Document NejVgQ48k0b1DdMapM76e3Xdg

Downloaded from oem.bmj.com on 19 June 2008 OEM ONLINE Excess of Mesotheliomas after Exposure to Chrysotile in Balangero, Italy Dario Mirabelli, Roberto Calisti, Francesco Barone Adesi, Elisa Fornero, Franco Merletti and Corrado Magnani Occup. Environ. Med. 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/abstract/oem.2007.037689v1 Rapid responses Email alerting service These include: You can respond to this article at: http://oem.bmj.com/cgi/eletter-submit/oem.2007.037689v1 Receive free email alerts when new articles cite this article - sign up in the box at the top right corner of the article Notes Online First contains unedited articles in manuscript form that have been peer reviewed and accepted for publication but have not yet appeared in the paper journal (edited, typeset versions may be posted when available prior to final publication). 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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 19 June 2008 OEM Online First, published on June 4, 2008 as 10.1136/oem.2007.037689 EXCESS OF MESOTHELIOMAS AFTER EXPOSURE TO CHRYSOTILE IN BALANGERO, ITALY Dario Mirabelli1'4, Roberto Calisti2, Francesco Barone-Adesi1,4 Elisa Fornero4, Franco Merletti1,4, Corrado 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 Tel. +39-011-633 4306 Fax +39-011- 633 4664 e-mail: franco merletti@unito.it Keywords (MeSH): asbestos, chrysotile, mesothelioma, carcinogens, environmental exposure Word count Abstract: 235. Text: 2760 The Corresponding Author has the right to grant on behalf of all authors and does grant on behalf of all authors, an exclusive licence (or non-exclusive for government employees) on a worldwide basis to the BMJ Publishing Group Ltd and its Licensees to permit this article to be published in Occupational and Environmental Medicine editions and any other BMJPGL products to exploit all subsidiary rights, as set out in our licence (http://oem.bmiiournals.com/ifora/licence.pdf ) 1 Copyright Article author (or their employer) 2008. Produced by BMJ Publishing Group Ltd under licence. Downloaded from oem.bmj.com on 19 June 2008 INTRODUCTION The carcinogenicity of chrysotile is established, although the issue of its potency relative to amphiboles for inducing mesotheliomas remains unresolved, with estimates ranging from 1:3 to 1:500.[1, 2] A related controversy is whether tremolite fibre contamination, rather than chrysotile, could be entirely responsible for mesothelioma causation. [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 of the Balangero mine reported only two deaths from pleural cancer up to 1987. [4, 6] This study has been regarded as contributing to the evidence that chrysotile has relatively low carcinogenic potency. [2] Published reports did not, however, include clerical workers or employees 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 etiologically related to the mine, including cases among non-occupationally exposed persons. POPULATION AND 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 taken away by railway and lorries. A cohort of miners and millers employed for at least one month by Amiantifera and active in 1946 or hired thereafter was established by Rubino et aland studied further by Piolatto etal.[4, 6] The cohort did not include white-collar workers or employees of sub-contractors. Fibre measurements during mining activities did not begin until 1969, and 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 ff/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 measurements are available of asbestos fibre concentrations in the general environment.[8, 11-12] Mine tailings from Balangero were used in several areas of Piedmont as ballast for road and railroad construction and for courtyard paving. Identification of cases Many asbestos industries were located in Piedmont, a region of 4.5 million inhabitants.[13] Since 1990, the RMM has accounted for newly diagnosed cases of malignant mesothelioma among residents; cases occurring in 1980-1989 were registered retrospectively.[10] Structured interviews with cases or respondents were conducted to obtain information on life-long occupational and nonoccupational exposure to asbestos. Initially interviews were conducted only with persons enrolled 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 with the National Registry of Mesotheliomas the RMM can identify persons exposed in Piedmont that were living in other Italian regions at the time of diagnosis.[16] Industrial hygienists performed qualitative and quantitative assessment of asbestos exposure for all successfully interviewed cases. They based their assessment 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, 3 Downloaded from oem.bmj.com on 19 June 2008 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 ideally belong to well-defined occupational populations, even if we could not explicitely list these populations as we lack their employment rolls. Cases occurring in the last two groups belong to the general population. Persons 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 in proximity of places where they had been dumped or used for pavings. 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 had no access to the files of the mortality cohort study on Balangero miners and millers, we did not know the age distribution of its 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 exercise could not be done for non-manual workers and for workers not employed by Amiantifera because their numbers were unknown. RESULTS Cases associated with exposure to chrysotile Among 2992 malignant mesothelioma cases registered in Piedmont residents in the period 1980 2007, information on exposures was collected and assessed for 1432 subjects. 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. 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 explicitely, and that the rater performing the exposure assessment 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 al. (1979) and Piolatto et al. (1990). Case 3, first diagnosed in 1985, was not included in these studies, perhaps because he became a manager in the last part of his career. Four cases occurred among manual workers after the follow-up was closed (cases 4-7), one case was a white-collar worker (case 8), and one was 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). 4 Table 1B. Cases of malignant mesothelioma among workers employed by sub-contractors at the Balangero mining site Case Sex Age Year Site Diagnosis Source of case Routes ofexposure 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). lla M 59 1992 Pleural Histol, IHC RMM Blue-collar worker at a sub-contractor, working at the mining site as miners' aid (1949). Bricklayer (1949-1957), worker in a nylon production facility (1957-1959), worker in the curing department of a tire production plant (1963-1977), marble cutter (1979-1989). 12 M 68 2003 Pleural Histol, IHC Riboldi et al. 2004 Blue-collar worker at a sub-contractor, working at the mining site as 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 at a sub-contractor 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 at a sub-contractor as lorry driver, carrying asbestos from the Amiantifera mine, 1958-1973. No other asbestos exposure at work. Lived in proximity of the mining area (1933 - 2006). Abbreviations. 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 a Possible exposure to other types of asbestos Downloaded from oem.bmj.com on 19 June 2008 6 Downloaded from oem.bmj.com on 19 June 2008 Three cases were never engaged 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. 7 Table 3. Cases of malignant mesothelioma due to household or environmental exposure Case Sex Age Year Site Diagnosis Source of case Routes ofexposure 18 F 55 1981 Pleural Histol RMM No definite/likely occupational exposure. Husband asbestos packer at the mining site, work clothes cleaned and washed at home (1948-1973). Lived in proximity of the mining area (1926-1981). 19 M 78 2003 Pleural Histol, IHC RMM No definite/likely occupational exposure. Lived in proximity of the mining area (1925-1926 and 1983 2003). 20 F 79 2003 Pleural Histol, IHC RMM No definite/likely occupational exposure. Lived in proximity of the mining area (1935-2003). 21 F 69 2003 Pleural Histol, IHC RMM No definite/likely occupational exposure. Lived in proximity of the mining area (1943 - 1980). 22 F 75 2007 Peritoneal Histol, IHC RMM Farmer 1944-2002, leaves collected in the surroundings of the mining area used for cattle litters. Lived in proximity of the mining area (1936 - 2007). Abbreviations. Histol: histological confirmation, IHC: immune staining pattern suggestive of a mesothelial neoplasm, based on histological material; RMM: Registry of Malignant Mesotheliomas Downloaded from oem.bmj.com on 19 June 2008 10 Table 4. Cases of malignant mesothelioma among persons exposed to mine tailings used outside mine Case Sex Age Year Site Diagnosis Source ofcase Routes ofexposure 23 F 52 1995 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). 24 a F 47 1996 Pleural Histol RMM 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) in proximity of railway tracks where Balangero mine tailings had been used as ballast. 25a F 74 1998 Pleural Histol RMM 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). 26 F 39 2000 Pleural Histol, IHC RMM No definite/likely occupational exposure. Lived in a district where Balangero tailings were used as road ballast (1982-2000). 27a M 74 2001 Pleural Histol, IHC RMM Employed by Italian railways as track maintenance worker (1951-1986), where Balangero mine tailings were used as ballast. No other asbestos exposure at work. Abbreviations. Histol: histological confirmation, IHC: immune staining pattern suggestive of a mesothelial neoplasm, based on histological material; RMM: Registry of Malignant Mesotheliomas a Possible exposure to other types of asbestos Downloaded from oem.bmj.com on 19 June 2008 11 Downloaded from oem.bmj.com on 19 June 2008 assessment of the burden of disease caused by asbestos should include workers hired by the subcontracting 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 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 an etiological role of exposure to Balangero chrysotile in the general environment. 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 environmental or household exposure. They were however 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 beds of railway lines up to the mid-1970s, but 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 would be due to contamination by fibrous tremolite.[3, 18] 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.[5, 19] 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 may play in the induction of human mesothelioma. Furthermore, balangeroite has never been tested for carcinogenicity 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 2-3 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, worldwide, in other cohorts - 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 the risks due to the continuing presence of mine tailings on railroad tracks, road beds and pavings, and perhaps to the incomplete remediation of the mining site. ACKNOWLEDGMENTS 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: 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. 13