Toxic Responses of the Respiratory System

Initially, lung injury caused by chemicals was primarily associated with certain professions and occupations. In his classic treatise of 1713, the Italian physician Bernardino Ramazzini provided detailed and harrowing accounts of the sufferings of miners, whose ailments had been known and described since antiquity. Two of Ramazzini’s quotations are noteworthy. With regard to miners of metals, he stated that “the lungs and brains of that class of workers are badly affected, the lungs especially, since they take in with the air mineral spirits and are the first to be keenly aware of injury.” Ramazzini also was aware of the important concept of exposure: “They (workers who shovel, melt, and cast and refine mined material) are liable of the same diseases, though in less acute form, because they perform their tasks in open air.” Thus, exposure to chemicals by inhalation can have two effects: on the lung tissues and on distant organs that are reached after chemicals enter the body by means of inhalation. Indeed, the term inhalation toxicology refers to the route of exposure, whereas respiratory tract toxicology refers to target-organ toxicity, in this case abnormal changes in the respiratory tract produced by airborne (and on occasion blood-borne) agents. We now know of numerous lung diseases prompted by occupational exposures, many crippling and some fatal. Examples include black lung in coal miners, silicosis and silicotuberculosis in sandblasters and tunnel miners, and asbestosis in shipyard workers and asbestos miners. Occupational exposures to asbestos or metals such as nickel, beryllium, and cadmium can also cause lung cancer. In the twentieth century, it has become obvious that disease caused by airborne agents may not be limited to certain trades. The ubiquitous presence of airborne chemicals is a matter of concern, since “air pollution” adversely affects human health and may be an important contributor to mortality (Zemp et al., 1999). To better understand environmental lung disease, we need more precise knowledge about the doses of toxic inhalants delivered to specific sites in the respiratory tract and an understanding