Toxicokinetics of Two Oxathiapiprolin Enantiomers in Rats and Their Stereoselective Interaction with Oxysterol Binding Protein.

Oxathiapiprolin is a chiral fungicide, and it can affect the metabolism of the cholesterol compounds by inhibiting oxysterol binding protein (OSBP) to exert its fungicidal effect. The application of oxathiapiprolin in agriculture is widespread, and its residue in the environment is a threat to both human and animal health. The two oxathiapiprolin enantiomers differ in their fungicidal activity, biotoxicity, and degradation by environmental forces. However, their biotoxicity has not been reported in animals. The toxicokinetics of a pesticide should be a crucial component for the evaluation of its toxicity in vivo. In this study, we investigated the absorption, bioavailability, tissue distribution, and excretion of the two oxathiapiprolin enantiomers in rats to verify their toxicokinetic process in animals. An ultrahigh-performance liquid chromatography triple quadrupole tandem mass spectrometry (UHPLC-QQQ/MS) method was established to quantify the two oxathiapiprolin enantiomers in vivo. The two oxathiapiprolin enantiomers were found to have approximately the same absorption rate and bioavailability, and both were excreted mainly in the feces. The half-life of R-(-)-oxathiapiprolin was nearly twice that of S-(+)-oxathiapiprolin. R-(-)-oxathiapiprolin also had greater distribution than S-(+)-oxathiapiprolin in the liver, lungs, heart, spleen, kidneys, stomach, large intestine, small intestine, brain, and pancreas, supporting the notion that R-(-)-oxathiapiprolin could better bind with OSBP. The stereoselectivity of S-(+)-oxathiapiprolin in these tissues may be responsible for it being readily metabolized in vivo. The molecular docking technique was subsequently used to verify the more superior binding between R-(-)-oxathiapiprolin and OSBP compared with the binding between S-(+)-oxathiapiprolin and OSBP. The findings of this study could provide more reliable data for determining the toxicokinetics of a single enantiomer of oxathiapiprolin in animals, thereby providing some theoretical basis for its subsequent toxicological study.

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