Radiation adverse outcome pathways (AOPs) are on the horizon: advancing radiation protection through an international Horizon-Style exercise

Julie J. Burtt, Julie Leblanc, Kristi Randhawa, Addie Ivanova, Murray A. Rudd, Ruth Wilkins, Edouard I. Azzam, Markus Hecker, Nele Horemans, Hildegarde Vandenhove, Christelle Adam-Guillermin, Olivier Armant, Dmitry Klokov, Karine Audouze, Jan Christian Kaiser, Simone Moertl, Katalin Lumniczky, Ignacia B. Tanaka, Yutaka Yamada, Nobuyuki HamadaIsaf Al-Nabulsi, R. Julian Preston, Simon Bouffler, Kimberly Applegate, Donald Cool, Danielle Beaton, Knut Erik Tollefsen, Jacqueline Garnier-Laplace, Dominique Laurier, Vinita Chauhan*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)


Purpose: 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 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. 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. Materials and methods: The HSE was guided by an international steering committee 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 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. Results: 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. Conclusion: 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.

Original languageEnglish
Pages (from-to)1763-1776
Number of pages14
JournalInternational Journal of Radiation Biology
Issue number12
Publication statusPublished - 2022

Bibliographical note

Funding Information:
The HSE was partially funded through the Canadian Organization on Health Effects from Radiation Exposure (COHERE), through project number R719.2 with the contract number 3000725863 provided by the Canadian Nuclear Safety Commission. The work of KET is partially funded by grants from the Research Council of Norway (RCN) through its Center of Excellence (CoE) funding scheme [Project No. 223268] and NIVAs Computational Toxicology Program, NCTP (www.niva.no/nctp, RCN Project no. 160016). The authors wish to acknowledge the assistance of Annick Laporte (CNSC) and Veronica Grybas (Health Canada) with developing graphics and the Research and Support team at the CNSC. The authors also thank CNSC and Health Canada staff for their valuable insights in reviewing this manuscript.

Publisher Copyright:
© 2022 Copyright of the Crown in Canada. Health Canada.


  • Adverse outcome pathway
  • low dose radiation
  • radiation protection
  • regulatory application
  • risk assessment
  • survey


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