PERCUTANEOUS ABSORPTION AND THE COSMETIC MANUFACTURER By EVEe. ETT L. S^uL* Presented September 23-25, 1959, Seminar, New York CRy TH•s SEymour^R, devoted entirely to the subject of percutaneous ab- sorption or penetration, is developed. out of an apparent need to clarify and summarize the status of an area which is becoming more vital and im- portant every day. It is important not only to the fundamental studies on skin but of great practical concern to the manufacturer of cosmetics and topically applied products. The reputable cosmetic manufacturer attempts to create and provide products which beneficially affect the skin. To do so he is seeking a ra- tionale for his product, as well as materials which he hopes will bring about these beneficial results. The manufacturer is therefore confronted with a number of serious problems. He requires basic information on the skin, knowledge of the consumer problems and skin pharmacology, methods of measuring beneficial and harmful effects on the skin and a thorough ap- preciation of the fate of the materials topically applied. Increasing knowledge, new materials and particularly biologically ac- tive ones, have broadened the horizons for the cosmetic chemist. Since he is concerned with the functional characteristics of his products, he ex- pects to elicit a reaction of one sort or another on the skin. Even if such a reaction seems to be purely local and superficial in nature, the inference is that a certain degree of absorption has taken place. Although by and large, the skin is a highly effective protective barrier, we are discovering that more and more kinds of molecules can penetrate it. We become in- volved in the rate and depth of penetration, in routes of penetration and the role of vehicles. The cosmetic chemist in seeking to create products beneficial to the skin, will not necessarily avoid the use of ingredients which penetrate the skin if they provide beneficial effects. His goal is to produce the best product so long as harmful side effects are absent. I do not believe that if substances penetrate the skin, it is good or bad. Constructive use must be made of advantages offered by such substances. If the problems of sensitization, * Bristol-Myers Products Division, Hillside 5, N.J. 57

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?