Inert multiple membrane-coated fibers predict dermal absorption of chemicals from mixtures.
Riviere-JE; Xia-X; Baynes-RE; Monteiro-Riviere-NA
Toxicologist 2006 Mar; 90(1):171
Skin absorption of compounds from chemical mixtures is affected by many factors including chemical-chemical, chemical-vehicle, chemical-skin and vehicle-skin interactions; with the rate-limiting process primarily being interactions with the stratum corneum. To address this, we have developed a multiple membrane-coated fiber (MCF) approach that unlike in vitro skin systems, has the advantages of relatively high throughput. Three diverse MCFs [polydimethylsiloxane (PDMS, lipophilic), polyacrylate (PA, polarizable) and CarboWax (wax, polar)] were selected to simulate the array of molecular interactions existing in the skin/chemical mixture systems. Skin permeability coefficient (log kp) of a set of 16 diverse compounds from chemical mixtures (water, water-ethanol, water surfactant) were measured by in vitro flow through diffusion experiments and membrane/chemical mixture partition coefficients (log KMCF/Mix) were determined. Concentrations of all chemicals were assayed using GC-MS. Multiple regression analysis was used to define equations linking log kp to log KMCF/Mix for the three MCFs across the three vehicle systems. Significant correlation equations were defined for each vehicle exposure: water - R2=0.96; 50% ethanol - R2=0.91; and 1% SLS - R2=0.86. Differences in equations across vehicles probably reflect mixture-skin interactions. These studies demonstrate that dermal absorption of a diverse series of compounds can be estimated from data collected in three inert fibers which reflect the physicochemical diversity of interactions seen when chemicals partition into the stratum corneum.
Skin-absorption; Chemical-analysis; Skin; In-vitro-studies; In-vivo-studies
Work Environment and Workforce: Mixed Exposures
The Toxicologist. Society of Toxicology 45th Annual Meeting and ToxExpo, March 5-9, 2006, San Diego, California
North Carolina State University, Raleigh, North Carolina