382 JOURNAL OF TI-IE SOCIETY OF COSMETIC CHEMISTS primary irritation in each of 3 rabbits was confirmed by human patch tests on 25 humans. 'We believe that the use of laboratory animals, under controlled conditions, is a valuable tool for screening new cosmetic pre- parations. Since all cosmetic manufacturers are desirous of producing safe preparations it would be wise to employ the methods described above. The knowledge obtained would aid them greatly in predicting any harmful effects, and indicating the ability of their product to be absorbed by the skin. They may reject a product which shows a reaction in the animal, but would not have done so in the human. This possibility, however, is statistically slight and is worth the risk. (Received: 30th September 1963.) I•EFEI•ENCE {1) E. A. Newmann Laboratory Animal Care 15 207 (1963). I)ISCUSSION MR. A. W. PoNt): When you were discussing the correlation between rabbit skin studies and human studies, you were talking in terms of the reactions obtained between 9 and 15 subjects out of 25. This is the sort of level that the cosmetic industry frankly is not very interested in, except perhaps when investigating a new raw material in its very initial stages. We are, however, worried about the reaction of 1 in 10,000 to a product of which many millions will be sold because if we are going to have 100 com- plaints of dermatitis for every million units sold every reputable company will be terribly worried. The difficulty is how to test for a sensitivity which is going to occur at a level of 1 in 10,000. It appears to be the normal thing that one starts to increase the severity of the tests in terms of the concentra- tion of the material used, and the frequency with which it is applied until some sort of reaction is obtained and one's consultant then says that this is a sensitizer. Nobody, however, appears to be able to answer the question concerning the likely risks in actual use, where the conditions vary tre- mendously from the quantitative tests. It therefore appears that all that we can do at the moment in the way of dermal testing is to sort out the real offenders for the other products there seems to be no alternative to market- ing. To me this seems highly unsatisfactory. TI• L•CTURER: You are correct. Animal testing is necessary for new products, new formulations or new components in old formulations. Using animals it is impossible in the laboratory, to develop a test sensitive enough to detect sensitivity in terms of a possible human exposure of 1 in 10,000. There is no formula which can be used to carry over to the human population results obtained in aniinals. This must be done by marketing,

RABBIT SKIN STUDIES IN EVALUATING COSMETIC SAFETY 383 and the per cent sensitivity can only be evaluated after many thousands of packs are used, and set off against the complaints of sensitization received. Sensitization in the human may depend not on one exposure to a specific product but upon several exposures to different products at the same time. It is impossible from animal experimentation, if the results in the animal are negative, to postulate how the human population will respond. It is necessary to perform experiments with animals in order to prove that, at least in the laboratory, the matehal under study will not develop primary irritation, or sensitization, in animals. MR. A. W. POND: I would not want you to think that I was making a plea for the abandonment of all sorts of testing--I would deprecate this as much as you would. I was stating that it would be desirable if we could have the type of testing which would be predictive in the sort of sense that we are required to be predictive. THE LECTURER: I am afraid that it is impossible to predict sensitivity of a low order. This type of sensitivity can only be evaluated after the product has been on the market, and has been used by many thousands. It is impossible for a dermatologist to test a preparation on two hundred humans, and after obtaining no response in each case to state that the next ten thou- sand people receiving the same matehal will show no response. In any population, the range of sensitivity to chemicals, and to cosmetic products, is tremendous and there will always be some individuals who will respond adversely to almost anything which is marketed. It is remarkable that the number of individuals, who react to the millions of cosmetics sold each year, is so small. Miss H. THORPE: What significance does the skin thickening observed in the rabbits have with regard to effects of the compound in the human ? Could this perhaps be the result of mechanical trauma ? Did you get any effect with controls ? THE LECTURER .' The skin thickening which we obtained in the rabbit was, we believe, a response to a specific chemical, the identity of which we do not know. The material was a leaf extract and may have contained many active ingredients. The response was such that the epidermis was three to four times thicker at the point of application than in the surrounding skin. Concerning the significance of the thickening I would say that any material which, after placing upon the skin, causes the response found may result, if applied over a long period of time, in a dangerous overgrowth of epithelial tissue. The thickening was not the result of mechanical trauma since control areas on the opposite side of the animal, treated with water and