Page 253 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

220 SECTION | II Organ Toxicity

VetBooks.ir mammals is typical of acute high-level oxidant exposure heavily on pulmonary alveolar macrophages and the
mucociliary escalator. Alveolar macrophages phagocytose
of a somewhat more intense nature than that associated
particles, then migrate to the bronchi and trachea for
with pulmonary edema (Pickrell et al., 1987a).
clearance. Ultrafine particles that enter the alveolar inter-
stitium may be cleared at a much slower rate (Shinohara
Particle Size and Clearance
et al., 2010). Particles can leave the lung and enter the
Particle Size and Deposition Mechanisms vascular system, causing a risk to organs downstream
from the lung (Nemmar et al., 2001; Borm et al., 2006).
Inhaled aerosol particles are frequently of multiple sizes
Alternatively, particles may be soluble in aqueous media
(polydispersed). Particles of different aerodynamic sizes
and can be dissolved in mucus. Fine and ultrafine (nano)
deposit in different anatomic areas of the mammalian and
particles with much of their mass in contact with the sur-
avian respiratory tracts. In mammalian lungs, particles
face are especially subject to such dissolution. Factors
with aerodynamic diameters of 5 30 μm mostly deposit
affecting this solubility are quite complex; they include
by inertial impaction in the nasopharyngeal region
but are not limited to composition of the aqueous fluid,
because they do not follow curving airflow well (Witschi
particle size, particle chemical composition, steepness of
and Last, 2001). Inertial impaction in bird respiratory
concentration gradient, curvature, agglomeration, and
tracts is influenced by flow velocity and Reynolds num-
aspect ratio (Nemmar et al., 2001; Borm et al., 2006).
bers (Re) (trachea 100 cm/s at Re 5 700; primary bronchi
Some ultrafine particles that are deposited in the nasal
130 cm/s and Re 5 600; narrowed primary bronchus
mucosa can be transported to the brain via the olfactory
200 cm/s and Re 5 550). The expected sites of inertial
bulb (Oberdo ¨rster et al., 2004).
impaction in birds are similar to those in mammals
Particle solubility and chemical reactivity are influ-
(Brown et al., 1997).
enced by the physical chemical environment. Bicarbonate
Slightly smaller particles (1 5 μm in aerodynamic
in lung simulant fluid, e.g., can enhance solubility in parti-
diameter) mostly deposit by gravitational sedimentation
cles moderately soluble in aqueous media. To obtain rele-
in the conducting airways—the trachea, bronchi and
vant data solubility and reactivity should be measured in
bronchioles—as airflow speed progressively slows down
an environment as near to that of the lung environment as
towards the airway terminals. In the human lung, sedi-
possible. This can sometimes be accomplished with
mentation is an important mechanism for deposition at
in vitro conditions closely simulating biological solutions
sizes greater than 0.2 μm in diameter (Witschi and Last,
(Powers et al., 2006). Solubility is thought to be a function
2001). In birds, deposition probability is a product of (res-
of chemical activity, specific surface area, radius and cur-
idence time)(aerodynamic diameter). In parabronchi,
vature, agglomeration, and specific chemicals that are
where flows are as low as 3 cm/s (Re 5 2), and residence
adsorbed to the NSP (Borm et al., 2006). It is important to
times may be up to 1 min for complete change of air sac
consider not just solubility in water, but in fluids that bear
volume at rest, deposition probabilities can be quite high
significant resemblance to that of the epithelial lining fluid
(Brown et al., 1997).
(ELF). ELF is the fluid than lines the epithelial cells in the
Particles ,1 μm in aerodynamic diameter have a good
respiratory tract. A volume of 40 100 mL is predicted for
probability to deposit by Brownian diffusion when their
mature humans. The pH varies from 6.9 at the end of inspi-
random movement causes them to bump into wet surfaces
ration to 7.5 at the end of expiration. Bicarbonate is a
(Witschi and Last, 2001). Diffusion, like sedimentation, is
major buffer, and the pH variation is caused by varying
most important where residence times are the longest.
CO 2 during expiration (Langmuir, 1965). Bicarbonate in
The probability of deposition by diffusion increases with
lung simulant fluid increases the solubility of magnesium
decreasing particle size, so that deposition of particles
oxide (MgO) (Pickrell et al., 2006). Stoichiometry of the
with aerodynamic diameters of less than 0.5 μm is largely
likely chemical species suggests a conversion of MgO to
by diffusion. Breathing pattern can be important. During
magnesium hydroxide (Mg(OH) 2 ) in aqueous media, and a
exercise particles acquire higher velocity, momentum and
subsequent conversion to the hydrated carbonate
inertia that increase impaction deposition higher up the
nesquehonite.
respiratory tract. Alternatively, breath holding causes
In chickens, small dust particles were found trapped in
more deposition by gravitational sedimentation and
the respiratory epithelial cell trilaminar surfactant (Brown
diffusion.
et al., 1997). No particles were found in the vascular sys-
tem, kidneys and heart, suggesting that at least those par-
Particle Clearance ticles did not enter the vascular system. After 1 h 54% of
Particle clearance in mammals is important to defense of the particles remained, while after 36 h approximately
the lung. Rapid clearance lessens exposure time and 36% remained, suggesting that appreciable clearance took
extent of injury. Clearance of intact particles depends place. The mechanism of the clearance is not completely