Exposure to flutolanil at environmentally relevant concentrations can induce image and non-image-forming failure of zebrafish larvae through neuro and visual disruptions

Numerous pesticides pose a threat to aquatic ecosystems, jeopardizing aquatic animal species and impacting human health. While the contamination of aquatic environment by flutolanil and its adverse effects on animal in the treatment of rich sheath blight have been reported, the neuro-visual effects of flutolanil at environmentally relevant concentrations remain unknown. In this study, we administered flutolanil to zebrafish embryos (0, 0.125, 0.50 and 2.0 mg/L) for 4 days to investigate its impact on the neuro and visual system. The results revealed that flutolanil induced abnormal behavior in larvae, affecting locomotor activity, stimuli response and phototactic response. Additionally, it led to defective brain and ocular development and differentiation. The disruption extended to the neurological system and visual phototransduction of larvae, evidenced by significant disturbances in genes and proteins related to neurodevelopment, neurotransmission, eye development, and visual function. Untargeted metabolomics analysis revealed that the GABAergic signaling pathway and increased levels of glutamine, glutamate, andγ-aminobutyric acid were implicated in the response to neuro and visual system injury induced by flutolanil, contributing to aberrant development, behavioral issues, and endocrine disruption. This study highlights the neuro-visual injury caused by flutolanil in aquatic environment, offering fresh insights into the mechanisms underlying image and non-image effects. Flutolanil is frequently found in aquatic systems and has been documented to pose substantial risks to various organisms. Nevertheless, the current control measures for early risks associated with flutolanil remain inadequate. This study establishes, for the first time, that environmentally relevant concentrations of flutolanil can adversely affect the neuro and visual systems of newly hatched zebrafish following embryonic exposure. This impact leads to both image and non-image failures by influencing amino acid metabolism. Behavioral changes in zebrafish can serve as early warning signs for potential risks, emphasizing the importance of setting a residual limit for flutolanil in water that is lower than the significantly toxic concentration of 0.125 mg/L.