ASSESSMENT OF SKIN ABSORPTION AND METABOLISM OF ARACHIDONIC ACID & GLYCERYL ARACHIDONATE USING IN VITRO DIFFUSION CELL TECHNIQUES.

• TR Number: 338
• Authors: Eppler1,2, A.R., Kraeling1, M.E.K., Wickett2, R.L., Bronaugh1, R.L. 1Office of Cosmetics and Colors/ Cosmetic Toxicology Branch, US Food & Drug Administration, Laurel, MD, 2College of Pharmacy, University of Cincinnati, Cincinnati, OH. Poster Presented at the Society of Toxicology Annual Meeting, Baltimore, MD. March 21-25, (2004).
• Materials Tested: AA, Arachidonic acid (AA), GA, Glyceryl arachidonate (GA)

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 partially metabolized by ester hydrolysis in skin to AA. Based on the Cosmetic Ingredient Review (CIR) Panel’s concern that there was a lack of dermal absorption data for AA, in vitro percutaneous absorption and metabolism studies were initiated. To simulate normal consumer use, AA and GA were applied in an oil in water emulsion (2mg/cm2) to skin samples 200um thick in flow-through diffusion cells perfused with a physiological buffer. To assay for permeation, viable fuzzy rat and human skin were dosed with [14C] AA containing ~0.5uCi (0.01mg) AA /cell while [3H]GA was applied to viable and cadaver human skin at ~0.5uCi (0.003mg) GA/cell. For metabolism analysis, the skin equivalent Epiderm was dosed with [3H]GA under similar conditions. Receptor fluid fractions were collected at 6h intervals over a 24h dosing period. Skin penetration was determined by liquid scintillation counting and expressed as a percent of the applied dose. High performance liquid chromatography was used to assess metabolism to AA. Absorption of AA through rat skin was 19.8 ± 5.3 % (mean ± SEM) compared to only 1.4 ± 0.3 % through human skin. Total AA penetration (receptor fluid plus skin levels) in rat and human skin was 52.3 ± 7.3 and 20.1 ± 5.4 %, respectively. Total GA penetration of viable skin was found to be 11.3 ± 2.1% with only 3.2 ± 0.5% absorbed through the skin. In cadaver skin, 4.8 ± 0.8% GA was absorbed through skin with a total penetration of 6.7 ± 1.2%. Assay of the Epiderm receptor fluid found ~50% absorption of radioactivity and 3.0 ± 2.1% GA conversion to AA. In conclusion, percutaneous absorption of AA was less through human than rat skin, while GA absorbed through Epiderm was metabolized to AA.