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Frameworks for organizing exposure and toxicity data - the Aggregate Exposure Pathway (AEP) and the Adverse Outcome Pathway (AOP)
Citation:
Tan, C. Frameworks for organizing exposure and toxicity data - the Aggregate Exposure Pathway (AEP) and the Adverse Outcome Pathway (AOP). 2017 ISES Annual Meeting, Durham, NC, October 15 - 19, 2017.
Impact/Purpose:
The recent paradigm shift in toxicity testing has occurred due to the recognition that the current in vivo testing methods cannot keep pace with the ever-increasing number of chemicals in commerce. As a result, in vitro toxicity testing methods are instituted to screen thousands of chemicals across hundreds of toxicity pathway endpoints at relatively lower cost and in shorter time. Applying results from these in vitro tests to estimate human or ecological health risks, not just for hazard identification, requires the comparison of the internal exposure in target species with an in vitro point of departure. Thus, it is critical to understand and integrate the following pieces of information: (1) the in vivo biological processes for which these in vitro targets are acting as surrogates; (2) the adverse outcomes of regulatory concerns of which the in vivo endpoints serve as the precursors; (3) the comparison between exposure levels likely to be experienced in a population and the in vitro doses at which bioactivity is observed; and finally (4) accurate estimation of exposure levels in the environment for target species. In the proposed session, organizational frameworks and computational tools that support these various linkages are presented to demonstrate their roles in elucidating the connections between exposure to environmental stressors and adverse outcomes. We hope that the audience will walk away from this session with a better insight on integrating exposure and hazard information into risk assessment with the aid of crowdsourcing efforts for information exchange and computational tools for organizing mechanistic data. The session comprises of three presentations. The first presentation introduces two organizational frameworks for organizing both exposure information and toxicity pathways. Knowledge gleaned from these two framework can then be integrated using quantitative tools to predict potential impact to ecological and public health arise from exposure to environmental chemicals.
Description:
The Adverse Outcome Pathway (AOP) framework organizes existing knowledge regarding a series of biological events, starting with a molecular initiating event (MIE) and ending at an adverse outcome. The AOP framework provides a biological context to interpret in vitro toxicity data; elaboration of prioritization strategies and the development of tiered testing approaches relying on in silico and in vitro tests. The Aggregate Exposure Pathway (AEP) framework organizes exposure data and predictions from multiple sources, starting with a source and ending at a target site of exposure (TSE). The TSE serves as the bridge between the AEP and the AOP, as it describes the state of a stressor at a target site that corresponds to an MIE. Thus, integration of these two frameworks provides a natural linkage from source to outcome. Disclaimer: This abstract has been cleared by the EPA but solely expresses the view of the authors.
