Metabolism of Esfenvalerate in Rats and Mice and Effects of Its Isomers on Metabolic Fates of Esfenvalerate

Abstract

On single or repeated oral administration of ¹⁴C-labeled esfenvalerate [(S)-α-cyano-3-phenoxybenzyl (S)-2-(4-chlorophenyl) isovalerate] to male and female rats and mice at 2.5mg/kg or 2.5mg/kg/day for successive 10 days, radiocarbon was rapidly and almost completely excreted into the urine and feces. ¹⁴C tissue residues after single oral administration were generally very low except for in the fat in both rats and mice. Major biotransformation reactions were 1) oxidation at the 2- and 3-positions of the acid moiety and the 2′- and 4′-phenoxy positions of the alcohol moiety, 2) cleavage of ester linkage, and 3) conjugation of the resultant carboxylic acids, alcohols and phenols with glucuronic acid, sulfuric acid, glycine or taurine. Treatment of rats and mice with single or repeated oral doses of a mixture of ¹⁴C-esfenvalerate and unlabeled [2S, αR]-, [2R, αS]- and [2R, αR]-isomers of fenvalerate [(RS)-α-cyano-3-phenoxybenzyl (RS)-2-(4-chlorophenyl) isovalerate] at the equal ratio revealed that the unlabeled isomers added hardly affected ¹⁴C excretion profiles, ¹⁴C tissue residues and amounts of metabolites of esfenvalerate, indicating that esfenvalerate behaved independently of other isomers. There were no significant differences in metabolic fates between esfenvalerate and fenvalerate except that ¹⁴C fenvalerate labeled in the acid moiety showed slightly higher ¹⁴C tissue residues than esfenvalerate, due to formation of cholesteryl (R)-2-(4-chlorophenyl) isovalerate from fenvalerate but not from esfenvalerate.