204 JOURNAL OF COSMETIC SCIENCE CONCLUSIONS: The split-face protocol design in combination with high resolution video imaging is capable of discriminating the small treatment effects afforded by commercial cosmetic formulations for hyperpigmented spot reduction. Both product formulations tested here significantly reduced facial hyperpigmented spot area aRer 1 month of use compared to their respective controls as assessed by computer image analysis of video images as well as by visual grading of BEFORE/AFTER image pairs. This benefit was maintained through 6 months of treatment. REFERENCES: 1. Kang S. and Sober AJ., "Disturbances of Melanin Pigmentation", in Dermatology, Moschella and Hurley, Ed., 3 rd Ed., Vol. 2, 1442-1474 (1992). 2. M. Jimbow and K. Jimbow, Pigmentmy Disorders in Oriental Skin, Clinics in Dermatology, 7, 11-27 (1989). 3. Caron D. et al., Split -face Comparison of Adapalene 0.1% Gel and Tretinoin 0.025% Gel in Ache Patients. JAm AcadDermato136 (6 Pt 2) S110-112 (1997). NEW POTENTIALS FOR SKIN LIGHTENING Durant Scholz, Suelien Bennett and Geoff Brooks Brooks Industries, Inc., So. Plainfield, NJ 07090 We live in a world where everyone wishes to enhance their appearances. For most of the world enhancing appearance involves reducing or evening the pigmentation of the skin. The largest perceived difference in skin tone is between constitutive pigmentation and adaptive pigmentation. This variation between sun-exposed and unexposed skin is typically about 1000 melanocytes per mm 2. Consfitutive pigmentation is the natural level of pigmentation in skin that has not been damaged or exposed to light. It is difficult to reduce the level of pigmentation of an individual below the constitutive level without significantly altering the individual's biochemistry. Considering that melanin blocks or absorbs 90% of the UV radiation penetrating through the stratum corneum, as well as the considerable anti-oxidant potential melanin offers, make the wisdom of looking to alter its constitutive levels questionable. Adaptive pigmentation is the additional pigmentation due to UV exposure, acne, skin damage, or pregnancy. To truly understand how we can influence adaptive pigmentation and the technology available to do so it is important to first discuss our current understanding of the tanning process. The most important concept is that the difference in pigmentation between light and dark skinned people is not in the number of melanocytes but the mechanism of transfer of melanosomes to the keratinocytes. Melanin synthesis is an oxidative process. Initial research seemed to show that melanin synthesis was solely controlled by tyrosinase, but now it seems that the process is significantly more complex. Tyrosinase converts tyrosine to dihydroxy phenylalanine (DOPA). Tyrosinase is a copper containing oxidase. DOPA is subsequently converted to dopaquinone (DQ). At this point melanin synthesis can be directed to pheomelanin, the yellow-orange melanin found in blond and red-haired people, or eumelanin, the dark brown melanin found in dark-haired people. For the purposes of this discussion we will confine ourselves to eumelanin production. Polymerization of dopaquinone produces leucodopachrome. Leucodopachrome is converted to dopachrome which in turn is converted to either 5,6 dihydroxyindole (DHI)

PREPRINTS OF THE 1998 ANNUAL SCIENTIFIC SEMINAR 205 or 5,6 dihydroxyindole-2-carboxylic acid (DIllCA). 5,6 dihydroxyindole and 5,6 dihydroxyindole-2--carboxylic acid are oxidized to indole-5,6-quinones, which is in turn further polymerized to form the less well defined melanochrome and finally eumelanin. Unfortunately for those Who are studying the process ofmelanogenesis, the actual synthesis of melanin is only part of the process. Melanogenesis also involves the development of the melanosomes, the organelle of the melanocyte in which melanin is synthesized, and the subsequent transfer of the melanosomes to keratinocytes. Melanosome development is generally divided into four phases. In phase I melanosomes contain tyrosinase but are clear. In the second phase the melanosome assumes an oblong shape as microtubules and microfilaments begin to expand. In phase II melanin is being formed. Phase III melanosomes are darker with a higher density and begin to migrate toward the dendrites of the melanocytes. In the final phase the melanosomes are opaque and are ready for transfer from the dendrites to keratinocytes. Once melanosomes have been transferred to keratinocytes their fate depends extensively on the race of the subject. In Caucasian subjects melanosomes begin to be hydrolyzed almost immediately upon uptake. The degradation continues until no melanosomes are detected by the time that the keratinocytes have migrated into the stratum corneum. In Black skin melanosomes remain intact in the stratum corneum, indicating that there is little or no enzymatic degradation. Melanosomes in Asian skin do degrade but not at the rate seen in Caucasian skin. To make the subject more interesting all of the aforementioned steps are influenced by environment, genetics, and hormone flux. Haven taken a basic look at the process of melanogenesis, we can now begin to look at ways to prevent or reverse adaptive pigmentation. There are several routes by which we can slow down melanogenesis. Perhaps the best way to slow down melanogenesis is to reduce the amount of UV light that reaches the skin. If people cannot stay out of the sun, they should attempt to regularly use sunscreens. UV radiation not only directly stimulates the generation oftyrosinase mRNA, but it also provokes the synthesis of Vitamin Ds, which activates tyrosinase, and o•-MSH (melanocyte stimulating hormone). As a result of the UV radiation, oxidative stress is generated which in turn generates inflammation. Inflammation, perhaps mediated by cytokines, increases pigmentation. Perhaps the most talked about means of minimizing adaptive pigmentation is reducing tyrosinase activity. This can be accomplished by blocking the production of tyrosinase, inhibiting the enzymatic activity of tyrosinase, or preventing the uptake of tyrosinase by the melanosomes. Lactic acid and placental extracts suppress tyrosinase production at a genetic level. Matehals such as licorice extract, or kojic acid inhibit the enzymatic activity oftyrosinase. Amino sugars such as glucosamine or galactosamine are capable of inhibiting the glycosylation oftyrosinase required for its uptake into melanosomes and subsequent activation. Another approach to reducing the development of pigmentation is to reduce the activity of melanocytes. Melanocyte activity can be reduced through the use of selectively cytotoxic materials such as hydroquinone. Alternatively materials which are o•-MSH antagonists, such as melatonin can be used to prevent the activation of the melanocytes.