In vitro methods for phototoxicity and photocarcinogenicity testing of drugs LINZ 2000

Abstract

Phototoxicity is an acknowledged property of some UV and/or visible light absorbing substances some of which are used as pharmaceuticals or in cosmetic preparations. In recent years attention has been called upon the fact that toxic intermediates that are generated upon photoactivation of a substance can also lead to DNA damage. Such damage may lead to mutated/ initiated skin cells which in turn can contribute to an elevated skin cancer risk. The method of choice to test for photo-related skin carcinogenesis is a 1-year study in genetically hairless mice in which the formation of skin papilloma and their latency time are assessed. Here, in vitro test approaches to test for photogenotoxicity can be used in a tiered assessment approach asking the use of in vitro genotoxicity tests for prediction of rodent/human carcinogenicity. In the past few years some effort has been put into the evaluation for such systems. In particular standard test protocols have been generated for the in vitro photo-micronucleus test and the in vitro photo-comet assay with Chinese hamster V79 cells. The data that have been produced so far show promising results regarding the implementation of these systems in a tiered approach for photocarcinogenicity assessment of UV- and/or visible light absorbing substances but the systems will have to be validated in further collaborative studies.