Considerations on photochemical genotoxicity: Report of the International Workshop on Genotoxicity Test Procedures Working Group

Recent toxicological observations have caused concern regarding the need to test, For example, pharmaceuticals and cosmetic products For photochemical genotoxicity. The objective of this report is to give assistance on how to adapt existing test methods to investigate the potential of light-absorbin g compounds to induce genotoxic effects on photoactivation. In general, the Organization For Economic Co-Operation & Economic Development (OECD) draft guideline on in vitro phototoxicity testing served as a basis for consider ation. Concomitant exposure of the cells to the test compound and solar sim ulated light was considered appropriate as the initial, basic test conditio n. Optimization of the exposure scheme, e.g., a change of the irradiation s pectrum, might be indicated depending on the initial test results. Selectio n of test compound concentrations should be based on results obtained with the dark version of the respective test system but might have to be modifie d if phototoxic effects are observed. Selection of the irradiation dose has to be performed individually For each test system based on dose-effect stu dies. The irradiation should induce per se a small, reproducible toxic or g enotoxic effect. The report includes a specification of necessary controls, discusses Factors that might have an impact on the irradiation characteris tics, and gives a rationale for the omission of an external metabolic activ ation system. It also addresses the question that physicochemical and pharm acokinetic properties might trigger the need to test cc chemical For photoc hemical genotoxicity. Relevant experimental observations are presented to b ack up the recommendations. The working group did not reach a consensus as to whether a single, adequately perfomed in vitro test for clastogenicity w ould be sufficient to exclude a photogenotoxic liability or whether a test battery including a gene mutation assay would be needed for product safety testing regarding photochemical genotoxicity. (C) 2000 Wiley-Liss, Inc.