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VetBooks.ir Chapter 13

Respiratory Toxicity

Deon van der Merwe

INTRODUCTION analyses help to pinpoint specific molecular reactions to
specific cell types. In addition, they help us describe the
The respiratory system is relevant in toxicology as a tar-
more relevant influence of each cell on the others in the
get of toxic effects, and also as a major route of absorp-
near neighborhood. Tissue culture, organ minces, and
tion of inhaled gases and atmospheric particles. If
in vivo animal exposure studies, such as broncho-alveolar
inhalation and subsequent absorption reach a toxic
lavage washings, further elucidate these interactions.
threshold, inhaled chemicals have the potential to pro-
duce lung disease. If the chemical is translocated to
other organs, disease can be produced in those organs. THE UPPER AIRWAYS
As a highly perfused organ system, the respiratory sys-
Normal Function
tem is also a potential target for toxic chemicals in the
blood circulation, irrespective of the route of absorption. The nasopharynx is lined by pseudostratified columnar
Inhalation toxicology refers to the respiratory system as ciliated epithelium with goblet cells (Dungworth, 1993).
a route of exposure. In contrast, respiratory toxicosis Abundant lymphoid nodules are present in the submu-
refers to respiratory organ toxicosis. The environments cosa. The eustachian tubes extend from the middle ear
in which animals live are directly relevant to respiratory to the nasal cavity. Many animals, including horses and
toxicosis (Pickrell, 1991). Different species may have small laboratory rodents, are obligate nose breathers.
anatomical features that lead to specific patterns of Other animals can breathe through either their nose
deposition and absorption of chemicals from the air, or mouth.
resulting in species variations in adverse effects (Morris The mucous membranes of the nasal passages produce
et al., 1986). secretions from serous and mucous glands, which produce
To understand respiratory toxicosis we need to under- mucopolysaccharides and mucoprotein, and goblet glands,
stand (1) the toxicant dose delivered to specific sites of which produce similar, but sulfated, secretions. Ciliated
the lung and (2) the effects of toxicants on respiratory epithelium covers a capillary net providing a rich blood
system tissues under conditions of acute and chronic supply. Mucous secretions protect the mucous membranes
exposures. Many lung diseases have their beginnings with and can retain particulate matter and substances that dis-
increases in oxidative lung burden. There is strong evi- solve in the mucous. It also allows for rapid heat transfer
dence that oxidative lung burden may favor development between the capillary net and the air (Taylor, 1974).
of lung diseases such as bronchitis, asthma, and interstitial Beating of cilia propels mucous and allergens, pathogens,
lung disease (Witschi and Last, 2001). and toxicants that become entrapped in the mucous
Advances in lung toxicology are augmented by inter- towards the glottis, from where it is shunted to the diges-
disciplinary collaboration between anatomists, physiolo- tive tract by swallowing (Dungworth, 1993). Effective
gists, immunologists, pathologists, molecular biologists, mucociliary clearance depends on coordinated secretions
epidemiologists, clinicians, and many other shared disci- by the goblet cells, submucous glands, and serous secre-
plines. Adaptation of pulmonary function tests to animals tory cells to form an upper mucous layer underlying a
has led to the comparison of human and animal data, gen- more aqueous layer, which allows the upper mucous layer
erally providing more robust conclusions compared to to be transported by cilia (Corcoran, 2010). Nonciliated
data from single species. Recent molecular measurements (Clara) epithelial cells have P-450 monooxygenase sys-
have brought home how closely tied many of these dis- tems that can metabolize xenobiotics, and they can pro-
eases are to specific protein changes. Such molecular duce inflammatory compounds such as prostaglandins.

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