Assessment of skin absorption and irritation potential of arachidonic acid and glyceryl arachidonate using in vitro diffusion cell techniques.
Arachidonic acid (AA), a precursor of pro-inflammatory mediators, and its glycerin ester, glyceryl arachidonate (GA), are reportedly used in cosmetic products. In vitro skin penetration of AA and GA and GA's ester hydrolysis was determined in flow-through diffusion cells. AA penetration with human and rat skin was 19.5% and 52.3% of the applied dose respectively, a substantial amount of which remained in the skin at 24h. Similar penetration results were obtained with GA in human skin. However, GA penetration through cultured skin (EpiDerm) was 51% of the applied dose, almost all of which appeared in the receptor fluid. At least 27.8% of GA penetrating skin was hydrolyzed to AA. In vitro methods were used to assess skin irritation in diffusion cells. Skin irritation of AA, sodium lauryl sulfate (SLS), and Tween 80 was determined by changes in transepidermal water loss (TEWL), skin viability (3-(4,5-dimethylthiaxol-2-yl)-2,5-diphenyltetrazolium bromide, MTT, formation), and cytokine release (IL-1alpha). SLS irritation was much less pronounced in an emulsion versus an aqueous vehicle. No significant irritation was observed in vitro from AA in an emulsion. This work predicts that AA would penetrate human skin in vivo and that it could be formed in skin from topically applied GA.
Eppler
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Office of Cosmetics and Colors/Division of Cosmetics and Compliance, US Food & Drug Administration, Laurel MD, United States. epplera@wyeth.com
Kraeling
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ME
Wickett
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Bronaugh
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RL
D000818:Animals; D016718:Arachidonic Acid / Q000009:adverse effects* / Q000493:pharmacokinetics*; D015194:Diffusion Chambers, Culture; D005260:Female; D005989:Glycerides / Q000009:adverse effects* / Q000493:pharmacokinetics*; D006801:Humans; D066298:In Vitro Techniques; D053582:Interleukin-1alpha / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D012869:Skin Absorption / Q000502:physiology*; D023422:Skin Irritancy Tests; D013997:Time Factors
D005989:Glycerides; D053582:Interleukin-1alpha; D016718:Arachidonic Acid; C026433:1-arachidonyl monoglyceride