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The Evolution of Best Practices for the Development and Description of AOPs Suitable to Support Regulatory Application of New Approach Methodologies
Citation:
Villeneuve, D. The Evolution of Best Practices for the Development and Description of AOPs Suitable to Support Regulatory Application of New Approach Methodologies. Society of Toxicology, 62nd Annual Meeting, Nashville, TN, March 19 - 23, 2023. https://doi.org/10.23645/epacomptox.24749478
Impact/Purpose:
Adverse Outcome Pathways (AOPs) provide convenient integrating organizational constructs for assembling and evaluating mechanistic information at different levels of biological organization in a form designed to support a range of regulatory applications. These include the development of integrated approaches to testing and assessment (IATA) and chemical specific assessment to inform predictive inference and mode of action (MOA) analysis. There has been much experience gained in the ten years since the introduction of the AOP development program by the Organization for Economic Co-operation and Development (OECD)—and in the more than five years since a similar course was offered to Society of Toxicology members. Guidance and an associated Handbook supports developers in the description and evaluation of AOPs in a user-friendly wiki of a publicly available Knowledgebase. The program also includes formal peer engagement in the form of coaching for AOP development, external scientific review, and endorsement by parent OECD committees on testing and assessment. Increasing experience in AOP development and application contributes to continuing evolution of the methodology to meet regulatory need. Areas of evolution include the more systematic consideration of supporting data, extension of qualitative weight of evidence considerations to quantitation of key event relationships, and increasing experience in application. This course builds on training developed within the OECD program on best practices of documentation and assessment, including updates to the AOP-Wiki to encourage the use of common ontologies and delineation of literature analysis strategies and factors that modulate quantitative relationships. Consideration of disease pathways associated with non-chemical stressors contributes also to expansion of evolving knowledge. The course includes practical demonstration of the wiki/Knowledgebase, tips for developers and assessors, and development and application examples. Each presentation will cover different aspects of AOP development and application and, using real examples, offer a comprehensive overall learning experience. Following the course, participants will be familiar with the most recent developments in best practices to support AOP development, assessment, and application, as well as evolving supportive resources within the OECD AOP program.
Description:
This presentation addresses current principles and best practices for developing AOPs and associated networks and quantitation of KERs. The speaker will discuss recent developments in an electronic version of the AOP Development Handbook, using specific examples drawn from the experience of “learning by doing” over the past several years, as AOP development and application has expended and diversified. Evolved guidance in the Handbook includes that related to stressors, domains of applicability and modulating factors. Additional developments to be addressed include recommendations to increase consistency in descriptions of common key events, such as those reflecting inflammatory processes. Examples of applications in the environmental domain illustrating best practice will be presented.
URLs/Downloads:
DOI: The Evolution of Best Practices for the Development and Description of AOPs Suitable to Support Regulatory Application of New Approach Methodologies
PRESENTATION.PDF (PDF, NA pp, 1552.247 KB, about PDF)