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The toxicological response of Brazilian chrysotile asbestos: A multi-dose sub-chronic 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., Füllinsdorf, 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 well characterised aerosol of chrysotile asbestos, a 90 day sub-chronic inhalation toxicology study was performed using a commercial Brazilian chrysotile (CA 300). The protocol was based upon that established be 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 fibre dose in the lung and the influence of fibre length.
Wistar male rats were randomly assigned to an air control group and to two CA 300 exposure groups at mean fibre aerosol concentrations of 76 fibres L>20 µm/cm3 (3,413 total fiber/cm3; 536 WHO fiber/cm3) or 207 fibres L>20 µm/cm3 (8,941 total fiber/cm3; 1,429 WHO fiber/cm3). The animals were exposed using a flow past, nose only exposure system for five days per week, 6 hours per day, during 13 consecutive weeks (65 exposures) followed by a subsequent non-exposure period lasting for 92 days. Animals were sacrificed after cessation of exposure and after 50 and 92 days of non-exposure recovery. At each sacrifice, sub-groups of rats were assessed for the determination of the lung burden; histopathological examination; cell proliferation response; broncho-alveolar lavage with the determination of inflammatory cells; clinical biochemistry and for analysis by confocal microscopy.
Though 90 days of exposure and 92 days of recovery, chrysotile at a mean exposure of 76 fibres L>20 µm/cm3 (3,413 total fiber/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 modelling has indicated that these particles are essentially amorphous silica. At an exposure concentration of 207 fibres L>20 µm/cm3 (8,941 total fiber/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 5,000 times greater than the US-Threshold Limit Value of 0.1 f(WHO)/cm3, chrysotile produces no significant pathological response.
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