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Advancing the adverse outcome pathway framework and its applications through a global horizon scanning exercise
Citation:
LaLone, C. AND M. Hecker. Advancing the adverse outcome pathway framework and its applications through a global horizon scanning exercise. To be Presented at Society of Toxicology, Baltimore, MD, March 12 - 16, 2017.
Impact/Purpose:
Not applicable
Description:
Regulatory agencies worldwide are confronted with the challenging task of assessing the risks of thousands of chemicals to protect both human health and the environment. Traditional toxicity testing largely relies on apical endpoints from whole animal studies, which, in addition to ethical concerns, is costly and time prohibitive. As a result, the utility of mechanism-based in silico, in vitro, and in vivo approaches to support chemical safety evaluations have increasingly been explored. An approach that has gained traction for capturing available knowledge describing the linkage between mechanistic data and apical toxicity endpoints, required for regulatory assessments, is the adverse outcome pathway (AOP) framework. A number of international workshops and expert meetings have been held over the past years focusing on the AOP framework and its applications to chemical risk assessment. Although, these interactions have illustrated the necessity of expert guidance in moving the science of AOPs and their applications forward, there is also the recognition that a broader survey of the scientific community could be useful in guiding future initiatives in the AOP arena. To that end, a Horizon Scanning exercise was conducted to solicit questions from the global scientific community concerning the challenges or limitations that must be addressed in order to realize the full potential of the AOP framework in research and regulatory decision making. Over a 4 month question solicitation period, 334 questions were collected from 158 global submissions to an online survey, with respondents self-identifying as 35% academia, 35% government, 20% industry, and 5% non-government organizations. The questions were separated into seven broad topic areas including, AOP networks, quantitative AOPs, collaboration and communication on AOPs, AOP discovery and development, extrapolation, exposure/ADME considerations, and AOP application. A ranking exercise was then conducted to identify the top 10 questions for each category. It is anticipated that ranked questions will be useful in directing future AOP research and regulatory initiatives.