316 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS In the case of laboratory animals we have not observed significant effects from external applications of hormone ointments in experiments conducted by our Skin Toxicity Branch. In one experiment an estrogenic ointment was inuncted daily using young virgin female albino rabbits as the test subjects. The dosages employed 250, 500, 1000 and 4000 I.U. estrone applied daily, five days a week for ninety days. Histopathologica] examination of the skin at termination of the experiment revealed a slight epidermal thickening which was no different than that exhibited in control animals treated in the same manner with the ointment base with no added estrone. In an attempt to determine if continued application of estrone would delay or prevent senile changes in the skin, another group of young animals were treated daily five days a week for eighteen months. The vehicles in this experiment were dimethyl phthalate and 70 per cent alcohol. Doses of 1000 and 5000 I.U. of each were employed in the above protocol. In these doses of massive estrone administration, the only skin changes ob- served were a slight increase in epidermal thickness and a slight reduction in numbers of hair follicles. These changes were overshadowed in the latter half of the experimental period by degenerative lesions attributable to old age and general debility. At these massive levels of estrone, uterine thickening and necrosis were observed also. Our conclusions from these experiments were: 1. No significant skin effects were obtained even from very large dosages of estrone. 2. At the levels at which minor skin changes did occur, systemic effects were also observed. 3. Skin deterioration (senile skin changes) were not prevented. VITAMINS A aND D These two vitamins are absorbed percutaneously in limited quantities. However, these are not absorbed in sufficient quantities by the percu- taneous route to produce changes in skin keratinization. It has been possible to alleviate conditions of vitamin A deficiency in man by topical application of the vitamin. Topical application of vitamin A has produced significant thickening of epidermis in rats, but this has not been duplicated in other species. ANTIBIOTICS Some of the more common uses of antibiotics in cosmetic type prepara- tions include: 1. Dentifrices 2. Antiperspirants 3. Mouth washes

DRUGS IN COSMETICS--SHOULD THEY MIX? 317 We believe that inclusion of antibiotics in these products should be approached with great caution. Cosmetics are used much more extensively, and by an entire regimen of dosage different from drug usage. Repeated application may produce serious sensitization to an antibiotic, and a sensitized person may have to be denied use of a lif•-saving drug in event of need in future drug therapy. There is also the potential danger in the indiscriminate use of antibiotics in cosmetics leading to the development of resistant strains of organisms. Hence this type of product is likely to fall in the "new drug" category for which applications establishing safety are required. MERCURY Mercury compounds have been used in cosmetics since antiquity. However, they cannot be regarded as innocuous. Actually, mercury and its compounds are extremely toxic. There is little or no margin of safety between effective and toxic levels. Sensitization to mercury compounds is not uncommon. The principal application of mercury is in the form of ammoniated mercury used in bleaching creams. The action of mercury is to arrest' DOPA, an enzyme, dihydroxy-phenyl alanine, which is essential in the process of conversion of tyrosine to melanine in the skin. We have regarded such articles in the category of drugs for self-medication that should conform to the following restrictions: 1. Ammoniated mercury preparations should not exceed 5 per cent concentration. 2. Mercuric bichloride and other mercurials must not exceed 0.2 per cent concentration. 3. "Use" to be immediately discontinued if irritation develops. 4. Not to be used on damaged skin, such as shaving "nicks" or after a depilatory. 5. There should be a preliminary test for sensitization to mercury. 6. Preparations are not to be used on children below twelve years of age. Mercury preservatives such as phenyl mercuric acetate and mercury nitrate are not present in sufficient concentration to cause concern, but may produce sensitization. ß ANTISEPTICS This represents a large class of chemicals of which the more common are: 1. 2. 3. 4. 5. Hexachlorophene and dichlorophene. Bithionol. TMTD, tetramethylthiuram disulfide, salicyl anilide and others. Resorcinol and hexylresorcinol. A large group of cationic surfactants.