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Predicting skin permeability of molecules from chemical mixtures using an inert membrane-coated fiber array.

Authors
Xia-XR; Baynes-RE; Monteiro-Riviere-NA; Riviere-JE
Source
Toxicologist 2007 Mar; 96(1):433-434
NIOSHTIC No.
20031942
Abstract
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.
Keywords
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
Publication Date
20070301
Document Type
Abstract
Funding Amount
746428
Funding Type
Grant
Fiscal Year
2007
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-R01-OH-007555; Grant-Number-R01-OH-003669
Issue of Publication
1
ISSN
1096-6080
Priority Area
Work Environment and Workforce: Mixed Exposures
Source Name
The Toxicologist. Society of Toxicology 46th Annual Meeting and ToxExpo, March 25-29, 2007, Charlotte, North Carolina
State
NC
Performing Organization
North Carolina State University, Raleigh, North Carolina
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