Adverse Outcomes Following Exposure to Perfluorooctanesulfonamide (PFOSA) in Larval Zebrafish (<em>Danio rerio</em>): A Neurotoxic and Behavioral Perspective

Toxicity mechanisms of per- and polyfluoroalkyl substances (PFAS), a chemical class present in diverse ecosystems, are not well characterized in aquatic species. Perfluorooctanesulfonamide (PFOSA, C8H2F17NO2S) is a common precursor of perfluorooctane sulfonic acid (PFOS), a long-chain PFAS. Here, we assessed sub-lethal endpoints related to development, oxidative stress, locomotor activity, and gene expression in zebrafish embryos and larvae following continuous exposure to PFOSA beginning at 6 hours post fertilization (hpf). PFOSA decreased survival in fish treated with 1 µg/L PFOSA, however the effect was modest relative to the controls (difference of 10%). Exposure up to 10 µg/L PFOSA did not affect hatch rate, nor did it induce reactive oxygen species in 7-day-old larvae fish. However, locomotor activity of larval fish treated with 100 µg/L PFOSA was reduced relative to the solvent control. Transcripts related to oxidative stress response and apoptosis were measured and BCL2 associated X, apoptosis regulator (bax), cytochrome c, somatic (cycs), catalase (cat), superoxide dismutase 2 (sod2) were induced with high concentrations of PFOSA. Genes related to neurotoxicity were also measured and transcript levels of acetylcholinesterase (ache), elav-like RNA binding protein 3 (elavl3), growth associated protein 43 (gap43), synapsin II (syn2a), and tubulin 3 (tubb3) levels were all increased in larval fish with higher PFOSA exposure. This study contributes to our knowledge regarding the relative toxicity of PFOSA to fish and contributes data to future risk assessment strategies of these concerning, persistent environmental pollutants.