226 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS study of weak irritants). Most cosmetics would not be sufficiently irritant to give a clear response in the ID50 test and the principle of varying the concentration is often inappropriate. The principle of an IT50 is undoubted- ly applicable in many respects but continuous exposure of the skin to a potential irritant, as in the test defined by Kligrnan and Wooding, is only justifiable in our opinion when patch testing is carried out under direct medical supervision. The intermittent exposure which is a feature of the Finkelstein et al (2) technique reduces the risk of serious discomfort or skin damage and does not require volunteers to wear unsightly patches or to refrain from taking baths in off-duty hours. We have therefore based our procedure on that of Finkelstein et al (2), modified in the light of experience, notably with some of the newer surgical tapes. Nevertheless improved statistical validity might be achieved by adopting the IT50 approach in the intermittent patch test procedure, though we doubt whether an irritancy assessment based on time of exposure yields as much pertinent information as an assessment of the degree or severity of response. With new cosmetic ingredients, laboratory animal studies should in- variably be carried out before they are tested on human skin even with well-known raw materials, it is prudent to screen new formulations simi- larly. The advisability of proceeding cautiously in this way is emphasized by the fact that 'closed' patch testing on human skin tends to exaggerate the response and introduces a distinct risk of severe reactions even with some formulations that would be virtually non-irritant in normal 'open' usage. Many shampoos applied in concentrated form under a 'closed' patch (even in the intermittent patch testing procedure) cause blistering of the skin before completion of a 5 day test. Obviously such a reaction has little or no predictive value in terms of normal usage and the test procedure must therefore be adapted in accordance with the type of formulation under investigation for example, shampoos are preferably tested at 10-20•o aqueous dilution. Since the appropriate conditions for human patch testing may not be known before the studies begin, it is clearly essential to conduct screening on laboratory animals as a preliminary. Considerable experience in using the mouse ear test has given us a good deal of confidence in its predictive value. However, irritancy tests should preferably be conducted on at least two different species and we now use both the mouse ear and rabbit flank as testing sites routinely. The ability to run a large number of tests in a relatively limited space is a distinct advan- tage for the mouse ear test. Another useful application for the test has been for examining complaint samples of various cosmetics, the test being

PRIMARY IRRITATION OF THE SKIN 227 used to compare the suspect preparation with a standard specimen of the same product. This is specially helpful when only a minute quantity of the complaint sample is available. We have also attempted to use the mouse ear for detection of sensitizing potential by making 'challenge' applications 10-14 days after the usual series of applications. Our experience is inade- quate, however, to indicate whether this has reliable predictive value. Excision and sectioning of the mouse ear after sacrifice may be carried out to obtain confirmation of oedematous changes due to irritation. Using the cartilage of the ear as a datum position, a semi-quantitative estimate of irritancy may thereby be derived. ACKNOWLEDGMENTS We should like to thank Mr D. B. Jones for his assistance in this work, and Mr H. Ashmore for the photographs. (Received: 9th February 1972) REFERENCES (1) Brown, D. M. and Robson, R. D. Nature, Lond. 202 812 (1964). (2) Finkelstein, P., Laden, K. and Miechowski, W. J. Invest. Dermatol. 40 11 (1963). (3) Siegal, S. Nonparametric statistics for the behavioural sciences (1956) (McGraw-Hill Book Co., London). (4) Kligman, A.M. and Wooding, W. M. J. Invest. DermatoL 49 78 (1967).