Tissue Fiber Studies as Indicators of Exposure
The analysis of human tissue for asbestos fibers is another area of continuing investigation, although there are many uncertainties associated with this approach of measuring bodily indicators of exposure (Pooley, 1976; Rogers, 1984; Gibbs et al., 1990; Srebro et al., 1995; De Vuyst et al., 1998; Roggli and Sharma, 2004). Quantification of exposure based on the retained fiber number is a relative index of (a) the fibers' ability to penetrate the alveoli of the lungs, and (b) the extent to which they are retained (Howard, 1984; Langer and Nolan, 1998). The analysis of tissues for asbestos focuses on the residual fiber population because the long, durable fibers are preferentially retained and chrysotile in the tissues has much less biopersistence. The long latency period for mesothelioma and new growth means that chrysotile fibers visible in pathological tissue specimens cannot be relevant to the induction of the malignancy. The range of tissue masses examined, the lack of information in terms of anatomical site, the possibility of contamination of specimens during necropsy and preparation, the lack of valid reference laboratory values for population groups rather than convenience case material (autopsies and lung cancer surgical samples), the lack of interlaboratory standardization for comparability purposes, and problems related to the number of fibers counted (e.g., short-fiber elimination bias and analytical sensitivity) are formidable laboratory challenges (Morgan and Holmes, 1983; Lee et al., 1995; De Vuyst et al., 1998). In general, asbestos fiber biomarkers in tissues can be used to confirm exposure to amphiboles (persistent fibers in the body) and chrysotile (probably more recent exposures for shorter fibers particularly).
In view of the many uncertainties, tissue fiber studies cannot be used in isolation to reach conclusions regarding causation. For example, asbestos fiber counts determined in the lung tissue and samples of tumor tissue and pleural plaques for mesothelioma cases at one institution suggested to the authors that chrysotile has a major causal role in mesothelioma, even if the fibers were short and very thin (Suzuki and Yuen, 2002; Suzuki et al., 2005). These short fibers are actually fine dust with no pathogenic effect, and their presence in malignant tissue is unexplained. Along with the lack of a comparison group for the case series, use of a nonstandard technique without controls, and possible asbestos fiber contamination of laboratory substances contacting the samples, their contention that very short asbestos fibers (particles) cause mesothelioma is not supported by comprehensive analyses, such as that performed as part of the proposed methodology for a quantitative human risk assessment based on epidemiological studies by Berman and Crump (2003) and by an expert panel for the Agency for Toxic Substances and Disease Registry (ATSDR, 2003). In a video-thoracoscopic study of the "black spots" of the pleura, normal appearing pleura and lung tissue of 14 patients with various pulmonary diagnoses, including 3 patients with mesothelioma and 6 without a history of asbestos exposures, amphiboles outnumbered chrysotile fibers in all samples. These results contradict those of Suzuki and Yuen (Boutin et al., 1996). Based on a series of 1445 cases having analyses of lung asbestos fibers, other investigators concluded that commercial amphiboles are responsible for most of the mesothelioma in the United States (Roggli et al., 2002).
Estimating a risk of mesothelioma based on tissue fiber analyses has been attempted (McDonald et al., 1989; Rogers et al, 1991, 1994; McDonald, 1994; Dufresne et al., 1996; Rodelsperger et al., 1999). A study examined lung tissues from 78 Canadian men and women who died of mesothelioma, as well as 78 lung tissues from age-, sex-, and hospital-matched controls. The lung samples were from the pathologists' stock without information on what parts of the lung the samples were collected. Relative risks for developing mesothelioma are reported for different fiber types and lengths. The study found that the risk of mesothelioma was significantly related to concentrations of amphibole fibers longer than 8 µm and that fibers shorter than 8 µm accounted for none of the cancer risk (McDonald et al. 1989). Rogers et al. (1991) indicated that fibers less than 10 µm in length increased risk, but with reanalysis the authors corrected that earlier conclusion (Rogers et al., 1994).
The lung tissue was studied in Sweden for 76 deceased asbestos cement workers (7 with mesothelioma) who were exposed to chrysotile and small amounts of amphiboles and of 96 control subjects. While chrysotile was the main fiber found, the difference between the groups was most pronounced for amphiboles, and strong correlations were found between duration of exposure and with the content of amphiboles in the lungs. The percentage of chrysotile fibers was similar for cases, exposed control subjects, and nonexposed subjects (Albin et al., 1990b). As noted earlier, these researchers published an analytic epidemiology study to test the hypothesis about mesothelioma and asbestos exposures, which showed an increased risk of exposures of mixed asbestos fibers among the workers (Albin et al., 199Oa).