Report of the 1st and 2nd Mystery of Reactive Oxygen Species Conferences

Abstract

336sient ROS play an important role in the defense mechanism of immune cells and redox signaling, whereas prolonged ROS elevation is involved in disease development and progression.With global progress in the AOP development field, multiple, slightly nuanced KEs related to ROS have been created in the AOP-Wiki 2 . Many of these KEs are highly similar and largely redundant, which has catalyzed a need to create harmonized consensus KEs on ROS that can be shared in a modular fashion between closely related pathways and networks.To address this need, a consortium of ROS and AOP experts has been formed to discuss the "Mystery of ROS" and develop consensus KEs for this field. This meeting report summarizes initial efforts of the "Mystery of ROS" consortium to harmonize the ROS-related KEs currently available in the AOP-Wiki. The two new modular KEs reflect discussion from the group relating to the effects of ROS presenting a "double-edged sword" by describing the concepts of "up-regulation of ROS" and "diminished protective response." Summary of the discussions in the consortiumThe international online conferences on the Mystery of ROS took place on May 31, 2021 and October 8, 2021. At the first conference on Mystery of ROS (I), a brief introduction of the ROS collaboration was followed by eight presentations, which are listed in Table 1.

Application of AOPs to assist regulatory assessment of chemical risks – Case studies, needs and recommendations

“…Increasing the communication and understanding between the communities of AOP developers and (potential) AOP users, and having a better overview of concrete examples of the successful application of AOPs in chemical RA, would help to overcome the obstacles in adopting AOPs for regulatory purposes. In that context, various activities have been organized within the European Partnership Human Biomonitoring for Europe, HBM4EU ( https://www.hbm4eu.eu/ ), the Eurion Cluster ( https://eurion-cluster.eu/ ), the United States Environmental Protection Agency (US EPA) ( https://www.epa.gov/ ), the OECD Working Party on Hazard Assessment (WPHA), Working Party on Exposure Assessment (WPEA) project, EU Horizon 2020 projects EuroMix ( https://www.euromixproject.eu/ ) and EU-ToxRisk ( https://www.eu-toxrisk.eu/ ), ASPIS cluster ( https://aspis-cluster.eu/ ) or the Mystery of ROS consortium ( Tanabe et al, 2022a , 2022b ). These initiatives also organized workshops ( Hoffmann, 2022 ; Paini et al, 2022 ) or OECD webinars on AOPs ( https://www.oecd.org/chemicalsafety/testing/webinars-on-testing-and-assessment-methodologies.htm ) .…”

Report of the 3rd and 4th Mystery of Reactive Oxygen Species Conference

“…The interconnected function of reactive oxygen species (ROS) in the adverse outcome pathway (AOP) framework is being discussed in an international consortium, the Mystery of ROS (MoR). At the MoR I and II conferences in 2021, the consortium created harmonized key events (KEs) on ROS (Tanabe et al, 2022a). Continuing discussions are focused on refining the description of ROS-related KEs in the AOP framework, terminologies, the mechanistic understanding of ROS production by endogenous and exogenous stimuli, and the stress responses associated with ROS.…”

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

“…One of the difficulties in the field of ROS research is the use of terminology whose meaning is interpreted differently in the different areas of expertise. To overcome the problems, the Mystery of ROS, an international consortium for creating harmonized Key Events (KEs) on ROS in the Adverse Outcome Pathway (AOP) framework has been established ( Tanabe et al, 2022 ). This review aims to provide some guidance on the definition of the harmonized KEs on ROS in the AOP framework.…”