Intratracheal inhalation

Detirelix Potent LHRH antagonist Sheep Intratracheal inhalation Successful systemic absorption via intratracheal administration or inhalation [73]... 

Dog Intratracheal inhalation Absorption from lung slow (Tmax 6.5 h relative bioavailability 29 10%) [74]... 

Various techniques of particle delivery are used to deduce pulmonary and systemic effects from the wide parameters of potential toxicological influences. The specific techniques that are currently employed in these studies include intratracheal instillation, intratracheal aspiration, and intratracheal inhalation. Of these different delivery techniques, intratracheal installation is a useful technique to assess the potential health effects of different particles efficiently and cost effectively. Intratracheal instillation is characterized by saline suspended particles administered directly into the trachea of the animal being tested. Intratracheal installation provides a relatively easy way to compare the toxicology between different materials. However intratracheal installation is not able to assess particle deposition. Intratracheal aspiration involves droplet administration of suspended particle matter in the form of a puff of air. Intratracheal inhalation is the most relevant for toxicity and risk assessment. Intratracheal inhalation involves nanoparticulate aerosol formation at constant concentrations during the exposure. 

The latter [NaCa(P03)3] fibers shows only a minimal potential at the high-exposure level and the absence of a tumor induction at any of the exposure levels. In addition, it is significant that there was no pleural reaction to the fiber either in the present chronic inhalation study or in the 6-month intratracheal instillation and intratracheal inhalation study. In conclusion, CSM ([NaCa(P03)3l ) fiber should have low potential for producing chronic adverse health effects, i.e., fibrosis or neoplasiar following inhalation exposure. ... 

J. Banister, G. Fegler and C. Hebb, Initial respiratory responses to the intratracheal inhalation of phosgene or ammonia, Exp Physiol, 1949, 35, 233-250. 

Oberdorster G, Cox C, Gelein R. Intratracheal instillation versus intratracheal inhalation of tracer particles for measuring lung clearance function. Exp Lung Res 1997 ... 

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). 

The effects of acute- and intermediate-duration inhalation lead exposure on local and systemic immune function following intratracheal, intraperitoneal, or intravenous immunization were studied in mice continuously exposed to lead nitrate for 14 or 28 days (Hillam and Ozkan 1986). Several parameters of local and systemic immune function were measured in the immunized, lead-exposed mice. Lead content... 

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-... 

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

Erichleb, M., Pharmacokinetics of gentamicin administered intratracheally or as an inhalation aerosol to guinea pigs, Drug Metab. Dispos. 1984, 12, 641-614. 

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. 

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. 

Li JG, Li WX, Xu JY, Cai XQ, Liu RL, Li YJ, Zhao QF, Li QN (2007a) Comparative study of pathological lesions induced by multiwalled carbon nanotabes in lungs of mice by intratracheal instillation and inhalation. Environ Toxicol 22 415—421. 

Leong BKJ, Coombs JK, Sabaitis CP, Rop DA, Aaron CS (1998) Quantitative morphometric analysis of pulmonary deposition of aerosol particles inhaled via intratracheal nebulization, intratracheal instillation or nose-only inhalation in rats. J Appl Toxicol 18 149-160. 

Schanker LS, Mitchell EW, Brown RA, Jr (1986) Species comparison of drug absorption from the lung after aerosol inhalation or intratracheal injection. Drug Metab Dispos 14 79-88. 

P>[a P has been carcinogenic in all animal species tested to date, including mouse, rat, hamster, rabbit, guinea pig, duck, newt, dog, monkey, and fish. Intratracheal instillation and inhalation studies in a number of species have resulted in elevated incidences of respiratory tract and upper digestive tract tumors, and intraperitoneal and subcutaneous injections... 

In animal studies, significant increases in adenocarcinomas and squamous cell carcinomas of the lung have occurred in rats after inhalation or intratracheal instillation in rats, but not in hamsters. Increasing in vitro and in vivo evidence suggests that the rat lung tumor response to crystalline silica exposure is a result of marked and persistent inflammation and epithelial proliferation. However, other pathways such as a role for crystalline silica surfacegenerated oxidants or a direct genotoxic effect cannot be ruled out. 

Mechanism of Action An intratracheal respiratory inhalant that splits the linkage of mucoproteins, reducingtheviscosityof pulmonary secretions.Tiierapeutic Effect Facilitates the removal of pulmonary secretions by coughing, postural drainage, mechanical means. Protects against acetaminophen overdose-induced hepatotoxicity. Pharmacokinetics Protein binding 83% (injection). Rapidly and extensively metabolized in liver. Deacetylated by the liver to cysteine and subsequently metabolized. Excreted in urine. Half-life 5.6 hr (injection). 

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