Radiation and Chemical Adverse Outcome Pathway Joint Topical Group (Rad/Chem AOP JTG)

A group of researchers and experts operating under the aegis of the High-Level Group of Low Dose Research, a working party of the Committee on Radiological Protection and Public Health (NEA CRPPH)


Source: Health Canada

AOPs in radiological protection

In recent decades, a wealth of biological information has emerged, delving into how radiation impacts both humans and non-human organisms. This data serves as a valuable addition to the insights gained from epidemiological studies, providing a more robust basis for decisions regarding radiological protection (RP) regulation. Yet, presently, there is a notable absence of unified incorporation of these varied datasets into a comprehensive framework guided by mechanistic knowledge. This integration is pivotal to fully leverage pertinent data and scientific understanding, aiding in radiation hazard and risk assessments while reducing existing uncertainties.

The Adverse Outcome Pathway (AOP) framework established by the Organisation for Economic Co-operation and Development (OECD) is designed to advance hazard and risk assessments with a foundation rooted in evidence and mechanistic understanding. AOPs represent a theoretical construct which defines the progression of a stressor's impact on a biological system across multiple levels of biological organisation originating with its initial interaction known as the molecular initiating event (MIE). This progression unfolds through a sequence of intermediary critical events (KEs) that are causally connected via key event relationships (KERs), culminating in the adverse outcome (AO).

Building AOPs in the area of radiological research serves several purposes, including the ability to:

  • Enhance the synthesis of scientific findings to those most relevant for hazard assessment and support development of risk assessment strategies;
  • Link mechanistic knowledge to physiological changes leading to pathological disorders with relevance to human and wildlife health;
  • Address uncertainties associated with current radiation risk estimates at low doses and dose-rates;
  • Prioritise research endeavours that are of particular significance in the context of radiation protection initiatives;
  • Facilitate co-ordination and co-operation in research undertakings;
  • Identify new and sensitive biomarkers and test assays to efficiently characterise effects along relevant toxicity pathways;
  • Identify commonalities and differences between how fundamentally different stressors affect organisms to inform multiple stressor assessments.
Related topics
  • Radiological protection
  • RAD/CHEM AOP Joint Topical Group

    radchemaop Source: Health Canada

    In June 2021, the NEA Committee on Radiological Protection and Public Health (CRPPH) established the High-Level Group on Low Dose Research (HLG-LDR) Rad/Chem AOP Joint Topical Group (JTG) to investigate that adaptation of AOPs into radiation research, reducing uncertainties in low dose health risks. The JTG aims to champion the use of AOPs in radiation hazard and risk assessment, promoting adoption in research and regulations. 

    The Rad/Chem AOP collaborative group is striving to produce significant outcomes in three main areas: 1) advocating for AOPs; 2) engaging radiation societies and journals; and 3) undertaking AOP development projects. This involves:

    • Enhancing comprehension of adverse effects and health outcomes in both human and non-human species;
    • Demonstrating the benefits of collaborative, comprehensive studies derived from constructing AOPs;
    • Contributing to and advancing the objectives of the OECD AOP Development Programme in relation to non-chemical stressors.

    Work plan 2021-2025




    Horizon style exercise

    Development of a survey that can be distributed to the radiation community to help identify the priority areas that will guide AOP development, identify the Subject Matter Experts, resources, areas for collaborative AOP development.

    Strategy for AOP workshops

    Development of a strategy and organisation of meetings and workshops to support addressing specific AOP challenges.

    Communication and engagement strategy

    Development of an actionable work plan for engaging journals and societies in promoting and reviewing AOPs.  Creating a web presence, infographics and podcasts.

    Building case examples of radiation relevant AOPs

    Case examples of AOP development that cover regulatory questions of interest, how to best capture the data using systematic review and data aggregation tools and other specific considerations relevant to radiation AOP development. 

    Case examples of radiation OMICS-informed AOPs

    Development of a strategy to apply omics data to an AOP relevant to the field of ionising radiation. What tools and methods are needed; consideration and drawbacks.

    Review of AOPs applied to radioecological challenges


    Providing a review of current knowledge of ionising radiation effects, availability of AOPs and challenges associated with application to radioecology. 





    Vinita C. et al. (2022), "Introduction to the special issue on adverse outcome pathways in radiation protection", International Journal of Radiation Biology (Volume 98, Issue 12), DOI: 10.1080/09553002.2022.2123183. This special issue entitled AOPs in Radiation Protection is driven by the increasing global interest in integrating information from radiation biology and epidemiology to enhance the understanding of low-dose radiation health risk assessment. It provides a comprehensive overview of Adverse Outcome Pathways (AOPs), including their origin, the goals of a newly formed topical group, current case examples, and how the radiation field can utilise AOPs to organise knowledge on the biological effects of radiation exposure. 

    Robert S. et al. (2021), "Challenges in the quantification approach to a radiation relevant adverse outcome pathway for lung cancer", International Journal of Radiation Biology, 97:1, 85-101,  DOI: 10.1080/09553002.2020.1820096

    Yang C. et al. (2023), "Comparison of a piecewise structural equation modeling and Bayesian network for de novo construction of a quantitative adverse outcome pathway network", ALTEX - Alternatives to animal experimentation, 40(2), pp. 287–298. DOI: 10.14573/altex.2207113 .This research explores quantifying data within AOPs, it evaluates the benefits and obstacles of quantification, gathering evidence from diverse studies to measure key event links.  

    Vinita C. et al. (2021), "Expert consultation is vital for adverse outcome pathway development", International Journal of Radiation Biology (Volume 97, Issue 11), DOI: 10.1080/09553002.2021.1969466. Experts employ the adverse outcome pathway (AOP) approach to understand how radiation exposure relates to cardiovascular diseases, organising information from molecular changes to adverse outcomes through scientific criteria. The paper stresses the significance of collective expertise in shaping these pathways.

    NEA endorsed AOPs

    Sherman, S. et al. (2023), "Adverse Outcome Pathway on deposition of energy leading to lung cancer", OECD Series on Adverse Outcome Pathways, No. 32, OECD Publishing, Paris, https://doi.org/10.1787/a8f262c2-en.

    The Adverse Outcome Pathway (AOP) for lung cancer describes how the Deposition of Energy (DoE), induced by stressors like radon gas, initiates a chain of events leading to DNA double strand breaks. These breaks, when inaccurately repaired, can cause mutations in crucial genes and chromosomal abnormalities. This disruption can promote unregulated cell proliferation, resulting in hyperplasia in lung epithelial cells and eventually leading to lung cancer. While there is strong evidence supporting this AOP, uncertainties remain, especially concerning the dose-effect relationships of low doses and dose-rates of DoE exposure.

    Educational videos

    OECD AOP training videos 

    AFSA Collaboration training resources

    The online learning series discusses development of the AOP framework, the utilisation of AOP Knowledge Base tools and the AOP Wiki, as well as the process of reviewing and evaluating AOPs. The e-course comprises two modules: the first module covers the overall history of AOPs with an introduction to associated tools, while the second module delves into the detailed exploration of the AOP Knowledge Base and AOP Wiki.

    AOPs in Radiological Protection

    In this informative video, the fundamental principles of Adverse Outcome Pathways (AOPs) are explored, examining their definition, purpose, and the methods for their application in the context of radiation protection. The reasons behind employing AOPs are discussed, their historical evolution, the essential elements required for constructing an AOP, factors to consider in evaluating evidence, and examples of radiation relevant AOPs.