title: Absorption of ethanol, acetone, benzene and 1,2-dichloroethane through human skin in vitro: a test of diffusion model predictions.
abstract: The overall goal of this research was to further develop and improve an existing skin diffusion model by experimentally confirming the predicted absorption rates of topically-applied volatile organic compounds (VOCs) based on their physicochemical properties, the skin surface temperature, and the wind velocity. In vitro human skin permeation of two hydrophilic solvents (acetone and ethanol) and two lipophilic solvents (benzene and 1,2-dichloroethane) was studied in Franz cells placed in a fume hood. Four doses of each (14)C-radiolabed compound were tested - 5, 10, 20, and 40μLcm(-2), corresponding to specific doses ranging in mass from 5.0 to 63mgcm(-2). The maximum percentage of radiolabel absorbed into the receptor solutions for all test conditions was 0.3%. Although the absolute absorption of each solvent increased with dose, percentage absorption decreased. This decrease was consistent with the concept of a stratum corneum deposition region, which traps small amounts of solvent in the upper skin layers, decreasing the evaporation rate. The diffusion model satisfactorily described the cumulative absorption of ethanol; however, values for the other VOCs were underpredicted in a manner related to their ability to disrupt or solubilize skin lipids. In order to more closely describe the permeation data, significant increases in the stratum corneum/water partition coefficients, Ksc, and modest changes to the diffusion coefficients, Dsc, were required. The analysis provided strong evidence for both skin swelling and barrier disruption by VOCs, even by the minute amounts absorbed under these in vitro test conditions.
authors.affiliation: James L. Winkle College of Pharmacy, University of Cincinnati Academic Health Center, Cincinnati, OH 45267-0004, USA.
authors.forename: Rachna M
authors.initials: RM
authors.lastname: Gajjar
authors.affiliation: James L. Winkle College of Pharmacy, University of Cincinnati Academic Health Center, Cincinnati, OH 45267-0004, USA. Electronic address: Gerald.Kasting@uc.edu.
authors.forename: Gerald B
authors.initials: GB
authors.lastname: Kasting
mesh_terms: D000096:Acetone / Q000008:administration & dosage / Q000378:metabolism*; D001554:Benzene / Q000008:administration & dosage / Q000378:metabolism*; D015194:Diffusion Chambers, Culture; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000008:administration & dosage / Q000378:metabolism*; D005025:Ethylene Dichlorides / Q000008:administration & dosage / Q000378:metabolism*; D005544:Forecasting; D006801:Humans; D012869:Skin Absorption / Q000187:drug effects / Q000502:physiology*
chemical_list: D005025:Ethylene Dichlorides; D000096:Acetone; D000431:Ethanol; C024565:ethylene dichloride; D001554:Benzene
keywords: Dermal absorption; Diffusion model; Evaporation; Percutaneous absorption; Skin disposition; Volatile organic compounds