58 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS irritation and systemic toxicity are too hazardous, we must simply write off the material and product as unacceptable. That there may be side effects is inevitable. They may be minor, how- ever. Cautionary statements on the label and package may also be neces- sary. As time goes on it may be apparent that we are toying with subtle differences between what has been defined as a cosmetic and as a drug. In some cases this may be a real difference and in others a meaningless distinction. As our knowledge increases, we may find that applications to the skin of so-called innocuous materials do involve tissue structures be- low the horny layer and have done so for hundreds of years. We are on the threshold of developing more refined techniques for measuring pene- tration and skin effects and needless to say we badly need the disciplines of physical chemistry and biophysics to elucidate the role of the skin as a semipermeable membrane. Precisely because the manufacturer is concerned with the phenomenon of penetration, he must be even more alert to the potential limitations of his product. He must even more carefully now consider the extent and nature of the skin area to which material is applied. He must bear in mind the frequency and duration of use, concentration of active agents and he must take into account whether he is dealing with so-called "normal" or damaged skin. He should be prepared to have sound evidence on sen- sitizing effects, irritation, "skin fatigue" and systemic manifestations. I think that most of the Seminar' speakers will agree with me that al- though there have been contributions made by many workers, the sta- tus of percutaneous absorption reveals some variance in findings and in- terpretation, a lack of precise methodology and of a clear enunciation of the principles involved in the penetration of materials into the skin. The purpose of this Seminar is to provide some degree of orientation on the subject of percutaneous absorption. We cannot side-step the problem and at least four questions must ultimately be answered: 1. Is it essential and desirable to have percutaneous absorption to ob- tain beneficial skin effects? 2. What are these effects and how do we measure them ? 3. What are the potential hazards of percutaneous absorption, and 4. How will the Food and Drug Adminstration and the cosmetic manufacturer mutually work out the potential problems involved?

PERCUTANEOUS ABSORPTION STATEMENT OF PROBLEM AND CRITICAL REVIEW OF PAST METHODS By IRv'if• H. B•,ANK* Presented September 23-2¾, 1959, Seminar, New York City IT SEEMS to me that the cosmetic chemist should continuously ask himself what he expects a cosmetic to accomplish and by what mechanism a given cosmetic may produce the desired results. I believe it is correct to say that the detailed mechanism of action of many cosmetics is unknown. Why do I bring up mechanism of action in a symposium on percutaneous absorption ? As most of you know, for several years I have been interested in emollients, and it is my contention that these substances can relieve a sensation of dryness without penetrating into the skin. In working with emollients it is, therefore, unnecessary to study the percutaneous absorp- tion of their ingredients in order to understand the way in which they function. But this is probably not true of many other types of cosmetics. Any antiperspirant capable of decreasing the activity of the sweat gland must penetrate into the skin and reach the gland. If a topically applied estrogen causes swelling of the collagen fibers, it must have penetrated and reached the dermis. Any cosmetic ingredient which has caused allergic sensitization must have penetrated the skin and reached the reticulo-endothelial system where antibodies are produced. It is entirely fitting, therefore, that the cosmetic chemists should be devoting a two-day seminar to the study of percutaneous absorption. In order to understand the way in which a cosmetic acts, it is usually helpful to know (a) whether any ingredient of that cosmetic can penetrate into the normal skin (b) how far into the skin it can penetrate, (c) with which specific tissues it comes in contact, and (d) the rate at which it penetrates. These, then, are some of the problems of percutaneous absorp- tion which confront the cosmetic chemists these are some of the questions which must be answered. As you know, and as you will hear in some detail during this symposium, percutaneous absorption has been studied in experimental animals and man * Dermatological Research Laboratories, Dept. of Dermatology, Harvard Medical School at the Massachusetts General Hospital, Boston 14, Mass. 59