PERCUTANEOUS ABSORPTION OF VITAMIN A 373 Several weeks elapsed between generalized vitamin A deficiency and the appearance of skin changes. There was also a time-lag between topical application of vitamin A and restoration of the skin. Although xeroph- Figure 7.--Four weeks after treatment, untreated site. Rat 84 days old. This is a histologi- cal picture of a grossly "A"-depleted animal (X 100). -. .• • ... . . _•. . .•. , • - • .-' '•i.. - ..... - '•'.' - ..... . .- .... - • ', . ß • .-•. • •-• '•- •..• • '-•. •.•:• • • . . •.. . '• •4.• :.. v . . • •.•: :.. •?• •.. . .. : :: •,. • • '.'. . -.. • • .:. -. , • •:: • • -:.. .• :.. • ...... •.... • .. Figure 8.•Four weeks after treatment, site of application. Rat 84 days old. Note ac- tive hair growth. The dermis has its usual component of fat, and the s•n appears normal in every way (X100).

374 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS thalmia disappeared and weight gain occurred shortly after commence- ment of topical treatment with the vitamin, restoration of the skin lagged four weeks behind, and was then apparent only at the site of application. These findings indicate that vitamin A is necessary for the normal reproduc- Figure 9.--Four weeks after treatment, site of application. Effect of aqueous dispersion. Rat 91 days old. Vitamin A plus Tween 20 was applied to the skin for 28 days. Note the extremely hypertrophied epidermis and the formation of deep epidermal pits (X 100). I LOGARITHMImVSoRATSFEDDAILY-STOCKOFA.,.-ORALVITAMINOFSTORAGE CURVES-P DOSE 5 I /,•-ORAL-"A" DEFICIENT RATS •,_[ .// ,.-TOPICAL-STOCK FED RATSae -TOPICAL-"A" DEFICIENT RATS I *-NET "..A'i. STORAGE(MINUS 132 MCGM.) I -•-•-NET "A" STORAGE(MINUS III MCGM.) 01 , , , , , 0 I 2 3 4 5 LOG OF DAILY DOSE Figure 10.--Logarithmic curves of liver storage of vitamin A following topical and oral administration in the stock-fed and "A"-deficient rats.