Abstract
On single oral administration of each of the 14C-acid, -alcohol and -CN-labeled preparations of fenvalerate [(RS)-α-cyano-3-phenoxybenzyl-(RS)-2-(4-chlorophenyl) isovalerate] and the [2S, αS]-isomer at 4.2 to 30mg/kg, the radiocarbon from the acid and alcohol moieties was almost completely eliminated from the body of rats and mice, and the 14C tissue residues were generally very low. On the other hand, radiocarbon from the CN-labeled preparations was somewhat slowly excreted and higher 14C residues were found in the hair, skin and stomach contents. There were no apparent differences in the total 14C recovery, biological half-life and 14C tissue residues in the two compounds or sexes. Two weeks pre-feeding of 500ppm unlabeled fenvalerate resulted in more complete elimination of the radiocarbon from the body and lower 14C tissue residues in rats and mice given a single dose of CN-labeled fenvalerate, as compared with the non-feeding treatment. Both fenvalerate and the [2S, αS]-isomer were similarly metabolized mainly by oxidation at the 2′- and 4′-phenoxy positions of the alcohol and at the C-2 and C-3 positions of the acid moiety, cleavage of the ester linkage, conversion of the CN group to SCN- and CO2, and conjugation of the resultant carboxylic acids and phenols with glucuronic acid, sulfuric acid and/or amino acids. Although no significant differences in the nature or amount of metabolites were seen between the sexes, dose levels or isomers, the following remarkable species differences were found: 1) taurine conjugate of 3-phenoxybenzoic acid was found in mice, but not in rats, 2) 4′-hydroxylation of the alcohol moiety and sulfate conjugate of 3-(4′-hydroxyphenoxy)benzoic acid occurred to greater extents in rats than in mice and, 3) a greater amount of thiocyanate was excreted in mice than in rats.
