Source: Health Canada
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:
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:
| Task |
Description |
| 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.
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.
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.
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.
