Citation:

Gaballah, S., A. Swank, T. Catron, J. McCord, M. Strynar, J. Sobus, E. Hines, C. Vogs, AND T. Tal. Exposure to PFOS, PFHxS, or PFHxA, but not GenX, ADONA, PFOA, or Nafion BP1 Elicits Developmental Neurotoxicity in Larval Zebrafish. Traingle Zebrafish Symposium, Durham, NC, May 14, 2018.

Impact/Purpose:

Numerous studies have identified negative neurodevelopmental effects of structurally related polyfluoroalkyl substances (PFAS) like perfluorooctane sulfonic acid (PFOS) or perfluorooctanoic acid (PFOA). Legacy PFAS have therefore been replaced with shorter carbon chain and polyfluoroether compounds like GenX, 4,8-dioxa-3H-perfluorononanoate (ADONA), perfluorohexanoic acid (PFHxA), and potassium perfluorohexane-1-sulfonate (PFHxS). EPA scientists have identified GenX in drinking water sources in North Carolina. There is currently no published in vivo data on the developmental toxicity of GenX. This abstract describes a study that compared the toxicity of GenX to well-studied compounds like PFOS and PFOA and less well-studied but more structurally similar perfluorinated compounds like PFHxS and PFHxA using zebrafish as a model organism. Specifically, developmental toxicity and locmotor activity, a functional readout of developmental neurotoxicity, were used. We found that exposure to test compounds containing a sulfonic acid moiety including PFOS and PFHxS provoked developmental toxicity characterized by failed swim bladder inflation and pronounced curved body axis. We also found that developmental exposure to PFOS, PFHxS, or PFHxA, but not GenX, ADONA, or PFOA elicited hyperactivity, a functional readout of developmental neurotoxicity, in larval zebrafish. Overall, these data support the use of multiple zebrafish assays to rapidly assess the toxicity of emerging environmental contaminants like GenX.

Description:

Exposure to per- and poly-fluoroalkyl substances (PFAS) like perfluorooctane sulfonic acid (PFOS) or perfluorooctanoic acid (PFOA) are associated with developmental toxicity, neurotoxicity, and carcinogenesis. Legacy PFAS have therefore been replaced with shorter carbon chain and polyfluoroether compounds. The replacement PFAS GenX was recently discovered in NC drinking water sources; however, little is known about its toxicity. To address this, zebrafish were exposed to 0.044-80.0 µM of PFOA, PFOS, GenX, 4,8-dioxa-3H-perfluorononanoate (ADONA), perfluorohexanoic acid (PFHxA), potassium perfluorohexane-1-sulfonate (PFHxS), perfluoro-3,6-dioxa-4-methyl-7-octene-1-sulfonic acid (Nafion BP1), or 0.4% DMSO with daily renewal on 0-5 days post fertilization (dpf). At 6 dpf, larvae were assessed for developmental toxicity (DevTox). Locomotor activity was also assessed as a functional readout of developmental neurotoxicity (DNT) over a 40 min testing period consisting of two consecutive 10 min light periods (20 lux; L1 and L2) and two consecutive 10 min dark periods (0 lux; D1 and D2). In the DevTox assay, exposure to PFOS and PFHxS resulted in failed swim bladder inflation and abnormal ventroflexion of the tail. Exposure to GenX, ADONA, Nafion BP1, PFHxA and PFOA failed to produce DevTox. In the DNT assay, exposure to non-teratogenic concentrations of PFOS (0.1-3.1 µM) or PFHxS (4.4-44.8 µM) triggered locomotor hyperactivity in the L1, L2, and D1 periods; exposure to 14.0 µM PFHxA produced hyperactivity in both dark phases. No significant locomotor changes were observed following exposure to GenX, ADONA, Nafion BP1, or PFOA. In summary, we identified developmental toxicity in zebrafish exposed to PFOS or PFHxS and DNT in zebrafish exposed to non-teratogenic concentrations of PFOS, PFHxS, or PFHxA. These data demonstrate the utility of using multiple zebrafish assays to rapidly assess the toxicity of replacement PFAS. This abstract does not necessarily reflect EPA policy

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