The integration of the adverse outcome pathway framework to radiation risk assessment

Abstract

Background

A large body of radiobiological data has been generated over the past century using in vitro, animal and epidemiological models. This information represents global efforts to understand the mechanistic basis of radiation-induced health effects. However, it has been difficult to effectively integrate this data to derive meaningful information for refining the guidance on chronic, low dose radiation exposure for workers and the public.

Methods

To increase our understanding of radiation risks and the biological processes that contribute to those risks, a paradigm shift is needed that will enable integration of information across levels of biological organization from a ‘stressor’ centric to an ‘adverse outcome’ approach to risk assessment. In chemical and ecological toxicity, a framework has been developed that captures available biologically-based knowledge in the literature and links it to outcomes of relevance to chemical toxicity, resulting in an adverse outcome pathway (AOP).

Results

In this paper, we discuss the AOP concept, how it can be applied to the radiation field, and our vision for the next steps. For the approach to be successful, the radiation research community will need to work collaboratively to vet the vast amount of literature and harness the data in a systematic manner for incorporation into a framework based on the AOP approach.

Conclusion

We anticipate that AOPs could be adopted as a method to synthesize current available information to facilitate the identification of knowledge gaps, better co-ordinate research and qualitatively and quantitatively link key events to an adverse outcome. This can further assist in identifying biomarkers relevant to radiation exposures, refining risk from co-exposures and understanding critical events at the molecular, cellular, tissue, organ and whole animal level related to low dose/dose-rate exposures.

Keywords:

• Adverse outcome pathway framework
• radiation risk assessment
• linear no threshold
• key events
• adverse outcome

Acknowledgements

The authors are grateful to Isaf Al-Nabulsi, Carole Yauk, Sami Qutob and Ruth Wilkins for critical review of the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Notes on contributors

Vinita Chauhan

Vinita Chauhan is a research scientist at Health Canada, Ottawa Ontario, Canada. DS is a program manager with the Department of Energy, Germantown, MD, US and DC is a technical executive with Electrical Power Research Institute, Charlotte, NC, US. DS contributed to this work prior to joining the US Department of Energy (DOE). Her contributions are solely from her own subject matter expertise and do not express the views of DOE or imply in any way DOE supported program funding or directions.