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

Abstract

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 (K L 's) or mesothelioma (K M '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 K L 's from 15 epidemiological studies and K M '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 µm, widths <0.4 µm, and widths <0.2 µm, 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 µm and 10 µm or longer than 10 µm. Using these metrics three parameters were estimated for lung cancer and, separately, for mesothelioma: K L A , the potency of longer (length >10 µm) amphibole fibers; rpc, the potency of pure chrysotile (uncontaminated by amphibole) relative to amphibole asbestos; and rps, the potency of shorter fibers (5 µm < length < 10 µm) 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 can...

Update of Potency Factors for Asbestos-Related Lung Cancer and Mesothelioma

“…However, unlike the present work, their conclusions were based on a meta-analysis that looked across studies, rather than analyzing the exposure responses within studies. A more complete comparison of our results with those of Hodgson and Darnton (2000) is presented in the companion to the present article (Berman and Crump, 2008).…”

“…Questions concerning the affect of fiber size and type are investigated more systematically in the accompanying article (Berman and Crump, 2008). In that article, K L 's and K M 's determined by fitting data across multiple studies are allowed to depend both on the mineralogical types and on the sizes (e.g., lengths and widths) of asbestos fibers.…”

“…However, unlike the present work, their conclusions were based on a meta-analysis that looked across studies, rather than analyzing the exposure responses within studies. A more complete comparison of our results with those of Hodgson and Darnton (2000) is presented in the companion to the present article (Berman and Crump, 2008).Further study to more rigorously elucidate the nature of the mathematical relationship between asbestos exposure and mesothelioma appears warranted. Among other things, it will be important to evaluate the degree that exposure error may be contributing to the appearance of supralinearity.…”

“…There is evidence from studies in both animals (Stanton et al, 1981;Davis et al, 1988;Berman et al, 1995) and humans ) that potency increases with increasing fiber length. And there is epidemiological evidence, including that obtained herein, of differences between the potency of chrysotile and amphibole asbestos, particularly with respect to mesothelioma (Figure 12).Questions concerning the affect of fiber size and type are investigated more systematically in the accompanying article (Berman and Crump, 2008). In that article, K L 's and K M 's determined by fitting data across multiple studies are allowed to depend both on the mineralogical types and on the sizes (e.g., lengths and widths) of asbestos fibers.…”

“…However, there is increasing evidence that neither of these assumptions is valid, which could account for the disparate estimates of potency obtained POTENCY FACTORS FOR ASBESTOS-RELATED LUNG CANCER 3 in different environments (Berman and Crump, 2003). In a follow-up paper (Berman and Crump, 2008) the EPA models are modified by allowing different types of asbestos to have different potencies and risk is predicted from exposures quantified using size fractions of asbestos different from the one determined by PCM. The ability of these different assumptions to reconcile potency estimates derived from different environments is evaluated.…”