Metabolism of metofluthrin in rats: I. Identification of metabolites

• Published in: Xenobiotica Vol. 48; no. 2; pp. 157 - 169
• Main Authors: Abe, Jun, Nagahori, Hirohisa, Tarui, Hirokazu, Tomigahara, Yoshitaka, Isobe, Naohiko
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 01.02.2018
• Subjects: Animals; Cyclopropanes - metabolism; Eminence; Fluorobenzenes - metabolism; Insecticides - metabolism; metabolism; metofluthrin; Pyrethrins - metabolism; pyrethroid; rat; Rats; SumiOne; Eminence; metabolism; metofluthrin; rat; SumiOne; pyrethroid
• ISSN: 0049-8254; 1366-5928
• DOI: 10.1080/00498254.2017.1283718

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 [ 14 C]-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.