Citation:

Hines, D., S. Edwards, R. Conolly, AND A. Jarabek. Cross-species integration of human health and ecological endpoints into risk assessment using the Aggregate Exposure Pathway and Adverse Outcome Pathway frameworks. Society of Toxicology, Baltimore, MD, March 12 - 16, 2017.

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:

Exposure to environmental contaminants can influence both human health and ecological endpoints. 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 work applies the Aggregate Exposure Pathway (AEP) and Adverse Outcome Pathway (AOP) frameworks to evaluate risks from exposure to a single chemical across multiple endpoints in multiple taxa. We present a case study using perchlorate (ClO4-), a known inhibitor of the sodium-iodide symporter (NIS) that is associated with a well-documented AOP affecting the hypothalamic-pituitary-thyroid axis, to demonstrate how AEPs and AOPs can be linked to provide a source-to-outcome construct for risk assessment in humans, fish, birds, amphibians, terrestrial mammals, terrestrial invertebrates, and aquatic invertebrates. Altered fetal development was examined as a human health endpoint resulting from ClO4- exposure and subsequent NIS inhibition, while decreased fecundity, altered growth, gross anomalies, and mortality were examined as assessment endpoints for non-human species. Reliable environmental exposure data was available for species examined in this study, therefore quantitative modeling of exposure pathways was not necessary for risk assessment and these linkages were represented through a conceptual model. Risk of adverse outcome for each endpoint was evaluated using empirical dose response data, and quantitative physiologically based pharmacokinetic models were used to bridge gaps in AOPs connecting exposure data to risk when necessary. The results demonstrate how an AEP-AOP-risk construct can facilitate identification of vulnerable species, highlight data gaps and uncertainties, and quantify of risk for multiple outcomes. This study provides an initial step toward a formal procedure for the integration of human health and ecological endpoints within risk assessment. The views expressed in this poster are those of the authors and do not necessarily reflect the views or policies of the U.S. Environmental Protection Agency.

Record Details: