Titanium dioxide nanoparticle genotoxicity: A review of recent <i>in vivo</i> and <i>in vitro</i> studies

Wani, Mohammad Rafiq; Shadab, G. G. H. A.

doi:10.1177/0748233720936835

Cited by 45 publications

(24 citation statements)

References 86 publications

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“…In addition to the mechanisms underlying ROS generation, it also remains unknown as to how the TiO 2 NPs interact with the TiO 2 NTs and how this interaction regulates the intracellular ROS levels. Nano-TiO 2 can cause genotoxicity [ 41 ]. Furthermore, the ROS-mediated stress within cells could be the main mechanism for the genotoxicity of nano-TiO 2 [ 42 ].…”

Section: Resultsmentioning

confidence: 99%

Combined Toxicity of TiO2 Nanospherical Particles and TiO2 Nanotubes to Two Microalgae with Different Morphology

et al. 2020

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The joint activity of multiple engineered nanoparticles (ENPs) has attracted much attention in recent years. Many previous studies have focused on the combined toxicity of different ENPs with nanostructures of the same dimension. However, the mixture toxicity of multiple ENPs with different dimensions is much less understood. Herein, we investigated the toxicity of the binary mixture of TiO2 nanospherical particles (NPs) and TiO2 nanotubes (NTs) to two freshwater algae with different morphology, namely, Scenedesmus obliquus and Chlorella pyrenoidosa. The physicochemical properties, dispersion stability, and the generation of reactive oxygen species (ROS) were determined in the single and binary systems. Classical approaches to assessing mixture toxicity were applied to evaluate and predict the toxicity of the binary mixtures. The results show that the combined toxicity of TiO2 NPs and NTs to S. obliquus was between the single toxicity of TiO2 NTs and NPs, while the combined toxicity to C. pyrenoidosa was higher than their single toxicity. Moreover, the toxicity of the binary mixtures to C. pyrenoidosa was higher than that to S. obliquus. A toxic unit assessment showed that the effects of TiO2 NPs and NTs were additive to the algae. The combined toxicity to S. obliquus and C. pyrenoidosa can be effectively predicted by the concentration addition model and the independent action model, respectively. The mechanism of the toxicity caused by the binary mixtures of TiO2 NPs and NTs may be associated with the dispersion stability of the nanoparticles in aquatic media and the ROS-induced oxidative stress effects. Our results may offer a new insight into evaluating and predicting the combined toxicological effects of ENPs with different dimensions and of probing the mechanisms involved in their joint toxicity.

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Section: Resultsmentioning

confidence: 99%

Combined Toxicity of TiO2 Nanospherical Particles and TiO2 Nanotubes to Two Microalgae with Different Morphology

et al. 2020

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“…TiO 2 is the most widely used nanomaterial worldwide, employed in a variety of applications ranging from medical devices to products used in everyday life [31,34]. The present work was carried out using TiO 2 NP as nanomaterial model since their genotoxicity has been extensively studied and they are known to induce MN in a variety of cell lines [12,[35][36][37][38]. Moreover, following OECD TG 487 and OECD report No.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, results observed in these experiments indicate that the two treatment options recommended for testing nanomaterials by the CBMN assay are not good options in this particular case, since they resulted similar than the standard cotreatment, and the data obtained substantially differed from those coming from FCMN test in the absence of Cyt-B. Following the recommendations provided by OECD WPMN [22], a number of researchers evaluated MN induction by TiO 2 NP exposure applying either post-treatment [12,[70][71][72] or delayed co-treatment [51,55,73,74] in a number of different cell types. Similar to our results, these studies frequently found increases in MN frequency after TiO 2 NP exposure.…”

Section: Discussionmentioning

confidence: 99%

“…So far, it is generally accepted that common cell-based toxicity tests might not be fully adequate for evaluating nanomaterials and may not provide reliable data, since the unique features of these materials are also responsible for unexpected interactions with assay components or detection systems [4][5][6][7]. Considering that hazard assessment is a key endpoint to address in management and regulation of manufactured nanomaterials [8,9], appropriate adaptations for nanomaterials in the currently validated protocols to assess potential harmful properties of chemicals are urgently needed to obtain both reliable toxicological profiles and specific standardized methods [10][11][12].…”

Section: Introductionmentioning

confidence: 99%

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Suitability of the In Vitro Cytokinesis-Block Micronucleus Test for Genotoxicity Assessment of TiO2 Nanoparticles on SH-SY5Y Cells

Fernández-Bertólez

Brandão

Costa

et al. 2021

IJMS

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Standard toxicity tests might not be fully adequate for evaluating nanomaterials since their unique features are also responsible for unexpected interactions. The in vitro cytokinesis-block micronucleus (CBMN) test is recommended for genotoxicity testing, but cytochalasin-B (Cyt-B) may interfere with nanoparticles (NP), leading to inaccurate results. Our objective was to determine whether Cyt-B could interfere with MN induction by TiO2 NP in human SH-SY5Y cells, as assessed by CBMN test. Cells were treated for 6 or 24 h, according to three treatment options: co-treatment with Cyt-B, post-treatment, and delayed co-treatment. Influence of Cyt-B on TiO2 NP cellular uptake and MN induction as evaluated by flow cytometry (FCMN) were also assessed. TiO2 NP were significantly internalized by cells, both in the absence and presence of Cyt-B, indicating that this chemical does not interfere with NP uptake. Dose-dependent increases in MN rates were observed in CBMN test after co-treatment. However, FCMN assay only showed a positive response when Cyt-B was added simultaneously with TiO2 NP, suggesting that Cyt-B might alter CBMN assay results. No differences were observed in the comparisons between the treatment options assessed, suggesting they are not adequate alternatives to avoid Cyt-B interference in the specific conditions tested.

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“…As such, exposure of human beings to TiO 2 materials is plausible. Although Ti has been considered as biologically inert element, it has still been suggested that exposure to TiO 2 NMs may induce adverse health effects, for instance, genotoxicity, developmental toxicity, vascular toxicity, and neurotoxicity (Cao et al, 2018; Chang et al, 2021; Wani & Shadab, 2020; Wu, Chen, et al, 2020). Indeed, reliable data already revealed that TiO 2 materials were genotoxic, and thus, TiO 2 materials have been classified as possible human carcinogen (Baranowska‐Wójcik et al, 2020; Guseva Canu et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Comparison of P25 and nanobelts on Kruppel‐like factor‐mediated nitric oxide pathways in human umbilical vein endothelial cells

Wang

Cao

Yan

et al. 2021

J of Applied Toxicology

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Recently, we reported that titanium dioxide (TiO2) materials activated endothelial cells via Kruppel‐like factor (KLF)‐mediated nitric oxide (NO) dysfunction, but the roles of physical properties of materials are not clear. In this study, we prepared nanobelts from P25 particles and compared their adverse effects to human umbilical vein endothelial cells (HUVECs). TiO2 nanobelts had belt‐like morphology but comparable surface areas as P25 particles. When applied to HUVECs, P25 particles or nanobelts did not induce cytotoxicity, although nanobelts were much more effective to increase intracellular Ti element concentrations compared the same amounts of P25 particles. Only nanobelts significantly induced THP‐1 adhesion onto HUVECs. Consistently, nanobelts were more significant to induce the expression of intracellular adhesion molecule‐1 (ICAM1) and the release of soluble ICAM‐1 (sICAM‐1), indicating that nanobelts were more potent to induce endothelial activation in vitro. As the mechanisms for endothelial activation, both P25 and nanobelts reduced the generation of intracellular NO as well as the expression of NO regulators KLF2 and KLF4. Combined, the results from this study indicated that the different morphologies of P25 particles and nanobelts only changed their internalization into HUVECs but showed minimal impact on KLF‐mediated NO signaling pathways.

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Titanium dioxide nanoparticle genotoxicity: A review of recent in vivo and in vitro studies

Cited by 45 publications

References 86 publications

Combined Toxicity of TiO2 Nanospherical Particles and TiO2 Nanotubes to Two Microalgae with Different Morphology

Combined Toxicity of TiO2 Nanospherical Particles and TiO2 Nanotubes to Two Microalgae with Different Morphology

Suitability of the In Vitro Cytokinesis-Block Micronucleus Test for Genotoxicity Assessment of TiO2 Nanoparticles on SH-SY5Y Cells

Comparison of P25 and nanobelts on Kruppel‐like factor‐mediated nitric oxide pathways in human umbilical vein endothelial cells

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