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5,3 TOXICITY AND RISKS INDUCED BY OCCUPATIONAL EXPOSURE TO CHEHICAL COMPOUNDS 265

standard includes size definitions for three mass fractions. The inhaiable frac-
tion consists of particles that can enter the upper airway. Its upper size limit is
100 (xrn (the diameter of human hair is 50-100fjim). The thoracic mass frac-
tion consists of particles that can penetrate past the larynx. Its upper size limit
is about 30 jam and median cut point 10 (xm. The respirable mass fraction
consists of particles that can enter the alveolar region. Its upper sixe limit is
about 10 fim and median cut point 4 jjtm (see Fig. 5.35).
5.3.3.2 Distribution
After absorption, a chemical compound enters the circulation, which
transfers it to all parts of the body. After this phase, the most important factor
affecting the distribution is the passage of the compound through biological
membranes. From the point of view of the distribution of a chemical com-
pound, the organism can be divided into three different compartments: (1) the
plasma compartment; (2) the intercellular compartment; and (3) the intracel-
lular compartment. In all these compartments, a chemical compound can be
bound to biological macromolecules. The proportion of bound and unbound
(free) chemical compound depends on the characteristics of both the chemical
63 64
and the binding macromolecules. '
In the plasma, most chemicals are bound to plasma proteins. Albumin is
quantitatively the most important binding protein but beta globulin and
acidic glycoprotein also bind chemicals. The number of binding sites is lim-
ited, and, therefore, high doses of chemicals may cause saturation of protein
binding. In most cases, an adverse effect does not require saturation of pro-
tein binding sites because free and bound chemical are in equilibrium in the
plasma, and the free chemical is available for toxic action in the target tis-
sues. The circulation is extremely important for distribution of chemicals.
Heavily perfused organs, i.e., the brain, liver, and kidneys, receive most of
the cardiac output, and in these organs the concentration of a chemical in-
creases much more rapidly than in the other organs. Organs whose perfu-
sion is small, e.g., resting muscles and adipose tissue, receive only a small
portion of the cardiac output, and therefore concentration of a chemical in
these organs increases much more slowly than in the heavily perfused or-
f>2 64
gans. ~

FIGURE 5.35 Regions of pulmonary pathways and size of particles that can reach different regions
of the lungs. 4