Adverse outcome pathway (AOP) development and evaluation
Citation:
Edwards, S., A. Terron, K. Sullivan, Dan Villeneuve, B. Meek, C. Yauk, AND G. Maxwell. Adverse outcome pathway (AOP) development and evaluation. Society of Toxicology Meeting and ToxExpo, New Orleans, LO, March 13 - 17, 2016.
Impact/Purpose:
Not applicable
Description:
The Adverse Outcome Pathway provides a construct for assembling mechanistic information at different levels of biological organization in a form designed to support regulatory decision making. In particular, it frames the link between molecular and cellular events that can be measured in high throughput toxicity testing and the organism or population-level events that are commonly relevant in defining risk. Recognizing the importance of this emerging framework, the Organisation for Economic Co-operation and Development (OECD) launched a program to support the development, documentation and consideration of AOPs by the international community in 2012 (http://www.oecd.org/chemicalsafety/testing/adverse-outcome-pathways-molecular-screening-and-toxicogenomics.htm). In 2014, a handbook (https://aopkb.org/common/AOP_Handbook.pdf) was developed to guide users in the documentation and evaluation of AOPs and their entry into an official knowledgebase. The handbook draws on longstanding experience in consideration of mechanistic data (e.g., mode of action analysis) to inform risk assessment. To further assist users, a training program was developed by members of the OECD Extended Advisory Group to teach users the basic principles of AOP development and the best practices as outlined in the OECD AOP handbook. Training sessions began in early 2015, and this course will provide training for interested SOT scientists. Following this course, all participants will be familiar with the core principles of AOP development and assessment and the OECD efforts to support this effort. They will also know how the OECD guidance for AOP development has been implemented in the Wiki module of the AOP Knowledgebase. They will learn how to assemble and evaluate the evidence supporting the AOPs using established best practices from Mode of Action analysis. To reinforce the concepts, they will participate in a live demo where an AOP is developed from a training case study with their assistance and entered into the AOP-Wiki. The value of AOP development will be highlighted using the skin sensitization AOP, which was endorsed by the OECD in 2012 (http://www.oecd.org/officialdocuments/publicdisplaydocumentpdf/?cote=env/jm/mono%282012%2910/part1&doclanguage=en).