SOME USES AND LIMITATIONS OF RADIOACTIVE ISOTOPES IN COSMETIC CHEMISTRY--FROM A DERMATOLOGIST'S POINT OF VIEW* By VICTOR H. WITTEN, M.D. Department of Dermatology and Syphilology, New York University, Bellevue Medical Center, New York, N.Y. AFTER CONSIDERING VARIOUS ways of presenting this subject, I decided to mention several possible investigative problems, ones that would point out at least some of the uses and limitations of radioactive isotopes in cosmetic chemistry. I believe that all of the problems to be mentioned are, in one way or another, of interest to both the cosmetic chemist and the dermatologist. As you are well aware, various methods have been used to demonstrate absorption of specific chemicals or compounds applied to the surface of the skin. Among these methods are the older chemical, colorimetric and spec- trophotometric determinations of the particular chemical or compound in urine and blood specimens and in sections of the skin. There are also the bioassays, for example, vaginal cornification produced by the topical application of estrogens to the mucous membranes or even to the glabrous skin and of course the use of chemical analysis to demonstrate the ac- cumulation of specific chemicals in various internal structures, etc. Radioactive isotopes are being used with greater frequency for the pur- poses of studying the absorption and distribution of various chemicals the particular chemical or compound being followed is given radioactive properties so that it may be traced by special methods. Perhaps it would be helpful if I review with you the reasons why this approach has proved advantageous in so many instances. 1. Radioactive isotopes are chemically identical with their stable isotope and therefore behave exactly the same in all chemical and bio- chemical processes. 2. The methods used to demonstrate radioactive elements are far more sensitive than the chemical methods employed to test for stable elements, thus making it possible to test for far greater dilutions of the radioactively * Presented at the March 23, 1955, Meeting of the New York Chapter, New York City. 399

400 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS tagged compounds. In many instances quantities of radioisotopes too small to be measured by chemical means can be readily detected by special electronic devices. 3. The presence of radioisotopes can be detected in situ in intact living organisms and tissues by means of special methods without the need for biopsy, sampling or extraction. 4. Radioisotopes make it possible to study such dynamic processes as the rate of chemical transfer, exchange of components across cellular membranes and intermediate metabolism such as synthesis and breakdown of organic complexes. 5. The site of localization of radioisotopes emitting alpha and beta rays can be demonstrated by autoradiography. In order to be used for experimental purposes, a radioactive tracer sub- stance must have the following properties: 1. Be of sufficient initial concentration to withstand dilution. 2. Be sufficiently stable chemically. 3. Not interfere with the normal series of biologic and/or pathologic events in which one is interested. 4. Have an adequate radioactive half-life. 5. Not be stored in any human organ or tissue in a concentration that might prove damaging. In undertaking any tracer study it is first necessary to label, with a radioactive tag, the particular chemical or compound to be traced. But this involves more than loosely attaching a tag as one might tie a stringed label to a suitcase for identification purposes. This radioactive tag must be an integral part of the chemical. If the substance being investigated is an inorganic element or its salt, the element itself should be radioactive if an organic compound the radioactive element should be a part of the central structure. If it is a side chain that bears the radioactive tag there is a greater chance of loosing it. Of course, giving a substance a radioactive label can present numerous difficulties, and may at times be one of the limitations to the use of radio- active isotopes for tracer purposes. In some instances, compounds can be synthesized in the laboratory where the radioactive atoms can be selected and introduced by chemical synthesis at any desired position in the chemi- cal structure. In other instances the tagging may be accomplished through biosynthesis by feeding a particular radioactive atom to a living system which in turn produces the desired radioactive molecule. Once the radioactively tagged chemical or compound has been prepared it is ready to be incorporated in a selected vehicle to be used for various studies. Since the radioactive form of the substance will behave both chemically and biochemically in an identical fashion as the non-radioactive form, only small amounts of the radioactively tagged substance need be