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Ensuring long-term utility of the AOP framework and knowledge for multiple stakeholders
Citation:
Ankley, G., A. Carusi, M. Davies, G. De Grandis, B. Escher, G. Hodges, K. Leung, M. Whelan, AND C. Willett. Ensuring long-term utility of the AOP framework and knowledge for multiple stakeholders. SETAC Europe, Rome, ITALY, May 13 - 17, 2018.
Impact/Purpose:
The adverse outcome pathway (AOP) framework serves as a knowledge assembly and communication tool to facilitate translation of mechanistic data into adverse apical outcomes meaningful to chemical risk assessment. Although initially designed for ecotoxicology applications, the framework has also received extensive attention relative to chemical safety assessments for human health. Moreover, as the AOP concept and associated knowledgebases have evolved, it has become recognized that the potential stakeholder community is broader than scientists and regulators directly involved in chemical safety assessment. For example, the application of AOP-based thinking for addressing biomedical challenges has become increasingly evident. This presentation will identify various stakeholders who currently, or could potentially, benefit from application of the AOP framework and knowledge to specific needs, and describes challenges and strategies to effectively engaging these stakeholders. We also present a “roadmap” on how to maintain a viable, sustainable network to support AOP stakeholders, including recommendations for governance and coordination of AOP development and knowledge dissemination in a multi-stakeholder consortium.
Description:
1.Introduction There is a need to increase the development and implementation of predictive approaches to support chemical safety assessment. These predictive approaches feature generation of data from tools such as computational models, pathway-based in vitro assays, and short-term in vivo tests with molecular/biochemical endpoints. While these types of tools can produce effects data more efficiently and rapidly than conventional whole-animal tests, there remains the challenge of translating this mechanistic information into the apical endpoints meaningful to risk assessors/managers. To help address this translation challenge, the adverse outcome pathway (AOP) concept was proposed by Ankley et al. (2010). The AOP framework provides a transparent depiction of casual linkages between initial chemical perturbation of a biological system and subsequent changes at progressively higher levels of biological organization that ultimately lead to an adverse outcome in individuals or populations. The AOP concept has attracted significant attention in terms of its application both to research and regulation. For example, in 2012 the Organization for Economic Cooperation and Development (OECD) initiated an effort to support development and use of AOPs to facilitate internationally harmonized chemical safety assessments. This has resulted in formalized guidelines for deriving and describing AOPs, including weight-of-evidence approaches for their evaluation, and an open-source AOP knowledgebase (AOP-KB) for developing and archiving AOP information. This presentation will provide a strategic vision to help ensure that the AOP framework can realize its full potential for multiple stakeholder groups. We detail the unique features/qualities of the AOP framework and AOP-KB, and go on to profile a variety of stakeholders, describing how they stand to benefit from the further development of the AOP framework and its application to problem solving. Our analysis also includes consideration of obstacles to a full, long-term engagement of the stakeholder community. Finally, we will provide recommendations regarding the steps that need to be taken to address these challenges, to ensure that the AOP framework/knowledge endure as a sustainable resource. 2. Materials and Methods This analysis stems from a Pellston workshop held April 2-6, 2017 in Cornwall, ON, Canada. The workshop was coordinated by the Society of Environmental Toxicology and Chemistry (SETAC), and financially supported by multiple governmental and business organizations. Pellston workshops typically assemble invited experts on a given topic, who are charged with defining and proposing paths forward to address challenge(s) in the topic area of interest. This Pellston workshop focused on a number of issues associated with AOP science and implementation, including the development of a “roadmap” to promote sustainable use of the concept. Specific needs addressed at the workshop were identified through a global horizon scanning effort that gathered input from scientists and risk assessors/managers from throughout the world (LaLone et al. 2017). In all, 41 experts representing government, academia and business, from nine different countries in North America, Europe and Asia participated in the workshop. 3. Results and Discussion The AOP approach cannot meet its full promise without a critical mass of stakeholders, representing different disciplines/sectors, engaging it in different ways. There is a wide range of existing and potential stakeholders in the framework, ranging from toxicologists and chemical risk assessors to scientists involved in drug development. For our analysis we profiled seven areas and four groups of stakeholders who are already engaged (or could easily become more engaged) with the AOP framework, outlining why they are (or would be) interested in AOPs and how they cou