Let's shed light on photogenotoxicity

• Published in: The Science of the total environment Vol. 954; p. 176354
• Main Authors: Diniz, Raiane R., de Pádula, Marcelo, de Souza, Alessandra M.T.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-12-2024
• Subjects: In silico toxicity; In vitro; NAMs; Photocytotoxicity; Photogenotoxicity; Phototoxicity; In silico toxicity; Phototoxicity; Photogenotoxicity; Photocytotoxicity; In vitro; NAMs
• ISSN: 0048-9697; 1879-1026; 1879-1026
• DOI: 10.1016/j.scitotenv.2024.176354

Photosensitization reactions caused by ultraviolet and visible radiation (UV–vis) absorbing chemicals can induce DNA damage through direct and indirect mechanisms. In this context, the investigation of phototoxicity is an essential part of the toxicological assessment programs for drugs, cosmetics and other chemicals that may be exposed to UV–vis light. The current battery of photosafety assessment tests includes an initial investigation of their photoreactive potential followed by in vitro phototoxicity testing. The in vitro 3T3 Neutral Red Uptake (NRU) and the Reconstructed Human Epidermis phototoxicity methods are currently the only validated and recognized tests for this purpose. However, they are not suitable for detecting the photogenotoxic potential of compounds, as they are based on photocytotoxicity measurement. Although there are adaptations of genotoxicity assays in the presence of UV–vis irradiation, these methods are not validated and standardized, and their biomodels have limitations. Additionally, even though computational toxicology is an already implemented strategy for human health hazard assessment, in silico photosafety models also have limitations. The currently available in silico models are based on the 3T3 NRU assay, thus limiting their ability to reliably predict photogenotoxicity. There is evidence of chemicals that present negative results in 3T3 NRU-based in vitro and in silico tests, yet exhibit photogenotoxic potential. This is exemplified by the agrochemical glyphosate, whose photomutagenic effect was recently reported using a promising yeast-based method as a New Approach Methodology. Therefore, the need to implement a battery of phototoxicity tests, including in vitro and/or in silico photogenotoxicity assessments, to complement the existing photocytotoxicity tests should be re-discussed. Otherwise, photosafety is not completely guaranteed.
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•Phototoxicity testing is part of the toxicological risk assessment programs.•The current photosafety test battery is restricted to photocytotoxicity measurement.•Photogenotoxicity tests are not yet mandatory for risk assessment.•There are non-photocytotoxic chemicals endowed with photogenotoxic potential.•Mandatory assessment of photogenotoxicity should be re-discussed.