title: Potential of the octanol-water partition coefficient (logP) to predict the dermal penetration behaviour of amphiphilic compounds in aqueous solutions.
abstract: Aqueous amphiphilic compounds may exhibit enhanced skin penetration compared with neat compounds. Conventional models do not predict this percutaneous penetration behaviour. We investigated the potential of the octanol-water partition coefficient (logP) to predict dermal fluxes for eight compounds applied neat and as 50% aqueous solutions in diffusion cell experiments using human skin. Data for seven other compounds were accessed from literature. In total, seven glycol ethers, three alcohols, two glycols, and three other chemicals were considered. Of these 15 compounds, 10 penetrated faster through the skin as aqueous solutions than as neat compounds. The other five compounds exhibited larger fluxes as neat applications. For 13 of the 15 compounds, a consistent relationship was identified between the percutaneous penetration behaviour and the logP. Compared with the neat applications, positive logP were associated with larger fluxes for eight of the diluted compounds, and negative logP were associated with smaller fluxes for five of the diluted compounds. Our study demonstrates that decreases or enhancements in dermal penetration upon aqueous dilution can be predicted for many compounds from the sign of logP (i.e., positive or negative). This approach may be suitable as a first approximation in risk assessments of dermal exposure.
authors.affiliation: Institute and Out-Patient Clinic of Occupational, Social and Environmental Medicine, University Erlangen-Nuremberg, Erlangen, Germany. Gintautas.Korinth@ipasum.uni-erlangen.de
authors.forename: Gintautas
authors.initials: G
authors.lastname: Korinth
authors.forename: Tanja
authors.initials: T
authors.lastname: Wellner
authors.forename: Karl Heinz
authors.initials: KH
authors.lastname: Schaller
authors.forename: Hans
authors.initials: H
authors.lastname: Drexler
mesh_terms: D000438:Alcohols / Q000493:pharmacokinetics*; D004987:Ethers / Q000493:pharmacokinetics*; D006018:Glycols / Q000493:pharmacokinetics*; D000442:Octanols / Q000737:chemistry; D012867:Skin / Q000737:chemistry*; D012869:Skin Absorption / Q000502:physiology*; D012995:Solubility; D012996:Solutions; D012997:Solvents; D014867:Water / Q000737:chemistry
chemical_list: D000438:Alcohols; D004987:Ethers; D006018:Glycols; D000442:Octanols; D012996:Solutions; D012997:Solvents; D014867:Water