216 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS Lastly, erythema, as well as other signs of inflammation, is much more difficult to observe and interpret in the skin of blacks. More importantly, black skin may be a more effective barrier than white skin. This finding has been demonstrated by challenge experiments with several known chemical irritants (13,14). The very best panel of subjects for conducting a Maximization Test would consist of those with highly sensitive skin--a combination of red hair and freckles, or light-complexioned blue-eyed blonds of Scots-Irish descent, or young, white females who give a history of always sunburning and never tanning. This sounds like shades of testing with different sunscreen formulations. PHOTODERMATITIS The recent finding that 6-methylcoumarin, a synthetic fragrance, is a potent photocon- tact allergen has had a sobering impact on all involved in the safety assessment of new formulations prior to marketing. Phototoxicity testing can be conducted under natural sunlight or in the laboratory under carefully controlled conditions. Sophisticated, well-calibrated, artificial light sources, complete with light-filtering capabilities, are currently available. Lamp testing is much more convenient, precise, and free from the finickiness of our ungovernable weather. Photomaximization testing has been described in detail by Kaidbey and Kligman in their report entitled "Photocontact allergy to 6-methylcoumarin" (15). This report defined how the induction phase was carried out with repeated applications of 5% 6-methylcoumarin in Hydrophilic Ointment, U.S.P., under an occlusive dressing. Then the test sites were exposed to 3 MED's of solar-simulating radiation. Ten (10) days after the last exposure, the sites were challenged with an appropriate UV-A dose (320-400 nm), the action spectrum characteristic for photoallergens. Of course, suitable controls--that is, an unexposed 6-methylcoumarin-treated site, a vehicle site and the full formulation of suspect suncreen product--were included in this testing. Observa- tions at 24, 48, and 72 hr pinpointed the reaction characteristic of photocontact allergy, namely, erythema and vesiculation, reaching a maximal intensity 48-72 hr after irradiation, spreading beyond the confines of the actual patch and associated with intense pruritus. Yes, products of the future, particularly those containing fragrances, dyes, sunscreens, bacteriostats and brand new ingredients, will be candidates for photosensitization testing with our rapidly improving and readily available methodol- ogy. THE 1980'S During the next decade, stricter attention will be paid to the possibility of percutaneous absorption of cosmetic ingredients from different vehicles. The unearth- ing of neurotoxic effects of acetyl tetramethyl tetralin (AETT) in animal studies has brought a new dimension to every fragrance supplier as he considers a safety testing program for new ingredients. The findings of the nitrosamine, N-nitrosodiethanol- amine, and 1,4-dioxane as contaminants in cosmetic products and cosmetic raw materials, respectively, are other examples of our increasing awareness of the possibility of systemic absorption. If these compounds cause cancer in laboratory animals, what are the implications when applied to human skin? Admittedly, as with

SAFETY TESTING IN THE EIGHTIES 217 all other carcinogens, the risk is dependent on potency, percutaneous absorption characteristics, and human exposure after conditions of normal usage. The inadequacy of the skin barrier in premature babies became painfully apparent with the saga of hexachlorophene. The variability in permeability of human skin as it relates to cosmetic products, ingredient to other ingredients, race to other races, individual to other individuals, and body region to other body regions has not received adequate attention to date. Lastly, as the years pass by, and the treatment for acne becomes more and more successful because of our systemic tetracycline therapy, topically applied retinoic acid, benzoyl peroxide and antibiotics, and, most recently, systemic 13-cis retinoic acid for the serious and disfiguring cystic acne, we will become increasingly aware that many cosmetic ingredients are capable of comedo formation. Noncomedogenicity will become a rule of thumb for our face makeup preparations and for our other cosmetics that are used for long time periods, especially by teenagers. Our future human testing procedures, which will follow screening in the appropriate animal model, for instance, the rabbit ear (16), need significant development and refinement. SUMMARY This paper has attempted to pinpoint those human tests that are appropriate for assessing the safety of cosmetic products and those that will endure during the next decade. Admittedly, animal testing for acute toxicity, eye irritation potential, inhala- tion toxicity, percutaneous absorption, mutagenesis, teratogenicity, and carcinogen- icity--because of reasons of practicality and inherent dangers in establishing target organ sites for toxic effects--will continue to be conducted. Nevertheless, the uniqueness of human skin will still make it the most satisfactory test model for irritation or sensitization with and without the participation of ultraviolet irradiation. REFERENCES (1) LD50 tests, The Lancet, 595 (September 15, 1979). (2) B. M. Lanman, W. B. Elvers, and C. S. Howard, The role of human patch testing in a product development program, in Proceedings, Joint Conference on Cosmetic Sciences, The Toilet Goods Association, Inc., Washington, D.C., 135-145 (April 21-23, 1968). (3) L. Phillips II, M. Steinberg, H. I. Maibach, and W. A. Akers, A comparison of rabbit and human skin response to certain irritants, ToxicoL AppL PharmacoL, 21,369-82 (1972). (4) P.J. Frosch and A.M. Kligman, The chamber-scarification test for assessing irritancy of topically applied substances, in *'Cutaneous Toxicity," V. A. Drill and P. Lazar, Eds., Academic Press: New York, 127-54, 1977. (5) P.J. Frosch and A.M. Kligman, The soap chamber test. A new method for assessing the irritancy of soap, J. Amer. Acad. DermatoL, 1, 35-41 (1979). (6) P.J. Frosch and A.M. Kligman, A method for appraising the stinging capacity of topically applied substances, J. Soc. Cosmet. Chem., 28, 197-209 (1977). (7) L. Schwartz and S. M. Peck, The patch test in contact dermatitis, Publ. Health Rep., 59, 546-57 (1944). (8) J. H. Draize, Dermal toxicity. Appraisal of the safety of chemicals in foods, drugs and cosmetics, in "The Associated Food and Drug Officials of the United States," Texas State Department of Public Health: Austin, Texas, 46-59 (1959). (9) H. A. Shelanski and M. V. Shelanski, A new technique of human patch tests, Proceedings Scientific Section Toilet Goods Association, 19, 46-9 (1953).