Permethrin absorption not detected in single-pass perfused rabbit ear, and absorption with oxidation of 3-phenoxybenzyl alcohol

Abstract

Isolated rabbit ears were single-pass perfused with a protein-free medium. Permethrin (0.05–23.5%, w/w) was applied in four distinct ointments. Permethrin, 3-phenoxybenzyl alcohol, 3-phenoxybenzaldehyde, and 3-phenoxybenzoic acid were analysed by HPLC. Permethrin was not detected in the effluent. The permeation coefficient, calculated from the detection limit was <7.3 × 10⁻¹² (cm/sec). The appearance rate of the 3-phenoxybenzyl moieties in the effluent agreed with the absorption of the corresponding impurities in the various ointments. In supernatant of homogenised skin, the hydrolysis rate of permethrin was linear; about 4 pmol/min per cm² at 10 μM substrate concentration. The proportion of 3-phenoxybenzoic acid, a further metabolite of 3-phenoxybenzyl alcohol increased when an oxidizing co-factor system was added. The appearance rate in the effusate of 3-phenoxybenzyl alcohol following the lipophobic ointment was five times faster than from isopropyl myristate. The formation rate of 3-phenoxybenzoic acid followed saturation kinetics. Occupational systemic poisoning by dermal absorption of permethrin seems very unlikely since humans bear more epithelial cell layers than rabbits. These experiments do not contradict, however, possible paraesthesia during systemic poisoning after inhalation or ingestion of the pyrethroid- containing aerosols used in agriculture.