J. Soc. Cosmet. Chem., 24, 135-146 (February 2, 1973) Animal, Human, and Microbiological Safety Testing of Cosmetic Products M. J. THOMAS, Ph.D., and P. A. MAJORS, M.S.* Presented October 27, 1971, before the California Chapter Synopsis-The three principal areas of TESTING pertinent to COSMETICS are discussed. These include SAFETY determination in ANIMALS, safety and efficacy studies in HUMANS, and MICROBIOLOGICAL STUDIES for safety and product stability. Prod- ucts must be shown safe to animals prior to use on humans. Most animal studies include, for the most part, acute and subacute studies. The former are done in accordance with the Federal Hazardous Substances Act (FHSA) requirements. There are a number of patch tests applicable to human safety testing of products. The modified Draize technique appears to be the preferred procedure. It serves as a good predictor of sensitizing potential and supplies information on the primary irritant charac- teristics and cmnulative primary irritant properties of the test materials. A test program is also presented for determination of adequacy of PRESERVATIVES in new and cur- rent cosmetic products. INTRODUCTION The increasing emphasis placed by our Government on the safety of foods, drugs, and similar products has been expanded into the area of cosmetic prod- ucts in the last few years. Those in the independent research and testing lab- oratory fields are very much aware of this change because they have been an integral part of the developing program and have seen the various regulations evolve. Just as the regulatory requirements for safety in food additives and drug products became more definitive as time passed, so will the regulatory requirements for cosmetic products be more specific and more pronounced as time goes on. The objective here is to summarize the present trends and methods used in testing for the safety and efficacy of cosmetic products. Recent action of the *Hill Top Research, Inc., Miamiville, Ohio 45147. 135

136 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS FDA relative to voluntary disclosure of product ingredients will not be dis- cussed in detail. Accompanying the publication of the ingredient disclosure regulations was the unexpected change in the classification of 13 cosmetic product categories as also being drugs. This reclassification does not neces- sarily mean that additional tests will be required. Many cosmetic manufactur- ers have product safety standards which exceed the standards which apply to new drug approvals. The one area of testing which will be affected is the evaluation of these products on humans. Before this can be done, proper investigational forms must be filed xvith the Food and Drug Administration. This requires submis- sion of detailed protocols for review, and review of these protocols by peer committees. The three ,principal aras of testing pertinent to the cosmetic field include (a) safety determinations in animals, (b) safety and efficacy studies in hu- man panelists, and (c) safety and product stability from the microbiological standpoint. When a product is submitted for human panelist testing, it is man- datory that sufficient animal toxicological data exist to show that the product is relatively nontoxic and will not induce excessive reactions in the testing on humans. After the product has been shown to be safe in animal and human panelist testing, it is ready for the market. However, there are still microbio- logical contamination factors which should be considered. During the manu- facturing process the product may be inadvertently exposed to unsanitary conditions in the plant or around equipment, or to contaminated air entering the plant, or to obiectionable microorganisms in the basic raw materials. ANIMAL TOXICOLOGY It is usually recommended that the animal toxicology programs follow the protocols specified by the Federal Hazardous Substances Act (FHSA) and its subsequent Regulations, published in the Federal Register (1), and those of additional studies which are frequently required. These programs wfil require one or more tests according to the type of product involved. These are: 1. Acute oral toxicity-rats 2. Acute eye irritation-rabbits 3. Primary skin irritation and corrosivity-rabbits 4. Acute dermal toxicity-rabbits 5. Acute inhalation toxicity-rats 6. Subacute dermal (21-day) toxicity-rabbits 7. Landsteiner skin sensitization in guinea pigs Acute Oral Toxicity These studies are conducted with six groups of five male albino rats (30 rats). A single oral dose of the test material is administered at graduated dos-