Final Report on the Safety Assessment of Urocanic Acid

Abstract

Urocanic Acid is a naturally occurring metabolite of histidine. The trans-Urocanic Acid isomer is found as a normal constituent of the epidermis, where it accumulates because there are only very low levels of the enzyme urocanase available to break it down; the accumulation causes trans-Urocanic Acid excretion in sweat. On exposure to UV radiation present in sunlight, the trans-Urocanic Acid isomer converts to the cis-Urocanic Acid isomer. In cosmetic formulations, Urocanic Acid is used as a skin-conditioning agent and as a sunscreen. Several questions were specifically considered in this safety assessment, including the extent to which applied Urocanic Acid is absorbed by the skin and, if absorbed, what the effect is on endogenous levels. Recognizing that photoisomerization is likely to occur in the skin, what is the resultant ability of cis-Urocanic Acid to act as an immunosuppressant? If the ingredient does cause immunosuppression, is there concomitant enhancement of photo-carcinogenesis? The available data indicate that Urocanic Acid is absorbed in mouse and human skin, although at a faster rate in mouse 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 Acid is an immunosuppressant, but the clinical data are inconclusive as to the immunosuppressant effect of Urocanic Acid in humans (it may be problematic that Urocanic Acid was not exposed to UV radiation in the clinical tests). To directly assess the question of enhanced photocarcinogenesis, the results of two studies were considered. In one study of hairless mice, no neoplasms were found in the group exposed only to trans-Urocanic Acid, carcinomas were found in the group that received UV exposure and no trans-Urocanic Acid, and a significantly greater number of carcinomas was found in the group exposed to trans-Urocanic Acid followed by UV exposure. In a second study, using three similar groups of hairless mice (Urocanic Acid alone, UV alone, and UV plus varying concentrations of Urocanic Acid), all groups showed comparable numbers of carcinomas, papillomas, and other tumors. While there was concern about the influence of the methodologies on the interpretation of results in these two studies, the results from neither study could be discounted. Only further study, therefore, can resolve the questions of the immunosuppressive effect of Urocanic Acid in humans and whether the immunosuppressive effect in animals is linked to the incidence of cancer in those animals. The additional information needed includes human photoimmunosuppression data, data on the modulation of photocarcinogenicity 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.