The human respiratory system is a complex set of organs that interact in a delicate balance to facilitate effective gas exchange. The lung itself possesses a surface area the size of an entire tennis court, which is available for interaction with the atmospheric environment and potential toxicants. Understanding the intricate dynamics behind exposure, effects, and resolution of symptoms requires expertise in the pathogenesis of toxicant-induced respiratory injury and disease, and a detailed knowledge of respiratory tract structure and function, metabolism of inhaled agents, aerosol physics, and source characterization.
Exponent’s expertise in respiratory health derives from Ph.D.-level scientists specializing in pulmonology, inhalation toxicology, pathology, biochemistry, bioengineering, epidemiology, industrial hygiene, and molecular biology. Our scientists have extensive practical experience in respiratory toxicology, and can clearly and concisely report on the intricacies of effects in this most important biological system.
Respiratory Toxicology involves the analysis of such exposure scenarios as the inhalation of inorganic and organic vapors such as hydrochloric acid or benzene, as well as particulates such as asbestos, silica, metals, asphalt fume, and particulate matter products of diesel exhaust, and coal combustion. Exponent scientists are also experienced in designing and conducting applied research studies in inhalation toxicology. Examples of this include design and monitoring of specialized acute inhalation studies to better characterize toxicity, toxic load (n), concentration (C) and duration (T), and generalized Haber’s-law (CnxT) relationships as well as help in derivations of RfD and AEGL values. Monitored endpoints of these studies have included the pathological assessment of target organs through histological and immunocytochemical techniques, neurobehavioral assessments based on analysis of functional testing, and immunological assessments, through cell sorting, cytokine assays and gene screens. Exponent scientists also have experience with design of inhalation/oral studies and PBPK analyses to extrapolate between different routes of exposure (e.g., inhalation vs. oral exposure), and between varying species (e.g., rat vs. human).
Particle size, shape, and water solubility are important factors that contribute to an inhaled substance’s potential toxicity. Research on inhalation of nano-scale particles indicates that in addition to these factors, surface reactivity may also be an important determinant of a particle’s toxicity. Exposure to chemicals and particles through inhalation can injure the respiratory system itself, as well as other distant organ systems. Effects associated with low-level or brief exposures may resolve without permanent damage. More serious respiratory pathology with higher doses and/or repeated exposures may manifest as chemically induced pneumonia, bronchitis, fibrosis, asthma, reactive airway disease, dyspnea, emphysema, bronchiolitis, mesothelioma, or cancer. Lung injury from toxicant exposure can also contribute to secondary organ-system effects such as cardiovascular, liver, kidney, reproductive system, or central nervous system dysfunction.
Knowledge of the multiple molecular mechanisms behind respiratory biology is essential for a thorough evaluation of airborne toxicant exposures and associated risks of adverse health effects, in the work place, surrounding community, and in the environment. Exponent has the exceptional combination of technical expertise, regulatory knowledge, and state-of-the-art technologies to properly assess complex respiratory health issues as well as develop health-protective respiratory measures based on the latest science.
Publications
Chunn JL, Mohsenin A, Young HY, Lee CG, Elias JA, Kellems RE, Blackburn MR. Partially adenosine deaminase deficient mice develop pulmonary fibrosis in association with adenosine elevations. Am J Physiol Lung Cell Mol Physiol 2006; 290:579–587.
Sun CX, Zhong H, Molina JG, Belardinelli L, Zeng D, Mohsennin A, Chunn JL, Blackburn MR. Role of A2B Receptor signaling in adenosine-dependent pulmonary inflammation and injury. J Clin Invest 2006; 116(8):2173–2182.
Chunn J, Molina JG, Mei T, Xia Y, Kellems R, Blackburn MR. Adenosine dependant pulmonary fibrosis in adenosine deaminase deficient mice. J Immunol 2005; 175:1937-1946.
Blackburn MR, Lee CG, Young HWJ, Chunn JL, Banerjee SK, Elias JA. Adenosine is an important mediator of IL-13 induced inflammation in the lung: Evidence for an IL-13-adenosine amplification pathway. J Clin Invest 2003; 112:332–343.
Chunn JL, Young WJ, Colasurdo GN, Banerjee SK, Blackburn MR. Adenosine-dependent airway inflammation and hyperresponsiveness in partially adenosine deaminase deficient mice. J Immunol 2001; 167:4676–4685.
Blackburn MR, Volmer JB, Chunn JL (Thrasher), Crosby JR, Lee JJ, Kellems RE. Metabolic consequences of adenosine deaminase deficiency in mice are associated with defects in alveogenesis, pulmonary inflammation and airway obstruction. J Exp Med 2000; 192:159-170.
Zhong H, Chunn JL, Volmer JB, Fozard JL Blackburn MR. Adenosine mediated mast cell degranulation in adenosine deaminase-deficient mice. J Pharmacol Exp Ther 2000; 298(2):433-440.
Book Chapters
Wagner M, Chunn JL. Allergy. In: The Encyclopedia of Epidemiology, 2007.
Chunn JL. Asthma. In: The Encyclopedia of Epidemiology, 2007