A Meta-Analysis of Asbestos-Related Cancer Risk That Addresses Fiber Size and Mineral Type

Critical Reviews in Toxicology. 2008 Aug 6:49-73. [Epub ahead of print] [Link]

Berman DW, Crump KS.

Aeolus, Inc., Albany, California, USA.


Quantitative estimates of the risk of lung cancer or mesothelioma in humans from asbestos exposure made by the U.S. Environmental Protection Agency (EPA) make use of estimates of potency factors based on phase-contrast microscopy (PCM) and obtained from cohorts exposed to asbestos in different occupational environments. These potency factors exhibit substantial variability. The most likely reasons for this variability appear to be differences among environments in fiber size and mineralogy not accounted for by PCM.

In this article, the U.S. Environmental Protection Agency (EPA) models for asbestos-related lung cancer and mesothelioma are expanded to allow the potency of fibers to depend upon their mineralogical types and sizes. This is accomplished by positing exposure metrics composed of nonoverlapping fiber categories and assigning each category its own unique potency. These category-specific potencies are estimated in a meta-analysis that fits the expanded models to potencies for lung cancer (KL‘s) or mesothelioma (KM‘s) based on PCM that were calculated for multiple epidemiological studies in our previous paper (Berman and Crump, 2008). Epidemiological study-specific estimates of exposures to fibers in the different fiber size categories of an exposure metric are estimated using distributions for fiber size based on transmission electron microscopy (TEM) obtained from the literature and matched to the individual epidemiological studies. The fraction of total asbestos exposure in a given environment respectively represented by chrysotile and amphibole asbestos is also estimated from information in the literature for that environment. Adequate information was found to allow KL‘s from 15 epidemiological studies and KM‘s from 11 studies to be included in the meta-analysis.

Since the range of exposure metrics that could be considered was severely restricted by limitations in the published TEM fiber size distributions, it was decided to focus attention on four exposure metrics distinguished by fiber width: “all widths,” widths > 0.2 μ m, widths < 0.4 μ m, and widths < 0.2 μ m, each of which has historical relevance. Each such metric defined by width was composed of four categories of fibers: chrysotile or amphibole asbestos with lengths between 5 μ m and 10 μ m or longer than 10 μ m. Using these metrics three parameters were estimated for lung cancer and, separately, for mesothelioma: KLA, the potency of longer (length > 10 μ m) amphibole fibers; rpc, the potency of pure chrysotile (uncontaminated by amphibole) relative to amphibole asbestos; and rps, the potency of shorter fibers (5 μ m < length < 10 μ m) relative to longer fibers.

For mesothelioma, the hypothesis that chrysotile and amphibole asbestos are equally potent (rpc = 1) was strongly rejected by every metric and the hypothesis that (pure) chrysotile is nonpotent for mesothelioma was not rejected by any metric. Best estimates for the relative potency of chrysotile ranged from zero to about 1/200th that of amphibole asbestos (depending on metric). For lung cancer, the hypothesis that chrysotile and amphibole asbestos are equally potent (rpc = 1) was rejected (p ≤ .05) by the two metrics based on thin fibers (length < 0.4 μ m and < 0.2 μ m) but not by the metrics based on thicker fibers.

The “all widths” and widths < 0.4 μ m metrics provide the best fits to both the lung cancer and mesothelioma data over the other metrics evaluated, although the improvements are only marginal for lung cancer. That these two metrics provide equivalent (for mesothelioma) and nearly equivalent (for lung cancer) fits to the data suggests that the available data sets may not be sufficiently rich (in variation of exposure characteristics) to fully evaluate the effects of fiber width on potency. Compared to the metric with widths > 0.2 μ m with both rps and rpc fixed at 1 (which is nominally equivalent to the traditional PCM metric), the “all widths” and widths < 0.4 μ m metrics provide substantially better fits for both lung cancer and, especially, mesothelioma.

Although the best estimates of the potency of shorter fibers (5 < length < 10 μ m) is zero for the “all widths” and widths < 0.4 μ m metrics (or a small fraction of that of longer fibers for the widths > 0.2 μ m metric for mesothelioma), the hypothesis that these shorter fibers were nonpotent could not be rejected for any of these metrics. Expansion of these metrics to include a category for fibers with lengths < 5 μ m did not find any consistent evidence for any potency of these shortest fibers for either lung cancer or mesothelioma.

Despite the substantial improvements in fit over that provided by the traditional use of PCM, neither the “all widths” nor the widths < 0.4 μ m metrics (or any of the other metrics evaluated) completely resolve the differences in potency factors estimated in different occupational studies. Unresolved in particular is the discrepancy in potency factors for lung cancer from Quebec chrysotile miners and workers at the Charleston, SC, textile mill, which mainly processed chrysotile from Quebec. A leading hypothesis for this discrepancy is limitations in the fiber size distributions available for this analysis. Dement et al. (2007) recently analyzed by TEM archived air samples from the South Carolina plant to determine a detailed distribution of fiber lengths up to lengths of 40 μ m and greater. If similar data become available for Quebec, perhaps these two size distributions can be used to eliminate the discrepancy between these two studies.

Keywords: Amphibole; asbestos; chrysotile; fiber size; lung cancer; mesothelioma; mineralogy; risk assessment.