Permeation of water contaminative phenols through hairless mouse skin

Abstract

As a means of determining the risk of absorption of water contaminative phenolic compounds through the skin, the permeation of a number of phenols, all on the U.S. Environmental Protection Agency's list of priority pollutants, through hairless mouse skin has been studied, usingin vitro diffusion cell methods. Experimentally determined permeability coefficients through intact skin and stratum corneum denuded skin and permeability coefficients derived therefrom for the viable tissue layer and the stratum corneum, which are the tissue's major contributing substrata, have been correlated with their log K_{octanol/water} partition coefficients. Permeability coefficients for the whole skin and the stratum corneum systematically increased with increasing phenol lipophilicity to limiting values of about 0.15 and 0.30 cm/hr, respectively. The values of the permeability coefficients for the viable tissue were roughly the same for all compounds (≈0.36 cm/hr). Because of the inductive effects of Cl and NO₂ substituents on the aromatic ring, phenolic analogs containing these moieties are acidic and, consequently, their overall skin permeabilities were highly pH-dependent in the range of pH values seen for surface waters. High fluxes were noted for such phenols at low pH, where they exist essentially in a non-ionized state. Though low, fluxes of the compounds were measurable at pH's ≫ pK_a's, indicating that phenolic anions also pass through the skin. With the exceptions of relatively polar phenol and the mono-nitro phenols, the free acid forms of all the phenols studied permeated skin with ease and at rates approaching those of denuded skin. The intact skin permeability coefficient of the free acid form of 4-nitro phenol was exceptionally low, which suggests that it might associate intermolecularly.