AQuantitative Source-to-Outcome Case Study To Demonstratethe Integration of Human Health and Ecological End Points Using theAggregate Exposure Pathway and Adverse Outcome Pathway Frameworks

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...