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|Title:||How Adverse Outcome Pathways Can Aid the Development and Use of Computational Prediction Models for Regulatory Toxicology|
|Authors:||WITTWEHR Clemens; ALADJOV Hristo; ANKLEY Gerald; BYRNE Hugh J.; DE KNECHT Joop; HEINZLE Elmar; KLAMBAUER Günter; LANDESMANN Brigitte; LUIJTEN Mirjam; MACKAY Cameron; MAXWELL Gavin; MEEK Bette; PAINI ALICIA; PERKINS Edward; SOBANSKI Tomasz; VILLENEUVE Dan; WATERS Katrina; WHELAN Maurice|
|Citation:||TOXICOLOGICAL SCIENCES p. 1-11|
|Publisher:||OXFORD UNIV PRESS|
|Type:||Articles in periodicals and books|
|Abstract:||Efforts are underway to transform regulatory toxicology and chemical safety assessment from a largely empirical science based on direct observation of apical toxicity outcomes in whole organism toxicity tests to a predictive one in which outcomes and risk are inferred from accumulated mechanistic understanding. The adverse outcome pathway (AOP) framework has emerged as a systematic approach for organizing knowledge that supports such inference. We argue that this systematic organization of knowledge can inform and help direct the design and development of computational prediction models that can further enhance the utility of mechanistic and in silico data for chemical safety assessment. Examples of AOP-informed model development and its application to the assessment of chemicals for skin sensitization and multiple modes of endocrine disruption are provided. 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 described. Finally, a proposal for actively engaging the modeling community in AOP-informed computational model development is made. The contents serve as a vision for how AOPs can be leveraged to facilitate development of computational prediction models needed to support the next generation of chemical safety assessment.|
|JRC Directorate:||Health, Consumers and Reference Materials|
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