Evidence for neurotoxicity and oxidative stress in zebrafish embryos/larvae treated with HFPO-DA ammonium salt (GenX)

• DOI: 10.1016/j.etap.2023.104315
• Publication Date: 2023-11-19T22:31:58Z
• Authors: Emma Ivantsova; Victoria Lopez-Sc...; Amany Sultan; Cole English; Angel Biju; Christopher L. So...; Natalia E. Padill...; Isaac Konig; Christopher J. Ma...
• Keywords: Oxidative Stress; Embryo, Nonmammalian; Larva; Ammonium Compounds; Animals; Reactive Oxygen Species; Zebrafish; Water Pollutants, Chemical

"GenX" [ammonium perfluoro (2-methyl-3-oxahexanoate] was developed as a replacement chemical for toxic perfluorinated compounds to be used in product manufacturing. Here, we assessed developmental, mitochondrial, and behavioral toxicity endpoints in zebrafish embryos/larvae exposed to GenX. GenX exerted low toxicity to zebrafish embryos/larvae up to 20 mg/L. GenX did not affect mitochondrial oxidative phosphorylation nor ATP levels. ROS levels were reduced in larvae fish exposed to 10 and 100 µg/L, indicative of an antioxidant defense; however, ROS levels were elevated in fish exposed to 1000 µg/L. Increased expression of cox1 and sod2 in GenX exposed 7-day larvae was noted. GenX (0.1 or 1 µg/L) altered transcripts associated with neurotoxicity (elavl3, gfap, gap43, manf, and tubb). Locomotor activity of larvae was reduced by 100 µg/L GenX, but only in light periods. Perturbations of anxiety-related behaviors in larvae were not observed with GenX exposure. These data inform risk assessments for long-lived perfluorinated chemicals of concern.