Comparative Metabolism of the Six Stereoisomers of Phenothrin in Rats and Mice

Abstract

On single oral administration of each of ¹⁴C-[1R, trans]-, [1RS, trans]-, [1S, trans]-, [1R, cis]-, [1RS, cis]- and [1S, cis]-phenothrin [3-phenoxybenzyl (1RS, trans/cis) chrysanthemate] labeled in the alcohol moiety to both rats and mice at 10mg/kg, the radiocarbon derived from each isomer was almost completely eliminated from the rat and mouse bodies within 6 days after administration and ¹⁴C tissue residue levels were generally very low. In both rats and mice, there seemed to be no significant differences in the ¹⁴C recovery and ¹⁴C tissue residues between the [1R, trans]- and [1RS, trans]-isomers and between the [1R, cis]-and [1RS, cis]-isomers, whereas the [1S]-isomers in both animals revealed slight differences in the ¹⁴C recovery from the other corresponding optical isomers. A predominant excretion route was urine with three trans isomers, whereas feces was a predominant route for three cis isomers in both animals. The major urinary and fecal metabolites were generally common in the nature to both rats and mice, although N-3-phenoxybenzoyltaurine was characteristic to mice. The ester cleaved metabolites in both animals were obtained to a larger extent from trans isomer than from cis isomer. Cleavage of the ester linkage and of hydroxylation at 4′-position of the alcohol moiety occurred to a larger extent in rats than in mice. Both [1S, trans]- and [1S, cis]-isomers in both animals received cleavage of ester linkage to slightly larger extents than other trans and cis optical isomers, respectively. It may be concluded that in both animals, there are virtually no differences in metabolic fates between the [1R, trans]- and [1RS, trans]-isomers and between the [1R, cis]- and [1RS, cis]-isomers. Metabolic fates of both the [1S, trans]- and [1S, cis]-isomers were, however, slightly different from the corresponding optical isomers to the point of the liability of ester cleavage. Overall, the [1RS]-isomers of both stereo isomers seem to show the metabolic fates close to the corresponding [1R]-isomers rather than the [1S]-isomers.