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Predicting skin permeability of molecules from chemical mixtures using an inert membrane-coated fiber array.
Xia-XR; Baynes-RE; Monteiro-Riviere-NA; Riviere-JE
Toxicologist 2007 Mar; 96(1):433-434
Predicting skin permeability of compounds from chemical mixtures is required for transdermal drug delivery, safety evaluation of cosmetics and risk assessment of chemicals, where most exposure occurs in complicated chemical mixtures, not individual chemicals. We have developed a membrane-coated fiber technique that can be used to measure the partition coefficients of molecules from chemical mixtures with high precision and throughput. This novel approach predicts skin permeability based on its correlation with the partition coefficients from chemical mixtures determined in a fiber array. Each of the membrane-coated fibers represents a pattern of molecular interactions: polydimethylsiloxane (PDMS, lipophilic), polyacrylate (PA, polarizable) and CarboWax (Wax, polar). Molecular interactions occurring during percutaneous absorption can be simulated by the multiple fibers: log(kp) = c + a logKMCF1+ b logKMCF2 + - + logKMCFn. The feasibility of this approach was demonstrated with 25 diverse chemicals; their skin permeability [log(kp)] from chemical mixtures were measured by in vitro flow through diffusion experiments and partition coefficients of the chemicals (logKMCFn) were determined by the membrane-coated fiber technique. Multiple regression analysis was used to define equations linking log(kp) to logKMCFn for the three MCFs. A significant correlation equation was defined: Log(kp)= -2.73 - 1.31 logKwax - 0.31 logKpdms + 2.34 logKpa with a R 2 of 0.92. The correlation coefficients in the equation reflected the mixture-skin interactions in different vehicles. These data clearly demonstrate that dermal absorption of diverse chemicals can be estimated from data collected in the inert fiber array which reflect the physicochemical diversity of interactions seen when chemicals partition into the stratum corneum.
Chemical-properties; Chemical-composition; Filter-fabrics; Filter-materials; Filter-membranes; Filtration; Physical-chemistry; Skin-exposure; Skin-irritants; Skin-sensitivity; Skin-absorption; Chemical-composition; Chemical-properties; Chemical-reactions; Chemoreceptors; Mathematical-models; Statistical-analysis
Issue of Publication
Work Environment and Workforce: Mixed Exposures
The Toxicologist. Society of Toxicology 46th Annual Meeting and ToxExpo, March 25-29, 2007, Charlotte, North Carolina
North Carolina State University, Raleigh, North Carolina
Page last reviewed: March 11, 2019
Content source: National Institute for Occupational Safety and Health Education and Information Division