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Analysis of the Developmental Toxicity Profile of Per- and Polyfluoroalkyl Substances (PFAS) Using a Larval Zebrafish Assay
Citation:
Britton, K., R. Judson, K. Jarema, J. Olin, B. Hill, B. Knapp, M. Lowery, M. Feshuk, J. Brown, AND S. Padilla. Analysis of the Developmental Toxicity Profile of Per- and Polyfluoroalkyl Substances (PFAS) Using a Larval Zebrafish Assay. Carolinas SETAC 2024 Annual Meeting, Boone, NC, April 14 - 16, 2024. https://doi.org/10.23645/epacomptox.25757805
Impact/Purpose:
Presentation to Carolinas SETAC 2024 Annual Meeting
Description:
Per- and polyfluoroalkyl substances (PFAS) are compounds found in many consumer and industrial products with ubiquitous spread in environmental matrices. While there is evidence that some PFAS, notably perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS), cause developmental toxicity in mammals, the vast majority of PFAS have not been studied regarding their developmental toxicity potential. Our goal was to use zebrafish data to fill this knowledge gap and paint a clearer picture of the overall pattern that many of these PFAS have on development in vertebrates. To assess this, we used a larval zebrafish, medium-throughput assay to conduct a dose-response study with 182 unique chemicals in the EPA PFAS chemical library. Embryos were collected the day of fertilization (0 days post fertilization [dpf]) and exposed to either dimethyl sulfoxide (vehicle, 0.4% v/v), or one of the PFAS (n=6 embryos/chemical/concentration; ≤ 100 µM; 8 concentrations per chemical). At 6 dpf, two independent observers, blinded to the treatment conditions, graded developmental landmarks (endpoints) for each larva (e.g., mortality, hatching, swim bladder inflation, edema, abnormal spine/tail, and cranial-facial abnormalities). Of the 182 PFAS tested, 53 (29%) produced developmental toxicity commonly seen as mortality, edema, or uninflated swim bladders. Interestingly, while PFOS was developmentally toxic to the zebrafish embryos with a benchmark concentration (BMC) of 7.5 µM, perfluorooctanesulfonamide (PFOSA) was the most potent with a BMC of 0.26 µM, followed by ((perfluorooctyl)ethyl)phosphonic acid (BMC = 0.58 µM), N-methylperfluorooctane sulfonamide (BMC = 0.70 µM) and perfluorohexane sulfonamide (BMC =1.45 µM). Therefore, both mammals and zebrafish have exhibited toxicity after developmental exposure to PFOS, but importantly, the developmental toxicity profile for these other sulfonamide-containing PFAS is largely unexplored in mammals. These observed effects in zebrafish may further inform the toxicity profile of these chemicals in mammals. This abstract does not reflect USEPA policy.
URLs/Downloads:
DOI: Analysis of the Developmental Toxicity Profile of Per- and Polyfluoroalkyl Substances (PFAS) Using a Larval Zebrafish Assay
KBRITTON_POSTER FOR CSETAC PFAS 4-10-24.PDF (PDF, NA pp, 435.423 KB, about PDF)