180 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS The cosmetic industry uses many such materials for example, lanolin, mineral oil, vitamin-containing creams, benzoin, and analogous materials. One may well question, however, whether the cosmetic industry is keeping pace with the development of new materials for therapeutics and their proper evaluation in cosmetic terms. It is to be hoped that the industry is abreast of this development so that it may take advantage in the future of what it has learned in the past. The question of investigating for other beneficial effects perhaps poses the greatest problem of all. Various types of skin, skin coloring, blemishes, age, texture and exposure are all important aspects in evaluating benefi- cial effects. Here, unfortunately, our experience lets us down somewhat. The cosmetic effect is best evaluated by sensory perception namely, visual, olfactory, and tactile. As a continuous procession of seminars attest, the standardization and comparison by sensory perception is an extremely unreliable field. We are faced, therefore, with the problem of methodology to assist in the standardization of sensory responses. Cer- tainly this would require an additional seminar by experts in many fields for one to even begin to appreciate the depths of this problem. From the above it is apparent that the cosmetic industry does have an interest in practically all skin evaluation whether they are fully aware of this or not. If we as cosmetic chemists are interested in a particular chem- ical or variation of formula, whether this has been brought to our attention through the magnanimous efforts of the sales representative or through deductive reasoning on our own part, it is my belief that animal skin evaluation fulfills many steps of the procedure in a manner superior to human testing. While animal skin and human skin have major and im- portant differences, experience has shown us certain major fields in which animal skin may be used to predict human skin reaction. Animals have the additional advantage of being readily available, quite controllable, and devoid of the individual rights and prerogatives which we like to associate with our fellow man. Their standardized living, standardized breeding, and relative space requirements are certainly advantages from a scientific experimental design and cost standpoint. Of the three major cosmetic interests--irritation, sensitization, and aesthetics--it would appear that the experimental animal serves his great- est function in the field of irritation. We in our laboratory feel that the use of animals is an essential preliminary in the evaluation of any new chemical, and that the future of cosmetic chemistry lies in the exploration of vast numbers of new chemicals rather than the miscellaneous juggling of old chemicals into new and slightly different formulations. Our staff physicians are extremely reluctant to expose any panel of human subjects to new chemicals until after the animal tests are completed. Choice of animals is of importance but mostly is related to personal experience of the

EVALUATION OF CHEMICALS TO ANIMAL SKIN 181 investigators. Rabbit skin can, I think, be said to be somewhat more sensitive to chemical irritation than the average human skin. Guinea pig and rat skin are widely used for irritation studies, however, and so long as the investigator has the background of comparative evaluation between the animal and human, it makes really very little difference which animal is selected. It is quite possible that the use of swine will become much more popular than it has in the past if some of the miniature breed programs now under way turn out successfully. Pharmacologically, irritation is synonymous with stimulation and one should not overlook the fact that a very mild degree of irritation which is controllable and reproducible may be exactly what one is seeking for certain cosmetic applications. Certainly it is the basis for much therapeutic pharamacology. As mentioned earlier, methodology is the big problem in evaluating irri- tation critically. Severe irritation, including necrosis, is of course readily observable but not readily comparable from one chemical to another. Certain types of chemicals, as for example the organic amines, do more subcutaneous damage than would be expected from the appearance of the epidermis. Elaborate methods for conducting and evaluating dermal studies have been published and I am sure that this group is familiar with them. Most of these, however, apply to one objective only and it is of fundamental importance that the biological scientist design and evaluate his program in such a manner that he obtains the answer tb the specific question under study. To be led astray by following methods applicable to other objectives is perhaps the most common mistake that one sees in this field, particularly by those lacking fundamental training and experi- ence to whom skin studies look so simple. While discussing the subject of irritation I should like to digress some- what from the skin and say that we feel the combination of eye and dermal studies is often more revealing than either study alone. This is particu- larly true when one is investigating a series of compounds or various con- centrations and vehicles for the same compound. We have observed that the reactions in the eye and in the skin sometimes correlate and sometimes are quite opposite. Another aspect of comparative testing which I think has not been adequately developed is that employing repeated daily application to both the skin and the eye. This is in effect an evaluation of the skin exhaustion capacity and is revealing in some cases. It is not unusual to find, when running parallel series on different compounds, that one compound or one formulation will cause no more reaction after many days of application than it caused on the first application and the reaction may in fact become more mild. On the other hand, a second material or formulation will cause practically no irritation during the first several days and then either abruptly or gradually, increase in degree of irritation