A high-level overview of the OECD AOP Development Programme

Abstract

Background

The Organisation for Economic Co-operation and Development (OECD), through its Chemical Safety Programme, is delegated to ensure the safety of humans and wildlife from harmful toxicants. To support these needs, initiatives to increase the efficiency of hazard identification and risk management are under way. Amongst these, the adverse outcome pathway (AOP) approach integrates information on biological knowledge and test methodologies (both established and new) to support regulatory decision making. AOPs collate biological knowledge from different sources, assess lines of evidence through considerations of causality, and undergo rigorous peer-review before being subsequently endorsed by the OECD. It is envisioned that the OECD AOP Development Programme will transform the toxicity testing paradigm by leveraging the strengths of mechanistic and modeling based approaches and enhance the utility of high throughput screening assays. Since its launch, in 2012, the AOP Development Programme has matured with a greater number of AOPs endorsed, and the attraction of new scientific disciplines (e.g. the radiation field). Recently, a radiation and chemical (Rad/Chem) AOP Joint Topical Group has been formed by the OECD Nuclear Energy Agency High-level Group on Low-dose Research (HLG-LDR) under the auspices of the Committee on Radiological Protection and Public Health (CRPPH). The topical group will work to evolve the development and use of the AOP framework in radiation research and regulation. As part of these efforts, the group will bring awareness and understanding on the program, as it has matured from the chemical perspective. In this context, this paper provides the radiation community with a high-level overview of the OECD AOP Development Programme, including examples of application using knowledge gleaned from the field of chemical toxicology, and their work toward regulatory implementation.

Conclusion

Although the drivers for developing AOPs in chemical sector differ from that of the radiation field, the principles and transparency of the approach can benefit both scientific disciplines. By providing perspectives and an understanding of the evolution of the OECD AOP Development Programme including case examples and work toward quantitative AOP development, it may motivate the expansion and implementation of AOPs in the radiation field.

Keywords:

• OECD
• adverse outcome pathway
• molecular initiating event
• key event
• adverse outcome
• hazard assessment
• risk communication
• risk management

Acknowledgments

The authors are grateful for the support of Drs. Nathalie Delrue (OECD), Magdalini Sachana (OECD), Carole Yauk (University of Ottawa, Canada), Ngoc Vuong (Health Canada, Canada), and Sami Qutob (Health Canada, Canada) for a critical review of the manuscript. The opinions expressed and arguments employed herein are those of the authors and do not necessarily reflect the official views of the Organisation for Economic Co-operation and Development, the OECD Nuclear Energy Agency or the governments of their member countries.

Disclosure statement

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

Additional information

Funding

This work is partially funded by grants from the Research Council of Norway (RCN) through its Center of Excellence (CoE) funding scheme [Project No. 223268], the RCN project 268294 MixRisk and NIVAs Computational Toxicology Program, NCTP (www.niva.no/nctp).

Notes on contributors

Vinita Chauhan

Vinita Chauhan, Ph.D, is a Senior Research Scientist at the Consumer and Clinical Radiation Protection Bureau of Health Canada. She is a Canadian delegate of the High-level group on low-dose research (HLG-LDR) and Extended Advisory Group on Molecular Screening and Toxicogenomics (EAGMST) of the OECD. She co-chairs the HLG-LDR Rad/Chem AOP Joint Topical Group and is the co-founder of Canadian Organization of Health Effects from Radiation Exposure (COHERE) initiative.

Nobuyuki Hamada

Nobuyuki Hamada, RT, Ph.D, is a Senior Research Scientist at CRIEPI and a Visiting Professor at Hiroshima University Research Institute for Radiation Biology and Medicine. He serves on ICRP Task Groups 102, 111 and 119, NCRP PAC 1, OECD/NEA/CRPPH/HLG-LDR/Rad/Chem AOP Joint Topical Group, IRPA Task Group on Tissue Reactions, and Consultation Committee on AOP development for space flight health outcomes (Canadian project).

Ruth Wilkins

Ruth C. Wilkins, Ph.D, is a Research Scientist at the Consumer and Clinical Radiation Protection Bureau of Health Canada and the Chief of the Ionizing Radiation Health Sciences Division. She graduated with a Ph.D in Medical Physics from Carleton University and has been employed at Health Canada since 1996. She is an Adjunct Professor and lecturer in Radiobiology in the Department of Physics at Carleton University and the alternative representative of Canada to the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR).

Jacqueline Garnier-Laplace

Jacqueline Garnier-Laplace, Ph.D, a Senior Radiation Protection Specialist, is on secondment from the French Institute of Radiation Protection and Nuclear Safety (IRSN, France) to the Scientific Secretary of the Committee on Radiological Protection and Public Health, and of the NEA HLG-LDR. Previously, she headed Radiation Protection research at France’s IRSN. She served as scientific secretary of ICRP Committee 1 from 2017 to 2021, and is currently serving on Committee 4 with the same function.

Dominique Laurier

Dominique Laurier, Ph.D, is a Senior Epidemiologist and deputy director of health at the Health and Environment Division of the French Institute for Radiation Protection and Nuclear Safety (IRSN). He is Chair of Committee 1 of the International Commission on Radiological Protection (ICRP), French representative to UNSCEAR, and Chair of the NEA HLG-LDR.

Danielle Beaton

Danielle Beaton, Ph.D, is a Research Scientist in the Environment and Waste Technologies Branch within the Isotopes, Radiobiology and Environment Directorate at Canadian Nuclear Laboratories (CNL). She assists the co-chairs for the NEA HLG-LDR Rad/Chem AOP Joint Topical Group and through this group contributes to the High-level group on low-dose research (HLG-LDR).

Knut Erik Tollefsen

Knut Erik Tollefsen, Ph.D, is a Chief Scientist at the Norwegian Institute for Water Research (NIVA) and an Adjunct professor at the Norwegian University of Life Sciences (NMBU). He is a Norwegian delegate of the HLG-LDR and OECD EAGMST, co-chairs the HLG-LDR Rad/Chem AOP Joint Topical Group, co-ordinates NIVA’s Computational Toxicology Program, NCTP (www.niva.no/nctp) and is an OECD EAGMST registered AOP coach.