Quantification of mixture interactions on dermal permeability - a solvatochromatic approach.
Baynes-RE; Barlow-BM; Xia-XR; Yeatts-JL; Brooks-JD; Riviere-JE
Toxicologist 2005 Mar; 84(Suppl 1):449-450
The influences of mixture-mixture interactions, differing solvent systems, and surfactants on permeability and dermal absorption have not been well studied. Past research has focused on the toxicity of a single solute dosed in an organic solvent; unfortunately, these conditions do not generally represent real world scenarios of occupational use. The scope of our study is to identify and quantify physicochemical interactions that drive dermal permeability using Linear Solvation Energy Relationships during complex mixture exposure. Seven solutes (propylbenzene, biphenyl, naphthalene, methyl benzoate, 4-nitrotoluene, phenol, and 3-methyl phenol) with a wide range of known physiochemical properties (Log p, solubility, molecular weights, etc.) and LSER solvatochromatic parameters were prepared in various mixtures (0-100% aqueous or ethanol solutions and/or 0.1%, 1% and 10% SLS), and applied to a porcine skin flow thru diffusion cell system. Dermal permeability was then calculated using the resultant perfusate and SPME GC/MS or GC/FID detection. The LSER system coefficients (r, s, a, b, v) were compared to derive an interaction coefficient value. Preliminarily results indicate that ethanol at 50% strength decreased both hydrogen bond acceptor activity and McGowan molecular volume, while the presence of surfactants increased both hydrogen bond acceptor activity, and McGowan molecular volume. These results indicated that system basicity and lipophilicity play a significant role in dermal permeability of solutes after exposure to complex solvent and surfactant mixtures. Further studies are aimed at discerning quantitatively the biological and chemical contributions of these interactions.
Solvents; Surfactants; Absorption-rates; Organic-solvents; Toxins; Toxic-effects; Quantitative-analysis; Biological-factors; Chemical-analysis; In-vitro-studies; Skin-exposure; Skin-irritants; Skin-sensitivity; Synergism; Dermatitis; Detergents; Detergent-enzymes
91-20-3; 93-58-3; 99-99-0; 108-95-2; 108-39-4
Disease and Injury: Allergic and Irritant Dermatitis
The Toxicologist. Society of Toxicology 44th Annual Meeting and ToxExpo, March 6-10, 2005, New Orleans, Louisiana
North Carolina State University, Raleigh, North Carolina