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Reactive Oxygen Species in the Adverse Outcome Pathway Framework: Toward Creation of Harmonized Consensus Key Events. 2022
Shihori Tanabe, and
Jason O'Brien, and
Knut Erik Tollefsen, and
Youngjun Kim, and
Vinita Chauhan, and
Carole Yauk, and
Elizabeth Huliganga, and
Ruthann A Rudel, and
Jennifer E Kay, and
Jessica S Helm, and
Danielle Beaton, and
Julija Filipovska, and
Iva Sovadinova, and
Natalia Garcia-Reyero, and
Angela Mally, and
Sarah Søs Poulsen, and
Nathalie Delrue, and
Ellen Fritsche, and
Karsta Luettich, and
Cinzia La Rocca, and
Hasmik Yepiskoposyan, and
Jördis Klose, and
Pernille Høgh Danielsen, and
Maranda Esterhuizen, and
Nicklas Raun Jacobsen, and
Ulla Vogel, and
Timothy W Gant, and
Ian Choi, and
Rex FitzGerald
Division of Risk Assessment, Center for Biological Safety and Research, National Institute of Health Sciences, Kawasaki, Japan.
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.
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