Computational toxicological evaluation of chiral dinotefuran risks: Enantioselective metabolism and processing-driven...

Current regulatory frameworks may severely underestimate pesticide exposure risks by ignoring stereochemistry. This study hypothesizes that the chiral neonicotinoid dinotefuran undergoes stereoselective dissipation during cultivation and processing-driven concentration in Chinese tea, leading to human health risks. To investigate this hypothesis, a rapid chiral RPLC-MS/MS method (LOQ: 0.001 mg/kg) was developed. Enantioselective degradation was observed in fresh tea leaves, with (R)-dinotefuran (t₁_/₂: 0.10-1.51 d) dissipating faster than (S)-dinotefuran (t₁_/₂: 0.20-1.91 d), leading to (S)-enantiomer enrichment. Processing dramatically concentrated residues, particularly in green tea (processing factor up to 49.3), resulting in a final concentration (37.74 mg/kg) exceeding China's maximum residue limit for fresh tea. Acute reference dose (ARfD) and acceptable daily intake (ADI) values for the individual enantiomers were derived from LD₅₀ values obtained in preliminary animal experiments, supplemented by computational toxicology. Integrated deterministic and probabilistic risk assessment revealed that while the racemate posed acceptable risks, the acute dietary risk of (S)-dinotefuran was 2.07-fold and > 55.3-fold higher than its (R)-counterpart and the racemate, respectively. The acute and chronic exposure risks of (S)-dinotefuran in green tea are up to 6.6-fold and 4.5-fold higher than the safety threshold, respectively, and its enantiomer specific risk is 6.2-fold that of (R)-dinotefuran, highlighting strong chiral selective toxicity. Our findings underscore the necessity for enantiomer-specific risk assessments and regulations for chiral pesticides in food commodities.