Asbestos Fibers and Other Elongate Mineral Particles: State of the ...

• For rats and hamsters, alveolar deposition
becomes practically zero when particle
AED exceeds 3.0 µm and aspect ratio exceeds
10. In contrast, considerable alveolar
deposition is found for humans breathing
at rest, even for EPs with AEDs approaching
5 µm and aspect ratio exceeding 10.
• Rodents have smaller-diameter airways
than humans, a characteristic which increases
the chance for particle deposition
via contact with airway surfaces.
• Turbulent air flow, which enhances particle
deposition via impaction, is common in
human airways but rare in rodent airways.
• Variations in airway branching patterns
may account for significant differences
in deposition between humans and rodents.
Human airways are characterized
by symmetrical branching, wherein each
bifurcation is located near the centerline
of the parent airway. This symmetry favors
deposition “hotspots” on carinal
ridges at the bifurcations due to disrupted
airstreams and local turbulence. Rodent
airways are characterized by asymmetric
branching, which results in a more diffuse
deposition pattern because the bulk flow
of inspired air follows the major airways
with little change in velocity or direction.
• Alveolar clearance is slower in humans
than in rats. Human dosimetry models
predict that, at nonoverloading exposure
concentrations, a greater proportion of
particles deposited in the alveolar region
will be interstitialized and sequestered in
humans than in rats.
An important consideration in the conduct and
interpretation of animal studies is the selection
of well characterized (with respect to chemical
and physical parameters) and appropriately
sized EMPs that take into account differences
NIOSH CIB 62 • Asbestos
in deposition and clearance characteristics
between rodents and humans. EMPs that are
capable of being deposited in the bronchoalveolar
region of humans cannot be completely
evaluated in animal inhalation studies because
the maximum thoracic size for particles in rodents
is approximately 2 µm AED, which is
less than the maximum thoracic size of about
3 µm AED for humans [Timbrell 1982; Su and
Cheng 2005].
3.4.2.1 Short-Term Animal Studies
There are several advantages to conducting
short-term animal studies in rats; one is that
the information gained (e.g., regarding overload
and maximum tolerated dose [MTD])
can be used to more effectively design chronic
inhalation studies [ILSI 2005]. The objectives
of these studies would be to
• Evaluate EMP deposition, translocation,
and clearance mechanisms;
• Compare the biopersistence of EMPs retained
in the lung with results from in vitro
durability assays;
• Compare in vivo pulmonary responses to
in vitro bioactivity for EMPs of different
dimensions; and
• Compare cancer and noncancer toxicities
for EMPs from asbestiform and nonasbestiform
amphibole mineral varieties of
varying shapes, as well as within narrow
ranges of length and width.
More fundamental studies should also be performed
to
• Identify biomarkers or tracer/imaging
methods that could be used to predict or
monitor active pulmonary inflammation,
pulmonary fibrosis, and malignant transformation;
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