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).

218 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS (10) A.M. Kligman, The identification of contact allergens by human assay. III The maximization test: A procedure for screening and rating contact sensitizers, J. Invest. Dermatol. 47, 393-409 (1966). (11) A.M. Kligman and W. Epstein, Updating the maximization test for identifying contact allergens, Contact Dermatitis, 1,231-39 (1975). (12) Spillover Effect, Food, Cosmet. ToxicoL, 13,683 (1975). (13) D. A. Weigand and M. M. Mershon, The cutaneous irritant reaction to agent 0-chlorobenzylidene malononitrile (CS). I. Quantitation and racial influence in human subjects, in "Edgewood Arsenal Technical Report 4332" (February 1970). (14) D. A. Weigand and J. R. Gaylor, Irritant reaction in negro and caucasian skin, South. ]tled. J, 67, 548-51 (1974). (15) Kaidbey and Kligman, Photocontact allergy to 6-methylcoumarin, Contact Dermatitis, 4, 277-282 (1978). (16) A.M. Kligman and A. Katz, Pathogenesis of ache vulgaris, I. Comedogenic properties of human sebum in external ear canal of the rabbit. Arch. Dermato/, 98, 53-66 (1968).