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Role of adverse outcome pathways in developing computational models for regulatory toxicology
Citation:
Ankley, G., C. Wittwehr, H. Aladjov, H. Byrne, J. de Knecht, E. Heinzle, G. Klambauer, B. Landesmann, M. Luijten, C. MacKay, G. Maxwell, M. Meek, A. Paini, E. Perkins, T. Sobansk, Dan Villeneuve, K. Waters, AND M. Whelan. Role of adverse outcome pathways in developing computational models for regulatory toxicology. SETAC North America, Orlando, FL, November 06 - 10, 2016.
Impact/Purpose:
not applicable
Description:
Regulatory toxicology for both human health and the environment increasingly is moving from a sole reliance on direct observation of apical toxicity outcomes in whole organism toxicity tests, to predictive approaches in which unacceptable outcomes and risk are inferred from mechanistic data. The adverse outcome pathway (AOP) framework has emerged as a key tool for organizing and communicating knowledge that supports such inference. In this context, AOPs also could support the systematic organization of knowledge to inform and help direct the design and development of predictive computational models to further enhance the utility of mechanistic data for chemical assessment. An international expert workshop exploring this premise was held in September, 2015 in Ispra, Italy. Outcomes from this workshop featured illustrative case studies of AOP-informed model development and application to the assessment of chemicals for skin sensitization in humans and endocrine disruption in fish. The role of problem formulation, not only as a critical phase of risk assessment, but also as guide for both AOP and complementary model development was elaborated. Finally, a proposal for actively engaging the modeling community in AOP-informed computational model development through crowd-sourced competitions was proposed. This presentation will provide an overview of the workshop outcomes relative to a vision for how AOPs can be leveraged to facilitate development of predictive computational models to help support the next generation of chemical safety assessment.