":"5-7","license":[{"start":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T00:00:00Z","timestamp":1784073600000},"content-version":"vor","delay-in-days":44,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"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":["Environ and Mol Mutagen"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Ethylene oxide (EtO) is primarily used as an intermediate in the manufacture of chemicals, with a minor use as a sterilant for medical equipment and food products. It is a direct\u2010acting alkylating agent that reacts with cellular macromolecules, including proteins and DNA. EtO has been shown to induce tumors in rodents and humans. DNA reactivity has been the postulated mode of action (MOA) for its carcinogenicity. The current study has investigated the dose response for EtO\u2010induced genetic damage to inform the biological plausibility of a dose\u2013response model for cancer risk assessment. Male and female B6C3F1 mice (\u2265\u200910\/sex\/concentration) were exposed to 0, 0.05, 0.1, 0.5, 1, 50, 100, or 200\u2009ppm EtO by whole\u2010body inhalation (6\u2009h\/day for 28\u2009days, 7\u2009days\/week). Mutagenicity was assessed by determining the frequency of mutant\n                    <jats:italic>Pig\u2010a<\/jats:italic>\n                    phenotype in reticulocytes (RET) and mature red blood cells (RBC) on Day 28. Cytogenetic damage was evaluated by the erythrocyte micronucleus (MN) test in blood samples collected on Days 5 and 28. EtO is a relatively weak genotoxicant with treatment\u2010related increases in\n                    <jats:italic>Pig\u2010a<\/jats:italic>\n                    and MN frequencies being seen primarily at 200\u2009ppm. The hockey\u2010stick shaped dose response for genetic damage may be conservatively interpreted as being no more than a linear response with a single slope. Thus, a cancer risk assessment dose\u2013response model consisting of a single shallow linear slope throughout the exposure range is biologically plausible and consistent if EtO were acting through a mutagenic MoA for its carcinogenicity.\n                  <\/jats:p>","DOI":"10.1002\/em.70072","type":"journal-article","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T10:25:17Z","timestamp":1784111117000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Investigation of Ethylene Oxide Genotoxicity Dose\u2013Response to Inform Cancer Risk Assessment"],"prefix":"10.1002","volume":"67","author":[{"given":"B. Bhaskar","family":"Gollapudi","sequence":"first","affiliation":[{"name":"Consulting Toxicologist  Midland Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James E.","family":"Bus","sequence":"additional","affiliation":[{"name":"Exponent  Alexandria Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip","family":"Cassidy","sequence":"additional","affiliation":[{"name":"SynTech  Hockessin Delaware USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey T.","family":"Weinberg","sequence":"additional","affiliation":[{"name":"Charles River Laboratories  Ashland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey C.","family":"Bemis","sequence":"additional","affiliation":[{"name":"Litron Laboratories  Rochester New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorothea K.","family":"Torous","sequence":"additional","affiliation":[{"name":"Litron Laboratories  Rochester New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen D.","family":"Dertinger","sequence":"additional","affiliation":[{"name":"Litron Laboratories  Rochester New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Lu","sequence":"additional","affiliation":[{"name":"University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Reiss","sequence":"additional","affiliation":[{"name":"Exponent  Alexandria Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abby A.","family":"Li","sequence":"additional","affiliation":[{"name":"Exponent  Alexandria Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,15]]},"reference":[{"key":"e_1_2_12_2_1","volume-title":"Documentation of the TLVs and BEIs: Ethylene Oxide","author":"ACGIH","year":"2015"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph16101738"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/mutage\/gep042"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1006\/taap.2001.9184"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2017.07.896"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/em.22408"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/01926230601063839"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajim.4700250607"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1080\/10937404.2020.1852988"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph220405977"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrrev.2015.11.001"},{"key":"e_1_2_12_13_1","first-page":"S65","article-title":"Bioanalytical, Molecular, and Genetic Alterations in Ethylene Oxide\u2010Exposed Male B6C3F1 Mice","volume":"53","author":"LeBaron M. 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