Document R714BwE4D1L4oDJXDNwDee2v

Downloaded from oem.bmj.com on 18 November 2008 OEM ONLINE Excess of mesotheliomas after exposure to chrysotile in Balangero, Italy D Mirabelli, R Calisti, F Barone-Adesi, E Fornero, F Merletti and C Magnani Occup. Environ. Med. 2008;65;815-819; originally published online 4 Jun 2008; doi:10.1136/oem.2007.037689 Updated information and services can be found at: http://oem.bmj.com/cgi/content/full/65/12/815 References Rapid responses Email alerting service These include: This article cites 17 articles, 4 of which can be accessed free at: http://oem.bmj.com/cgi/content/full/65/12/815#BIBL 1 online articles that cite this article can be accessed at: http://oem.bmj.com/cgi/content/full/65/12/815#otherarticles One rapid response has been posted to this article, which you can access for free at: http://oem.bmj.com/cgi/content/full/65/12/815#responses You can respond to this article at: http://oem.bmj.com/cgi/eletter-submit/65/12/815 Receive free email alerts when new articles cite this article - sign up in the box at the top right corner of the article Topic collections Articles on similar topics can be found in the following collections Air pollution, air quality (2 articles) Other exposures (9 articles) Notes To order reprints of this article go to: http://journals.bmj.com/cgi/reprintform To subscribe to Occupational and Environmental Medicine go to: http://journals.bmj.com/subscriptions/ Downloaded from oem.bmj.com on 18 November 2008 Original article Excess of mesotheliomas after exposure to chrysotile in Balangero, Italy D Mirabelli,1,4 R Calisti,2 F Barone-Adesi,1,4 E Fornero,4 F Merletti,1,4 C Magnani3,4 1 Unit of Cancer Epidemiology, CeRMS and CPO-Piemonte, University of Turin, Turin, Italy; 2 Occupational Safety and Health Unit, Local Health Authority, Civitanova Marche, Italy; 3 Unit of Medical Statistics and Cancer Epidemiology, CPO-Piemonte, University of Eastern Piedmont, Novara, Italy; 4 Interdepartmental Centre G. Scansetti for Studies on Asbestos and Other Toxic Particulates, University of Turin, Turin, Italy Correspondence to: Franco Merletti, Unit of Cancer Epidemiology, Via Santena 7, 10026 Turin (TO), Italy; franco.merletti@unito.it Accepted 22 February 2008 Published Online First 4 June 2008 ABSTRACT Background: Chrysotile from the mine in Balangero, Italy is considered to be free of tremolite. In a cohort study of miners and millers only two pleural cancers were reported, a finding considered to indicate that chrysotile has a low potency for inducing mesothelioma. However, follow-up ended in 1987 and white-collar workers and the employees of subcontractors were not studied. Methods: To complete the case ascertainment, the study searched the Registry of Malignant Mesotheliomas of Piedmont for records of cases of pleural mesothelioma among the following: mine employees; employees of subcontractors or of other firms transporting or refining Balangero asbestos, asbestos ore or mine tailings; individuals exposed to air pollution from the mine or living with mine employees; and individuals exposed to mine tailings from Balangero. Results: The study identified four new cases of pleural mesothelioma among blue-collar workers in the mine, in addition to the two reported in the cohort study. Thus, six mesotheliomas occurred, compared to the 1.5 expected (p<0.01). The study also identified three mesothelioma cases among white-collar employees at the mine, five in workers in the mine hired by subcontracting firms, and three among workers processing Balangero chrysotile outside the mine. Finally, 10 additional cases due to nonoccupational exposure or exposure to re-used mine tailings were identified. Conclusions: The cluster of 14 mesothelioma cases among workers who were active in the mine and 13 among other people exposed to Balangero chrysotile provides further evidence that tremolite-free chrysotile is carcinogenic. The carcinogenicity of chrysotile is established, although the issue of its potency relative to amphiboles for inducing mesothelioma remains unresolved, with estimates ranging from 1:3 to 1:500.1 2 A related controversy is whether contam ination with tremolite fibre, rather than chrysotile, could be entirely responsible for causing mesothelioma.3 Chrysotile from the Balangero mine (Piedmont, northern Italy) is tremolite-free and contains trace amounts of balangeroite, a non asbestos fibrous mineral similar in shape to amphiboles.4 5 A study on workers at the Balangero mine reported only two deaths from pleural cancer up to 1987.4 6 This study has been regarded as contribut ing to the evidence that chrysotile has relatively low carcinogenic potency.2 Published reports did not, however, include clerical workers or employ ees of subcontractors, and four cases of malignant mesothelioma, one in a worker engaged at the mining site by a subcontractor, have been described after 1987.7-9 In Piedmont a Registry of Malignant Mesotheliomas (RMM) has been maintained since 1990.10 We report on a survey of data in the RMM, conducted to identify cases aetiologically related to the mine, including cases among non-occupationally exposed individuals. METHODS The plant The Balangero mine, active from 1917 to 1985, was an open-pit operation, flanked by a mill for opening, separating and mixing fibres of different length. Amiantifera, the company that owned the mine, officially ceased its activities in 1990. Asbestos and the mine tailings, which are crushed serpentine rocks left over after fibre extraction and which still contain up to 1% chrysotile fibres by weight, were removed by trains and lorries. A cohort of miners and millers employed for at least 1 month by Amiantifera and active in 1946 or hired thereafter was established by Rubino et al and studied further by Piolatto et al.4 6 The cohort did not include white-collar workers or employees of subcontractors. Fibre measurement during mining activities did not begin until 1969, so Rubino and coworkers experimentally reproduced working conditions for the period 1946-1975. They used these simulated conditions to estimate average fibre concentrations for different jobs and calendar periods, as well as individual cumulative exposures.6 Occupational exposure was in the range of 100-400 f/mly for about 30% of workers, and >400 for another 30%.4 6 Fall-out from the mine affected the surrounding towns but, apart from anecdotal descriptions of episodes of very high air pollution in the literature, few measure ments are available of asbestos fibre concentrations in the general environment.811 12 Mine tailings from Balangero were used in several areas of Piedmont as ballast for road and railroad construc tion and for courtyard paving. Identification of cases Many asbestos industries were located in Piedmont, a region with 4.5 million inhabitants.13 Since 1990, the RMM has recorded newly diag nosed cases of malignant mesothelioma among residents; cases occurring in 1980-1989 were registered retrospectively.10 Structured interviews with subjects with malignant mesothelioma and with respondents were conducted to obtain information on life-long occupational and nonoccupational exposure to asbestos. Initially inter views were conducted only with persons enrolled Occup Environ Med 2008;65:815-819. doi:10.1136/oem.2007.037689 815 Original article Downloaded from oem.bmj.com on 18 November 2008 in surveys and case-control studies.14 15 Over the years, the RMM has increased its efforts to obtain exposure data, which are now available for approximately 50% of all mesotheliomas diagnosed between 1990 and 2001. Through the network of regional registries connected to the National Registry of Mesotheliomas, the RMM can identify individuals exposed in Piedmont who were living in other Italian regions at the time of diagnosis.16 Industrial hygienists performed qualitative and quantitative assessment of asbestos exposure for all interviewed subjects with malignant mesothelioma. They based their assessments on descriptions of the relevant exposure circumstances and on available knowledge of the industrial and non-industrial settings involved. Records have been kept of all settings where exposures occurred. From the RMM records we extracted cases occurring in the following groups: employees of Amiantifera or of its subcontractors at the Balangero mine; employees of other firms transporting or refining asbestos, asbestos ore or tailings from the Balangero mine; individuals either exposed to the fall-out of dust from the mine (environmental exposure) or living with an employee of the mine (household exposure); and individuals reporting exposure to mine tailings from Balangero. Cases occurring in all but the last two groups belong to well-defined occupational populations, although we could not explicitly list these populations as we lack their employment rolls. Cases occurring in the last two groups belong to the general population. People living in the four towns closest to the mine (Balangero, Corio, Coassolo, Lanzo) were considered to have environmental exposure. Sharing a home with an employee of the mine who brought home his working clothes was classified as household exposure. Exposure to mine tailings was assumed for individuals who reported in the interview that they handled such materials or lived close to places where they had been dumped or used for paving. We did not include cases among workers at industries manufacturing asbestos-based products using Balangero asbestos, because most of these workers were also exposed to asbestos from other sources. Calculation of the expected number of cases in the cohort of miners and millers Because we did not have access to the files of the mortality cohort study on Balangero miners and millers, we did not know the age distribution of the 631 members alive at the last follow-up in 1987.4 We estimated the 1988-2006 person-years of observation by applying the following conservative assumptions: no mortality up to 31 December 2006, and all cohort members at least 60 years of age in 1987. We then computed the expected number of cases on the basis of the average incidence of malignant pleural mesothelioma (10.4/100 000 per year) for the period 1990-2001 among men aged 60 or older in the appropriate province (Turin). Reference rates were obtained from the RMM. The corresponding calculation could not be carried out for non-manual workers or for workers not employed by Amiantifera because their numbers were unknown. RESULTS Cases associated with exposure to chrysotile Information on exposures was collected and assessed for 1432 of the 2992 malignant mesothelioma cases registered in Piedmont residents in the period 1980-2007. By reviewing exposure assessment records, we identified 25 cases possibly related to exposure to chrysotile from the Balangero mine, bringing to 27 the overall number of cases considered in the present report. 816 In the accompanying tables, the exposure patterns of these cases are summarised in brief descriptions of all occupations and circumstances considered to have entailed exposure. Unexposed jobs and life events were not reported. The sentence ``no other asbestos exposure at work'' recorded for a case meant that the individual held other jobs apart from those mentioned explicitly, and that the rater performing the exposure assess ment considered them unexposed. Of the nine cases of malignant mesothelioma in employees of Amiantifera (table 1A), the first two are those reported by Rubino et a/6 and Piolatto et a/.4 Case 3, first diagnosed in 1985, was not included in these studies, perhaps because he became a manager in the latter part of his career. Four cases occurred among manual workers after follow-up was closed (cases 4-7), one case in a white-collar worker (case 8), and one in a manual worker who later became a technical staff member (case 9). Five cases occurred in employees of firms subcontracted by Amiantifera, who reported having worked at the same site, being engaged in the same production processes and using the same machinery as employees of Amiantifera (table 1B). Three cases were never employed at the Balangero mining site but had worked with asbestos, asbestos ore and mine tailings from the mine (table 2). Cases 15 and 17 had worked at a mill outside the mining site that was not owned by Amiantifera, where low-grade ore yielding short fibres was treated and asbestos was separated, mixed and packaged. Case 16 repeatedly handled materials from the Balangero mine: he worked on extracting nickel from ``sterile'' Balangero serpentinite and on a project for ``wet'' extraction of asbestos fibres. Five cases occurred in the population living in the neighbour hood of the mining area (table 3). Case 18 also reported household exposure. Finally, five cases occurred among persons exposed to mine tailings from Balangero at work or at home (table 4). Three were women who lived for a long time in areas where the surroundings were paved with tailings from Balangero. Expected number of mesotheliomas in the cohort of miners and millers The expected number of cases cannot be computed with precision without knowing the age distribution of the cohort of miners and millers. Piolatto et at reported that 0.3 deaths from pleural cancer were expected between 1946 and 1987.4 Since the incidence of pleural mesothelioma is very close to that of pleural cancer, we assume that 0.3 cases would be expected during the same period. Based on our calculations, a further 1.2 cases are expected in 1988 2006, giving a total of 1.5 cases expected between 1946 and 2006. Six cases were recorded (cases 1, 2 and 4-7) in blue-collar employees of Amiantifera, corresponding to a standardised incidence ratio (SIR) of 4.00, with a 95% confidence interval (95% CI) of 1.47 to 8.71. We excluded the following cases from the number of malignant mesotheliomas observed in the cohort: case 8 because he was a clerk, and cases 3 and 9 because, although they had been manual workers, they became clerks and staff members and may not have been included in the cohort study since this was restricted to miners and millers.4 6 DISCUSSION Information on exposure is available for 50% of all cases in the RMM, so additional cases due to the exposures of interest may exist among those whose personal histories are unknown. Despite this limitation, our survey allowed the identification of a cluster of malignant mesotheliomas in persons who were Occup Environ Med 2008;65:815-819. doi:10.1136/oem.2007.037689 Downloaded from oem.bmj.com on 18 November 2008 Original article Table 1 Cases of malignant mesothelioma among workers at the Balangero mining site Case Sex Age Year Site Diagnosis Source of case Routes of exposure A. Cases of malignant mesothelioma among workers employed by Amiantifera at the Balangero mining site 1 M 51 1975 Pleural Cytol Piolatto et al4 Blue-collar worker at Amiantifera (1940-1973). No further data currently available. 2 M 62 1977 Pleural Histol Piolatto et al4 Blue-collar worker at Amiantifera (1942-1967). No further data currently available. 3 M 64 1985 Pleural Histol RMM Blue-collar worker at Amiantifera (1954-1985): miner in the first years of employment, later technical staff and lastly manager. 4 M 68 1989 Pleural Cytol, ICC RMM Blue-collar worker at Amiantifera (1936-1941 and 1942-1944): miners' aid, and later rock driller, then miller and fibre mixer. No other asbestos exposure at work. 5 M 73 1992 Pleural Histol, IHC RMM Blue-collar worker at Amiantifera (1942-1969) as miners' aid and later miller. No other asbestos exposure at work. 6 M 77 1994 Pleural Clinical RMM Blue-collar worker at Amiantifera (1938-1965). No further data currently available. 7* M 67 2002 Pleural Cytol, ICC RMM Blue-collar worker at Amiantifera as plant electrician (1964-1965). Electrician in a steel mill (1953-1955), in railway coach construction (1955-1958), in an iron foundry (1959-1963 and 1966-1971), and in a motor vehicle assembly plant (1971-1989). 8 M 76 2005 Pleural Clinical RMM White-collar worker, then manager at Amiantifera (1956-1985). No other asbestos exposure at work. 9 M 78 2006 Pleural Histol, IHC RMM Blue-collar worker at Amiantifera (1959-1967), asbestos bagger. White-collar worker at Amiantifera (1967-1987). No other asbestos exposure at work. Lived close to the mining area (1959-1987). B. Cases of malignant mesothelioma among workers employed by subcontractors at the Balangero mining site 10 M 36 1989 Pleural Histol RMM Bricklayer and roofer, engaged in building an asbestos mill at the mining site (1968-1972). Lift mechanic (1967-1968). No other asbestos exposure at work. Lived inside the mining site (1968-1972). 11* M 59 1992 Pleural Histol, IHC RMM Blue-collar worker for a subcontractor, working at the mining site as a miners' aid (1949). Bricklayer (1949-1957), worker in a nylon production facility (1957-1959), worker in the curing department of a tyre production plant (1963-1977), marble cutter (1979-1989). 12 M 68 2003 Pleural Histol, IHC Riboldi et al9 Blue-collar worker for a subcontractor, working at the mining site as a lorry driver, carrying asbestos ore from the mine to the mill and tailings from the mill to the dumping site (1955). No other asbestos exposure at work. 13 M 74 2003 Pleural Histol, IHC RMM Blue-collar worker for a subcontractor transporting asbestos from the Amiantifera mine to different industries (1967-1989). Furnace worker in a steel mill (1966-1967). 14 M 72 2006 Pleural Cytol, ICC RMM Blue-collar worker for a subcontractor as a lorry driver, carrying asbestos from the Amiantifera mine (1958-1973). No other asbestos exposure at work. Lived close to the mining area (1933-2006). `Possible exposure to other types of asbestos. Cytol, cytological confirmation; Histol, histological confirmation; IHC/ICC: immune staining pattern suggestive of a mesothelial neoplasm, based on histological or cytological material, respectively; RMM, Registry of Malignant Mesotheliomas. Table 2 Cases of malignant mesothelioma in workers never employed at the Balangero mining site but occupationally exposed to chrysotile from the mine Case Sex Age Year Site Diagnosis Source of case Routes of exposure 15* F 53 1990 Pleural Histol, IHC RMM 16* M 56 1996 Pleural Histol, IHC RMM 17* M 68 2001 Peritoneal Histol, IHC RMM White-collar worker at a mill outside the mining site treating Balangero ore working in an office in the yard of the factory (1957 1990). The mill also treated tremolite-contaminated talc from local mines. Lived close to the mining area (1937-1990). Researcher and teacher at the Turin Institute of Technology (1964 1969). Analysed ore from the Balangero mine and built/managed pilot plants for ore exploitation (1964-1966, 1968-1969 and 1987). Engineering consultant (1969-1997). Sampled air in brake/clutch lining production plants (1978-1983). Asbestos hand bagger (1950-1961) at a mill outside the mining site treating Balangero ore. The mill (but not the worker) also treated tremolite-contaminated talc from local mines. Lived close to the mining area (1933-1972). `Possible exposure to other types of asbestos. Histol, histological confirmation; IHC, immune staining pattern suggestive of a mesothelial neoplasm, based on histological material; RMM, Registry of Malignant Mesotheliomas. Occup Environ Med 2008;65:815-819. doi:10.1136/oem.2007.037689 817 Original article Downloaded from oem.bmj.com on 18 November 2008 Table 3 Cases of malignant mesothelioma due to household or environmental exposure Case Sex Age Year Site Diagnosis Source of case Routes of exposure 18 F 55 1981 Pleural Histol RMM 19 M 78 2003 Pleural Histol, IHC RMM 20 F 79 2003 Pleural Histol, IHC RMM 21 F 69 2003 Pleural Histol, IHC RMM 22 F 75 2007 Peritoneal Histol, IHC RMM No definite/likely occupational exposure. Husband asbestos packer at the mining site, work clothes cleaned and washed at home (1948-- 1973). Lived close to the mining area (1926-1981). No definite/likely occupational exposure. Lived close to the mining area (1925-1926 and 1983-2003). No definite/likely occupational exposure. Lived close to the mining area (1935-2003). No definite/likely occupational exposure. Lived close to the mining area (1943-1980). Farmer 1944-2002, leaves collected in the surroundings of the mining area used for cattle litter. Lived close to the mining area (1936-2007). Histol, histological confirmation; IHC, immune staining pattern suggestive of a mesothelial neoplasm, based on histological material; RMM, Registry of Malignant Mesotheliomas. exposed to chrysotile from Balangero but not, or only to a limited extent, to other types of asbestos. The expected number of mesothelioma cases in the cohort of Balangero miners and millers may have been overestimated in our calculations, first because we had to make some conserva tive assumptions to compute the number of person-years accrued during 1988-2006, and secondly because we used the population of Turin province as a reference. We had to approximate the calculation of person-years as we had no access to the individual records of the cohort members alive in 1987, when Piolatto and coworkers ended their follow-up study.4 The population of Turin province may bias the mesothelioma SIR estimate towards the null, because it includes substantial numbers of former workers in asbestos industries.13 Nevertheless, it is preferable to the alternatives: national incidence rates are unavailable for the calendar period con sidered, and estimates based on regional rates would be even more biased due to the overwhelming influence of the atypical epidemiological situation of Casale Monferrato.1415 Thus, an SIR of 4.00 (95% CI 1.47 to 8.71), based on six observed cases, can be tentatively estimated for manual workers hired by the firm running the mine. In the most recent update of the mortality study, the standardised mortality ratio (SMR) for pleural cancer was reported to be 6.67 (95% CI 0.8 to 24.1), based on two observed deaths.4 Both deaths could be confirmed as due to pleural mesothelioma, and they correspond to cases 1 and 2 in the present report. Current and earlier risk estimates are in agreement if their confidence intervals are taken into account. Opportunities for occupational exposure to asbestos of Amiantifera employees outside the mine could be identified only for case 7, a man who worked as an electrician in other plants where asbestos use was possible. No data were available to estimate expected cases of malignant mesothelioma among non-manual workers or employees of subcontracting firms. However, the detection of three and five cases in these groups, respectively, can hardly be attributed to chance. In particular, regarding the occurrence of malignant mesothelioma in non-manual employees (cases 3, 8 and 9), it is important to note that cases 3 and 9 were manual workers in their first years of employment. Regarding case 8, there are strong suggestions that substantial levels of airborne asbestos fibres were present in all the areas of the mining site. One of us observed a case of fatal asbestosis in a woman (diagnosed in 1989, died in 1993 at age 63) who never worked at the mine but lived in a house inside the Amiantifera premises, close to the fibre separation plant (R Calisti, unpublished data). The administrative offices were located in the same area. Thus, our present findings indicate that Balangero chrysotile miners and millers experienced increased risk of malignant mesothelioma. In addition, the results suggest that, in work places entailing exposure to asbestos in which some activities are carried out by subcontracting firms, any assessment of the burden of disease caused by asbestos should include workers hired by the subcontracted firms, for which nominal rosters for use in conventional cohort studies are rarely collected. We identified three new cases among workers employed by subcontractors or consultants to Amiantifera who had never worked at the mining site but who used or were in close contact Table 4 Cases of malignant mesothelioma among persons exposed to mine tailings used outside the mine Case Sex Age Year Site Diagnosis Source of case Routes of exposure 23 F 52 1995 Pleural Histol, IHC RMM 24* F 47 1996 Pleural Histol RMM 25* F 74 1998 Pleural Histol RMM 26 F 39 2000 Pleural Histol, IHC RMM 27* M 74 2001 Pleural Histol, IHC RMM Corn mill owner. Possibly used asbestos-contaminated bags discarded from the Balangero mine (1961-1995). Lived in a town where Balangero tailings were widely used as road ballast (1943 1995). Employed by Italian railways (1970-1991), where Balangero mine tailings were used as ballast up to the mid-1970s. No other asbestos exposure at work. Lived (1948-1996) close to railway tracks where Balangero mine tailings had been used as ballast. No definite/likely occupational exposure. Lived in a house with Balangero tailings as gravel substitute in the garden (1980-1998). Possible fall-out from an asbestos textile workshop 600 m from home (1978-1990). No definite/likely occupational exposure. Lived in a district where Balangero tailings were used as road ballast (1982-2000). Employed by Italian railways as a track maintenance worker (1951 1986) where Balangero mine tailings were used as ballast. No other asbestos exposure at work. *Possible exposure to other types of asbestos. Histol, histological confirmation; IHC, immune staining pattern suggestive of a mesothelial neoplasm, based on histological material; RMM, Registry of Malignant Mesotheliomas. 818 Occup Environ Med 2008;65:815-819. doi:10.1136/oem.2007.037689 Downloaded from oem.bmj.com on 18 November 2008 Original article Main messages Policy implications c Potency for mesothelioma induction was estimated to be two to three orders of magnitude lower for chrysotile than for amphiboles, based on findings from Quebec miners and millers and because of the absence or very small number of cases in other cohorts, including Balangero miners and millers. c The study identified 14 cases of malignant mesothelioma in workers active in the mine and 13 in other persons exposed to Balangero chrysotile, a situation less reassuring and more complex than previously reported. with its ore, its products or its tailings (table 2). Their common exposure feature is Balangero chrysotile, although cases 15 and 17 may also have been exposed to fibrous tremolite. Cases 18-22 suggest exposure to Balangero chrysotile in the general environment has an aetiological role. Asbestos fibres have recently been found in the lungs of animals raised in the Balangero area, where the mining site was by far the most important source of asbestos fibres. This is still true today, due to incomplete remediation of the mining site.17 Cases 23-27 neither worked at the mine nor reported circumstances corresponding to our definitions of environmen tal or household exposure. However, they were exposed to Balangero mine tailings used as ballast. Possible exposure to tremolite may have played a role in cases 23 and 27: ballast from Balangero was used for the beds of railway lines up to the mid1970s, although it was later replaced by other serpentinites, some of which were contaminated with tremolite. The hypothesis has been advanced that chrysotile itself would not induce malignant mesotheliomas and that their occurrence in Quebec miners and millers could be due to contamination by fibrous tremolite.318 The occurrence of mesotheliomas in individuals with exposure to Balangero chrysotile is important because no tremolite has been detected in it.4 Instead, balangeroite is present, especially in serpentinites at the northern side of the mine, and represents 0.2-1% by weight of extracted fibres. Recognised in 1983 as a new mineral, it is a fibrous magnesium-iron silicate, appearing as bundles of brownish fibres strictly associated with long-fibre chrysotile.519 It is morphologically similar to amphiboles, and it produced nitrite accumulation, lipid peroxidation and nitrous oxide synthase activation in a human lung epithelial cell line, similarly to crocidolite.19 20 Thus it exhibited a potential for producing oxidative cellular damage in vitro. However, it is unclear what role these factors play in the induction of human mesothelioma. Furthermore, balangeroite has never been tested for carcino genicity in long-term animal experiments. Therefore, in light of current knowledge, it cannot be considered a carcinogen, nor it can be implied to cause mesotheliomas instead of chrysotile. In a meta-analysis of occupational cohort studies, chrysotile carcinogenic potency in inducing mesothelioma was estimated to be two to three orders of magnitude less than that of amphiboles.2 The major contribution to this assessment came from the results of the cohort study on Quebec chrysotile miners and millers.18 Supporting evidence was provided by the fact that in other cohorts worldwide - including that of Amiantifera workers - no or very few cases were found.4 21 Our assessment of the burden of mesotheliomas caused by chrysotile from Balangero is based on incomplete data. Nevertheless, the overall picture linking Balangero chrysotile to malignant mesothelioma is less reassuring than previously reported. Our findings also raise concern about c Further investigations are needed to better estimate the carcinogenic potency of chrysotile. c It may prove difficult to complete enumeration of at-risk individuals and in-case ascertainment, at least in certain settings, so these difficulties will have to be fully addressed in future research. risks caused by the continuing presence of mine tailings on railroad tracks, road beds and paving, and perhaps by incomplete remediation of the mining site. Acknowledgements: We thank B Terracini and N Pearce for their comments, the personnel of the Registry of Malignant Mesotheliomas, and in particular M Bertolotti, M Gangemi, A Stura, V Macerata, L Davico, G Cammarieri Diglio, C Brentisci, M Gilardetti, A Todesco and P Dalmasso. Funding: This study was partially supported by AIRC, Compagnia di San Paolo and Regione Piemonte. Francesco Barone Adesi and Elisa Fornero were supported by a grant from Regione Piemonte, Assessorato all'Ambiente, project ''Asbestos Hazard in the Western Alps''. Competing interests: None. REFERENCES 1. Boffetta P. Health effects of asbestos exposure in humans: a quantitative assessment. Med Lav 1998;89:471-80. 2. Hodgson JT, Darnton A. The quantitative risk of mesothelioma and lung cancer in relation to asbestos exposure. Ann Occup Hyg 2000;44:565-601. 3. McDonald AD, Case BW, Churg A, etal. Mesothelioma in Quebec chrysotile miners and millers: epidemiology and aetiology. Ann Occup Hyg 1997;41:707-19. 4. Piolatto G, Negri E, La Vecchia C, et al. An update of cancer mortality among chrysotile asbestos miners in Balangero, northern Italy. BrJIndMed 1990;47:810-14. 5. Compagnoni R, Ferraris G, Fiora L. Balangeroite, a new fibrous silicate related to gageite from Balangero, Italy. Am Mineral 1983;68:214-19. 6. Rubino GF, Piolatto G, Newhouse ML, et al. Mortality of chrysotile asbestos workers at the Balangero mine, northern Italy. Br J Ind Med 1979;36:187-94. 7. Calisti R, De Giuli P, Ghione GL. An update of cancer mortality among chrysotile asbestos miners in Balangero, northern Italy. Br J Ind Med 1992;49:144. 8. Silvestri S, Magnani C, Calisti R, et al. 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. In: Nolan RP, Langer AM, Ross M, et al, eds. The health effects of chrysotile asbestos: contribution of science to riskmanagement decisions. Ottawa: Mineralogical Association of Canada, 2001:177-1. 9. Riboldi L, Mensi C, Giordano S, et al. Mesotelioma maligno della pleura in un lavoratore con breve esposizione atipica ad amianto crisotilo. Med Lav 2004;95:320-4. 10. Mirabelli D, Stura A, Gangemi M, et al. Incidenza del mesotelioma maligno in Piemonte, 1990-2001. Epidemiol Prev 2007;31:132-9. 11. Calvino I. La fabbrica della montagna. Battaglia Democratica 28 February 1954. 12. Levi P. The periodic table. London: Penguin, 2000:55-6. 13. Rubino GF, Scansetti G, Donna A, et al. Epidemiology of pleural mesothelioma in north-western Italy (Piedmont). Br J Ind Med 1972;29:436-42. 14. Magnani C, Agudo A, Gonzalez CA, et al. Multicentric study on malignant pleural mesothelioma and non-occupational exposure to asbestos. Br J Cancer 2000;83:104-11. 15. Magnani C, Dalmasso P, Biggeri A, et al. Increased risk of malignant mesothelioma of the pleura after residential or domestic exposure to asbestos: a case-control study in Casale Monferrato, Italy. Environ Health Perspect 2001;109:915-19. 16. Nesti M, Marinaccio A, Chellini E. Malignant mesothelioma in Italy, 1997. Am J Ind Med 2004;45:55-62. 17. Fornero E. Asbestos hazard in the western Alps: mineral burden investigation in humans and animals to assess the environmental exposure in the Susa and Lanzo valleys [PhD dissertation]. Turin, Italy: Dipartimento di Scienze Mineralogiche e Metrologiche, Universita degli Studi di Torino, 2005. 18. Liddell FDK, McDonald AD, McDonald JC. The 1891-1920 birth cohort of Quebec chrysotile miners and millers: development from 1904 and mortality to 1992. Ann Occup Hyg 1997;41:13-36. 19. Groppo C, Tomatis M, Turci F, et al. Potential toxicity of nonregulated asbestiform minerals: balangeroite from the Western Alps. Part 1: identification and characterization. J Toxicol Environ Health 2005;68:1-19. 20. Turci F, Tomatis M, Gazzano E, et al. Potential toxicity of nonregulated asbestiform minerals: balangeroite from the Western Alps. Part 2: oxidant activity of the fibers. J Toxicol Environ Health 2005;68:21-39. 21. Dement JM, Brown DP, Okun A. Follow-up study of chrysotile asbestos textile workers: cohort mortality and case-control analyses. Am J Ind Med 1994;26:431-44. Occup Environ Med 2008;65:815-819. doi:10.1136/oem.2007.037689 819