PROBLEMS OF PREDICTIVE TESTING 357 but not least, the change in testing facilities may have been the influenc- ing factor. Interestingly enough, the incidence of complaints from con- sumers did not change during the intervening years. What does this all mean? Are our tests too sophisticated or are the artificial test conditions too severe and thus prejudicial to the product? Of course, we do not know the answer, although Baer's (23) report on the changing sensitivity of the population may offer a clue. Regardless, this is a typical example of how the responses to chance patch testing can trig- ger research activities.. A more interesting example is a fairly recent experience using a trans- lucent facial make-up product. This product was put through the bat- tery of tests using established patch test methods and found to be free of irritation and sensitizing liability. However, in an in-use test, over 75% of the test panelists were unable to tolerate the test product. At first it was believed that the geographical location of the test site might have pre- cipitated the responses. Alternately, exposure to natural sunlight could have caused the reactions. Accordingly, photopatch tests (on the back) were conducted with negative results. Another in-use test was initiated at another site, which confirmed the results of the first in-use test. In view of these adverse results, the product was reformulated in an attempt to eliminate the offending agent or agents. After much work, some minor constituents were eliminated from the formulation, and a third in-use test was conducted. Now, the revised product was tolerated by 100% of the test population. It was concluded that neither light nor oc- clusion triggered the reaction. In this case it seems evident that the lo- cation of the skin, i.e., face vs. back, was the primary factor in producing the adverse effects. If the initial patch test results had been used as the sole criteria in judging the product safe, the original product would have been marketed on the basis of established procedures and in good faith. , The product would, nevertheless, have caused adverse reactions in many consumers. Based on this example, exaggerated in-use testing would seem to be an important part of any predictive skin testing program. It should be emphasized that the two examples cited here are unusual. Normally, repetitive patch tests of the same product yield comparable results. Similarly, in-use tests normally confirm the safeness of products established in a patch test series. Our many years of experience indicate that a well-designed and well-conducted predictive testing program is an almost foolproof method of establishing the safety of products before they are marketed.

358 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS CONCLUSION Potential problems of predictive testing of the safety of a cosmetic product have been pointed out. Particularly troublesome are the follow- ing: The selection of the test(s) and of the test population inadvertent experimental errors problems of interpretation, which are related pri- marily to the absence of well-documented scientific information. It is pointed out that in-use testing under clinical supervision is highly desir- able and should be seriously considered as an adjunct to the battery of known skin predictive procedures. Two unusual examples from the authors' files illustrate these problems and support these inferences. In the authors' experience, the results of a sound predictive testing program are useful for anticipating the product's safety in the market place. (Received December 21, 1970) REFERENCES (1) Kligman, A.M., The identification of contact allergens by human assay. I. A critique of standard methods, J. Invest. Dermatol., 47, 369-74 (1966). (2) Brunner, M. J., Pitfalls and problcms in predictive testing, J. Soc. Cosmet. Chem., 18, 323-31 (1967). (3) Idson, B., Topical toxicity and testing, ]. Pharm. Sci., 57, 1-11 (1968). (4) Kligman, A.M., The identification of contact allergens by human assay. 111. The maxi- mization test: a procedure for screening and rating contact sensitizers, J. Invest. Dermatol., 47, 393-409 (1966). (5) Wooding, W. M., and Opdyke, D. L., A statistical approach to the cvaluation of cutaneous responses to irritants, J. Soc. Cosmet. Chem., 18, 809-29 (1967). (6) Barron, B. A., Variations on a theinc--The evaluation of ncccssary and unnecessary risks, Toxicol. Ap•t•l. Pharmacol., Suppl. 3, 72-5 (1969). (7) Opdykc, D. L., and Burnett, C. M., Practical problems in tire evaluation of the safety of cosmetics, Proc. Sci. Yecl. Toilet Goods Ass., 44, 3-4 (1965). (8) Food and Drug Administration, Appraisal of the Safety of Chemicals in Foods, Drugs, and Cosmetics, Association of Food and Drug Officials of the U.S., Texas S,tate Depart- ment of Health, Austin, Tex., 1959. (9) Wolven, A., and Levcnstein, I., Techniques for evaluating derreal irritation, ]. Soc. Cosmet. Chem., 18, 199-203 (1967). (10) Marzulli, F. N., et al., Delayed contact hypersensitivity studies in man and animals, Proc. Joint Co•f. Cosmet. $ci., Washington, D.C., 107-22 (1968). (11) Magnusson, B., and Klignnan, A.M., The identification of contact allcrgcns by animal assay. The guinea pig maximization test, J. Invest. Dermatol., 52, 268-76 (1969). (12) Maibach, H. I., and Epstein, W. L., Predictive patch testing for allergic sensitization in man, Toxicol. Appl. Pharmacol., Suppl. 2, 39-43 (1965). (13) Rubenkoenig, H. L., and Quisno, R. A., Use of the patch test in estimating hazards to the skin, Proc. Sci. Sect. Toilet Goods Ass., 28, 6-8 (1957). (14) Magnusson, B., and Hersle, K., Patch test methods. I. A comparative study of six dif- ferent typcs of patch tests, Acta Dermato-Venereol., 45, 123-8 (1965).