PERCUTANEOUS ABSORPTION OF VITAMINS 163 cally significant quantities. Vitamin A does not appear to penetrate dead skin unless salicylate is added to the medium (29). Blank (30) has commented that it is probable that vitamin A "penetrates intact human skin slowly and that only a small portion of the amount applied reaches the granular and Malpighian layer where any faulty keratinization might be corrected." According to Stiittgen and Wrist (26) the inability to find increased serum levels after topical application does not mean that vitamin A is not absorbed since the removal of vitamin A from the blood stream can well be as rapid as its absorption. In recent experiments Stiittgen (20, 21) applied both tritium-labeled and carbon- labeled vitamin A to human skin, and in both in vitro and in vivo tests found a small but significant absorption through the skin. In these human tests the low rate of absorption necessitated great care to avoid contamination of the various skin layers with radioactive material. A new blade was used for each cut and cuts were made successively from a layer having the lowest activity to layers of anticipated increasingly higher activity. A tendency was observed for saturation in the lower layer of the skin in vivo, which indicates a low rate of systemic absorption. In view of this, it is not surprising that blood levels of vitamin A in humans are not increased by topically applied vitamin A. The amount of vitamin A contained in normal skin is not known. Corn- bleet and Popper (31) attempted to detect vitamin A in normal epidermis, but the fluorometric method used did not reveal the presence of vitamin A except in the adjacent fat tissue, even after large oral doses of vitamin A. It is likely, however, as stated by Rothman (32) that, since vitamin A is required for the maintenance of normal epidermal cell life, it is not feasible that it should not reach the epidermis. Topical application of vitamin A has been reported effective in a number of dermatological conditions. As these reports have been reviewed by Siemers and Sleezer (3), De Ritter et al. (2) and Eller and Wolff (1), only the most recent papers will be discussed. Marked improvement in four out of six cases of ichthyosis and one with multiple epidermal dysplasia has been reported by Flesch (25) after application of vitamin A ointments. Improvement was limited to the site of application of the ointments control areas, treated with the ointment bases alone, did not show any change. Reiss and Campbell (23) studied the effect of vitamin A ointment on the aging skin associated with dryness and scaliness and on a number of dermatoses in four of five subjects, topical vitamin A improved the condition of the senile skin: dryness was alleviated, scaliness and follicular hyperkeratosis disappeared. The control area treated with the ointment base also showed diminution of dryness but to a much lesser degree. Ichthyosis lichen pilaris, pityriasis tabescentium and winter eczema were noticeably improved, whereas psoriasis was unaffected. The clinical

164 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS effect on skin of large doses of vitamin A may be due either to alleviation of a local, relative hypovitaminosis A of the skin (33) or to a pharmacody- namic or pharmacological effect (25, 34). Shelmire (35) studied factors influencing the diffusion of vitamin A to the skin surface and concluded that vitamin A diffuses best from a non- volatile, water miscible vehicle which maintains the least hydration of the skin-vehicle interface. OTHER FAT SOLUBLE VITAMI•rS The effects of topical application of vitamin D have been reviewed by De Ritter eta/. (2) and Eller and Wolff (1). Vitamin D applied to the skin in sufficient amounts has been reported to cure rickets in animals and human beings (1, 2). Volliner et aL (36) reported successful percutaneous therapy with vitamin K in infants suffering from prothrombinopenia. Vitamin E, in combination with vitamin A, increases storage of vitamin A in the rat when both are applied topically (37). WATF. R SOLUBLE Panthenol Panthenol, the alcohol analog of pantothenic acid, is rapidly converted to pantothenic acid when administered orally or topically. When ad- ministered orally it shows full vitamin activity in the cure of pantothenate deficient rats. Topical application of panthenol cures deficiency symp- toms in animals. In humans, local application of panthenol has been shown to aid healing of the skin by promoting granulation and epitheliza- tion. ,4nimals Burlet (38) found that the pantothenic acid content of the skin of normal rats is increased significantly after panthenol application. Similar increases in skin pantothenic acid in areas where panthenol was not applied are indicative of systemic penetration of panthenol. In pantothenate- deficient rats topical application of panthenol resulted in increased con- centration of pantothenic acid in the skin, muscle, liver and blood. The restoration of hair color in the pantothenate-deficient black rat and the cure of alopecia in the pantothenate-deficient mouse through topical application of panthenol, has been reported by Pfaltz (39), who found local application of panthenol to give more favorable results than oral dosage. Stfittgen (40), using tritium-labeled material, has demonstrated the sorption of panthenol through animal skin. Man An increase in the pantothenic acid content of human hair after applying