The Toxicological Response of Brazilian Chrysotile Asbestos: A Multidose Subchronic 90-Day Inhalation Toxicology Study with 92-Day Recovery to Assess Cellular and Pathological Response
David M. Bernstein, Consultant in Toxicology, Geneva, Switzerland
Rick Rogers, Rogers Imaging Corporation, Needham, Massachusetts, USA
Paul Smith, Research & Consulting Company Ltd., F¨ullinsdorf, Switzerland
Jörg Chevalier, EPS Experimental Pathology Services AG, Muttenz, Switzerland
Inhalation toxicology studies with chrysotile asbestos have in the past been performed at exceedingly
high doses without consideration of fiber number or dimensions. As such, the exposures
have exceeded lung overload levels, making quantitative assessment of these studies difficult
if not impossible. To assess the cellular and pathological response in the rat lung to a wellcharacterized
aerosol of chrysotile asbestos, a 90-day subchronic inhalation toxicology study
was performed using a commercial Brazilian chrysotile (CA 300). The protocol was based on
that established by the European Commission for the evaluation of synthetic vitreous fibers.
The study was also designed to assess the potential for reversibility of any such changes and to
permit association of responses with fiber dose in the lung and the influence of fiber length.Wistar
male rats were randomly assigned to an air control group and to 2 CA 300 exposure groups
at mean fiber aerosol concentrations of 76 fibers L>20 µm/cm3 (3413 total fibers/cm3; 536
WHO fibers/cm3) or 207 fibers L>20 µm/cm3 (8941 total fibers/cm3; 1429 WHO fibers/cm3).
The animals were exposed using a flow-past, nose-only exposure system for 5 days/wk, 6 h/day,
during 13 consecutive weeks (65 exposures), followed by a subsequent nonexposure period lasting
for 92 days. Animals were sacrificed after cessation of exposure and after 50 and 92 days of
nonexposure recovery. At each sacrifice, subgroups of rats were assessed for the determination
of the lung burden; histopathological examination; cell proliferation response; bronchoalveolar
lavage with the determination of inflammatory cells; clinical biochemistry; and for analysis by
confocal microscopy. Through 90 days of exposure and 92 days of recovery, chrysotile at a mean
exposure of 76 fibers L>20 µm/cm3 (3413 total fibers/cm3) resulted in no fibrosis (Wagner
score 1.8 to 2.6) at any time point. The long chrysotile fibers were observed to break apart into
small particles and smaller fibers. In vitro modeling has indicated that these particles are essentially
amorphous silica. At an exposure concentration of 207 fibers L>20 µm/cm3 (8941 total
fibers/cm3) slight fibrosis was observed. In comparison with other studies, chrysotile produced
less inflammatory response than the biosoluble synthetic vitreous fiber CMS. As predicted by
the recent biopersistence studies on chrysotile, this study clearly shows that at that at an exposure
concentration 5000 times greater than the U.S. threshold limit value of 0.1 f(WHO)/cm3,
chrysotile produces no significant pathological response.
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