168 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS actions, depending on severity and number, may indicate only that further testing is in order. The effect of occlusive dressings on the absorption of drugs has recently been the subject of intensive study. Stoughton and his group (11-13) attribute increased drug absorption from occluded (with Saran ©* ) areas of the skin to hydration of the skin. This may explain why a cosmetic preparation is much more penetrating and irritating under a closed patch than when exposed to normal air circulation. Typical examples of products that might yield positive responses under occlusive patches are detergent-containing preparations, which usually elicit "soap" reactions under these test conditions. These reactions can be differentiated from actual primary irritation by the physical character of the reaction itself. Nevertheless, this type of reaction is almost never re- lated to skin irritation resulting from normal use of the product. Another example involves products containing volatile solvents which are capable of eliciting rather severe reactions under closed patch tests, erroneously suggesting that the product could not be used safely on human skin. In fact, many products are currently being marketed which do not cause adverse effect in common usage but elicit skin reactions under the con- ditions of a closed patch test. Nevertheless, the 48-hour closed patch test for the detection of primary irritation can be a valuable tool when interpreted properly and used as a guide or index for further human testing. In skin patch testing, it is im- portant that the investigator be familiar with the shortcomings of the test and utilize this knowledge in the final analysis and judgment of the safety of the product in question. If the results of a closed patch test of an in- frequently used cosmetic show a minimal response in a small percentage of subjects, the product can probably be considered free of primary irritation potential in normal usage. On the other hand, if the results of the routine test suggest primary ir- ritation liability, the product should be tested under actual use conditions, possibly exaggerating the conditions of normal usage, i.e., the amount and frequency. Perhaps, variations and modifications of the routine skin patch test might prove useful at this point or might even be substituted for the routine test. Recently, Kligman (14) demonstrated a method for routinely screening products for their irritation liability by comparing the test substance with a commercial product. Although this technique requires few patients, it is claimed to predict (with reasonable certainty) that a product is as safe as, not as safe as, or safer than the product used as the standard. Of equal importance during predictive safety testing of cosmetics, or of any compound, are the selection of the test and the interpretation of the * Saran is a trade name of Dow Chemical Co., Midland, Mich.

EXPERIENCES IN SAFETY TESTING OF COSMETICS 169 results. In the experience of the authors, the ideal safety test has not yet been evolved. Such a test would be one that predicts unfailingly, on the basis of a "routine laboratory" procedure, that a product is either safe or unsafe when used on the population at large. Pending the design of this ideal test, a procedure has been evolved which combines the patch test with a use test. Although this procedure is considered superior to other tech- niques, much more experience will be required to establish its validity. In brief, this procedure utilizes 100 volunteers who are issued a supply of test material with a written set of instructions for use. The subjects use the material daily for a period of 30 consecutive days. Additional material is issued as needed at weekly interviews, and examinations by the in- vestigator are carried out weekly. At the end of the trial use period, the test subject is not allowed to use the product for a period of seven days, at the end of which time the patient is patch tested, using the 48-hour closed patch procedure. In essence, the patch test is a challenge after a known exposure to determine whether the subject has in any way become sensitive to the product in question or whether any primary irritation is elicited. This technique has been found particularly valuable in establishing the safety of products which are used daily on a routine basis but is less applicable to shampoos and other products which are used at less frequent intervals. Care must also be exercised in the planning of in-use tests if the results are to be of any value in judging the safety of cosmetics. The reliability of the data obtained is directly related to the judgment used in designing the proper test procedures. The above mentioned neutralizer is a case in point: In-use tests conducted in a beauty salon and/or by skilled home users did not elicit any adverse reactions, probably because of the skill and care of the user in not allowing the neutralizer to come in contact with the eye. Not until the product was placed into the hand of the inexperienced were any adverse effects reported. THE RELATIONSHIP BETWEEN SAFETY OF RAW MATERIALS AND FINISHED PRODUCTS Despite their most careful efforts, even the best cosmetic chemists will occasionally make preparations which prove to be irritating, either during the use of the product or in predictive testing procedures. Unfortunately, the results of such tests are too frequently not examined in their fullest detail, and much valuable information is lost to the formulatot at the bench. An attempt to pin-point the basis for any observed irritation will frequently yield important and significant information. Usually, spot examination of the formula itself may disclose that no known irritants, sensitizers, etc., have been incorporated into the product. Under these circumstances, the 48-hour closed patch test has been found a very helpful