Let's shed light on photogenotoxicity

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 a...

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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
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Abstract	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. [Display omitted] •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.
AbstractList	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. [Display omitted] •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. 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.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. 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.
ArticleNumber	176354
Author	de Pádula, Marcelo Diniz, Raiane R. de Souza, Alessandra M.T.
Author_xml	– sequence: 1 givenname: Raiane R. surname: Diniz fullname: Diniz, Raiane R. organization: Laboratório de Modelagem Molecular & QSAR (ModMolQSAR), Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil – sequence: 2 givenname: Marcelo surname: de Pádula fullname: de Pádula, Marcelo organization: Laboratório de Microbiologia e Avaliação Genotóxica (LAMIAG), Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil – sequence: 3 givenname: Alessandra M.T. surname: de Souza fullname: de Souza, Alessandra M.T. email: amtsouza@pharma.ufrj.br organization: Laboratório de Modelagem Molecular & QSAR (ModMolQSAR), Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/39304165$$D View this record in MEDLINE/PubMed
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Snippet	Photosensitization reactions caused by ultraviolet and visible radiation (UV–vis) absorbing chemicals can induce DNA damage through direct and indirect... Photosensitization reactions caused by ultraviolet and visible radiation (UV-vis) absorbing chemicals can induce DNA damage through direct and indirect...
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SubjectTerms	In silico toxicity In vitro NAMs Photocytotoxicity Photogenotoxicity Phototoxicity
Title	Let's shed light on photogenotoxicity
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