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

the current paradigm because their biopersistence
and distributions of fiber lengths are not
substantially different from those of the amphiboles.
The biochemical basis of the enhanced
pathogenicity of these two fiber types has not
been elucidated. This suggests that some fiber
types may possess surface or chemical reactivity
that imparts added pathogenicity over and
above what would be anticipated for long biopersistent
fibers. Because of the many variations
in elemental composition, crystalline structure,
and other characteristics of these minerals,
it will be impossible to study all variants.
Therefore, a strategy will need to be developed
for selecting minerals for testing. This strategy
should include consideration of occupationally
relevant minerals and habits in order to complement
available information, availability of
appropriate and well-characterized specimens
for testing, and practical relevance of the results
to be achieved through testing.
EPA’s Office of Pollution Prevention and Toxics,
NIEHS, NIOSH, and OSHA assembled an
expert panel in the 1990s to consider major issues
in the use of animal models for chronic
inhalation toxicity and carcinogenicity testing
of thoracic-size elongate particles. Issues considered
included the design of animal tests of
chronic inhalation exposure to EMPs; preliminary
studies to guide them; parallel mechanistic
studies to help interpret study results and
to extrapolate findings with regard to potential
health effects in humans; and available screening
tests for identifying and assigning a priority
for chronic inhalation study. There was general
agreement that (1) chronic inhalation studies of
EMPs in the rat are the most appropriate tests
for predicting inhalation hazard and risk of
EMPs to humans; (2) no single assay or battery
of short-term assays could predict the outcome
of a chronic inhalation bioassay for carcinogenicity;
and (3) several short-term in vitro and in
72
vivo studies may be useful to assess the relative
potential of various EMPs to cause lung toxicity
or carcinogenicity [Vu et al. 1996].
Such short-term assays and strategies were considered
by an expert working group assembled
by the International Life Sciences Institute’s
Risk Science Institute to arrive at a consensus
on current assays useful for screening EMPs
for potential toxicity and carcinogenicity [ILSI
2005]. Dose, dimension, durability, and possible
surface reactivities were identified as critical
parameters for study, although it was noted
that no single physicochemical property or
mechanism can now be used to predict carcinogenicity
of all EMPs. The strategy for shortterm
(i.e., 3 months or less) testing in animal
models included sample preparation and characterization
(composition, crystallinity, habit,
size distribution); testing for biopersistence in
vivo with use of a standard protocol such as
that of the European Union [European Commission
1999]; and a subchronic inhalation or
instillation challenge of the rat, with evaluation
of lung weight and fiber burden, bronchoalveolar
lavage profile, cell proliferation, fibrosis, and
histopathology. Additionally, other nonroutine
analyses for particle surface area and surface reactivities
and short-term in vitro cellular toxicological
assays might be evaluated. The use of in
vitro tests should be tempered by the observations
that standard protocols fail to distinguish
relative pathogenic potentials of even nonelongate
silicates (such as quartz versus clay dusts)
and that treatment of particle surfaces (such as
modeling their conditioning upon deposition
on the lipoprotein-rich aqueous hypophase
surface of the deep lung) can greatly affect their
expression of toxicities [ATSDR 2003].
EMPs encountered in any particular work environment
are frequently heterogeneous, which
limits the ability of epidemiological and other
NIOSH CIB 62 • Asbestos