Reactive Oxygen Species in the Adverse Outcome Pathway Framework: Toward Creation of Harmonized Consensus Key Events

Abstract

Reactive Oxygen Species in the Adverse Outcome Pathway Framework: Toward Creation of Harmonized Consensus Key Events Tanabe S, O'Brien J, Tollefsen KE, Kim Y, Chauhan V, Yauk C, Huliganga E, Rudel RA, Kay JE, Helm JS, Beaton D, Filipovska J, Sovadinova I, Garcia-Reyero N, Mally A, Poulsen SS, Delrue N, Fritsche E, Luettich K, La Rocca C, Yepiskoposyan H, Klose J, Danielsen PH, Esterhuizen M, Jacobsen NR, Vogel U, Gant TW, Choi I, FitzGerald R. Reactive Oxygen Species in the Adverse Outcome Pathway Framework: Toward Creation of Harmonized Consensus Key Events. Front Toxicol. 2022 Jul 6;4:887135. doi: 10.3389/ftox.2022.887135. 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. Open access paper: frontiersin.org

AI evidence extraction

Main findings

This review discusses how reactive oxygen and nitrogen species (RONS) may function as key events within adverse outcome pathways (AOPs) or modulate events along the AOP continuum. It summarizes workshop discussions on RONS in disease and adverse effects associated with stressors including nanoparticles, chemicals, and ionizing and non-ionizing radiation, and provides guidance toward harmonized terminology for AOP developers.

Outcomes measured

• Reactive oxygen species (ROS) / reactive nitrogen species (RNS) / reactive oxygen and nitrogen species (RONS) as key events in adverse outcome pathways (AOPs)
• Harmonized terminology and consensus key events for AOP development related to RONS

Limitations

• No specific exposure parameters (e.g., frequency, SAR, duration) for non-ionizing radiation are provided in the abstract
• No specific health endpoints or quantitative effect estimates are reported in the abstract (conceptual/terminology-focused review)

Suggested hubs

• who-icnirp (0.2)
  Mentions non-ionizing radiation in a broad toxicology/AOP context, but no specific guideline or policy focus is stated.

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    "outcomes": [
        "Reactive oxygen species (ROS) / reactive nitrogen species (RNS) / reactive oxygen and nitrogen species (RONS) as key events in adverse outcome pathways (AOPs)",
        "Harmonized terminology and consensus key events for AOP development related to RONS"
    ],
    "main_findings": "This review discusses how reactive oxygen and nitrogen species (RONS) may function as key events within adverse outcome pathways (AOPs) or modulate events along the AOP continuum. It summarizes workshop discussions on RONS in disease and adverse effects associated with stressors including nanoparticles, chemicals, and ionizing and non-ionizing radiation, and provides guidance toward harmonized terminology for AOP developers.",
    "effect_direction": "unclear",
    "limitations": [
        "No specific exposure parameters (e.g., frequency, SAR, duration) for non-ionizing radiation are provided in the abstract",
        "No specific health endpoints or quantitative effect estimates are reported in the abstract (conceptual/terminology-focused review)"
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    "evidence_strength": "insufficient",
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    "peer_reviewed_likely": "yes",
    "keywords": [
        "reactive oxygen species",
        "reactive nitrogen species",
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        "nanoparticles",
        "chemicals",
        "ionizing radiation",
        "non-ionizing radiation",
        "workshops"
    ],
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            "reason": "Mentions non-ionizing radiation in a broad toxicology/AOP context, but no specific guideline or policy focus is stated."
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}

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