PRINCIPLES OF TOXICOLOGY

9.1 LUNG ANATOMY AND PHYSIOLOGY 179
system, before reaching the alveolar regions of the lung. The condition of the alveocapillary membrane
is also important. Poor health conditions in a patient might lead to the engorgement of the interstitial
space with fluid, which would impair the diffusion of toxic chemicals across the alveocapillary
membrane. While this protects the affected individual from the toxic effects of the inhaled
chemical, it also prevents the free exchange of oxygen and carbon dioxide, which can have obvious
life-threatening outcomes.
The degree of uptake of inhaled gases and vapors can be quite significant in workers in many
occupations. Following the initiation of inhalation, rapid uptake of perchloroethylene, a commonly
used dry cleaning solvent for which there are thousands of potential exposures, can be observed in
many different tissues (Figure 9.10). In this case, the uptake of perchloroethylene in circulating blood
and seven tissues was remarkably rapid, and for many industrial chemicals, it is often within minutes
of exposure. It is often interesting to note that the levels of the inhaled solvent remained fairly constant
throughout the inhalation exposure period. This can have important ramifications in occupational
exposures, as workers who enter an environment with a potentially toxic gas can experience systemic
toxic effects almost immediately, and these effects can persist for long periods of time (while the
inhalation exposure period continues). For instance, many industrial solvents cause neurobehavioral
depression following inhalation exposure, and workers have been known to be injured as a result of
falls or mishaps with industrial machinery almost immediately after breathing the chemicals.
Obviously, the length of exposure affects the amount of chemical inhaled. However, for many gases
and vapors a steady-state equilibrium can be established after a certain period of inhalation exposure.
In this way, the level of chemical in the blood does not continue to increase, despite the continued
inhalation exposure to the compound (Figure 9.10). This has important ramifications in industrial
exposures because it helps explain why workers sometimes do not experience toxic effects to certain
chemicals despite long-term exposure.
Figure 9.10 The uptake and disposition of perchloroethylene (PER) in the blood and seven tissues of laboratory
rats is shown. The animals inhaled 2500 ppm of perchloroethylene for 120 min in dynamic inhalation exposure
chambers, and blood and tissues were analyzed for the solvent by electron capture-gas chromatography. (Supported
by US Air Force Grants AFOSR 870248 and 910356.)