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270 CHAPTER 5 PHYSIOLOGICAL AND TOXICOLOGICAL CONSIDERATIONS

low, the compound will be rapidly excreted (see Section 2.3.9), The determi-
nation of alveolar air concentration can be used as biological exposure test for
organic solvents. This test is also widely applied to control for drunken driv-
ing. The concentration of a solvent in the blood is obtained by multiplying the
62 74
alveolar air concentration by the blood solubility coefficient. '
Lungs also secrete nonvolatile compounds. Lipid-soluble compounds may
thus be transported with the alveobronchotracheal mucus to the pharynx,
where they are swallowed. They may then be excreted or reabsorbed. Particles
are also removed by this rnucociliary escalator.
The particle size is the most important factor that contributes to the clear-
ance of particles. For particles deposited in the anterior parts of the nose, wip-
ing and blowing are important mechanisms whereas particles on the other
areas of the nose are removed with mucus. The cilia move the mucus toward
the glottis where the mucus and the particles are swallowed. In the tracheo-
bronchial area, the mucus covering the tracheobronchial tree is moved up-
ward by the cilia beating under the mucus. This rnucociliary escalator
transports deposited particles and particle-filled macrophages to the pharynx,
where they are also swallowed. Mucociliary clearance is rapid in healthy
adults and is complete within one to two days for particles in the lower air-
ways. Infection and inflammation due to irritation or allergic reaction can
markedly impair this form of clearance.
Particles deposited in the alveoli are phagocytized by alveolar macroph-
ages and cleared either through the rnucociliary escalator or through the lym-
phatic drainage system. Fibers may be too long to become phagocytized by
single macrophages. In such a case, several macrophages can participate in the
phagocytosis in a cooperative manner {see Fig. 5.39). Macrophages are able to
dissolve synthetic miner fibers to some extent but asbestos (especially arnfi-
boles) fibers remain mostly unaffected. This leads to the production of oxygen
radicals and inflammation mediators which induce macrophages to kill them-
selves. Another macrophage will then phagocytize the asbestos fiber and it too
will die. This vicious cycle will continue and it may ultimately lead to lung fi-
brosis and cancer. Small particles may also directly penetrate the epithelial
membrane and enter the blood stream.

5.3.3.5 Movements of Chemical Compounds in the Body
Absorption, distribution, biotransformation, and excretion of chemical
compounds have been discussed as separate phenomena. In reality all these
processes occur simultaneously, and are integrated processes, i.e., they all af-
fect each other. In order to understand the movements of chemicals in the
body, and for the delineation of the duration of action of a chemical in the or-
ganism, it is important to be able to quantify these toxicokinetic phases. For
this purpose various models are used, of which the most widely utilized are
the one-compartment, two-compartment, and various physiologically based
pharmacokinetic models. These models resemble models used in ventilation
engineering to characterize air exchange.

One-Comportment Mode/
The simplest toxicokinetic analysis involves measurement of the plasma
concentrations of a chemical at several time points after the administration of