Stereoselective toxicity of (E)-kresoxim-methyl to zebrafish (Danio rerio) embryos during development and metabolomic approaches using GC-MS/MS

Kresoxim-methyl (KM) is a stereoselective strobilurin fungicide with low toxicity to humans, mammals, and beneficial insects. At the frequent detection of KM in aquatic environments, its stereoisomeric form may cause different acute toxicity for aquatic organisms. The acute toxicities of both stereoisomers, (E)-KM and (Z)-KM, as well as their demethylated metabolite, kresoxim, were evaluated in zebrafish (Danio rerio) embryos. Specifically, the embryos were exposed to the three compounds to assess survival rate, hatchability, and morphological changes. The results showed that embryos exposed to (E)-KM at 0.5 mg/L exhibited various abnormal phenotypes, including yolk swelling and pericardiac edema. In the Tg(cmlc2:EGFP) line, the heart rate was significantly reduced upon exposure to 0.5 mg/L of (E)-KM. Vascular development was assessed using the Tg(fli1a:EGFP) line. (E)-KM induced apoptosis in a dose-dependent manner, leading to highly upregulated expression of il-1β, a biomarker of inflammasome activation. Metabolomic changes in (E)-KM-treated embryos were strongly associated with the downregulation of energy metabolism. Taken together, our findings demonstrate that (E)-KM displays stereoselective toxicity to zebrafish embryos, affecting their early development stages and posing a potential risk to various aquatic organisms.