Evaluation of the Biopersistence of Commercial and Experimental Fibers Following Inhalation

Models for Mesothelioma Incidence Following Exposure to Fibers in Terms of Timing and Duration of Exposure and the Biopersistence of the Fibers

“…In both of these studies it was found that the longer fibers were eliminated more rapidly than the shorter fibers. Bernstein et al (1995) found that long fibers (>15 µm) were cleared about twice as rapidly as shorter fibers and also that the three fibers (MMVF11, Fiber B, Fiber J) cleared considerably faster than reported for crocidolite by Musselman et al (1994). The clearance rate after inhalation was four to five times more rapid than after intratracheal (IT) instillation, which they suggested was related to the IT method rather than the dose.…”

“…Another factor is the lower durability of the man-made fibers in the lungs, so that those that reach the target organ remain there for a shorter period before dissolution; a fuller discussion of these points is given by . Bernstein et al (1995Bernstein et al ( , 1996 investigated the biopersistence of a number of synthetic mineral fibers by exposing rats to an aerosol for 5 days and sacrificing subgroups at intervals up to 1 yr following exposure. The half-times of fibers in the lung ranged from 8 to 54 days, corresponding to elimination rates (l ) of 4.7 to 31.6/yr.…”

MATERIAL PROPERTIES OF MMVFs AND THEIR TIME-DEPENDENT FAILURE IN LUNG ENVIRONMENTS

“…This behavior is detected only for very soluble fibers, and only if one plots the peak value for the diameter distributions (Eastes et al, 1995), as opposed to the geometric mean diameters (Bernstein et al, 1995). Thus, we conclude that congruent dissolution of long fibers is an unlikely general clearance mechanism.…”

“…Thus, we conclude that congruent dissolution of long fibers is an unlikely general clearance mechanism. This conclusion is reinforced by the observation that for many MMVFs the long fibers (say > 20 µm) clear, apparently, much faster than short fibers (Bernstein et al, 1995;Bellmann & Muhle, 1995), which immediately introduces a length dependency of clearance that cannot be explained by a simple, single dissolution model, or by slower intracellular dissolution of the short fibers. As we have seen in Table 4, K dis at pH 4.5 is significantl y lower than at pH 7 for a limited range of MMVF compositions.…”

“…Closer examination of the in vivo clearance data (Bernstein et al, 1995(Bernstein et al, , 1996Bellmann & Muhle, 1995;Collier et al, 1997;ECB, 1997) shows that there is a systematic relationship between the ratio of clearance half-life for fibers longer than 20 µm to that of WHO fibers versus K dis , for which the WHO fibers are mostly those of length <20 µm, but >5 µm and aspect ratio >3 ( Figure 12). These data are consistent with the proposed mechanism of each long fiber of high K dis failing by enhanced brittle fracture to form two (at least) shorter fibers.…”