Famoxadone is a chiral fungicide frequently found in the environment and agricultural products. However, the health risks of famoxadone enantiomers are not well understood. This study investigated the stereoselective cytotoxicity and metabolic behavior of famoxadone enantiomers in mammals. Results showed that R -famoxadone was 1.5 times more toxic to HepG2 cells than S -famoxadone. R -famoxadone induced more pronounced ferroptosis compared to S -famoxadone. It caused greater upregulation of genes related to iron transport and lipid peroxidation, and greater downregulation of genes related to peroxide clearance. Furthermore, R -famoxadone induced more severe lipid peroxidation and reactive oxygen species (ROS) accumulation through ACSL4 activation and GPX4 inhibition. Additionally, the bioavailability of R -famoxadone in mice was six times higher than that of S -famoxadone. Liver microsome assays, cytochrome P450 (CYP450) inhibition assays, human recombinant CYP450 assays, and molecular docking suggested that the lower binding affinities of CYP2C8, CYP2C19, and CYP2E1 for R -famoxadone caused its preferential accumulation. Overall, R -famoxadone poses a higher risk than S -famoxadone due to its greater cytotoxicity and persistence. This study provides the first evidence of ferroptosis-induced stereoselective toxicity, offering insights for the comprehensive health risk assessment of chiral famoxadone and valuable references for the application of high-efficiency, low-risk pesticide enantiomers.
Based on the size and surface properties of dimethomorph and flumorph, we used a computer simulation-assisted size exclusion hapten design strategy to develop group-specific monoclonal antibodies that can simultaneously recognize dimethomorph and flumorph. For this, we performed quantitative and visual semi-quantitative time-resolved fluorescence immunochromatography (TRFICA) to simultaneously detect dimethomorph and flumorph in potatoes and apples. In potato samples, the visual limit of detection (vLOD) for dimethomorph and flumorph was 4 ng/mL and 8 ng/mL, respectively, whereas the quantitative limit of detection (qLOD) for dimethomorph and flumorph was 0.26 and 0.33 ng/mL, respectively. The vLOD of dimethomorph and flumorph in apple samples was 8 ng/mL, whereas the qLOD of dimethomorph and flumorph was 0.17 and 0.38 ng/mL, respectively. The average recovery of potato and apple samples ranged from 77.5% to 121.7%, which indicated that the method can be used to rapidly detect dimethomorph and flumorph in food samples.