This document presents the ICRP's updated vision on “Areas of Research to Support the System of Radiological Protection”, which have been previously published in 2017. It aims to complement the research priorities promoted by other relevant international organisations, with the specificity of placing them in the perspective of the evolution of the System of Radiological Protection. This document contributes to the process launched by ICRP to review and revise the System of Radiological Protection that will update the 2007 General Recommendations in ICRP Publication 103.

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Areas of research to support the system of radiological protection.

The purpose of toxicology is to protect human health and the environment. To support this, the Organisation for Economic Co-operation and Development (OECD), operating via its Extended Advisory Group for Molecular Screening and Toxicogenomics (EAGMST), has been developing the Adverse Outcome Pathway (AOP) approach to consolidate evidence for chemical toxicity spanning multiple levels of biological organization. The knowledge transcribed into AOPs provides a structured framework to transparently organize data, examine the weight of evidence of the AOP, and identify causal relationships between exposure to stressors and adverse effects of regulatory relevance. The AOP framework has undergone substantial maturation in the field of hazard characterization of chemicals over the last decade, and has also recently gained attention from the radiation community as a means to advance the mechanistic understanding of human and ecological health effects from exposure to ionizing radiation at low dose and low dose-rates. To fully exploit the value of such approaches for facilitating risk assessment and management in the field of radiation protection, solicitation of experiences and active cooperation between chemical and radiation communities are needed. As a result, the Radiation and Chemical (Rad/Chem) AOP joint topical group was formed on June 1, 2021 as part of the initiative from the High Level Group on Low Dose Research (HLG-LDR). HLG-LDR is overseen by the OECD Nuclear Energy Agency (NEA) Committee on Radiation Protection and Public Health (CRPPH). The main aims of the joint AOP topical group are to advance the use of AOPs in radiation research and foster broader implementation of AOPs into hazard and risk assessment. With global representation, it serves as a forum to discuss, identify and develop joint initiatives that support research and take on regulatory challenges.The Rad/Chem AOP joint topical group will specifically engage, promote, and implement the use of the AOP framework to: (a) organize and evaluate mechanistic knowledge relevant to the protection of human and ecosystem health from radiation; (b) identify data gaps and research needs pertinent to expanding knowledge of low dose and low dose-rate radiation effects; and (c) demonstrate utility to support risk assessment by developing radiation-relevant case studies. It is envisioned that the Rad/Chem AOP joint topical group will actively liaise with the OECD EAGMST AOP developmental program to collectively advance areas of common interest and, specifically, provide recommendations for harmonization of the AOP framework to accommodate non-chemical stressors, such as radiation. 

https://www.tandfonline.com/doi/pdf/10.1080/09553002.2021.2020363?needAccess=true

Adverse outcome pathway: a path toward better data consolidation and global co-ordination of radiation research

Background Epidemiological studies have indicated that exposure of the heart to doses of ionizing radiation as low as 0.5 Gy increases the risk of cardiac morbidity and mortality with a latency period of decades. The damaging effects of radiation to myocardial and endothelial structures and functions have been confirmed radiobiologically at high dose, but much less are known at low dose. Integration of radiation biology and epidemiology data is a recommended approach to improve the radiation risk assessment process. The adverse outcome pathway (AOP) framework offers a comprehensive tool to compile and translate mechanistic information into pathological endpoints which may be relevant for risk assessment at the different levels of a biological system. Omics technologies enable the generation of large volumes of biological data at various levels of complexity, from molecular pathways to functional organisms. Given the quality and quantity of available data across levels of biology, omics data can be attractive sources of information for use within the AOP framework. It is anticipated that radiation omics studies could improve our understanding of the molecular mechanisms behind the adverse effects of radiation on the cardiovascular system. In this review, we explored the available omics studies on radiation-induced cardiovascular disease (CVD) and their applicability to the proposed AOP for CVD.Results The results of 80 omics studies published on radiation-induced CVD over the past 20 years have been discussed in the context of the AOP of CVD proposed by Chauhan et al. Most of the available omics data on radiation-induced CVD are from proteomics, transcriptomics, and metabolomics, whereas few datasets were available from epigenomics and multi-omics. The omics data presented here show great promise in providing information for several key events (KEs) of the proposed AOP of CVD, particularly oxidative stress, alterations of energy metabolism, extracellular matrix (ECM), and vascular remodeling.Conclusions The omics data presented here shows promise to inform the various levels of the proposed AOP of CVD. However, the data highlight the urgent need of designing omics studies to address the knowledge gap concerning different radiation scenarios, time after exposure, and experimental models. This review presents the evidence to build a qualitative omics-informed AOP and provides views on the potential benefits and challenges in using omics data to assess risk-related outcomes. 

https://www.tandfonline.com/doi/pdf/10.1080/09553002.2022.2110325?needAccess=true

Application of radiation omics in the development of adverse outcome pathway networks: an example of radiation-induced cardiovascular disease

In 2012, the Council of Canadian Academies published the expert panel on integrated testing of pesticide’s report titled: Integrating emerging technologies into chemical safety assessment. This report was prepared for the Government of Canada in response to a request from the Minister of Health and on behalf of the Pest Management Regulatory Agency. It examined the scientific status of the use of integrated testing strategies for the regulatory health risk assessment of pesticides while noting the data-rich/poor dichotomy that exists when comparing pesticide formulations to most industrial chemicals. It also noted that the adoption of integrated approaches to testing and assessment (IATA) strategies may refine and streamline testing of chemicals, as well as improve results in the future. Moreover, the experts expected to see an increase in the use of integrated testing strategies over the next decade, resulting in improved evidence-based decision-making. Subsequent to this report, there has been great advancements in IATA strategies, which includes the incorporation of adverse outcome pathways (AOPs) and new approach methodologies (NAMs). This perspective provides the first Canadian regulatory update on how Health Canada is also advancing the incorporation of alternative, non-animal strategies, using a weight of evidence approach, for the evaluation of pest control products and industrial chemicals. It will include specific initiatives and describe how this work is leading to the creation of next generation risk assessments. It also reflects Health Canada’s commitment towards implementing the 3Rs of animal testing: reduce, refine and replace the need for animal studies, whenever possible.

Canadian Regulatory Perspective on Next Generation Risk Assessments for Pest Control Products and Industrial Chemicals

Abstract Background Studies on human health and ecological effects of ionizing radiation are rapidly evolving as innovative technologies arise and the body of scientific knowledge grows. Structuring this information could effectively support the development of decision making tools and health risk models to complement current system of radiation protection. To this end, the adverse outcome pathway (AOP) approach is being explored as a means to consolidate the most relevant research to identify causation between exposure to a chemical or non-chemical stressor and disease or adverse effect progression. This tool is particularly important for low dose and low dose rate radiation exposures because of the latency and uncertainties in the biological responses at these exposure levels. To progress this aspect, it is essential to build a community of developers, facilitators, risk assessors (in the private sector and in government), policy-makers, and regulators who understand the strengths and weaknesses of, and how to appropriately utilize AOPs for consolidating our knowledge on the impact of low dose ionizing radiation. Through co-ordination with the Organisation of Economic Co-operation and Development (OECD) Nuclear Energy Agency (NEA) High-Level Group on Low-Dose Research (HLG-LDR) and OECD’s AOP Programme, initiatives are under way to demonstrate this approach in radiation research and regulation. Among these, a robust communications strategy and stakeholder engagement will be essential. It will help establish best practices for AOPs in institutional project development and aid in dissemination for more efficient and timely uptake and use of AOPs. In this regard, on June 1, 2021, the Radiation and Chemical (Rad/Chem) AOP Joint Topical Group was formed as part of the initiative from the NEA’s HLG-LDR. The topical group will work to develop a communication and engagement strategy to define the target audiences, establish the clear messages and identify the delivery and engagement platforms. Conclusion The incorporation of the best science and better decision making should motive the radiation protection community to develop, refine and use AOPs, recognizing that their incorporation into radiation health risk assessments is critical for public health and environmental protection in the 21st century.

Establishing a communication and engagement strategy to facilitate the adoption of the adverse outcome pathways in radiation research and regulation

Decades of research to understand the impacts of various types of environmental occupational and medical stressors on human health have produced a vast amount of data across many scientific discipl...

Bringing together scientific disciplines for collaborative undertakings: a vision for advancing the adverse outcome pathway framework

The Linear-No-Threshold (LNT) model predicts a dose-dependent linear increase in cancer risk. This has been supported by biological and epidemiological studies at high-dose exposures. However, at low-doses (LDR ≤ 0.1 Gy), the effects are more elusive and demonstrate a deviation from linearity. In this study, the effects of LDR on the development and progression of mammary cancer in FVB/N-Tg(MMTVneu)202Mul/J mice were investigated. Animals were chronically exposed to total doses of 10, 100, and 2000 mGy via tritiated drinking water, and were assessed at 3.5, 6, and 8 months of age. Results indicated an increased proportion of NK cells in various organs of LDR exposed mice. LDR significantly influenced NK and T cell function and activation, despite diminishing cell proliferation. Notably, the expression of NKG2D receptor on NK cells was dramatically reduced at 3.5 months but was upregulated at later time-points, while the expression of NKG2D ligand followed the opposite trend, with an increase at 3.5 months and a decrease thereafter. No noticeable impact was observed on mammary cancer development, as measured by tumor load. Our results demonstrated that LDR significantly influenced the proportion, proliferation, activation, and function of immune cells. Importantly, to the best of our knowledge, this is the first report demonstrating that LDR modulates the cross-talk between the NKG2D receptor and its ligands.

Holly Laakso

Papers

Bringing together scientific disciplines for collaborative undertakings: a vision for advancing the adverse outcome pathway framework

Effects of Chronic Low-Dose Internal Radiation on Immune-Stimulatory Responses in Mice.