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A hallmark of cataract development is lens opacification, typically associated not only with aging but also radiation exposure as encountered by interventional radiologists and astronauts during the long\u2010term space mission. To better understand radiation\u2010induced cataracts, the adverse outcome pathway (AOP) framework was used to structure and evaluate knowledge across biological levels of organization (e.g., macromolecular, cell, tissue, organ, organism and population). AOPs identify a sequence of key events (KEs) causally connected by key event relationships (KERs) beginning with a molecular initiating event to an adverse outcome (AO) of relevance to regulatory decision\u2010making. To construct the cataract AO and retrieve evidence to support it, a scoping review methodology was used to filter, screen, and review studies based on the modified Bradford Hill criteria. Eight KEs were identified that were moderately supported by empirical evidence (e.g., dose\u2010, time\u2010, incidence\u2010concordance) across the adjacent (directly linked) relationships using well\u2010established endpoints. Over half of the evidence to justify the KER linkages was derived from the evidence stream of biological plausibility. Early KEs of oxidative stress and protein modifications had strong linkages to downstream KEs and could be the focus of countermeasure development. Several identified knowledge gaps and inconsistencies related to the quantitative understanding of KERs which could be the basis of future research, most notably directed to experiments in the range of low or moderate doses and dose\u2010rates, relevant to radiation workers and other occupational exposures.<\/jats:p>","DOI":"10.1002\/em.22594","type":"journal-article","created":{"date-parts":[[2024,4,22]],"date-time":"2024-04-22T02:38:16Z","timestamp":1713753496000},"page":"31-56","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["<scp>AOP<\/scp>\n                    report: Development of an adverse outcome pathway for deposition of energy leading to cataracts"],"prefix":"10.1002","volume":"65","author":[{"given":"Emma","family":"Carrothers","sequence":"first","affiliation":[{"name":"Consumer and Clinical Radiation Protection Bureau, Environmental and Radiation Health Sciences Directorate Health Canada  Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meghan","family":"Appleby","sequence":"additional","affiliation":[{"name":"Consumer and Clinical Radiation Protection Bureau, Environmental and Radiation Health Sciences Directorate Health Canada  Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vita","family":"Lai","sequence":"additional","affiliation":[{"name":"Consumer and Clinical Radiation Protection Bureau, Environmental and Radiation Health Sciences Directorate Health Canada  Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana","family":"Kozbenko","sequence":"additional","affiliation":[{"name":"Consumer and Clinical Radiation Protection Bureau, Environmental and Radiation Health Sciences Directorate Health Canada  Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dalya","family":"Alomar","sequence":"additional","affiliation":[{"name":"Consumer and Clinical Radiation Protection Bureau, Environmental and Radiation Health Sciences Directorate Health Canada  Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin J.","family":"Smith","sequence":"additional","affiliation":[{"name":"Consumer and Clinical Radiation Protection Bureau, Environmental and Radiation Health Sciences Directorate Health Canada  Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuyuki","family":"Hamada","sequence":"additional","affiliation":[{"name":"Biology and Environmental Chemistry Division Sustainable System Research Laboratory, Central Research Institute of Electric Power Industry (CRIEPI)  Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Hinton","sequence":"additional","affiliation":[{"name":"Defense Research &amp; Development Canada Canadian Forces Environmental Medicine Establishment  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth A.","family":"Ainsbury","sequence":"additional","affiliation":[{"name":"Radiation, Chemical and Environmental Hazards Division UK Health Security Agency  Birmingham UK"},{"name":"Environmental Research Group within the School of Public Health, Faculty of Medicine at Imperial College of Science Technology and Medicine  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robyn","family":"Hocking","sequence":"additional","affiliation":[{"name":"Learning and Knowledge and Library Services Health Canada  Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carole","family":"Yauk","sequence":"additional","affiliation":[{"name":"Department of Biology University of Ottawa  Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth C.","family":"Wilkins","sequence":"additional","affiliation":[{"name":"Consumer and Clinical Radiation Protection Bureau, Environmental and Radiation Health Sciences Directorate Health Canada  Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinita","family":"Chauhan","sequence":"additional","affiliation":[{"name":"Consumer and Clinical Radiation Protection Bureau, Environmental and Radiation Health Sciences Directorate Health Canada  Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,4,21]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.3109\/09553002.2012.695097"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1080\/15321819.2020.1726774"},{"issue":"1","key":"e_1_2_11_4_1","first-page":"78","article-title":"Early responses to low\u2010dose ionizing radiation in cellular lens epithelial models","volume":"197","author":"Ahmadi M.","year":"2022","journal-title":"Radiation Research"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrrev.2016.07.010"},{"key":"e_1_2_11_6_1","doi-asserted-by":"crossref","unstructured":"Alc\u00f3cer G. 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