Deposition behavior of inhaled nanostructured TiO2in rats: fractions of particle diameter below 100 nm (nanoscale) and the slicing bias of transmission electron microscopy (original) (raw)
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Inhalation Toxicology, 2012
Context: In experimental studies with nanomaterials where translocation to secondary organs was observed, the particle sizes were smaller than 20 nm and were mostly produced by spark generators. Engineered nanostructured materials form microsize aggregates/agglomerates. Thus, it is unclear whether primary nanoparticles or their small aggregates/agglomerates occur in non-negligible concentrations after exposure to real-world materials in the lung. Objective: We dedicated an inhalation study with nanostructured TiO 2 to the following research question: Does the particle size distribution in the lung contain a relevant subdistribution of nanoparticles? Methods: Six rats were exposed to 88 mg/m 3 TiO 2 over 5 days with 20% (count fraction) and <0.5% (mass fraction) of nanoscaled objects. Three animals were sacrificed after cessation of exposure (5 days), others after a recovery period of 14 days. Particle sizes were determined morphometrically by transmission electron microscopy (TEM) of ultra-thin lung slices. Since the particles visible are two-dimensional surrogates of three-dimensional structures we developed a model to estimate expected numbers of particle diameters below 100 nm due to the TEM slicing bias. Observed and expected numbers were contrasted in 2 × 2 tables by odds ratios. Results: Comparisons of observed and expected numbers did not present evidence in favor of the presence of nanoparticles in the rat lungs. In simultaneously exposed satellite animals agglomerates of nanostructured TiO 2 were observed in the mediastinal lymph nodes but not in secondary organs. Conclusions: For nanostructured TiO 2 , the deposition of nanoscaled particles in the lung seem to play a negligible role.
Particle and Fibre Toxicology, 2013
Background The exact role of primary nanoparticle (NP) size and their degree of agglomeration in aerosols on the determination of pulmonary effects is still poorly understood. Smaller NP are thought to have greater biological reactivity, but their level of agglomeration in an aerosol may also have an impact on pulmonary response. The aim of this study was to investigate the role of primary NP size and the agglomeration state in aerosols, using well-characterized TiO2 NP, on their relative pulmonary toxicity, through inflammatory, cytotoxic and oxidative stress effects in Fisher 344 male rats. Methods Three different sizes of TiO2 NP, i.e., 5, 10–30 or 50 nm, were inhaled as small (SA) (< 100 nm) or large agglomerates (LA) (> 100 nm) at 20 mg/m3 for 6 hours. Results Compared to the controls, bronchoalveolar lavage fluids (BALF) showed that LA aerosols induced an acute inflammatory response, characterized by a significant increase in the number of neutrophils, while SA aerosols ...
International Journal of Nanomedicine
Background: Titanium dioxide nanoparticles have numerous applications, resulting in human exposure. Nonetheless, available toxicological and safety data are insufficient regarding aspherical particles, such as rod-shaped nanoparticles. Methods: In a combined in vitro-in vivo approach, cultured A549 lung alveolar adenocarcinoma cells were treated with approximately 15×65 nm TiO 2 nanorod-containing medium, while young adult rats received the same substance by intratracheal instillation for 28 days in 5 and 18 mg/kg bodyweight doses. Nanoparticle accumulation in the lungs and consequent oxidative stress, cell damage, and inflammation were assessed by biochemical and histopathological methods. Results: Titanium was detected in tissue samples by single-particle inductively coupled plasma mass spectrometry. Nanoparticles were visualized inside cultured A549 cells, within pulmonary macrophages, and in hilar lymph nodes of the rats. A549 cells showed dose-dependent oxidative stress and lethality, and the observed nanoparticle-laden endosomes suggested deranged lysosomal function and possible autophagy. Strongly elevated Ti levels were measured in the lungs of nanorod-treated rats and moderately elevated levels in the blood of the animals. Numerous cytokines, indicating acute and also chronic inflammation, were identified in the lung samples of TiO 2-exposed rodents. Conclusion: Several signs of cell and tissue damage were detected in both the cultured alveolar cells and in treated rats' lungs. Rod-shaped nanoparticulate TiO 2 may consequently be more harmful than has generally been supposed. The occupational health risk suggested by the results calls for improved safety measures.
J Nanopart Res, 2011
This study presents a novel exposure protocol for synthesized nanoparticles (NPs). NPs were synthesized in gas phase by thermal decomposition of metal alkoxide vapors in a laminar flow reactor. The exposure protocol was used to estimate the deposition fraction of titanium dioxide (TiO 2 ) NPs to mice lung. The experiments were conducted at aerosol mass concentrations of 0.8, 7.2, 10.0, and 28.5 mg m -3 . The means of aerosol geometric mobility diameter and aerodynamic diameter were 80 and 124 nm, and the geometric standard deviations were 1.8 and 1.7, respectively. The effective density of the particles was approximately from 1.5 to 1.7 g cm -3 . Particle concentration varied from 4 9 10 5 cm -3 at mass concentrations of 0.8 mg m -3 to 12 9 10 6 cm -3 at 28.5 mg m -3 . Particle phase structures were 74% of anatase and 26% of brookite with respective crystallite sized of 41 and 6 nm. The brookite crystallites were approximately 100 times the size of the anatase crystallites. The TiO 2 particles were porous and highly agglomerated, with a mean primary particle size of 21 nm. The specific surface area of TiO 2 powder was 61 m 2 g -1 . We defined mice respiratory minute volume (RMV) value during exposure to TiO 2 aerosol. Both TiO 2 particulate matter and gaseous by-products affected respiratory parameters. The RMV values were used to quantify the deposition fraction of TiO 2 matter by using two different methods. According to individual samples, the deposition fraction was 8% on an average, and when defined from aerosol mass concentration series, it was 7%. These results show that the exposure protocol can be used to study toxicological effects of synthesized NPs.
Journal of Nanoparticle Research, 2011
This study presents a novel exposure protocol for synthesized nanoparticles (NPs). NPs were synthesized in gas phase by thermal decomposition of metal alkoxide vapors in a laminar flow reactor. The exposure protocol was used to estimate the deposition fraction of titanium dioxide (TiO 2 ) NPs to mice lung. The experiments were conducted at aerosol mass concentrations of 0.8, 7.2, 10.0, and 28.5 mg m -3 . The means of aerosol geometric mobility diameter and aerodynamic diameter were 80 and 124 nm, and the geometric standard deviations were 1.8 and 1.7, respectively. The effective density of the particles was approximately from 1.5 to 1.7 g cm -3 . Particle concentration varied from 4 9 10 5 cm -3 at mass concentrations of 0.8 mg m -3 to 12 9 10 6 cm -3 at 28.5 mg m -3 . Particle phase structures were 74% of anatase and 26% of brookite with respective crystallite sized of 41 and 6 nm. The brookite crystallites were approximately 100 times the size of the anatase crystallites. The TiO 2 particles were porous and highly agglomerated, with a mean primary particle size of 21 nm. The specific surface area of TiO 2 powder was 61 m 2 g -1 . We defined mice respiratory minute volume (RMV) value during exposure to TiO 2 aerosol. Both TiO 2 particulate matter and gaseous by-products affected respiratory parameters. The RMV values were used to quantify the deposition fraction of TiO 2 matter by using two different methods. According to individual samples, the deposition fraction was 8% on an average, and when defined from aerosol mass concentration series, it was 7%. These results show that the exposure protocol can be used to study toxicological effects of synthesized NPs.
Morfeld 2013 Lung Deposition Ti O2
Context: In experimental studies with nanomaterials where translocation to secondary organs was observed, the particle sizes were smaller than 20 nm and were mostly produced by spark generators. Engineered nanostructured materials form microsize aggregates/agglomerates. Thus, it is unclear whether primary nanoparticles or their small aggregates/agglomerates occur in non-negligible concentrations after exposure to real-world materials in the lung. Objective: We dedicated an inhalation study with nanostructured TiO 2 to the following research question: Does the particle size distribution in the lung contain a relevant subdistribution of nanoparticles? Methods: Six rats were exposed to 88 mg/m 3 TiO 2 over 5 days with 20% (count fraction) and <0.5% (mass fraction) of nanoscaled objects. Three animals were sacrificed after cessation of exposure (5 days), others after a recovery period of 14 days. Particle sizes were determined morphometrically by transmission electron microscopy (TEM) of ultra-thin lung slices. Since the particles visible are two-dimensional surrogates of three-dimensional structures we developed a model to estimate expected numbers of particle diameters below 100 nm due to the TEM slicing bias. Observed and expected numbers were contrasted in 2 × 2 tables by odds ratios. Results: Comparisons of observed and expected numbers did not present evidence in favor of the presence of nanoparticles in the rat lungs. In simultaneously exposed satellite animals agglomerates of nanostructured TiO 2 were observed in the mediastinal lymph nodes but not in secondary organs. Conclusions: For nanostructured TiO 2 , the deposition of nanoscaled particles in the lung seem to play a negligible role.
Particle and fibre toxicology, 2007
Translocation of nanoparticles (NP) from the pulmonary airways into other pulmonary compartments or the systemic circulation is controversially discussed in the literature. In a previous study it was shown that titanium dioxide (TiO2) NP were "distributed in four lung compartments (air-filled spaces, epithelium/endothelium, connective tissue, capillary lumen) in correlation with compartment size". It was concluded that particles can move freely between these tissue compartments. To analyze whether the distribution of TiO2 NP in the lungs is really random or shows a preferential targeting we applied a newly developed method for comparing NP distributions. Rat lungs exposed to an aerosol containing TiO2 NP were prepared for light and electron microscopy at 1 h and at 24 h after exposure. Numbers of TiO2 NP associated with each compartment were counted using energy filtering transmission electron microscopy. Compartment size was estimated by unbiased stereology from systemati...
Journal of Nanoparticle Research, 2011
The intensive use of nano-sized titanium dioxide (TiO 2 ) particles in many different applications necessitates studies on their risk assessment as there are still open questions on their safe handling and utilization. For reliable risk assessment, the interaction of TiO 2 nanoparticles (NP) with biological systems ideally needs to be investigated using physico-chemically uniform and well-characterized NP. In this article, we describe the reproducible production of TiO 2 NP aerosols using spark ignition technology. Because currently no data are available on inhaled NP in the 10-50 nm diameter range, the emphasis was to generate NP as small as 20 nm for inhalation studies in rodents. For anticipated in vivo dosimetry analyses, TiO 2 NP were radiolabeled with 48 V by proton irradiation of the titanium electrodes of the spark generator. The dissolution rate of the 48 V label was about 1% within the first day. The highly concentrated, polydisperse TiO 2 NP aerosol (3-6 9 10 6 cm -3 ) proved to be constant over several hours in terms of its count median mobility diameter, its geometric standard deviation, and number concentration. Extensive characterization of NP chemical composition, physical structure, morphology, and specific surface area was performed. The originally generated amorphous TiO 2 NP were converted into crystalline anatase TiO 2 NP by thermal annealing at 950°C. Both crystalline and amorphous 20-nm TiO 2 NP were chain agglomerated/aggregated, consisting of primary particles in the range of 5 nm. Disintegration of the deposited TiO 2 NP in lung tissue was not detectable within 24 h.
The effects of Nano titanium dioxide (TiO2NPs) on lung tissue
Bratislava Medical Journal, 2015
OBJECTIVES: The application of nanoparticles is widely spread in all aspects of modern life because of their unique features such as small size and high surface area. High surface area can be very reactive and produce reactive oxygen species (ROS). These nanoparticles can damage human and animal cells by increasing oxidative stress mechanism. Titanium dioxide nanoparticles (TiO 2 NPs) are among the top fi ve nanoparticles used in consumer products, paints, and pharmaceutical preparations.TiO 2 NPs have various capabilities such as robust oxidation, biocompatibility and photocatalytic properties. They are frequently used in a wide range of sciences, including pharmaceuticals, cosmetics, medicine and engineering. The ever increasing industrial and consumer applications of TiO 2 NPs raise concern over the possible risk association with their environmental exposure. METHODS: This study investigates the effects of TiO 2 NP on lung tissue by intraperitoneal injection to rats at different doses (15, 30, 60 and 70 mg/kg). RESULTS: Our results showed that intraperitoneal injection of TiO 2 NP creates capillary congestion and hemorrhage in alveolar wall, granulomas in lung parenchyma, and hemosiderin depositions in blood vessels adjacent to bronchioles without any infl ammation. The pulmonary side effects could be due to the production of ROS post TiO 2 NP exposure (Tab. 1, Fig. 5, Ref. 27).