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Development of an adverse outcome pathway for deposition of energy leading to cataracts
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  • Emma Carrothers,
  • Meghan Appleby,
  • Vita Lai,
  • Tatiana Kozbenko,
  • Dalya Alomar,
  • Benjamin Smith,
  • Nobuyuki Hamada,
  • Patricia Hinton,
  • Elizabeth Ainsbury,
  • Robyn Hocking,
  • Carole Yauk,
  • Ruth Wilkins,
  • Vinita Chauhan
Emma Carrothers
Health Canada Radiation Protection Bureau
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Meghan Appleby
Health Canada Radiation Protection Bureau
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Vita Lai
Health Canada Radiation Protection Bureau
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Tatiana Kozbenko
Health Canada Radiation Protection Bureau
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Dalya Alomar
Health Canada Radiation Protection Bureau
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Benjamin Smith
Health Canada Radiation Protection Bureau
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Nobuyuki Hamada
Central Research Institute of Electric Power Industry
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Patricia Hinton
Canadian Forces Environmental Medicine Establishment
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Elizabeth Ainsbury
UK Health Security Agency Radiation Chemical and Environmental Hazards Directorate
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Robyn Hocking
Health Canada
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Carole Yauk
University of Ottawa
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Ruth Wilkins
Health Canada Radiation Protection Bureau
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Vinita Chauhan
Health Canada Radiation Protection Bureau

Corresponding Author:vinita.chauhan@hc-sc.gc.ca

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Abstract

Cataracts are one of the leading causes of blindness, with estimated 95 million people affected worldwide. 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-term space mission. To better understand radiation-induced cataracts, the adverse outcome pathway (AOP) framework was used to structure and evaluate knowledge across biological levels of organization. AOPs identify a sequence of key events (KEs) connected by key event relationships (KERs) beginning with a molecular initiating event (MIE) to an adverse outcome (AO) of relevance to regulatory decision-making. To construct the cataract AOP, a scoping review methodology was used to filter, screen, and review studies based on the modified Bradford Hill criteria. Eight KEs were moderately supported by empirical evidence across the adjacent (directly-linked) relationships using well-established endpoints. Over half of the evidence collected was informed by biological plausibility. Early KEs of oxidative stress and protein modifications could be the focus of countermeasures. Several identified knowledge gaps and inconsistencies in the AOP can be the basis of future research, most notably directed to experiments at low or moderate doses and dose-rates, relevant to radiation workers and other occupational exposures.
12 May 2023Submitted to Environmental and Molecular Mutagenesis
12 May 2023Submission Checks Completed
12 May 2023Assigned to Editor
12 May 2023Review(s) Completed, Editorial Evaluation Pending
30 May 2023Reviewer(s) Assigned