Phototoxicity

Phototoxicity, or photoirritation, is an inflammatory skin reaction caused by exposure to a chemical and subsequent exposure to sunlight or ultraviolet radiation. Phototoxicity typically appears as exaggerated sunburn, which is characterized by the presence of a rash, swelling, and inflammation. This endpoint is mainly a concern for drugs and pharmaceuticals that are either ingested or applied directly to the skin in the form of a cream.The only regulatory agency in the U.S. that routinely requires phototoxicity studies is the Food and Drug Administration.

Animal Test

Mice or guinea pigs are locked into restraints and different concentrations of a test chemical are applied to patches of shaved skin on their backs. Half the animals are then exposed to ultraviolet radiation for two or more hours, after which the chemical is removed. The animals are then kept restrained for several days while experimenters examine their skin. Swelling and sores are common. No painkillers are provided. Despite their years of use, animal-based phototoxicity studies have never been properly validated to establish their relevance to people or even codified into a standardized test guideline. In fact, the only internationally recognized guideline for phototoxicity studies is the non-animal, cell-based test described at right.

Non-Animal Test

The 3T3 Neutral Red Uptake (NRU) Phototoxicity Test was developed and validated in Europe and has since been accepted at the international level as a total replacement for animal-based phototoxicity studies. In this test, cells from the 3T3 cell line are exposed to a test chemical in the presence and absence of light. Photo-cytotoxicity is evaluated by the relative reduction in viability of cells exposed to the chemical in the presence versus absence of light, where cell viability is measured by degree to which they are able to absorb the dye, neutral red.

Although the reliability and relevance of the 3T3 NRU Phototoxicity Test have been established through rigorous, inter-laboratory validation studies overseen by the European Centre for the Validation of Alternative Methods (ECVAM), and this method has been accepted as an official test guideline of the Organization for Economic Cooperation and Development (OECD), the Food and Drug Administration and the National Institute of Environmental Health Sciences continue to rely on animal testing to assess the phototoxic potential of new drugs and pharmaceuticals.