Toxicology of Industrial Compounds

118 PULMONARY TOXICITY STUDIES WITH MAN-MADE ORGANIC FIBRES
lung and mesothelial cell proliferation at 0 hrs, 5 days 1, 3, 6 and 12
months postexposure.
Fibre preparation and inhalation exposure
Ultrafine Kevlar ® p-aramid fibrils were supplied by DuPont Fibres. A
special preparation of respirable p-aramid fibrils which had been prepared
for the 2-year inhalation study (Lee et al., 1988) was utilized for this study.
Bulk Canadian chrysotile asbestos fibres were obtained from Mr John
Addison of the Institute of Occupational Medicine in Edinburgh, Scotland.
Attempts were made to size-separate the bulk fibre preparation (i.e.
selectively enhance the percentages of long fibres while removing the short
fibres) by placing the fibres in a rotating sieve shaker and sieving through a
series of metal mesh screens. The fraction containing the longer fibres (and
a number of short fibres) was collected and generated for inhalation
studies; fibres were collected on a filter and dimensional analysis (i.e. length
and diameter assessments) was performed using scanning electron
microscopy. The results showed that this technique was partially successful
as the median and mean lengths of fibres were increased from 3 and 5 µm,
respectively, in the original bulk sample to 6 and 9 µm in the generated
sample preparation. The median lengths and diameters of p-aramid fibrils
used in the study were 9 µm and 0.3 µm, respectively.
The methods for aerosol generation of p-aramid fibrils have previously
been reported (Warheit et al., 1992). Final mean fibre concentrations for
the p-aramid exposures were 772 and 419 f cm −3 .
Aerosols of chrysotile asbestos fibres were generated in a similar
manner, i.e. with a binfeeder and baffles, but without the microjet
apparatus. Final mean fibre concentrations for the chrysotile asbestos
exposures were 782 and 458 f cm −3 . Fibre lung burdens were quantified
from digested lung tissue of animals sacrificed immediately after the end of
the 2-week exposure.
Pulmonary lavage and biochemical assays on lavaged
fluids
Bronchoalveolar lavage procedures, cell quantification, and biochemical
assays were conducted according to methods previously described (Warheit
et al., 1984a, 1992). In addition, the methods for measuring lactate
dehydrogenase (LDH), N-acetyl-β-glucosaminidase (NAG), and alkaline
phosphatase (ALP) and protein in BAL fluids have been reported (Warheit
et al., 1992).