182 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS produced. Studies such as this can conveniently be conducted only in animals if large numbers of chemicals and multiple conditions are to be evaluated in any type of a mass scale. Time, economics, and availability of almost unlimited subjects militate strongly for the use of animal rather than human panels for investigations such as these. In actual practice the use of animals serves a very important function in screening candidate materials for eventual human tests. While it is true that there is a statistical chance that a valuable candidate may be passed over, this is a calculated risk and certainly the risk is nowhere near as great as would be experienced in human testing only, with all of its multiple limitations. Perhaps the most confusing application of animal testing is in the field of evaluating sensitization. I should like to say at the outset that our staff members have had appreciable experience with the various sensitizing techniques in animals. I should also like to add that we do not believe any technique is completely reliable for the determination of sensitizing potential. From the time of Landsteiner, the literature is replete with discussions of sensitization in animals. Many of these papers cover such aspects as the species of animal, the purity of breed, the Mendelian charac- teristics, the age, the sex, the diet, the method of application, the frequency of application, the number of applications, the interval of challenge ex- posure after sensitizing exposure and countless other variables. It seems to be self-evident that ifsensitization in animals were a reliable phenomenon the attention would be spent on studies involving sensitization as an es- tablished entity rather than to the discussion of the variables which tend to explain away the negative result. The above is not meant to say that true sensitization does not occur in animals. I am sure that most of us in the field have seen true sensitization, but the interpretation from animals to humans is extremely inconsistent and unreliable. Most of us also know of examples, published or unpub- lished, where animals have not reacted as humans have, and vice versa. Here again, objective is an extremely important consideration. We do feel that new materials, particularly new individual chemicals, should be screened for strong sensitizing potentials in animals prior to human exposure. Our final evaluation on this subject is that if animals are sensitized we are extremely cautious with that material in humans. Certainly it is a suspect chemical until proved otherwise. On the other hand, a negative result in animals serves only to indicate that the chemical is probably not a strong inherent sensitizer and that with reasonable caution we should not obtain severe sensitizing reactions in humans. The evaluation of aesthetic benefits on animal skin is obviously a long jump and, by and large, is not correlated with the human results. Ex- perienced operators learn to evaluate subjective appearances such as tone,

EVALUATION OF CHEMICALS TO ANIMAL SKIN 183 texture, color and sheen. However, this is still only a guidepost to human reactions since animal skin is normally much more constant in appearance than the human skin. Certainly the application of a cosmetic formulation to the soft, smooth pink skin of the freshly clipped rabbit gives one no real idea of what that same formulation might do on the sun-tanned, wind- roughened facial skin of the human being. Certain cosmetic properties can be evaluated under these same sets of circumstances. For example although the rabbit skin is deficient in melanin and does not tan under excessive exposure to ultraviolet light, it does react with edema and erythema and hence it can be used for comparing the efficacy of sunscreen candidates. Such a screening program is purely mechanical, however, and would not give one a clear-cut insight into ease, degree, and color of suntan to be achieved in the human with such a candidate compound. This is an example of carefully delineating the objective, knowing the possibilities and limitations of the animal experimentation, and exploiting the method to its fullest without being misled by its eventual application. To the extent that cosmetic effects include the healing of superficial cuts, scrapes, and abrasions, these properties can be evaluated in animal skins under controlled conditions. Keratin staining and discoloration can be evaluated, as can the degree of roughening or sloughing under con- ditions of repeated application. These, then, do give us some examples of evaluation of the cosmetic effects, but certainly the final answer must come from the eventual user of the cosmetic and not from the rabbit. As is frequently pointed out, methodology is the big void in our present approach, not only to animal but to human evaluation of skin reaction. More adequate methods of evaluating vascularity, color, smoothness, reflection or gloss, pH and even chemical composition of the superficial layers are obviously necessary. The use of radioisotopes is one new method which is beginning to find application. This method may eventually find its proper place in the cosmetic evaluation scheme. I should like to caution, however, against overenthusiasm for it in the cosmetic field, lest we not profit from the experiences in the related fields of biochemistry, pharma- cology and therapeutics. The technical traps are many and dangerous and perhaps the greatest of these problems is that of interpretation. I am sure there are those attending the seminar who are more qualified to discuss this subject than I am, though I mention it here primarily to be sure that it is included in the discussion agenda. It is probable that, as radioisotope techniques develop, animals will play a very important part in the ap- plication. In summarizing the applications of animal testing of chemicals, I should like to emphasize that, whether the test subject be animal or human, the test can be no better than the team of investigators conducting it. strongly feel that the chemical evaluation from the cosmetic standpoint is