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A Case Study Application of the Aggregate Exposure Pathway (AEP) and Adverse Outcome Pathway (AOP) Frameworks to Facilitate the Integration of Human Health and Ecological End Points for Cumulative Risk Assessment (CRA)
Hines, D., S. Edwards, R. Conolly, AND A. Jarabek. A Case Study Application of the Aggregate Exposure Pathway (AEP) and Adverse Outcome Pathway (AOP) Frameworks to Facilitate the Integration of Human Health and Ecological End Points for Cumulative Risk Assessment (CRA). ENVIRONMENTAL SCIENCE & TECHNOLOGY. American Chemical Society, Washington, DC, 52(2):839-849, (2018).
This paper contributes to efforts in the Human Health Risk Assessment (HHRA) research program to develop approaches that support cross-species data integration into cumulative risk assessment (CRA) (HHRA Task 6.1). More specifically, this work applies modeling techniques to integrate human health and ecological indicators (Subtask 6.1.3). We discuss how the Aggregate Exposer Pathway (AEP) and Adverse Outcome Pathway (AOP) frameworks can be used to organize and evaluate exposure and dose response data across multiple species and endpoints. When combined, these frameworks have the potential to provide an organized construct for considering the available data and informing considerations of the mechanistic determinants of risk across species. Furthermore, this construct can guide the assembly of existing information that might be used to infer possible exposure scenarios or toxicities in cases where direct data are limited or don’t exist. We present a case study focused on an AOP affected by the perchlorate anion (ClO4-) in multiple taxa to demonstrate the potential application of this mechanistic approach for cross-species data integration. We highlight that, when coupled with a similar organization of exposure information using the AEP framework, this technique could provide a mechanism-based approach to CRA, and thereby could inform HHRA risk assessments.
Cumulative risk assessment (CRA) methods promote the use of a conceptual site model (CSM) to apportion exposures and integrate risk from multiple stressors. While CSMs may encompass multiple species, evaluating end points across taxa can be challenging due to data availability and physiological differences among organisms. Adverse outcome pathways (AOPs) describe biological mechanisms leading to adverse outcomes (AOs) by assembling causal pathways with measurable intermediate steps termed key events (KEs), thereby providing a framework for integrating data across species. In this work, we used a case study focused on the perchlorate anion (ClO4-) to highlight the value of the AOP framework for cross-species data integration. Computational models and dose-response data were used to evaluate the effects of ClO4- in 12 species and revealed a dose-response concordance across KEs and taxa. The aggregate exposure pathway (AEP) tracks stressors from sources to the exposures and serves as a complement to the AOP. We discuss how the combined AEP-AOP construct helps to maximize the use of existing data and advances CRA by (1) organizing toxicity and exposure data, (2) providing a mechanistic framework of KEs for integrating data across human health and ecological end points, (3) facilitating cross-species dose-response evaluation, and (4) highlighting data gaps and technical limitations.