Subchronic Inhalation of TiO2 Nanoparticles Leads to Deposition in the Lung and Alterations in Erythrocyte Morphology in Mice

. 2025 Jun ; 45 (6) : 1004-1018. [epub] 20250211

Jazyk angličtina Země Anglie, Velká Británie Médium print-electronic

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/pmid39933250

Grantová podpora
RO0523 Ministry of Agriculture of the Czech Republic
24-10051S Czech Science Foundation

TiO2 nanoparticles (NPs) are extensively used in various applications, highlighting the importance of ongoing research into their effects. This work belongs among rare whole-body inhalation studies investigating the effects of TiO2 NPs on mice. Unlike previous studies, the concentration of TiO2 NPs in the inhalation chamber (130.8 μg/m3) was significantly lower. This 11-week study on mice confirmed in vivo the presence of TiO2 NPs in lung macrophages and type II pneumocytes including their intracellular localization by using the electron microscopy and the state-of-the-art methods detecting NPs' chemical identity/crystal structure, such as the energy-dispersed X-ray spectroscopy (EDX), cathodoluminescence (CL), and detailed diffraction pattern analysis using powder nanobeam diffraction (PNBD). For the first time in inhalation study in vivo, the alterations in erythrocyte morphology with evidence of echinocytes and stomatocytes, accompanied by iron accumulation in spleen, liver, and kidney, are reported following NP's exposure. Together with the histopathological evidence of hyperaemia in the spleen and kidney, and haemosiderin presence in the spleen, the finding of NPs containing iron might suggest the increased decomposition of damaged erythrocytes. The detection of TiO2 NPs on erythrocytes through CL analysis confirmed their potential systemic availability. On the contrary, TiO2 NPs were not confirmed in other organs (spleen, liver, and kidney); Ti was detected only in the kidney near the detection limit.

Zobrazit více v PubMed

Asharani, P. V. , Sethu S., Vadukumpully S., et al. 2010. “Investigations on the Structural Damage in Human Erythrocytes Exposed to Silver, Gold, and Platinum Nanoparticles.” Advanced Functional Materials 20: 1233–1242. 10.1002/adfm.200901846. DOI

Avsievich, T. , Popov A., Bykov A., and Meglinski I.. 2019. “Mutual Interaction of red Blood Cells Influenced by Nanoparticles.” Scientific Reports 9, no. 1: 5147. 10.1038/s41598-019-41643-x. PubMed DOI PMC

Baranowska‐Wójcik, E. , Szwajgier D., Oleszczuk P., and Winiarska‐Mieczan A.. 2020. “Effects of Titanium Dioxide Nanoparticles Exposure on Human Health—A Review.” Biological Trace Element Research 193, no. 1: 118–129. 10.1007/s12011-019-01706-6. PubMed DOI PMC

Barberio, M. , Barone P., Pingitore V., and Bonanno A.. 2012. “Optical Properties of TiO2 Anatase—Carbon Nanotubes Composites Studied by Cathodoluminescence Spectroscopy.” Superlattices and Microstructures 51, no. 1: 177–183. 10.1016/j.spmi.2011.11.011. DOI

Bermudez, E. , Mangum J. B., Wong B. A., et al. 2004. “Pulmonary Responses of Mice, Rats, and Hamsters to Subchronic Inhalation of Ultrafine Titanium Dioxide Particles.” Toxicological Sciences 77, no. 2: 347–357. 10.1093/toxsci/kfh019. PubMed DOI

Bian, Y. , Chung H. Y., Bae O. N., Lim K. M., Chung J. H., and Pi J.. 2021. “Titanium Dioxide Nanoparticles Enhance Thrombosis Through Triggering the Phosphatidylserine Exposure and Procoagulant Activation of red Blood Cells.” Particle and Fibre Toxicology 18, no. 1: 28. 10.1186/s12989-021-00422-1. PubMed DOI PMC

Boffetta, P. , Gaborieau V., Nadon L., Parent M. F., Weiderpass E., and Siemiatycki J.. 2001. “Exposure to Titanium Dioxide and Risk of Lung Cancer in a Population‐Based Study From Montreal.” Scandinavian Journal of Work, Environment & Health 27, no. 4: 227–232. 10.5271/sjweh.609. PubMed DOI

Boffetta, P. , Soutar A., Cherrie J. W., et al. 2004. “Mortality Among Workers Employed in the Titanium Dioxide Production Industry in Europe.” Cancer Causes & Control 15, no. 7: 697–706. 10.1023/b:Caco.0000036188.23970.22. PubMed DOI

Cameron, S. J. , Sheng J., Hosseinian F., and Willmore W. G.. 2022. “Nanoparticle Effects on Stress Response Pathways and Nanoparticle–Protein Interactions.” International Journal of Molecular Sciences 23, no. 14: 7962. 10.3390/ijms23147962. PubMed DOI PMC

Carriere, M. , Arnal M. E., and Douki T.. 2020. “TiO2 Genotoxicity: An Update of the Results Published Over the Last Six Years.” Mutation Research, Genetic Toxicology and Environmental Mutagenesis 854‐855: 503198. 10.1016/j.mrgentox.2020.503198. PubMed DOI

Coenen, T. , and Haegel N. M.. 2017. “Cathodoluminescence for the 21st Century: Learning More From Light.” Applied Physics Reviews 4: 031103. 10.1063/1.4985767. DOI

Cohignac, V. , Landry M. J., Boczkowski J., and Lanone S.. 2014. “Autophagy as a Possible Underlying Mechanism of Nanomaterial Toxicity.” Nanomaterials (Basel) 4, no. 3: 548–582. 10.3390/nano4030548. PubMed DOI PMC

Coméra, C. , Cartier C., Gaultier E., 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, no. 1: 26. 10.1186/s12989-020-00357-z. PubMed DOI PMC

Commission Regulation (EU) 2022/63 Amending Annexes II and III to Regulation (EC) No 1333/2008 of the European Parliament and of the Council as Regards the Food Additive Titanium Dioxide (E 171) (14 January 2022).

COT . (2024) Statement on the Safety of Titanium Dioxide (E171) as a Food Additive. COT/2024/05, Last Updated: 02 October 2024. Committee on Toxicity, Food Standards Agency.

de la Harpe, K. M. , Kondiah P. P. D., Choonara Y. E., Marimuthu T., du Toit L. C., and Pillay V.. 2019. “The Hemocompatibility of Nanoparticles: A Review of Cell–Nanoparticle Interactions and Hemostasis.” Cells 8, no. 10: 1209. 10.3390/cells8101209. PubMed DOI PMC

Disdier, C. , Devoy J., Cosnefroy A., et al. 2015. “Tissue Biodistribution of Intravenously Administrated Titanium Dioxide Nanoparticles Revealed Blood–Brain Barrier Clearance and Brain Inflammation in rat.” Particle and Fibre Toxicology 12: 27. 10.1186/s12989-015-0102-8. PubMed DOI PMC

Driscoll, K. E. , and Borm P. J. A.. 2020. “Expert Workshop on the Hazards and Risks of Poorly Soluble Low Toxicity Particles.” Inhalation Toxicology 32, no. 2: 53–62. 10.1080/08958378.2020.1735581. PubMed DOI

Dumková, J. , Smutná T., Vrlíková L., et al. 2020. “A Clearance Period After Soluble Lead Nanoparticle Inhalation Did Not Ameliorate the Negative Effects on Target Tissues due to Decreased Immune Response.” International Journal of Molecular Sciences 21, no. 22: 8738. 10.3390/ijms21228738. PubMed DOI PMC

Elgrabli, D. , Beaudouin R., Jbilou N., et al. 2015. “Biodistribution and Clearance of TiO2 Nanoparticles in Rats After Intravenous Injection.” PLoS ONE 10, no. 4: e0124490. 10.1371/journal.pone.0124490. PubMed DOI PMC

Fabian, E. , Landsiedel R., Ma‐Hock L., Wiench K., Wohlleben W., and van Ravenzwaay B.. 2008. “Tissue Distribution and Toxicity of Intravenously Administered Titanium Dioxide Nanoparticles in Rats.” Archives of Toxicology 82, no. 3: 151–157. 10.1007/s00204-007-0253-y. PubMed DOI

FAO/WHO . 2023, Ninety‐Seventh Meeting (Safety Evaluation of Certain Food Additives) 31 October–9 November 2023, Summary and Conclusions. The Joint FAO/WHO Expert Committee on Food Additives (JECFA).

Fryzek, J. P. , Chadda B., Marano D., et al. 2003. “A Cohort Mortality Study Among Titanium Dioxide Manufacturing Workers in the United States.” Journal of Occupational and Environmental Medicine 45, no. 4: 400–409. 10.1097/01.jom.0000058338.05741.45. PubMed DOI

Gaté, L. , Disdier C., Cosnier F., et al. 2017. “Biopersistence and Translocation to Extrapulmonary Organs of Titanium Dioxide Nanoparticles After Subacute Inhalation Exposure to Aerosol in Adult and Elderly Rats.” Toxicology Letters 265: 61–69. 10.1016/j.toxlet.2016.11.009. PubMed DOI

Geiser, M. , Casaulta M., Kupferschmid B., Schulz H., Semmler‐Behnke M., and Kreyling W.. 2008. “The Role of Macrophages in the Clearance of Inhaled Ultrafine Titanium Dioxide Particles.” American Journal of Respiratory Cell and Molecular Biology 38, no. 3: 371–376. 10.1165/rcmb.2007-0138OC. PubMed DOI

Geiser, M. , and Kreyling W. G.. 2010. “Deposition and Biokinetics of Inhaled Nanoparticles.” Particle and Fibre Toxicology 7: 2. 10.1186/1743-8977-7-2. PubMed DOI PMC

General Court . 2022. “Judgment of the General Court in Joined Cases T‐279/20 and T‐288/20 and in case T‐283/20.” CWS Powder Coatings GmbH and Others v Commission (23 November 2022).

Ghosh, M. , Chakraborty A., and Mukherjee A.. 2013. “Cytotoxic, Genotoxic and the Hemolytic Effect of Titanium Dioxide (TiO2) Nanoparticles on Human Erythrocyte and Lymphocyte Cells in Vitro.” Journal of Applied Toxicology 33, no. 10: 1097–1110. 10.1002/jat.2863. PubMed DOI

Grassian, V. H. , O'Shaughnessy P. T., Adamcakova‐Dodd A., Pettibone J. M., and Thorne P. S.. 2007. “Inhalation Exposure Study of Titanium Dioxide Nanoparticles With a Primary Particle Size of 2 to 5 nm.” Environmental Health Perspectives 115, no. 3: 397–402. 10.1289/ehp.9469. PubMed DOI PMC

Gualtieri, M. , Mantecca P., Corvaja V., et al. 2009. “Winter Fine Particulate Matter From Milan Induces Morphological and Functional Alterations in Human Pulmonary Epithelial Cells (A549).” Toxicology Letters 188, no. 1: 52–62. 10.1016/j.toxlet.2009.03.003. PubMed DOI

Guillard, A. , Gaultier E., Cartier C., et al. 2020. “Basal Ti Level in the Human Placenta and Meconium and Evidence of a Materno‐Foetal Transfer of Food‐Grade TiO(2) Nanoparticles in an ex Vivo Placental Perfusion Model.” Particle and Fibre Toxicology 17, no. 1: 51. 10.1186/s12989-020-00381-z. PubMed DOI PMC

Guseva Canu, I. , Gaillen‐Guedy A., Antilla A., et al. 2022. “Lung cancer Mortality in the European Cohort of Titanium Dioxide Workers: A Reanalysis of the Exposure–Response Relationship.” Occupational and Environmental Medicine 79: 637–640. 10.1136/oemed-2021-108030. PubMed DOI

Han, C. , Lalley J., Namboodiri D., Cromer K., and Nadagouda M. N.. 2016. “Titanium Dioxide‐Based Antibacterial Surfaces for Water Treatment.” Current Opinion in Chemical Engineering 11: 46–51. 10.1016/J.COCHE.2015.11.007. DOI

Hansa, J. , Merzenich H., Cascant Ortolano L., Klug S. J., Blettner M., and Gianicolo E.. 2023. “Health Risks of Titanium Dioxide (TiO2) Dust Exposure in Occupational Settings—A Scoping Review.” International Journal of Hygiene and Environmental Health 252: 114212. 10.1016/j.ijheh.2023.114212. PubMed DOI

Harrison, P. M. , and Arosio P.. 1996. “The Ferritins: Molecular Properties, iron Storage Function and Cellular Regulation.” Biochimica et Biophysica Acta 1275, no. 3: 161–203. 10.1016/0005-2728(96)00022-9. PubMed DOI

He, Z. , Liu J., and Du L.. 2014. “The Unexpected Effect of PEGylated Gold Nanoparticles on the Primary Function of Erythrocytes.” Nanoscale 6, no. 15: 9017–9024. 10.1039/c4nr01857e. PubMed DOI

Health Canada . 2022. State of the Science of Titanium Dioxide (TiO2) as a Food Additive. Health Canada: Food Directorate.

Heinrich, U. , Fuhst R., Rittinghausen S., et al. 1995. “Chronic Inhalation Exposure of Wistar Rats and two Different Strains of Mice to Diesel Engine Exhaust, Carbon Black, and Titanium Dioxide.” Inhalation Toxicology 7, no. 4: 533–556. 10.3109/08958379509015211. DOI

Heringa, M. B. , Peters R. J. B., Bleys R., et al. 2018. “Detection of Titanium Particles in Human Liver and Spleen and Possible Health Implications.” Particle and Fibre Toxicology 15, no. 1: 15. 10.1186/s12989-018-0251-7. PubMed DOI PMC

Hu, H. , Guo Q., Wang C., et al. 2015. “Titanium Dioxide Nanoparticles Increase Plasma Glucose via Reactive Oxygen Species‐Induced Insulin Resistance in Mice.” Journal of Applied Toxicology 35, no. 10: 1122–1132. 10.1002/jat.3150. PubMed DOI

Chu, Z. , Zhang S., Zhang B., et al. 2014. “Unambiguous Observation of Shape Effects on Cellular Fate of Nanoparticles.” Scientific Reports 4: 4495. 10.1038/srep04495. PubMed DOI PMC

Iancu, T. C. 1992. “Ferritin and Hemosiderin in Pathological Tissues.” Electron Microscopy Reviews 5, no. 2: 209–229. 10.1016/0892-0354(92)90011-e. PubMed DOI

Iancu, T. C. 2011. “Ultrastructural Aspects of iron Storage, Transport and Metabolism.” Journal of Neural Transmission (Vienna) 118, no. 3: 329–335. 10.1007/s00702-011-0588-7. PubMed DOI

IARC . 2010. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Carbon Black, Titanium Dioxide, and Talc. Vol. 93. Lyon, France: International Agency for Research on Cancer. PubMed PMC

Ichihara, S. , Li W., Omura S., et al. 2016. “Exposure Assessment and Heart Rate Variability Monitoring in Workers Handling Titanium Dioxide Particles: A Pilot Study.” Journal of Nanoparticle Research 18: 52. 10.1007/s11051-016-3340-2. DOI

Iversen, T.‐G. , Skotland T., and Sandvig K.. 2011. “Endocytosis and Intracellular Transport of Nanoparticles: Present Knowledge and Need for Future Studies.” Nano Today 6, no. 2: 176–185. 10.1016/j.nantod.2011.02.003. DOI

Jafari, S. , Mahyad B., Hashemzadeh H., Janfaza S., Gholikhani T., and Tayebi L.. 2020. “Biomedical Applications of TiO2 Nanostructures: Recent Advances.” International Journal of Nanomedicine 15: 3447–3470. 10.2147/ijn.S249441. PubMed DOI PMC

Keevend, K. , Coenen T., and Herrmann I. K.. 2020. “Correlative Cathodoluminescence Electron Microscopy Bioimaging: Towards Single Protein Labelling With Ultrastructural Context.” Nanoscale 12, no. 29: 15588–15603. 10.1039/d0nr02563a. PubMed DOI

Konczol, M. , Ebeling S., Goldenberg E., et al. 2011. “Cytotoxicity and Genotoxicity of Size‐Fractionated iron Oxide (Magnetite) in A549 Human Lung Epithelial Cells: Role of ROS, JNK, and NF‐kappaB.” Chemical Research in Toxicology 24, no. 9: 1460–1475. 10.1021/tx200051s. PubMed DOI

Krug, H. F. 2014. “Nanosafety research—are we on the right track?” Angewandte Chemie (International Ed. in English) 53, no. 46: 12304–12319. 10.1002/anie.201403367. PubMed DOI

Krug, H. F. , and Wick P.. 2011. “Nanotoxicology: An Interdisciplinary Challenge.” Angewandte Chemie (International Ed. in English) 50, no. 6: 1260–1278. 10.1002/anie.201001037. PubMed DOI

Křůmal, K. , Mikuška P., Večeřová K., Urban O., Pallozzi E., and Večeřa Z.. 2016. “Wet Effluent Diffusion Denuder: The Tool for Determination of Monoterpenes in Forest.” Talanta 153: 260–267. 10.1016/j.talanta.2016.03.032. PubMed DOI

Kumar, N. , Chauhan N. S., Mittal A., and Sharma S.. 2018. “TiO2 and Its Composites as Promising Biomaterials: A Review.” Biometals 31, no. 2: 147–159. 10.1007/s10534-018-0078-6. PubMed DOI

Lammel, T. , Mackevica A., Johansson B. R., and Sturve J.. 2019. “Endocytosis, Intracellular Fate, Accumulation, and Agglomeration of Titanium Dioxide (TiO2) Nanoparticles in the Rainbow Trout Liver Cell Line RTL‐W1.” Environmental Science and Pollution Research International 26, no. 15: 15354–15372. 10.1007/s11356-019-04856-1. PubMed DOI PMC

Lee, K. P. , Trochimowicz H. J., and Reinhardt C. F.. 1985a. “Pulmonary Response of Rats Exposed to Titanium Dioxide (TiO2) by Inhalation for two Years.” Toxicology and Applied Pharmacology 79, no. 2: 179–192. 10.1016/0041-008x(85)90339-4. PubMed DOI

Lee, K. P. , Trochimowicz H. J., and Reinhardt C. F.. 1985b. “Transmigration of Titanium Dioxide (TiO2) Particles in Rats After Inhalation Exposure.” Experimental and Molecular Pathology 42, no. 3: 331–343. 10.1016/0014-4800(85)90083-8. PubMed DOI

Lehotska Mikusova, M. , Busova M., Tulinska J., et al. 2023. “Titanium Dioxide Nanoparticles Modulate Systemic Immune Response and Increase Levels of Reduced Glutathione in Mice After Seven‐Week Inhalation.” Nanomaterials 13, no. 4: 767 Retrieved from https://www.mdpi.com/2079‐4991/13/4/767. PubMed PMC

Li, S. Q. , Zhu R. R., Zhu H., et al. 2008. “Nanotoxicity of TiO2 Nanoparticles to Erythrocyte in Vitro.” Food and Chemical Toxicology 46, no. 12: 3626–3631. 10.1016/j.fct.2008.09.012. PubMed DOI

Lojk, J. , Bregar V. B., Rajh M., et al. 2015. “Cell Type‐Specific Response to High Intracellular Loading of Polyacrylic Acid‐Coated Magnetic Nanoparticles.” International Journal of Nanomedicine 10: 1449–1462. 10.2147/ijn.S76134. PubMed DOI PMC

Lord, J. M. , and Roberts L. M.. 1998. “Retrograde Transport: Going Against the Flow.” Current Biology 8, no. 2: R56–R58. 10.1016/s0960-9822(98)70034-x. PubMed DOI

Luo, Y. H. , Wu S. B., Wei Y. H., et al. 2013. “Cadmium‐Based Quantum Dot Induced Autophagy Formation for Cell Survival via Oxidative Stress.” Chemical Research in Toxicology 26, no. 5: 662–673. 10.1021/tx300455k. PubMed DOI

Martin, N. , Wassmur B., Baun A., and Lammel T.. 2022. “Availability and Effects of n‐TiO2 and PCB77 in Fish in Vitro Models of the Intestinal Barrier and Liver Under Single‐ and/or Co‐Exposure Scenarios.” Aquatic Toxicology 253: 106343. 10.1016/j.aquatox.2022.106343. PubMed DOI

Meijer, A. J. , and Codogno P.. 2009. “Autophagy: Regulation and Role in Disease.” Critical Reviews in Clinical Laboratory Sciences 46, no. 4: 210–240. 10.1080/10408360903044068. PubMed DOI

Mohammadparast, V. , and Mallard B. L.. 2023. “The Effect and Underlying Mechanisms of Titanium Dioxide Nanoparticles on Glucose Homeostasis: A Literature Review.” Journal of Applied Toxicology 43, no. 1: 22–31. 10.1002/jat.4318. PubMed DOI PMC

Moravec, P. , Schwarz J., Vodička P., and Koštejn M.. 2016. “Study of TiO2 Nanoparticle Generation for Follow‐Up Inhalation Experiments With Laboratory Animals.” Aerosol Science and Technology 50, no. 10: 1068–1076. 10.1080/02786826.2016.1224803. DOI

Muhle, H. , Kittel B., Ernst H., Mohr U., and Mermelstein R.. 1995. “Neoplastic Lung Lesions in Rat After Chronic Exposure to Crystalline Silica.” Scandinavian Journal of Work, Environment & Health 21, no. Suppl 2: 27–29. PubMed

Muhle, H. , Mermelstein R., Dasenbrock C., et al. 1989. “Lung Response to Test Toner Upon 2‐Year Inhalation Exposure in Rats.” Experimental Pathology 37, no. 1–4: 239–242. 10.1016/s0232-1513(89)80059-3. PubMed DOI

Mühlfeld, C. , Geiser M., Kapp N., Gehr P., and Rothen‐Rutishauser B.. 2007. “Re‐Evaluation of Pulmonary Titanium Dioxide Nanoparticle Distribution Using the “Relative Deposition Index”: Evidence for Clearance Through Microvasculature.” Particle and Fibre Toxicology 4: 7. 10.1186/1743-8977-4-7. PubMed DOI PMC

NIOSH . 2011. Occupational Exposure to Titanium Dioxide. Vol. 63. Cincinnati, OH, USA: National Institute for Occupational Safety and Health.

Oberdörster, G. 2001. “Pulmonary Effects of Inhaled Ultrafine Particles.” International Archives of Occupational and Environmental Health 74, no. 1: 1–8. 10.1007/s004200000185. PubMed DOI

Peters, R. J. B. , Oomen A. G., van Bemmel G., et al. 2020. “Silicon Dioxide and Titanium Dioxide Particles Found in Human Tissues.” Nanotoxicology 14, no. 3: 420–432. 10.1080/17435390.2020.1718232. PubMed DOI

Plugaru, R. 2008. “Optical Properties of Nanocrystalline Titanium Oxide.” Thin Solid Films 516, no. 22: 8179–8183. 10.1016/j.tsf.2008.04.039. DOI

Pujalté, I. , Dieme D., Haddad S., Serventi A. M., and Bouchard M.. 2017. “Toxicokinetics of Titanium Dioxide (TiO2) Nanoparticles After Inhalation in Rats.” Toxicology Letters 265: 77–85. 10.1016/j.toxlet.2016.11.014. PubMed DOI

Ravikumar, B. , Sarkar S., Davies J. E., et al. 2010. “Regulation of Mammalian Autophagy in Physiology and Pathophysiology.” Physiological Reviews 90, no. 4: 1383–1435. 10.1152/physrev.00030.2009. PubMed DOI

Reibman, J. , Hsu Y., Chen L. C., et al. 2002. “Size Fractions of Ambient Particulate Matter Induce Granulocyte Macrophage Colony‐Stimulating Factor in Human Bronchial Epithelial Cells by Mitogen‐Activated Protein Kinase Pathways.” American Journal of Respiratory Cell and Molecular Biology 27, no. 4: 455–462. 10.1165/rcmb.2001-0005OC. PubMed DOI

Rennick, J. J. , Johnston A. P. R., and Parton R. G.. 2021. “Key Principles and Methods for Studying the Endocytosis of Biological and Nanoparticle Therapeutics.” Nature Nanotechnology 16, no. 3: 266–276. 10.1038/s41565-021-00858-8. PubMed DOI

Riediker, M. , Zink D., Kreyling W., et al. 2019. “Particle Toxicology and Health—Where Are We?” Particle and Fibre Toxicology 16, no. 1: 19. 10.1186/s12989-019-0302-8. PubMed DOI PMC

Rossner, P. , Vrbova K., Strapacova S., et al. 2019. “Inhalation of ZnO Nanoparticles: Splice Junction Expression and Alternative Splicing in Mice.” Toxicological Sciences 168, no. 1: 190–200. 10.1093/toxsci/kfy288. PubMed DOI PMC

Saito, H. 2014. “Metabolism of iron Stores.” Nagoya Journal of Medical Science 76, no. 3–4: 235–254. PubMed PMC

Sandvig, K. , Skotland T., van Deurs B., and Klokk T. I.. 2013. “Retrograde Transport of Protein Toxins Through the Golgi Apparatus.” Histochemistry and Cell Biology 140, no. 3: 317–326. 10.1007/s00418-013-1111-z. PubMed DOI

Shi, H. , Magaye R., Castranova V., and Zhao J.. 2013. “Titanium Dioxide Nanoparticles: A Review of Current Toxicological Data.” Particle and Fibre Toxicology 10: 15. 10.1186/1743-8977-10-15. PubMed DOI PMC

Skotland, T. , Iversen T.‐G., and Sandvig K.. 2021. “Cellular Uptake of Nanoparticles: Involvement of Caveolae?” Precision Nanomedicine 4: 782–786. 10.33218/001c.22201. DOI

Skoupý, R. , Boltje D. B., Slouf M., et al. 2023. “Robust Local Thickness Estimation of sub‐Micrometer Specimen by 4D‐STEM.” Small Methods 7: e2300258. 10.1002/smtd.202300258. PubMed DOI

Slouf, M. , Skoupy R., Pavlova E., and Krzyzanek V.. 2021a. “High Resolution Powder electron Diffraction in Scanning electron Microscopy.” Materials (Basel) 14, no. 24: 7550. 10.3390/ma14247550. PubMed DOI PMC

Slouf, M. , Skoupy R., Pavlova E., and Krzyzanek V.. 2021b. “Powder Nano‐Beam Diffraction in Scanning Electron Microscope: Fast and Simple Method for Analysis of Nanoparticle Crystal Structure.” Nanomaterials (Basel) 11, no. 4: 962. 10.3390/nano11040962. PubMed DOI PMC

Smutná, T. , Dumková J., Kristeková D., et al. 2022. “Macrophage‐Mediated Tissue Response Evoked by Subchronic Inhalation of Lead Oxide Nanoparticles Is Associated With the Alteration of Phospholipases C and Cholesterol Transporters.” Particle and Fibre Toxicology 19, no. 1: 52. 10.1186/s12989-022-00494-7. PubMed DOI PMC

Solarska‐Ściuk, K. , Adach K., Cyboran‐Mikołajczyk S., et al. 2021. “Are Biogenic and Pyrogenic Mesoporous SiO(2) Nanoparticles Safe for Normal Cells?” Molecules 26, no. 5: 1427. 10.3390/molecules26051427. PubMed DOI PMC

Stern, S. T. , Adiseshaiah P. P., and Crist R. M.. 2012. “Autophagy and Lysosomal Dysfunction as Emerging Mechanisms of Nanomaterial Toxicity.” Particle and Fibre Toxicology 9: 20. 10.1186/1743-8977-9-20. PubMed DOI PMC

Sun, B. , Wang X., Ji Z., Li R., and Xia T.. 2013. “NLRP3 Inflammasome Activation Induced by Engineered Nanomaterials.” Small 9, no. 9–10: 1595–1607. 10.1002/smll.201201962. PubMed DOI PMC

Thyssen, J. , Kimmerle G., Dickhaus S., Emminger E., and Mohr U.. 1978. “Inhalation Studies With Polyurethane Foam Dust in Relation to Respiratory Tract Carcinogenesis.” Journal of Environmental Pathology and Toxicology 1, no. 4: 501–508. PubMed

Tian, Y. , Tian Z., Dong Y., Wang X., and Zhan L.. 2021. “Current Advances in Nanomaterials Affecting Morphology, Structure, and Function of Erythrocytes.” RSC Advances 11: 6958–6971. PubMed PMC

Valentini, X. , Rugira P., Frau A., et al. 2019. “Hepatic and Renal Toxicity Induced by TiO2 Nanoparticles in Rats: A Morphological and Metabonomic Study.” Journal of Toxicology 2019: 5767012. 10.1155/2019/5767012. PubMed DOI PMC

Verleysen, E. , Brassinne F., Van Steen F., et al. 2022. “Towards a Generic Protocol for Measuring the Constituent Particle Size Distribution of E171 in Food by Electron Microscopy.” Food Control 132: 108492. 10.1016/j.foodcont.2021.108492. DOI

Vysloužil, J. , Kulich P., Zeman T., et al. 2020. “Subchronic Continuous Inhalation Exposure to Zinc Oxide Nanoparticles Induces Pulmonary Cell Response in Mice.” Journal of Trace Elements in Medicine and Biology 61: 126511. 10.1016/j.jtemb.2020.126511. PubMed DOI

Winter, M. , Beer H.‐D., Hornung V., Krämer U., Schins R. P. F., and Förster I.. 2011. “Activation of the Inflammasome by Amorphous Silica and TiO2 Nanoparticles in Murine Dendritic Cells.” Nanotoxicology 5, no. 3: 326–340. 10.3109/17435390.2010.506957. PubMed DOI

Yamano, S. , Goto Y., Takeda T., et al. 2022. “Pulmonary Dust Foci as Rat Pneumoconiosis Lesion Induced by Titanium Dioxide Nanoparticles in 13‐Week Inhalation Study.” Particle and Fibre Toxicology 19, no. 1: 58. 10.1186/s12989-022-00498-3. PubMed DOI PMC

Yamano, S. , Takeda T., Goto Y., et al. 2022. “No Evidence for Carcinogenicity of Titanium Dioxide Nanoparticles in 26‐Week Inhalation Study in rasH2 Mouse Model.” Scientific Reports 12, no. 1: 14969. 10.1038/s41598-022-19139-y. PubMed DOI PMC

Yan, M. , Zhang Y., Qin H., et al. 2016. “Cytotoxicity of CdTe Quantum Dots in Human Umbilical Vein Endothelial Cells: The Involvement of Cellular Uptake and Induction of Pro‐Apoptotic Endoplasmic Reticulum Stress.” International Journal of Nanomedicine 11: 529–542. 10.2147/ijn.S93591. PubMed DOI PMC

Yazdi, A. S. , Guarda G., Riteau N., et al. 2010. “Nanoparticles Activate the NLR Pyrin Domain Containing 3 (Nlrp3) Inflammasome and Cause Pulmonary Inflammation Through Release of IL‐1α and IL‐1β.” Proceedings of the National Academy of Sciences of the United States of America 107, no. 45: 19449–19454. 10.1073/pnas.1008155107. PubMed DOI PMC

Younes, M. , Aquilina G., Castle L., et al. 2021. “EFSA FAF Panel. Safety Assessment of Titanium Dioxide (E171) as a Food Additive.” EFSA Journal 19, no. 5: e06585. 10.2903/j.efsa.2021.6585. PubMed DOI PMC

Younis, A. B. , Haddad Y., Kosaristanova L., and Smerkova K.. 2022. “Titanium Dioxide Nanoparticles: Recent Progress in Antimicrobial Applications.” Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology 15: e1860. 10.1002/wnan.1860. PubMed DOI

Yu, K. N. , Sung J. H., Lee S., et al. 2015. “Inhalation of Titanium Dioxide Induces Endoplasmic Reticulum Stress‐Mediated Autophagy and Inflammation in Mice.” Food and Chemical Toxicology 85: 106–113. 10.1016/j.fct.2015.08.001. PubMed DOI

Zeman, T. , Loh E. W., Čierný D., and Šerý O.. 2018. “Penetration, Distribution and Brain Toxicity of Titanium Nanoparticles in Rodents' Body: A Review.” IET Nanobiotechnology 12, no. 6: 695–700. 10.1049/iet-nbt.2017.0109. PubMed DOI PMC

Zhang, X. , Zhang H., Liang X., et al. 2016. “Iron Oxide Nanoparticles Induce Autophagosome Accumulation Through Multiple Mechanisms: Lysosome Impairment, Mitochondrial Damage, and ER Stress.” Molecular Pharmaceutics 13, no. 7: 2578–2587. 10.1021/acs.molpharmaceut.6b00405. PubMed DOI

Zhao, J. , Bowman L., Zhang X., et al. 2009. “Titanium Dioxide (TiO2) Nanoparticles Induce JB6 Cell Apoptosis Through Activation of the Caspase‐8/Bid and Mitochondrial Pathways.” Journal of Toxicology and Environmental Health. Part A 72, no. 19: 1141–1149. 10.1080/15287390903091764. PubMed DOI

Najít záznam

Citační ukazatele

Nahrávání dat ...

Možnosti archivace

Nahrávání dat ...