Page 256 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

Respiratory Toxicity Chapter | 13 223

VetBooks.ir more extensive, fibroblast proliferation and the excess carcinomas. Occasionally, lung tissue injury causes bron-
chogenic adenocarcinoma, which is an unusual lung
production of collagen may result in fibrosis. In a still
tumor in cats; it may metastasize to the digits and to the
higher level of injury, even fibroblasts cannot effectively
fill voids, healing by secondary intent fails and lung tissue abdominal wall. Average survival time for tumors metas-
is lost and emphysema forms. The extent to which this tasizing to the digits is only B5 weeks (Van der Linde-
varied may be related to variations in local dose, the Sippman, 2000; Petterino et al., 2005).
reserve of biological antioxidants, or the balance between Certain mouse strains (strain A and Swiss-Webster
proteinase antiproteinase (Pickrell et al., 1983, 1987a,b). mice) with mutations in the K-ras genes similar to human
carcinomas develop adenomas that increase in incidence
Asthma after the inhalation of certain toxicants or carcinogens.
These mice are potential models for human lung carcino-
In asthma, small conducting airways constrict at lower irritant
genesis (Witschi and Last, 2001).
concentrations than in normal lungs. Bronchoconstriction
Rat lungs occasionally contain lesions of epithelial
reduces airway diameter resulting in increased small airway
cells surrounding material identified as keratin (Witschi
airflow resistance. Symptoms include coughing, wheezing,
and Last, 2001). The cells may compress lung paren-
and progressive dyspnea (Witschi and Last, 2001).
chyma and occasionally invade it. These lesions are found
Guinea pigs are highly sensitive to upper airway irrita-
more frequently in long-term tests of animals exposed to
tion and to subsequent development of bronchial asthma.
substances not considered to be carcinogens such as car-
Other animals that develop syndromes similar to human
bon black, titanium dioxide and certain man-made fibers.
asthma include horses, dogs and cats (Padrid, 2000; Davis
Controversy exists as to whether these are cysts filled
and Rush, 2002; McCue et al., 2003; Pirie et al., 2003;
with keratin, or can be classified as tumors.
Reinero et al., 2006). In horses, an asthmatic condition
In humans, it has been estimated that 80% 90% of all
known as heaves is associated with inhaled endotoxins
lung tumors are caused by inhaling cigarette smoke
and organic dust particulates, which are thought to be
(Witschi and Last, 2001). Dogs are companion animals
synergistic in their effects (Pirie et al., 2003). Potentially
that live with their owners over long periods of time.
detrimental effects can be reduced by maintaining horses
Although rare, some dogs developed either nasal or lung
in “low dust” stables or at pasture, since these environ-
tumors after being exposed to owner’s second-hand ciga-
ments have significantly lower airborne dust and endo-
rette smoke. In described cases, the tumors were carcino-
toxin levels (McGorum et al., 1998). Poultry farmers have
mas epithelial in origin and malignant. Dogs living for
significantly higher incidences of chronic bronchitis. The
protracted periods of time in a home with a smoker were
major risk factor for respiratory symptoms was shown to
more susceptible to lung cancer than those in homes of
be inadequate ventilation of animal houses (Radon et al.,
nonsmokers (odds ratio 5 1.6, 95% confidence interval
2002). Airborne endotoxin can cause flu like symptoms in
0.7 3.7). No relations were found between cancer rates
birds; this condition must be differentiated from infectious
and increasing the number of packs of cigarettes smoked
avian influenza (Joseph and Subbarao, 2005).
per day or the proportion of time the dog spent within the
Specific allergen immunotherapy is a potential therapy
home. However, dog breeds with short- and medium-
for feline asthma. In one study, Rush Immunotherapy
length noses had an increased tendency to develop lung
(RIT) blunted eosinophilic airway inflammation in experi-
cancer (odds ratio 5 2.4, 95% confidence interval
mental feline asthma. BAL cytokine profiles favoring a
0.7 7.8). Dogs with long noses (dolocephalic breeds)
Th2 response developed after giving Bermuda grass anti-
tend to deposit carcinogenic particles in the nasal cavity,
gen. RIT shifted the response to increased IFN-γ, and
and may develop nasal carcinomas. Alternatively, dogs
IL-10 thereafter. The mechanism of RIT may involve
with shorter noses (brachycephalic breeds) tend to allow
changes in allergen-specific immunoglobulin production,
carcinogenic particles to deposit in the upper airways and
induction of hyporesponsive lymphocytes or alteration of
develop bronchogenic carcinomas (Reif et al., 1992). The
cytokine profiles (Reinero et al., 2006).
most frequent tumors in dog lungs, however, are mam-
mary tumors that metastasize to the lung.
Lung Cancer
In laboratory animals, spontaneously occurring malignant
pulmonary tumors are rare, except for very old animals. If Agents Known to Produce Lung Injury in
lung tumors do develop in laboratory rodents, they are Animals
generally peripheral adenomas instead of the more central
tumors seen in humans. Adenomas usually originate from Zinc Phosphide
type II pulmonary epithelial cells, or Clara cells. These Poultry are highly susceptible to zinc phosphide poison-
adenomas rarely have sufficient time to develop into ing. For example, approximately 200 chickens