Intratracheal instillation as an exposure technique for the evaluation of respiratory tract toxicity: uses and limitations.

The evaluation of respiratory tract toxicity from airborne materials frequently involves exposure of animals via inhalation. This provides a natural route of entry into the host and, as such, is the preferred method for the introduction of toxicants into the lungs. However, for various reasons, this technique cannot always be used, and the direct instillation of a test material into the lungs via the trachea has been employed in many studies as an alternative exposure procedure. Intratracheal instillation has become sufficiently widely used that the Inhalation Specialty Section of the Society of Toxicology elected to develop this document to summarize some key issues concerning the use of this exposure procedure. Although there are distinct differences in the distribution, clearance, and retention of materials when administered by instillation compared to inhalation, the former can be a useful and cost-effective procedure for addressing specific questions regarding the respiratory toxicity of chemicals, as long as certain caveats are clearly understood and certain guidelines are carefully followed.

[1]  Wolfgang Koch,et al.  Chronic Inhalation Exposure of Wistar Rats and two Different Strains of Mice to Diesel Engine Exhaust, Carbon Black, and Titanium Dioxide , 1995 .

[2]  L. M. Holland,et al.  Lung cancer in rats exposed to fibrogenic dusts , 1984 .

[3]  K. Driscoll,et al.  Stimulation of rat alveolar macrophage fibronectin release in a cadmium chloride model of lung injury and fibrosis. , 1992, Toxicology and applied pharmacology.

[4]  H. Ritz,et al.  Respiratory allergenicity of detergent enzymes in the guinea pig intratracheal test: association with sensitization of occupationally exposed individuals. , 1997, Fundamental and applied toxicology : official journal of the Society of Toxicology.

[5]  F. J. Miller,et al.  Correlation of effects of inhaled versus intratracheally injected males on susceptibility to respiratory infection in mice. , 1981, The American review of respiratory disease.

[6]  D. L. Harris,et al.  Recruitment of antibody-forming cells in the lung after local immunization is nonspecific. , 1982, The American review of respiratory disease.

[7]  J. Little,et al.  Localization of polycyclic hydrocarbon carcinogens in the lung following intratracheal instillation in gelatin solution. , 1975, Cancer research.

[8]  W. Blair Chemical Induction of Lung Carcinomas in Rats , 1974 .

[9]  H. Ritz,et al.  Proteolytic detergent enzymes enhance the allergic antibody responses of guinea pigs to nonproteolytic detergent enzymes in a mixture: implications for occupational exposure. , 1997, The Journal of allergy and clinical immunology.

[10]  G. J. Newton,et al.  Early damage indicators in the lung. III. Biochemical and cytological response of the lung to inhaled metals salts. , 1979, Toxicology and applied pharmacology.

[11]  R. T. Drew,et al.  Pulmonary changes resulting from subchronic exposure to cadmium chloride aerosol. , 1986, Journal of toxicology and environmental health.

[12]  G. M. Ridder,et al.  Pulmonary response to silica or titanium dioxide: inflammatory cells, alveolar macrophage-derived cytokines, and histopathology. , 1990, American journal of respiratory cell and molecular biology.

[13]  R. E. Kouri,et al.  Studies on pulmonary aryl hydrocarbon hydroxylase activity in inbred strains of mice. , 1976, Chemico-biological interactions.

[14]  D. Kaufman,et al.  Respiratory tract carcinogenesis in hamsters induced by different numbers of administrations of benzo(a)pyrene and ferric oxide. , 1972, Cancer research.

[15]  S. Takenaka,et al.  Chronic effects on the respiratory tract of hamsters, mice and rats after long‐term inhalation of high concentrations of filtered and unfiltered diesel engine emissions , 1986, Journal of applied toxicology : JAT.

[16]  Dennis Reil Forum. , 1996, Environmental health perspectives.

[17]  J. Mauderly Bronchopulmonary lavage of small laboratory animals. , 1977, Laboratory animal science.

[18]  S. Stinson,et al.  Lung cancer induction by crystalline silica: Relationships to granulomatous reactions and host factors , 1988 .

[19]  A. Seidel,et al.  Behaviour of spherical and irregular (U,Pu)O2 particles after inhalation or intratracheal instillation in rat lung and during in vitro culture with bovine alveolar macrophages. , 1989, International journal of radiation biology.

[20]  E. Chi,et al.  Comparative effects of inhaled volcanic ash and quartz in rats. , 1983, The American review of respiratory disease.

[21]  E. G. Damon,et al.  Acute toxicity of polyethylene glycol p-isooctylphenol ether in syrian hamsters exposed by inhalation or bronchopulmonary lavage. , 1982, Toxicology and applied pharmacology.

[22]  R. E. Kouri,et al.  Lung cancer model system using 3-methylcholanthrene in inbred strains of mice. , 1981, Cancer research.

[23]  K. Driscoll,et al.  Alveolar macrophage cytokine and growth factor production in a rat model of crocidolite-induced pulmonary inflammation and fibrosis. , 1995, Journal of toxicology and environmental health.

[24]  W. Foster Deposition and Clearance of Inhaled Particles , 1999 .

[25]  Mauderly Jl Bronchopulmonary lavage of small laboratory animals. , 1977 .

[26]  B. D. Beck,et al.  The pulmonary toxicity of an ash sample from the MT. St. Helens Volcano. , 1981, Experimental lung research.

[27]  J. Evans,et al.  The distribution of dust in the rat lung following administration by inhalation and by single intratracheal instillation. , 1985, Environmental research.

[28]  F. Law,et al.  Toxicokinetics and Bioavailability of Paraquat in Rats following Different Routes of Administration , 1988, Toxicology and industrial health.

[29]  D. Costa,et al.  Transoral tracheal intubation of rodents using a fiberoptic laryngoscope. , 1986, Laboratory animal science.

[30]  R. Henderson,et al.  Early damage indicators in the lungs. IV. Biochemical and cytologic response of the lung to lavage with metal salts. , 1979, Toxicology and applied pharmacology.

[31]  W. Seeger,et al.  Ultrasonic nebulization for efficient delivery of surfactant in a model of acute lung injury. Impact on gas exchange. , 1997, American journal of respiratory and critical care medicine.

[32]  R. E. Kouri,et al.  Correlation of inducibility of aryl hydrocarbon hydroxylase with susceptibility to 3-methylcholanthrene-induced lung cancers. , 1980, Cancer letters.

[33]  J. Mauderly,et al.  Toxic and carcinogenic effects of solid particles in the respiratory tract , 1994 .

[34]  D. W. Baxter,et al.  Large-Volume Intratracheal Instillation of Particulate Suspensions to Hamsters , 1974 .

[35]  U Saffiotti,et al.  A method for the experimental induction of bronchogenic carcinoma. , 1969, Cancer research.

[36]  P. Valberg,et al.  Heterogeneity of phagocytosis for inhaled versus instilled material. , 1992, The American review of respiratory disease.

[37]  H. Reynolds,et al.  Mechanism for the inflammatory response in primate lungs. Demonstration and partial characterization of an alveolar macrophage-derived chemotactic factor with preferential activity for polymorphonuclear leukocytes. , 1977, The Journal of clinical investigation.

[38]  K. Driscoll,et al.  Pulmonary response to inhaled silica or titanium dioxide. , 1991, Toxicology and applied pharmacology.

[39]  R. Henderson,et al.  A comparison of the inflammatory response of the lung to inhaled versus instilled particles in F344 rats. , 1995, Fundamental and applied toxicology : official journal of the Society of Toxicology.

[40]  P. Germann,et al.  Lung Tumours in Rats after Intratracheal Instillation of Dusts , 1994 .

[41]  R. Schlesinger Deposition and Clearance of Inhaled Particles , 1995 .

[42]  M. Davis,et al.  Pulmonary distribution of particles given by intratracheal instillation or by aerosol inhalation. , 1976, Environmental research.

[43]  A. Dahl,et al.  Clearance of sulfuric acid-introduced 35S from the respiratory tracts of rats, guinea pigs and dogs following inhalation or instillation. , 1983, Fundamental and applied toxicology : official journal of the Society of Toxicology.

[44]  A. Cantin,et al.  Contributions of Experimental Asbestosis in Sheep to the Understanding of Asbestosis a , 1991, Annals of the New York Academy of Sciences.

[45]  G. Oberdörster,et al.  Pulmonary retention of ultrafine and fine particles in rats. , 1992, American journal of respiratory cell and molecular biology.

[46]  P. Morrow,et al.  Pulmonary response to toner upon chronic inhalation exposure in rats. , 1991, Fundamental and applied toxicology : official journal of the Society of Toxicology.

[47]  R. Henderson,et al.  Early damage indicators in the lung. V. Biochemical and cytological response to NO2 inhalation. , 1981, Toxicology and applied pharmacology.

[48]  E. Wheeldon,et al.  Intratracheal aerosolization of endotoxin in the rat: a model of the adult respiratory distress syndrome (ARDS) , 1992, Laboratory animals.

[49]  P. Nettesheim,et al.  Induction of squamous cell carcinoma in the respiratory tract of mice. , 1971, Journal of the National Cancer Institute.

[50]  A. Furst,et al.  Intratracheal instillation method for mouse lungs. , 1973, Oncology.

[51]  C. Aaron,et al.  Quantitative morphometric analysis of pulmonary deposition of aerosol particles inhaled via intratracheal nebulization, intratracheal instillation or nose‐only inhalation in rats , 1998, Journal of applied toxicology : JAT.

[52]  J. Linehan,et al.  The effect of immunization on the uptake of intratracheally administered antigen. , 1978, Clinical immunology and immunopathology.

[53]  H. Ritz,et al.  Respiratory and immunological responses of guinea pigs to enzyme-containing detergents: a comparison of intratracheal and inhalation modes of exposure. , 1993, Fundamental and applied toxicology : official journal of the Society of Toxicology.

[54]  D. Romberger,et al.  Respiratory tract responses to dust: relationships between dust burden, lung injury, alveolar macrophage fibronectin release, and the development of pulmonary fibrosis. , 1990, Toxicology and applied pharmacology.

[55]  K. Driscoll,et al.  The comparison of a fibrogenic and two nonfibrogenic dusts by bronchoalveolar lavage. , 1990, Toxicology and applied pharmacology.

[56]  K. Leslie,et al.  Dose-responsive increases in pulmonary fibrosis after inhalation of asbestos. , 1994, American journal of respiratory and critical care medicine.