Page 356 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

Toxicity of Nanomaterials Chapter | 18 323

VetBooks.ir INTRANASAL EXPOSURE Current understanding implies that the small particles
released from heated PTFE rapidly condense into larger
High doses of carbon black, given intranasally, showed
and less biologically potent particles (Lee and Seidel,
adjuvant activity as indicated by enlargement of peribron-
1991). Aged particles collected as agglomerates were not
chial lymph nodes and ovalbumin specific production of
toxic when given intratracheally to rats, but the particles
thymocyte (Th) 2 specific IL4, IL5, and IL10. Local cyto-
became toxic when rats were given inhalation exposure to
kine production after carbon black exposure is predictive
fumes evolved from the reheated agglomerate. Rats died
of allergic airway inflammation (De Haar et al., 2005).
with pulmonary edema and hemorrhage reflecting Type I
pneumocyte damage (Lee and Seidel, 1991).
INHALATION EXPOSURE
EPIDEMIOLOGICAL DATA
Both particle size and solubility are important determi-
nants of biological response after lung exposure. If Epidemiological studies show an association between par-
cleared rapidly they will be less injurious; if not they will ticulate air pollution and acute mortality and morbidity
remain as a chronic irritating source (Pickrell et al., 2004, down to ambient particle concentrations below 100 μg/
3
2009). Particles must be small enough to be inhaled into m . Whether this association also indicates causality
deep lung—usually taken to be , 4 μm (4000 nm). between acute health effects and particle exposure at
Particles between 4000 and 500 nm will be phagocytized these low levels is still unclear, but several examples of
and cleared rapidly. Particles , 500 nm aggregate size associations between particulate air pollution and adverse
will be less efficiently phagocytized by phagocytes and health effects are available, and it suggests a high proba-
may translocate to the pulmonary interstitium and remain bility that a cause and effect relationship exists.
there for relatively long periods of time. For example, in
a recent study of fullerene particles with a geometric Sulfur Dioxide (Oxides of Sulfur Particles)
mean diameter of 96 nm (based on number) in rat lungs,
it was estimated that .99% of particles remaining in the Sulfur dioxide (oxide of sulfur particles) comes mainly
lung 6 months after exposure were in the interstitium, from burning sulfur containing fuels (Sullivan et al.,
while particles that did not enter the interstitium were 2006), causing both indoor and outdoor pollution. For
cleared by alveolar macrophages relatively rapidly with a example, poorly ventilated kerosene space heaters are
half-life of 15 24 days (Shinohara et al., 2010). sources of indoor sulfur dioxide. Sulfur dioxide particles
Thermodegradation products of polytetrafluoroethy- are hygroscopic and tend to grow larger with increasing
lene (PTFE) contain singlet ultrafine particles (median hydration of the atmosphere (Sullivan et al., 2006).
diameter 26 nm); the fumes are toxic to rats at inhaled Nasal breathing filters out much of the inhaled sulfur
6
3
concentrations of 0.7 1.0 3 10 particles/cm . Inhalation dioxide; it is water-soluble and is often absorbed in the
studies with ultrafine particles ( 100 nm; NP) in rats upper portion of the respiratory tract (Sullivan et al.,
suggest that particles 50 nm in diameter, may contribute 2006). Sulfur dioxide is irritating to the eyes, nose and
to increased mortality and morbidity. Inhalation exposure airways, and its odor is detected at concentrations as low
rats caused an acute hemorrhagic pulmonary inflamma- as 0.5 ppm. At .6 ppm, companion animals often show
tion and death after 10 30 min (Oberdo ¨rster et al., 1995). acute clinical signs including tearing, runny nose, cough,
These results confirmed reports from other laboratories bronchospasm, and shortness of breath. Additional
that the toxicity of PTFE fumes should not be attributed chronic signs that come from prolonged exposure at lower
only to gas-phase components of these fumes. Aging of exposure concentrations include cough, mucus hyperse-
PTFE fumes with concomitant aggregation of the ultrafine cretion, and frequent clearing of the throat; these reflect
particles greatly decreases their toxicity (Oberdo ¨rster airway inflammation and chronic bronchitis. Massive
et al., 1995). exposure is capable of inducing severe, permanent pulmo-
Fumes from overheated Teflon (PTFE)-coated frying nary damage (Sullivan et al., 2006). Low level prolonged
pans cause a fatal hemorrhagic pneumonitis in caged birds human exposures correlate well with bronchial asthma.
directly adjacent in both time and space to the overheat-
ing (Blandford et al., 1975). Birds appear to be more sen- Swine Barn Dust Exposure
sitive than rats and humans to direct inhalation of Teflon
fumes from overheated skillets; this sensitivity probably Gases and/or ultrafine particles in swine barns can be
reflects their physiologically more efficient respiratory important factors in the development of increased bron-
system. When birds are removed from the overheating chial responsiveness both in animals and their human
event by a short period of time, or when birds are in an caretakers. For example, healthy human volunteers weigh-
adjacent room, there is a comparatively minimal reaction. ing pigs for 3 h developed a neutrophilic pneumonitis,