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Permethrin absorption not detected in single-pass perfused rabbit ear, and absorption with oxidation of
G E Bast1, D Taeschner, H G Kampffmeyer
1Walther-Straub-Institute for Pharmacology and Toxicology, Faculty of Medicine, Ludwig-Maximilians-University, Munich, Germany.
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 x 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 microM 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.
Insights
Dermal absorption of permethrin is unlikely to cause systemic poisoning in humans, as rabbit skin showed very low permethrin permeation. Further research is needed for inhalation or ingestion exposure risks.
Area of Science:
- Toxicology
- Dermal Absorption Studies
- Environmental Health
Background:
- Permethrin is a widely used pyrethroid insecticide.
- Concerns exist regarding potential systemic toxicity from dermal exposure.
Purpose of the Study:
- To investigate the dermal absorption and metabolism of permethrin using isolated rabbit ears.
- To assess the risk of systemic poisoning via dermal contact.
Main Methods:
- Isolated rabbit ears were perfused with protein-free medium.
- Permethrin was applied in various ointments (0.05-23.5%).
- Permethrin and its metabolites were analyzed using High-Performance Liquid Chromatography (HPLC).
Main Results:
- Permethrin was not detected in the perfusate, indicating minimal dermal penetration (< 7.3 x 10(-12) cm/sec).
- Skin homogenates showed linear hydrolysis of permethrin (4 pmol/min per cm2).
- Metabolite appearance rates varied with ointment composition and co-factor addition.
Conclusions:
- Dermal absorption of permethrin is very low, making occupational systemic poisoning unlikely in humans due to thicker skin.
- These findings do not rule out paraesthesia from inhalation or ingestion exposure to permethrin aerosols.