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

widths are greater for the prismatic tremolite
samples. Although the prismatic tremolite samples
clearly generated fewer mesotheliomas than
the asbestiform tremolite samples, it is not apparent
whether the tumorigenic potency per EMP is
lower for the nonasbestiform tremolites.
In a comparison of one asbestiform and two
nonasbestiform tremolites, cellular in vitro assays
for LDH release, beta-glucuronidase release,
cytotoxicity, and giant cell formation showed relative
toxicities that parallel the differences seen in
an in vivo rat IP injection study of tumorigenicity
using the same samples [Wagner et al. 1982].
In vitro cellular or organ tissue culture studies
showed squamous metaplasia and increased
DNA synthesis in tracheal explant cultures treated
with long glass fibers or with crocidolite or
chrysotile fibers, whereas cleavage fragments
from their nonasbestiform analogues, riebeckite
and antigorite, were not active [Woodworth
et al. 1983]. For alveolar macrophages in vitro,
crocidolite fibers induced the release of ROS
at an order of magnitude greater than cleavage
fragments from nonasbestiform riebeckite
[Hansen and Mossman 1987]. Similar differences
were observed in hamster tracheal cells for
• induction of ornithine decarboxylase, an
enzyme associated with mouse skin cell
proliferation and tumor promotion [Marsh
and Mossman 1988];
• stimulating survival or proliferation in a
colony-forming assay using those hamster
tracheal epithelial cells [Sesko and
Mossman 1989];
• activation of proto-oncogenes in tracheal
epithelial and pleural mesothelial cells in
vitro [Janssen et al. 1994]; and
• cytotoxicity [Mossman and Sesko 1990].
NIOSH CIB 62 • Asbestos
A recent review concludes that a large body of
work shows that cleavage fragments of amphiboles
are less potent than asbestos fibers in a
number of in vitro bioassays [Mossman 2008].
Several studies have investigated induction of
molecular pathways in cells exposed to EMPs.
The goals of such studies were to elucidate
mechanisms involved in fiber-induced pathogenicity
and to compare the relative potency of
asbestiform and nonasbestiform EMPs. However,
seemingly contradictory findings between
some experiments suggest that improved methods
for preparation of size-selected test particles
and more extensive characterization of
EMPs are needed.
Although few animal studies of nonasbestiform
amphibole dusts have been conducted, this research
has revealed generally significant differences
in pathogenicity between nonasbestiform
and asbestiform amphiboles. There are few findings
of biological effects or tumorigenicity induced
by samples classified as nonasbestiform,
and there are rational hypotheses as to the
cause of those effects. There are general fundamental
uncertainties concerning EMP properties
and biological mechanisms that determine
mineral particle toxicities and pathogenicities,
specifically concerning the similarities or differences
in disease mechanisms between EMPs
from asbestiform versus nonasbestiform amphiboles.
In vitro studies have generally shown
differences in specific toxic activities between
some asbestiform and nonasbestiform amphibole
EMPs, although in vitro systems are
not yet able to predict relative pathogenic risk
for mineral fibers and other EMPs. This suggests
a focus of research to determine if and
when nonasbestiform amphibole EMPs are active
for tumorigenicity or other pathology, if
there is a threshold for those activities, and if
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