I. Soc. Cosmet. Chem., 25, 639-644 (December 1974) The Hairless Mouse as an Experimental Model for Evaluating the Effectiveness of Sunscreen Preparations HANNA WOLSKA, M.D.,* ANDRZEJ LANGNER, M.D.,t and FRANCIS N. MARZULLI, Ph.D.* Synopsis-SKIN REACTIONS were observed in HAIRLESS MICE (4 to 6 months old) which were administered different amounts of ultraviolet (UV) IRRADIATION with a solar simulator. An identical minimal erythema dose (MED) was found in all animals, demonstrating a highly reproducible dose-effect response in this species. The skin of this species appears to be more responsive to UV irradiation than human skin. Additional mice were similarly irradiated 30 minutes after 8 commercial SUNSCREENS were applied separately. In unprotected animals these UV exposures would have been equivalent to up to 10 MED. The best protection was obtained with two sunscreens, one of which con- tained 5.4% p-dimethylaminobenzoic acid, the other 2.7% alkyl p-aminobenzoate. The least protection was provided by one containing 4.4% homomenthyl salicylate and one containing 1.6% alkyl p-dimethylaminobenzoate. The results obtained on hairless mice are consistent with those reported on man, suggesting that this species is likely to prove useful in evaluating the in vivo effectiveness of sunscreen preparations. INTRODUCTION During the past decade, dermatologists have been vigorous in alerting the public about the destructive potential of solar radiation for skin (1). Kligman (2) and others pronounce sunlight a greater threat to the skin's integrity than *Supported by Proiect 05-607-4, PL-480 Agreement Apr. 1972, May 1974, between the Food and Drug Administration, U.S. Department of Health, Education, and Welfare, and Warsaw Medical Academy, Warsaw, Poland (Prof. S. Jablonska, Director). '•Department of Dermatology, Warsaw Medical Academy, Warsaw, Poland. $Division of Toxicology, Bureau .of Foods, Food and Drug Administration, Washington, D.C. 639

640 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS ageing. The term solar or actinic elastosis is considered more descriptive of the changes observed in skin damaged by time and the elements than the more classical term senile elastosis. This increased attention has produced a more critical assessment of sun- screens which are marketed to protect the skin from the damaging effects of solar radiation and the techniques used for their evaluation. A cursory review of the subject reveals that the requirements for sunscreens under use condi- tions are not easily satisfied. In addition to the obvious need that they have a proper absorption spectrum and be nonirritating, nontoxic, reasonably stable, and not easily dissipated or removed by sweat or bathing, the manufacturer must consider marketing factors among which are included easy application, cosmetic acceptability, and suitable price. Fulfilling all these requirements provides a stimulus to further research. Most investigations on sunscreens have been carried out on human subjects (3). Although man is the ultimate user of these products, the possibility of producing hyperpigmentation on large areas of skin, together with problems of obtaining human subjects, suggests the need for a suitable animal model, at least for the exploratory phases of sunscreen development. MacLeod and Frain-Bell (4) report that in vitro studies are frequently unreliable in deter- mining the in vivo efficacy of sunscreen preparations. The present study in- volves the use of the hairless mouse in evaluating one aspect of the efficacy of sunscreens, namely, their photobiologic protection potential for skin. MATERIALS AND METHODS Exploratory studies were conducted on 30 male and 30 female hairless mice 4 to 6 months of age. They were irradiated (3000 FW/cm'-') with a 150-W Xenon lamp* with WG-320 Schott filter in 20 groups of 3. The distance from final filter to skin was 7 cm. Intensity of irradiation was monitored with a long- wave UV-meter.* Four skin areas each about 1 cm 2 were exposed to solar simulating spectrum (which includes the erythema spectrum, 290-320 nm) for periods ranging from 15 sec to 3 min in 15-sec increments to find the mini- mal erythema dose (MED). Skin reactions were observed and recorded for 10 days at 1-hr intervals during the first 12 hr and then at 24-hr intervals. The mice gave uniform responses. After completion of the exploratory studies, 8 commercial sunscreens were tested to evaluate their protection potential. Each preparation was applied to a 1-em 2 area of skin of 10 hairless mice (about 4 mg for ereams and 60/xl for liquids) and 30 min later the mice were irradiated with 2.5, 5, 7.5, or 10 MED. Control animals were irradiated without sunscreen protection with 1.5, 2.5, 5, 7.5, and 10 MED (3, 5, 10, 15, and 20-min exposure, respectively). *Solar Light Co., Philadelphia, Pa. '•Ultraviolet Products Inc., San Gabriel, Calif., J-221.