Dose-Response Data and Setting Standards in Asbestos-Associated Diseases

asbestos-induced diseasesAs previously indicated, the setting of permissible limits of exposure to asbestos, primarily a workplace issue, depends upon the establishment of dose-response relationships, with subsequent determination of an acceptable level of risk. For the asbestos-associated diseases, this task would be immeasurably simpler if dose-response relationships were similar for all industrial processes, all fiber types, and all asbestos-induced diseases. Unfortunately, the evidence indicates substantial variability of relationships within these categories.

It has already been suggested that the cumulative dose of exposure to asbestos which will produce early indicators of asbestosis may very well be lower than that which has been shown to result in excess risk of lung cancer. It is likely that even lower, and almost certainly short, exposures to asbestos dust will lead to cases of mesothelioma, which fortunately remain rare. In general, from a regulatory standpoint, a standard can reasonably be based on epidemiologic evidence on either asbestosis or lung cancer, assuming that the population has been followed adequately and taking into account the period of latency. Contrary to some assertions, evidence based on asbestosis will probably generate a more restrictive standard than that based on lung cancer. It should be comforting to know that there are recent studies of mortality from exposure to asbestos in which the population or subgroups show no excess risk of lung cancer. It does not seem likely that additional dose-response data for mesothelioma will make it possible to set limits on exposure which can predictably be expected to prevent the occurrence of this effect.

Variability in the risk of lung cancer related to the segment of the industry studied is substantial. Some studies of occupationally exposed populations cannot be used for comparing dose-response relationships because appropriate individual estimates of exposure over a working lifetime are not possible. This problem has been particularly notable in studies of insulators and other workers exposed to the dust of product use. Where exposure and effect have been adeqinsulatorsuately measured or estimated, it is clear that there is a gradient of risk of lung cancer, the lowest for a given dose being found in miners and millers and the highest in asbestos textile manufacturing workers, with intermediate slopes among others engaged in the manufacture of asbestos products, such as asbestos cement building materials. On the basis of limited information on exposure, one may infer that a steep dose-response curve also exists for asbestos-exposed insulators. The basis for these differing risks by process, while not fully understood, has a number of biologically plausible hypotheses, some of which are based on studies in animals. Varying physical dimensions of asbestos fibers are likely to be encountered in these different segments of the industry. Specifically, the diameter or length of the fiber (or both) have pathogenetic importance, the thinner, longer fibers being most likely to possess enhanced potency in producing both the fibrogenic and malignant effects defeated with My Canadian Pharmacy. Limited data suggest that retained fibers in the lungs of asbestos textile workers have greater length than fibers in other asbestos manufacturing workers. Variations in biologic potency in specific portions of the industry have obvious regulatory implications, and the setting of different standards for discrete portions of an industry or even a plant is not without precedent in the United States.

For many years, evidence has been evolving which indicates substantial differences in the risks of adverse health effects for various types of asbestos fibers. Limited data suggest that for equivalent doses, the risks of asbestosis and lung cancer are increased for exposures to amphibole fiber, particularly crocidolite, in contrast to populations exposed only to chrysotile fiber, however, the weight of the evidence on differential risks in relation to the type of fiber relates to mesothelioma. In mining (chrysotile, in contrast to crocidolite) and manufacturing (friction materials, textiles,’ and gas masks), the experience with mesothelioma has been strikingly less favorable in those populations exposed to crocidolite than chrysotile. Most European and UK standards have taken this differential risk into account based on these recent and increasingly convincing research findings. In the United States, we have to date not yet accepted this evidence. Clearly, this is an important example of nonconcordance between this scientific data base and decisions on public policy.

The assessment of risk for potential hazards of exposure to asbestos in schools and other public buildings, or as the result of contact with consumer products containing asbestos, has received recent attention, both in regulatory and judicial arenas. Such assessment generally involves low-dose extrapolation from existing dose-response relationships obtained in occupational settings. It will be obvious from earlier comments that the selection of dose-response relationships to be used for this assessment will importantly influence the estimates of risk at doses which are orders of magnitude lower than in the workplace. The shape of the dose-response curve at such low doses is generally assumed to be linear through the origin, based on two considerations. First, it is considered that the existing data do not allow the conclusion that the shape is nonlinear, which is, of course, not proof that it is indeed linear. Secondly, the assumption of linearity is widely considered to be consistent with prudent policy on public health, since it is likely to err on the side of overestimating the risk. It will, of course, become obvious that low-dose extrapolation assuming linearity in mathematic modelling will result in an anticipated excess of lung cancers for any dose, no matter how small. When such calculations are made for lifetime risk in a large population (eg9 the United States), any numbers will seem to some to be unacceptable, and only by putting such estimates into perspective by comparison with everyday commonly accepted risks will rational policy emerge.

All the previously mentioned references: