Adverse outcome pathways (AOPs) for radiation-induced reproductive effects in environmental species: state of science and identification of a consensus AOP network

Abstract

Background

Reproductive effects of ionizing radiation in organisms have been observed under laboratory and field conditions. Such assessments often rely on associations between exposure and effects, and thus lacking a detailed mechanistic understanding of causality between effects occurring at different levels of biological organization. The Adverse Outcome Pathway (AOP), a conceptual knowledge framework to capture, organize, evaluate and visualize the scientific knowledge of relevant toxicological effects, has the potential to evaluate the causal relationships between molecular, cellular, individual, and population effects. This paper presents the first development of a set of consensus AOPs for reproductive effects of ionizing radiation in wildlife. This work was performed by a group of experts formed during a workshop organized jointly by the Multidisciplinary European Low Dose Initiative (MELODI) and the European Radioecology Alliance (ALLIANCE) associations to present the AOP approach and tools. The work presents a series of taxon-specific case studies that were used to identify relevant empirical evidence, identify common AOP components and propose a set of consensus AOPs that could be organized into an AOP network with broader taxonomic applicability.

Conclusion

Expert consultation led to the identification of key biological events and description of causal linkages between ionizing radiation, reproductive impairment and reduction in population fitness. The study characterized the knowledge domain of taxon-specific AOPs, identified knowledge gaps pertinent to reproductive-relevant AOP development and reflected on how AOPs could assist applications in radiation (radioecological) research, environmental health assessment, and radiological protection. Future advancement and consolidation of the AOPs is planned to include structured weight of evidence considerations, formalized review and critical assessment of the empirical evidence prior to formal submission and review by the OECD sponsored AOP development program.

Keywords:

• Adverse outcome pathway
• ionizing radiation
• reproduction
• hazard assessment
• risk assessment
• radiosensitivity
• non-human biota
• wildlife

Correction Statement

This article has been corrected with minor changes. These changes do not impact the academic content of the article.

Acknowledgments

The authors are grateful to the benefit from the dedicated workshop co-organized by the European Multidisciplinary Low Dose Initiative (MELODI) and the European Alliance in Radioecology (ALLIANCE) from 12 to 15 April (2021) to initiate the discussions at the origin of this work.

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 [RCN Project no. 223268], NIVAs Computational Toxicology Program, NCTP (www.niva.no/nctp, RCN Project no. 160016) and Euratom research and training programme 2019–2020 under grant agreement No 900009 (RadoNorm).

Notes on contributors

Knut Erik Tollefsen

Knut Erik Tollefsen, Ph.D., is a Chief Scientist at the Norwegian Institute for Water Research (NIVA), an Adjunct professor at the Norwegian University of Life Sciences (NMBU) and is a principal investigator and research area co-lead in the Center for Environmental Radioactivity (CERAD CoE). He is also the 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 a registered OECD AOP coach.

Frédéric Alonzo

Frédéric Alonzo, Ph.D., is a researcher at the French Institute of Radiological Protection and Nuclear Safety (IRSN), in the laboratory of ecotoxicology of radionuclides (LECO), where he investigates and model effects of ionizing radiation and radionuclides in aquatic invertebrate species and contributes to various ALLIANCE and UN IAEA programmes.

Nicholas A. Beresford

Nicholas A. Beresford, Ph.D., is the Environmental Contaminants Group Leader at the UK Center for Ecology & Hydrology and Honorary Professor at the University of Salford. He has co-ordinated IAEA working groups on radiological environmental protection and contributes to ICRP activities in this field.

Dag Anders Brede

Dag Anders Brede, Ph.D., is a professor of Radioecology at the Faculty of Environmental Sciences and Natural Resource Management/Norwegian University of Life Sciences (NMBU). He is a principal investigator at the Center for Environmental Radioactivity (CERAD CoE) and co-lead on CERAD research on biological effects of ionizing radiation and species radiosensitivity.

Elizabeth Dufourcq-Sekatcheff

Elizabeth Dufourcq Sekatcheff, Ph.D. candidate in Environmental Sciences/Radioecology at the French Institute of Radiological Protection and Nuclear Safety (IRSN).

Rodolphe Gilbin

Rodolphe Gilbin, Ph.D. in ecotoxicology, leads the research team on the transfers and effects of radionuclides in ecosystems (SRTE) at the French Institute of Radiological Protection and Nuclear Safety (IRSN). He is involved int the Board of Directors of the European Radioecology Alliance and European research projects in Radioecology.

Nele Horemans

Nele Horemans, Ph.D., leads the research group Biosphere Impact Studies at the Belgian Nuclear Research Center (SCK CEN). Additionally, she is guest docent at the Center of Environmental sciences at Hasselt University (Belgium) and within the radioecology platform ALLIANCE she leads the working group on transgenerational effects and species sensitivity to radiation.

Selma Hurem

Selma Hurem, Ph.D., is an associate professor of food toxicology at the Faculty of Veterinary Medicine/Norwegian University of Life Sciences (NMBU). She is a principal investigator in the Center for Environmental Radioactivity (CERAD CoE) for biological effects of ionizing radiation and other environmental contaminants at different levels of biological organization in zebrafish and other model organisms.

Patrick Laloi

Patrick Laloi, Ph.D., HdR in molecular genetics, leads a Laboratory dealing with radioecology and ecotoxicology of radionuclides (LECO) at the French Institute of Radiological Protection and Nuclear Safety (IRSN).

Erica Maremonti

Erica Maremonti, Ph.D. in Environmental Sciences/Radioecology is a post-doctoral researcher at the Center for Environmental Radioactivity (CERAD), Norwegian University of Life Sciences (NMBU), where she investigates effects of ionizing radiation and other environmental stressors at different levels of biological organization in different species and model organisms.

Deborah Oughton

Deborah Oughton, Ph.D., is a professor of nuclear/environmental chemistry at Norwegian University of Life Sciences (NMBU), and director of the Center for Environmental Radioactivity (CERAD CoE). She has worked on the impacts of ionizing radiation on non-human species since the late 1990s, contributing to IAEA, ICRP, and IUR programmes.

Olivier Simon

Olivier Simon, Ph.D. in radiobiology, is a researcher at the French Institute of Radiological Protection and Nuclear Safety (IRSN), in a laboratory dealing with radioecology and ecotoxicology of radionuclides (LECO). Expertise about reprotoxicity in fish after multigenerational irradiation.

You Song

You Song, Ph.D. is a senior research scientist in ecotoxicology at Norwegian Institute for Water Research (NIVA). He is an expert in predictive ecotoxicology, radioecology and molecular biology. He has substantial experience in the assessment of low-dose effects of ionizing and non-ionizing radiation on fish and crustaceans. He is a registered AOP coach at OECD and has developed more than 30 AOPs.

Michael D. Wood

Michael D. Wood, Ph.D., is professor of applied ecology and Director of the Environmental Research & Innovation Center at the University of Salford. He is Chartered Radiation Protection Professional, Council Member and Trustee of the Society for Radiological Protection and a long-standing contributor to various UN IAEA programmes.

Li Xie

Li Xie, Ph.D. in radioecology, is a post-doctoral researcher at the Norwegian Institute for Water research (NIVA), and a guest at Center for Environmental Radioactivity (CERAD), Norwegian University of Life Sciences (NMBU). He investigates the single and combined effects of ionizing and non-ionizing radiations on aquatic primary producers and invertebrates.

Sandrine Frelon

Sandrine Frelon, Ph.D. in radiobiology, is a researcher at the French Institute of Radiological Protection and Nuclear Safety (IRSN), in a laboratory dealing with radioecology and ecotoxicology of radionuclides (LECO). Expertise about multi-elemental analysis and biochemistry of adverse effects after exposure of organisms (chronic/acute).