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Metabolism of per- and polyfluoroalkyl substances (PFAS) in rainbow trout (Oncorhynchus mykiss) using an ex vivo model.
Citation:
Daley, S., J. Serrano, Rick Kolanczyk, AND M. Tapper. Metabolism of per- and polyfluoroalkyl substances (PFAS) in rainbow trout (Oncorhynchus mykiss) using an ex vivo model. Society of Toxicology Annual Meeting and ToxExpo, Nashville, TN, March 19 - 23, 2023. https://doi.org/10.23645/epacomptox.24749319
Impact/Purpose:
This study addresses the environmental and health problem of defining the potential metabolism perfluoroalkylated substances (PFAS) in aquatic species. The current work used an ex vivo rainbow trout liver slice assay to study the metabolism of PFAS. The results from this study provides insight into the fate of different types of PFAS in an aquatic organism giving further context to bioaccumulation, toxicity, and kinetics research. Additionally, these results will contribute to the growing Metapath database of PFAS metabolic pathways.
Description:
Per-and Polyfluoroalkyl Substances (PFAS) are an organic chemical class defined by their carbon-chains bonded with fluorine. PFAS are contaminants of emerging concern (CEC) as well as methodologically challenging chemicals (MCCs). A critical aspect of assessing exposure and effect characterizations is understanding xenobiotic metabolic capabilities. A systematic process for collection and compiling of metabolism map information from across the open literature was developed for entry of data into an existing Metabolic Pathways knowledgebase platform (MetaPath) for building metabolism databases. However, there is limited availability of fish PFAS metabolic pathways, which contributes to inherent uncertainties in ecological risk assessments. The ex vivo rainbow trout liver slice model has proven to be an effective tool to study the metabolic fate of a chemical within rainbow trout (Oncorhynchus mykiss) liver slices. The advantage of ex vivo modeling includes reduced number of live fish needed for testing and maintenance of elevated level of biological matrix complexity. Using slices allows for testing of several different chemicals and time points from one fish liver. In this study, individual liver slices were exposed to PFAS for 72 hours at 11° C in 12 well culture plates. Both incubation media and slices samples were taken at various times and analyzed for parent chemical concentration. For the analysis of chemicals, a method was developed that allows analysis of multiple classes of PFAS using a modified SPE approach combined with a universal LCMS method for both voltile and nonvolatile chemicals including perfluoroalkylcarboxylic acids and fluorotelomer alcohols. This approach allows for the assessment of Phase I metabolism of the chemical and Phase II metabolism screening simultaneously. If loss of parent chemicals was observed, further tests were carried out to identify metabolites. In general, most PFAS chemicals were not metabolized by rainbow trout liver slice tissue. The fluorinated acids (Perfluorobutanoic Acid, Perfluoropentanoic Acid, Perfluorohexanoic Acid, Perfluoroheptanoic Acid, Perfluorooctanoic Acid) and perfluoroalkylcarboxylic acids (4:3 Fluorotelomer carboxylic acid, 6:2 Fluorotelomer carboxylic acid) demonstrated no metabolism of parent chemical. Results from this assay will further contribute to the growing Metapath database of PFAS metabolic pathways as well give further context to bioaccumulation, toxicity, and kinetics research. Disclaimer: The views expressed in this article are those of the authors and do not necessarily reflect the views or policies of the US Environmental Protection Agency. Mention of trade names or commercial products does not constitute endorsement or recommendation for use. Declaration of Interest: All studies reported in this manuscript were supported by the US EPA, Office of Research and Development. The authors report no declaration of interest.
URLs/Downloads:
DOI: Metabolism of per- and polyfluoroalkyl substances (PFAS) in rainbow trout (Oncorhynchus mykiss) using an ex vivo model.
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