392 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS DR. I. LEVENSTEIN: You mentioned the fact that you were able to obtain good responses with intradermal injections, and you feel that you can then screen out fairly hazardous materials without using the eye. I just wonder if you are using the same physiological system to screen out these prepara- tions. Injecting into the skin, and applying to a mucous membrane are entirely different. Can you correlate the two responses ? TI•F. L•CTURF. R: I am in complete agreement with you that application to a mucous membrane is rather different from injecting intradermally into the skin, but I do feel that the skin test picks out very irritant substances, like phenols and nitric acid, which would cause severe damage to the eye. All I am saying is that we must be a little humane in eye studies. If we have a substance, which in the intracutaneous test looks remarkably irritant, we should approach the eye test with caution. Dilute the test solution first--do not just instil the concentrated solution into the eye and blind the rabbit. There is no virtue in that at all. DR. L. GO•.BF. RG: I wonder whether you would comment on the work that has been carried out on the importance of lubricating oil on the electric clippers which are used to prepare the skin, and their influence on the result ? There is also the question of the use of a positive control when carrying .out tests for primary irritation. I have always looked on hydroxycitronellal as a very reliable positive control material. I may be quite wrong there, but I have heard of cases recently where it was applied to human skin and in the whole group it produced negative results. I would be interested to hear what other people use as a positive control material. T}•F. LECTURF. R: I do not think that the minute amount of oil that is -really necessary can have any influence at all. Perhaps it depends on the type of clippers which one uses. With regard to controls, I am in complete agreement. What we do need are substances of known irritancy in man, which can be used as controls for •comparisons in our animal tests. There is a great lack of information on substances which are known to be minor irritants in man I have sorbic acid in mind which shows nothing in the animal but does in man. There are a number of these examples which I think Dr. Levenstein has drawn .attention to. What is the reliability of our animal tests in these border line substances ? DR. P. H. WlTJENS: We have tested dinitromonochlorobenzene by intradermal injection in the normal guineapig sensitization test, and found that this product has no sensitizing properties according to the requirements ß of the F.D.A. because the reaction obtained in the first tests is just the :same as in the later challenge tests. According to the test requirements it

TESTING DRUGS FOR DERMAL TOXICITY 393 has no sensitizing properties although we know that it is one of the strongest sensitizers when used on the skin instead of by intradermal injection. I cannot explain it, but we have to accept it. THE LECTURER: To avoid confusion, I am speaking of two types of intradermal tests one for local irritant properties--you are quite clear about this. With regard to sensitization tests I feel quite strongly that any sensitization studies of this nature in animals are quite useless we need to do them in man--this applies also to drugs. You cannot sensitize animals to penicillin and yet it is known that this is a very real problem in man. We can only do it in man himself. In this country I do not think that we place any reliance at all on the animal tests for sensitization. DR. B. LESSEL: I should like to comment on the predictive value of the rabbit skin test. Nine topical antibacterial creams, as marketed, were examined for primary irritation by repeated application to rabbit skin and by patch tests in human volunteers. Some provoked a severe skin reaction in rabbits and had little or no effect on human skin while other preparations had the converse effect. The skin reaction in rabbits that appeared most predictive of irritancy to human skin was oedema or necrosis, whereas erythema of rabbit skin appeared to be a non-specific reaction. }V[R. J. }V[cL. PHILP: Have you had any experience of the use of rabbits for photosensitizing tests, and if so, could you give some details ? Do you place greater reliance on photosensitization tests in the rabbit than on guineapig sensitization tests ? I disagree with your statement that animals are of little value in sensitiza- tion tests, and that studies can only be made on man. One cannot have certainty from either animal or human tests. The animal test can be most useful, and may be a valuable prelude to human tests. Your reference to penicillin as being a sensitizer to the human was hardly relevant as it would have required a test panel of some thousands of human beings to show this sensitivity prior to the use of the material.. Tests carried out on humans can give erroneous results--nickel, for example, is well-known as a cause of contact sensitization in the human but cannot be shown to be a sensitizer by human tests it is, however, confirmed as a sensitizer using the guineapig test. THE LECTURER: In general I agree with the sensitization test in guinea- pigs. I was not suggesting that the test be abolished, it may be of some value. What I am stressing is that the test is not reliable. It will detect potent sensitizers. These substances would affect nearly everyone on whom they are applied. We are more concerned with the abnormal reactor that is the one person, perhaps one in a thousand, who has a different skin or