Toxicity mechanisms of per- and polyfluoroalkyl substances (PFASs), a chemical class present in diverse ecosystems, as well as many of their precursors, have been increasingly 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, transcript levels, and distance moved in zebrafish embryos and larvae following continuous exposure to PFOSA beginning at 6 h 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 ROS in 7-day-old larvae fish. The 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) were all increased in larval fish with higher PFOSA exposure. These data improve our understanding of the potential sub-lethal toxicity of PFOSA in fish species.

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.

Aquatic species are exposed to several long-chain per- and polyfluoroalkyl substances (PFASs) in the environment but their potential toxicity is not well studied. In this study, we assessed the effects of perfluoroundecanoic acid (PFUnDA) exposure on developing zebrafish. To do this, we investigated the potential for oxidative stress and neurotoxicity by measuring reactive oxygen species, apoptosis, gene expression, and locomotor activity. Mortality was evident in fish exposed to 1000 µg/L PFUnDA, and apoptosis was indicated in fish exposed to 100 µg/L PFUnDA via an increase in casp3 transcription. No change in reactive oxygen species in 7-day-old larval fish exposed to 0.01 up to 1000 µg/L PFUnDA was detected. Visual motor response analysis revealed hypoactivity in different light–dark periods that occurred in a concentration-specific manner. At the transcriptional level, several neurotoxicity-related genes (casp3, bdnf, gfap, gmfb, nkx2-2a) were significantly upregulated, further supporting neurotoxic effects. Overall, these findings indicate that PFUnDA disrupts neurodevelopment and behavior in zebrafish larvae, raising concerns for this long-chain PFAS.

Strobilurins are a prominent class of fungicides capable of entering aquatic environments via runoff and leaching from the soil. Findings from previous studies suggest that strobilurins are highly toxic in aquatic environments, and evidence of acute developmental toxicity and altered behavioral responses have been emphasized. The objective here was to determine the effects of a new strobilurin, metyltetraprole (MTP), on zebrafish using developmental endpoints, gene expression, and behavioral locomotor assays. We hypothesized that MTP would cause developmental toxicity and induce hyperactivity in zebrafish (Danio rerio). To test this, developing zebrafish embryos/larvae were exposed to environmentally relevant levels of MTP (0.1, 1, 10, and 100 µg/L) until 7 days post-fertilization. Survival percentages did not differ among the treatment groups. No change in reactive oxygen species production was detected, but two genes involved in the mitochondrial electron transport chain (mt-nd3 and uqcrc2) were altered in abundance following MTP exposure. Moreover, the highest concentration (100 µg/L) of MTP caused notable hyperactivity in the zebrafish in the visual motor response test. Overall, results from this study increase our knowledge regarding sub-lethal effects of MTP, helping inform risk assessment for aquatic environments.

Strobilurins are a prominent class of fungicides capable of entering aquatic environments via runoff and leaching from the soil. Findings from previous studies suggest that strobilurins are highly toxic in aquatic environments, and evidence of acute developmental toxicity and altered behavioral responses have been emphasized. The objective here was to determine the effects of a new strobilurin, metyltetraprole (MTP), on zebrafish using developmental endpoints, gene expression, and behavioral locomotor assays. We hypothesized that MTP would cause developmental toxicity and induce hyperactivity in zebrafish (Danio rerio). To test this, developing zebrafish embryos/larvae were exposed to environmentally relevant levels of MTP (0.1, 1, 10 and 100 μg/L) until 7 days post-fertilization. Survival percentage did not differ among the treatment groups. No change in reactive oxygen species production was detected, but two genes involved in the mitochondrial electron transport chain (mt-nd3 and uqcrc2) were altered in abundance following MTP exposure. Moreover, the highest concentration (100 µg/L) of MTP caused notable hyperactivity in the zebrafish in the visual motor response test. Overall, results from this study increase our knowledge regarding sub-lethal effects of MTP, helping inform risk assessment for aquatic environments.

Background/Objectives: Per- and polyfluoroalkyl substances (PFAS) are environmentally persistent chemicals widely detected in aquatic systems and drinking water. Perfluorononanoic acid (PFNA), a long-chain PFAS, has been reported globally in environmental matrices and fish tissues. Although PFNA has been linked to developmental, metabolic, and neurological toxicity, its effects on lipid-related pathways and neurotoxicity remain poorly characterized. Methods: This study evaluated the developmental and neurotoxic effects of PFNA exposure in zebrafish embryos and larvae following a 7-day exposure to environmentally relevant PFNA concentrations. Results: PFNA exposure did not significantly affect survival or deformity rates at the concentrations tested. Apoptosis was significantly increased in larvae exposed to 1 µg/L PFNA compared to controls, whereas reactive oxygen species levels were unaffected. Two concentrations (0.1 µg/L and 10 µg/L) were further examined for transcriptomic responses, and the transcriptome response was largely different for each concentration. Low-dose PFNA exposure primarily affected lipid transport, cholesterol metabolism, sphingolipid signaling, and neurodegeneration-related pathways, whereas high-dose PFNA altered transcripts related to synaptic signaling, axon guidance, and thyroid hormone synthesis. Hypoactivity was observed in the movement of larval zebrafish based on a Visual Motor Response test. Conclusions: Taken together, PFNA exposure induced molecular changes related to neurotoxicity and lipid metabolism in zebrafish, which may contribute to adverse neurodevelopmental outcomes.