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

Environ Toxicol Pharmacol. 2023 Nov:104:104315. doi: 10.1016/j.etap.2023.104315. Epub 2023 Nov 19.

Abstract

"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.

Keywords: Aquatic toxicology; Development; GenX; Oxidative stress; Perfluorinated compounds.

MeSH terms

  • Ammonium Compounds* / metabolism
  • Ammonium Compounds* / toxicity
  • Animals
  • Embryo, Nonmammalian / metabolism
  • Larva
  • Oxidative Stress
  • Reactive Oxygen Species / metabolism
  • Water Pollutants, Chemical* / metabolism
  • Water Pollutants, Chemical* / toxicity
  • Zebrafish / metabolism

Substances

  • ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate
  • Reactive Oxygen Species
  • Ammonium Compounds
  • Water Pollutants, Chemical