Tadaaki Unai

Metabolism of permethrin isomers in American cockroach adults, house fly adults, and cabbage looper larvae

Abstract Forty-two insect metabolites of [1 RS,trans ]-and [1 RS,cis ]-permethrin are tentatively identified in studies with Periplaneta americana adults, Musca domestica adults, and Trichoplusia ni larvae involving administration of 14 C preparations labeled in either the alcohol or acid moieties. The less-insecticidal trans isomer is generally metabolized more rapidly than the more-insecticidal cis isomer, particularly in cabbage looper larvae, and metabolites retaining the ester linkage appear in larger amount with cis -permethrin. Although the dichlorovinyl group effectively blocks oxidation in the acid side chain, the permethrin isomers are metabolized by hydrolysis and hydroxylation at the geminal-dimethyl group (either trans - or cis -methyl substituent) and the phenoxybenzyl group (predominantly at the 4′-position in all species but also at the 6-position in house flies). The alcoholic and phenolic metabolites are excreted as glucosides, and the carboxylic acids are excreted as glucosides and amino conjugates (glycine, glutamic acid, glutamine, and serine) with considerable species variation in the preferred conjugating moiety.

Stereochemical considerations in the formation and biological activity of the rotenone metabolites

Abstract The rotenone metabolites formed by enzymatic hydroxylation at one or more of the 12a-, 8′- or 6′, 7′-positions are now available from synthesis. Cochromatographic comparisons of these authentic compounds with the metabolites confirm that in addition to the hydroxylations in the 5′-isopropenyl side chain the enzymatic attack at the B C ring juncture introduces a hydroxyl group in the 12aβ- or 12aα-position with retention of the original stereochemical configuration at other positions. 5′-Hydroxyrotenone or its equivalent keto phenol and rotenolones derived from this material are not present as rotenone metabolites. The only metabolites with high potency as NADH oxidase inhibitors are those retaining the original 6aβ, 12aβ-configuration and with one hydroxyl group at the 12aβ- or 8′-position, but even these two metabolites are much less inhibitory than rotenone. The relatively high intraperitoneal toxicity to mice of 6aβ, 12aβ-rotenolone and 8′-hydroxyrotenone despite their reduced activity as NADH oxidase inhibitors suggests that these compounds are not metabolically detoxified as rapidly as rotenone.