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

Evidence from in vivo studies in rodents and in
vitro studies indicates that EPs (vitreous glass
and EMPs) with a length equal to or greater
than the diameter of rodent lung macrophages
(about 15 µm) are most closely linked to biological
effects observed in rodent lungs [Blake
et al. 1998]. Alveolar macrophages appear to
be capable of phagocytizing and removing EPs
shorter than approximately 15 µm, either by
transport to the mucociliary system or to local
lymph channels. With increasing length above
approximately 15 µm, alveolar macrophages appear
to be increasingly ineffective at physical removal,
resulting in differential removal rates for
EPs of different lengths. Although EP lengths
greater than 15 µm appear to be associated with
toxicity in experimental studies with rodents, a
“critical” length for toxicity in humans is probably
greater than 15 µm [Zeidler-Erdely et al.
2006]. For long EPs that cannot be easily cleared
by macrophages, biopersistence in the lung is
influenced by the ease with which the EPs break
into shorter lengths.
2.9.3 Biopersistence and Other
Potentially Important Particle
Characteristics
It has been hypothesized that the differences
in crystalline structure between amphibole
asbestos fibers and amphibole cleavage fragments
account for apparent differences in toxicological
response to these particles. Cleavage
fragments that meet the dimensional criteria
for countable particles under federal regulatory
policies for asbestos fibers are generally
shorter and wider than asbestos fibers
[Siegrist and Wylie 1980; Wylie 1988]. This
dimensional difference between populations
of asbestos fibers and populations of cleavage
fragments might contribute to generally
shorter biopersistence in the lung for cleavage
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fragments than for asbestos fibers. Asbestos fibers
also tend to separate longitudinally once
deposited in the lung, thus increasing the total
number of retained fibers without an accompanying
reduction in lengths of the retained
fibers [NRC 1984]. In contrast, cleavage fragments
tend to break transversely because of
dissolution of their weaker crystalline structure,
resulting in shorter particles that can be
more easily cleared through phagocytosis and
mucociliary clearance [Zoltai 1981]. The impact
of these structural differences on solubility
in lung fluids warrants study, because substantial
differences in solubility in lung fluids
between asbestos fibers and other EMPs (including
amphibole cleavage fragments) could
translate into differences in toxicity.
2.9.3.1 Biopersistence
Dissolution of EPs in the lung is a poorly understood
process that is dependent on particle
characteristics, biological processes, and concomitant
exposure to other particulates. The
ability of an EP to be retained and remain intact
in the lung is considered an important factor in
the process of an adverse biological response.
EPs of sufficient length that remain intact and
are retained in the lung are thought to pose the
greatest risk for respiratory disease. The ability
of an EP to reside long-term in the lung is generally
referred to as biopersistence. Biopersistence
of EPs in the lung is a function of site and rate
of deposition, rates of clearance by alveolar
macrophages and mucociliary transport, solubility
in lung fluids, breakage rate and breakage
pattern (longitudinal or transverse), and rates
of translocation across biological membranes.
The rates of some of these processes can affect
the rates of other processes. For example, a high
rate of deposition in the alveolar region could
potentially overwhelm macrophage clearance
NIOSH CIB 62 • Asbestos