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Bringing Together Scientific Disciplines for Collaborative Undertakings: A Vision for Advancing the Adverse Outcome Pathway Framework

Chauhan V; Wilkins R; Beaton D; Sachana M; Delrue N; Yauk, C; O’Brien J; Marchetti F; Halappanavar S; Boyd M; Villeneuve D; Barton-Maclaren T S; Meek B; Anghel C; Heghes C; Barber CG; Perkins E; Leblanc J; Burtt J; Laakso H; Laurier D; Lazo T; Whelan M; Thomas Russel; Cool D;


Background: 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 disciplines. Organizing these data in a meaningful way to support risk assessment has been a significant challenge. To address this and other challenges in modernizing chemical health risk assessment, the Organisation for Economic Cooperation and Development (OECD) formalized the Adverse Outcome Pathway (AOP) framework, an approach to consolidate knowledge into measurable key events (KEs) at various levels of biological organization causally linked to disease based on the weight of scientific evidence ( Currently, AOPs have been considered predominantly in chemical safety but are relevant to radiation. In this context, the Nuclear Energy Agency’s (NEA’s) High-Level Group on Low Dose Research (HLG-LDR) is working to improve research co-ordination, including radiological research with chemical research, identify synergies between the fields and to avoid duplication of efforts and resource investments. To this end, a virtual workshop was held on October 7-8th, 2020 with experts from the OECD AOP Programme together with the radiation and chemical research/regulation communities. The workshop, was a coordinated effort of Health Canada, the Electric Power Research Institute (EPRI), and the Nuclear Energy Agency (NEA). The AOP approach was discussed including key issues to fully embrace its value and catalyze implementation in areas of radiation risk assessment.

Conclusion: A joint chemical and radiological expert group was proposed as a means to encourage cooperation between risk assessors and an initial vision was discussed on a path forward. A global survey was suggested as a way to identify priority health outcomes of regulatory interest for AOP development. Multidisciplinary teams were needed to address the challenge of producing the appropriate data for risk assessments. Data management and machine learning tools were highlighted as a way to progress from weight of evidence to computational causal inference.