Subchronic Inhalation of TiO2 Nanoparticles Leads to Deposition in the Lung and Alterations in Erythrocyte Morphology in Mice
Jazyk angličtina Země Anglie, Velká Británie Médium print-electronic
Typ dokumentu časopisecké články
Grantová podpora
RO0523
Ministry of Agriculture of the Czech Republic
24-10051S
Czech Science Foundation
PubMed
39933250
PubMed Central
PMC12061548
DOI
10.1002/jat.4759
Knihovny.cz E-zdroje
- Klíčová slova
- cathodoluminescence, electron microscopy, lung, powder nanobeam diffraction, titanium dioxide nanoparticles,
- MeSH
- aplikace inhalační MeSH
- erytrocyty * účinky léků patologie MeSH
- inhalační expozice * škodlivé účinky MeSH
- kovové nanočástice * toxicita MeSH
- myši MeSH
- nanočástice * toxicita MeSH
- plíce * účinky léků metabolismus patologie MeSH
- testy subchronické toxicity MeSH
- titan * toxicita farmakokinetika aplikace a dávkování MeSH
- tkáňová distribuce MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- titan * MeSH
- titanium dioxide MeSH Prohlížeč
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.
Department of Bionanoscience Delft University of Technology Delft The Netherlands
Department of Pharmacology and Toxicology Veterinary Research Institute Brno Czech Republic
Institute of Scientific Instruments Czech Academy of Sciences Brno Czech Republic
Kavli Institute of Nanoscience Delft University of Technology Delft The Netherlands
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