Asbestos-Related Disease - Amphiboles, Tremolite
Asbestos, Safe occupational exposure level
Thus the cancer risk of high past exposures to asbestos has been established. In most industries, however, progress has been made and exposures markedly lowered. The most important practical question of the last decade then is: how far down must the exposure be lowered to remove, if possible, the increased risk of cancer, or of any disease? Obviously there would be no increased risk with no exposure. But what is the level of exposure, if any, which is low enough to be also tolerated without increased incidence of cancer or any disease? Such a no-effect level of exposure seems to be reported by all epidemiological studies and demonstrated by common experience in industrial populations. Reaching some scientific decision on this question would have far-reaching practical consequences.
In consideration of this problem some questions of principle of carcinogenicity must be kept in mind. There are two schools of thinking. According to the "one-hit" hypothesis one molecule of a carcinogen, or one fibre, by damage to the biologically vulnerable material such as DNA of its nucleus, can change one cell into a cancerous cell. This one cell then multiplies and eventually produces cancer. On the other hand the "threshold" hypothesis recognises the possibility of repair of lesions in DNA and the existence of a complex defence mechanism in the body which copes with individual deviated cells, such as cancer cells, spontaneously appearing throughout the lifetime; cancer can only develop if and when the defence system is overcome by large numbers of such cells, created by a large number of "hits", i.e. if and when the "threshold of tolerance" is overstepped.
The results of epidemiological studies seem to support the "threshold" hypothesis: in all studies there are lower levels of exposure to asbestos under which no excess of cancer is found. However, the supporters of the "one-hit" hypothesis argue that negative findings do not truly reflect reality; that any exposure to asbestos leads to damage and that in principle there cannot be any safe level of exposure to a carcinogen; and that the excess of cancers in low exposures is simply so small that the epidemiological methods are not sensitive enough to detect it and never will be. Therefore, those holding this view say the response (excess of cancer in low exposure) cannot be measured but must be calculated from the dose-response curve established at higher exposures, by extrapolating it into low exposure levels, provided the assumption is correct that the relation is linear and the line tends to the zero-point (see figure 1).
In contrast with, or in addition to calculations and extrapolations, an alternative approach to objective evaluation of the health effect of low doses of asbestos is available: to relate the finding of pulmonary health or disease to the lung burden, as represented by the kinds and numbers of fibres present in the lung tissue. The rationale of this approach is that in the case of a durable mineral like asbestos the fibres found in the lung should reasonably well reflect the relevant past exposure, both qualitatively and quantitatively, and that it should be possible to identify objectively past low exposures and evaluate their effect or lack of effect on health.
In was demonstrated and repeatedly confirmed in the lungs from autopsies that there are significant differences: very high numbers of asbestos fibres were found in the lungs of persons with cancer and with asbestosis (with or without cancers), much less in persons with no asbestos-linked disease but with past occupational exposure to asbestos, and still less in persons with no asbestos-linked disease and no occupational exposure to asbestos. The differences between the groups were found to be in orders of magnitude with virtually no overlapping. The strength of the evidence has been such that some scientists argue that, whatever disease is in a person with low numbers of fibres in the lungs, that this disease is unlikely to be caused by asbestos and must have had another cause. That there is no "asbestos cancer" with less than 0.5-1 million fibres/g of lung tissue (which is considered the upper limit of the low burden found in those not occupationally exposed).
Obviously, these conclusions are valid only with certain precautions: the fibres may be very unevenly distributed through the lungs, and very different readings may be obtained from various parts of the same lung. This particularly applies to results of biopsies. A standardised technique for tissue sampling, preparing and counting the fibres is required if the quantitative results even from the post-mortem lungs are to be compared between laboratories. The fibres, mainly the very small ones, migrate through the lungs and through the body. Has their presence in some locations relevance to disease or is it a simple consequence of their mobility? The various kinds of asbestos have various durability. Chrysotile seems to disappear gradually from the living lung, whereas the amphiboles mostly remain. When death occurred long after exposure had ceased, then even when past exposure was limited to mining chrysotile, more admixed tremolite than chrysotile was found in the lungs. When there had been mixed exposure to chrysotile and amosite or crocidolite, then again much more amphibole was found in the lung than chrysotile. Also, in persons not occupationally exposed to asbestos, among the few fibres found in the lungs are almost only amphiboles, although 95% of asbestos mined and used is chrysotile.
With these limitations in mind, however, the assessment and measuring of the lung burden appears to be a promising approach. It may offer an objective measure of the dose required to produce one or another asbestos-related disease, or a dose which produces no disease, and enables us to assess the levels of past exposures leading to the lung dose in question. If this is achieved, perhaps the gap in the dose-response curve left by epidemiology can be filled by data rather than by extrapolation. Then an answer may be found to the very practical question: Is there a tolerable level of exposure to asbestos, and if so, what is that level?
Somewhat similar information on lung burden can be obtained by bronchopulmonary lavage. The information is less direct than counting asbestos bodies or fibres in the lung tissue, but can be gained during life, and the result reflects more uniformly the situation of the whole lung than biopsy.
Animal experiments have not added much information about asbestos-linked pulmonary cancer, mainly because inhalation studies did not produce many cases of bronchogenic carcinoma.
Neither animal experiments nor epidemiology have been able to show convincingly any substantial difference in pulmonary carcinogenicity between the various kinds of asbestos, between chrysotile and the amphiboles. All kinds have proved to be carcinogenic and excess of pulmonary cancer was found even in exposure to anthophyllite, although this amphibole has never been shown to cause mesothelioma in man.