Magnitude of the mesothelioma problem

Some general observations on approaches to risk assessment on society and on epidemiological studies of asbestos-related cancers

1. 
   The documentation supplied to the WTO includes estimates of risks from low-level exposure to chrysotile in proportion to various other risk factors in society: in fact, the relative risk of mesothelioma from low-level exposure to asbestos in place is the focus of considerable controversy. Clearly, detailed analysis of this issue is beyond the scope of this report, but the excess risk of mesothelioma from very low-level exposure to asbestos — e.g. simple occupancy of public buildings or schoolrooms where average asbestos fibre concentrations are about < 0.001-0.02 fibres per litre — appears to be very slight: about ≤ 5.5 mesotheliomas per million lifetimes of 80 years, or < 1 case per 10,000,000 per year.
   
2. 
   The estimated mesothelioma risk for a 10-year exposure to low levels of airborne asbestos in schools (age start 7-8 years; fibre concentration 0.00065-0.001 fibre per ml¹⁶ is in the range 6.6-20 per million lifetimes (0.0825-0.25 per million person-years). Estimates of this type are predicated on linear dose-response models with no threshold, and these have been the subject of argument and criticism. The occupational groups from which they were derived were exposed to mixtures of asbestos types, but one might expect the risk to be even less or "undetectably low" in nations where only chrysotile was used. At this point, it is sufficient to emphasize that - even if one accepts for a moment the no-threshold linear dose-response relationship - calculations indicate that a single asbestos fibre (the so-called "one fibre" hypothesis) would only have a 50-50 chance of producing a single excess mesothelioma among all the humans who have ever inhabited Planet Earth.
   
3. 
   These observations on mesothelioma risk estimates for very low-level exposure to asbestos in buildings do not contradict the earlier suggestion in this report that Western Australian and Australian increases in mesothelioma incidence among females were a possible consequence of general environmental exposure to asbestos: the two-fold rise in incidence in Western Australia could be due to environmental fibre levels higher than those recorded in public buildings elsewhere.
   
4. 
   If it exists, the risk of mesothelioma from very low-level environmental exposure to asbestos needs to be considered in proportion to other risks of death in society. The lowest death-risk at any age occurs in girls aged 4-14 years and is ~ 100 per million per year, but the risk in late teenage increases by 300-400 per million per year — attributable largely to increased travel by motor vehicle. A 40-year-old man at risk of mesothelioma from low-level exposure to asbestos during childhood (excess mesothelioma risk < 1 per million person-years) has an annual risk of death from all causes of about 2000 per million. In 1990, de Klerk [128] had this to say on the subject:
   

5. 
   Within this context, one might ask what constitutes a negligible as opposed to an acceptable (or unacceptable) risk? In the context of the foregoing discussion, one might argue that a negligible risk is a statistical and scientific concept: a risk so slight that it does not require preventive or remedial steps in comparison to other risks in society (although some might argue about the dividing line between negligibility and unacceptability in this context). With acceptability or unacceptability other factors come into play: they include, for example, social, political and industrial considerations — and the likelihood of litigation over any situation wherein the theoretical or estimated risk is elevated to a background level, no matter how slightly. Accordingly, a risk, though slight or even negligible, might still be considered unacceptable in legal or sociopolitical terms.
   
6. 
   Others may dissent from the acceptability of the Royal Society approach to low, moderate and high risks discussed above. Conclusions about the acceptability or unacceptability of risk will also vary according to the seriousness of the risk (e.g. the approach to a lethal risk such as mesothelioma would be quite different from a factor that caused a large proportion of the population to sneeze once or twice); these assessments will also vary according to the avoidability of the risk, the individuals making the assessment, and the question of informed consent by those at risk.
   
7. 
   Furthermore, society abounds with inconsistencies and contradictions over the relativity of various risks. For example, some societies that regulate or propose a ban on chrysotile asbestos make extensive use of radioactive materials — e.g. in nuclear power stations and the production of radioactive isotopes for medical purposes. Even so, the use of fissionable materials for these purposes may be justified and justifiable within those societies, because: (i) the risk of morbidity or death from well-publicized mishaps at nuclear reactors is still substantially less than the risk of death from alternative energy sources (e.g. higher mortality rates among coalminers); and (ii) because the materials in question can be regulated and controlled so that they are accessible to only a small fraction of society (i.e. workers who can be trained in the controlled use of radioactive substances); and (iii) nuclear power does not contribute significantly to air pollution or greenhouse gas emissions in comparison to the burning of fossil fuels.
   
8. 
   In addition, Nicholson [129] places the problem into the perspective of voluntary versus involuntary risks:
   

9. 
   In fact, it is my view that over-reaction to the low risks produced by asbestos in place may lead to a greater risk — i.e. the carcinogenic risks imposed by asbestos removal programmes. Two mesotheliomas encountered in my own practice during 1999 occurred not in asbestos removal workers, but in others who sustained bystander exposure as a result of this activity: (i) pleural mesothelioma in a lecturer who had walked to and from her classroom at an Australian university each day over a period of weeks, through a building where an asbestos insulation removal programme was being carried out; (ii) pleural mesothelioma in a fireman who attended fires in buildings that contained asbestos-cement products and who participated in clean-up operations thereafter; about once a month for some years, he also attended and examined buildings where fire alarms had been activated by high atmospheric concentrations of asbestos fibres produced by removal programmes. (In addition, a recent survey in Finland found "occasional high fibre concentrations even inside personal protectors during asbestos removal work" [130]).
   
10. 
    Two other important points are worth emphasis. First, because they usually focus on specific cohorts or groups of workers, epidemiological studies may fail to identify a small but real risk, because of low statistical power. In this respect, the documents submitted to the WTO state that it may be impossible to prove a negative (absence of risk), but one can also state that absence of proof does not constitute proof of absence. For example, a number of investigations have failed to identify a statistically significant increase in the relative risk (RR) of cancer among individuals with parietal pleural fibrous plaques. In an extensive review of asbestos and lung cancer, Henderson et al. [131] commented along the following lines in relation to pleural plaques and lung cancer:
    

11. 
    In a discussion of the Hughes-Weill study [133] on radiological asbestosis and lung cancer in New Orleans asbestos-cement factory workers — one of the three key investigations that proposed an obligate intermediary step of pulmonary fibrosis for the induction of lung cancer by asbestos — Henderson et al. [131] also commented in the same review:
    

12. 
    The point is that a low, non-significant or undetectable risk in a small cohort may nonetheless translate into a substantial body of disease when spread over a large population: e.g. an RR of 1.1 representing an increase in risk of 10 per cent may require a population size of 300,000 to be detectable at a level of statistical significance of 0.05, whereas this 10 per cent increase in a common disease such as lung cancer may amount to a substantial burden of disease when spread across a

    population of, say, 1,000,000, 10,000,000, or 100,000,000. (Please see also later discussion on mesothelioma among brake mechanics: answer to Question 2.)

    
    
13. 
    Another point is that a high frequency of a cancer such as mesothelioma in a small population may be overshadowed in absolute numbers by a lower occurrence rate for the same disorder spread over a large population. For example, among non-smoking former Wittenoom workers, mesothelioma is now the most common cause of death [70] (in most cohorts exposed to amphibole asbestos, < 10 per cent will develop mesothelioma). Nonetheless, mesotheliomas among the Wittenoom cohort contribute only 5-6 per cent of the total burden of mesothelioma across the Australian population [AMR 99]. For example, the 1999 Report for the Register records 189 mesotheliomas among the former Wittenoom population with only a single exposure to asbestos, in comparison to 187 mesotheliomas among carpenters/joiners with only a single exposure to asbestos; the point is that the lower risk of mesothelioma from asbestos exposure among carpenters has produced almost the same number of cases, because carpenters among the Australian workforce constitute a much larger occupational group than the entire Wittenoom cohort of about 6000.
    
14. 
    This observation also applies to the numbers of mesotheliomas among chrysotile miners and millers in Quebec, in proportion to other cases among the general population of Quebec. Bégin et al. [134] divided Quebec mesotheliomas into three groups, as shown in the following Table:
    

15. 
    In this study, Bégin et al. [134] also commented that "the incidence of pleural mesothelioma in chrysotile miners and millers, although not as high as in the crocidolite workers, is well above the North American male rate". They also observed that "asbestos exposures in Group 3, although difficult to quantify on the basis of the record, appear to be often very low intensity". Bégin et al. also commented in the following terms:
    

Thus, our observations add information of interest to the on-going debate regarding the relative carcinogenicity of different types of asbestos fibers. Our data suggest that some of the cases of malignant mesothelioma in Québec chrysotile miners and millers may not be necessarily attributable to amphibole and could be chrysotile-induced. Lung tissue burden analyses, a better indication of exposure than tumour tissue burden, will be done on these cases to further investigate this point. ....

1. 
   In one of the documents submitted to the WTO, it is argued that evaluation of, and actions on, risks should be based on probability rather than mere possibility. This proposition is open to dispute. For example, action is often taken to avoid the possibility of harm — by regulation or prohibition — even though the likelihood of injury is remote, because of the seriousness of the potential outcome. In medical ethics, this is the principle of first, do no harm (primum non nocere). Two examples follow: (i) the antibiotic chloramphenicol was known to be highly effective in the treatment of various infections, including typhoid fever, but on rare occasions it induced bone marrow aplasia; despite the low likelihood of this side-effect — about 1 in 250,000 — the use of chloramphenicol was restricted to only a few life-threatening infections (e.g. typhoid fever), and it is now almost never used because safer effective alternatives are available; (ii) over recent years, there has been a flood of publicity over global warming and greenhouse gas emissions. A causal or direct relationship between greenhouse gases (such as CO₂ and methane) and climate change is open to argument, and Earth undergoes repeated cycles of natural cooling and warming; in this respect, there is also evidence that melting of the Antarctic ice cap has been going on for some thousands of years, and global warming for over 100 years. Nonetheless, the consequences of inaction over greenhouse gas emissions are potentially so serious that strategies to reduce the release of these gases into the atmosphere are entirely appropriate, despite uncertainty over the link between them and global warming.
   
1. 
   
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