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Application of the adverse outcome pathway framework - advances and challenges
Citation:
Villeneuve, Dan. Application of the adverse outcome pathway framework - advances and challenges. Society of Toxicology, Arlington, VA, November 19 - 20, 2015.
Impact/Purpose:
not applicable
Description:
The adverse outcome pathway (AOP) framework, while not new in concept, has gained attention in recent years as a set of organizing principles and tools that can help facilitate greater use of mechanistic or pathway-based data in risk assessment and regulatory decision-making. Regulatory application of scientific information organized into AOPs is facilitated through the use of a centralized knowledgebase (aopkb.org), developed around a set of core principles, that systematically and transparently presents weight of evidence supporting qualitative or quantitative inference of potential adverse effects based on pathway perturbation data. Ultimate utility of this knowledgebase now hinges on a number of critical scientific and organizational challenges. First, the AOP knowledgebase must continue to expand in content. Currently containing just over 90 AOPs in various stages of development, the knowledgebase must grow in its depth and breadth of coverage of critical toxicological pathways. This necessitates incentivizing broader engagement from the scientific community. Further, in order to effectively harness the power of the AOP framework’s modular organization to facilitate systems-based AOP network development, ontological conventions that can allow for effective linkage of key events and key event relationships across pathways are needed along with tools and strategies for analyzing those networks. Both advances and challenges facing the AOP framework will be highlighted.