Pulmonary Toxicity of Single-Wall Carbon Nanotubes in Mice 7 and 90 Days After Intratracheal Instillation

NASA, Вашингтон, West Virginia, United States
Toxicological Sciences (Impact Factor: 3.85). 02/2004; 77(1):126-34. DOI: 10.1093/toxsci/kfg243
Source: PubMed


Nanomaterials are part of an industrial revolution to develop lightweight but strong materials for a variety of purposes. Single-wall carbon nanotubes are an important member of this class of materials. They structurally resemble rolled-up graphite sheets, usually with one end capped; individually they are about 1 nm in diameter and several microns long, but they often pack tightly together to form rods or ropes of microscopic sizes. Carbon nanotubes possess unique electrical, mechanical, and thermal properties and have many potential applications in the electronics, computer, and aerospace industries. Unprocessed nanotubes are very light and could become airborne and potentially reach the lungs. Because the toxicity of nanotubes in the lung is not known, their pulmonary toxicity was investigated. The three products studied were made by different methods and contained different types and amounts of residual catalytic metals. Mice were intratracheally instilled with 0, 0.1, or 0.5 mg of carbon nanotubes, a carbon black negative control, or a quartz positive control and euthanized 7 d or 90 d after the single treatment for histopathological study of the lungs. All nanotube products induced dose-dependent epithelioid granulomas and, in some cases, interstitial inflammation in the animals of the 7-d groups. These lesions persisted and were more pronounced in the 90-d groups; the lungs of some animals also revealed peribronchial inflammation and necrosis that had extended into the alveolar septa. The lungs of mice treated with carbon black were normal, whereas those treated with high-dose quartz revealed mild to moderate inflammation. These results show that, for the test conditions described here and on an equal-weight basis, if carbon nanotubes reach the lungs, they are much more toxic than carbon black and can be more toxic than quartz, which is considered a serious occupational health hazard in chronic inhalation exposures.

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    • "Research of nanomaterial toxicology is presently at an early development stage. Associated research has been conducted on carbon nanomaterials first, and the test objective has been extended from mouse [2] to aquatic organisms (largemouth bass, Daphnia magna, Tetrahymena thermophila, and crucian carp) and human cells [3]. Therefore, the biological safety of NPs has aroused great concerns by governments and academic circles. "
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    ABSTRACT: Owing to the wide use of novel nanoparticles (NPs) such as zinc oxide (ZnO) in all aspects of life, toxicological research on ZnO NPs is receiving increasing attention in these days. In this study, the toxicity of ZnO NPs in a human pulmonary adenocarcinoma cell line LTEP-a-2 was tested in vitro. Log-phase cells were exposed to different levels of ZnO NPs for hours, followed by colorimetric cell viability assay using tetrazolium salt and cell survival rate assay using trypan blue dye. Cell morphological changes were observed by Giemsa staining and light microscopy. Apoptosis was detected by using fluorescence microscopy and caspase-3 activity assay. Both intracellular reactive oxygen species (ROS) and reduced glutathione (GSH) were examined by a microplate-reader method. Results showed that ZnO NPs (≥0.01 μg/mL) significantly inhibited proliferation (P < 0.05) and induced substantial apoptosis in LTEP-a-2 cells after 4 h of exposure. The intracellular ROS level rose up to 30-40% corresponding to significant depletion (approximately 70-80%) in GSH content in LTEP-a-2 cells (P < 0.05), suggesting that ZnO NPs induced apoptosis mainly through increased ROS production. This study elucidates the toxicological mechanism of ZnO NPs in human pulmonary adenocarcinoma cells and provides reference data for application of nanomaterials in the environment.
    09/2015; 2015:423287. DOI:10.1155/2015/423287
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    • "Recent studies have shown that the toxicity of CNTs is determined by their morphology, number of the walls, and functional groups. Lam et al. [14] found that single walled carbon nanotubes are more toxic than carbon black in lungs, and SWNTs can induce dose-dependent epithelioid granulomas and interstitial inflammation in the animals. When carbon nanotubes were induced into the abdominal cavity of mice, they would result in asbestos-like, pathogenic behavior [15]. "
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    ABSTRACT: Single walled carbon nanotubes (SWNTs) decorated with polyhedral oligomeric silsesquioxane (POSS) were synthesized via the amide linkages between the acid treated SWNTs and amine-functionalized POSS. The successful modification of SWNTs with POSS was confirmed by Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), and UV-Vis spectra. The resulting SWNTs-POSS can be dispersed in both water and organic solutions. The biocompatibility and cytotoxicity of the SWNTs and SWNTs-POSS were evaluated by CCK-8 viability assays, which indicated that SWNTs-POSS exhibit very extremely low toxicity. The low toxicity of the POSS modified SWNTs leads to more opportunities for using carbon nanotubes in biomedical fields.
    Journal of Nanomaterials 01/2015; 2015:1-7. DOI:10.1155/2015/407437 · 1.64 Impact Factor
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    • "The biological effects of ENMs, including carbon nanotubes 55 (CNTs), remain poorly understood and are an object of debate 56 regardless of several attempts to fully characterize them 57 [7] [11] [12] [20] [23]. Despite this, it is commonly accepted that inhala- 58 tion of ENMs, the primary route of exposure for CNTs, can cause 59 major airway and lung disorders [4] [7] [12]. Recent research has 60 divulged potential harmful effects of CNTs in the lungs including 61 oxidative stress, inflammatory cytokine production, fibrosis, gran- 62 uloma formation, and lung cancer promotion [8] [16] [20] [31], while 63 other studies have found similar effects as a result of various alter- 64 native ENMs such as cerium dioxide [14] [15] and titanium dioxide 65 [3] [25]. "
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    ABSTRACT: Pulmonary barrier function plays a pivotal role in protection from inhaled particles. However, some nano-scaled particles, such as carbon nanotubes (CNT), have demonstrated the ability to penetrate this barrier in animal models, resulting in an unusual, rapid interstitial fibrosis. To delineate the underlying mechanism and specific bio-effect of inhaled nanoparticles in respiratory toxicity, models of lung epithelial barriers are required that allow accurate representation of in vivo systems; however, there is currently a lack of consistent methods to do so. Thus, this work demonstrates a well-characterized in vitro model of pulmonary barrier function using Calu-3 cells, and provides the experimental conditions required for achieving tight junction complexes in cell culture, with trans-epithelial electrical resistance measurement used as a biosensor for proper barrier formation and integrity. The effects of cell number and serum constituents have been examined and we found that changes in each of these parameters can greatly affect barrier formation. Our data demonstrate that use of 5.0x104 Calu-3 cells/well in the Transwell cell culture system, with 10% serum concentrations in culture media is optimal for assessing epithelial barrier function. In addition, we have utilized CNT exposure to analyze the dose-, time-, and nanoparticle property- dependent alterations of epithelial barrier permeability as a means to validate this model. Such high throughput in vitro cell models of the epithelium could be used to predict the interaction of other nanoparticles with lung epithelial barriers to mimic respiratory behavior in vivo, thus providing essential tools and bio-sensing techniques that can be uniformly employed.
    Sensing and Bio-Sensing Research 12/2014; 3. DOI:10.1016/j.sbsr.2014.12.002
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