Frontiers in Toxicology (Jul 2022)
Reactive Oxygen Species in the Adverse Outcome Pathway Framework: Toward Creation of Harmonized Consensus Key Events
- Shihori Tanabe,
- Jason O’Brien,
- Knut Erik Tollefsen,
- Knut Erik Tollefsen,
- Knut Erik Tollefsen,
- Youngjun Kim,
- Vinita Chauhan,
- Carole Yauk,
- Elizabeth Huliganga,
- Ruthann A. Rudel,
- Jennifer E. Kay,
- Jessica S. Helm,
- Danielle Beaton,
- Julija Filipovska,
- Iva Sovadinova,
- Natalia Garcia-Reyero,
- Angela Mally,
- Sarah Søs Poulsen,
- Nathalie Delrue,
- Ellen Fritsche,
- Karsta Luettich,
- Cinzia La Rocca,
- Hasmik Yepiskoposyan,
- Jördis Klose,
- Pernille Høgh Danielsen,
- Maranda Esterhuizen,
- Nicklas Raun Jacobsen,
- Ulla Vogel,
- Timothy W. Gant,
- Ian Choi,
- Rex FitzGerald
Affiliations
- Shihori Tanabe
- Division of Risk Assessment, Center for Biological Safety and Research, National Institute of Health Sciences, Kawasaki, Japan
- Jason O’Brien
- Wildlife Toxicology Research Section, Environment and Climate Change Canada, Toronto, ON, Canada
- Knut Erik Tollefsen
- Norwegian Institute for Water Research (NIVA), Oslo, Norway
- Knut Erik Tollefsen
- Norwegian University of Life Sciences (NMBU), Ås, Norway
- Knut Erik Tollefsen
- Centre for Environmental Radioactivity, Norwegian University of Life Sciences (NMBU), Ås, Norway
- Youngjun Kim
- Korea Institute of Science and Technology (KIST) Europe, Saarbrücken, Germany
- Vinita Chauhan
- Health Canada, Ottawa, ON, Canada
- Carole Yauk
- University of Ottawa, Ottawa, ON, Canada
- Elizabeth Huliganga
- University of Ottawa, Ottawa, ON, Canada
- Ruthann A. Rudel
- Silent Spring Institute, Newton, MA, United States
- Jennifer E. Kay
- Silent Spring Institute, Newton, MA, United States
- Jessica S. Helm
- Silent Spring Institute, Newton, MA, United States
- Danielle Beaton
- 0Canadian Nuclear Laboratories, Chalk River, ON, Canada
- Julija Filipovska
- 1Independent Researcher, Ohrid, North Macedonia
- Iva Sovadinova
- 2RECETOX, Faculty of Science, Masaryk University, Brno, Czech Republic
- Natalia Garcia-Reyero
- 3U.S. Army Engineer Research and Development Center (ERDC), Vicksburg, MS, United States
- Angela Mally
- 4Department of Toxicology, University of Würzburg, Würzburg, Germany
- Sarah Søs Poulsen
- 5National Research Centre for the Working Environment, Copenhagen, Denmark
- Nathalie Delrue
- 6Organisation for Economic Co-operation and Development (OECD), Paris, France
- Ellen Fritsche
- 7Group of Alternative Method Development for Environmental Toxicity Testing, IUF—Leibniz-Research Institute for Environmental Medicine, Duesseldorf, Germany
- Karsta Luettich
- 8Philip Morris International R&D, Philip Morris Products SA, Neuchatel, Switzerland
- Cinzia La Rocca
- 9Center for Gender-specific Medicine, Italian National Institute of Health, Rome, Italy
- Hasmik Yepiskoposyan
- 8Philip Morris International R&D, Philip Morris Products SA, Neuchatel, Switzerland
- Jördis Klose
- 7Group of Alternative Method Development for Environmental Toxicity Testing, IUF—Leibniz-Research Institute for Environmental Medicine, Duesseldorf, Germany
- Pernille Høgh Danielsen
- 5National Research Centre for the Working Environment, Copenhagen, Denmark
- Maranda Esterhuizen
- 0University of Helsinki, Ecosystems and Environment Research Programme, Faculty of Biological and Environmental Sciences, Lahti, Finland, and Helsinki Institute of Sustainability Science (HELSUS), Helsinki, Finland
- Nicklas Raun Jacobsen
- 5National Research Centre for the Working Environment, Copenhagen, Denmark
- Ulla Vogel
- 5National Research Centre for the Working Environment, Copenhagen, Denmark
- Timothy W. Gant
- 1UK Health Security Agency, Public Health England, London, United Kingdom
- Ian Choi
- Korea Institute of Science and Technology (KIST) Europe, Saarbrücken, Germany
- Rex FitzGerald
- 2Universities of Basel and Geneva, Basel, Switzerland
- DOI
- https://doi.org/10.3389/ftox.2022.887135
- Journal volume & issue
-
Vol. 4
Abstract
Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are formed as a result of natural cellular processes, intracellular signaling, or as adverse responses associated with diseases or exposure to oxidizing chemical and non-chemical stressors. The action of ROS and RNS, collectively referred to as reactive oxygen and nitrogen species (RONS), has recently become highly relevant in a number of adverse outcome pathways (AOPs) that capture, organize, evaluate and portray causal relationships pertinent to adversity or disease progression. RONS can potentially act as a key event (KE) in the cascade of responses leading to an adverse outcome (AO) within such AOPs, but are also known to modulate responses of events along the AOP continuum without being an AOP event itself. A substantial discussion has therefore been undertaken in a series of workshops named “Mystery or ROS” to elucidate the role of RONS in disease and adverse effects associated with exposure to stressors such as nanoparticles, chemical, and ionizing and non-ionizing radiation. This review introduces the background for RONS production, reflects on the direct and indirect effects of RONS, addresses the diversity of terminology used in different fields of research, and provides guidance for developing a harmonized approach for defining a common event terminology within the AOP developer community.
Keywords
- adverse outcome pathway (AOP)
- oxidative stress
- reactive nitrogen species (RNS)
- disease
- reactive oxygen species (ROS)
