| The Cosmetic Ingredient Review Panel's final report on the safety assessment of arachidonic acid (AA) noted its use in cosmetic skin preparations although there is a lack of dermal absorption data. The safety concern of topical applied AA arises upon its metabolism to pro-inflammatory mediators. In vitro percutaneous absorption/metabolism studies were initiated in flow-through diffusion cells. AA, and its glycerin monoester, glyceryl arachidonate (GA), were each applied in an o/w emulsion to simulate cosmetic consumer use conditions. AA was analyzed for absorption/metabolism in viable rat and human skin while GA was tested in cultured (EpiDerm(TM)), viable human, and human cadaver skin. Absorption data on both compounds was collected every 6hr over a 24hr period. The highest absorption was observed through EpiDerm(TM) (50%) and rat skin (20%). To a lesser extent, AA and GA penetrated human skin about 20%, of which ∼2% absorbed. A reservoir of AA was observed in cadaver skin during an extended absorption study (72hr), in which absorption increased to 4%. Ester hydrolysis of GA occurred in each of the analyzed tissue samples.; Additionally, in vitro methods (as an alternative to the Draize test) were evaluated for their prediction of skin irritation potential in conjunction with flow-through diffusion cell absorption/metabolism measurements. Model compounds, with known irritation potential in vivo, were evaluated in vitro by measuring transepidermal water loss (TEWL), cytokine release (IL-1alpha), and skin viability (MTT) of rat and cultured skin in flow-through diffusion cells. Irritation potential of the model compounds was less pronounced in the emulsion formulation compared to an aqueous vehicle. No significant irritation from AA in an emulsion vehicle was observed with the alternative methods. As a supplementary assessment, TEWL was analyzed for its relationship to the 3H2O skin barrier integrity test, however no direct correlation was found to exist.; Absorption of topically applied AA and GA was observed, indicating a potential for systemic availability. Furthermore, ester hydrolysis of GA occurred during absorption. The in vitro alternative methods for measuring skin irritation in flow-through diffusion cells were able to differentiate between the potency of irritants in an aqueous but not an emulsion formulation. |
