The metabolism of cypermethrin in man: differences in urinary metabolite profiles following oral and dermal administration
Abstract
1. The pyrethroid insecticide cypermethrin was administered orally to six male volunteers as a single dose of 3.3 mg ( cis: trans 1 : 1) and dermally to six volunteers at a dose of 31 mg/800 cm 2 ( cis : trans 56 : 44) as a soya oil-based formulation. Urine samples were collected for up to 5 days and analysed for the metabolites cis and trans 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (DCVA), 3-phenoxybenzoic acid (3PBA) and 3-(4′-hydroxyphenoxy) benzoic acid (4OH3PBA) following an acid hydrolysis procedure. 2. Following oral dosing approx. equal amounts of ( cis + trans DCVA) and (3PBA + 4OH3PBA) were excreted with peak excretion rates occurring between 8 and 24 h after dosing. The ratio of trans:cis DCVA was on average 2:1. Based on DCVA measurements the amount of cypermethrin absorbed was estimated to be between 27% and 57% (mean 36%) of the administered dose. 3. Peak urinary excretion rates of metabolites occurred between 12 and 36h after dermal dosing. The amount of metabolites derived from the phenoxybenzyl moiety (3PBA + 4OH3PBA) was on average 4 times greater than the amount of ( cis + trans DCVA) recovered in urine. The ratio of trans :cis DCVA was, on average 1 : 1.2. Based on the recovery of the phenoxybenzyl metabolites it is estimated that 0.85-1.8% (mean 1.2%) of the administered cypermethrin was absorbed. 4. These studies demonstrate marked differences in the urinary metabolite profile by the two routes, and provide an improved basis for determining the extent and main route of absorption of cypermethrin under occupational exposure conditions.