LP-25: the curious case of Adverse Outcome Pathways: the stressor agnostic approach bridging disciplines by embracing evidence from diverse initiating factors

The Adverse Outcome Pathways (AOP) framework emerged in the context of regulatory toxicology toguide an effective paradigm shift towards using relevant, scientifically robust, humane and more efficient, high throughput tools and practices. The framework is operationalised through the following five core principles: (a) AOPs are a pragmatic, mostly linear, representation of key perturbations at different levels of biological organisation. (b) AOPs are stressor agnostic i.e.without prejudice to the identity and even type of stressor triggering a particular (sets of) perturbations; (c) AOPs are modular, as its main building blocks (Key Events – KEs and Key Event Relationships – KERs) can be re-used among AOPs; (d) AOPs are living documents and evolve with knowledge accumulation; (e) Networks of interconnected AOPs, emerging from the application of the previous four principles, are best suited for application to regulatory or research questions. The stressor agnostic principle has made the AOP approach feasible for many other disciplines beyond chemical risk assessment (e.g. biomedicine, nanotechnology, radiation) to use it and its knowledge management tool AOP-Wiki for modelling biological pathways of perturbations initiated by a wide range of complex chemical and non-chemical stressors. Here we present lessons learned from our multidisciplinary crowdsourcing approach to modelling COVID-19 using the AOP approach (www.ciao-covid.net). We highlight the challenges of multidisciplinary approach and adopting a viral stressor into the toxicology-inspired AOP framework. We also extend the considerations to other biological (microbial pesticides and engineered cells-based therapeutics) and physical stressors (radiation). This will help to inform the development of new practical ways to represent chemical and non-chemical stressors within the AOP-Wiki and support the increased uptake of the AOP approach across disciplines.*J Filipovska and LA Clerbaux Contributed equally to this presentation