Stereoselective endocrine-disrupting effects of the chiral triazole fungicide prothioconazole and its chiral metabolite

The wide use of chiral fungicides has generated interest in the stereoselectivity of their ecotoxicological effects. However, there are few studies about the potential endocrine-disrupting effects (EDEs) of chiral fungicides. This study evaluated the hormone receptor activities of the chiral triazole fungicide prothioconazole and its metabolite using reporter gene assays. The results indicated that prothioconazole and its metabolite possessed EDEs, and the metabolite exerted more activities than the activities of the parent compound, suggesting that the metabolic process is toxification. Stereoselective EDEs were observed, and the S-enantiomers possessed greater hormonal effects than those possessed by the R-enantiomers; the REC20 values ranged from 7.9 × 10−10 to 6.4 × 10−7 M for the thyroid hormone effects and from 3.2 × 10−9 to 7.8 × 10−8 M for the estrogenic effects. The molecular docking results revealed that the stereoselective EDEs of prothioconazole and its metabolite were partially attributed to enantiospecific receptor binding affinities. Overall, our results reveal that prothioconazole and its metabolite might disrupt the balance of the endocrine system by affecting the function of multiple nuclear hormone receptors and that they have the potential to affect the developmental and reproductive systems in humans. [Display omitted] •Prothioconazole and its metabolite exerted endocrine-disrupting effects.•The metabolite possessed more thyroid hormone and estrogenic activities than the parent.•The S-enantiomers possessed more potent hormonal activities than R-enantiomers.•Molecular docking revealed the mechanism of stereoselectivity. Prothioconazole and its metabolite enantiomer exerted stereoselective endocrine-disrupting effects and the metabolic process of prothioconazole generates a toxic metabolite.