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A quantitative source-to-outcome case study to demonstrate the integration of human health and ecological endpoints using the Aggregate Exposure Pathway and Adverse Outcome Pathway frameworks
Citation:
Hines, D., R. Conolly, AND A. Jarabek. A quantitative source-to-outcome case study to demonstrate the integration of human health and ecological endpoints using the Aggregate Exposure Pathway and Adverse Outcome Pathway frameworks. ENVIRONMENTAL SCIENCE & TECHNOLOGY. American Chemical Society, Washington, DC, 53(8):11002-11012, (2019). https://doi.org/10.1021/acs.est.9b04639
Impact/Purpose:
This work expands a previous case study, which focused on integration of toxicity mechanisms using the Adverse Outcome Pathway (AOP) for a data rich chemical (perchlorate anion, ClO4-), and suggested linking this toxicity data to a hypothetical exposure model to demonstrate a quantitative source-to-outcome approach. Here, we extend the AOP component to do that by developing the Aggregate Exposure Pathway component using a fate and transport model to represent the movement of this chemical through a hypothetical wetland. We quantitatively describe external exposure under three different hypothetical contamination scenarios for humans, small mammals, and fishes. We then apply previously published, species-specific Physiologically Based Pharmacokinetic (PBPK) models to link external exposure predictions to internal exposure in these three groups of organisms, and demonstrate how these predictions, along with the integrated AEP and AOP frameworks, can inform a comprehensive source-to-outcome approach to CRA that includes both human health and ecological endpoints together.
Description:
Exposure to environmental contaminants can lead to adverse outcomes in both human and nonhuman receptors. The Aggregate Exposure Pathway (AEP) and Adverse Outcome Pathway (AOP) frameworks can mechanistically inform cumulative risk assessment for human health and ecological end points by linking together environmental transport and transformation, external exposure, toxicokinetics, and toxicodynamics. This work presents a case study of a hypothetical contaminated site to demonstrate a quantitative approach for implementing the AEP framework and linking this framework to AOPs. We construct an AEP transport and transformation model and then quantify external exposure pathways for humans, fishes, and small herbivorous mammals at the hypothetical site. A Monte Carlo approach was used to address parameter variability. Source apportionment was quantified for each species, and published pharmacokinetic models were used to estimate internal target site exposure from external exposures. Published dose-response data for a multispecies AOP network were used to interpret AEP results in the context of species-specific effects. This work demonstrates (1) the construction, analysis, and application of a quantitative AEP model, (2) the utility of AEPs for organizing mechanistic exposure data and highlighting data gaps, and (3) the advantages provided by a source-to-outcome construct for leveraging exposure data and to aid transparency regarding assumptions.
