Developing Adverse Outcome Pathways to support radioecological risk assessment: Challenges and insights.

Environmental pollution associated with long term effects, especially in the case of ionizing radiation, poses significant risks to wildlife, necessitating a more nuanced approach to Ecological Risk Assessment (ERA). In radioecology, current methods, as outlined by the International Commission on Radiological Protection (ICRP), focus primarily on exposure and individual/population-level effects, often both suffering a lack of ecological realism due to the nature of data used, and, sidelining a big amount of critical non-individual effects such as sub-individual one like genotoxicity. This review aims to address these gaps by suggesting the integration of New Approach Methods (NAMs) and the Adverse Outcome Pathway (AOP) framework in the field of radioecology. NAMs encompass innovative techniques, such as in silico and in vitro methodologies, that can provide predictive insights without relying solely on traditional animal testing. The AOP framework, developed by the Organization for Economic Cooperation and Development (OECD), structures effects data into a sequence of causally linked events, enabling a clearer understanding of how molecular changes lead to adverse ecological outcomes. In the first section of the review, we explore the challenges of applying AOPs within radioecology, including the complexities of modelling realistic exposure scenarios, the temporal dynamics of effects, and the impacts of multiple stressors. The second section highlights the potential and the application of some NAMs within an AOP framework to contribute improving risk assessment methodologies (in species realism issue and the use of sub-individual data). This part also offers other potential solutions to increase the number of data to be used in ERA as well as their ecological realism, through the use of AOP framework with relevant biological scales and ecological endpoints still uninvestigated in such way. In conclusion, leveraging NAMs and AOPs is much valuable for bridging molecular data and ecological implications, thereby advancing regulatory practices in radioecology and ensuring more comprehensive protection of ecosystems from radiological hazards.