Developmental Toxicity and Mechanistic Insights into the Novel Fungicide Fluindapyr in Zebrafish Embryos

Abstract

Succinate dehydrogenase inhibitor (SDHI) fungicides pose potential risks to nontarget aquatic organisms. Fluindapyr, a newly registered SDHI fungicide, is likely to enter aquatic environments, yet its toxicity remains largely unexplored. Here, zebrafish (Danio rerio) embryos were used to assess their developmental toxicity and underlying mechanisms. Fluindapyr exhibited high toxicity, with a 96 h LC50 of 0.36 mg/L, and induced multiple developmental defects including edema, growth retardation, reduced locomotion, and bradycardia. Transcriptomic analysis revealed that differentially expressed genes were enriched in pathways related to cardiac muscle contraction and adrenergic signaling, indicating cardiac dysfunction as the primary target. Molecular docking further showed the strong binding of fluindapyr to the L-type calcium channel CaV1.2, suggesting a potential involvement of calcium signaling. Additionally, reduced ATP levels and the suppression of glycolysis-related genes indicated impaired energy metabolism. At higher concentrations, immune- and inflammation-related pathways were activated. These findings highlight cardiotoxicity and energy disruption as key mechanisms underlying fluindapyr-induced developmental toxicity.