title: Further development of an in vitro model for studying the penetration of chemicals through compromised skin.
abstract: A new in vitro model based on the electrical resistance properties of the skin barrier has been established in this laboratory. The model utilises a tape stripping procedure in dermatomed pig skin that removes a specific proportion of the stratum corneum, mimicking impaired barrier function observed in humans with damaged skin. The skin penetration and distribution of chemicals with differing physicochemical properties, namely; Benzoic acid, 3-Aminophenol, Caffeine and Sucrose has been assessed in this model. Although, skin penetration over 24h differed for each chemical, compromising the skin did not alter the shape of the time course profile, although absorption into receptor fluid was higher for each chemical. Systemic exposure (receptor fluid, epidermis and dermis), was marginally higher in compromised skin following exposure to the fast penetrant, Benzoic acid, and the slow penetrant Sucrose. The systemically available dose of 3-Aminophenol increased to a greater extent and the absorption of Caffeine was more than double in compromised skin, suggesting that Molecular Weight and Log Pow, are not the only determinants for assessing systemic exposure under these conditions. Although further investigations are required, this in vitro model may be useful for prediction of dermal route exposure under conditions where skin barrier is impaired.
authors.affiliation: Dermal Technology Laboratory Ltd, Keele, Staffordshire, UK.
authors.forename: Diane J
authors.initials: DJ
authors.lastname: Davies
authors.affiliation: Dermal Technology Laboratory Ltd, Keele, Staffordshire, UK. Electronic address: j.heylings@dermaltechnology.com.
authors.forename: Jon R
authors.initials: JR
authors.lastname: Heylings
authors.affiliation: Dermal Technology Laboratory Ltd, Keele, Staffordshire, UK.
authors.forename: Heather
authors.initials: H
authors.lastname: Gayes
authors.affiliation: Johnson & Johnson Consumer Inc., Skillman, NJ, USA.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: McCarthy
authors.affiliation: Johnson & Johnson Consumer Inc., Skillman, NJ, USA.
authors.forename: M Catherine
authors.initials: MC
authors.lastname: Mack
mesh_terms: D020003:1-Octanol / Q000737:chemistry; D000279:Administration, Cutaneous; D000627:Aminophenols / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D019817:Benzoic Acid / Q000737:chemistry / Q000493:pharmacokinetics; D002110:Caffeine / Q000737:chemistry / Q000493:pharmacokinetics; D066298:In Vitro Techniques; D008970:Molecular Weight; D012867:Skin / Q000293:injuries* / Q000378:metabolism*; D012869:Skin Absorption; D013395:Sucrose / Q000737:chemistry / Q000493:pharmacokinetics; D013552:Swine; D014867:Water / Q000737:chemistry
chemical_list: D000627:Aminophenols; D014867:Water; D002110:Caffeine; D013395:Sucrose; D019817:Benzoic Acid; C055528:3-aminophenol; D020003:1-Octanol
keywords: Barrier function; Compromised skin; Dermatomed pig skin; Electrical Resistance (ER); In vitro percutaneous absorption; Tape stripping