Effects of the Novel Triazole Fungicide Ipfentrifluconazole on Different Endpoints in Zebrafish Larvae

The potential hazards of triazole fungicides to non-target organisms necessitate environmental risk assessment. This study, therefore, focused on characterizing the differential toxicity of the enantiomers of Ipfentrifluconazole (IFZ), a new triazole fungicide, in zebrafish larvae using a multi-endpoint approach. Acute toxicity tests determined the LC₅₀ values of 1.709 mg/L for rac-IFZ, 1.531 mg/L for (+)-IFZ, and 1.809 mg/L for (-)-IFZ, indicating a higher toxicity of the (+)-enantiomer. To avoid overt mortality while revealing organ-level effects, we chose a concentration of approximately 20% of the LC50 of (+)-IFZ, which is 340 μg/L, as the exposure concentration. Exposure to IFZ induced developmental defects, including swim bladder malformation, cardiac blood pooling, and metabolic disturbances during the early developmental stage of zebrafish. Additionally, cardiac and hepatic development and function were disrupted in zebrafish larvae following IFZ exposure. Biochemical and transcriptomic analyses revealed distinct toxic mechanisms: (+)-IFZ primarily disrupted lipid metabolism through alterations in PPAR signaling pathway and fatty acid degradation, while (-)-IFZ significantly impaired cardiac function by affecting adrenergic signaling in cardiomyocytes and cardiac muscle contraction. Rac-IFZ mainly influenced drug metabolism, particularly cytochrome P450-related pathways. These findings demonstrated the toxic effects of IFZ, emphasizing the need for evaluating environmental and health risks of chiral pesticides. The study provides valuable insights into the molecular mechanisms underlying IFZ toxicity.