Impacts after inhalation of nano- and fine-sized titanium dioxide particles: morphological changes, translocation within the rat lung, and evaluation of particle deposition using the relative deposition index

A 3-week inhalation study with nano- and fine-sized titanium dioxide (TiO2) with 3, 28, and 90 days recovery time was performed in female Wistar rats. Lung volume measurements, histology, electron microscopy, hematology, and bronchoalveolar lavage (BAL) fluid analyses were conducted and the relative deposition index (RDI) was calculated. Minimal inflammatory changes in the lungs, leucopenia, and a decrease in β-glucuronidase were observed. Particles were mainly deposited in alveolar macrophages and, to a lesser extent, in type-I pneumocytes, and this was quantified using the RDI. Rarely, particle-laden cells were observed inside capillaries. Therefore, minimal translocation of particles into the bloodstream has to be considered. Significant changes, e.g. in elicited effects or translocation behavior, between nano- and fine-particle-treated groups were not observed.

[1]  E K Fram,et al.  Morphometric characteristics of cells in the alveolar region of mammalian lungs. , 2015, The American review of respiratory disease.

[2]  Chung-Min Liao,et al.  Assessing the potential exposure risk and control for airborne titanium dioxide and carbon black nanoparticles in the workplace , 2011, Environmental science and pollution research international.

[3]  Santosh Yadav,et al.  Titanium dioxide nanoparticles cause apoptosis in BEAS-2B cells through the caspase 8/t-Bid-independent mitochondrial pathway. , 2010, Toxicology letters.

[4]  Sonja Boland,et al.  Carbon black and titanium dioxide nanoparticles elicit distinct apoptotic pathways in bronchial epithelial cells , 2010, Particle and Fibre Toxicology.

[5]  Yin-Sheng Ma,et al.  Interaction of nano-TiO2 with lysozyme: insights into the enzyme toxicity of nanosized particles , 2010, Environmental science and pollution research international.

[6]  Helinor J Johnston,et al.  Identification of the mechanisms that drive the toxicity of TiO2 particulates: the contribution of physicochemical characteristics , 2009, Particle and Fibre Toxicology.

[7]  K. L. de Mesy Bentley,et al.  Nanoparticle (NP) uptake by type I alveolar epithelial cells and their oxidant stress response , 2009, Nanotoxicology.

[8]  Christian Mühlfeld,et al.  The effect of titanium dioxide nanoparticles on pulmonary surfactant function and ultrastructure , 2009, Respiratory research.

[9]  Paride Mantecca,et al.  Lung toxicity induced by intratracheal instillation of size-fractionated tire particles. , 2009, Toxicology letters.

[10]  T. Hansen,et al.  Nano- and microscaled titanium dioxide: Comparative study on the inflammatory and genotoxic effects after a 3-week inhalation in rats , 2009 .

[11]  E. Fabian,et al.  Comparing fate and effects of three particles of different surface properties: nano-TiO(2), pigmentary TiO(2) and quartz. , 2009, Toxicology letters.

[12]  Matthias Ochs,et al.  A review of recent methods for efficiently quantifying immunogold and other nanoparticles using TEM sections through cells, tissues and organs. , 2009, Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische Gesellschaft.

[13]  B. van Ravenzwaay,et al.  Development of a Short-Term Inhalation Test in the Rat Using Nano-Titanium Dioxide as a Model Substance , 2009, Inhalation toxicology.

[14]  N. Herlin‐Boime,et al.  In vitro investigation of oxide nanoparticle and carbon nanotube toxicity and intracellular accumulation in A549 human pneumocytes. , 2008, Toxicology.

[15]  Jongheop Yi,et al.  Oxidative stress and apoptosis induced by titanium dioxide nanoparticles in cultured BEAS-2B cells. , 2008, Toxicology letters.

[16]  Su Jin Kang,et al.  Titanium dioxide nanoparticles trigger p53‐mediated damage response in peripheral blood lymphocytes , 2008, Environmental and molecular mutagenesis.

[17]  Manuela Semmler-Behnke,et al.  The role of macrophages in the clearance of inhaled ultrafine titanium dioxide particles. , 2008, American journal of respiratory cell and molecular biology.

[18]  T. Mayhew,et al.  A novel quantitative method for analyzing the distributions of nanoparticles between different tissue and intracellular compartments. , 2007, Journal of aerosol medicine : the official journal of the International Society for Aerosols in Medicine.

[19]  Christian Mühlfeld,et al.  Re-evaluation of pulmonary titanium dioxide nanoparticle distribution using the "relative deposition index": Evidence for clearance through microvasculature , 2007, Particle and Fibre Toxicology.

[20]  P. Borm,et al.  Endocytosis, oxidative stress and IL-8 expression in human lung epithelial cells upon treatment with fine and ultrafine TiO2: role of the specific surface area and of surface methylation of the particles. , 2007, Toxicology and applied pharmacology.

[21]  Mark R Wiesner,et al.  Comparison of the abilities of ambient and manufactured nanoparticles to induce cellular toxicity according to an oxidative stress paradigm. , 2006, Nano letters.

[22]  Andrew D. Maynard,et al.  Nanotechnology: assessing the risks , 2006 .

[23]  W. J. Brock,et al.  Comparative pulmonary toxicity inhalation and instillation studies with different TiO2 particle formulations: impact of surface treatments on particle toxicity. , 2005, Toxicological sciences : an official journal of the Society of Toxicology.

[24]  Wolfgang Kreyling,et al.  Ultrafine Particles Cross Cellular Membranes by Nonphagocytic Mechanisms in Lungs and in Cultured Cells , 2005, Environmental health perspectives.

[25]  R. Cabrini,et al.  Effect of titanium dioxide on the oxidative metabolism of alveolar macrophages: an experimental study in rats. , 2005, Journal of biomedical materials research. Part A.

[26]  G. Oberdörster,et al.  Nanotoxicology: An Emerging Discipline Evolving from Studies of Ultrafine Particles , 2005, Environmental health perspectives.

[27]  Wolfgang Kreyling,et al.  Electron energy loss spectroscopy for analysis of inhaled ultrafine particles in rat lungs , 2004, Microscopy research and technique.

[28]  J. Everitt,et al.  Pulmonary responses of mice, rats, and hamsters to subchronic inhalation of ultrafine titanium dioxide particles. , 2004, Toxicological sciences : an official journal of the Society of Toxicology.

[29]  David B Warheit,et al.  Long-term pulmonary responses of three laboratory rodent species to subchronic inhalation of pigmentary titanium dioxide particles. , 2002, Toxicological sciences : an official journal of the Society of Toxicology.

[30]  Qamar Rahman,et al.  Evidence that ultrafine titanium dioxide induces micronuclei and apoptosis in Syrian hamster embryo fibroblasts. , 2002, Environmental health perspectives.

[31]  K. Donaldson,et al.  INFLAMMATION CAUSED BY PARTICLES AND FIBERS , 2002, Inhalation toxicology.

[32]  J. Paulauskis,et al.  Endocytosis of ultrafine particles by A549 cells. , 2001, American journal of respiratory cell and molecular biology.

[33]  Güunter Oberdürster.  Toxicology of ultrafine particles: in vivo studies , 2000, Philosophical Transactions of the Royal Society of London. Series A: Mathematical, Physical and Engineering Sciences.

[34]  K. Donaldson,et al.  Differences in the extent of inflammation caused by intratracheal exposure to three ultrafine metals: role of free radicals. , 1998, Journal of toxicology and environmental health. Part A.

[35]  G. Hatch,et al.  Evidence that exposure of particulate air pollutants to human and rat alveolar macrophages leads to differential oxidative response. , 1997, Biochemical and biophysical research communications.

[36]  D. Warheit,et al.  Inhalation of high concentrations of low toxicity dusts in rats results in impaired pulmonary clearance mechanisms and persistent inflammation. , 1997, Toxicology and applied pharmacology.

[37]  D. Warheit,et al.  Subchronic inhalation of high concentrations of low toxicity, low solubility particulates produces sustained pulmonary inflammation and cellular proliferation. , 1996, Toxicology letters.

[38]  G. Oberdörster,et al.  Macrophage-associated responses to chrysotile. , 1994, The Annals of occupational hygiene.

[39]  E. Schmidt,et al.  Recommendation for the determination of the catalytic concentration of lactate dehydrogenase at 37 degrees C. Standardization Committee of the German Society for Clinical Chemistry, Enzyme Working Group of the German Society for Clinical Chemistry. , 1993, European journal of clinical chemistry and clinical biochemistry : journal of the Forum of European Clinical Chemistry Societies.

[40]  G. Oberdörster,et al.  Pulmonary retention of ultrafine and fine particles in rats. , 1992, American journal of respiratory cell and molecular biology.

[41]  G. M. Ridder,et al.  Pulmonary response to silica or titanium dioxide: inflammatory cells, alveolar macrophage-derived cytokines, and histopathology. , 1990, American journal of respiratory cell and molecular biology.

[42]  K. P. Lee,et al.  Chronic inhalation exposure of rats to titanium dioxide dust. , 1988, Journal of applied toxicology : JAT.

[43]  P. Morrow,et al.  Possible mechanisms to explain dust overloading of the lungs. , 1988, Fundamental and applied toxicology : official journal of the Society of Toxicology.

[44]  K. P. Lee,et al.  Pulmonary response to impaired lung clearance in rats following excessive TiO2 dust deposition. , 1986, Environmental research.

[45]  K. P. Lee,et al.  Pulmonary response of rats exposed to titanium dioxide (TiO2) by inhalation for two years. , 1985, Toxicology and applied pharmacology.

[46]  K. P. Lee,et al.  Transmigration of titanium dioxide (TiO2) particles in rats after inhalation exposure. , 1985, Experimental and molecular pathology.

[47]  R. Henderson.  Use of bronchoalveolar lavage to detect lung damage. , 1984, Environmental health perspectives.

[48]  W. Scherle,et al.  A simple method for volumetry of organs in quantitative stereology. , 1970, Mikroskopie.

[49]  Oliver H. Lowry,et al.  Protein measurement with the Folin phenol reagent. , 1951, The Journal of biological chemistry.

[50]  E. Weibel,et al.  American Thoracic Society Documents An Official Research Policy Statement of the American Thoracic Society/European Respiratory Society: Standards for Quantitative Assessment of Lung Structure , 2010 .

[51]  Günter Oberdörster,et al.  Toxicology of ultrafine particles: in vivo studies , 2000 .

[52]  K. Donaldson,et al.  Inhalation of poorly soluble particles. I. Differences in inflammatory response and clearance during exposure. , 2000, Inhalation toxicology.

[53]  K. Donaldson,et al.  Inhalation of poorly soluble particles. II. Influence Of particle surface area on inflammation and clearance. , 2000, Inhalation toxicology.

[54]  Robert Gelein,et al.  Increased Pulmonary Toxicity of Inhaled Ultrafine Particles: Due to Lung Overload Alone? , 1994 .

[55]  W. Koch,et al.  Clearance and retention of inhaled diesel exhaust particles, carbon black, and titanium dioxide in rats at lung overload conditions , 1990 .

[56]  S. Takenaka,et al.  Alveolar distribution of fly ash and of titanium dioxide after long-term inhalation by Wistar rats , 1986 .

[57]  V. Castranova,et al.  Particle and Fibre Toxicology Pulmonary Response to Intratracheal Instillation of Ultrafine versus Fine Titanium Dioxide: Role of Particle Surface Area , 2022 .