There are several reasons for questioning the apparent conclusion reached by Mirabelli and colleagues (Mirabelli et al. 2008) that their data provide evidence for the mesothelioma-inducing potential of what they refer to as “tremolite-free chrysotile”. Most of the reasons may already be well-known to the authors. No longer a traditional follow-up of the cohort study to which they refer (Rubino et al. 1979; Piolatto et al. 1990; Silvestri et al. 2001), this account is essentially a case series assembled retrospectively, as best they could, unfortunately subject to several sources of bias, and analysed entirely without controls (or, as they acknowledge, even true estimates of exposed and unexposed populations). Information about “exposure” is incomplete and of doubtful reliability both for chrysotile and for fibrous amphibole and its analogues, including “tremolite” (which, unlike “balangeroite”, is not always, or even usually, “asbestos”; in the Jeffrey Mine in Québec for example it has been estimated that over 99% of the “tremolite” present is nonasbestiform (Williams-Jones et al. 2001)).

This is not the issue – the issue is whether or not the material present causes mesothelioma. For the “tremolite” levels present in some Quebec mines and the lungs of some Quebec miners and millers employed therein, we believe the case is proven (Case et al. 1997; McDonald, AD et al. 1997). There is strong evidence that it is true not only for male miners and millers, as well as factory workers using imported crocidolite in manufacture at one mine site proven not to contain that mineral. It is also true for women, without exception exposed in the highest tremolite area although shown in some cases by lung-retained fiber analyses and occupational histories to have had as well some occupational exposures to commercial amphibole (Case et al. 2002).

Similarly, in the cases reported by these authors (some of which they say were exposed to “tremolite”, without defining what they mean by that term mineralogically or any other detail), the amount of “balangeroite” reported by the authors to be “in the mine” is similar to the amount of “tremolite” (whether asbestiform or not) reported to be present in Thetford Mines locations in Québec. The difference is that, unlike tremolite, “balangeroite” has been classed as an “iron-rich asbestiform” fiber with structural, biochemical, and perhaps most important biodurability characteristics similar to crocidolite (Gazzano et al. 2005; Groppo et al. 2005; Turci et al. 2005). The authors appear to believe that the fact that balangeroite has not yet been “classed as a carcinogen” somehow absolves it. This is hardly a precautionary approach, and were it taken with richterite and/ or winchite, both unregulated amphiboles, the mesotheliomas in the workforce at Libby, Montana (McDonald, JC et al. 2004; Sullivan 2007) could be considered as much caused by ‘vermiculite’ as the authors appear to believe their cases are caused by chrysotile.

The most fundamental deficiency however is the complete absence of lung-retained fibre analyses. Such analyses have been performed by the authors in other locations (Barone-Adesi et al. 2008), so they have the capability and hopefully the plans to do this. Such analyses would almost certainly make clear whether and to what extent chrysotile alone or the specific amphiboles present are responsible, and lead to a better understanding of balangeroite’s toxicity, at least for mesothelioma. Certainly the Québec experience is instructive in that regard, in that our studies would not even have been thought of were it not for the discovery by other investigators that “tremolite” is selectively and preferentially retained in the lung (Pooley 1976; Rowlands et al. 1982); such is likely to be the case for balangeroite as well. Several of the Italian cases are quite recent, so lung tissue from biopsy (if adequate), surgical intervention with partial or total pneumonectomy, or autopsy may well be available. Even if not, broncho-alveolar lavage fluid from exposed individuals, or even sputum asbestos body content, which proved so useful in 70% of Libby workers (Sébastien et al. 1988) and was a better predictor of radiographic changes than was cumulative exposure, may be useful.

This is not simply an academic exercise: too many journals in occupational and environmental medicine and disease, public health science, epidemiology, and general medicine are so poorly equipped for peer review on mineralogical exposure parameters and assessment that some questionable aspects of papers in this area slip through the cracks. Perhaps the best-known example is the study by Yano and colleagues with the possibly misleading title “Cancer mortality among workers exposed to amphibole-free chrysotile asbestos” (Yano et al. 2001). Amphibole contamination was at the time of publication not assessed in the lungs of the victims but in four samples of “processed chrysotile” from “two mines” by methods not specified other than by “personal communication” with the scientist (Kohyama) who performed them, who is not an author of the paper. The authors were perhaps understandably not aware of the contemporaneous findings of (Tossavainen et al. 2001) who found tremolite in ten of ten samples from six Chinese mines, but noted that 71% of fibres found in the lungs of workers exposed to these were in fact anthophyllite, a fibre type only present (at the detection limit) in one of the ten bulk samples. Neither Dr. Yano nor Dr. Kohyama have yet updated the record with lung- retained fibre analysis information; only if and when they do will their work be reconciled with that of the Finnish investigators.

Given that chrysotile is also known at the very least to cause lung cancer, at sufficient dose and fiber length and often in interaction with smoking, do the details concerning the magnitude of the differential in fibre type risk for mesothelioma matter? We believe they do: Mesothelioma is the health outcome of greatest concern for low doses, and is therefore of greatest concern for public health. Regulatory agencies and other bodies charged with protecting the public depend on good science to determine where to spend their dollars in prevention and remediation. Ultimately, as such, they need the best information available. Given the hypothetical financial choice of, for example, exacting an adequate cleanup in Libby, Montana (where unregulated amphiboles are of great concern for mesothelioma), versus the two per cent of the surface area of the State of California covered with serpentine rock, we believe it is evident from the published work where the most effective use of resources should be placed.

REFERENCES

Barone-Adesi, F., D. Ferrante, M. Bertolotti, et al. (2008). "Long- term mortality from pleural and peritoneal cancer after exposure to asbestos: Possible role of asbestos clearance." Int J Cancer.

Case, B. W., M. Camus, L. Richardson, et al. (2002). "Preliminary findings for pleural mesothelioma among women in the Québec chrysotile mining regions." Ann. Occup. Hyg 46(S1): 128-131.

Case, B. W., A. Churg, A. Dufresne, et al. (1997). "Lung Fibre Content for Mesothelioma in the 1891-1920 Birth Cohort of Quebec Chrysotile Workers: A Descriptive Study." Ann Occup Hyg 41(S1): 231-236.

Gazzano, E., C. Riganti, M. Tomatis, et al. (2005). "Potential toxicity of nonregulated asbestiform minerals: balangeroite from the western Alps. Part 3: Depletion of antioxidant defenses." J Toxicol Environ Health A 68(1): 41-9.

Groppo, C., M. Tomatis, F. Turci, et al. (2005). "Potential toxicity of nonregulated asbestiform minerals: balangeroite from the western Alps. Part 1: Identification and characterization." J Toxicol Environ Health A 68(1): 1-19.

McDonald, A. D., B. W. Case, A. Churg, et al. (1997). "Mesothelioma in Quebec chrysotile miners and millers: epidemiology and aetiology." Ann Occup Hyg 41(6): 707-19.

McDonald, J. C., J. Harris and B. Armstrong (2004). "Mortality in a cohort of vermiculite miners exposed to fibrous amphibole in Libby, Montana." Occup Environ Med 61(4): 363-6.

Piolatto, G., E. Negri, C. La Vecchia, et al. (1990). "An update of cancer mortality among chrysotile asbestos miners in Balangero, northern Italy." Br J Ind Med 47(12): 810-4.

Pooley, F. D. (1976). "An examination of the fibrous mineral content of asbestos lung tissue from the Canadian chrysotile mining industry." Environmental Research 12: 281-298.

Rowlands, N., G. W. Gibbs and A. D. McDonald (1982). "Asbestos fibres in the lungs of chrysotile miners and millers--a preliminary report." Ann Occup Hyg 26(1-4): 411-5.

Rubino, G. F., G. Piolatto, M. L. Newhouse, et al. (1979). "Mortality of chrysotile asbestos workers at the Balangero Mine, Northern Italy." Br J Ind Med 36(3): 187-94.

Sébastien, P., B. Armstrong, B. W. Case, et al. (1988). " Estimation of amphibole exposure from asbestos body and macrophage counts in sputum: a survey in vermiculite miners." Ann Occup Hyg 32(S1): 195-201.

Silvestri, S., C. Magnani, R. Calisti, et al. (2001). "The experience of the Balangero chrysotile asbestos mine in Italy: Health effects among workers mining and milling asbestos and the health experience of persons living nearby." Canadian Mineralogist: 177-186.

Sullivan, P. A. (2007). "Vermiculite, respiratory disease, and asbestos exposure in Libby, Montana: update of a cohort mortality study." Environ Health Perspect 115(4): 579-85. Tossavainen, A., M. Kotilainen, K. Takahashi, et al. (2001). "Amphibole fibres in Chinese chrysotile asbestos." Ann Occup Hyg 45(2): 145-52.

Turci, F., M. Tomatis, E. Gazzano, et al. (2005). "Potential toxicity of nonregulated asbestiform minerals: balangeroite from the western Alps. Part 2: Oxidant activity of the fibers." J Toxicol Environ Health A 68(1): 21-39.

Williams-Jones, A. E., C. Normand, J. R. Clark, et al. (2001). "Controls of amphibole formation in chrysotile deposits: Evidence from the Jeffrey Mine, Asbestos, Quebec." Canadian Mineralogist: 89-104.

Yano, E., Z. M. Wang, X. R. Wang, et al. (2001). "Cancer mortality among workers exposed to amphibole-free chrysotile asbestos." Am J Epidemiol 154(6): 538-43.

Dear Sir

I would like to respond to some of the issues raised by Palmer et al's recent paper "How common is repetitive strain injury?" and the associated editorial by Fred Gerr on the surveillance of work related musculoskeletal disorders.

The central issue is that of the reliability with which individuals can attribute their musculoskeletal symptoms or conditions to work. The question would be easier to resolve if there was a "gold standard" test against which such attributions could be tested. As Fred Gerr points out, this is not the case: our choice is between a number of imperfect methods.

Palmer et al claim that self reports will systematically overestimate the numbers of work-related cases, and seem to imply that there is sufficient error in such reports that they should not play an important role in the formulation of policy.

In respect of the over attribution claim, it is important to realise that Palmer et al's findings do not imply that the estimates HSE has drawn from the LFS for (self-reported) work-related upper limb disorders are exaggerated. On the contrary, their study implies that the prevalence (by their preferred attributable fraction measure) of work-related arm pain over a 12 month period was 6.5% (14% times 46%), while HSE's LFS measure gives an estimate of 0.9%.

In any survey the context in which questions are asked, and precise wording, can make substantial differences to the proportions of respondents who respond positively. The fact that a version of HSE's LFS question performed very differently in the context of the MRC research than it does in the LFS is not surprising. The MRC version of the HSE LFS question produced, in their study, a prevalence of work-related arm pain of 25% (46% times 54%) compared to 0.9% from the LFS. It is not surprising that this kind of question met in the context of a survey of "aches and pains in the community" will elicit a different response than a similar question in the LFS where the central topic is jobs and related matters.

What Palmer et al's study shows is that if you take an "attributable fraction" estimate due to specifically identified work activities, you get a different, and in this case lower, overall estimate than can arise from self reports. What the research cannot show is whether this difference is due to fundamentally mistaken attribution in the self reports, or from respondents applying different cut-offs for work-relatedness along a basically valid scale. The MRC research could not address this question because the attributable fraction approach only gives you an overall estimate, and does not identify individual cases as work-related or not.

If people's responses to questions about attribution were purely driven by their psychological makeup, with no connection to the true sources of their condition then, of course, such measures would carry no information relevant to the understanding and prevention of genuinely work -related musculoskeletal harm. However this would be an extreme, and somewhat implausible, claim. It is more likely that individuals have effectively different thresholds for identifying what seems to them worth describing as "work-related". No doubt, individual psychology plays a role in determining how these thresholds are set, but that is by no means the same thing as saying that the scale they are working on is essentially flawed.

The measurement of work-related ill-health is not straightforward. HSE responds to these difficulties by using a range of sources, including self reports in the LFS, but also using medical surveillance, compensation data and death certificates. In any measure it is important to be consistent from year to year so as to have the best possible chance of detecting the underlying trends. It is these trends, particularly over the medium and long term, which are important, rather than the precise levels.

We also keep our statistical methods under review and are currently working on analyses to improve our understanding of the recent rise in the self-reported work-related illness measure from the LFS. We will also be organising a workshop on the measurement of work-related ill-health to consider this and a range of related issues later this year.

Yours sincerely

John Hodgson Head of Statistics Health and Safety Executive

Sir

I welcome the caution shown by Amick (1) in his editorial on forearm support and mouse design for computer users. He praises the study design used by Conlon et al (2), but is a randomised control trial really the best way to assess ergonomic aids when there are so many confounders? Simple observation of a group of computer users will identify a range of postures, as well as a wide variation in arm length, wrist diameter, hand size etc. etc.. I have seen individuals who have undoubtedly benefitted from ergonomic adjustments to workstations, however the adjustments have been different in each case. I have seen similar numbers of individuals harmed by ‘ergonomic supports’ who responded rapidly once the desk was cleared of squidgy pads.

Consider another aid; we know that safety boots have a key part to play in reducing injuries, but we do not advocate issuing size 12 boots of one design to all. Not only should we ensure the boot fits, but some individuals will just not suit some designs. A randomised control trial of size 12 boots in a normal workforce may well show that safety boots cause slips, trips and falls and foot pain (because they don’t fit) rather than save feet (because they have a steel toe-cap). The same will inevitably apply to pointing devices and keyboards combined with desk size and height, chair design and position of equipment; some individuals will just happen to be ill-suited to the one design bulk-purchased for the department, while many individuals will be fine with the £25 chair and £5 keyboard and mouse from the discount catalogue.

Similar problems seem to arise with ergonomic assessments such as those undertaken by Access to Work and others. I have seen too many reports recommending the same standard ‘ergonomic aids’ for widely differing conditions (such as pneumatically adjustable chairs for visual difficulties and wrist extensor tendinitis) to have much faith in any ergonomic assessment that is based on ‘standard evidence’.

Evidence clearly shows that some individuals get problems, others don’t. Rather than trying to identify a single solution, should we focus more on analysing the problem, considering the ‘causal pathway’ as Amick suggests, but for individuals not populations? Then we can consider the best individual solution. This means that the issue is not one that should be based on research evidence, but on the observations of the occupational physician or nurse on the ground, on clinical assessment and clinical judgement. This may be a case where ‘more research is not needed’ unless it is much more clearly focussed; it may just muddy the waters. Instead we should have two messages:

1. If it ain’t broke, don’t fix it.

2. Assess and intervene early with a tailored solution when problems do arise.

Tony Williams

(1) Amick BC. Growing knowledge about ‘what works’ to prevent work injuries. Occupational and Environmental Medicine 2008;65:297-8 (2) Conlon C et al. A randomised controlled trial evaluating an alternative mouse and forearm support on upper extremity body discomfort and musculoskeletal disorders among engineers. Occupational and Environmental Medicine 2008;65:311-18.