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Inhalation Exposure Systems: Design, Methods and Operation

CT Centers for Health Research, Research Triangle Park, NC 27709, USA, bwong{at}ciit.org

The respiratory system, the major route for entry of oxygen into the body, provides entry for external compounds, including pharmaceutic and toxic materials. These compounds (that might be inhaled under environmental, occupational, medical, or other situations) can be administered under controlled conditions during laboratory inhalation studies. Inhalation study results may be controlled or adversely affected by variability in four key factors: animal environment; exposure atmosphere; inhaled dose; and individual animal biological response. Three of these four factors can be managed through engineering processes. Variability in the animal environment is reduced by engineering control of temperature, humidity, oxygen content, waste gas content, and noise in the exposure facility. Exposure atmospheres are monitored and adjusted to assure a consistent and known exposure for each animal dose group. The inhaled dose, affected by changes in respiration physiology, may be controlled by exposure-specific monitoring of respiration. Selection of techniques and methods for the three factors affected by engineering allows the toxicologic pathologist to study the reproducibility of the fourth factor, the biological response of the animal.

Key Words: Inhalation exposure • exposure systems • aerosol generation • gas generation • bioaerosols • nanoparticles.

References

• Baron, P.A., Mazumder, M.K., and Cheng, Y.S. (2001). Direct-Reading techniques using particle motion and optical detection. In: Aerosol Measurement, 2nd Ed. (P. A. Baron and K. Willeke, eds.), pp. 495—535. John Wiley & Sons, New York.
• Barr, E.B., Cheng, Y.S., and Mauderly, J.L. (1987). Determination of oxygen depletion in a nose-only exposure chamber. In: Annual Report of the Inhalation Toxicology Research Institute, pp. 72—5. NTIS, Springfield, VA.
• Bide, R.W., Armour, S.J., and Yee, E. (2000). Allometric respiration/body mass data for animals to be used for estimates of inhalation toxicity to young adult humans. J Appl Toxicol 20(4), 273—90.[CrossRef][ISI][Medline] [Order article via Infotrieve]
• Bernstein, D.M., Mast, R., Anderson, R., Hesterberg, T.W., Musselman, R., Kamstrup, O., and Hadley, J. (1994). An experimental approach to the evaluation of the biopersistence of reprable synthetic fibers and minerals. Environ Health Perspect 102, 15—18.[CrossRef]
• Cannon, W.C., Blanton, E.F., and McDonald, K.E. (1983). The flow-past chamber: an improved nose-only exposure system for rodents. Amer Indust Hygiene Asso J 44, 923—8.
• Cassee, F.R., Muijser, H., Duistermaat, E., Freijer, J.J., Geerse, K.B., Marijnissen, J.C.M., and Arts, J.H.E. (2002). Particle size-dependent total mass deposition in lungs determines inhalation toxicity of cadmium chloride aerosols in rats. Application of a multiple path dosimetry model. Arch Toxicol 76, 277—86.[CrossRef][ISI][Medline] [Order article via Infotrieve]
• Chang, J., Gross, E., Swenberg, J., and Barrow, C. (1983). Nasal cavity deposition, histopathology, and cell proliferation following single and repeated formaldehyde exposures in B6C3F1 mice and F-344 rats. Toxicol Appl Pharmacol 68, 161—76.[CrossRef][ISI][Medline] [Order article via Infotrieve]
• Chen, B.T., and John, W. (2001). Instrument calibration. In Aerosol Measurement, 2nd Ed. (P. A. Baron, and K. Willeke, eds.), pp. 627—66. John Wiley & Sons, New York.
• Cheng, Y.S., Barr, E.B., Benson, J.M., Damon, E.G., Medinsky, M.A., Hobbs, C.H., and Goehl, T.J. (1988). Evaluation of a real-time aerosol monitor (RAM-S) for inhalation studies. Fund Appl Toxicol 10, 321—8.[CrossRef][ISI][Medline] [Order article via Infotrieve]
• Cheng, Y.-S., Barr, E.B., Carpenter, R.L., Benson, J.M., and Hobbs, C.H. (1989). Improvement of aerosol distribution in whole-body inhalation exposure chambers. Inhal Toxicol 1, 153—66.
• Cheng, Y.S., Barr, E.B., and Yeh, H.C. (1989). A venturi disperser as a dry powder generator for inhalation studies. Inhal Toxicol 1, 365—71.
• Cheng, Y.-S., and Moss, O.R. (1995). Inhalation exposure systems. In: Concepts in Inhalation Toxicology, 2nd Ed., (R. O. McClellan and R. F. Henderson, eds.), pp. 25—66. Taylor & Francis, Washington, DC.
• Colvin, V. (2003). The potential environmental impact of engineered nanomaterials. Nature Biotechnol 21, 1166—70.[CrossRef][ISI][Medline] [Order article via Infotrieve]
• Commentary. (1992). Recommendations forthe conduct of acute inhalation limit tests. Fund Appl Toxicol 18, 321—7.[CrossRef][ISI][Medline] [Order article via Infotrieve]
• Crisp, S., Hardcastle, W.A., Nunan, J.M., and Smith, A.F. (1981). An improved generator for the production of metal oxide fume. Amer Indust Hygiene Asso J 42, 590—5.
• DeLorme, M.P., and Moss, O.R. (2002). Pulmonary function assessment by whole-body plethysmography in restrained versus unrestrained mice. J Pharmacol Toxicol Meth 47, 1—10.[CrossRef][ISI][Medline] [Order article via Infotrieve]
• Dorman, D., Wong, B., Struve, M., James, R., LaPerle, K., Marshall, M., and Bolon, B. (1996). Development of a mouse whole-body exposure system from a directed-flow rat nose-only system. Inhal Toxicol 8, 107—20.[CrossRef][ISI]
• Driscoll, K.E., Costa, D.L., Hatch, G., Henderson, R., Oberdorster, G., Salem, H., and Schleisinger, R.B. (200). Intratracheal instillation as an exposure technique for the evaluation of respiratory tract toxicity: uses and limitations. Toxicol Sci 55, 24—35.[CrossRef]
• Foster, W.M., Walters, D.M., Longphre, M., Macri, K., and Miller, L.M. (2001). Methodology for the measurement of mucociliary function in the mouse by scintigraphy. J Appl Physiol 90, 1111—8.[Abstract/Free Full Text]
• Gardner, D.E. (1982). Effects of gases and airborne particles on lung infections. In: Air Pollution—Physiological Effects (J. J. McGrath and C. D. Barnes, eds.), pp. 47—79. Academic Press, New York.
• Gebhart, J. (2001). Optical direct-reading techniques: light intensity systems. In: Aerosol Measurement, 2nd Ed. (P. A. Baron, and K. Willeke, eds.), pp. 419—454. John Wiley & Sons, New York.
• Gerde, P., Cheng, Y.S., and Medinsky, M.A. (1991). In vivo deposition of ultrafine aerosols in the nasal airway of the rat. Fund Appl Toxicol 16, 330—6.[CrossRef][ISI][Medline] [Order article via Infotrieve]
• Grinshpun, S.A., Willeke, K., Ulevicius, V., Juozaitis, A., Terzieva, S., Donnelly, J., Stelma, G.N., and Brenner, K.P. (1997). Effect of impaction, bounce and reaerosolization on the collection efficiency of impingers. Aero Sci Technol 26, 326—42.
• Guyton, A.C. (1947). Analysis of respiratory patterns in laboratory animals. Am J Physiol 150, 70—7.[Free Full Text]
• Hartings, J.M., and Roy, C.J. (2004). The automated bioaerosol exposure system: Preclinical platform development and a respiratory dosimetry application with nonhuman primates. J Pharmacol Toxicol Meth 49, 39—55.[CrossRef][Medline] [Order article via Infotrieve]
• Hinds, W.C. (1999). Aerosol Technology, 2nd ed. John Wiley & Sons, New York.
• Hinners, R.G., Burkhart, J.K., and Punte, C.L. (1968). Animal inhalation exposure chambers. Arch Environ Health 16, 194—206.[ISI][Medline] [Order article via Infotrieve]
• Kanapilly, G.M., Raabe, O.G., and Newton, G.J. (1970). A new method for the generation of aerosols of insoluble particles.J Aero Sci 1, 313— 23.
• Kanapilly, G.M., Tu, K.W., Larsen, T.B., Fogel, G.R., and Luna, R.J. (1978). Controlled production of ultrafine metallic aerosols by vaporization of an organic chelate of the metal. J Coll Interf Sci 65, 533—47.
• Kelly, J.T., Bobbitt, C.M., and Asgharian, B. (2001). In vivo measurement of fine and coarse aerosol deposition in the nasal airways of female Long— Evans rats. Toxicol Sci 64, 253—8.[Abstract/Free Full Text]
• Koch, W., Lödding, H., Oenning, G., and Muhle, H. (1986). The generation and the measurement of dry aerosols in large-scale inhalation experiments. J Aero Sci 17, 499—504.
• Leavens, T.L., Moss, O.R., and Bond, J.A. 1996. Dynamic inhalation system for individual whole-body exposure of mice to volatile organic chemicals. Inhal Toxicol 8, 655—77.[CrossRef][ISI]
• Lee, K.W., and Mukund, R. (2001). In: Aerosol Measurement, 2nd Ed. (P. A. Baron and K. Willeke, eds.), pp. 197—228. John Wiley & Sons, New York.
• Lin, W.-H., and Li, C.-S. (1998). The effect of sampling time and flow rates on the bioefficiency of three fungal spore sampling methods. Aero Sci Technol 28, 511—22.
• Mainelis, G., Berry, D., An, H.R., Yao, M., DeVoe, K., Fennell, D.E., and Jaeger, R. (2005). Performance and design of a single-pass bubbling bioaerosol generator. Atmos Environ 39(19), 3521—33.
• Marple, V.A., Olsen, B.A., and Rubow, K.L. (2001). Inertial, gravitational, centrifugal, and thermal collection techniques. In: Aerosol Measurement, 2nd ed. (P. A. Baron and K. Willeke, eds.), pp. 229—60. John Wiley & Sons, New York.
• Miller, F.J. (1999). Dosimetry of particles in laboratory animals and humans. In: Toxicology of the Lung, 3rd ed. (D. E. Gardner, J. D. Crapo, and R. O. McClellan, eds.), pp. 513—55. Taylor and Francis, Philadelphia, PA.
• Miller, R., Letts, R., Potts, W., and McKenna, M. (1980). Improved methodology for generating controlled test atmospheres. Amer Indust Hygiene Asso J 41, 844—6.
• Moss, O.R. (1981). Comparison of three methods of evaluating inhalation toxicology chamber performance. In: Inhalation Toxicology and Technology, (B. K. J. Leong, ed.), pp. 19—28. Ann Arbor Science, Ann Arbor, MI.
• Moss, O.R. (2001). Inhalation toxicology: sampling strategies related to control of exposure atmospheres. In: Aerosol Measurement, 2nd Ed. (P. A. Baron and K. Willeke, eds.), pp. 1053—63. John Wiley & Sons, New York.
• Moss, O.R., James, R.A., and Asgharian, B. (2006). Influence of exhaled air on inhalation exposure delivered through a directed-flow nose-only exposure system. Inhal Toxicol 18, 45—51.[CrossRef][ISI][Medline] [Order article via Infotrieve]
• Moss, O.R., and Cheng, Y.-S. (1995). Generation and characterization of test atmospheres: particles and droplets. In: Concepts in Inhalation Toxicology, 2nd ed. (R. O. McClellan and R. F. Henderson, eds.), pp. 91—126. Taylor & Francis, Washington, DC.
• Multiple path particle dosimetry model MPPD (2002). v. 1.0, CIIT Centers for Health Research (CIIT) and Dutch National Institute of Public Health and the Environment: http://www.ciit.org/techtransfer/tt_technologies.asp .
• National Research Council (1996). Guide for the Care and Use of Laboratory Animals. National Academy Press, Washington, DC.
• Nelson, G. (1992). Gas Mixtures: Preparation and Control. Lewis Publishers, Inc., Chelsea, MI.
• Oberdörster, G., Gelein, R.M., Ferin, J., and Weiss, B. (1995). Association of particulate air pollution and acute mortality: involvement of ultrafine particles? Inhal Toxicol 7, 111—24.[ISI][Medline] [Order article via Infotrieve]
• Oberdörster, G., Oberdörster, E., and Oberdörster, J. (2005). Nanotoxicology: an emerging discipline evolving from studies of ultrafine particles. Environ Health Perspect 113, 823—39.[ISI][Medline] [Order article via Infotrieve]
• Organization for European Cooperation and Development (OECD). (2004). OECD Guideline for the Testing of Chemicals. Draft Proposal for guideline 436. Acute Inhalation Toxicology—Acute Toxic Class (ATC) Method. http://www.oecd.org .
• Pauluhn, J. (1994). Validation of an improved nose-only exposure system for rodents. J Appl Toxicol 14, 55—62.[CrossRef][ISI][Medline] [Order article via Infotrieve]
• Phalen, R.F. (1997). Methods in Inhalation Toxicology. CRC Press, Boca Raton, FL.
• Pott, F. (1993). Testing the carcinogenicity of fibers in laboratory animals: results and conclusions. In: Fiber Toxicology (D. B. Warheit, ed.), pp. 395—424. Academic Press, San Diego, CA.
• Prasad, S.B., Rao, V.S., Mannix, R.C., and Phalen, R.F. (1988). Effects of pollutant atmospheres on surface receptors of pulmonary macrophages. J Toxicol Environ Health 24, 385—402.[ISI][Medline] [Order article via Infotrieve]
• Raabe, O.G., Bennick, J.E., Light, M.E., Hobbs, C.H., Thomas, R.L., and Tillery, M.I. (1973). An improved apparatus for acute inhalation exposure of rodents to radioactive aerosols. Toxicol Appl Pharmacol 26, 264—73.[CrossRef][ISI][Medline] [Order article via Infotrieve]
• Rao, G.V.S., Tinkle, S., Weissman, D.N., Antonini, J.M., Kashon, M.L., Salmen, R., Battelli, L.A., Willard, P.A., Hubbs, A.F., and Hoover, M.D. (2003). Efficacy of a technique for exposing the mouse lung to particles aspirated from the pharynx. J Toxicol Environ Health Pt A 66, 1441— 52.[CrossRef]
• Reponen, T., Willeke, K., Grinshpun, S., and Nevalainen, A. (2001). Biological particle sampling. In: Aerosol Measurement, 2nd Ed. (P. A. Baron, and K. Willeke, eds.), pp. 751—78. John Wiley & Sons, New York.
• Reponen, T., Willeke, K., Ulevicius, V., Grinshpun, S.A., and Donnelly, J. (1997). Techniques for dispersion of microorganisms into air. Aero Sci Technol 27, 405—21.
• Roth, C., Ferron, G.A., Karg, E., Lentner, B., Schumann, G., Takenaka, S., and Heyder J. (2004). Generation of ultrafine particles by spark discharging. Aero Sci Technol 38, 228—35.
• Schroeter, J.D., Kimbell, J.S., Bonner, A.M., Roberts, K.C., Andersen, M.E., and Dorman, D.C. (2006). Incorporation of tissue reaction kinetics in a computational fluid dynamics model for nasal extraction of inhaled hydrogen sulfide in rats. Toxicol Sci 90, 198— 207.
• Schwartz, J. (1994). Airpollution and daily mortality: a review and meta analysis. Environ Res 64, 36—52.[Medline] [Order article via Infotrieve]
• Silver, S.D. (1946). Constant flow gassing chambers: principles influencing design and operation. J Lab Clin Med 31, 1153—6.[ISI]
• Sioutas, C., and Koutrakis, P. (1996). Inertial separation of ultrafine particles using a condensational growth/virtual impaction system. Aero Sci Technol 25, 424—36.
• Sioutas, C., Koutrakis, P., and Burton, R.M. (1994). Development of a low cutpoint slit virtual impactor for sampling ambient fine particles. J Aero Sci 25, 1321—30.
• Smith, D.M., Ortiz, L.W., Archuleta, R.F., Spaulding, J.F., Tillery, M.I., Ettinger, H.J., and Thomas, R.G. (1981). A method for chronic nose-only exposures of laboratory animals to inhaled fibrous aerosols. In: Inhalation Toxicology and Technology (B. K. J. Leong, ed.), pp. 89—105. Ann Arbor Science, Ann Arbor, MI.
• Snellings, W., and Dodd, D. (1990). Inhalation studies. In: Handbook of In Vivo Toxicity Testing (D. A. Arnold, H. C. Grice, and D. R. Krewski, eds.), pp. 189—246. Academic Press, San Diego, CA.
• Thompson, M.W., Donnelly, J., Grinshpun, S.A., Juozaitis, A., and Willeke, K. (1994). Method and test system for evaluation of bioaerosol samplers. J Aero Sci 25, 1579—93.
• Tilbury, L., Butterworth, B., Moss, O., and Goldsworthy, T. (1993). Hepatocyte cell proliferation in mice after inhalation exposure to unleaded gasoline vapor. J Toxicol Environ Health 38, 293—307.[ISI][Medline] [Order article via Infotrieve]
• Tomaides, M., Liu, B.Y.H., and Whitby, K.T. (1971). Evaluation of the condensation aerosol generator for producing monodispersed aerosols. J Aero Sci 2, 39—46.[CrossRef]
• Ulevicius, V., Willeke, K., Grinshpun, S.A., Donnelly, J., Lin, X., and Mainelis, G. (1997). Aerosolization of particles from a bubbling liquid: characteristics and generator development. Aero Sci Technol 26, 175—90.
• U.S. Environmental Protection Agency (US EPA), 1998. Health effects test guidelines: OPPTS 87.1300. Acute inhalation toxicity. EPA 712-C-98-193. Available at: http://www.epa.gov/epahome/resarch/htm.
• Vitarella, D., James, R.A., Miller, K.L., Struve, M.F., Wong, B.A., and Dorman, D.C. (1998). Development of an inhalation system for the simultaneous exposure of rat dams and pups during developmental neurotoxicity studies. Inhal Toxicol 10, 1095—117.[CrossRef][ISI]
• Wong, B.A. (1999). Inhalation exposure systems design, methods, and operation. In: Toxicology of the Lung, 3rd ed. (D. E. Gardner, J. D. Crapo, and R. O. McClellan, eds.), pp. 1—53. Taylor and Francis, Philadelphia, PA.
• Wong, Brian A. (2003). Automated feedback control of an inhalation exposure system with discrete sampling intervals: testing, performance, and modeling. Inhal Toxicol 15, 729—43.[CrossRef][ISI][Medline] [Order article via Infotrieve]
• Wong, B.A., and Moss, O.R. (1996). Application of a building management system to automate a 90-day chloroform inhalation study. Toxicol Meth 6, 53—64.[CrossRef]

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Wong, B. A. Search for Related Content PubMed PubMed Citation Articles by Wong, B. A. Social Bookmarking                   What's this?