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A closer look at the AOP framework: Review, steps forward and new chances

OpenTox Euro Conference 2020 Session 12

Regulatory Toxicology encompasses the collection, processing and evaluation of epidemiological as well as experimental toxicology data to permit toxicologically based decisions directed towards the protection of health against harmful effects of chemical substances. In regulatory toxicology, an Adverse Outcome Pathway (AOP) is a conceptual construct that portrays existing knowledge concerning the linkage between a direct molecular initiating event and an adverse outcome at a biological level of organization relevant to risk assessment. Efforts are underway to transform regulatory toxicology and chemical safety assessment from a largely empirical science based on direct observation of apical toxicity outcomes in whole organism toxicity tests to a predictive one in which outcomes and risk are inferred from accumulated mechanistic understanding. The AOP Framework provides a systematic approach for organizing knowledge that may support such inference.

The AOP Framework was introduced in 2010, and it is time to take stock of what was achieved and what needs to be done next: This session will feature two talks and two posters covering exactly that:

  • The European Commission, in collaboration with the OECD, has commissioned a study to retrospectively and prospectively analyse the AOP Framework's past, present and future in terms of its suitability to achieve the ultimate goal of better regulatory decisions. The study also delivered actionable recommendations and suggestions to increase the uptake of the AOP Framework in the relevant stakeholder communities. The study author Annamaria Carusi (Stonehaven Consulting) will give a presentation about her findings.
  • Based on the study recommendations, the AOP Knowledge Base will undergo significant changes. Before a complete overhaul, quick wins are already being implemented in the current version. A poster presentation by Travis Karschnik (US-EPA) will show these changes.
  • AOPs can be useful far beyond the toxicology domain. Stressors triggering a Molecular Initiating Event are not only chemicals, but also nanomaterials, radiation – and viruses. The European Commission has therefore started the CIAO project, which stands for “Modelling the pathogenesis of COVID-19 using the AOP Framework”. CIAO aims at compiling AOPs and an AOP network describing the COVID-19 disease, which can act as an interdisciplinary entry point for scientists to get a quick overview of the current status of COVID-19 knowledge. Penny Nymark (Karolinska Institute) will present the project.