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Translocation pathway of the intratracheally instilled ultrafine particles from the lung into the blood circulation in the mouse
- Toxicol Pathol
, 2006
"... Ultrafine particles are ubiquitous in ambient urban and indoor air from multiple sources and may contribute to adverse respiratory and cardiovascular diseases. Recently, it has been demonstrated that ultrafine particles (UFPs) are translocated from the lung into the systemic circula-tion. The exact ..."
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Ultrafine particles are ubiquitous in ambient urban and indoor air from multiple sources and may contribute to adverse respiratory and cardiovascular diseases. Recently, it has been demonstrated that ultrafine particles (UFPs) are translocated from the lung into the systemic circula-tion. The exact pathway, however, for the translocation in the lung remains unclear. In this study, we examined the translocation pathway of intra-tracheally instilled C60 fullerene particles from the lung into the blood circulation in the mouse. Using light microscopy, aggregated particles of fullerene were observed in the capillary lumen in the lung and the pulmonary lymph nodes immediately after instillation. Electron microscopic anal-ysis demonstrated an increased number of pinocytotic vesicles (caveolae) of various sizes in the type 1 alveolar epithelial cells (AEC) and endothelial cells; occasional caveolae containing some particulate substances were observed. In addition, particles of various sizes were observed throughout the structure of the air-blood barrier (ABB). These findings suggest that fullerene particles may pass the ABB by both diffusion and caveolae-mediated pinocytosis, resulting in immediate translocation into the systemic circulation.
Research Exposure to Ultrafine Particles from Ambient Air and Oxidative Stress–Induced DNA Damage
"... through generation of oxidative stress, with resulting damage to DNA and other macromolecules. OBJECTIVE: We investigated oxidative damage to DNA and related repair capacity in peripheral blood mononuclear cells (PBMCs) during controlled exposure to urban air particles with assignment of number conc ..."
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through generation of oxidative stress, with resulting damage to DNA and other macromolecules. OBJECTIVE: We investigated oxidative damage to DNA and related repair capacity in peripheral blood mononuclear cells (PBMCs) during controlled exposure to urban air particles with assignment of number concentration (NC) to four size modes with average diameters of 12, 23, 57, and 212 nm. DESIGN. Twenty-nine healthy adults participated in a randomized, two-factor cross-over study with or without biking exercise for 180 min and with exposure to particles (NC 6169-15362/cm3) or filtered air (NC 91-542/cm3) for 24 hr. METHODS: The levels of DNA strand breaks (SBs), oxidized purines as formamidopyrimidine DNA glycolase (FPG) sites, and activity of 7,8-dihydro-8-oxoguanine-DNA glycosylase (OGG1) in PBMCs were measured by the Comet assay. mRNA levels of OGG1, nucleoside diphosphate linked moiety X-type motif 1 (NUDT1), and heme oxygenase-1 (HO1) were determined by real-time reverse transcriptase–polymerase chain reaction. RESULTS: Exposure to UFPs for 6 and 24 hr significantly increased the levels of SBs and FPG sites, with a further insignificant increase after physical exercise. The OGG1 activity and expression of
Research Metal Oxide Nanoparticles Induce Unique Inflammatory Footprints in the Lung: Important Implications for Nanoparticle Testing
"... Ba c k g r o u n d: Metal oxide nanoparticles (NPs) have been widely used in industry, cosmetics, and biomedicine. Objectives: We examined hazards of several well-characterized high production volume NPs because of increasing concern about occupational exposure via inhalation. Met h o d s: A panel o ..."
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Cited by 9 (0 self)
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Ba c k g r o u n d: Metal oxide nanoparticles (NPs) have been widely used in industry, cosmetics, and biomedicine. Objectives: We examined hazards of several well-characterized high production volume NPs because of increasing concern about occupational exposure via inhalation. Met h o d s: A panel of well-characterized NPs [cerium oxide (CeO2NP), titanium dioxide (TiO2NP), carbon black (CBNP), silicon dioxide (SiO2NP), nickel oxide (NiONP), zinc oxide (ZnONP), copper oxide (CuONP), and amine-modified polystyrene beads] was instilled into lungs of rats. We evaluated the inflammation potencies of these NPs 24 hr and 4 weeks postinstillation. For NPs that caused significant inflammation at 24 hr, we then investigated the characteristics of the inflammation. All exposures were carried out at equal-surface-area doses. Res u l t s: Only CeO2NP, NiONP, ZnONP, and CuONP were inflammogenic to the lungs of rats at the high doses used. Strikingly, each of these induced a unique inflammatory footprint both acutely (24 hr) and chronically (4 weeks). Acutely, patterns of neutrophil and eosinophil infiltrates differed after CeO2NP, NiONP, ZnONP, and CuONP treatment. Chronic inflammatory responses also differed after 4 weeks, with neutrophilic, neutrophilic/lymphocytic, eosinophilic/
Hellweg S: Exposure to manufactured nanostructured particles in an industrial pilot plant. Ann Occup Hyg 2008
"... materials are increasing. Yet, little is known on the association between exposure and corre-sponding risks, such as pulmonary inflammation and oxidative stress. Methods: Condensation Particle Counters, a DustTrak and Scanning Mobility Particle Sizer quantified real-time size, mass and number conc ..."
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Cited by 9 (1 self)
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materials are increasing. Yet, little is known on the association between exposure and corre-sponding risks, such as pulmonary inflammation and oxidative stress. Methods: Condensation Particle Counters, a DustTrak and Scanning Mobility Particle Sizer quantified real-time size, mass and number concentrations in a nanostructure particle pilot-scale production facility, using a high-temperature gas-phase process, over a 25-day pe-riod. Temporal and spatial analysis of particle concentrations and sizes was performed during production, maintenance and handling. Number-based particle retention of breathing mask fil-ters used under real-time production and exposure conditions in the workplace was quantified. Results: The results demonstrate elevated number concentrations during production, which can be an order of magnitude higher than background levels. Average concentrations during production were 59 100 cm23 and 0.188 mg m23 for submicron particles. Mask filters de-creased particle number concentrations by>96%. Conclusions: This study demonstrates real-time worker exposure during gas-phase nanopar-ticle manufacturing. Qualitative and quantitative analysis of emission sources and concentra-tion levels in a production plant is accomplished. These results are important for workers, employers and regulators in the nanotechnology field as they provide information on encoun-tered exposures and possibilities for mitigation measures.
Electrical Mobility Spectrometer Using a Diethylene Glycol Condensation Particle Counter for Measurement of Aerosol Size Distributions Down to 1 nm. Aerosol Sci.
, 2011
"... We report a new scanning mobility particle spectrometer (SMPS) for measuring number size distributions of particles down to ∼1 nm mobility diameter. This SMPS includes an aerosol charger, a TSI 3085 nano differential mobility analyzer (nanoDMA), an ultrafine condensation particle counter (UCPC) usi ..."
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We report a new scanning mobility particle spectrometer (SMPS) for measuring number size distributions of particles down to ∼1 nm mobility diameter. This SMPS includes an aerosol charger, a TSI 3085 nano differential mobility analyzer (nanoDMA), an ultrafine condensation particle counter (UCPC) using diethylene glycol (DEG) as the working fluid, and a conventional butanol CPC (the "booster") to detect the small droplets leaving the DEG UCPC. The response of the DEG UCPC to negatively charged sodium chloride particles with mobility diameters ranging from 1-6 nm was measured. The sensitivity of the DEG UCPC to particle composition was also studied by comparing its response to positively charged 1.47 and 1.70 nm tetra-alkyl ammonium ions, sodium chloride, and silver particles. A high resolution differential mobility analyzer was used to generate the test particles. These results show that the response of this UCPC to sub-2 nm particles is sensitive to particle composition. The applicability of the new SMPS for atmospheric measurement was demonstrated during the Nucleation and Cloud Condensation Nuclei (NCCN) field campaign (Atlanta, Georgia, summer 2009). We operated the instrument at saturator and condenser temperatures that allowed the efficient detection of sodium chloride particles but not of air ions having the same mobility. We found that particles as small as 1 nm were detected during nucleation events but not at other times. Factors affecting size distribution measurements, including aerosol charging in the 1-10 nm size range, are discussed. For the charger used in this study, bipolar charging was found to be more effective for sub-2 nm particles than unipolar charging. No ion induced nucleation inside the charger was observed during the NCCN campaign.
Cellular Response to Diesel Exhaust Particles Strongly Depends on the Exposure Method
, 2008
"... In vitro exposure to aerosols at the air–liquid interface (ALI) preserves the physical and chemical characteristics of aerosol particles. Although frequently described as being a more physiologic exposure method, ALI exposure has not been directly compared with conventional in vitro exposures where ..."
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In vitro exposure to aerosols at the air–liquid interface (ALI) preserves the physical and chemical characteristics of aerosol particles. Although frequently described as being a more physiologic exposure method, ALI exposure has not been directly compared with conventional in vitro exposures where the particles are suspended in medium. We exposed immortalized human bronchial epithelial cells (16HBE14o) to aerosolized diesel exhaust particles at the ALI and to suspensions of collected particles. The response of the cells was determined from measurements of the cell viability and interleukin-8 (IL-8) secretion. The deposited size distribution at the cell surface was measured with transmission electron microscopy to obtain a dose for the ALI exposure. Although exposure by either method caused a slight decrease in cell viability and induced IL-8 secretion, the response to ALI exposure occurred at doses several orders of magnitude lower than
Research Efficient Elimination of Inhaled Nanoparticles from the Alveolar Region: Evidence for Interstitial Uptake and Subsequent Reentrainment onto Airways Epithelium
"... BACKGROUND: There is ongoing discussion that inhaled nanoparticles (NPs, < 100 nm) may translocate from epithelial deposition sites of the lungs to systemic circulation. OBJECTIVES AND METHODS: We studied the disappearance of NPs from the epithelium by sequential lung retention and clearance and ..."
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BACKGROUND: There is ongoing discussion that inhaled nanoparticles (NPs, < 100 nm) may translocate from epithelial deposition sites of the lungs to systemic circulation. OBJECTIVES AND METHODS: We studied the disappearance of NPs from the epithelium by sequential lung retention and clearance and bronchoalveolar lavage (BAL) measurements in healthy adult Wistar Kyoto (WKY) rats at various times over 6 months after administration of a single 60- to 100-min intratracheal inhalation of iridium-192 ( 192Ir)–radiolabeled NPs. A complete 192Ir balance of all organs, tissues, excretion, remaining carcass, and BAL was performed at each time point. RESULTS: Directly after inhalation we found free NPs in the BAL; later, NPs were predominantly associated with alveolar macropages (AMs). After 3 weeks, lavageable NP fractions decreased to 0.06 of the actual NP lung burden. This is in stark contrast to the AM-associated fraction of micron-sized particles reported in the literature. These particles remained constant at about 0.8 throughout a 6-month period. Three weeks after inhalation, 80 % of the retained Ir NPs was translocated into epithelium and interstitium. CONCLUSION: There is a strong size-selective difference in particle immobilization. Furthermore, AM-mediated NP transport to the larynx originates not only from the NP fraction retained on the
Nanotoxicology—A pathologist’s perspective
- Toxicol Pathol
, 2011
"... Advances in chemistry and engineering have created a new technology, nanotechnology, involving the tiniest known manufactured products. These products have a rapidly increasing market share and appear poised to revolutionize engineering, cosmetics, and medicine. Unfortunately, nano-toxicology, the s ..."
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Advances in chemistry and engineering have created a new technology, nanotechnology, involving the tiniest known manufactured products. These products have a rapidly increasing market share and appear poised to revolutionize engineering, cosmetics, and medicine. Unfortunately, nano-toxicology, the study of nanoparticulate health effects, lags behind advances in nanotechnology. Over the past decade, existing literature on ultrafine particles and respirable durable fibers has been supplemented by studies of first-generation nanotechnology products. These studies suggest that nanosizing increases the toxicity of many particulates. First, as size decreases, surface area increases, thereby speeding up dissolution of soluble particulates and exposing more of the reactive surface of durable but reactive particulates. Second, nanosizing facilitates movement of particulates across cellular and intracellular barriers. Third, nanosizing allows particulates to interact with, and sometimes even hybridize with, subcellular struc-tures, including in some cases microtubules and DNA. Finally, nanosizing of some particulates, increases pathologic and physiologic responses, including inflammation, fibrosis, allergic responses, genotoxicity, and carcinogenicity, and may alter cardiovascular and lymphatic function. Know-ing how the size and physiochemical properties of nanoparticulates affect bioactivity is important in assuring that the exciting new products of nano-technology are used safely. This review provides an introduction to the pathology and toxicology of nanoparticulates.
Coping with uncertainty: Assessing nanotechnologies in a citizen panel
- in Switzerland. In: Public Understanding of Science (http://pus.sagepub.com/content/18/5/498) published 3.01.2012
, 2009
"... a citizen panel in Switzerland ..."
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Research Long-Term Inhalation Exposure to Nickel Nanoparticles Exacerbated Atherosclerosis in a Susceptible Mouse Model
"... Ba c k g r o u n d: Because associations have been reported between inhaled ambient ultrafine particles and increased risk of cardiopulmonary disease, it has been suggested that inhaled engineered nanoparticles (NPs) may also induce adverse effects on the cardiovascular system. Obj e c t i v e: We e ..."
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Ba c k g r o u n d: Because associations have been reported between inhaled ambient ultrafine particles and increased risk of cardiopulmonary disease, it has been suggested that inhaled engineered nanoparticles (NPs) may also induce adverse effects on the cardiovascular system. Obj e c t i v e: We examined the long-term cardiovascular effects of inhaled nickel hydroxide NPs (nano‑NH) using a sensitive mouse model. Met h o d s: Hyperlipidemic, apoprotein E-deficient (ApoE –/ – ) mice were exposed to nano‑NH at either 0 or 79 μg Ni/m 3, via a whole-body inhalation system, for 5 hr/day, 5 days/week, for either 1 week or 5 months. We measured various indicators of oxidative stress and inflammation in the lung and cardiovascular tissue, and we determined plaque formation on the ascending aorta. Results: Inhaled nano‑NH induced significant oxidative stress and inflammation in the pulmonary and extrapulmonary organs, indicated by up‑regulated mRNA levels of certain antioxidant enzyme and inflammatory cytokine genes; increased mitochondrial DNA damage in the aorta; significant signs of inflammation in bronchoalveolar lavage fluid; changes in lung histopathology; and induction of acute-phase response. In addition, after 5-month exposures, nano‑NH exacerbated the progression of atherosclerosis in ApoE –/ – mice. Con c l u s i o n s: This is the first study to report long-term cardiovascular toxicity of an inhaled nanomaterial. Our results clearly demonstrate that long-term exposure to inhaled nano‑NH can induce oxidative stress and inflammation, not only in the lung but also in the cardiovascular system, and that this stress and inflammation can ultimately contribute to progression of atherosclerosis in ApoE –/ – mice. Key w o r d s: atherosclerosis, cardiovascular toxicity, inhalation, nanoparticles, nickel. Environ
