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Toxicology of Industrial Compounds

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8<br />

Pulmonary Toxicity Studies with Man-made<br />

Organic Fibres: Preparation and Comparisons <strong>of</strong><br />

Size-separated Para-aramid with Chrysotile<br />

Asbestos Fibres<br />

DAVID B.WARHEIT, 1 MARK A.HARTSKY, 1 CHARLES<br />

J.BUTTERICK 2 and STEVEN R.FRAME 1<br />

1 DuPont Haskell Laboratory, Newark, DE, 2 Texas Tech<br />

Health Sciences Center Lubbock, TX<br />

Introduction<br />

This study was designed to compare the pulmonary toxic effects <strong>of</strong><br />

inhaled, size-separated preparations <strong>of</strong> chrysotile asbestos fibres with paraaramid<br />

fibrils at similar aerosol fibre concentrations. Chrysotile samples<br />

are known to have an abundance <strong>of</strong> short fibres, with mean lengths<br />

generally in the range <strong>of</strong> 2 µm. This is important to note because one <strong>of</strong> the<br />

critical factors influencing the pathogenesis <strong>of</strong> fibre-related lung disease is<br />

fibre dimension (Davis et al., 1986). As a consequence, attempts were made<br />

to selectively enhance the mean lengths <strong>of</strong> chrysotile asbestos fibres used in<br />

this inhalation toxicity study, in order to make reasonable comparisons<br />

between the two fibre-types.<br />

Methods<br />

General experimental design<br />

Groups <strong>of</strong> male Crl: CDBR rats (7–8 weeks old, Charles River Breeding<br />

Laboratories, Kingston, New York) were used to assess the pulmonary<br />

effects <strong>of</strong> 2-week inhalation exposures to size-separated preparations <strong>of</strong><br />

Kevlar ® para-aramid fibrils or chrysotile asbestos fibres. Animals were<br />

exposed 6 hr day −1 , 5 days week −1 for 2 weeks. For this study, Kevlar ® was<br />

utilized as a representative para-aramid fibril. The two commercial types <strong>of</strong><br />

para-aramid fibres are Twaron ® , made by Akzo, and Kevlar ® , made by<br />

DuPont. Following exposure, the lungs <strong>of</strong> p-aramid or chrysotile-exposed<br />

animals and age-matched sham controls were subsequently evaluated by<br />

bronchoalveolar lavage fluid analysis at 0 h, 5 days, 1 and 3 months<br />

postexposure. The lungs <strong>of</strong> additional animals were evaluated for<br />

biodurability, pulmonary clearance, pulmonary histopathologic lesions and

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