Toxicology of Industrial Compounds

120 PULMONARY TOXICITY STUDIES WITH MAN-MADE ORGANIC FIBRES
were increased from 3 µm in the original generated sample to 6 µm in the
size-separated sample. In comparison to the chrysotile asbestos sample,
there was a significantly greater proportion of long p-aramid fibrils which
were used in the inhalation study with median lengths >9 µm.
Lung burden analysis
Although the aerosol fibre concentrations were similar throughout the
study (p-aramid high conc.=772 f cm −3 , chrysotile high conc.=782 f cm −3 ;
p-aramid low conc.=419 f cm −3 , chrysotile low conc.=458 f cm −3 ),
measurement of lung fibre burdens from digested lung tissue at time 0 (i.e.
immediately after exposure) demonstrated a substantial difference in lung
burden between the two fibre-types as measured by phase contrast optical
microscopy (PCOM). The mean lung fibre (>5 µm) burden from 3 rats/
dose group exposed to chrysotile asbestos was 3.7×10 7 (±7.4×10 6 ) fibres/
lung for the high dose group and 1.3×10 7 (±4×10 6 ) fibres/lung for the low
dose group. In contrast, the mean lung fibre burden from 3 rats/dose group
exposed to para-aramid fibres was 7.6×10 7 (±1.9×10 7 ) fibres per lung for
the high dose group and 4.8×10 7 ( ±2.1×10 7 ) fibres/lung for the low dose
group. In addition, the count median length of chrysotile fibres recovered
from the lungs of exposed animals immediately after 2-week exposure was
3.5 µm, while the count median diameter was 0.15 µm. In contrast, the
count median length of para-aramid fibres recovered from the lungs of
exposed animals immediately after 2-week exposure was 8.6 µm, while the
count median diameter was 0.3 µm (Figure 8.2(A) and (B); numerical data
not shown). These data indicate that our attempts to size-separate
Canadian chrysotile fibres were only partially successful. The lung burden
data also suggest that comparisons of the effects of chrysotile vs paraaramid
at high and low doses are difficult to make since the doses were not
equivalent.
Bronchoalveolar lavage data
Two-week exposures to p-aramid fibrils or chrysotile asbestos fibres
produced transient pulmonary inflammatory responses as measured by
bronchoalveolar lavage fluid analysis (see Table 8.1).
Light microscopic histopathology
Exposures to p-aramid and chrysotile were associated with minimal to mild
centriacinar inflammation and fibrosis (increased trichrome staining)
immediately after and 5 days after 2-week exposures. Lesions were slightly
more prominent in p-aramid-exposed rats due to increased inflammation.
Lesions were less severe at 1 month and essentially resolved at 6 months