Aerosol characterization and lung deposition of synthesized TiO2 nanoparticles for murine inhalation studies (original) (raw)
Related papers
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
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.
Environmental Toxicology and Pharmacology, 2007
The acute pulmonary toxicity induced by 3-nm TiO 2 primary particles was preliminary investigated after they were intratracheally instilled at doses of 0.4, 4 and 40 mg/kg into lungs of mice. The biochemical parameters in bronchoalveolar lavage fluid (BALF) and pathological examination were used as endpoints to assess their pulmonary toxicity at 3-day postexposure. As such, the pulmonary toxicity assessment of 20-nm TiO 2 primary particles was performed using the same method. It was found that the 3-nm TiO 2 primary particles induced no pulmonary toxicity at dose of 0.4 mg/kg, moderate toxicity at 4 mg/kg and lung overload at 40 mg/kg, and this kind of particles did not produce more pulmonary toxicity than the 20-nm ones at any instilled doses. As regards physicochemical characteristics of the two TiO 2 particles, their pH values in medium, other than particle size, surface area and aggregation, may play important role in affecting their pulmonary toxicity.
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.
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.
Study of TiO2 nanoparticle generation for follow-up inhalation experiments with laboratory animals
Aerosol Science and Technology, 2016
A method of long-lasting TiO 2 nanoparticle generation was tested for use in follow-up studies of the health impacts of nanoparticles on laboratory animals during several weeks' long exposure experiments. Nanoparticles were synthesized in an externally heated tube reactor by pyrolysis and oxidation of titanium tetraisopropoxide. Particle production was studied under varying reactor temperature, reactor flow rate, and precursor vapor pressure. A total of 264 h of particle generation were performed in four experimental campaigns using one batch of precursor without an observable decrease of particle production. As a result, particle production with number concentrations high above 1.0 £ 10 7 #/cm 3 and with primary particle sizes well below 50 nm could be achieved in most of the investigated experimental conditions. Maximum of particle mass concentration reached the value 9500 mg/m 3 , which corresponds with emission rate 29 mg/min. The dependence of nanoparticle production and characteristics on experimental conditions was evaluated and the most suitable parameters for exposure experiments were specified. A comparison of the results with data from the literature shows that the material of the reactor plays a significant role in the process of particle formation.
Toxicology, 2007
Surface properties are critical to assess effects of ultrafine-TiO 2 particles. The aim of this study was to assess lung toxicity in rats of newly developed, well characterized, ultrafine-TiO 2 particles and compare them to TiO 2 samples in two different size ranges and surface modifications. Groups of rats were intratracheally instilled with doses of 1 or 5 mg/kg of either two ultrafine rutile TiO 2 particles (uf-1 or uf-2); rutile R-100 fine-TiO 2 (F-1); 80/20 anatase/rutile P25 ultrafine-TiO 2 (uf-3); or ␣-quartz particles. Phosphatebuffered saline (PBS) solution instilled rats served as vehicle controls. Following exposures, the lungs of PBS and particle-exposed rats were evaluated for bronchoalveolar lavage (BAL) fluid inflammatory markers, cell proliferation, and by histopathology at post-instillation time points of 24 h, 1 week, 1 and 3 months.
Particle and Fibre Toxicology, 2009
This review focuses on outlining the toxicity of titanium dioxide (TiO2) particulates in vitro and in vivo, in order to understand their ability to detrimentally impact on human health. Evaluating the hazards associated with TiO2 particles is vital as it enables risk assessments to be conducted, by combining this information with knowledge on the likely exposure levels of humans. This review has concentrated on the toxicity of TiO2, due to the fact that the greatest number of studies by far have evaluated the toxicity of TiO2, in comparison to other metal oxide particulates. This derives from historical reasons (whereby the size dependency of particulate toxicity was first realised for TiO2) and due to its widespread application within consumer products (such as sunscreens). The pulmonary and dermal hazards of TiO2 have been a particular focus of the available studies, due to the past use of TiO2 as a (negative) control when assessing the pulmonary toxicity of particulates, and due to its incorporation within consumer products such as sunscreens. Mechanistic processes that are critical to TiO2 particulate toxicity will also be discussed and it is apparent that, in the main, the oxidant driven inflammatory, genotoxic and cytotoxic consequences associated with TiO2 exposure, are inherently linked, and are evident both in vivo and in vitro. The attributes of TiO2 that have been identified as being most likely to drive the observed toxicity include particle size (and therefore surface area), crystallinity (and photocatalytic activity), surface chemistry, and particle aggregation/agglomeration tendency. The experimental set up also influences toxicological outcomes, so that the species (or model) used, route of exposure, experiment duration, particle concentration and light conditions are all able to influence the findings of investigations. In addition, the applicability of the observed findings for particular TiO2 forms, to TiO2 particulates in general, requires consideration. At this time it is inappropriate to consider the findings for one TiO2 form as being representative for TiO2 particulates as a whole, due to the vast number of available TiO2 particulate forms and large variety of potential tissue and cell targets that may be affected by exposure. Thus emphasising that the physicochemical characteristics are fundamental to their toxicity.
Toxics, 2017
Nanoparticles (NPs) can be released in the air in work settings, but various factors influence the exposure of workers. Controlled inhalation experiments can thus be conducted in an attempt to reproduce real-life exposure conditions and assess inhalation toxicology. Methods exist to generate aerosols, but it remains difficult to obtain nano-sized and stable aerosols suitable for inhalation experiments. The goal of this work was to characterize aerosols of titanium dioxide (TiO 2) NPs, generated using a novel inhalation system equipped with three types of generators-a wet collision jet nebulizer, a dry dust jet and an electrospray aerosolizer-with the aim of producing stable aerosols with a nano-diameter average (<100 nm) and monodispersed distribution for future rodent exposures and toxicological studies. Results showed the ability of the three generation systems to provide good and stable dispersions of NPs, applicable for acute (continuous up to 8 h) and repeated (21-day) exposures. In all cases, the generated aerosols were composed mainly of small aggregates/agglomerates (average diameter <100 nm) with the electrospray producing the finest (average diameter of 70-75 mm) and least concentrated aerosols (between 0.150 and 2.5 mg/m 3). The dust jet was able to produce concentrations varying from 1.5 to 150 mg/m 3 , and hence, the most highly concentrated aerosols. The nebulizer collision jet aerosolizer was the most versatile generator, producing both low (0.5 mg/m 3) and relatively high concentrations (30 mg/m 3). The three optimized generators appeared suited for possible toxicological studies of inhaled NPs.
Toxicokinetics of titanium dioxide (TiO2) nanoparticles after inhalation in rats
Toxicology Letters, 2017
The kinetics of TiO 2 nanoparticles was studied in rats after a 6-h inhalation. TiO 2 persisted in lungs, where highest tissue levels were found. TiO 2 in lungs reached peak values only at 48 h and levels decreased over 14 days. Fecal amounts suggest a mucociliary clearance of inhaled NPs and ingestion. A certain translocation to the olfactory bulb and the brain was also observed.