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Pathway-based predictive approaches for assessing the ecological rffects of per- and polyfluoroalkyl substances (PFAS)
Citation:
Ankley, G. Pathway-based predictive approaches for assessing the ecological rffects of per- and polyfluoroalkyl substances (PFAS). SETAC North America Focused Topic, Durham, NC, August 12 - 15, 2019.
Impact/Purpose:
Some PFAS are widespread environmental contaminants that could produce adverse effects in fish and wildlife; however, there currently are not sufficient data to make definitive statements as to ecological risk. This talk will present a conceptual strategy for assessing the potential hazard of PFAS in the environment using pathway-based predictive tools.
Description:
Emphasis to date concerning PFAS has been mostly on human health, but there is growing realization that these chemicals also are of substantial concern in terms of potential ecological effects. While some ecotoxicity data exist for high-visibility PFAS like PFOS and PFOA, there is a lack of information suitable for assessing ecological risks of the great majority of PFAS that might enter the environment. Further, most testing that has been done with PFAS has been limited to just a few fish and (mostly aquatic) invertebrate species. Given the large number of PFAS and biological species of potential ecological concern, it is not reasonable to expect that knowledge gaps can be adequately addressed through collection of empirical data from whole animal tests. This is not a challenge limited to PFAS. There is an increasing awareness in regulatory toxicology of the need to develop and implement time/cost-effective predictive approaches to support chemical safety assessment. These predictive approaches feature generation of data from tools such as computational models, pathway-based in vitro systems (including high-throughput assays), and short-term in vivo tests with molecular/biochemical endpoints indicative of perturbation of biological pathways/processes of concern. While these types of tools can produce response data more efficiently and rapidly than conventional whole-animal tests, there remains the task of translating this mechanistic information into apical endpoints (survival, growth, reproduction) meaningful to risk assessors/managers. To help address this translation challenge the adverse outcome pathway (AOP) concept was proposed about a decade ago. The AOP framework provides a transparent depiction of casual linkages between initial chemical perturbation of a biological system (the molecular initiating event) and subsequent measurable changes at progressively higher levels of biological organization (key events), that ultimately lead to an adverse outcome in individuals or populations. This presentation will describe how mechanistic data developed and evaluated in the context of the AOP framework can help address key knowledge gaps in assessing the ecological effects of PFAS, including lack of substantive in vivo toxicity data for most PFAS structures of concern, and comparatively little information concerning cross-species susceptibility/sensitivity to the chemicals.