186 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS REFERENCES (1) T.J. Franz and P. A. Lehman, The use of water permeability as a means of validation for skin integrity in in vitro percutaneous absorption studies,J. Invest. Dermatol., 94, 525-528 (1990). (2) R.L. Bronaugh, R. F. Stewart, and M. Simon, Methods for in vitro percutaneous absorption studies. VII: Use of excised human skin, J. Pharm. Sci., 75, 1094-1097 (1986). (3) S. R. May and J. F. Wainwright, Integrated study of the structural and metabolic degeneration of skin during 4øC storage in nutrient medium, Cryobiology, 22, 18-34 (1985). (4) M.D. Rosenquist, A. E. Cram, and G. P. Kealey, Skin preservation at 4øC: A species comparison, Cryobiology, 25, 31-37 (1988). (5) G. S. Hawkins and W. G. Reinfenrath, Development of an in vitro model for determining the fate of chemicals applied to skin, Fund. Appl. Toxicol., 4, S133-S144 (1984). (6) R. Dulbecco and M. Vogt, Plaque formation and isolation of pure lines with poliomyelitis viruses,J. Exp. Med., 99, 167-182 (1954). (7) R.L. Bronaugh, R. F. Stewart, and E. R. Congdon, Differences in permeability of rat skin related to sex and body site, J. Soc. Cosmet. Chem., 34, 127-135 (1983).

j. Soc. Cosmet. Chem., 48, 187-197 (July/August 1997) In vitro percutaneous absorption of alpha hydroxy acids in human skin MARGARET E. K. KRAELING and ROBERT L. BRONAUGH, Office of Cosmetics and Colors, Food and Drug Administration, Laurel, MD 20708. Accepted for publication Septewzber 3 O, 1997. Presented in part at the Annual Scientific Meeeting of the Society of Cosmetic Chemists, New York, Decewzber 12-13, 1996 Synopsis Alpha hydroxy acids (AHAs) are used in many cosmetic products as exfoliants, moisturizers, and emollients. The activity of AHAs on skin is likely influenced by their ability to be absorbed into the different layers of skin. The absorption of a homologous series of AHAs was measured through hunnan skin by using in vitro diffusion cell techniques. The [•4C] radiolabeled compounds were applied to the skin in an oil-in-water emulsion vehicle. The absorption of the AHAs was measured at pH 3.0, to simulate the pH of the most acidic cosmetic formulations, and at pH 7.0, to observe the effect of complete ionization of AHAs on skin penetration. Much greater absorption of the AHAs was seen at pH 3.0. We also observed substantial absorption into the various skin layers (stratum corneum, viable epidermis and dermis) as well as the receptor fluid. Total absorption of glycolic acid and lactic acid was similar (27-30%). Absorption of the longer-chain AHAs decreased to 21.0% and 19.3%, for 2-hydroxyoctanoic and 2-hydroxydecanoic acids, respectively. At the end of the 24-h studies, these longer-chain AHAs did not form a depot in the skin. The stratum corneum was shown to have a pH gradient with an average pH near 7 at the viable epidermal layer. Therefore, the AHAs ionize to polar molecules as they enter and diffuse through the stratum corneum. INTRODUCTION Alpha hydroxy acids (AHAs) are widely used in cosmetic products. The small, short- chained compounds glycolic acid and lactic acid are most widely used, but longer-chain AHAs have been found to increase stratum corneum extensibility and flexibility (1) and have been used in some products. The effects of AHAs on skin structure are noticed in the stratum corneum (2), the viable epidermis (3), and even deeper in the dermal layer (3). The mechanism of AHA action is still unknown. Van Scot et al. have suggested that AHAs reduce stratum corneum corneocyte cohesion by interference with ionic bonding (4). But structural changes in the epidermis and dermis suggest that effects on the stratum corneum could originate from AHA activity in these deeper layers. Understand- ing the extent of absorption of AHAs is important, particularly with regard to the 187