Application of the Aggregate Exposure Pathway and Adverse Outcome Pathway frameworks to advance cumulative risk assessment by integrating human health and ecological endpoints
Citation:
Hines, D., S. Edwards, R. Conolly, AND A. Jarabek. Application of the Aggregate Exposure Pathway and Adverse Outcome Pathway frameworks to advance cumulative risk assessment by integrating human health and ecological endpoints. Society of Toxicology, san antonio, Tx, March 11 - 15, 2018.
Impact/Purpose:
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.
Description:
Evaluating risk of adverse outcomes from chemical exposure is essential for understanding the impacts of environmental contaminants. While human health outcomes are of primary concern and are often the focus of risk assessments, important non-human species are also exposed to contaminants and may be adversely affected at different concentrations than humans. This work uses a case study approach to demonstrate how cumulative risk assessment (CRA) for multiple outcomes spanning human health and ecological endpoints can be advanced by linking the Aggregate Exposure Pathway (AEP) and Adverse Outcome Pathway (AOP) frameworks to integrate data across species. AEPs describe the movement of a contaminant through key exposure states in the environment from source to exposure of a target human or non-human receptor. AOPs analogously describe the biological mechanism of action for a chemical from the molecular initiating event (MIE), through key events, to an adverse outcome. These frameworks are linked by target site exposures, which describe the amount of contaminant that is relevant to the MIE in the species exposed. The joint AEP-AOP construct provides a mechanistic approach for linking environmental contaminants to risk of adverse outcomes in multiple species through multiple routes of exposure, and can be used to characterize species vulnerability, highlight knowledge gaps in exposure and toxicity data, and facilitate community-based CRAs. We present an application of this concept for perchlorate, a well-documented inhibitor of iodide uptake into the thyroid, to demonstrate how these frameworks can facilitate data integration across species. Perchlorate toxicity models and data were evaluated from eight species of vertebrates and four species of invertebrates, and we observed a dose-response concordance across species in the AOP. Results suggested that frogs (Xenopus laevis) and rats (Rattus sp.) may be more sensitive to perchlorate exposure than other organisms, but also highlighted knowledge gaps for some groups such as fish (Danio rerio and Gambusia holbrooki). Furthermore, the combined AEP-AOP structure highlighted relevant exposure routes for these organisms, which were largely through ingestion. The methods presented in this mechanistic framework 1) organize data, 2) highlight data gaps, and 3) facilitate analyses and visualizations of risk. 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.