Inhalation Toxicology Methods: the Generation and Characterization of Exposure Atmospheres and Inhalational Exposures

Overview

Journal Curr Protoc Toxicol

Specialty Toxicology

Date 2015 Feb 4

PMID 25645246

Citations 9

Authors

Lung-Chi Chen

Morton Lippmann

Affiliations

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Abstract

In this unit, the need for laboratory-based inhalation toxicology studies, the historical background on adverse health effects of airborne toxicants, and the benefits of advance planning for the building of analytic options into the study design to maximize the scientific gains to be derived from the investments in the study are outlined. The following methods are described: (1) the generation and characterization of exposure atmospheres for inhalation exposures in humans and laboratory animals; (2) the delivery and distribution into and within whole-body exposure chambers, head-only exposure chambers, face-masks, and mouthpieces or nasal catheters; (3) options for on-line functional assays during and between exposures; and (4) options for serial non-invasive assays of response. In doing so, a description beyond exposures to single agents and simple mixtures is presented, and included are methods for evaluating biological responses to complex environmental mixtures. It is also emphasized that great care should be taken in the design and execution of such studies so that the scientific returns can be maximized both initially, and in follow-up utilization of archived samples of the exposure atmospheres, excreta, and tissues collected for histology.

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References

Albert R, SPIEGELMAN J, Shatsky S, Lippmann M . The effect of acute exposure to cigarette smoke on bronchial clearance in the miniature donkey. Arch Environ Health. 1969; 18(1):30-41. DOI: 10.1080/00039896.1969.10665369. View

Carey M, Card J, Bradbury J, Moorman M, Haykal-Coates N, Gavett S . Spontaneous airway hyperresponsiveness in estrogen receptor-alpha-deficient mice. Am J Respir Crit Care Med. 2006; 175(2):126-35. PMC: 1899278. DOI: 10.1164/rccm.200509-1493OC. View

Liberda E, Cuevas A, Qu Q, Chen L . The acute exposure effects of inhaled nickel nanoparticles on murine endothelial progenitor cells. Inhal Toxicol. 2014; 26(10):588-97. PMC: 4212263. DOI: 10.3109/08958378.2014.937882. View

Veronesi B, Makwana O, Pooler M, Chen L . Effects of subchronic exposures to concentrated ambient particles. VII. Degeneration of dopaminergic neurons in Apo E-/- mice. Inhal Toxicol. 2005; 17(4-5):235-41. DOI: 10.1080/08958370590912888. View

Weitkamp E, Sage A, Pierce J, Donahue N, Robinson A . Organic aerosol formation from photochemical oxidation of diesel exhaust in a smog chamber. Environ Sci Technol. 2007; 41(20):6969-75. DOI: 10.1021/es070193r. View

Kang G, Gillespie P, Gunnison A, Rengifo H, Koberstein J, Chen L . Comparative pulmonary toxicity of inhaled nickel nanoparticles; role of deposited dose and solubility. Inhal Toxicol. 2011; 23(2):95-103. DOI: 10.3109/08958378.2010.543440. View

Chen L, Lam H, Ainsworth D, Guty J, Amdur M . Functional changes in the lungs of guinea pigs exposed to sodium sulfite aerosols. Toxicol Appl Pharmacol. 1987; 89(1):1-8. DOI: 10.1016/0041-008x(87)90170-0. View

Seagrave J, Campen M, McDonald J, Mauderly J, Rohr A . Oxidative stress, inflammation, and pulmonary function assessment in rats exposed to laboratory-generated pollutant mixtures. J Toxicol Environ Health A. 2008; 71(20):1352-62. DOI: 10.1080/15287390802271566. View

Feletou M, Vanhoutte P . Endothelial dysfunction: a multifaceted disorder (The Wiggers Award Lecture). Am J Physiol Heart Circ Physiol. 2006; 291(3):H985-1002. DOI: 10.1152/ajpheart.00292.2006. View

10.

Kang G, Gillespie P, Gunnison A, Moreira A, Tchou-Wong K, Chen L . Long-term inhalation exposure to nickel nanoparticles exacerbated atherosclerosis in a susceptible mouse model. Environ Health Perspect. 2010; 119(2):176-81. PMC: 3040603. DOI: 10.1289/ehp.1002508. View

11.

Chen L, Lam H, Kim E, Guty J, Amdur M . Pulmonary effects of ultrafine coal fly ash inhaled by guinea pigs. J Toxicol Environ Health. 1990; 29(2):169-84. DOI: 10.1080/15287399009531381. View

12.

Ng S, Silverstone A, Lai Z, Zelikoff J . Effects of prenatal exposure to cigarette smoke on offspring tumor susceptibility and associated immune mechanisms. Toxicol Sci. 2005; 89(1):135-44. DOI: 10.1093/toxsci/kfj006. View

13.

Lippmann M, Albert R . The effect of particle size on the regional deposition of inhaled aerosols in the human respiratory tract. Am Ind Hyg Assoc J. 1969; 30(3):257-75. DOI: 10.1080/00028896909343120. View

14.

Godleski J, Rohr A, Kang C, Diaz E, Ruiz P, Koutrakis P . Toxicological evaluation of realistic emission source aerosols (TERESA): introduction and overview. Inhal Toxicol. 2011; 23 Suppl 2:1-10. PMC: 3703945. DOI: 10.3109/08958378.2010.568019. View

15.

Fraser D, BALES R, Lippmann M, STOKINGER H . Exposure chambers for research in animal inhalation: design, construction, operation, and performance. Public Health Monogr. 1959; 57:1-54. View

16.

Chen L, SCHLESINGER R . Response of the bronchial mucociliary clearance system in rabbits to inhaled sulfite and sulfuric acid aerosols. Toxicol Appl Pharmacol. 1983; 71(1):123-31. DOI: 10.1016/0041-008x(83)90051-0. View

17.

Giannotti G, Landmesser U . Endothelial dysfunction as an early sign of atherosclerosis. Herz. 2007; 32(7):568-72. DOI: 10.1007/s00059-007-3073-1. View

18.

Amdur M, Sarofim A, Neville M, Quann R, McCarthy J, Elliott J . Coal combustion aerosols and sulfur dioxide: an interdisciplinary analysis. Environ Sci Technol. 2012; 20(2):138-45. DOI: 10.1021/es00144a004. View

19.

Tahara S, Matsuo M, Kaneko T . Age-related changes in oxidative damage to lipids and DNA in rat skin. Mech Ageing Dev. 2001; 122(4):415-26. DOI: 10.1016/s0047-6374(00)00257-8. View

20.

Chen L, Hwang J, Lall R, Thurston G, Lippmann M . Alteration of cardiac function in ApoE-/- mice by subchronic urban and regional inhalation exposure to concentrated ambient PM2.5. Inhal Toxicol. 2010; 22(7):580-92. DOI: 10.3109/08958371003596579. View