194 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS s. Ap I.Ap strips 2h 6h 24h 24h 72h 61.7 26.8 12.2 7.5 7.5 1-5 + + + + + 11.8 5.1 3.4 0.7 1.7 18.2 5.9 4.9 6.7 6.2 6-20 + + + + + 3,6 1,3 ],2 0,7 ].3 lb 1'5 2'0 Number of strips Figure 1. Distribution profile of •4C linoleic acid in the horny layer, 24 h after a single application. Total quantities expressed as }xg/cm 2 found in the first five strips and in the last fifteen strips for each experi- ment. S. Ap: Single application I. Ap: Interative applications.

PERCUTANEOUS PENETRATION OF LINOLEIC ACID 195 lOO 50. HORNY LAYER m m EPIDERMIS PLUS DERMIS m mm m m m m m m m m m m m m 2 H 6 H 24 H 24 H 72 H SINGLE APPLICATION ITERATIVE APPLICATION Figure 2. Total quantities of •4C linoleic acid in the horny layer and in the epidermis plus dermis after a single application or iterative applications. DISCUSSION Linoleic acid diffuses slowly toward the living layers of the skin, as evidenced by a significant decrease in its concentration in the stratum comeurn between 2 and 24 h after a single application and a significant concurrent increase in its concentration in the epidermis and dermis (Figure 2). In the case of multiple applications, distribution pro- files in the horny layer were the same 24 and 72 h after the last treatment, and corre- sponding total quantities were equal to those found 24 h after a single application. These data suggest that 24 h are necessary to establish the epidermal-dermal concentra- tion gradient. Then, daily repeated applications compensate for the uptake of the dif- fusing substance by the living layers, so that the level of linoleic acid in the horny layer remains stable. This behavior is characteristic of a reservoir effect (16). In the living tissues, radioactive counts were greater at a depth of 150 to 200 l•m than at the epidermal level, for both single application and repetitive application experi- ments (Figures 3 and 4). Histological studies (17) show that sebaceous glands are lo- cated at this level. This suggests some storage of linoleic acid in sebaceous glands and ducts of the hairless rat. This storage increases significantly with time and is several times more important at 24 h than at 2 h after a single application.