Dm. Bernstein et al., EVALUATION OF SOLUBLE FIBERS USING THE INHALATION BIOPERSISTENCE MODEL, A 9-FIBER COMPARISON, Inhalation toxicology, 8(4), 1996, pp. 345
The biopersistence of nine fibers was evaluated using an inhalation mo
del. The fibers studied were compositions with different in vitro acel
lular solubility. The commercial and new glass wool fibers were essent
ially sodium borosilicates and the commercial and new stone wools were
essentially calcium modified silicates. Fischer 344 male rats were ex
posed to a well-defined rat respirable aerosol (mean diameter of simil
ar to 1 mu m) at a concentration of 30 mg/m(3), 6 h/day for 5 days wit
h postexposure sacrifices at 1 h, 1 day, 5 days, 4 wk, 13 wk, and 26 w
k. At sacrifice, the whole lung was removed weighed, and frozen at -20
degrees C for subsequent digestion by low-temperature plasma ashing.
The number and bivariate size distribution of the fibers in the aeroso
l and lung were determined. At 1 h following the last exposure, the 9
fibers were found to have lung burdens ranging from 7.4 to 33 x 10(6)
fibers/lung with geometric mean diameters (CMD) of 0.40-0.54 mu m. The
range of initial lung burdens was found to reflect the different biva
riate distributions in the exposure aerosol. The fibers were found to
be removed from the lung following the cessation of exposure with weig
hted half-lives of WHO fibers ranging from 11 to 54 days. The WHO clea
rance was found to closely reflect the clearance of fibers in the 5-20
mu m length range. An important difference in removal was seen betwee
n the long fiber (L > 20 mu m) and shorter fiber (L between 5 and 20 m
u m and L < 5 mu m) fractions depending upon composition. For all glas
s wools and the new stone wools, the longer fibers were removed notabl
y faster than the shorter fibers. It was found that the time for compl
ete fiber dissolution based on the acellular in vitro dissolution rate
at pH 7.4 was highly correlated (r = .97, p < .01) with the clearance
half-times of fibers > 20 mu m in length when using a double exponent
ial fit to the data. No such correlations were found with any of the l
ength fractions using the acellular in vitro dissolution rate at pH 4.
5. Examination of the fiber length distribution and particles in the l
ung from 1 h through 5 days of exposure indicated that, especially for
those fibers that form leached layers, a certain amount of fiber brea
kage may have occurred during this early period. These results demonst
rate that the inhalation biopersistence model can be used in the proce
ss of evaluating the optimal composition for the reduction of fiber bi
odurability in the lung, and that for fibers with high acellular solub
ility at pH 7.4, the clearance of long fibers is very rapid.