Page 357 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

324 SECTION | III Nanoparticles, Radiation and Carcinogens

VetBooks.ir and they had an increased bronchial responsiveness to (Zornoff et al., 2006). These data are probably most relevant
animals.
obese
companion
methacholine. Wearing a mask reduced, but did not abol-
to
cardiac-compromised
ish, the inflammatory response (Larsson et al., 2002). In
Differential diagnoses or conditions that must be adequately
vitro data suggest that airway epithelial cell swine dust distinguished from smoke inhalation include asthma, heart
extract exposure enhances subsequent lymphocyte adhe- disease, allergic pulmonary disease, inhalation of toxic sol-
sion to epithelial cells by a modulation of the expression vents or sprays, pneumonia, neoplasia, trauma, COPD, and
of intracellular adhesion molecule 1, and protein kinase C pneumothorax (Fitzgerald and Vera, 2006).
α (Mathiesen et al., 2004). The associated inflammation Household use of metal oxide ENMs in sunscreens
is characterized by increased numbers of neutrophils, (mostly zinc oxide or titanium dioxide), or as cosmetics,
macrophages, and lymphocytes to a lesser degree, in pigs has not led to reports of toxicities in humans (Nel et al.,
and their caretakers. The inflammation is associated with 2006). Other metal oxide ENMs such as ferric oxide,
increased IL-6 in cultured cells, suggesting an asthma-like however, are cytotoxic to mesothelioma cells and fibro-
reaction (Pickrell et al., 2010). Interestingly, this inflam- blasts in vitro (Brunner et al., 2006). In comparison, zinc
3
mation is most pronounced in caretakers with no oxide fumes at high doses (500 μg/m ), in an occupational
prior exposure to this environment, which suggests a setting, cause fume fever (fatigue, chills, fever, myalgia,
tolerance to endotoxin or other substances in this environ- cough and leukocytosis) (Nel et al., 2006).
ment associated with repeated exposures (Von Essen and
Romberger, 2003).
Dog Exposures to Automobile Exhaust
Aerosols
Nanoparticle Exposure in the Home
Repeated, high exposures to the complex pollutant mix-
Environmental tobacco smoke (ETS) is a health risk for tures in automobile exhaust aerosols cause lung structural
companion animals. It is a major source of indoor particles, changes induced by sustained inflammatory processes
and can release more than 4000 potential toxicants into the resulting in airway and vascular remodeling and altered
air (Sullivan et al., 2006). While the effects of smoke repair. These exposures are complicated by a heavy load
inhalation may be mostly due to toxic gases (e.g., carbon of oxidant gases. Bronchoalveolar lavage from dogs in
monoxide), ETS particles, such as acrolein, are capable of heavily exhaust-polluted environments show increased
producing pulmonary damage (Fitzgerald and Vera, 2006). numbers of activated alveolar macrophages in association
Frequently observed signs include wheezing, chronic cough, with ultrafine particles in alveolar type I and II cells.
chronic hyper reactive airways, and chronic bronchitis. Cytokines released from both circulating inflammatory
Water soluble toxins are absorbed and injure mostly the cells and resident lung cells, in response to endothelial
upper respiratory tract, while less soluble materials go dee- and epithelial injury, are thought to play important roles.
per into the lungs and injure the pulmonary parenchyma The lung changes are typically associated with myocardial
(Fitzgerald and Vera, 2006). The EPA has classified ETS a and endothelial pathology (Calderon-Garciduenas et al.,
group A carcinogen, meaning that there is sufficient evi- 2001a,b).
dence to indicate that it will produce cancer in humans
(Sullivan et al., 2006). Epidemiological evidence in humans
EMERGING CHALLENGES
demonstrates a strong relationship between ETS and cancer.
Mice exposed to ETS experimentally at high doses devel- A question that received recent scientific scrutiny is the
oped increased incidences of cancer (Hecht, 2005). potential indirect impact that ENMs may have as contam-
Although most investigators continue to compare experi- inant carriers. For example, the uptake of phenanthrene
mental results in animals with human data in humans, most by daphnids is increased by C 60 nanoparticles, and it
animals appear to be less sensitive than man (Coggins, increases phenanthrene toxicity to algae. Effects on
2002). Beta-carotene supplementation attenuated cardiac uptake and toxicity are, however, variable depending on
remodeling induced by 1-month of tobacco smoke exposure the organism and the toxicant (Baun et al., 2008). The
in rats (Zornoff et al., 2006). After 1-month’s exposure to significance of these observations is still unclear, but it
ETS cardiac remodeling was present as indicated by disor- indicates that the possibility of ENMs affecting the
ganization or loss of myofilaments, infolding of plasma potency and/or kinetics of toxicant coexposures should be
membrane, dilatation of the sarcoplasmic reticulum, and considered. On the other hand, ENMs can be used to
polymorphic mitochondria with swollen or decreased cris- reduce the impacts of environmental contaminants. Iron
tae. Rats given beta-carotene during cigarette smoke expo- (0 valence/charge) particles, e.g., may be used to remove
sure had minimal or no significant cardiac remodeling. chromium and lead in drinking water (Iseli et al., 2009).
These data suggest beta carotene attenuates, reduces, or Evidence of ecotoxicological effects associated with
minimizes cardiac remodeling induced by cigarette smoke nanomaterials is emerging. For example, leachates from