Lung, Pleura, and Mediastinum

The lung is constantly exposed to a large volume of inhaled air that may contain toxicant xenobiotics. With the possibility of exposure to a variety of respiratory toxicants from airborne pollutants in our environment during the course of daily activities, in occupational settings, the use of aerosol sprays for household products, and the development of inhalant bronchial therapies, pulmonary toxicology has become an important subspecialty of toxicology. The lung is susceptible to injury following hematogenous exposure to toxicants. Susceptibility to injury and the type of response following exposure to air- or blood-borne toxicants is largely dependent on the physiochemical characteristics and concentration of the toxicant, duration of exposure, site/tissue specific sensitivity, and the integrity of the defense mechanisms of the lung. In this chapter, nonneoplastic and neoplastic spontaneous lesions and those that develop in the lungs of rats following exposure to toxicants by various routes, but primarily by inhalation, are discussed in detail which provides insight into our understanding of how human lungs respond to toxic chemicals. In addition, the gross and microscopic anatomy of the rat lung is also discussed some detail. Although inhalation is the primary route of exposure in experimental studies, in the past, many studies used intratracheal instillation or direct injection of known carcinogens into the lung. These experiments often resulted in the development of squamous cell carcinomas even though they are very rare as a naturally occurring neoplasm. Instillation of chemicals or particles into the trachea or pleura or direct injection into the lung results in lesions or responses that may not be as relevant to understanding the mechanism of pulmonary carcinogenesis as inhalation of materials under more normal conditions. There remain, however, many areas where our understanding of the response of the lung to toxic chemicals is incomplete.