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|Title:||Building and Applying Quantitative Adverse Outcome Pathway Models for Chemical Hazard and Risk Assessment|
|Authors:||PERKINS EDWARD; ASHAUER ROMAN; BURGOON LYLE; CONOLLY RORY; LANDESMANN BRIGITTE; MACKAY CAMERON; MURPHY CHERYL; POLLESCH NATHAN; WHEELER JAMES; ZUPANIC ANZE; SCHOLZ STEFAN|
|Citation:||ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY vol. 38 no. 9 p. 1850-1865|
|Type:||Articles in periodicals and books|
|Abstract:||An important goal in toxicology are the development of new ways to increase the speed, accuracy and applicability of chemical hazard and risk assessment approaches. Here we examine how the Adverse Outcome Pathway (AOP) framework can be used to develop pathway based quantitative models useful for regulatory chemical safety assessment. By using AOPs as initial conceptual models and the AOP knowledge base as a source of data on key event relationships, different modeling methods can be applied to develop computational quantitative AOP models (qAOPs) relevant for decision making. A qAOP model may not necessarily have the same structure as the AOP it is based on. Useful AOP modeling methods range from statistical, Bayesian networks, regression, and ordinary differential equations to individual-based and population models and should be chosen according to the problem being addressed and the data available. When using qAOPs for risk assessment, we demonstrate that toxicokinetic models provide linkages between exposure and qAOPs, discuss in vitro to in vivo extrapolation, and extrapolation across species. We discuss best practices for modeling, model building and the necessity for transparent and comprehensive documentation to gain confidence in the use of a model.|
|JRC Directorate:||Health, Consumers and Reference Materials|
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