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Advancing the Adverse Outcome Pathway Framework - an International Horizon Scanning Approach
Citation:
LaLone, C., G. Ankley, S. Belanger, M. Embry, G. Hodges, D. Knapen, S. Munn, E. Perkins, M. Rudd, Dan Villeneuve, M. Whelan, C. Willett, X. Zhang, AND M. Hecker. Advancing the Adverse Outcome Pathway Framework - an International Horizon Scanning Approach. SOCIETY OF ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY JOURNAL. Society of Environmental Toxicology and Chemistry, Pensacola, FL, 36(6):1411-1421, (2017).
Impact/Purpose:
The article provides a summary of the output from a global ‘Horizon Scanning’ (question solicitation) Exercise that aimed to identify challenges or limitations that must be addressed to realize the full potential of the AOP framework in research and regulatory decision making. A subsequent expert ranking exercise of the 340 questions submitted, led to the development of key initiatives for advancing the AOP framework. This paper also serves as a platform to answers FAQs to aid in eliminating common misperceptions and allow for clarification of AOP topics. Additionally, AOP resources were compiled and provided to increase awareness of the AOP framework and present tools and training material that can assist in AOP development and collaboration.
Description:
The ability of scientists to conduct whole organism toxicity tests to understand chemical safety has been significantly outpaced by the rapid synthesis of new chemicals. Therefore, to increase efficiencies in chemical risk assessment, scientists are turning to mechanistic-based studies, making greater use of in vitro and in silico methods, to screen for potential environmental and human health hazards. A framework 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). A number of international activities have focused on AOP development and plausible applications to regulatory decision-making. These interactions have prompted dialog between research scientists and regulatory communities to consider how best to use the AOP framework in risk assessment. While expert-facilitated discussions have been instrumental in moving the science of AOPs forward, it was recognized that a survey of the broader scientific community would aid in identifying shortcomings and guiding future initiatives for the AOP framework. To that end, a ?‘Horizon Scanning’ exercise was conducted to solicit questions from the global scientific and regulatory communities concerning the challenges or limitations that must be addressed to realize the full potential of the AOP framework in research and regulatory decision making. The majority of questions received fell into broad topic areas including AOP networks, quantitative AOPs, collaboration and communication on AOPs, AOP discovery and development, chemical and cross-species extrapolation, exposure/ADME considerations, and AOP application. An expert ranking exercise was then conducted to identify the most important questions for each category. These questions were then used to develop four broad themes to inform and guide future AOP research and regulatory initiatives. In addition, frequently asked questions (FAQs) were identified and addressed by experts in the field. Answers to FAQs will aid in eliminating, or encouraging further discussions about, common misperceptions and allow for clarification of AOP topics. The need for clarification occurred with surprising frequency, indicating that improvements are needed in communicating the AOP framework among the scientific and regulatory communities. Overall, the ?‘Horizon Scanning’ effort brought together the global scientific community to guide the direction of future initiatives and identify key questions surrounding the AOP framework.
