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The enantiomerization and enantioselective metabolism of benalaxyl in mice after a single gavage administration were investigated in the present study. The pharmacokinetic result indicated that elimination of (−)-R-benalaxyl in plasma was slightly faster with the t 1/2 of 26.65 h and 28.88 h for (−)-R- and (+)-S-benalaxyl, respectively. Consistent with this, elimination in tissues and excretion were also enantioselective, with (+)-S-benalaxyl enriched in all tissues, urine and feces. And formation of the metabolites also exhibited an enantioselective manner. Both benalaxyl and most of its metabolites exhibited a potent excretion to feces and urine. In addition, significant enantiomerization of benalaxyl enantiomers was observed in plasma, with a larger extent from R to S than S to R. Thus, this difference in enantiomerization may be one of the reasons to explain the enantioselective enrichment of (+)-S-benalaxyl in mice observed in this study. Data from this study proves that besides metabolic enzymes, enantiomerization could be another important factor that contributes to the enantioselective metabolism of a chiral pesticide. Thus, research at enantiomeric level is necessary for efficient risk assessment of chiral pesticides. [ABSTRACT FROM AUTHOR]

Metalaxyl [N-(2,6-dimethylphenyl)-N-(methoxyacetyl)-D,L-alaninemethylester] is a systemic fungicide widely used in agriculture. In this study, the enantioselective distribution, degradation and excretion of metalaxyl were investigated after oral gavage administration of rac -metalaxyl to mice. Concentration of metalaxyl and its enantiomers was determined by HPLC–MS/MS. The results showed that R-metalaxyl was much higher than S-metalaxyl in heart, liver, lung, urine and feces. As for the strong first pass effect, concentrations of metalaxyl in liver were much higher than those in other tissues. The total body clearance (CL) of metalaxyl in mice was 1.77 L h −1  kg −1 and degradation half-lives of (t 1/2 ) of S-metalaxyl and R-metalaxyl in liver were 2.2 h and 3.0 h, respectively. Such results indicated the enantioselectivity of metalaxyl lies in distribution, degradation and excretion processes in mice. Main metabolites were also determined and biotransformation reactions were hydroxylation, demethylation and didemethylation. Furthermore, metabolite concentrations in urine and feces were much higher than those in tissues. These results may have potential implications to predict toxicity and provide additional information associated with adverse health effects for risk assessment of metalaxyl. [ABSTRACT FROM AUTHOR]