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

the mechanisms by which asbestos fibers and
some other EMPs cause lung cancer, mesothelioma,
and nonmalignant respiratory diseases.
As these mechanisms become understood,
biologically based models can be developed to
extrapolate from exposure-dose-response relationships
observed in animals to estimates of
disease risk in exposed humans. In addition,
such studies would provide (1) an opportunity
to measure molecular and cellular outcomes
that can be used to determine why one animal
species responds differently from another and
(2) information on EMP characteristics associated
with eliciting or potentiating various biological
effects. The outcomes of these studies can
then be evaluated in subsequent experiments to
provide (1) risk assessors with a useful understanding
of the various disease mechanisms by
which animals respond to EMP exposures; and
(2) regulatory agencies and industrial hygiene
and occupational health professionals with information
needed to implement appropriate
exposure limits and risk management programs
for monitoring worker exposure and health.
It is anticipated that it may be difficult to find
populations of workers that are exposed to EMPs
with characteristics (e.g., dimension, composition)
of interest that are sufficiently large to provide
adequate statistical power, and where exposures
are not confounded or where confounding
can be effectively controlled in the analysis.
NIOSH retains exposure information and, in
some cases, personal air sample filters collected
and archived from past epidemiological studies
of workers exposed to asbestos. Such existing
data might be used to update and extend findings
from these studies. Where appropriately balanced
epidemiological studies can be identified,
it may be possible to conduct meta-analyses to
investigate important EMP characteristics. The
analysis of archived samples may help to elucidate
how more detailed characteristics of exposure
96
(e.g., particle dimension) relate to disease outcomes.
New epidemiological (retrospective and
prospective) studies should not be undertaken
unless feasibility studies (e.g., preliminary assessments
of study population size, exposure latencies,
records of exposure, and confounders) have
been appropriately considered.
Because the opportunities for informative epidemiological
studies are likely to be limited,
it will be necessary to complement them with
toxicological testing, and an integrated approach
to toxicological research will be needed
to understand how various types of EMPs induce
disease. Where epidemiological studies of
new cohorts are possible, or where epidemiological
studies of previously studied cohorts
can be updated, attempts should be made to
link their results with those of toxicological
studies to assess the ability of various types
of toxicological testing to predict health outcomes
in humans. Toxicological testing should
be done with attention to collecting more specific
information, including: (1) physical characteristics
(e.g., dimension); (2) chemical composition;
(3) in vitro acellular data (dissolution,
durability); and (4) in vitro/in vivo cellular data
(e.g., cytotoxicity, phagocytosis, chromosomal
damage, mediator release).
To help elucidate which physicochemical properties
are important for inducing a biological effect,
it may be necessary to generate exposures
to EMPs of specific dimensions and composition.
Several approaches are being pursued by
NIOSH to overcome technological difficulties
in generating sufficient quantities of well-characterized
and dimensionally restricted EMPs.
Efforts to generate mineral samples of appropriate
particle-size dimensions by grinding techniques
have met with some success but have
not consistently generated EMPs in restricted
size ranges of interest or in sufficient quantity
NIOSH CIB 62 • Asbestos