Radiation Adverse Outcome Pathways (AOPs) are on the Horizon: Advancing Radiation Protection through an International Horizon-Style Exercisewe
Creators: name: Burtt, Julie J.
name: Leblanc, Julie
name: Randhawa, Kristi
name: Ivanova, Addie
name: Rudd, Murray A.
name: Wilkins, Ruth
name: Azzam, Edouard I.
name: Hecker, Markus
name: Horemans, Nele
name: Vandenhove, Hildegarde
name: Adam-Guillermin, Christelle
name: Armant, Olivier
name: Klokov, Dmitry
name: Audouze, Karine
name: Kaiser, Jan Christian
name: Moertl, Simone
name: Lumniczky, Katalin
name: Tanaka, Ignacia B.
name: Yamada, Yutaka
name: Hamada, Nobuyuki
name: Al-Nabulsi, Isaf
name: Preston, Julian
name: Bouffler, Simon
name: Applegate, Kimberly
name: Cool, Donald
name: Beaton, Danielle
name: Tollefsen, Knut Erik
name: Garnier-Laplace, Jacqueline
name: Laurier, Dominique
name: Chauhan, Vinita
Publisher: name: Taylor & Francis
Year: 2022
Subjects: subject: Medicine
subject: Pharmacology
subject: Immunology
subject: FOS: Clinical medicine
subject: 69999 Biological Sciences not elsewhere classified
subject: FOS: Biological sciences
subject: Cancer
subject: Science Policy

description: <b><i>Purpose:</i></b> The Adverse Outcome Pathway (AOP) framework, a systematic tool that can link available mechanistic data with phenotypic outcomes of relevance to regulatory decision-making, is being explored in areas related to radiation risk assessment. To examine the challenges including the use of AOPs to support the radiation protection community, an international horizon-style exercise (HSE) was initiated through the Organisation for Economic Co-operation and Development Nuclear Energy Agency High-Level Group on Low Dose Research Radiation/Chemical AOP Joint Topical Group (JTG). The objective of the HSE was to facilitate the collection of ideas from a range of experts, to short-list a set of priority research questions that could, if answered, improve the description of the radiation dose-response relationship for low dose/dose-rate exposures, as well as reduce uncertainties in estimating the risk of developing adverse health outcomes following such exposures. <b><i>Materials and methods:</i></b> The HSE was guided by an international steering committee (SC) of radiation risk experts. In the first phase, research questions were solicited on areas that can be supported by the AOP framework, or challenges on the use of AOPs in radiation risk assessment. In the second phase, questions received were refined and sorted by the SC using a best-worst scaling (BWS) method. During a virtual 3-day workshop, the list of questions was further narrowed. In the third phase, an international survey of the broader radiation protection community led to an orderly ranking of the top questions. <b><i>Results:</i></b> Of the 271 questions solicited, 254 were accepted and categorized into 9 themes. These were further refined to the top 25 prioritized questions. Among these, the higher ranked questions will be considered as ‘important’ to drive future initiatives in the low dose radiation protection community. These included questions on the ability of AOPs to delineate responses across different levels of biological organization, and how AOPs could be applied to address research questions on radiation quality, doses or dose-rates, exposure time patterns and deliveries, and uncertainties in low dose/dose-rate effects. A better understanding of these concepts is required to support the use of the AOP framework in radiation risk assessment. <b><i>Conclusion</i></b><i>:</i> Through dissemination of these results and considerations on next steps, the JTG will address select priority questions to advance the development and use of AOPs in the radiation protection community. The major themes observed will be discussed in the context of their relevance to areas of research that support the system of radiation protection.