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An application of the Aggregate Exposure Pathway (AEP) and Adverse Outcome Pathway (AOP) frameworks to mechanistically integrate data sources across multiple species into cumulative risk assessment (CRA)
Hines, D., S. Edwards, R. Conolly, AND A. Jarabek. An application of the Aggregate Exposure Pathway (AEP) and Adverse Outcome Pathway (AOP) frameworks to mechanistically integrate data sources across multiple species into cumulative risk assessment (CRA). International Symposium on Systematic Review and Meta-Analysis of Laboratory Animal Studies, Durham, North Carolina, August 24 - 25, 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.
Toxicologists use dose-response data from both in vivo and in vitro experiments to evaluate the effects of chemical contaminants on organisms. Cumulative risk assessments (CRAs) consider the effects of multiple stressors on multiple endpoints, and utilize environmental exposure and toxicological data to estimate the likelihood of adverse outcomes (AOs) that can span human and non-human species. Meta-analyses can provide the data integration necessary for CRAs, but mechanism-based approaches to cross-species data integration are lacking due to differences among organisms that include exposure scenarios, physiological traits, experimental design and measurement techniques, endpoint characterization, and terminology. This work develops methods for the integration of data into CRAs from various studies that investigate toxicological effects in different species. We use the Aggregate Exposure Pathway (AEP) and Adverse Outcome Pathway (AOP) frameworks to organize data and provide a common platform to evaluate risk. We present a case study focused on perchlorate to demonstrate how this technique can facilitate integration of data sources from multiple taxa into CRAs through a meta-analysis spanning eight vertebrate and four invertebrate species. The AEP illustrated exposure differences among species, while we observed a dose-response concordance across species in the AOP. Results suggested that endpoints in frogs and rats (Xenopus laevis and Rattus sp., respectively) may be more sensitive to perchlorate exposure than AOs in other organisms, but also highlighted knowledge gaps for groups such as fish (Danio rerio and Gambusia holbrooki). This mechanistic framework 1) organizes data, 2) highlights data gaps, and 3) facilitates analyses and visualizations of risk. Connecting data with key events in AOPs across species illustrates the need for a common ontology to facilitate systematic review of data sources. 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.
Record Details:Record Type: DOCUMENT (PRESENTATION/SLIDE)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY
INTEGRATED SYSTEMS TOXICOLOGY DIVISION
GENETIC AND CELLULAR TOXICOLOGY BRANCH