Abstract
The adverse outcome pathway (AOP) framework has gained significant international traction as a systematic approach for capturing toxicological knowledge to transparently link mechanistic data to apical endpoints that inform research and regulatory decision-making. While the framework has evolved significantly since its introduction in 2010, it was recognized that a survey of the broader scientific community would be useful in identifying shortcomings and guiding further development. In 2016 we reached out to this community through an international horizon scanning exercise to gather information on key outstanding challenges that must be addressed in order to realize the full potential of the AOP framework. Four key themes emerged from this exercise, which were then addressed by international experts representing industry, government, academia, and non-governmental organizations at a 2017 Society of Environmental Toxicology & Chemistry (SETAC) Pellston(™) Workshop. These themes were 1) AOP networks and their applications; 2) quantitative AOPs (qAOPs) and their applications; 3) regulatory use of the AOP framework; and 4) expanding awareness and acceptance of AOPs to support aspects of predictive toxicology and regulatory decision-making. Herein we provide an overview of the workshop discussions and describe the outcomes and recommendations that emerged to advance the AOP framework. Common themes that spanned the main topics are also presented, and outstanding questions and future needs are discussed. In short, the current momentum of the AOP framework, driven by increased AOP development, publication and interest by regulatory communities, provides an unique opportunity to advance the AOP framework both technically (e.g., via networks and qAOPs) and socially (e.g., by strategic engagement of various stakeholder communities and applications). Such advances were collectively deemed essential for the overall sustainabilitiy of the AOP framework, and are addressed by six companion papers repesenting the products of the Pellston(™) Workshop.