D-15
Assessment of Skin Absorption and Metabolism of Arachidonic Acid & Glyceryl Arachidonate Using In Vitro Diffusion Cell Techniques
A. R. Eppler1, M. E. Kraeling1, R. R. Wickett2, R. L. Bronaugh1, 1Office of Cosmetics and Colors, USFDA, Laurel, MD 20708, 2University of Cincinnati, Cincinnati, OH 45267
Arachidonic acid (AA) has been used in cosmetics as a surfactant-cleansing and -emulsifying agent. Glyceryl arachidonate (GA), a skin conditioning agent and emollient, may be hydrolyzed in skin to AA, whose metabolites are pro-inflammatory mediators of irritation. In vitro percutaneous absorption/metabolism studies were initiated because of the lack of AA dermal absorption data observed by the Cosmetic Ingredient Review Panel. AA and GA were applied in an oil in water emulsion (2mg/cm2) for 24hr to 200um thick skin samples in flow-through diffusion cells. Skin penetration, expressed as a percent of the applied dose, was analyzed on viable fuzzy rat and human skin with [14C]AA, while [3H]GA was applied to viable and cadaver human skin. To assess for skin metabolism, Epiderm was similarly dosed with [3H]GA, then analyzed by HPLC. Absorption of AA through rat skin was 19.8 ± 2.5% (mean ± SEM) compared to only 1.3 ± 0.1% through human skin. Total AA penetration (receptor fluid plus skin levels) in rat and human skin was 50.3 ± 3.1% and 18.4 ± 2.0%, respectively. Total GA penetration of viable skin was 21.4 ± 1.1% with only 3.2 ± 0.2% absorbed through the skin. In cadaver skin, 2.2 ± 0.3% GA was absorbed through skin with a total penetration of 14.8 ± 0.9%. Epiderm receptor fluid analysis found ~50% absorption and 3.0 ± 2.1% GA conversion to AA. In conclusion, AA and GA penetration was observed through human and/or rat skin while GA absorbed through Epiderm exhibited metabolism to AA.
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Last updated on 2004-JUN-02 by frf