Collaborative efforts are needed among the scientific community to advance the adverse outcome pathway concept in areas of radiation risk assessment

Abstract

Disease prevention and prediction have led to the generation of phenotypically based methods for deriving the limits of safety across toxicological disciplines. In the ionizing radiation field, human data has formed the basis of the linear-no-threshold (LNT) model for risk estimates. However, uncertainties around its accuracy at low doses and low dose-rates have led to passionate debates on its effectiveness to derive radiation risk estimates under these conditions. Concerns arise from the linear extrapolation of data from high doses to low doses, below 0.1 Gy where there is considerable variability in the scientific literature. Efforts to address these controversies have led to a mountain of mechanistic data to improve the understanding of molecular and cellular effects related to phenotypic changes. These data provide fragments of information that have yet to be combined and used effectively to improve modeling, reduce uncertainties, and update radiation protection approaches. This paper suggests a better consolidation of mechanistic research may serve to guide priority research and facilitate translation to risk assessment. An effective approach that may be implemented is the organization of data using the adverse outcome pathway (AOP) framework, a programme that has been launched by the Organization for Economic Cooperation and Development in the chemical toxicology field. The AOP concept has proved beneficial to human health and ecological toxicological fields, demonstrating possibilities for better linkages of mechanistic data to phenotypic effects. A similar approach may be beneficial to the field of radiation research. However, for this to work effectively, collaborative efforts are needed among the scientific communities in the area of AOP development and documentation. Studies will need to be evaluated, re-organized and integrated into AOPs. Here, details of the AOP approach and areas it could support in the radiation field are discussed. In addition, challenges are highlighted and steps to integration are outlined. Organizing studies in this manner will facilitate a better understanding of our current knowledge in the radiation field and help identify areas where more focused work can be undertaken. This will, in turn, allow for improved linkage of mechanistic data to human relevance and better support radiation risk assessments.