title: In vitro dermal absorption of pyrethroid pesticides in human and rat skin.
abstract: Dermal exposure to pyrethroid pesticides can occur during manufacture and application. This study examined the in vitro dermal absorption of pyrethroids using rat and human skin. Dermatomed skin from adult male Long Evans rats or human cadavers was mounted in flow-through diffusion cells, and radiolabeled bifenthrin, deltamethrin or cis-permethrin was applied in acetone to the skin. Fractions of receptor fluid were collected every 4h. At 24h, the skins were washed with soap and water to remove unabsorbed chemical. The skin was then solubilized. Two additional experiments were performed after washing the skin; the first was tape-stripping the skin and the second was the collection of receptor fluid for an additional 24 h. Receptor fluid, skin washes, tape strips and skin were analyzed for radioactivity. For rat skin, the wash removed 53-71% of the dose and 26-43% remained in the skin. The cumulative percentage of the dose at 24 h in the receptor fluid ranged from 1 to 5%. For human skin, the wash removed 71-83% of the dose and 14-25% remained in the skin. The cumulative percentage of the dose at 24 h in the receptor fluid was 1-2%. Tape-stripping removed 50-56% and 79-95% of the dose in rat and human skin, respectively, after the wash. From 24-48 h, 1-3% and about 1% of the dose diffused into the receptor fluid of rat and human skin, respectively. The pyrethroids bifenthrin, deltamethrin and cis-permethrin penetrated rat and human skin following dermal application in vitro. However, a skin wash removed 50% or more of the dose from rat and human skin. Rat skin was more permeable to the pyrethroids than human skin. Of the dose in skin, 50% or more was removed by tape-stripping, suggesting that permeation of pyrethroids into viable tissue could be impeded. The percentage of the dose absorbed into the receptor fluid was considerably less than the dose in rat and human skin. Therefore, consideration of the skin type used and fractions analyzed are important when using in vitro dermal absorption data for risk assessment.
authors.affiliation: Integrated Systems Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA. hughes.michaelf@epa.gov
authors.forename: Michael F
authors.initials: MF
authors.lastname: Hughes
authors.forename: Brenda C
authors.initials: BC
authors.lastname: Edwards
mesh_terms: D000328:Adult; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D007306:Insecticides / Q000493:pharmacokinetics*; D008297:Male; D009570:Nitriles / Q000493:pharmacokinetics; D026023:Permethrin / Q000493:pharmacokinetics; D011722:Pyrethrins / Q000493:pharmacokinetics*; D051381:Rats; D020318:Rats, Long-Evans; D012869:Skin Absorption
chemical_list: D007306:Insecticides; D009570:Nitriles; D011722:Pyrethrins; C017180:decamethrin; D026023:Permethrin; C099952:bifenthrin