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Research Articles

Genotoxicity assessment of titanium dioxide nanoparticles using a standard battery of in vivo assays

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Pages 497-510 | Received 27 Jun 2023, Accepted 25 Sep 2023, Published online: 15 Oct 2023

References

  • Ajdary, M., M. Moosavi, M. Rahmati, M. Falahati, M. Mahboubi, A. Mandegary, S. Jangjoo, et al. 2018. “Health Concerns of Various Nanoparticles: A Review of Their in Vitro and in Vivo Toxicity.” Nanomaterials (Basel, Switzerland) 8 (9): 634. https://doi.org/10.3390/nano8090634
  • Akbari-Alavijeh, S., R. Shaddel, and S. M. Jafari. 2022. “In Vivo Assessments for Predicting the Bioavailability of Nanoencapsulated Food Bioactives and the Safety of Nanomaterials.” Critical Reviews in Food Science and Nutrition 62 (27): 7460–7478. https://doi.org/10.1080/10408398.2021.1915239
  • Ali, S. A., M. Z. Rizk, M. A. Hamed, E. I. Aboul-Ela, N. S. El-Rigal, H. F. Aly, and A.-H Z. Abdel-Hamid. 2019. “Assessment of Titanium Dioxide Nanoparticles Toxicity via Oral Exposure in Mice: effect of Dose and Particle Size.” Biomarkers : Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals 24 (5): 492–498. https://doi.org/10.1080/1354750X.2019.1620336
  • Alkilany, A. M. and C. J. Murphy. 2010. “Toxicity and Cellular Uptake of Gold Nanoparticles: what we Have Learned so Far?” Journal of Nanoparticle Research: An Interdisciplinary Forum for Nanoscale Science and Technology 12 (7): 2313–2333. https://doi.org/10.1007/s11051-010-9911-8
  • Baranowska-Wójcik, E., D. Szwajgier, P. Oleszczuk, and A. Winiarska-Mieczan. 2020. “Effects of Titanium Dioxide Nanoparticles Exposure on Human Health—A Review.” Biological Trace Element Research 193 (1): 118–129. https://doi.org/10.1007/s12011-019-01706-6
  • Chen, R.-J., Y.-Y. Chen, M.-Y. Liao, Y.-H. Lee, Z.-Y. Chen, S.-J. Yan, Y.-L. Yeh, et al. 2020. “The Current Understanding of Autophagy in Nanomaterial Toxicity and Its Implementation in Safety Assessment-Related Alternative Testing Strategies.” International Journal of Molecular Sciences 21 (7): 2387. https://doi.org/10.3390/ijms21072387
  • Chen, Z., Y. Wang, T. Ba, Y. Li, J. Pu, T. Chen, Y. Song, et al. 2014. “Genotoxic Evaluation of Titanium Dioxide Nanoparticles in Vivo and in Vitro.” Toxicology Letters 226 (3): 314–319. https://doi.org/10.1016/j.toxlet.2014.02.020
  • Chen, Z., J. Shi, Y. Zhang, S. Han, J. Zhang, and G. Jia. 2022. “DNA Oxidative Damage as a Sensitive Genetic Endpoint to Detect the Genotoxicity Induced by Titanium Dioxide Nanoparticles.” Nanomaterials (Basel, Switzerland) 12 (15): 2616. https://doi.org/10.3390/nano12152616
  • Cockburn, A., R. Bradford, N. Buck, A. Constable, G. Edwards, B. Haber, P. Hepburn, et al. 2012. “Approaches to the Safety Assessment of Engineered Nanomaterials (ENM) in Food.” Food and Chemical Toxicology: An International Journal Published for the British Industrial Biological Research Association 50 (6): 2224–2242. https://doi.org/10.1016/j.fct.2011.12.029
  • Collett, A., J. Tanianis-Hughes, G. L. Carlson, M. D. Harwood, and G. Warhurst. 2005. “Comparison of P-Glycoprotein-Mediated Drug–Digoxin Interactions in Caco-2 with Human and Rodent Intestine: Relevance to in Vivo Prediction.” European Journal of Pharmaceutical Sciences: Official Journal of the European Federation for Pharmaceutical Sciences 26 (5): 386–393. https://doi.org/10.1016/j.ejps.2005.07.013
  • Coméra, C., C. Cartier, E. Gaultier, O. Catrice, Q. Panouille, S. El Hamdi, K. Tirez, et al. 2020. “Jejunal Villus Absorption and Paracellular Tight Junction Permeability Are Major Routes for Early Intestinal Uptake of Food-Grade TiO2 Particles: An in Vivo and Ex Vivo Study in Mice.” Particle and Fibre Toxicology 17 (1): 26. https://doi.org/10.1186/s12989-020-00357-z
  • ECHA (European Chemicals Agency). 2017. Guidance on Information Requirements and Chemical Safety Assessment: Appendix R7-1 for Nanomaterials Applicable to Chapter R7a Endpoint Specific Guidance. Version 2.0. Helsinki, Finland: ECHA
  • EFSA. 2005. “Opinion of the Scientific Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food on a Request from the Commission Related to the Safety in Use of Rutile Titanium Dioxide as an Alternative to the Presently Permitted Anatase Form.” EFSA Journal 3 (3): 12. https://doi.org/10.2903/j.efsa.2005.163
  • EFSA Panel on Food Additives and Flavourings (FAF). 2019. “Scientific Opinion on the Proposed Amendment of the EU Specifications for Titanium Dioxide (E 171) with Respect to the Inclusion of Additional Parameters Related to Its Particle Size Distribution.” EFSA Journal 17 (7): 1–23. https://doi.org/10.2903/j.efsa.2019.5760
  • EFSA Panel on Food Additives and Flavourings (FAF). 2021. “Safety Assessment of Titanium Dioxide (E171) as a Food Additive.” EFSA Journal 19 (5): 1–130. https://doi.org/10.2903/j.efsa.2021.6585
  • EFSA Scientific Committee. 2021. “Guidance on Risk Assessment of Nanomaterials to Be Applied in the Food and Feed Chain: Human and Animal Health.” EFSA Journal 19 (8):e06768. https://doi.org/10.2903/j.efsa.2021.6768
  • Elespuru, R., S. Pfuhler, M. J. Aardema, T. Chen, S. H. Doak, A. Doherty, C. S. Farabaugh, et al. 2018. “Genotoxicity Assessment of Nanomaterials: Recommendations on Best Practices, Assays, and Methods.” Toxicological Sciences: An Official Journal of the Society of Toxicology 164 (2): 391–416. https://doi.org/10.1093/toxsci/kfy100
  • FDA. 2012. “International Conference on Harmonisation; Guidance on S2(R1) Genotoxicity Testing and Data Interpretation for Pharmaceuticals Intended for Human Use; Availability. Notice.” Federal Register.77 (110): 2.
  • FDA. 2014. “Guidance for Industry. Assessing the Effects of Significant Manufacturing Process Changes, Including Emerging Technologies, on the Safety and Regulatory Status of Food Ingredients and Food Contact Substances, Including Food Ingredients that are Color Additives.”
  • Ferrante, M., A. Grasso, R. Salemi, M. Libra, B. Tomasello, M. Fiore, and C. Copat. 2023. “DNA Damage and Apoptosis as in-Vitro Effect Biomarkers of Titanium Dioxide Nanoparticles (TiO2-NPs) and the Food Additive E171 Toxicity in Colon Cancer Cells: HCT-116 and Caco-2.” International Journal of Environmental Research and Public Health 20 (3): 2002. https://doi.org/10.3390/ijerph20032002
  • Feynman, R. P. 1960. “There’s Plenty of Room at the Bottom.” Engineering and Science 23 (5): 22–36.
  • Gliga, A. R., S. Skoglund, I. Odnevall Wallinder, B. Fadeel, and H. L. Karlsson. 2014. “Size-Dependent Cytotoxicity of Silver Nanoparticles in Human Lung Cells: The Role of Cellular Uptake, Agglomeration and Ag Release.” Particle and Fibre Toxicology 11 (1): 11. https://doi.org/10.1186/1743-8977-11-11
  • Grissa, I., J. Elghoul, L. Ezzi, S. Chakroun, E. Kerkeni, M. Hassine, L. El Mir, et al. 2015. “Anemia and Genotoxicity Induced by Sub-Chronic Intragastric Treatment of Rats with Titanium Dioxide Nanoparticles.” Mutation Research Genetic Toxicology and Environmental Mutagenesis 794: 25–31. https://doi.org/10.1016/j.mrgentox.2015.09.005
  • Guillard, A., E. Gaultier, C. Cartier, L. Devoille, J. Noireaux, L. Chevalier, M. Morin, et al. 2020. “Basal Ti Level in the Human Placenta and Meconium and Evidence of a Materno-Foetal Transfer of Food-Grade TiO2 Nanoparticles in an Ex Vivo Placental Perfusion Model.” Particle and Fibre Toxicology 17 (1): 51. https://doi.org/10.1186/s12989-020-00381-z
  • He, L., H. Wang, S. Duan, Y. Gao, L. Lyu, X. Ou, N. Yu, et al. 2022. “Characterization of Titanium Dioxide Nanoparticles in Confectionary Products and Estimation of Dietary Exposure Level among the Chinese Population.” NanoImpact 28: 100435. https://doi.org/10.1016/j.impact.2022.100435
  • Heringa, M. B., R. J. B. Peters, R. Bleys, M. K. van der Lee, P. C. Tromp, P. C. E. van Kesteren, J. C. H. van Eijkeren, et al. 2018. “Detection of Titanium Particles in Human Liver and Spleen and Possible Health Implications.” Particle and Fibre Toxicology 15 (1): 15. https://doi.org/10.1186/s12989-018-0251-7
  • ISO (International Organization for Standardization). 2019. “ISO/TR 22019:2019. Nanotechnologies—Considerations for Performing Toxicokinetic Studies with Nanomaterials.”
  • JECFA. 2022. Food Additives: Ninety-seventh meeting—Joint FAO/WHO Expert Committee on Food Additives (JECFA). List of substances scheduled for evaluation and request for data. Journal [Online] Available at: https://www.who.int/news-room/articles-detail/call-for-data-jecfa-97-meeting. Accessed on 6 December 2022.
  • Jo, M.-R., J. Yu, H.-J. Kim, J. Song, K.-M. Kim, J.-M. Oh, and S.-J. Choi. 2016. “Titanium Dioxide Nanoparticle-Biomolecule Interactions Influence Oral Absorption.” Nanomaterials (Basel, Switzerland) 6 (12): 225. https://doi.org/10.3390/nano6120225
  • Jugan, M.-L., S. Barillet, A. Simon-Deckers, N. Herlin-Boime, S. Sauvaigo, T. Douki, and M. Carriere. 2012. “Titanium Dioxide Nanoparticles Exhibit Genotoxicity and Impair DNA Repair Activity in A549 Cells.” Nanotoxicology 6 (5): 501–513. https://doi.org/10.3109/17435390.2011.587903
  • Kirkland, D., M. J. Aardema, R. V. Battersby, C. Beevers, K. Burnett, A. Burzlaff, A. Czich, et al. 2022. “A Weight of Evidence Review of the Genotoxicity of Titanium Dioxide (TiO2).” Regulatory Toxicology and Pharmacology 136: 105263. https://doi.org/10.1016/j.yrtph.2022.105263
  • Kladko, D. V., A. S. Falchevskaya, N. S. Serov, and A. Y. Prilepskii. 2021. “Nanomaterial Shape Influence on Cell Behavior.” International Journal of Molecular Sciences 22 (10): 5266. https://doi.org/10.3390/ijms22105266
  • Kreyling, W. G., U. Holzwarth, N. Haberl, J. Kozempel, S. Hirn, A. Wenk, C. Schleh, et al. 2017. “Quantitative Biokinetics of Titanium Dioxide Nanoparticles after Intravenous Injection in Rats: Part 1.” Nanotoxicology 11 (4): 434–442. https://doi.org/10.1080/17435390.2017.1306892
  • Lama, S., O. Merlin-Zhang, and C. Yang. 2020. “In Vitro and in Vivo Models for Evaluating the Oral Toxicity of Nanomedicines.” Nanomaterials (Basel, Switzerland) 10 (11): 2177. https://doi.org/10.3390/nano10112177
  • Landsiedel, R., M. D. Kapp, M. Schulz, K. Wiench, and F. Oesch. 2009. “Genotoxicity Investigations on Nanomaterials: Methods, Preparation and Characterization of Test Material, Potential Artifacts and Limitations—Many Questions, Some Answers.” Mutation Research 681 (2-3): 241–258. https://doi.org/10.1016/j.mrrev.2008.10.002
  • Landsiedel, R., E. Fabian, L. Ma-Hock, W. Wohlleben, K. Wiench, F. Oesch, and B. van Ravenzwaay. 2012. “Toxico-/Biokinetics of Nanomaterials.” Archives of Toxicology 86 (7): 1021–1060. https://doi.org/10.1007/s00204-012-0858-7
  • Landsiedel, R., N. Honarvar, S. B. Seiffert, B. Oesch, and F. Oesch. 2022. “Genotoxicity Testing of Nanomaterials.” Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology 14 (6): e1833. https://doi.org/10.1002/wnan.1833
  • Liang, C., J. Hu, X. Zhang, W. Cui, and Z. Yu. 2018. “Optimized Procedure to Obtain Good Dispersion of TiO2 and ZnO Nanoparticles for Toxicity Evaluation.” Nanomedicine: Nanotechnology, Biology and Medicine.14 (5): 1788. https://doi.org/10.1016/j.nano.2017.11.136
  • Liang, C., J. Fang, J. Hu, X. Geng, H. Liu, Y. Feng, W. Wang, et al. 2022. “Toxicokinetics of Zinc Oxide Nanoparticles and Food Grade Bulk-Sized Zinc Oxide in Rats after Oral Dosages.” NanoImpact 25: 100368. https://doi.org/10.1016/j.impact.2021.100368
  • Ling, C., H. An, L. Li, J. Wang, T. Lu, H. Wang, Y. Hu, et al. 2021. “Genotoxicity Evaluation of Titanium Dioxide Nanoparticles in Vitro: A Systematic Review of the Literature and Meta-Analysis.” Biological Trace Element Research 199 (5): 2057–2076. https://doi.org/10.1007/s12011-020-02311-8
  • Martins, A. D. C., Jr., L. F. Azevedo, C. C. de Souza Rocha, M. F. H. Carneiro, V. P. Venancio, M. R. de Almeida, L. M. G. Antunes, et al. 2017. “Evaluation of Distribution, Redox Parameters, and Genotoxicity in Wistar Rats Co-Exposed to Silver and Titanium Dioxide Nanoparticles.” Journal of Toxicology and Environmental Health. Part A 80 (19-21): 1156–1165. https://doi.org/10.1080/15287394.2017.1357376
  • OECD. 2014. Genotoxicity of Manufactured Nanomaterials: Report of the OECD Expert Meeting. Journal [Online] Available at: https://one.oecd.org/document/env/jm/mono(2014)34/en/pdf. Accessed on 8 June 2023
  • OECD. 2016a. "OECD Guideline for the testing of chemicals: Mammalian Erythrocyte Micronucleus Test." OECD.
  • OECD. 2016b. "OECD Guideline for the testing of chemicals: Mammalian Bone Marrow Chromosomal Aberration Test." OECD.
  • OECD. 2016c. “OECD Guideline for the Testing of Chemicals.” In Vivo Mammalian Alkaline Comet Assay. OECD Guideline Test 489." Paris: OECD.
  • Perlman, R. L. 2016. “Mouse Models of Human Disease: An Evolutionary Perspective.” Evolution, Medicine, and Public Health 2016 (1): 170–176. https://doi.org/10.1093/emph/eow014
  • Peters, R. J. B., A. G. Oomen, G. van Bemmel, L. van Vliet, A. K. Undas, S. Munniks, R. L. A. W. Bleys, et al. 2020. “Silicon Dioxide and Titanium Dioxide Particles Found in Human Tissues.” Nanotoxicology 14 (3): 420–432. https://doi.org/10.1080/17435390.2020.1718232
  • Regulation Commission. 2022. “Commission Regulation (EU) 2022/63, amending Annex II and III to Regulation (EC) No 1333/2008 of the European Parliament and of the Council as regards the food additives titanium dioxide (E171).”
  • Ridhwan, Y., L. T. H. Nguyen, P. Chiew, Z. M. Wang, and K. W. Ng. 2018. “Comparative Differences in the Behavior of TiO2 and SiO2 Food Additives in Food Ingredient Solutions.” Journal of Nanoparticle Research 20 (3): 13. https://doi.org/10.1007/s11051-018-4176-8
  • Rodriguez-Garraus, A., M. Alonso-Jauregui, A.-G. Gil, I. Navarro-Blasco, A. López de Cerain, and A. Azqueta. 2022. “Genotoxicity and Toxicity Assessment of a Formulation Containing Silver Nanoparticles and Kaolin: An in Vivo Integrative Approach.” Nanomaterials (Basel, Switzerland) 13 (1): 3. https://doi.org/10.3390/nano13010003
  • Sadeghi, R., R. J. Rodriguez, Y. Yao, and J. L. Kokini. 2017. “Advances in Nanotechnology as They Pertain to Food and Agriculture: Benefits and Risks.” Annual Review of Food Science and Technology 8 (1): 467–492. https://doi.org/10.1146/annurev-food-041715-033338
  • Sadiq, R., J. A. Bhalli, J. Yan, R. S. Woodruff, M. G. Pearce, Y. Li, T. Mustafa, et al. 2012. “Genotoxicity of TiO2 Anatase Nanoparticles in B6C3F1 Male Mice Evaluated Using Pig-A AND Flow Cytometric Micronucleus Assays.” Mutation Research 745 (1–2): 65–72. https://doi.org/10.1016/j.mrgentox.2012.02.002
  • Sengul, A. B. and E. Asmatulu. 2020. “Toxicity of Metal and Metal Oxide Nanoparticles: A Review.” Environmental Chemistry Letters 18 (5): 1659–1683. https://doi.org/10.1007/s10311-020-01033-6
  • Shi, J., S. Han, J. Zhang, Y. Liu, Z. Chen, and G. Jia. 2022. “Advances in Genotoxicity of Titanium Dioxide Nanoparticles in Vivo and in Vitro.” NanoImpact 25: 100377. https://doi.org/10.1016/j.impact.2021.100377
  • Shukla, R. K., A. Kumar, N. V. Vallabani, A. K. Pandey, and A. Dhawan. 2014. “Titanium Dioxide Nanoparticle-Induced Oxidative Stress Triggers DNA Damage and Hepatic Injury in Mice.” Nanomedicine (London, England) 9 (9): 1423–1434. https://doi.org/10.2217/nnm.13.100
  • Siivola, K. M., M. J. Burgum, B. Suárez-Merino, M. J. D. Clift, S. H. Doak, and J. Catalán. 2022. “A Systematic Quality Evaluation and Review of Nanomaterial Genotoxicity Studies: A Regulatory Perspective.".” Particle and Fibre Toxicology 19 (1): 59. https://doi.org/10.1186/s12989-022-00499-2
  • Storch, J., J. H. Veerkamp, and K.-T. Hsu. 2002. “Similar Mechanisms of Fatty Acid Transfer from Human Anal Rodent Fatty Acid-Binding Proteins to Membranes: Liver, Intestine, Heart Muscle, and Adipose Tissue FABPs.” Molecular and Cellular Biochemistry 239 (1-2): 25–33. https://doi.org/10.1023/A:1020546321508
  • Stuparu-Cretu, M., G. Braniste, G.-A. Necula, S. Stanciu, D. Stoica, and M. Stoica. 2023. “Metal Oxide Nanoparticles in Food Packaging and Their Influence on Human Health.” Foods (Basel, Switzerland) 12 (9): 1882. https://doi.org/10.3390/foods12091882
  • Sungur, Ş., P. Kaya, and M. Koroglu. 2020. “Determination of Titanium Dioxide Nanoparticles Used in Various Foods.” Food Additives & Contaminants. Part B, Surveillance 13 (4): 260–267. https://doi.org/10.1080/19393210.2020.1769193
  • Taurozzi, J. S., V. A. Hackley, and M. R. Wiesner. 2013. “A Standardized Approach for the Dispersion of Titanium Dioxide Nanoparticles in Biological Media.” Nanotoxicology 7 (4): 389–401. https://doi.org/10.3109/17435390.2012.665506
  • Wani, M. R. and G. Shadab. 2020. “Titanium Dioxide Nanoparticle Genotoxicity: A Review of Recent in Vivo and in Vitro Studies.” Toxicology and Industrial Health 36 (7): 514–530. https://doi.org/10.1177/0748233720936835
  • Xie, G., C. Wang, J. Sun, and G. Zhong. 2011. “Tissue Distribution and Excretion of Intravenously Administered Titanium Dioxide Nanoparticles.” Toxicology Letters 205 (1): 55–61. https://doi.org/10.1016/j.toxlet.2011.04.034
  • Zijno, A., I. De Angelis, B. De Berardis, C. Andreoli, M. T. Russo, D. Pietraforte, G. Scorza, et al. 2015. “Different Mechanisms Are Involved in Oxidative DNA Damage and Genotoxicity Induction by ZnO and TiO2 Nanoparticles in Human Colon Carcinoma Cells.” Toxicology in Vitro : An International Journal Published in Association with BIBRA 29 (7): 1503–1512. https://doi.org/10.1016/j.tiv.2015.06.009

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