FINAL REPORT ON THE SAFETY ASSESSMENT OF UROCANIC ACID

Urocanic Acid is a naturally occurring metabolite of histidine. The tr ans-Urocanic Acid isomer is found as a normal constituent of the epide rmis, where it accumulates because there are only very low levels of t he enzyme urocanase available to break it down; the accumulation cause s trans-Urocanic Acid excretion in sweat. On exposure to UV radiation present in sunlight, the trans-Urocanic Acid isomer converts to the ci s-Urocanic Acid isomer. In cosmetic formulations, Urocanic Acid is use d as a skin-conditioning agent and as a sunscreen. Several questions w ere specifically considered in this safety assessment, including the e xtent to which applied Urocanic Acid is absorbed by the skin and, if a bsorbed, what the effect is on endogenous levels. Recognizing that pho toisomerization is likely to occur in the skin, what is the resultant ability of cis-Urocanic Acid to act as an immunosuppressant? If the in gredient does cause immunosuppression, is there concomitant enhancemen t of photocarcinogenesis? The available data indicate that Urocanic Ac id is absorbed in mouse and human skin, although at a faster rate in m ouse skin. Limited human data suggest that there is no increase in the total level (endogenous + applied) of Urocanic Acid in the skin over a 16-week period. Extensive animal data indicate that cis-Urocanic Aci d is an immunosuppressant, but the clinical data are inconclusive as t o the immunosuppressant effect of Urocanic Acid in humans (it may be p roblematic that Urocanic Acid was not exposed to UV radiation in the c linical tests). To directly assess the question of enhanced photocarci nogenesis, the results of two studies were considered. In one study of hairless mice, no neoplasms were found in the group exposed only to t rans-Urocanic Acid, carcinomas were found in the group that received U V exposure and no trans-Urocanic Acid, and a significantly greater num ber of carcinomas was found in the group exposed to trans-Urocanic Aci d followed by UV exposure. In a second study, using three similar grou ps of hairless mice (Urocanic Acid alone, UV alone, and UV plus varyin g concentrations of Urocanic Acid), all groups showed comparable numbe rs of carcinomas, papillomas, and other tumors. While there was concer n about the influence of the methodologies on the interpretation of re sults in these two studies, the results from neither study could be di scounted. Only further study, therefore, can resolve the questions of the immunosuppressive effect of Urocanic Acid in humans and whether th e immunosuppressive effect in animals is linked to the incidence of ca ncer in those animals. The additional information needed includes huma n photoimmunosuppression data, data on the modulation of photocarcinog enicity using specified procedures, and a DNA adduct study in vivo and in vitro. Until these data are available, it cannot be concluded that Urocanic Acid is safe for use in cosmetic formulations.