USES AND LIMITATIONS OF RADIOACTIVE ISOTOPES 401 diluted with the non-radioactive tbrm in order to carry out tracer experi- ments. Of course, the amount that must be added will depend on the nature and purpose of the experiment and the particular radioactive iso- tope being used. With the incorporation of the radioactive substance in, let us say, an ointment base, it occurred to me that the radioactive properties of the tag could be put to its first practical use--that of demonstrating even disper- sion of the substance through the ointment base. This, of course, could be done simply enough by taking an aliquot of the mixed ointment and meas- uring its radioactivity. Knowing the total weight of the ointment and the total radioactivity of the substance added, simple calculation should tell if even distribution has taken place. Furthermore, this method should be an easy means of telling how soon after the start of the mixing process the dispersion of a particular substance in a base is complete. One might even use autoradiography to visualize the distribution of a tagged compound through an ointment or any other vehicle. (But perhaps I am complicating existing simpler methods which are being used in the industry and with which I am not familiar.) In addition to the methods now being used by pharmaceutical chemists to test for diffusion of active ingredients from a particular base (e.g., leeching of soluble dyes, colorimetric tests) it appears to me that here again radioactively tagged ingredients could be used to advantage. It should not be diflScult to measure the amounts of radioactive ingredients leaving an ointment which has been applied to a given surface. With the proper set-up, not only the amount could be measured, but also the rate and distribution of the diffusion. And of course, similar methods could be applied in various ways to test for stability, correctness of packaging and compatibility of the tagged ingredient with other added ingredients. I refer to those instances in which the changes that take place are not dis- cernible to the naked eye nor detectable by ordinary chemical means. Here the radioactive tag should be capable of demonstrating minor shifts and accumulations of the substances being studied which otherwise might go unobserved within the ointment. Whereas, the amount of radioac- tivity of the tagged ingredient could be measured in aliquots of the oint- ment taken from various parts of its container the newer needle-type Geiger probes should serve to advantage in doing measurements of radio- activity in situ. These probes could be inserted into the ointment at any point thus permitting direct measurement of the radioactively tagged ingredient without disturbing the packaging in any other way. There must certainly be many other applications for radioisotopes in the laboratory, but it is time I say something about the clinical applications of our selected ointment containing the radioactive ingredient. As for most bio-assays, the laboratory animal is usually the first to be

402 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS subjected to experimental studies. While there may be good reasons for using the rat, guinea pig, rabbit or other animals for preliminary physio- logic, pharmacologic and toxicity studies, etc., I can see no good reason for using these animals for the type of studies I am going to mention, unless it is to establish and become familiar with working technics. The need for work on laboratory animals is particularly little if the non-radioactive form of the ointment has previously been used on man without demon- strable harm and if the amount of radioactivity is known to be within safe limits for both topical application and systemic absorption. It might be well to point out, that before radioactive isotopes may be used on human beings, approval must be granted by the Subcommittee on Human Ap- plication of the Isotope Division of the U.S. Atomic Energy Commission. I doubt that I need to do more than mention some of the differences between the skin of the commonly used laboratory animal and that of man for you to understand why conclusions drawn from animal experimentation cannot be applied specifically to the human skin. In contrast to the human skin, the ordinary experimental animal (1) has a heavy coat of hair, which if clipped, shaved or plucked undoubtedly injures the skin to some degree making for unnatural points of entry for any externally applied preparation and, of course, the animal has many more hair follicles per square area which interrupt the continuity of the skin and afford many more portals of entry (2) does not possess sweat glands as does human skin, thus undoubtedly making for differences in the flow of materials over the surface, the extraction of sweat soluble ingredients from the base, the emulsification of sebaceous secretions, which in turn undoubtedly in- fluence penetration and absorption (3) possesses sebaceous glands whose secretions must be different than those of man in the relative amounts secreted and in their chemical contents--again causing differences in the behavior of topically applied preparations and (4) the ordinary external exposures of animal and man are immensely different--who ever heard of a guinea pig wearing underclothes of silk, rayon or nylon using soap or detergents being exposed to extreme changes in temperature and humid- ity or using estrogen creams, perfumes, colognes, after-shave preparations, deodorants, or bubble baths. Certainly for these reasons alone, the human skin should be used whenever possible for the type of investigations I will mention. When planning studies which are to be done on human skin, in vivo, other considerations become important in the selection of the radioactively tagged compound to be used. For our problem, it is necessary to have a radioactive compound that: (1) chemically, in the concentration used, is not a primary irritant and is not known to have a high sensitizing index when applied topically (2) is not toxic if readily absorbed (3) possesses such radioactive properties (type of radiation emitted), has such a half-life