EFFECTS OF ISOPROPYL MYRISTATE & SQUALANE 277 several investigations have suggested the existence of control mechanisms and substances like chalones (20, 22), cyclic nucleotides (22, 23) and others (20, 24). Figures 4-12 indicated that the effects of squalane, isopropyl myristate and decane on rabbit skin increased in this order, but the irritation potentials of these oils were found to be significantly weak as compared with those of carcinogens (16, 25) or physical damages like plucking (19) and abrasion (17). In terms of the ratio of RNA to DNA, the oils in the present study increased the ratio in rabbit skin to twice the normal at best, while methylcholanthrene (25) or physical abrasion (17) induced an increase of 3-4 times in the epidermis of mice. The magnitude of the effect of vitamin A acid, when topically applied on the ear skin of guinea pig daily for 6 d (23), was found to be similar to that of these oils in terms of the stimulation of DNA synthesis. Skin is a metabolically vigorous tissue, with continuing multiplication of cells in the basal layer and exfoliation of cornified cells in the stratum comeurn. It possesses a great ability for healing the damaged epidermis by a highly active regeneration process. When chemical or physical treatments are applied to the skin, therefore, significant changes in proliferative activity will occur biochemically even though irritation potentials are weak as indicated by squalane. This finding indicates that care should be given to selection of cosmetic ingredients, even though they show low irritation potentials macroscopically or histologically, since cosmetics are applied repeatedly on the skin for many years. CONCLUSION A very sensitive method was employed to study the changes in the epidermis caused by cosmetic oils. In our previous paper (5), it was found that histological changes in the skin induced by a chemical irritant after percutaneous absorption bear no relation to the fate of the irritant in the skin. In the present study, more subtle changes in epidermis could be detected blocheroically, especially for squalane which caused changes in 32p incorporation periodically even after histological changes disappeared. The magnitude of the biochemical effects for the three oils in this study was found to be weak in comparison with other chemical and physical irritations and to increase in the order of squalane, isopropyl myristate and decane, which was consistent with the results of macroscopic and histological observations. Some feedback mechanisms were suggested to control the processes of repairing the damaged skin. REFERENCES (1) K. Aso and T. Okazaki, Effect of 0.1% vitamin A acid ointment on the metabolism of epidermis,Jap. J. Dermatol., 82, 72-82 (1972). (2) C. Prottey, P. J. Hartop and T. F. M. Ferguson, The effect of soap upon certain aspects of skin biochemistry,J. Soc. Cosmet. Chem., 24, 473-492 (1973). (3) M. Mezei, Effect of polysorbate 85 on human skin,J. Invest. DermatoL, 64, 165-168 (1975). (4) S.J. Stegman, K. Fukuyama and W. L. Epstein, Inhibition of the in vivo effects of concanavalin-A on mammalian epidermis by c•-methyl-D-glucopyranoside,J. Invest. Dermatol., 66, 17-21 (1976). (5) M. Suzuki, K. Asaba, H. Komatsu and M. Mochizuka, Autoradiographic study on percutaneous absorption of several oils useful for cosmetics,J. Soc. Cosmet. Chem., 29, 265-282 (1978). (6) K. Asaba, H. Komatsu and M. Suzuki, unpublished data. (7) M. Mezei and G. White, Dermatitic effect of nonionic surfactants III: Incorporation of 32p into

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