The metabolism of the pyrethroid insecticide (±)‐α‐cyano‐3‐phenoxybenzyl 2,2,3,3‐tetramethyl‐cyclopropanecarboxylate, WL 41706, in the rat

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Abstract
The metabolism of the pyrethroid insecticide α‐cyano‐3‐phenoxybenzyl 2,2,3,3‐tetramethylcyclopropanecarboxylate (WL 41706) has been studied in rats using two forms of 14C‐labelling (benzyl‐ and cyclopropyl‐). Excretion of benzyl−14C was rapid, 57% of the administered dose being eliminated in the urine 48 h after treatment and 40% in the faeces. No significant sex difference was observed. The amount of radioactivity excreted via expired gases was 0.005% of the administered dose and less than 1.5% of the dose remained in the animals 8 days after treatment. The mean percentage recovery of administered dose was 104% for male rats and 97% for female rats. Urinary and faecal metabolites from these rats, and from rats dosed similarly with [cyclopropyl−14C]‐WL 41706 were studied. The rapid metabolism of WL 41706 is due to efficient cleavage of the ester bond by rats in vivo to afford 2,2,3,3‐tetramethylcyclopropanecarboxylic acid (partly as glucuronide) and the 3‐phenoxybenzyl moiety. Before this cleavage occurs, however, about half of the intake suffers aryl hydroxylation giving the α‐cyano‐3‐(4‐hydroxyphenoxy)benzyl ester, part of which is excreted in the bile as a conjugate(s) and part of which is cleaved and eliminated as the O‐sulphate of 3‐(4‐hydroxyphenoxy)benzoic acid and the glucuronide of 2,2,3,3‐tetramethylcyclopropanecarboxylic acid. A minor amount of hydroxylation occurs at a trans‐methyl group on the cyclopropane acid moiety. The metabolism of WL 41706 by rat liver occurs mainly in the microsomes and mainly via oxidative processes.