This proposal, "Phototoxicity Screen using the Chorioallantoic Membrane" (PhotoCAM) is an alternative phototoxicity screening test to identify chemical mediators and substances with phototoxic properties, which is in demand by the pharmaceutical, chemical, and consumer product industries. The chorioallantoic membrane (CAM) of the fertile chicken egg has already shown to be a useful, sensitive model for detecting irritants. The purpose of this proposal is to demonstrate the feasibility of employing the CAM assay, as well as endpoints of PGE2 and cytokine production by the epidermal cells comprising the tissue, as test systems to identify potential phototoxins or photoirritants. There have only been two papers published in the literature using this model, thus this is a relatively novel application of this model system. The use of an intact tissue has several advantages over existing cell culture-based phototoxicity screening assays. These include the presence of multiple cell types found in the skin, and a readily accessible circulatory system that is in contact with metabolically functional hepatic tissue. The PhotoCAM Assay described herein will provide a sensitive test system while (1) complying with the Animal Welfare Act (AWA) by directly addressing the 3Rs, by reducing animal usage; (2) increasing the discriminating power and quality of data generated when compared to cell culture methods; and (3) greatly reducing the costs associated with the use of animals for phototoxicity screening studies.