Health Assessment Document for Diesel Emissions - NSCEP | US ...

1 volume basis (Table 4-1 ). This is due to larger alveolar diameters in humans and concomitantly
2 lower surface area per unit of lung volume.
3 The alternative, perhaps more accurate physiologically, is to consider deposition rate
4 relative to exposure concentration; the deposition rate will initiate particle redistribution
5 · processes (e.g., Clearance mechanisms, phagocytosis) that transfer the particles to various
6 subcompartments, including the alveolar macrophage pool, pulmonary interstitium, and lymph
7 nodes. Over time, therefore, only small amounts of the original particle intake would be
8 associated with the alveolar surface.
9
10 4.3. RESPIRATORY TRACT CLEARANCE RATES
11 4.3.1. Tracheobronchial Clearance
12 The dynamic relationship between deposition and clearance is responsible for
13 determining lung burden at any point in time. Clearance of highly insoluble particles from the
14 tracheobronchial region is mediated primarily by mucociliary transport and is a more rapid
15 process than those operating in alveolar regions. Mucociliary transport (often referred to as the
16 . mucociliary escalator) is accomplished by the rhythmic beating of cilia that line the respiratory
· 17 tract from the trachea through the terminal bronchioles. This movement propels the mucous
18 layer containing deposited particles (or particles within alveolar macrophages [AMs]) toward the
19 larynx. Clearance rate by this system is determined primarily by the flow velocity of the mucus,
20 which is greater in the proximal airways and decreases distally. These rates also exhibit
21 inte.rspecies and individual variability. Considerable species-dependent variability in
22 tracheobronchial clearance has been reported, with dogs generally having faster clearance rates
23 than guinea.pigs, rats, or rabbits (Felicetti et al., 1981). The half-time (t 112 ) values for
24 tracheobronchial clearance of relatively insoluble particles are usually on the order ofhours;
25 those for alveolar clearance may be hundreds of days in humans and dogs. The clearance of
26 particulate matter from the tracheobronchial region is generally recognized as being biphasic or
27 multiphasic (Raabe, 1982). Some studies have shown that particles are cleared from large,
28 intermediate; and small airways with t 112 of0.5, 2.5, and 5 h, respectively. However, reports have
29 indicated that clearance from conducting airways .is biphasic and that the long-term component
30 for humans may take much longer for a significant fraction of particles deposited in this region
31 and may not be complete within 24 h, as generally believed (Stahlhofen et al., 1990).
32 Although most of the particulate matter cleared from the tracheobronchial region will
33 ultimately be swallowed, the contribution of this fraction relative to carcinogenic potential is
34 unclear. With the exception of conditions of impaired bronchial clearance, the desorption t 112 for
35 particle-associated organics is generally longer than the tracheobronchial clearance times,
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