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A case study to illustrate the utility of the Aggregate Exposure Pathway and Adverse Outcome Pathway frameworks for integrating human health and ecological data into cumulative risk assessment
Hines, D., S. Edwards, R. Conolly, AND A. Jarabek. A case study to illustrate the utility of the Aggregate Exposure Pathway and Adverse Outcome Pathway frameworks for integrating human health and ecological data into cumulative risk assessment. International Society of Exposure Science Annual Meeting, Research Triangle Park, NC, October 15 - 19, 2017.
Chemical risk assessments combine exposure and toxicity data to estimate the likelihood of adverse outcomes for these endpoints, but are rarely conducted in a manner that integrates risk across species due to physiological differences among affected organisms, diversity of endpoints, and the range of relevant exposure mechanisms. This project seeks to integrate human health and ecological endpoints into chemical risk assessment using the Adverse Outcome Pathway (AOP) framework. This framework provides a common platform for integrating human health and ecological endpoints and facilitates simultaneous evaluation of risk in multiple species. The results of this work demonstrate how an AOP-risk construct can facilitate identification of vulnerable species, highlight data gaps and uncertainties, and quantify of risk for multiple outcomes.
Cumulative risk assessment (CRA) methods, which evaluate the risk of multiple adverse outcomes (AOs) from multiple chemicals, promote the use of a conceptual site model (CSM) to integrate risk from relevant stressors. The Adverse Outcome Pathway (AOP) framework can inform these risk assessments by describing biological mechanisms of action for chemicals from molecular initiating events (MIEs), through key events, to AOs. However, AOPs do not consider the exposures that a target organism may encounter. The Aggregate Exposure Pathway (AEP) framework was created to track stressors from the source, through key exposure states, to a target site exposure. Together, the joint AEP-AOP construct can act as a mechanistic, source-to-outcome summary, which can be used as the basis for a CSM. The resulting CSM can allow for consideration of multiple stressors from multiple sources impacting multiple outcomes in multiple species. In this work, we demonstrate how this construct can support the mechanistic integration of human health and ecological endpoints into a CRA. We use a case study of perchlorate, an environmental contaminant that is found in multiple media and affects a clearly identified MIE for AOPs across multiple species, to illustrate the application this approach. Quantitative computational models and dose-response data were used to evaluate responses to perchlorate exposure in eight vertebrates (Homo sapiens, Rattus sp., Oryctolagus cuniculus, Microtus sp., Xenopus laevis, Danio rerio, Gambusia holbrooki, and Collinus virginianus) and four invertebrates (Eisenia foetida, Daphnia magna, Culex quinquefasciatus, and Paronella japonica). The AEP-AOP construct was used to investigate and visualize relative risk among species and highlight data gaps. The views expressed in this abstract are those of the authors and do not necessarily reflect the views or policies of the U.S. Environmental Protection Agency.