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Updated assessment of the genotoxic potential of titanium dioxide based on reviews of in vitro comet, mode of action and cellular uptake studies, and recent publications

David Kirkland, Arne Burzlaff, Andreas Czich, shareen Doak, Paul Fowler Orcid Logo, Stefan Pfuhler, Leon F. Stankowski

Regulatory Toxicology and Pharmacology, Volume: 154, Start page: 105734

Swansea University Author: shareen Doak

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DOI (Published version): 10.1016/j.yrtph.2024.105734

Abstract

In 2021 the European Food Safety Authority (EFSA) concluded that "A concern for genotoxicity of TiO2 particles that may be present in E 171 could therefore not be ruled out.". A detailed review of the genotoxicity of titanium dioxide (TiO ) was subsequently published by Kirkland et al. (20...

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Published in: Regulatory Toxicology and Pharmacology
ISSN: 0273-2300 1096-0295
Published: Elsevier BV 2024
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URI: https://cronfa.swan.ac.uk/Record/cronfa68585
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(2022) using a comprehensive weight of evidence (WoE) approach in which test systems and endpoints were allocated different levels of relevance. At that time only 34 publications met the reliability and quality criteria for being most relevant in the evaluation of genotoxicity, and based on these it was concluded that the existing evidence did not support a direct DNA damaging mechanism for TiO . Recently a number of regulatory opinions have been published, in which papers were cited that described in vitro DNA damage (mainly comet), mode of action, and cellular uptake studies that were not discussed in Kirkland et al. (2022). Furthermore, a number of additional papers have been published recently or have been identified from the regulatory opinions as a result of using extended search criteria. A total of 70 publications not previously reviewed in Kirkland et al. (2022) have been reviewed here, and again show that the published data on the genotoxicity of TiO are inconsistent, often of poor quality, and in some cases difficult to interpret. The cellular uptake studies show some evidence of cytoplasmic uptake, particularly in cells treated in vitro, but there is no convincing evidence of nuclear uptake. In terms of genotoxicity, the conclusions of Kirkland et al. (2022) that existing evidence does not support a direct DNA damaging mechanism for titanium dioxide (including nano forms), and that the main mechanism leading to TiO genotoxicity is most likely indirect damage to DNA through generation of reactive oxygen species (ROS), are still valid. [Abstract copyright: Copyright &#xA9; 2024. 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spelling 2025-01-29T14:54:22.8114315 v2 68585 2024-12-17 Updated assessment of the genotoxic potential of titanium dioxide based on reviews of in vitro comet, mode of action and cellular uptake studies, and recent publications 8f70286908f67238a527a98cbf66d387 shareen Doak shareen Doak true false 2024-12-17 In 2021 the European Food Safety Authority (EFSA) concluded that "A concern for genotoxicity of TiO2 particles that may be present in E 171 could therefore not be ruled out.". A detailed review of the genotoxicity of titanium dioxide (TiO ) was subsequently published by Kirkland et al. (2022) using a comprehensive weight of evidence (WoE) approach in which test systems and endpoints were allocated different levels of relevance. At that time only 34 publications met the reliability and quality criteria for being most relevant in the evaluation of genotoxicity, and based on these it was concluded that the existing evidence did not support a direct DNA damaging mechanism for TiO . Recently a number of regulatory opinions have been published, in which papers were cited that described in vitro DNA damage (mainly comet), mode of action, and cellular uptake studies that were not discussed in Kirkland et al. (2022). Furthermore, a number of additional papers have been published recently or have been identified from the regulatory opinions as a result of using extended search criteria. A total of 70 publications not previously reviewed in Kirkland et al. (2022) have been reviewed here, and again show that the published data on the genotoxicity of TiO are inconsistent, often of poor quality, and in some cases difficult to interpret. The cellular uptake studies show some evidence of cytoplasmic uptake, particularly in cells treated in vitro, but there is no convincing evidence of nuclear uptake. In terms of genotoxicity, the conclusions of Kirkland et al. (2022) that existing evidence does not support a direct DNA damaging mechanism for titanium dioxide (including nano forms), and that the main mechanism leading to TiO genotoxicity is most likely indirect damage to DNA through generation of reactive oxygen species (ROS), are still valid. [Abstract copyright: Copyright © 2024. Published by Elsevier Inc.] Journal Article Regulatory Toxicology and Pharmacology 154 105734 Elsevier BV 0273-2300 1096-0295 1 12 2024 2024-12-01 10.1016/j.yrtph.2024.105734 COLLEGE NANME COLLEGE CODE Swansea University Another institution paid the OA fee This review was partly funded by the Titanium Dioxide Manufacturers Association (TDMA) although not all contributing experts were paid for their time. All of the opinions expressed herein were the authors own, and TDMA did not have any influence over the outcomes discussed in this publication. 2025-01-29T14:54:22.8114315 2024-12-17T15:25:28.2969623 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Biomedical Science David Kirkland 1 Arne Burzlaff 2 Andreas Czich 3 shareen Doak 4 Paul Fowler 0000-0002-8705-3003 5 Stefan Pfuhler 6 Leon F. Stankowski 7 68585__33166__3c82ce4dae924d308aa56ca3cce6fadf.pdf 68585.VOR.pdf 2024-12-17T15:30:42.6672575 Output 895699 application/pdf Version of Record true Crown Copyright © 2024. This is an open access article distributed under the terms of the Creative Commons CC-BY license. true eng http://creativecommons.org/licenses/by/4.0/
title Updated assessment of the genotoxic potential of titanium dioxide based on reviews of in vitro comet, mode of action and cellular uptake studies, and recent publications
spellingShingle Updated assessment of the genotoxic potential of titanium dioxide based on reviews of in vitro comet, mode of action and cellular uptake studies, and recent publications
shareen Doak
title_short Updated assessment of the genotoxic potential of titanium dioxide based on reviews of in vitro comet, mode of action and cellular uptake studies, and recent publications
title_full Updated assessment of the genotoxic potential of titanium dioxide based on reviews of in vitro comet, mode of action and cellular uptake studies, and recent publications
title_fullStr Updated assessment of the genotoxic potential of titanium dioxide based on reviews of in vitro comet, mode of action and cellular uptake studies, and recent publications
title_full_unstemmed Updated assessment of the genotoxic potential of titanium dioxide based on reviews of in vitro comet, mode of action and cellular uptake studies, and recent publications
title_sort Updated assessment of the genotoxic potential of titanium dioxide based on reviews of in vitro comet, mode of action and cellular uptake studies, and recent publications
author_id_str_mv 8f70286908f67238a527a98cbf66d387
author_id_fullname_str_mv 8f70286908f67238a527a98cbf66d387_***_shareen Doak
author shareen Doak
author2 David Kirkland
Arne Burzlaff
Andreas Czich
shareen Doak
Paul Fowler
Stefan Pfuhler
Leon F. Stankowski
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container_start_page 105734
publishDate 2024
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hierarchy_top_title Faculty of Medicine, Health and Life Sciences
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department_str Swansea University Medical School - Biomedical Science{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Biomedical Science
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description In 2021 the European Food Safety Authority (EFSA) concluded that "A concern for genotoxicity of TiO2 particles that may be present in E 171 could therefore not be ruled out.". A detailed review of the genotoxicity of titanium dioxide (TiO ) was subsequently published by Kirkland et al. (2022) using a comprehensive weight of evidence (WoE) approach in which test systems and endpoints were allocated different levels of relevance. At that time only 34 publications met the reliability and quality criteria for being most relevant in the evaluation of genotoxicity, and based on these it was concluded that the existing evidence did not support a direct DNA damaging mechanism for TiO . Recently a number of regulatory opinions have been published, in which papers were cited that described in vitro DNA damage (mainly comet), mode of action, and cellular uptake studies that were not discussed in Kirkland et al. (2022). Furthermore, a number of additional papers have been published recently or have been identified from the regulatory opinions as a result of using extended search criteria. A total of 70 publications not previously reviewed in Kirkland et al. (2022) have been reviewed here, and again show that the published data on the genotoxicity of TiO are inconsistent, often of poor quality, and in some cases difficult to interpret. The cellular uptake studies show some evidence of cytoplasmic uptake, particularly in cells treated in vitro, but there is no convincing evidence of nuclear uptake. In terms of genotoxicity, the conclusions of Kirkland et al. (2022) that existing evidence does not support a direct DNA damaging mechanism for titanium dioxide (including nano forms), and that the main mechanism leading to TiO genotoxicity is most likely indirect damage to DNA through generation of reactive oxygen species (ROS), are still valid. [Abstract copyright: Copyright © 2024. Published by Elsevier Inc.]
published_date 2024-12-01T05:26:58Z
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