THE EVALUATION OF CHEMICALS BY APPLICATION TO ANIMAL SKIN* By L. W. HAZLETON, PH.D. Hazleton Laboratories, Falls Church, Va. SINCE OUR SOCIETY has had the benefit of many authorities on the subject of skin in previous programs, it would be unrealistic to take time at this point to discuss the anatomical and functional aspects of skin. Con- tinuing this process of delineating our subject matter, it does not seem appropriate to spend a great deal of time citing previous literature and abstracting or reviewing the significance of this vast volume of information as it pertains to our topic today. Rather, it would seem best to assume at least a working knowledge of this background and to refer to it only in general terms at appropriate times. This narrowing of scope brings us to the real heart of our topic namely, what is the objective to be achieved by evaluating chemical reactions on animal skin ? In the day-by-day operation of the laboratory our technical staff is faced with the problem of designing experiments to provide the answer to many questions based on skin reactions. I regret the necessity of calling so widely on their experience and presenting their opinions, as well as mine, without having them here to discuss this subject in detail. Our only real objective in evaluating skin reactions following application of chemicals is to achieve answers to specific questions. The vast volume of work conducted along these lines is that of evaluating hazards which might result from dermal exposure to chemicals. In our rapidly expanding chemical economy new chemicals are the rule rather than the exception. We have learned long ago that each chemical poses a hazard until evidence indicates otherwise. I am sure that this group would find any of these hazard studies extremely interesting if they were afforded an opportunity to see them and to interpret them into actual safety precautions, as we are required to do in order to safeguard research chemists and chemical users throughout the industry. This hazard, which may be defined as the probability of injury following exposure under conditions of use, may take the form of irritation, contact * Presented at the September 23, 1954, Seminar, New York City. 178

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.