Page 251 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

218 SECTION | II Organ Toxicity

VetBooks.ir proximity to blood with the lowest oxygen concentration. reached in 30 90 min. Patients only infrequently require
more than monitoring and rudimentary support measures.
Oxygen is extracted about twice as efficiently as in mam-
Full recovery from such injuries is likely, but permanent
mals, which is necessary for the increased oxygen demand
associated with sustained flight. Air sacs and air mem- loss of function is possible in cases of exposure to very
brane spaces provide a reduction in density to birds; high levels of chlorine (Winder, 2001). Humans exposed to
reduced density is helpful in staying afloat on water. The chlorine may have a decreased VC (limited forced expira-
increased gas exchange efficiency in birds makes them tory volume) (Mehta et al., 2005). This limitation is fre-
more susceptible to some inhaled toxicants, such as the quently reversible and less than that of seasonal allergic
fumes released from overheated nonstick cookware coated rhinitis (Shusterman et al., 2004).
with polytetrafluoroethylene (Lightfoot and Yeager,
2008). This sensitivity can also be exploited as a very sen- Ammonia
sitive monitor of air quality. An example of this is the
Animals and caretakers are frequently exposed to elevated
canary in the mine that predicts toxicity to the miners
levels of ammonia (NH 3 ) gas in swine confinement facili-
(Brown et al., 1997; West et al., 2006).
ties (Carson, 2004). At greater than 100 ppm, ammonia
irritates eyes and respiratory membranes, increases the
incidence and intensity of microbial or parasitic infec-
GENERAL PRINCIPLES IN THE
tions, and reduces growth rate. High levels of ammonia
PATHOGENESIS OF LUNG DAMAGE
found in poultry houses have about the same level of tox-
CAUSED BY CHEMICALS icity to birds as they would to other animals (Brown
et al., 1997). Ammonia concentrations greater than
Oxidant Burden
60 ppm cause kerato-conjunctivitis in broilers; reduced
Oxidant burden in the lung is frequently associated with bacterial clearance and enhanced sensitivities to bacterial
airborne prooxidants such as nitrogen dioxide (NO 2 ), sul- infections (Carson, 2004).
fur dioxide, oxidants such as ozone, free radicals, tobacco
smoke, or is caused by an overzealous defense by phago- Anhydrous Ammonia
cytic cells (Pickrell et al., 1987a; Pickrell and Mageed,
Anhydrous ammonia (NH 3 ) is injected from pressurized
1995; Witschi and Last, 2001). Exposure to oxidants can
tanks into the ground as a fertilizer nitrogen source. It can
lead to changes in lung structure and biochemistry
be lethal to animals and humans if pressurized tanks are
(Pickrell et al., 1987b; Witschi and Last, 2001). Pivotal
breached or large containers are spilled in transit (Carson,
roles have been established for superoxide, prooxidant
2004). Anhydrous ammonia reacts with air moisture to
peroxy nitrites, and hydroxyl radicals. Responses depend
form a vapor cloud that can either remain for several
on the oxidant burden in combination with the glutathione
hours or disperse efficiently, depending on wind velocity
or biological antioxidant concentration. With sufficient
and humidity. In animals and man, the eyes and upper
oxidant burden and depletion of glutathione, all lung tox-
respiratory tract are prime targets. If the air ammonia con-
ins have an inflammatory disease component. In the pres-
centration is higher than 5000 ppm, it can cause a fatal
ence of significant oxidant burden, but in the presence of
apnea or laryngeal edema. Survivors may be blinded by
high levels of glutathione, lung defensive metabolic
corneal lesions and sloughed epithelium. Removal of ani-
enzymes are activated. At intermediate glutathione levels,
mals is important if the vapor cloud does not disperse rap-
inflammation is activated using nuclear factor kappa beta.
idly. Supportive therapy may be curative in moderate
At lower levels of glutathione, mitochondrial enzymes are
exposures. In humans, loss of olfactory ability was associ-
activated. The relation of programmed cell death (apopto-
ated with exposure to anhydrous ammonia, as well as a
sis) to mitochondrial enzyme activation is being investi-
history of wheezing and asthma, and of flu-like illness
gated (Nel et al., 2006).
(Snyder et al., 2003).
Toxic Inhalant Gases Carbon Dioxide
Carbon dioxide (CO 2 ) is well tolerated, even at concentra-
Chlorine tions as high as 5%. Higher concentrations stimulate the
Exposure to chlorine may originate from the manufacture rate and depth of respiration (Carson, 2004). It is, however,
of pulp, paper, plastics, and chlorinated chemicals (Witschi being explored as a novel human stressor (Kaye et al.,
and Last, 2001). Chlorine gas is irritating to the upper air- 2004). It is an asphyxiant at extremely high concentrations
ways, and can cause hemoptysis, dyspnea, tracheobronchi- (.40%). Because it is heavier than air, it collects in the
tis, or even bronchopneumonia in animals inhaling lower portion of animal facilities (Carson, 2004). It is used
sufficient concentrations. Peak symptoms are typically as a euthanasia agent in some laboratory animal species.