J. Soc. Cosmet. Chem., 22, 349-359 (May 27, 1971) Some Problems of Predictive Testing G. •q. BATTISTA, Ph.D., and M. M. RIEGER, Ph.D.* Presented December 1-2, 1970, New York City Synopsis--TEST PROCEDURES available for the SAFETY EVALUATION of toiletties and COSMETICS are reviewed. Some obvious deficiencies of these tests, possible pitfalls, ques- tionable parameters, and the organization of an evaluation program are discussed. The in- terpretation of preclinical animal and of clinical human safety data and the importance of in-use tests in determining whether or not a product is safe are also considered. A few clini- cal experiences are presented to illustrate the discussion. INTRODUCTION Product safety is one of the primary concerns of all drug and cos- merit manufacturers. In the case of drugs, the term safety becomes rela- tive, and any side effects can be weighed against the benefits derived. The safety of drugs is one of degree, and consumer inconvenience or even risk can be tolerated depending on the product and what it will do for the patient. Drugs can be and often are an essential part of one's health and, in severe circumstances, can be life saving. On the other hand, cosmetics are not life saving, but contribute to general well-being by virtue of beautification, decoration, and camouflage. •qithin this framework, the manufacturer of cosmetics and toiletries must assume great responsibility for consumer safety, whether it be for reasons of morality or just plain good business sense. Consumer tolerance to irritation or inconvenience resulting from the use of cosmetics is very low there is no room for side * Warner Lambert Research Institute, 170 Tabor Rd., Morris Plains, N.J. 07950. 349

350 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS effects and safety under conditions of use must be as close to 100% as possible. As a result, the manufacturer of cosmetics needs reliable information on the probability of adverse reactions to his product in advance o[ its marketing. Cosmetics in general are a fairly innocuous class of products' if they were not, the manufacturers would have had to close their doors long ago. The fact that billions of dollars are spent annually on cos- metics confirms that consumers as a whole do not find cosmetics irritating. The skin of man has been constantly exposed to a wide variety of dif- ferent chemicals. The milieu of our modern industrial society further insults our skin with a wide range of chemicals in the form of clothing, industrial finishes, and dusts. Experience has made the elimination of known skin offenders from cosmetics a fairly simple task. Most potential irritants have been identified, and their use in cosmetics is almost nonex- istent. Kligman (1) pointed out, on the other hand, that "practically all substances are capable of being contact sensitizers for some persons under some conditions." However, the exclusion of all chemicals which--under one condition or other-could act as irritants or sensitizers would make the formulation of cosmetics impossible. With this in mind it becomes apparent why an evaluation of currently available predictive test procedures is important. A description of pre- dictive testing techniques, especially as they are applied to cosmetics, has recently been made by Brunner (2). A thoroughly annotated review of this subject has been prepared by Idson (3). In addition, a well-reasoned critique of standard test methods for cutaneous contact allergy has been published by Kligman (1), who concludes that the techniques are "insen- sitive" to moderately strong known sensitizers. In view of this he de- veloped his so called "maximization test" (4). In spite of some obvious deficiencies, predictive testing techniques for cosmetics appear to be reasonably reliable. If they were not, the inci- dence of reaction to newly introduced cosmetics would be expected to be much more common in our industry. In fact, we feel that a well-executed predictive program is most useful in keeping potentially troublesome products off the market. The purpose of this discussion is not to suggest new tests. Instead, the need for careful selection of predictive testing procedures and for judicious interpretation of the resulting data will be pointed out. In ad- dition, some problems which may be encountered during predictive test- ing will be explored.