PRINCIPLES OF TOXICOLOGY

44 ABSORPTION, DISTRIBUTION, AND ELIMINATION OF TOXIC AGENTS
Solid and Liquid Particulates The lung can be thought of as consisting of three basic regions: the
nasopharyngeal region, the tracheobronchiolar region, and the distal or alveolar region. Particles that
are roughly 5 µm or greater in diameter are generally deposited in the nasopharyngeal region. If they
are deposited very close to the surface, they can be sneezed out, blown out, or wiped away. If they are
deposited slightly farther back, they may be picked up by the mucus-blanketed cilia lining the lung in
this region (the mucociliary “escalator”) and moved back up into the nasopharyngeal region, where
they may be swallowed and absorbed in the GI tract in accordance with their solubility and absorption
characteristics. Particles that fall into the size range of 2–5 µm generally reach the tracheobronchial
region before they impact the lung surface. Most of these particles are also cleared by the mucociliary
escalator back up to the nasopharyngeal region, where they are either eliminated directly or swallowed
and absorbed or excreted in the GI tract. Particles smaller than 1 µm in diameter may reach the alveolar
regions of the lung. Absorption in the lung, if it takes place at all, will most likely take place in the
alveolar region, although there may be some absorption in the tracheobronchiolar region, particularly
if the material is soluble in the mucus.
Size is probably the most important single characteristic determining the efficiency of particulate
absorption in the lung. Size determines the region of the lung in which the aerosol is likely to be
deposited. Even within the range of very small particles that reach the alveolar region and may be
absorbed there, size is inversely proportional to the magnitude of particle deposition.
Figure 2.5 shows the dependence of lead deposition in the human lung on the size of the lead
particles in an artificially generated lead sesquioxide aerosol that was inhaled by the subjects. Size is
expressed as diffusion mean equivalent diameter (DMED), a measure of mean particle diameter. The
amount deposited was calculated as the difference between the amount of lead that entered the lung
and the amount that the subject exhaled. Thus, the lung regions in which the particles were actually
deposited were not identified. However, the DMEDs for all three aerosols were less than 1 µm. For a
standard subject, with a breathing cycle of about 4 s, the lung deposition of lead varied from about 24
percent for particles with a DMED of 0.09 µm to 68 percent for very small particles with a DMED of
Figure 2.5 Deposition in the human lung of lead particles of various sizes: • DMED, 0.02 µm; " DMED, 0.04
µm; H DMED, 0.09 µm. Data from Chamberlain et al., 1978, Table 5.2.