S3: Development and Use of Quantitative AOPs to Support Decision Making

Development and Use of Quantitative AOPs to Support Decision Making

S3: Development and Use of Quantitative Adverse Outcome Pathways, OpenTox USA 2017

Edward J Perkins


Army Corps of Engineers Vicksburg, MS


Senior Research Scientist


As events occurring in Adverse Outcome Pathways (AOPs) are causally linked by response-response relationships within a biological pathway to an apical effect of regulatory concern, AOPs form a logical point and potentially valuable resource for development of quantitative models to support decisions on the potential hazards and risks of chemicals. Here we present development of quantitative toxicological models in the context of AOPs. We have developed several different approaches that utilize quantitative AOPs to answer different questions depending on the regulatory need and the amount of  information or concentration/response-response data available.  We will discuss how modeling points of departure for in vitro data or omics data in an AOP context can provide a quantitative assessment of when a pathway has been perturbed leading to an adverse outcome. We will describe how Bayesian networks can be used to rapidly model the likelihood that interaction of a chemical with key events (or in vitro assays) in an AOP network will result in adverse effect using a liver steatosis network. We will also discuss the advantages of developing coupled component models with biological feedback and mechanistic details providing high biological fidelity using aromatase inhibition in fish.