Inhalation Exposure and Absorption of Toxicants

Inhalation is a common route by which individuals are exposed to toxicants. The primary function of the respiratory tract is to provide the organism with oxygen and remove carbon dioxide. This function presents a particular dilemma with respect to exposure to airborne toxicants, in that the necessity of breathing means that short of using personal air filters, gas masks, or breathing apparatus, an individual will be exposed to whatever pollutants are in the air of his or her immediate environment. Some pollutants, such as many of those listed in the 1990 Clean Air Act Amendment (United States Environmental Protection Agency), are practically ubiquitous in the air environment and the control or reduction of their ambient concentrations requires costly measures. Therefore, it is desirable to use good science and quantitative methods to quantify the dosimetry of these materials in the human respiratory tract, so that we can best estimate the air concentrations that will be protective of public (and environmental) health with an appropriate margin of safety. Depending upon the physical and chemical characteristics of the toxicant, the respiratory tract can also be a target organ in addition to a portal of entry (see Volume 8 for more details on respiratory toxicology). Sufficient information is not always available on the potential adverse effects of inhaled materials on the respiratory tract tissues. Often the fate of the toxicant following inhalation is not known. Key factors that determine the fate of inhaled toxicants include the physical and chemical characteristics of the toxicant, the unique anatomy of the respiratory tract itself, the mechanisms by which inhaled materials deposit in the respiratory tract, and the mechanisms for removal or clearance of inhaled materials. Consideration of these key factors will improve predictions of the exposure scenarios to inhaled toxicants that are likely to result in inhalation hazards. The purpose of this chapter is to introduce key concepts and principles which underpin and determine inhalation dosimetry, to describe some of the ways in which these concepts and principles are integrated to predict or quantify that dosimetry (i.e., using mathematical models), and to illustrate how understanding of this information helps one to understand and interpret toxicological data for inhaled materials. The volume of scientific information now available on this topic is far more than we can comprehensively review in this limited space. Nevertheless we have attempted to point the reader to a sufficient body of references, such that this chapter can serve as a good starting point for further investigation into the topic.