Page 338 - Industrial Ventilation Design Guidebook

294 CHAPTER 5 PHYSIOLOGICAL AND TOXICOLOGICAL CONSIDERATIONS

first engulf the particles and then destroy them by bombarding them with
proteolytic enzymes. The immunological system is responsible for providing
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specific responses against specific antigens. '
Inhaled gaseous compounds are absorbed in all parts of the respiratory
system whereas particle size determines how deep into the airways the parti-
cles will be transported in the airstream. Shortness of breath is a typical sign ot
a chemical exposure that has affected the lungs, and it may be evoked through
immunological mechanisms (e.g., formaldehyde, ethyleneoxide), or through
toxic irritation (formaldehyde, isocyanates, sulfur dioxide, nitrogen dioxide,
ozone). Frequently the mechanism depends on the concentration of the com-
pound in the inhaled air. The accident in Bhopal, India, is an example of a poi-
soning epidemic that caused serious lung injuries. There, an explosion of a
large container led to poisoning of thousands of individuals by rnethylisocyan-
ate, and subsequently to blindness, serious lung injuries, and deaths in the ex-
41
posed population.
Acute Lung Toxicity Toxic compounds can induce acute deleterious ef-
fects in various parts of the airway. Irritating compounds may cause bron-
choconstriction within the bronchial tree, edema of its mucous membranes,
and increased secretion of mucus. In addition, ciliar activity may decrease in
the bronchial and bronchiolar regions, and thereby prevent the clearance of
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mucus and foreign particles from the airway. ' '
Bronchoconstriction may take place without any cellular injury. For exam-
ple, low concentrations of sulfur dioxide induce bronchoconstrktion. Asthmat-
ics are especially sensitive; a concentration of sulfur dioxide as low as 0.4 ppm
58 59
may induce bronchoconstriction. ' Cholinergic activation mediated via the
vagal nerve is responsible for this reaction because it can be prevented with anti-
74
cholinergic compounds. An inflammatory reaction may also cause bronchoc-
onstriction. Inflammatory mediators, such as metabolites of arachidonic acid
released from the epithelial cells of the airways, may increase the extent of the
bronchoconstriction. Epithelial cells also produce relaxing compounds that an-
tagonize bronchoconstriction, but in inflammation, there is reduced production
of these compounds (e.g., prostaglandin E 2). Also, exposure to inorganic parti-
cles may induce a dramatic acute inflammation in the lungs, leading to the ex
cretion of a number of bioactive molecules from pulmonary phagocytic cells.
Compounds that induce bronchoconstriction include tobacco smoke, formal-
dehyde, and diethyl ether. Several other compounds, such as acidic fumes (e.g.,
sulfuric acid) and gases, such as ozone and nitrogen dioxide, as well as isocyan-
ates, can cause bronchoconstriction. Also, cellular damage in the airways induces
bronchoconstriction because of the release of vasoactive compounds. Frequently,
different mechanisms work at the same time, provoking bronchoconstriction and
58 59
increased secretion of mucus, both of which interfere with respiration. '
The alveolar surface is predominantly covered by alveolar type I cells. These
cells are the primary targets of chemical compounds causing alveolar damage.
Typically, alveolar type I cells are replaced by alveolar type II cells subsequent to
alveolar damage induced by deep lung irritants (e.g., nitrogen dioxide and
74
ozone), On the other hand, when small particles reach the alveolar region, spe-
cialized phagocytes, mainly macrophages, phagocytize the particles and are then
removed from the lungs by the mucociliary escalator in the trachea, or by the lym-