Pulmonary toxicity screening studies in male rats with TiO(2 )particulates substantially encapsulated with pyrogenically deposited, amorphous silica

The aim of this study was to evaluate the acute lung toxicity in rats of intratracheally instilled TiO(2 )particles that have been substantially encapsulated with pyrogenically deposited, amorphous silica. Groups of rats were intratracheally instilled either with doses of 1 or 5 mg/kg of hydrophilic Pigment A TiO(2 )particles or doses of 1 or 5 mg/kg of the following control or particle-types: 1) R-100 TiO(2 )particles (hydrophilic in nature); 2) quartz particles, 3) carbonyl iron particles. Phosphate-buffered saline (PBS) instilled rats served as additional 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 hrs, 1 week, 1 month and 3 months. The bronchoalveolar lavage results demonstrated that lung exposures to quartz particles, at both concentrations but particularly at the higher dose, produced significant increases vs. controls in pulmonary inflammation and cytotoxicity indices. Exposures to Pigment A or R-100 TiO(2 )particles produced transient inflammatory and cell injury effects at 24 hours postexposure (pe), but these effects were not sustained when compared to quartz-related effects. Exposures to carbonyl iron particles or PBS resulted only in minor, short-term and reversible lung inflammation, likely related to the effects of the instillation procedure. Histopathological analyses of lung tissues revealed that pulmonary exposures to Pigment A TiO(2 )particles produced minor inflammation at 24 hours postexposure and these effects were not significantly different from exposures to R-100 or carbonyl iron particles. Pigment A-exposed lung tissue sections appeared normal at 1 and 3 months postexposure. In contrast, pulmonary exposures to quartz particles in rats produced a dose-dependent lung inflammatory response characterized by neutrophils and foamy (lipid-containing) alveolar macrophage accumulation as well as evidence of early lung tissue thickening consistent with the development of pulmonary fibrosis. Based on our results, we conclude the following: 1) Pulmonary instillation exposures to Pigment A TiO(2 )particles at 5 mg/kg produced a transient lung inflammatory response which was not different from the lung response to R-100 TiO(2 )particles or carbonyl iron particles; 2) the response to Pigment A was substantially less active in terms of inflammation, cytotoxicity, and fibrogenic effects than the positive control particle-type, quartz particles. Thus, based on the findings of this study, we would expect that inhaled Pigment A TiO(2 )particles would have a low risk potential for producing adverse pulmonary health effects

Particle length-dependent titanium dioxide nanomaterials toxicity and bioactivity

<p>Abstract</p> <p>Background</p> <p>Titanium dioxide (TiO₂) nanomaterials have considerable beneficial uses as photocatalysts and solar cells. It has been established for many years that pigment-grade TiO₂(200 nm sphere) is relatively inert when internalized into a biological model system (in vivo or in vitro). For this reason, TiO₂nanomaterials are considered an attractive alternative in applications where biological exposures will occur. Unfortunately, metal oxides on the nanoscale (one dimension < 100 nm) may or may not exhibit the same toxic potential as the original material. A further complicating issue is the effect of modifying or engineering of the nanomaterial to be structurally and geometrically different from the original material.</p> <p>Results</p> <p>TiO₂nanospheres, short (< 5 μm) and long (> 15 μm) nanobelts were synthesized, characterized and tested for biological activity using primary murine alveolar macrophages and in vivo in mice. This study demonstrates that alteration of anatase TiO₂nanomaterial into a fibre structure of greater than 15 μm creates a highly toxic particle and initiates an inflammatory response by alveolar macrophages. These fibre-shaped nanomaterials induced inflammasome activation and release of inflammatory cytokines through a cathepsin B-mediated mechanism. Consequently, long TiO₂nanobelts interact with lung macrophages in a manner very similar to asbestos or silica.</p> <p>Conclusions</p> <p>These observations suggest that any modification of a nanomaterial, resulting in a wire, fibre, belt or tube, be tested for pathogenic potential. As this study demonstrates, toxicity and pathogenic potential change dramatically as the shape of the material is altered into one that a phagocytic cell has difficulty processing, resulting in lysosomal disruption.</p

“Nanostandardization” in action: implementing standardization processes in a multidisciplinary nanoparticle-based research and development project

Nanomaterials have attracted much interest in the medical field and related applications as their distinct properties in the nano-range enable new and improved diagnosis and therapies. Owing to these properties and their potential interactions with the human body and the environment, the impact of nanomaterials on humans and their potential toxicity have been regarded a very significant issue. Consequently, nanomaterials are the subject of a wide range of cutting-edge research efforts in the medical and related fields to thoroughly probe their potential beneficial utilizations and their more negative effects. We posit that the lack of standardization in the field is a serious shortcoming as it has led to the establishment of methods and results that do not ensure sufficient consistency and thus in our view can possibly result in research outputs that are not as robust as they should be. The main aim of this article is to present how NanoDiaRA, a large FP7 European multidisciplinary project that seeks to investigate and develop nanotechnology-based diagnostic systems, has developed and implemented robust, standardized methods to support research practices involving the engineering and manipulation of nanomaterials. First, to contextualize this research, an overview of the measures defined by different regulatory bodies concerning nano-safety is presented. Although these authorities have been very active in the past several years, many questions remain unanswered in our view. Second, a number of national and international projects that attempted to ensure more reliable exchanges of methods and results are discussed. However, the frequent lack of publication of procedures and protocols in research can often be a hindrance for sharing those good practices. Subsequently, the efforts made through NanoDiaRA to introduce standardized methods and techniques to support the development and utilization of nanomaterials are discussed in depth. A series of semi-structured interviews were conducted with the partners of this project, and the interviews were analyzed thematically to highlight the determined efforts of the researchers to standardize their methods. Finally, some recommendations are made towards the setting up of well-defined methods to support the high-quality work of collaborative nanoparticle-based research and development projects and to enhance standardization processes

Pulmonary and systemic responses of highly pure and well-dispersed single-wall carbon nanotubes after intratracheal instillation in rats

The present study was conducted to assess the pulmonary and systemic responses in rats after intratracheal instillation of highly pure, well-dispersed, and well-characterized SWCNTs. Exposure to SWCNTs up to 2mg/kg did not produce mortality, changes in clinical signs, or body weights during the observation period. Dose-dependent changes were observed in the lung weight, BALF inflammatory cells, and biochemical parameters such as LDH value, protein content, IL-1β and IL-6 activity, and histopathology. In the 0.04 mg/kg SWCNT-exposed group, almost no changes were observed during the observation period. In the 0.2 mg/kg SWCNT-exposed group, pulmonary inflammatory responses were observed after instillation. In the 1 mg/kg and 2 mg/kg SWCNT-exposed group, acute lung inflammation and subsequent granuloma accompanied by increased lung weights were observed. Furthermore, the histopathological findings in the lungs of rats exposed to SWCNTs showed inflammatory responses related with the vital reaction to the foreign substance that was instilled intratracheally, and there were no fibrosis, atypical lesion, or tumor-related findings even at the highest dose (2 mg/kg) of SWCNT-exposed groups up to 6 months after instillation. For all groups, histopathological changes due to the instillation exposure of SWCNTs were observed only in the lungs and lung-associated lymph nodes and not in the other tissues examined (i.e. the liver, kidney, spleen, and cerebrum)

Vapor phase mediated cellular uptake of sub 5 nm nanoparticles

Nanoparticles became an important and wide-used tool for cell imaging because of their unique optical properties. Although the potential of nanoparticles (NPs) in biology is promising, a number of questions concerning the safety of nanomaterials and the risk/benefit ratio of their usage are open. Here, we have shown that nanoparticles produced from silicon carbide (NPs) dispersed in colloidal suspensions are able to penetrate into surrounding air environment during the natural evaporation of the colloids and label biological cells via vapor phase. Natural gradual size-tuning of NPs in dependence to the distance from the NP liquid source allows progressive shift of the fluorescence color of labeled cells in the blue region according to the increase of the distance from the NP suspension. This effect may be used for the soft vapor labeling of biological cells with the possibility of controlling the color of fluorescence. However, scientists dealing with the colloidal NPs have to seriously consider such a NP's natural transfer in order to protect their own health as well as to avoid any contamination of the control samples

Assessment of the potential in vivo ecotoxicity of Double-Walled Carbon Nanotubes (DWNTs) in water, using the amphibian Ambystoma mexicanum

Because of their specific properties (mechanical, electrical, etc), carbon nanotubes (CNTs) are being assessed for inclusion in many manufactured products. Due to their massive production and number of potential applications, the impact of CNTs on the environment must be taken into consideration. The present investigation evaluates the ecotoxic potential of CNTs in the amphibian larvae (Ambystoma mexicanum). Acute toxicity and genotoxicity were analysed after 12 days of exposure in laboratory conditions. The genotoxic effects were analysed by scoring the micronucleated erythrocytes in the circulating blood of the larvae according to the French standard micronucleus assay. The results obtained in the present study demonstrated that CNTs are neither acutely toxic nor genotoxic to larvae whatever the CNTs concentration in the water, although black masses of CNTs were observed inside the gut. In the increasing economical context of CNTs, complementary studies must be undertaken, especially including mechanistic and environmental investigations

Nanoquartz in Late Permian C1 coal and the high incidence of female lung cancer in the Pearl River Origin area: a retrospective cohort study

<p>Abstract</p> <p>Background</p> <p>The Pearl River Origin area, Qujing District of Yunnan Province, has one of the highest female lung cancer mortality rates in China. Smoking was excluded as a cause of the lung cancer excess because almost all women were non-smokers. Crystalline silica embedded in the soot emissions from coal combustion was found to be associated with the lung cancer risk in a geographical correlation study. Lung cancer rates tend to be higher in places where the Late Permian C1 coal is produced. Therefore, we have hypothesized the two processes: C1 coal combustion --> nanoquartz in ambient air --> lung cancer excess in non-smoking women.</p> <p>Methods/Design</p> <p>We propose to conduct a retrospective cohort study to test the hypothesis above. We will search historical records and compile an inventory of the coal mines in operation during 1930–2009. To estimate the study subjects' retrospective exposure, we will reconstruct the historical exposure scenario by burning the coal samples, collected from operating or deserted coal mines by coal geologists, in a traditional firepit of an old house. Indoor air particulate samples will be collected for nanoquartz and polycyclic aromatic hydrocarbons (PAHs) analyses. Bulk quartz content will be quantified by X-ray diffraction analysis. Size distribution of quartz will be examined by electron microscopes and by centrifugation techniques. Lifetime cumulative exposure to nanoquartz will be estimated for each subject. Using the epidemiology data, we will examine whether the use of C1 coal and the cumulative exposure to nanoquartz are associated with an elevated risk of lung cancer.</p> <p>Discussion</p> <p>The high incidence rate of lung cancer in Xuan Wei, one of the counties in the current study area, was once attributed to high indoor air concentrations of PAHs. The research results have been cited for qualitative and quantitative cancer risk assessment of PAHs by the World Health Organization and other agencies. If nanoquartz is found to be the main underlying cause of the lung cancer epidemic in the study area, cancer potency estimates for PAHs by the international agencies based on the lung cancer data in this study setting should then be updated.</p

Loss of Proliferation and Antigen Presentation Activity following Internalization of Polydispersed Carbon Nanotubes by Primary Lung Epithelial Cells

Interactions between poly-dispersed acid functionalized single walled carbon nanotubes (AF-SWCNTs) and primary lung epithelial (PLE) cells were studied. Peritoneal macrophages (PMs, known phagocytic cells) were used as positive controls in this study. Recovery of live cells from cultures of PLE cells and PMs was significantly reduced in the presence of AF-SWCNTs, in a time and dose dependent manner. Both PLE cells as well as PMs could take up fluorescence tagged AF-SWCNTs in a time dependent manner and this uptake was significantly blocked by cytochalasin D, an agent that blocks the activity of acto-myosin fibers and therefore the phagocytic activity of cells. Confocal microscopic studies confirmed that AF-SWCNTs were internalized by both PLE cells and PMs. Intra-trachially instilled AF-SWCNTs could also be taken up by lung epithelial cells as well as alveolar macrophages. Freshly isolated PLE cells had significant cell division activity and cell cycling studies indicated that treatment with AF-SWCNTs resulted in a marked reduction in S-phase of the cell cycle. In a previously standardized system to study BCG antigen presentation by PLE cells and PMs to sensitized T helper cells, AF-SWCNTs could significantly lower the antigen presentation ability of both cell types. These results show that mouse primary lung epithelial cells can efficiently internalize AF-SWCNTs and the uptake of nanotubes interfered with biological functions of PLE cells including their ability to present BCG antigens to sensitized T helper cells

Comparison of dust released from sanding conventional and nanoparticle-doped wall and wood coatings

Introduction of engineered nanoparticles (ENPs) into traditional surface coatings (e.g., paints, lacquers, fillers) may result in new exposures to both workers and consumers and possibly also a new risk to their health. During finishing and renovation, such products may also be a substantial source of exposure to ENPs or aggregates thereof. This study investigates the particle size distributions (5.6 nm–19.8 μm) and the total number of dust particles generated during sanding of ENP-doped paints, lacquers, and fillers as compared to their conventional counterparts. In all products, the dust emissions from sanding were found to consist of five size modes: three modes under 1 μm and two modes around 1 and 2 μm. Corrected for the emission from the sanding machine, the sanding dust, was dominated by 100–300 nm size particles, whereas the mass and surface area spectra were dominated by the micrometer modes. Adding ENPs to the studied products only vaguely affected the geometric mean diameters of the particle modes in the sanding dust when compared to their reference products. However, we observed considerable differences in the number concentrations in the different size modes, but still without revealing a clear effect of ENPs on dust emissions from sanding