No abstract

Nanomaterials are frontier technological products used in different manufactured goods. Because of their unique physicochemical, electrical, mechanical, and thermal properties, single-walled carbon nanotubes (SWCNT) are finding numerous applications in electronics, aerospace devices, computers, and chemical, polymer, and pharmaceutical industries. SWCNT are relatively recently discovered members of the carbon allotropes that are similar in structure to fullerenes and graphite. Previously, we (47) have reported that pharyngeal aspiration of purified SWCNT by C57BL/6 mice caused dose-dependent granulomatous pneumonia, oxidative stress, acute inflammatory/cytokine responses, fibrosis, and decrease in pulmonary function. To avoid potential artifactual effects due to instillation/agglomeration associated with SWCNT, we conducted inhalation exposures using stable and uniform SWCNT dispersions obtained by a newly developed aerosolization technique (2). The inhalation of nonpurified SWCNT (iron content of 17.7% by weight) at 5 mg/m(3), 5 h/day for 4 days was compared with pharyngeal aspiration of varying doses (5-20 microg per mouse) of the same SWCNT. The chain of pathological events in both exposure routes was realized through synergized interactions of early inflammatory response and oxidative stress culminating in the development of multifocal granulomatous pneumonia and interstitial fibrosis. SWCNT inhalation was more effective than aspiration in causing inflammatory response, oxidative stress, collagen deposition, and fibrosis as well as mutations of K-ras gene locus in the lung of C57BL/6 mice.

Size-fractionated aerosol particles were collected in a hospital emergency department to test for airborne influenza virus. Using real-time polymerase chain reaction, we confirmed the presence of airborne influenza virus and found that 53% of detectable influenza virus particles were within the respirable aerosol fraction. Our results provide evidence that influenza virus may spread through the airborne route.

ABSTRACT. Oral and nas al airways are entryways to the respiratory tract. Most people breathe through the nasal airway during rest or light exercise, then switch to oral r r r r r nasal breathing during heavy exercise or work. Resistance through the oral airways is much lower than through the n asal airways , so fewer aerosol particles are deposited in the oral airways. Aerosol drugs are usually delivered by inhalation to the lung via the oral route for that reason. Oral deposition data from humans are limited, and those available show great intersubject variability. The purpose of this study was to investigate the effects of particle size and breathing rate on the deposition pattern in a human or al airway cast with a de® ned geometry. The airway replica included the oral cavity, ph arynx, larynx, trachea, an d 3 generations of bronchi. The oral portion of the cast was molded from a dental impression of the oral cavity in a hum an volunteer, while the other airway portions of the cast were made from a cadaver. Nine different sizes of polystyrene latex¯uorescent particles in the size ran ge of 0.93± 30 m m were used in the study. Regional deposition was measured at a constant inspiratory¯ow rate of 15, 30, and 60 L min I 1 . Deposition in the oral airway appeared to increase with an increasinḡ ow rate an d particle diameter. Deposition at the highest¯ow rate of 60 L min I 1 was close to 90% for particles ) 20 m m. Particles ) about 10 m m deposited mainly in the oral cavity. Deposition ef® ciency has been found to be a unique function of the Stokes number, suggesting that impaction is the dominant deposition mech anism. Oral deposition can be approximated by a theoretical deposition model of inertial impaction in a 1808 curved tube, assuming perfect mixing in a turbulent ow. Our model suggests th at the minimum dimension near the larynx and the average cross-sectional area are important parameters for oral airway deposition; however, addition al data from the oral airway replica are needed to ascertain wh ether these are indeed the critical dimensions. Information from the present study will add to our knowledge of the deposition mech anism, the correlation of particle deposition with airway geometry, and eventually the best way to deliver aerosol drugs.

Background : We have shown that pulmonary exposure to fine particulate matter (PM) impairs endothelium dependent dilation in systemic arterioles. Ultrafine PM has been suggested to be inherently more toxic by virtue of its increased surface area. The purpose of this study was to determine if ultrafine PM (or nanoparticle) inhalation produces greater microvascular dysfunction than fine PM. Rats were exposed to fine or ultrafine TiO 2 aerosols (primary particle diameters of 1 µm and ~21 nm, respectively) at concentrations which do not alter bronchoalveolar lavage markers of pulmonary inflammation or lung damage.

BackgroundEngineered carbon nanotubes are currently used in many consumer and industrial products such as paints, sunscreens, cosmetics, toiletries, electronic processes and industrial lubricants. Carbon nanotubes are among the more widely used nanoparticles and come in two major commercial forms, single-walled carbon nanotubes (SWCNT) and the more rigid, multi-walled carbon nanotubes (MWCNT). The low density and small size of these particles makes respiratory exposures likely. Many of the potential health hazards have not been investigated, including their potential for carcinogenicity. We, therefore, utilized a two stage initiation/promotion protocol to determine whether inhaled MWCNT act as a complete carcinogen and/or promote the growth of cells with existing DNA damage. Six week old, male, B6C3F1 mice received a single intraperitoneal (ip) injection of either the initiator methylcholanthrene(MCA, 10 μg/g BW, i.p.), or vehicle (corn oil). One week after i.p. injections, mice were exposed by inhalation to MWCNT (5 mg/m3, 5 hours/day, 5 days/week) or filtered air (controls) for a total of 15 days. At 17 months post-exposure, mice were euthanized and examined for lung tumor formation.ResultsTwenty-three percent of the filtered air controls, 26.5% of the MWCNT-exposed, and 51.9% of the MCA-exposed mice, had lung bronchiolo-alveolar adenomas and lung adenocarcinomas. The average number of tumors per mouse was 0.25, 0.81 and 0.38 respectively. By contrast, 90.5% of the mice which received MCA followed by MWCNT had bronchiolo-alveolar adenomas and adenocarcinomas with an average of 2.9 tumors per mouse 17months after exposure. Indeed, 62% of the mice exposed to MCA followed by MWCNT had bronchiolo-alveolar adenocarcinomas compared to 13% of the mice that received filtered air, 22% of the MCA-exposed, or 14% of the MWCNT-exposed. Mice with early morbidity resulting in euthanasia had the highest rate of metastatic disease. Three mice exposed to both MCA and MWCNT that were euthanized early had lung adenocarcinoma with evidence of metastasis (5.5%). Five mice (9%) exposed to MCA and MWCNT and 1 (1.6%) exposed to MCA developed serosal tumors morphologically consistent with sarcomatous mesotheliomas, whereas mice administered MWCNT or air alone did not develop similar neoplasms.ConclusionsThese data demonstrate that some MWCNT exposures promote the growth and neoplastic progression of initiated lung cells in B6C3F1 mice. In this study, the mouse MWCNT lung burden of 31.2 μg/mouse approximates feasible human occupational exposures. Therefore, the results of this study indicate that caution should be used to limit human exposures to MWCNT.

This study investigated the in vivo pulmonary toxicity of inhaled multi-walled carbon nanotubes (MWCNT). Mice-inhaled aerosolized MWCNT (10 mg/m³, 5 h/day) for 2, 4, 8 or 12 days. MWCNT lung burden was linearly related to exposure duration. MWCNT-induced pulmonary inflammation was assessed by determining whole lung lavage (WLL) polymorphonuclear leukocytes (PMN). Lung cytotoxicity was assessed by WLL fluid LDH activities. WLL fluid albumin concentrations were determined as a marker of alveolar air-blood barrier integrity. These parameters significantly increased in MWCNT-exposed mice versus controls and were dose-dependent. Histopathologic alterations identified in the lung included (1) bronciolocentric inflammation, (2) bronchiolar epithelial hyperplasia and hypertrophy, (3) fibrosis, (4) vascular changes and (5) rare pleural penetration. MWCNT translocated to the lymph node where the deep paracortex was expanded after 8 or 12 days. Acute inhalation of MWCNT induced dose-dependent pulmonary inflammation and damage with rapid development of pulmonary fibrosis, and also demonstrated that MWCNT can reach the pleura after inhalation exposure.

Airborne particles containing influenza and RSV RNA were detected throughout a health care facility. The particles were small enough to remain airborne for an extended time and to be inhaled deeply into the respiratory tract. These results support the possibility that influenza and RSV can be transmitted by the airborne route and suggest that further investigation of the potential of these particles to transmit infection is warranted.