306 JOURNAL OF COSMETIC SCIENCE of the grafts was obvious both visually and from the gradual positive increase in '1L * compared to the vehicle-treated control. The increase in '1L * started for dA at the two-week treatment point and increased gradually over the eight-week treatment pe­ riod. In addition, TBP-treated grafts developed clear vitiligo-like patches. This discrep­ ancy may result from the high SE and low number of animals in each group. For instance, in order to be able to detect a significant difference for the dA-treated group eight weeks after treatment, using the two-sided two-sample test, we needed at least five animals in each group. The effect of dA on reversing hyperpigmentation demonstrated in the xenograft model system was recapitulated in a clinical trial. Hyperpigmentation induced by UV exposure was effectively reduced by dA. The lightening effect of dA on pathologic hyperpigmen­ tary disorders like melasma, solar lentigo, and post-inflammatory hyperpigmentation is yet to be determined. An interesting observation is that mice treated with HQ developed brown coloration of the albinistic hair adjacent to the grafts. Presumably this is a staining artifact from the by-products of hydroquinone oxidation. This brown pigmentation matches the reported nail plate discoloration that can develop during use of topical hydroquinone-containing cream (38--40). This color change of the nail was considered to be due to the oxidation products of hydroquinone. Hydroquinone readily oxidized to quinone and subsequently to hydroxyquinone, which is unstable and polymerizes to a brown compound. CONCLUSIONS In this report we have provided evidence that currently used skin-depigmenting agents have drawbacks in either their efficacy or their safety. Deoxyarbutin is demonstrated to be less cytotoxic than the standard skin-lightening product in the market (i.e., HQ). The cytotoxicity dA exhibited is not associated with dramatic degenerative changes in the morphology of keratinocytes as compared with HQ. Our overall goal is to provide the market with an effective skin depigmenting agent due to the fact that available depig­ menting agents in the market are far from satisfactory. We have clearly demonstrated that dA has the potential to be a safe and effective depigmenting agent. It also offers the potential to be an effective alternative to hydroquinone, the skin-depigmenting standard in the market with known safety drawbacks. REFERENCES (1) R. E. Boissy, M. Visscher, and M.A. deLong. DeoxyArbutin, A novel tyrosinase inhibitor with effective skin lightening potency, Exp. Dermatol., 14, 601-608 (2005). (2) J.P. Ortonne and]. J. Nordlund, Mechanisms that cause abnormal skin color, in The Pigmentary System: Physiology and Pathophysiology, J. J. Nordlund, R. E. Boissy, V. J. Hearing, R. A. King, and J. P., Ortonne, Eds. (Oxford University Press, New York, 1998), pp. 489-502. (3) A. Perez-Bernal, M.A. Mufioz-Perez, and F. Camacho, Management of facial hyperpigmentation, Am. ]. Clin. Dermatol., l, 261-268 (2000). (4) S. Briganti, E. Camera, and M. Picardo, Chemical and instrumental approaches to treat hyperpig­ mentation (review), Pigment Cell Res., 16, 101-110 (2003). (5) S. Passi and M. Nazzaro-Porro, Molecular basis of substrate and inhibitory specificity of tyrosinase: Phenolic compounds, Br.]. Dermatol., 104, 659-665 (1981).

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