Stereoselective environmental behavior and biological effects of the chiral bitertanol

Bitertanol is a widely used chiral triazole fungicide. The stereoselective environmental behavior and biological effects of bitertanol are not clear. The present study evaluated the stereoselectivity of bitertanol, including its degradation in five typical soils (under laboratory controlled aerobic, anaerobic and sterilization conditions), metabolism in rat liver microsomes (RLM; in vitro), and the endocrine disruption effects on the estrogen receptor (ER) and thyroid hormone receptor (TR) using reporter gene assays. The results indicated that (1S,2R)-bitertanol and (1R,2S)-bitertanol had faster degradation rates in soil than the other stereoisomers. The half-lives of four bitertanol stereoisomers ranged from 9.1 d to 86.6 d in different soils under different conditions. (1S,2R)-bitertanol was preferentially metabolized in RLM. The molecular docking results confirmed the in vitro experiments that (1S,2R)-bitertanol had shortest binding distances and lowest energies with cytochrome P450 enzymes (CYPs). Four bitertanol stereoisomers showed stereoselective antagonistic effects on ER. Additionally, (1S,2R)-bitertanol and (1R,2S)-bitertanol exhibited antagonistic effects on TR. These results suggest that the use of pure (1S,2R)-bitertanol instead of the commercial stereoisomer mix, may help reduce environmental pollution and biological toxicity. [Display omitted] •Stereoselective degradation of bitertanol in different types of soil was illustrated.•(1S,2R)-bitertanol had the fastest metabolism rate in rat liver microsomes.•The stereoselective metabolism mechanism was revealed using homology modeling and molecular docking.•Endocrine disruption effects of bitertanol were demonstrated at the enantiomers level.