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j. Soc. Cosmet. Chem., 32, 303-315 (September/October 1981) The evaluation in vitro of fragrance materials for phototoxic activity E.H. WEINBERG and S.T. SPRINGER, International Flavors and Fragrances, I515 Highway 36, Union Beach, NJ. 07735. Received.June 4, I98I. Presented at the Society of Cosmetic Chemists Annual Scientific Seminar, May 21-22, I98I, lVashington, D.C. Synopsis Phototoxicity or photoirritation, has historically been evaluated in mice or pigs by various methods as a safety test prior to initial exposure of humans. These methods have been expensive. We have modified an assay for routine evaluation of fragrance chemicals for phototoxic potential prior to HUMAN TESTING. Our method uses ultraviolet (UVA) irradiation during diffusion of test chemicals from a paper disc placed upon agar freshly seeded with Fleischman's Baker's Yeast. A concurrent positive control, 8- METHOXYPSORALEN is tested at 10-4%. The test for each chemicall: is contained within a four-compartment plastic unit. Light-specific zones of inhibited yeast growth 'r•flect phototoxic events. Duplicate units are run in the absence of ultraviolet light to account for any direct, UV-independent anti-fungal activity. Correlations are made with UV ABSORPTION data. The test is inexpensive, simple to conduct and provides results within 72 hours. Correlations with positive human phototoxicity results have been excellent. The test provides a tool to easily pre-screen for phototoxic changes related to structural modifications of useful chemicals. It is used primarily to set safe initial dose levels for human panelists in the hazard assessment program. i'• INTRODUCTION This paper presents work on the adaptation and evaluation of the procedure of Daniels (1) for the detection of fragrance chemicals which may produ•ce ultra-violet-light- induced irritation to human skin. The commercial and medical significance of such photochemical irritation has been universally accepted. The hairless mouse screen is being used by the fragrance industry to safeguard human panelists from excessive hazard during the conduct of safety studies (2). Much of the data developed by the Research Institute for Fragrance Manufacturers (RIFM) is ge'nerated in this system however, naturally hairless parts of normal mice are also used (3). This animal assay is both expensive and time consuming. For these reasons we have been encouraged to seek simpler methods to evaluate new chemicals for phototoxic potential. These procedures should allow for studying the effects of structural modifications on photoreactivity as well as provide data adequate to set initial concentrations for the safe testing of new fragrance ingredients on the skin of human volunteers. We envision the subsequent use of animal tests only in cases where ia vitro methods indicate very 303