312 JOURNAL OF COSMETIC SCIENCE SUNLIGHT AND SKIN: AN IMMUNOLOGIST'S POINT OF VIEW Paul Bergstresser, M.D. University of Texas Southwestern Medical Center The sun emits a spectrum of electromagnetic radiation (solar spectrum) with profound effects on the earth and it's biomass. The principal wave lengths that affect skin are found in the visible (400 to 800 nm) and ultraviolet (295 to 400 nm) regions. We have learned over the last two decades that ultraviolet radiation (UVR) has the capacity to distort immune responses that are initiated and expressed in skin. Events of relevance to humans include surveillance against skin cancer and against the infectious diseases, as well as hypersensitivity reactions against foreign chemicals. Importantly, UVR is also used as a therapeutic tool in diseases such as psoriasis, mycosis fungoides, and atopic dermatitis. Normally, immunity in skin is initiated by dendritic cells, including epidermal dendritic cells (Langerhans cells) and dermal dendritic cells. When a dendritic cell encounters elements derived from necrotic cells or from infectious agents, portions are metabolized into small immunogenic peptides (antigens). This is accompanied by cell activation as the dendritic cell moves from skin to draining lymph nodes. Within nodes, lymphocytes reactive against these antigens are recruited, activated, and then expanded greatly in number. These lymphocytes then circulate via blood and lymph, ready to kill or to cause inflammation wherever such antigens may be found. UVR distorts this process at several points. It causes the production of cytokines that tend to suppress the development of immunity for example, IL-10 inhibits the activation ofThi (CD4+) cells. It causes the immigration into skin of antigen-presenting cells that promote the development of suppression. It also causes the photo-isomerization of trans-urocanic acid, a normal constituent of skin, into cis-urocanic acid, which tends to suppress immunity. UVR even has the capacity to distort antigen presentation by Langerhans cells, and it has directly detrimental effects on lymphocyte survival. Recently there has been debate concerning the extent to which UVR-absorbing sunscreens are able to prevent these detrimental effects. Ultimately, knowledge of UVR-mediated effects in skin will allow us to protect and perhaps even to reverse it's effects. That is the goal of contemporary research in photoimmunology.

2002 ANNUAL SCIENTIFIC SEMINAR 3 ! 3 SUBSTANTIATION OF BROAD SPECTRUM & UVA RADIATION ATTENUATION CLAIMS FOR TITANIUM DIOXIDE Art Georgalas and Elizabeth Kasprzyk Tri-K Industries, Inc., Northvale, New Jersey 07647-0128 UVA sunscreen substantiation has been a contentious issue since FDA and the industry first decided to address it separately from the sunburn preventing conventional sunscreens governed by the original OTC Sunscreen Monographs. The chronic effects of long-term UVA exposure display as visible signs of aging and possibly increased incidence of some skin cancers. A reproducible bioassay to give immediate assessment of UVA attenuation can only be made with effects that are acute or instrumental methods that simply measure the light flux efI•cts. One acceptable in vivo method is the measurement of the effects on persistent pigment darkening (PPD) compared to untreated skin. In vitro broad-spectrum capability is demonstrated by identification of the critical wavelength of subject product. This is the wavelength at which the area under the absorbance curve beginning at 290 nm is 90% of the total solar UV irradiance as measured instrumentally from 290-400 nm. Additionally, instrumental measurement can estimate a UVA protective factor and a ratio of UVA to UVB attenuation. These are measures accepted or being considered by dermatologists, industry formulators and regulatory agencies worldwide. To petition FDA by their deadline of Sept .6, 2000, we embarked on a program to demonstrate conclusively that Titanium Dioxide in its different commercial variations for the personal care industry could be claimed as an effective UVA sunscreen and hence boast the claim of Broad Spectrum Sunscreen. In order to fully investigate and document our thesis we planned and carried out a multipart experiment to look at both the in vitro and in vivo efficacy of a series of formulations with Titanium Dioxide as the only active sunscreen. Then, subsequent to the FDA petition, we continued with additional variations in types of titanium dioxide coatings and mixtures we tested. Different grades of titanium dioxide were chosen to represent the full range of varieties available. These included ultra small particle, 15 nm, hydrophobically and hydrophilically coated particles, microtitanium dioxide, 35 nm particle size, both uncoated and hydrophobically coated and a larger pigmentary grade of 180 nm. To test variability in different types of formulas, both a simple oil-in-water cream and a water-in-oil silicone formulation were evaluated. Tests performed in vitro were via the Optometrics 290 SPF Analyzer utilizing IMS Vitro Skin 'rM as substrate to better mimic skin application. Clinical studies performed at AMA labs used FDA protocol for SPF and JCIA protocol for PPD assessment of UVA protection. Overall the experiments demonstrated that Titanium Dioxide could fulfill the requirements promulgated by the American Academy of Dermatology for UVA sunscreens: meet or exceed the in vitro critical wavelength of 370 nm, achieve in vivo a protective factor of four (4) as measured by PPD or UVAPF, and show some reasonable proportionality to SPF when increasing the active concentration.