title: Metabolism of metofluthrin in rats: I. Identification of metabolites.
abstract: 1. Metofluthrin (2,3,5,6-tetrafluoro-4-(methoxymethyl)benzyl (Z/E)-(1R)-trans-2,2-dimethyl-3-(1-propenyl)-cyclopropanecarboxylate) is a novel pyrethroid insecticide, which has E/Z isomers at prop-1-enyl group. 2. Rats were orally dosed with each [14C]-labelled E/Z isomer, and the excreta were collected for isolation and identification of metabolites. Analysis of the excreta by LC/MS and NMR revealed formation of 33 and 23 (total 42) metabolites from rats dosed with Z-isomer and E-isomer, respectively. 3. Major metabolic reactions were cleavage of ester linkage, O-demethylation, hydroxylation, epoxidation or reduction of double bond, glutathione conjugation and its further metabolism, hydroxylation of epoxide and formation of lactone ring. Notably, the acid side, 2,2-dimethyl-3-(1-propenyl)-cyclopropanecarboxylic acid, was much more variously metabolised compared to chrysanthemic acid, the acid side of the known pyrethroids. 4. Major metabolites for Z-isomer mostly retained ester linkage with 1,2-dihydroxypropyl group and/or 2-methylalcohol of cyclopropane ring, while most of those for E-isomer received hydrolysis of the ester linkage without oxidation at the 1-propenyl group or the gem-methyl groups, suggesting epoxidation and hydroxylation could occur more easily on Z-isomer. 5. As the novel metabolic pathways for pyrethroids, isomerisation of ω-carboxylic acid moiety, reduction or hydration of double bond and cleavage of cyclopropane ring via epoxidation were suggested.
authors.affiliation: a Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd , Osaka , Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Abe
authors.affiliation: a Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd , Osaka , Japan.
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Nagahori
authors.affiliation: a Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd , Osaka , Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Tarui
authors.affiliation: a Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd , Osaka , Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Tomigahara
authors.affiliation: a Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd , Osaka , Japan.
authors.forename: Naohiko
authors.initials: N
authors.lastname: Isobe
mesh_terms: D000818:Animals; D003521:Cyclopropanes / Q000378:metabolism*; D005464:Fluorobenzenes / Q000378:metabolism*; D007306:Insecticides / Q000378:metabolism*; D011722:Pyrethrins / Q000378:metabolism; D051381:Rats
chemical_list: D003521:Cyclopropanes; D005464:Fluorobenzenes; D007306:Insecticides; D011722:Pyrethrins; C492600:(2,3,5,6-tetrafluoro-4-methoxymethylphenyl)methyl-2,2-dimethyl-3-(1-propenyl)cyclopropanecarboxylate
keywords: Eminence; SumiOne; metabolism; metofluthrin; pyrethroid; rat