Enantioselective Behavior Of Chiral Pesticides Fluroxypyr Methylheptyl Ester And Ethofumesate In Laboratory Animals

We investigated the stereoselective degradation kinetics and toxicity of fluroxypyr methylheptyl ester (FPMH) and ethofumesate (ETO) in laboratory animals using a chiral high-performance liquid chromatographic (HPLC) method.The stereoselective degradation of FPMH enantomers in rabbits was investigated by a single ear intravenous (i.v.) administration at doses of50mg/kg bd wt of racemate. The degradation of (+)-FPMH was also much faster than that of the (-)-FPMH in the kidney, lung, and muscle, whereas the concentrations of FPMH v.ere below the limit of quantification in other tissues, we also examined the hydrolyzed product fluroxypyr (FP) in rabbit plasma and tissues in vivo. Its concentration was higher in the urine than in the other tissues. The rank concentrations of FP in the tissues after480min were urine> lung> kidney> plasma>heart> bile. The concentrations of FP in the other tissues were below the LOQ. FP was rapidly excreted unchanged, principally in the urine. In20%rabbit plasma, the half lives of (+)-FPMH and(-)-FPMH were2.5and10.9min, respectively. Thus, the enantioselective degradation was faster for (+)-FPMH than for (-)-FPMH in rabbit plasma in vitro, and there was no chiral conversion or transformation during incubation of the plasma. Furthermore,98%rac-FPMH was quickly (within10min) hydrolyzed to fluroxypyr in rabbit liver microsomes.We investigated the stereoselective degradation kinetics and toxicity of FPMH and in rat hepatocytes in vitro. The T1/2of (-)-FPMH was about two times longer than that of (+)-FPMH after the rat hepatocytes were incubated with10,20, and50μM of rac-FPMH.The degradation of10,20, and50μM of rac-FPMH in rat hepatocytes was enantioselective. There was no chiral conversion or transformation during their incubation with the hepatocytes. The results of the MTT assays showed that pesticide exposure exhibited significant cytotoxicity at concentrations from0to1000μM. There were slight increases in mitochondrial function at the low doses (0-100μM) of (+)-FPMH and (-)-FPMH, but these were not statistically significant. Toxicity differences were observed among the two enantiomers of FPMH and FP in their EC50values in rat hepatocytes. Of all the tested compounds, FP was most toxic to the rat hepatocytes. The (-)-FPMH enantiomer showed higher toxicity than the (+)-FPMH, whereas the racemic mixture displayed intermediate toxicity.We investigated the metabolic kinetics and toxicity of ethofumesate (ETO) in rat and chicken hepatocytes in vitro. The metabolic of ETO in rat hepatocytes was enantioselective, whereas it was not in chicken hepatocytes. The T1/2of (-)-ETO was about two times longer than that of (+)-ETO after the rat hepatocytes had been incubated with20μM rac-ETO. There was no chiral conversion or transformation during their incubation with the hepatocytes. Toxicity differences were observed between the two enantiomers of ETO, reflected in their EC50values in rat and chicken hepatocytes. The stereoselective cytotoxicity of the two enantiomers was opposite in rat and chicken hepatocytes.