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Pulmonary absorption of carboxyfluorescein in the rat.

The pulmonary absorption of the fluorescent marker 6-carboxyfluorescein (CF) has been characterized. CF was administered intratracheally (i.t.) as a fluid instillate to pentobarbitone-anaesthetized rats at doses of 0.5 and 2 mg kg-1. The absorption was characterized by both model-independent and model-dependent pharmacokinetic analyses of blood concentration data with reference to previous intravenous (i.v.) studies. The mean fraction available (F) of CF was 90 and 112% with a mean absorption time of 107 and 109 min for the lower and higher doses, respectively. The terminal half-life for the i.t. administered CF (73 and 83 min for the 0.5 and 2 mg kg-1 doses, respectively) was significantly longer (P less than 0.001) than after i.v. dosing (18 min). This indicates a slow pulmonary absorption of CF. Blood concentration-time profiles could not be adequately described by models involving a simple first-order absorption process; a model incorporating two simultaneous first-order inputs gave a much better description, its absorption rate constants differing by almost two orders of magnitude.

Absorption↗

Pulmonary toxicity of dust generated during weaving of carpets.

The dust generated during weaving (carpet dust) tibbati, knotted and tuffted carpets in carpet industry was studied for its toxicity in vitro and in vivo. Carpet dust (0.5, 1.0, 2.5 and 5.0 mg/1 x 10(6) cells) caused in vitro cytotoxicity in rat alveolar macrophages (AM) in a concentration-dependent manner. The cytotoxic, inflammatory and oxidative responses were observed in bronchoalveolar lavage fluid (BALF) of rats at 1, 4, 8 and 16 days after exposure. Rats were intratracheally exposed at 5 mg/rat individually to all three types of carpet dust. All types of carpet dusts produced increased AM, lymphocytes (PMN) population in BALF suggesting their inflammatory reactions. Cytotoxic nature of carpet dust was shown by the increased activities of lactate dehydrogenase (LDH) and acid phosphatase (AP) in BALF. Increased AM population and in vitro cytotoxicity due to carpet dusts have shown some correlation with the levels of LDH and AP activities in BALF. The gradual enhanced profile of hydrogen peroxide (H2O2) and nitric oxide (NO) along with depletion of reduced glutathione (GSH) in AM due to these carpet dusts are suggestive of their oxidant nature. The enzyme activities of both glutathione peroxidase (GPx) and glutathione reductase (GR) in AM were marginally reduced in exposed rats. In conclusion, the data suggest the cytotoxic, inflammatory and oxidant nature of carpet dusts. It is extrapolated that health effects on carpet weavers would be associated with the concentration and nature of airborne dust generated during weaving of carpets.

Acid Phosphatase↗

Toxicity of a low level of indium phosphide (InP) in rats after intratracheal instillation.

To clarify the instillation toxicity of low level of indium phosphide (InP), 0, 1.2, 6.0 and 62.0 micrograms/kg body weight of InP particles were instilled intratracheally in male Fischer 344 rats, and the effects of InP were examined on the following day (day 1) and on the 8th day (day 8) after instillation. Indium was measured but not detected in the serum, liver, kidney, spleen, thymus and brain. Dose-related mild elevation of superoxide dismutase (SOD) activity and lactate dehydrogenase (LDH) activity in bronchoalveolar lavage fluid (BALF) were found on day 1 without increases of inflammatory cells and total protein (TP) in BALF, which suggested the response of neutrophils and alveolar macrophages to instilled InP, and/or the manifestation of a very early stage of inflammation. Only in the 62.0 micrograms/kg-instilled group on day 8, were neutrophils, lymphocytes, TP, LDH, total phospholipid and total cholesterol in BALF increased, and desquamation of alveolar epithelial cells and amorphous exudate in alveolar lumen observed by histopathological examination. These results suggested that InP caused pulmonary inflammation and epithelial cell damage up to 8 days following instillation dose of 62.0 micrograms/kg, but that its effect was considered irrelevant at instillation doses of 6.0 micrograms/kg or below in rat.

Animals↗

Lung toxicity of hard metal particles and production of interleukin-1, tumor necrosis factor-alpha, fibronectin, and cystatin-c by lung phagocytes.

Hard metal alloys (WC-Co) are made of a mixture of cobalt (Co; 6%) and tungsten carbide (WC; 94%) particles. Chronic inhalation of hard metal dust can lead to the development of a fibrosing alveolitis, the pathogenesis of which is still undefined. The present investigation was undertaken to assess the effect of Co, WC, and WC-Co particles on the release by lung phagocytes of interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-alpha), fibronectin, and cystatin-c. The responses were compared with those induced by two other lung toxicants, i.e., crystalline silica (DQ12) and arsenic trioxide (As2O3). IL-1 and TNF-alpha activities produced in the presence and absence of LPS stimulation were measured with the aid of bioassays while fibronectin and cystatin-c were determined by latex immunoassays. In vitro, maximal noncytotoxic doses of As2O3, Co, WC, or WC-Co did not significantly affect the production of these mediators by rat alveolar macrophages. In contrast, DQ12 enhanced the production of TNF-alpha (with and without LPS stimulation) and IL-1 (after LPS stimulation) and decreased cystatin-c release (in the absence of LPS). Following a single intratracheal instillation of the different test preparations in the rat, the response of the lung phagocytes obtained by bronchoalveolar lavage (BAL) 24 hr later was examined. We were unable to detect any consistent effect of Co (0.06 mg/100 g body wt), WC (1 mg/100 g body wt), or WC-Co treatment (1 mg/100 g body wt) on the production of the above mediators. In contrast, after LPS stimulation, As2O3 (0.5 mg/100 g body wt) and DQ12 (1 mg/100 g body wt) stimulated the production of TNF-alpha and IL-1. In the absence of LPS, As2O3 stimulated fibronectin and cystatin-c production and DQ12 stimulated cystatin-c release. Since the dose of WC-Co used in vivo (1 mg/100 g body wt) caused pronounced lung inflammation (increased LDH, protein, and albumin levels in BAL fluid), we conclude that the acute lung toxicity of WC-Co particles is not mediated through enhanced production of the examined mediators by lung phagocytes.

Alloys↗

Selenium and cadmium induced pulmonary functional impairment and cytotoxicity.

Ovalbumin-sensitized (50 mg/kg, i.p.) male Hartley-guinea-pigs (550-610 g; n = 6) were treated 14 days later intratracheally with saline, cadmium (Cd 0.3 mg), selenium (Se 0.3 mg or 0.06 mg) or Se (0.06 mg) with Cd (0.3 mg). After 24 h, baseline dynamic-lung-compliance (Cdynl) and pulmonary-resistance (Rp), and percent change after ovalbumin-aerosol-challenge (10 mg/ml, 60 s) were assessed. Cadmium or Se (0.3 mg), Se (0.06 mg) and/or Cd (0.3 mg) decreased Cdynl (P < 0.05). Selenium (0.3 mg) increased Rp (P < 0.05). Ovalbumin-challenge decreased Cdynl and increased Rp in all groups. Analysis of bronchoalveolar-lavage-fluid (BALF) displayed increased activities of lactate-dehydrogenase (LDH), beta-glucuronidase (beta-G), alkaline-phosphatase (AP), and protein due to 0.3 mg Se, 0.3 mg Cd alone or with 0.06 mg Se (P < 0.05). Findings indicated that, 0.3 mg Se is more detrimental than 0.3 mg Cd to lung-dynamics despite a modest protection by 0.06 mg Se against Cd illustrated by an ameliorated Cdynl and lower protein in BALF.

Animals↗

Effects of intratracheal pretreatment with yttrium chloride (YCl3) on inflammatory responses of the rat lung following intratracheal instillation of YCl3.

We investigated pulmonary clearance of yttrium (Y) and acute lung injury following intratracheal instillation (i.t.) of yttrium chloride (YCl3) in saline- or YCl3-pretreated rats (30 days before the second challenge). About 67% of the initial dose of Y remained in the lung even 31 days after the i.t. treatment. The pretreatment with YCl3 significantly reduced i.t.-YCl3-induced increases in biochemical inflammatory indicators in bronchoalveolar lavage fluid (BALF), such as lactate dehydrogenase, beta-glucuronidase, and alkaline phosphatase activities and protein concentration, while the pretreatment increased the number of polymorphonuclear leukocyte (PMN) in BALF. These results suggest that the augmentation of PMN infiltration does not play an important role, if any, in i.t. YCl3-induced increases in biochemical indicators in BALF. The reduction of the increases in those biochemical inflammatory indicators may be due, at least in part, to the increase of manganese-superoxide dismutase (Mn-SOD) activity in the lung tissue, because the lung Mn-SOD activity in the YCl3-pretreated group was two times higher than that of the saline-pretreated group.

Animals↗

The alpha 4 beta 1 (very late antigen (VLA)-4, CD49d/CD29) and alpha 5 beta 1 (VLA-5, CD49e/CD29) integrins mediate beta 2 (CD11/CD18) integrin-independent neutrophil recruitment to endotoxin-induced lung inflammation.

The beta(2) integrin cell adhesion molecules (CAM) mediate polymorphonuclear leukocyte (PMNL) emigration in most inflamed tissues, but, in the lung, other yet to be identified CAMs appear to be involved. In Lewis rats, the intratracheal injection of Escherichia coli-LPS induced acute (6-h) PMNL accumulation in the lung parenchyma (280 x 10(6) by myeloperoxidase assay; PBS control = 35 x 10(6)) and bronchoalveolar lavage fluid (BALF = 27 x 10(6); PBS = 0.1 x 10(6)). Parenchymal accumulation was not inhibited by a blocking Ab to beta(2) integrins and only minimally inhibited (20.5%; p < 0.05) in BALF. We examined the role of alpha(4)beta(1) and alpha(5)beta(1) integrins and of selectins in this PMNL recruitment. Treatment with mAbs to alpha(4)beta(1) or alpha(5)beta(1), even in combination, had no effect on PMNL accumulation induced by intratracheal LPS. However, anti-alpha(4) combined with anti-beta(2) mAbs inhibited PMNL recruitment to the parenchyma by 56% (p < 0.001) and to BALF by 58% (p < 0.01). The addition of anti-alpha(5) mAb to beta(2) plus alpha(4) blockade inhibited PMNL accumulation further (by 79%; p < 0.05). In contrast, blockade of L-, P-, and E-selectins in combination or together with beta(2), alpha(4), and alpha(5) integrins had no effect. LPS-induced BALF protein accumulation was not inhibited by treatment with anti-beta(2) plus alpha(4) mAbs, but was prevented when alpha(5)beta(1) was also blocked. Thus, while selectins appear to play no role, alpha(4)beta(1) and alpha(5)beta(1) function as major alternate CAMs to the beta(2) integrins in mediating PMNL migration to lung and to pulmonary vascular and epithelial permeability.

Animals↗

Intratracheal versus intravenous administration of bleomycin in mice: acute effects.

We examined whether intratracheal instillation (IT) of bleomycin would produce similar or dissimilar lesions when compared to lung damage following intravenous (iv) injection of the drug. BALB/c mice were treated with either 4 U/kg IT or 100 U iv bleomycin and killed at intervals up to 21 days after treatment. Cell proliferation, histopathology, lung lavage, and hydroxyproline content were examined. There was a biphasic response in the cell proliferation in the IT-treated mice, while the iv-treated mice showed a single delayed peak in proliferation. The histopathologic features of interstitial pneumonitis, elevation of lung lavage enzyme activities, and lung hydroxyproline content were qualitatively similar between the two routes of administration, although the IT mice response was always greater in magnitude. Differences exist between the lung reaction to these two routes of administration, but these differences reflect nonspecific inflammatory response and magnitude of initial injury. We conclude that the response to bleomycin administered IT is basically similar to the changes produced by intravenous injection of the drug.

Animals↗

Comparative toxicity of standard nickel and ultrafine nickel in lung after intratracheal instillation.

A comparison was made of the bronchoalveolar lavage fluid (BALF) response to ultrafine nickel (Uf-Ni) and standard-sized nickel (Std-Ni). Rats were intratracheally instilled with 0, 0.1, 0.5, 1 and 5 mg Uf-Ni and Std-Ni, respectively. At 3 d after instillation, the body weight and wet lung weight were determined. At the same time, BALF was analyzed for lactate dehydrogenase (LDH), total protein (TP), tumor necrosis factor-alpha (TNF-alpha), and total cell and differential cell counts. The results showed that indicators of lung injury and inflammation in BALF were markedly raised with increased Uf-Ni and Std-Ni for each from 0 to 1 mg, and there were no differences in the indices between instillation of Uf-Ni at 1 mg and 5 mg. The results also showed that the effects of Uf-Ni on the indices were significantly higher than those of Std-Ni. Additional groups of rats were intratracheally instilled with 1 mg of Uf-Ni or Std-Ni, and wet lung weight and BALF profiles were analyzed at 1, 3, 7, 15 and 30 d later. The effect of Uf-Ni and Std-Ni on indices that can be presumed to reflect epithelial injury and permeability (LDH or TP), and release of proinflammatory cytokine (TNF-alpha) were increased throughout the 30 d post-exposure and the effects of Uf-Ni on these indices were significantly higher than those of Std-Ni from 1 to 30 d after instillation. Moreover, the number of neutrophils and LDH activity in BALF of rats after exposure to Uf-Ni were significantly greater than those of Std-Ni-exposed rats up to 30 d after instillation. Our findings suggest that Uf-Ni has a much more toxic effect on the lung than St-Ni, but the mechanism remains to be elucidated.

Analysis of Variance↗

Comparison of intranasal and intratracheal oxygen administration in healthy awake dogs.

Intranasal (IN) and intratracheal (IT) oxygen administration techniques were compared by measuring inspired oxygen concentrations (FIO2) and partial pressures of arterial oxygen (PaO2) in 5 healthy dogs at various IN (50, 100, 150, and 200 ml/kg of body weight/min) and IT (10, 25, 50, 100, 150, 200, and 250 ml/kg/min) oxygen flow rates. Intratracheal administration of oxygen permitted lower oxygen flow rates than IN administration. Each IT oxygen flow rate produced significantly higher FIO2 and PaO2 than the corresponding IN flow rate. An IT oxygen flow rate of 25 ml/kg/min produced FIO2 and PaO2 values equivalent to those produced by an IN oxygen flow rate of 50 ml/kg/min. An IT oxygen flow rate of 50 ml/kg/min produced FIO2 and PaO2 values equivalent to those produced by IN oxygen flow rates of 100 and 150 ml/kg/min. All IT oxygen flow rates greater than or equal to 100 ml/kg/min produced FIO2 and PaO2 values that were greater than FIO2 and PaO2 values produced by IN oxygen flow rates of 200 ml/kg/min. The lowest flow rates studied (50 ml/kg/min, IN, and 10 ml/kg/min, IT) produced PaO2 capable of maintaining 97% hemoglobin saturation, which should be adequate for most clinical situations. Arterial blood gas analysis and FIO2 measurements are necessary to accurately guide oxygen flow adjustments to achieve the desired PaO2 and to prevent oxygen toxicity produced by excessive FIO2.

Administration, Intranasal↗

Cell-specific expression of the alpha 1 (I) collagen promoter-CAT transgene in skin and lung: a response to TGF-beta subcutaneous injection and bleomycin endotracheal instillation.

Transgenic mice containing a rat collagen alpha 1 (I) promoter (3.6 kilobases) fused to the reporter gene chloramphenicol acetyl transferase (CAT) express the reporter gene parallel to endogenous gene in most connective tissues other than vascular tissue [Pavlin et al. (1992): J Cell Biol 116:227-236; Bedalov et al. (1994): J Biol Chem 269:4903-4909]. We have challenged transgenic mice with subcutaneous injections of transforming growth factor-beta (TGF-beta) or intratracheal instillation of bleomycin. In situ hybridization studies of skin revealed increased CAT expression in the papillary dermis of TGF-beta treated animals. In contrast, alpha 1 (I) collagen mRNA was expressed throughout the dermis including granulation tissue and reticular dermis. Therefore, the transgenic promoter responds to TGF-beta in a subset of dermal fibroblasts. Endotracheal instillation of bleomycin induces lung fibrosis which is thought to be mediated in part by TGF-beta. CAT gene expression in lungs was increased 6-8-fold at 2 weeks post bleomycin treatment. In situ hybridization studies revealed focal areas of cells expressing both CAT and collagen genes in the interstitium. However, most regions, especially around airways, contained a subset of cells expressing the endogenous gene with little or no CAT expression as judged by in situ hybridization. These cells could be myofibroblasts that require additional cis-acting elements to activate alpha 1 (I) collagen gene expression similar to smooth muscle cells.

Animals↗

Anticoagulant activity and operative blood loss after intrapulmonary heparin.

The safety and efficacy of heparin given by the intrapulmonary route are further assessed in this study. A single dose of heparin (2000 units/kg) was given by intratracheal instillation in dogs and measurements of plasma heparin concentration, whole blood clotting time and partial thromboplastin time made at intervals for 48 h. These values rose progressively and in parallel for 7 h and remained elevated for 48 h. A series of operations was performed on dogs within 3 h of a single dose of intrapulmonary heparin (1500 units/kg). Operations involving minimal dissection (small bowel resection) and extensive dissection (resection of muscle) were performed in two separate groups. Within each group the animals were randomly given heparin or saline. In the limited dissection group there were no differences in operative blood loss, wound healing, or sequential haemoglobin and haematocrit measurements. In the group subjected to muscle resection there was increased postoperative wound drainage and a slightly greater fall in haemoglobin and haematocrit in those given heparin. It is concluded that heparin is absorbed from the lung causing significant changes in coagulation parameters. Even with the relatively high dose of 1500 units/kg, operations were performed with minimal hazard. Intrapulmonary heparin may have important clinical applications after further investigation.

Animals↗

Aerosol delivery of an enhanced helper-dependent adenovirus formulation to rabbit lung using an intratracheal catheter.

BACKGROUND: Poor transduction of the ciliated airway epithelium and inefficient airway delivery of viral vectors are common difficulties encountered in lung gene therapy trials with large animals and humans. METHODS: We delivered a helper-dependent adenovirus vector, incorporating a human epithelial cell-specific expression cassette, to rabbit lung. An intratracheal device was used to aerosolize a moderate dose of virus (5 x 10(11) particles), mixed with the enhancing agent LPC (L-alpha-lysophosphatidylcholine), directly into the airways. Lung mechanics, body weight and temperature, transgene expression and histopathology were studied at day 5. RESULTS: Transgene expression was seen in the epithelium of large and small airways, from trachea to terminal bronchioles, with a strong tendency toward the right lung. All cell types of the surface epithelium were transduced. Extensive transduction of the epithelium (66% of cells in trachea) was obtained using virus formulated in isotonic 0.1% LPC, while virus formulated in 0.01% LPC transduced fewer cells (24% in trachea). A transient decrease in dynamic lung compliance was observed immediately following aerosol delivery. Fever and mild-to-moderate patchy pneumonia without edema were also observed. CONCLUSION: These data demonstrate a strategy for efficient and effective transduction of airway epithelium in a large animal.

Adenoviridae↗

Effects of nano particles on cytokine expression in murine lung in the absence or presence of allergen.

Particulate matter (PM) can exacerbate allergic airway diseases. Health effects of PM with a diameter of less than 100 nm, called nano particles, have been focused. We have recently demonstrated that carbon nano particles (14, 56 nm) exaggerate allergic airway inflammation in mice. In the present study, we investigated the effects of repeated pulmonary exposure to carbon nano particles on the expression of a variety of cytokines in the absence or presence of allergen in mice. ICR mice were divided into six experimental groups. Vehicle, two sizes of carbon nano particles, ovalbumin (OVA), and OVA + nano particles were administered intratracheally. Nano particles increased the lung protein levels of thymus and activation-regulated chemokine (TARC), macrophage inflammatory protein (MIP)-1alpha, and granulocyte-macrophage colony-stimulating factor (GM-CSF) in the absence or presence of allergen. The enhancement was more prominent with 14 nm of nano particles than with 56 nm of nano particles in overall trend. 14 nm nano particle exposure significantly enhanced the lung expressions of interleukin (IL)-2 and IL-10 in the presence of allergen as compared with allergen exposure. These results suggest that pulmonary exposure to nano particles can induce the lung expression of TARC, MIP-1alpha, GM-CSF in the absence of allergen and can enhance that of TARC, MIP-1alpha, GM-CSF, IL-2, and IL-10 in the presence of allergen. The enhancing effects are more prominent with smaller particles.

Allergens↗

Intratracheal pulmonary ventilation and congenital diaphragmatic hernia: a report of two cases.

Previous studies from our institution have shown that neonates with congenital diaphragmatic hernia (CDH), whose best postductal PaO2 (BPDPO2) was less than 100 mm Hg while on maximal conventional mechanical ventilation (CMV), had a mortality exceeding 90%. When combined with extracorporeal membrane oxygenation (ECMO), the mortality rose to 100% in those infants who developed hypercarbia following decannulation. Historically, those patients have required increasing ventilator support, leading to iatrogenic lung damage, and eventual death. Intratracheal pulmonary ventilation (ITPV) using the reverse thrust catheter (RTC) developed by Kolobow incorporates a continuous flow of humidified gas through a reverse Venturi catheter positioned at the distal end of the endotracheal tube. In animal studies, ITPV was shown to result in a reduced physiological dead-space (VD), to facilitate expiration, and to enhance CO2 elimination. In our current study, we have applied ITPV in two neonates with CDH who could not be weaned from ECMO because of uncontrollable hypercapnia, and who met above criteria for 100% mortality. In both cases, ITPV restored normal PaCO2 at low peak inspiratory pressure (PIP) with a substantial decrease in VD. We believe ITPV is suited to ventilating newborns with CDH in whom barotrauma is known to be common. Beyond its present use, ITPV may be useful to ventilate children with other forms of respiratory failure, and should be so considered along with other now available methods of mechanical pulmonary ventilation.

Hernia, Diaphragmatic↗

Clearance and excretion of intratracheally and orally administered aflatoxin B1 in the rat.

The pharmacokinetic disposition of intratracheally (i/t) and orally administered [3H]AFB1 was studied in male Sprague-Dawley rats. Blood, urine and faeces were collected at selected intervals following administration of a single i/t or oral dose of AFB1 (600 micrograms/kg) in saline. Blood-concentration data from both groups approximated a two-compartment open model. The time-to-peak for the i/t group (hr) was less than that for the oral group (3 hr), but the disappearance of label from the blood followed a nearly identical course in both groups. The plasma half-lives (t1/2) were 87.7 and 91.8 hr for the i/t and oral groups, respectively. In addition, urinary and faecal excretion profiles were similar. By day 23, urinary excretion of label had accounted for 16.4 and 15.0% of the dose in the i/t and oral groups, respectively, and faecal excretion for 56.0 and 54.6%. At this time, however, significantly more label was recovered from the lungs and upper airways of the rats of the i/t group than in those treated orally.

Absorption↗

Repeated intratracheal inoculation of house dust mite (Dermatophagoides farinae) induces pulmonary eosinophilic inflammation and IgE antibody production in mice.

BACKGROUND: In vitro studies have shown that the biologic activities of dust mite allergens probably contribute to their allergenicity. However, little is known about their in vivo effect, which may lead to allergic inflammation and sensitization. OBJECTIVE: In this study we characterized the pathologic and immunologic responses of mice after repetitive challenge with dust mite Dermatophagoides farinae. METHODS: Der f crude extract was intratracheally instilled into female BALB/c mice either once or a total of 10 times at 1-week intervals. The inflammatory responses, morphologic changes, IgE antibody and cytokine levels, and costimulatory molecular B7 expression in the airways were then monitored. RESULTS: We demonstrated that single Der f challenge provoked an acute neutrophilic inflammation in the airways. After repeated Der f challenge, there was chronic inflammation characterized by increased numbers of lymphocytes and eosinophils in bronchoalveolar lavage (BAL) fluids. Histopathologically, the numbers of goblet cells and mast cells were significantly increased in the airways of these mice. Repetitive challenge elicited Der f-specific IgE antibody, increased IL-5 and IFN-gamma level in BAL fluids, and enhanced costimulatory B7 molecule expression on BAL cells. CONCLUSIONS: Our findings are in agreement with those of other in vitro studies concerning the properties of dust mite allergens. Prolonged inhalation of Der f without adjuvant may represent an optimal condition to develop experimental animal models of allergic lung diseases.

Animals↗

Pulmonary toxicity of single-wall carbon nanotubes in mice 7 and 90 days after intratracheal instillation.

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.

Animals↗