Intratracheal instillation

Costa etal. (1986) under enfluorane anaesthesia depressed the tongue and illuminated the pharynx with a fibre-optic laryngoscope. A bevelled Teflon tube was inserted into the trachea to a level just cephalic of the Carina. Injection of the material to be dehvered was accomphshes rapidly with the use of a No. 19 gauge hypodermic needle inserted directly into the tracheal tube. Tronic et al. (1996) used ha-lothan putting rats for 30 s into a chamber saturated with the anaesthetic, which has been shown to produce a negligible effect of pulmonary monooxygenases, as well as on cell viabihty (Morgan et al. 1980). 

Brain (1971) increasingly used hamsters since they are more resistant to lung diseases than rats and have tolerated intratracheal injections better than rats. 

In Sprague-Dawley rats, addition of pig s pulmonary surfactant (10 mg) to quartz did not influence the outcome of any parameter after 5 weeks (Zet-terberg etal. 1998). In vitro, respirable fibres coated with sheep surfactant released more Fe than native fibres at both pH 4.5 and 7.2 (Fisher et al. 1998). 

Intratracheal instillation is a highly artificial system and must be interpreted with great caution (Sekhon et al. 1995). The primary mechanism responsible for rapid alveolar liquid clearance de- 

However, insoluble suspensions tend to localise in the medium-sized bronchi and seldom reach the alveoli (Brain et al. 1976). 

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Jordana, M., Richards, C., Irving, L.B. and Gauldie, J. (1988). Spontaneous in vitro release of alveolar macrophage cytokines after the intratracheal instillation of bleomycininrats. Am. Rev. Resp. Dis. 137, 1135-1140. 

Available information from human exposures indicates that airborne americium-containing particles are deposited in the respiratory tract, cleared to some extent via mucociliary action, and swallowed or expelled (Edvardsson and Lindgren 1976 Fry 1976 Newton et al. 1983 Sanders 1974 Toohey and Essling 1980). Descriptions of human respiratory tract models that can be used for radiation protection also include relevant information regarding biokinetics of inhaled particles (ICRP 1994b, 1995 NCRP 1997). Quantitative data are not available, however. Supporting animal studies include inhalation exposure to aerosols of americium (Buldakov et al. 1972 DOE 1978 Gillett et al. 1985 Sanders and Mahaffey 1983 Talbot et al. 1989 Thomas et al. 1972) or intratracheal instillation of americium compounds (Moushatova et al. 1996). 

In summary, intratracheal instillation of CNTs has shown that their potential in eliciting adverse pulmonary effects is influenced by exposure time, CNT dose, CNT biopersistence, surface defects, and metal contamination [71, 72]. Despite the use of surfactants, all studies showed that intratracheal instillation caused major difficulties due to the agglomerative nature of CNTs in a biological environment. More realistic exposure methods, namely inhalation rather than intratracheal administration, are therefore needed for determining the pulmonary toxicity [59, 65, 73]. Several investigations have been performed by using administration different from intra-... 

If persistent, these molecules (coding for inflammation, oxidative stress, remodeling, and thrombosis) can cause endothelial dysfunction and acceleration of arthrosclero-sis progression [117]. SWNTs were shown also to alter the cardiac activity by affecting the arterial baroreflex function (BRF) of sinus mode in rats exposed by intratracheal instillation [118]. 

C]taurine-labeled MWNTs were administered to mice by three different exposure routes (intravenous injection, gavage, and intratracheal instillation) and their biodistribution was monitored [134], After intravenous injection, [14C]taurine-labeled MWNTs accumulated in the liver, heart, and lung after gavage administration, [14C]taurine-labeled MWNTs was only detectable in the stomach, intestine, and feces. No [14C]taurine-labeled MWNTs were detected in the blood. Finally, [14C] taurine-labeled MWNTs were partly cleared from the lungs after intratracheal instillation. Since various cell and tissue types have demonstrated a high affinity for uptake of taurine, it should be noted that the label used in this investigation may have influenced the biodistribution of the MWNTs tested [101]. 

CNTs Arc discharge Guinea pigs Intratracheal instillation 28 d None [63]... 

Purified MWNTs Catalytic decomposition (<2.2wt.% catalyst) Rats Intratracheal instillation 60 d Toxic [68]... 

MWNTs Catalytic decomposition Rats Intratracheal instillation 60 d Defect-dependent acute toxic reactions [69]... 

MWNTs CVD Guinea pigs Intratracheal instillation 90 d Time-dependent [66]... 

Intratracheal instillation Inhalation 24 d Pulmonary toxicity induced only by intratracheal instillation [75]... 

Elgrabli, D. et al. (2008) Induction of apoptosis and absence of inflammation in rat lung after intratracheal instillation of multiwalled carbon nanotubes. Toxicology, 253 (1-3), 131-136. 

Li, J.G. et al. (2007) Comparative study of pathological lesions induced by multiwalled carbon nanotubes in lungs ofmice by intratracheal instillation andinhalation. Environmental Toxicology, 22 (4), 415-421. 

Park, E.J. et al. (2009) Pro-inflammatory and potential allergic responses resulting from B cell activation in mice treated with multi-walled carbon nanotubes by intratracheal instillation. Toxicology,... 

Intratracheal instillation 14d Alveolar macrophages activation production pro-inflammatory cytokines Blood high-levels pro-inflammatory cytokines differentiation of CD4+ T cell to Thl and Th2 cells [108]... 

Hirano, S., T. Shimada, J. Osugi, N. Kodama, and K.T. Suzuki. 1994. Pulmonary clearance and inflammatory potency of intratracheally instilled or acutely inhaled nickel sulfate in rats. Arch. Toxicol. 68 548-554. 

Webb, D.R., S.E. Wilson, and D.E. Carter. 1986. Comparative pulmonary toxicity of gallium arsenide, gallium (III) oxide, or arsenic (III) oxide intratracheally instilled into rats. Toxicol. Appl. Pharmacol. 82 405-416. 

Richard RJ, Atkins J, Marrs TC, et al. 1989. The biochemical and pathological changes produced by the intratracheal instillation of certain components of zinc-hexachloroethane smoke. Toxicology 54 79-88. 

At least 75% of intratracheally deposited nickel chloride had been absorbed 72 h after the operation in rats [265]. Nickel chloride was cleared from the lungs of rats more rapidly after intratracheal instillation compared with nickel oxide [266], the slower clearance being attributed to an increased solubility of nickel chloride compared with the oxide. 

After intratracheal instillation of nickel chloride or nickel sulphate in rats, a modest inflammatory response with increased number of macrophages and polynuclear leucocytes was obtained, together with increased activities of lactate dehydrogenase and -glucuronidase in bronchoalveolar fluid [351]. More severe lesions were characterized by type II cell hyperplasia with epithelialization of alveoli, and in some animals, fibroplasia of the pulmonary interstitium. By inhalation in rats, the nickel salts produced chronic inflammation and degeneration of the bronchiolar epithelium [352, 353]. There was also atrophy of the olfactory epithelium and hyperplasia of the bronchial and mediastinal lymph nodes. Nickel sulphate also produced a low incidence of emphysema and fibrosis [353]. 

In critical evaluation of the effect of a gas, vapor, or aerosol inhaled in to the respiratory tract of an animal, the dosimetric method has been recommended (Oberst, 1961). However, due to the complexity of measuring the various parameters simultaneously, only a few studies on gaseous drugs or chemicals have employed the dosimetric method (Weston and Karel, 1946 Adams et al., 1952 Leong and MacFarland, 1965 Landy et al., 1983 Stott and McKenna, 1984 Dallas et al., 1986, 1989). For studies on liquid or powdery aerosols, modified techniques such as intratracheal instillation (Brain et al., 1976) or endotracheal nebulization (Leong et al., 1988) were used to deliver an exact dose of the test material into the lower respiratory tract (LRT) while bypassing the URT and ignoring the ventilatory parameters. 

Brain, J.D., Knudson, D.E., Sorokin, S.P. and Davis, M.A. (1976). Pulmonary distribution of particles given by intratracheal instillation or be aerosol inhalation. Environ. Res. 11 13-33. 

In rats, the administration of fullerene by inhalation, as nano- and microparticles generated by aerosol, does not lead to lesions and only a little increase of protein concentration in bronchoalveolar lavage fluid was obtained (Baker et al., 2007). Recently, Sayes et al. (2007) analyzed in vivo pulmonary toxicity of C60 and C60(OH)24, after intratracheal instillation in rats. They verified only transient inflammatory and cell injury effects, 1 day postexposure, without differences from water-instilled controls. No adverse lung tissue effects were measured, and the results demonstrated little or no differences in lung toxicity effects between the C60 and fiillerols, compared to controls. 

Lam CW, James JT, McCluskey R, Hunter RL (2004) Pulmonary toxicity of single-wall carbon nanotubes in mice 7 and 90 days after intratracheal instillation. Toxicol. Sci. 77 126-134. 

Ernst H, Rittinghausen S, Bartsch W, Creutzenberg O, Dasenbrock C, Gorlitz BD, Hecht M, Kairies U, Muhle H, Muller M, Heinrich U, Pott F (2002) Pulmonary inflammation in rats after intratracheal instillation of quartz, amorphousSiO(2),carbon black, and coal dust and the influence of poly-2-vinylpyridine-N-oxide (PVNO). Experimental and Toxicologic Pathology 54 109-126. 

MWNTs (0.05mg/mouse) Female Kunming mice Intratracheal instillation 8 days, 16 days, The aggregates led to inflammation in the lining and 24 days walls of the bronchi and severe destruction to the alveoli Li et al. (2007)... 

SWNT soot (1 or 5 mg/kg) Male Crl CD (SD)IGS BR Rats Intratracheal instillation 24 h, 1 week, 1 A non-dose-dependent series of multifocal month, and granulomas 3 months Warheit et al. (2004)... 

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