EVALUATION OF CHEMICALS TO ANIMAL SKIN 179 dermatitis, sensitization, or outright and frank systemic toxicity. Each of these aspects will be discussed in a later portion of our topic. A second question to be answered is whether or not a chemical might have a therapeutic effect. By definition, a therapeutic effect would have to be achieved following application to diseased or otherwise damaged skin. A third important question is whether or not a chemical might have some beneficial effect on normal skin. The use of the term "normal" in this connection poses many questions which are all too familiar to this group. Equally the question of diseased, pathological or traumatized skin poses many problems of definition. Somewhere within this group of objectives, however, must lie the question of interest to cosmetic chemists. It would seem logical, therefore, to further delineate our objectives to those of cosmetic interest and then to evaluate derreal testing on animals. Hazard evaluation can be a fascinating study, and extremely complex experimental designs have been proposed. These are aimed at placing the proper emphasis on a large number of variable factors, including con- centration, total duration of exposure, total surface of exposure, physical state of chemical subdivision, effect of repeated discrete exposures and the simulation of conditions approximating the probable exposure under conditions of use. In the broadest sense the two general reactions observed in this type of study are systemic toxicity which follows absorption of the chemical through the skin and into the blood stream, or those of local, strictly dermal reactions. From the cosmetic standpoint each and all of these studies can be of interest. It is well to know, for example, that under severe conditions of surface concentration and exposure time, a given chemical appears to cause no local or systemic reaction in animals. While this knowledge is the answer to the original question of hazard, it might also have a secondary interest to the cosmetic chemist were he aware of such data. Certainly here would be a chemical which could be of cosmetic interest and on which a preliminary assumption of safety for use could be made. The alternate result from the above example may be that the new chemical was irritating at various concentrations but under certain con- ditions was not injurious to the skin. This would be the answer to the question of industrial or chemical hazard, but it is far from the answer to whether or not there might be a cosmetic interest. As I have pointed out on other occasions before this group and as others before me have pointed out, there is a vast amount of investigation required to bring our knowledge of cosmetic chemical potential up to anywhere near a current status. To move on quickly to the second objective, that of therapeutics, we again face the problem of whether or not a material which is therapeu- tically beneficial to diseased or traumatized skin might be also cosmeti- ca'ly beneficial under proper conditions and for clearly defined objectives.

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