You are here:
Collaborative efforts are needed among the scientific community to advance the adverse outcome pathway concept in areas of radiation risk assessment
Citation:
Chauhan, V., Dan Villeneuve, AND D. Cool. Collaborative efforts are needed among the scientific community to advance the adverse outcome pathway concept in areas of radiation risk assessment. International Journal of Radiation Biology. Taylor & Francis, Inc., Philadelphia, PA, 97(6):815-823, (2021). https://doi.org/10.1080/09553002.2020.1857456
Impact/Purpose:
Radiation-related risk assessment has generally involved extrapolation of acute exposures to high doses of radiation to potential low dose hazards on the basis of the linear-no-threshold model. However, in light of on-going scientific debate about the accuracy of this model, many mechanistic data have been collected to try to better understand the impacts of chronic exposures to low dose radiation. This paper is targeted at members of the radiation risk assessment community challenged with assembling this disparate and widely dispersed experimental and mechanistic data into an improved understanding of the hazards posed by low dose radiation exposure. The AOP framework is proposed as a means to systematically organize and evaluate these data, with a focus on isolating responses that are causally linked to adverse outcomes from those that are simply correlated with exposure, but not necessarily indicative of adverse health impacts. Engaging the low dose radiation risk assessment and research community in the process of AOP development is expected to aid their ability to integrate existing data into more meaningful outputs as well as strategically fill key data gaps, leading to improved understanding of low dose radiation hazards.
Description:
Disease prevention and prediction have led to the generation of phenotypic-based methods for deriving the limits of safety across toxicological disciplines. Efforts are now moving towards an integrated tactic to assessment and testing that leverages mechanistic data to predict downstream apical effects. Generally, animal models are used when calculating risk to humans, and the dose to disease induction is identified for one hazard in isolation of other stressors, under well-defined exposure conditions. 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. The data represents fragments of information that have yet to be combined and used effectively to improve modeling, reduce uncertainties, and update radiation protection approaches. This raises the question of whether there is a better way to consolidate all this mechanistic research and translate it into a useful tool for risk assessment practices. One approach is to organize the data using the adverse outcome pathway (AOP) approach. The concept has proved beneficial to chemical and ecological toxicological fields, demonstrating possibilities for better linkages of mechanistic data to phenotypic effects. 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 vetted, re-organized and integrated into AOPs. This will allow for a better understanding of our current knowledge and help identify areas where more focused work can be undertaken. Through this process, concepts in radiation risk assessment can be modernized.
URLs/Downloads:
DOI: Collaborative efforts are needed among the scientific community to advance the adverse outcome pathway concept in areas of radiation risk assessment