PERCUTANEOUS ABSORPTION OF VITAMIN A 375 tion of the basal cells of the skin. When the basal cells are deprived of vitamin A, the derived cells are "A"-deficient when the basal cells are provided with vitamin A, the derived cells produce normal skin. These findings also indicate that topical application of vitamin A affects resto- ration of the skin directly rather than through absorption and recirculation of "A." The relation between vitamin A storage and topical application of var- ious amounts of the vitamin is illustrated in Fig. 10. In these experiments the vitamin was administered in corn oil and a daily dose applied for twenty- eight days. Vitamin A storage was proportional to the dose, and the amount stored from absorption across the skin of normal rats fed the stock diet was about twice that from absorption across the skin of vitamin A de- ficient rats. Thus it was evident that the deficiency causes changes in the skin, which in turn make it more difficult for the vitamin to penetrate. Water-dispersing agents such as Tween 20, while enhancing percutaneous absorption, have a detrimental action upon the skin structure (Fig 9). The sparing action of tocopherols on the storage of vitamin A is a well- known biological phenomenon (4). To determine whether vitamin E has a similar influence in storage from topical applications, the following experi- ments were set up. To corn oil which had been made vitamin E-free, vitamin A plus vitamin E were added applications were made to the skin 200- THE EFFECT OF VITAMIN E ON THE STORAGE OF VITAMIN A IN RATS ON "A" DEFICIENT DIETS I-3o + 3oo ,,E, 3 •-30• '•" ORAL •-30• '•" + 3OO• "E'3TOPiCAL • - 3o• 'X" I I ORAL TOPICAL Figure 11.

376 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS of "A"-deficient rats and results compared to those obtained from topical application of "A" alone. For reference, the same preparation of vitamin A plus E was compared to vitamin A alone, administered orally. As seen in Fig. 11, the storage of "A" was about twice as much following either oral or topical application in the presence of vitamin E, as mixed tocopherols, than following application of vitamin A alone. SVMMAR¾ 1. Vitamin A is absorbed through the skin of "A"-dcficicnt as well as that of normal rats. 2. The amount of vitamin A found stored in liver and kidney depends on the medium of application as well as the amount of the vitamin present in a given medium. 3. Of the ointments tested, the petrolatum lanolin-based ointment, "Desitin," was found to be the most superior as a medium for topical appli- cation of the vitamin. Although it did not enhance storage of vitamin A, it was completely harmless to skin structure. 4. Water-dispersing agents, such as Tween 20, while possibly enhancing percutaneous absorption, have a detrimental action on the skin structure. 5. Although vitamin A in a suitable medium can be transferred through the skin of the "A"-depleted albino rats for several weeks, at least, remission from the "A"-deficiency occurs only at the site of application and not at neighboring sites. 6. Vitamin E augments storage of vitamin A. REFERENCES (1) Sobel, A. E., "Vitamins and Hormones," Vol. 10, New York, Academic Press Inc. (1952), pp. 47-56. (2) Sobel, A. E., Rosenberg, A., and Engel, E., y. Nutrition, 48, 183 (1952). (3) Gerber, A., Raab, A., and Sobel, A. E., Alto. y. Med., 16, 729 (1954). (4) Moore, T., "Vitamin A," Amsterdam, Elsevier Publishing Company (1957). (5) Sobel, A. E., •1.•[.•1. •lrch. Dermatol., 73, 388 (1956). (6) A. •., Parnell, J.P., Sherman, B. S., and Bradley, D. K., 5 t. Invest. Dermatol., 30, 315 (1958. Sobel, zlcknowledgmenls: The D-ointments, L-ointments and DAotion ployed in this study were supplied by the Desitin Chemical Company of Providence, R.I. The D-ointment and D-lotion are commercial prepara- tions marketed under company trademark. The D-ointment-fortified and L-ointment and the L-ointment plus tocopherols were specially prepared for these studies. The E-ointment (Table 3) was an experimental preparation made by the Endo Corporation of Richmond Hill, N.Y.