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FILE NAME Brakes BRK DATE 2003 Jan DOC BRK142 DOCUMENT DESCRIPTION Journal Article - Exposure to Brake Dust and Malignant Mesothelioma - Case Studies Ann occup Hyg Vol 47 No. 4 pp 325-330 2003 '2003 British Occupational Hygiene Society Published by Oxford University Press DOI meg048 Exposure to Brake Dust and Malignant Mesothelioma A Study of 10 Cases with Mineral Fiber Analyses KELLY J. BUTNOR,,THOMAS A. SPORNand VICTOR L. ROGGLI University of Vermont Medical Center Department of Pathology Burlington VT 05405 Duke University Medical Center Department of Pathology Box 3712 Durham NC 27710 USA Received 18 June 2002 in final form 27 January 2003 Objectives A large number of workers in the USA are exposed to chrysotile asbestos through brake repair yet only a few cases of malignant mesothelioma MM have been described in this population Epidemiologic and industrial hygiene studies have failed to demonstrate an increased risk of MM in brake workers We present our experience of MM in individuals whose only known asbestos exposure was to brake dust and correlate these findings with lung asbestos fiber burdens Methods Consultation files of one of the authors were reviewed for cases of MM in which brake dust was the only known asbestos exposure Lung fiber analyses were performed using scanning electron microscopy SEM in all cases for which formalin or paraffinembedded lung tissue was available Results Ten cases of MM in brake exposed individuals were males aged 51-73 yr Nine cases arose in the pleura and one in the peritoneum Although the median lung asbestos body count 19 AB is at our upper limit of normal range 0 2A 0 B half of the cases had levels within our normal range In every case with elevated asbestos fiber levels by SEM excess commercial amphibole fibers were also detected Elevated levels of chrysotile and commercial amphibole fibers were detected only in cases that also had increased commercial amphibole fibers Conclusions Brake dust contains exceedingly low levels of respirable chrysotile much of which consists of short fibers subject to rapid pulmonary clearance Elevated lung levels of commercial amphiboles in some brake workers suggest that unrecognized exposure to these fibers plays a critical role in the development of MM Keywords asbestos auto repair brake dust chrysotile fiber analysis mechanic mesothelioma occupation peritoneum pleura INTRODUCTION It is estimated that nearly 1000000 workers are involved in installing and repairing clutch facings and brake shoes and linings Huncharek 1990 Because these automotive friction materials contain asbestos there is concern that brake repair workers are at increased risk for developing malignant mesothelioma MM Numerous studies have examined airborne asbestos fiber concentrations during brake maintenance operations demonstrating measurable levels for considerable periods of time and at distances extending several meters from the actual operation Author to whom correspondence should be addressed Tel 1-919-286-4111 Fax 1-919-681-7377 mail rogg1002@mc.duke.edu rogg1002@mc.duke.edu Hickish and Knight 1970 Lorimer et al 1976 Rohl et al 1976 Levine 1978 Rodelsperger et al 1986 Kauppinen and Korhonen 1987 Moore 1988 Roggli and Pratt 1988 Despite the large number of such workers only a few cases of MM in individuals exposed to brake dust have been described mostly in the form of case reports Newhouse and Thompson 1965 Langer and McCaughey 1982 Jarvholm and Brisman 1988 Huncharek et al 1989 Analyses of brake dust have shown that it contains % asbestos most of which is short chrysotile fibers < ...min length with much of the asbestos having been converted to forsterite due to the heat generated during the braking process Williams and Muhlbaier 1982 Conclusions on the relationship between brake dust exposure and MM have been based predominantly on epidemiological studies which have 325 326 K. J. Butnor T. A. Sporn and V. L. Roggli shown no increased risk of MM resulting from exposure to automotive friction products McDonald and McDonald 1980 Teta et al 1983 Spirtas et al 1985 1994 Woitowitz and Rodelsperger 1994 Teschke et al 1997 Agudo et al 2000 A metaanalysis of epidemiologic data concluded that the relative risk of MM in brake workers was 0.9 indicating no excess risk above that expected in the general population Wong 2001 Studies correlating exposure with the actual concentration of asbestos fibers in the lungs of brake repair workers with MM are sparse Langer and McCaughey 1982 Woitowitz and Rodelsperger 1994 Roggli et al 2002 Most of these reports have included cases with substantial exposure to asbestos through other types of employment We describe our findings including data from lung fiber analyses in individuals with MM whose only known exposure to asbestos was to automotive friction materials MATERIALS AND METHODS The 10 cases selected for the current study were obtained from one of the authors V.L.R. consultation files which contain data on more than 1900 cases of MM These cases were all medico consultations which included five referred by plaintiffs and five by defendants of brake manufacturers The diagnosis of MM was based on the gross distribution of tumor histologic appearance and the results of histochemical and immunohistochemical studies using previously described criteria Roggli et al 1992a In all cases the diagnosis of MM was made independent of asbestos exposure history and tissue mineral fiber content Information regarding age sex primary tumor site occupation smoking history and duration of exposure was also obtained Occupational exposure information was obtained by direct patient interview and thorough review of the medical records Only cases in which occupational contact with brake dust was the sole recognized source of asbestos exposure were included in our study Fiber analyses were performed on formalin or embedded lung parenchyma using the sodium hypochlorite digestion procedure as previously described Roggli et al 1992b Digested lung tissue was collected on 0.4 ...mpore size Nuclepore filters For light microscopic analysis the filter was mounted on a glass slide Asbestos bodies were quan- tified using a magnification of 400x Only ferruginous bodies exhibiting typical morphology with thin translucent cores were counted as asbestos bodies Roggli 1992a Results were reported as asbestos bodies per gram wet lung tissue AB with a detection limit of -3 AB for a 0.3 g sample Roggli 1992b For scanning electron microscopic SEM analysis the filter was mounted on a carbon disc with colloidal graphite and then sputter with gold A JEOL 6400 scanning electron microscope JEOL Peabody MA with a screen size of 22.7 ^ 17.3 cm was used to quantify uncoated fibers and AB at a screening magnification of 1000x Only fibers 5 ...min length with a length to width ratio of at least 3 and approximately parallel sides were counted Fibers meeting these criteria were quantified by examining 100 consecutive fields with a total area of -2.53 mmor until a 200 fiber count was reached The thinnest fibers we have observed at this screening magnification are -0.15 ...min diameter The limit of detection is -400 fibers for a 0.3 g sample Roggli 1992b For cases in which no asbestos fibers were detected the value was reported as less than the detection limit for that case The chemical composition of fibers was determined by energy dispersive ray analysis Asbestos fibers were classified as commercial amphiboles specifically amosite + crocidolite AC commercial amphiboles including tremolite anthophyllite and actinolite TAA or chrysotile Roggli et al 1992b Tissue concentration of AC TAA and chrysotile was calculated in each case using the proportion of each type of fiber and the total asbestos fiber concentration asbestos mineral fibers NAMF were classified according to their morphology and Xray spectra Roggli et al 1992b For cases in which no fibers of a particular category were detected the value was reported as less than the detection limit for that case The results of fiber analysis for MM cases were compared with 20 reference cases which as previously described had normal lungs no history of asbestos exposure and no evidence of asbestos- related disease at autopsy Srebro et al 1995 RESULTS Ten cases of histologically confirmed MM in which the only identified asbestos exposure was to brake dust were retrieved from the files of one of the authors V.L.R. Salient clinical features of the cases are summarized in Table 1. All were men nine of whom had tumors arising in the pleura and one in the peritoneum The age ranged from 51 to 73 median 60 yr Information regarding smoking was available in seven cases All seven smoked or were ex- smokers The length of exposure to brake dust ranged from 7 to 40 median 24 yr All patients had direct exposure to brake dust as automotive mechanics The predominant histologic pattern was epithelial in five cases while three were biphasic and one showed desmoplastic features Information regarding tumor type was not available in one case Pleural plaques were present in four of seven informative cases Asbestosis was not evident histologically in any case Brake dust and mesothelioma 327 Table 1. Demographic pathologic and occupational information Case 1 2 Age sex M 58 Tumor type PL PL Occupation Auto machinist Brake mechanic Smoking pack 2 XS 43 3 55 PL Brake mechanic 60 4 73 PL Auto mechanic 20+ 5 51 PE Brake repair XS 6 53 PL Auto mechanic ND 7 ND ND Brake repair ND 8 66 PL Brake repair XS 9 71 PL Auto repair 21 XS 10 ND PL Brakeline repair ND Exposure duration Pleural plaque yr 37 Yes 27 Yes 24 ND 40 No 11 ND 7 No 15 ND 40 Yes 17 Yes 24 No B biphasic D desmoplastic E epithelial M male ND not determined PE peritoneal PL pleural XS smoker Table 2. Results of lung tissue analysis Case 1 AB 1490 2 25 3 50 4 5 5 24 6 13.4 7 9.1 8 2.6 9 560 10 14 Median Reference cases 19 3 0.2-22 ACb TAAb 3270 2180 4810 440 380 4630 720 720 580 1160 490 490 340 340 120 240 6000 3280 1440 2170 440 940 600 2540 600 170-2540 Chrysotileb 2180 440 660 720 580 490 340 120 2180 720 620 600 100-1000 NAMFb 9800 1750 660 2880 5780 980 340 850 6550 2890 2320 600 210-10 160 AB asbestos bodies AC commercial amphiboles amosite + crocidolite NAMF asbestos mineral fiber TAA noncommercial amphiboles tremolite + anthophyllite + actinolite AB asbestos bodies wet lung by light microscopy Total coated AB and uncoated fibers 5...mlength wet lung as determined by scanning electron microscopy and energy dispersive ray analysis Median values and range in parentheses for 20 cases with normal lungs at autopsy no history of asbestos exposure or evidence of asbestos disease Srebro et al 1995 The results of the fiber analyses are summarized in Table 2. The median asbestos body count in brake exposed individuals 19 AB is at our upper limit of normal range 0-20 AB Roggli et al 1992b In five of the 10 cases the asbestos body content was within our normal range cases 4 6 8 and 10 commercial amphiboles principally tremolite with some actinolite and anthophyllite predominated over commercial amphibole fibers in half of the cases and were elevated in two cases cases 3 and 9 Excess commercial amphibole fibers were detected in five of the six cases with elevated tissue asbestos content cases 1-3 9 and 10 Amosite was the principal commercial amphibole in four of these cases and crocidolite predominated in the fifth case 9 In one additional case case 5 asbestos body counts by light microscopy were marginally elevated but neither commercial amphi- bole fibers nor chrysotile were detected and noncommercial amphibole fibers were within our normal range by SEM Chrysotile was detected in three cases and exceeded our normal range in two of these cases cases 1 and 9 All cases with excess chrysotile or commercial amphibole fibers also showed increased levels of commercial amphibole fibers Pleural plaques were present in four cases , 2 8 and 9 Commercial amphibole fibers were detected in all four of these cases and elevated in three Nonasbestos mineral fibers included among others talc silica miscellaneous silicates and rutile These were within our normal range in all cases DISCUSSION AND CONCLUSIONS By virtue of its heat resistance and tensile strength asbestos has found an application in the manufacture 328 K. J. Butnor T. A. Sporn and V. L. Roggli of brake and clutch products Greenberg and Darcy 1992 Since the 1940s the only form of asbestos used in automotive friction materials is chrysotile Langer and McCaughey 1982 Chrysotile is a major component of friction materials accounting for 30-80 of the finished product Greenberg and Darcy 1992 However according to most studies the concentration of respirable chrysotile liberated by various brake maintenance operations such as blowing out brake surfaces and grinding brake shoes is low Lynch 1968 Hickish and Knight 1970 Lorimer et al 1976 Rodelsperger et al 1986 In a number of industrial hygiene reports detailing asbestos exposures among automotive mechanics the concentration of airborne asbestos has been below the Occupational Safety and Health Administration's permissible exposure limit PEL of 0.1 fiber National Institute for Occupational Safety and Health 1980a Cheng and O'Kelly 1986 Rodelsperger et al 1986 Kauppinen and Korhonen 1987 The low level of airborne chrysotile liberated during brake repair is consistent with the results of analyses of brake dust samples Williams and Muhlbaier 1982 Chrysotile fibers in unworn brake linings are entirely in a bonded or encapsulated state During braking temperatures exceeding 700-800 are reached Much of the chrysotile is broken down into forsterite a asbestos anhydrous magnesium silicate Williams and Muhlbaier 1982 Wong 2001 Of the small number of residual intact chrysotile fibers most remain embedded in the plastic binding material Less than 0.1-1 of the fibers in brake dust are free chrysotile the majority of which are short fibers < ...min length Lynch 1968 Hatch 1970 Davis and Coniam 1973 Williams and Muhlbaier 1982 Wong 2001 Of note a considerably higher concentration 2-15 of free chrysotile has been detected in used brake linings Rohl et al 1976 However this material may not be representative of brake dust particles that become airborne Williams and Muhlbaier 1982 There has been considerable debate regarding the relative pathogenicity of chrysotile Evidence from a number of studies on workers exposed to chrysotile suggests that chrysotile asbestos poses a lower risk of MM than does amphibole asbestos McDonald and McDonald 1978 Wagner et al 1982 Churg et al 1984 McDonald et al 1984 Dunnigan 1988 McDonald 1988 Roggli and Pratt 1988 Newhouse and Sullivan 1989 The relative low potency for inducing MM has been ascribed to the low pulmonary retention of chrysotile Churg et al 1989 Mossman and Gee 1989 Churg and Vedal 1994 Fiber size also appears to play an important role in the development of MM Experimental animal studies have shown a very low fibrogenic and carcinogenic potential for short asbestos fibers Wagner et al 1974 Stanton et al 1981 Davis and Jones 1988 This finding is of particular relevance in the case of brake workers as the majority of chrysotile fibers in brake dust are < min length Williams and Muhlbaier 1982 A number of studies have examined workers with exposure to chrysotile through the mining and milling of asbestos commercial amphibole fibers are natural contaminants of Canadian chrysotile Lung fiber burden analyses performed many years after exposure show that commercial amphibole levels often exceed chrysotile concentrations Churg and Warnock 1980 Churg and Wiggs 1986 Among the few lung fiber burden analyses performed in workers exposed solely to chrysotile in brake dust Langer found only chrysotile fibers 1 ...gg wet lung the overwhelming majority of which were 10 ...min length Langer and McCaughey 1982 However in other cases only amphibole fibers have been identified Woitowitz and Rodelsperger 1994 In the present series the lung fiber burden of workers whose only identified asbestos exposure was to chrysotile in brake dust was within our normal range in half of the analyzed cases The other analyzed cases showed increased levels of commercial amphi- boles in all but one The few cases with elevated chrysotile or commercial amphibole fibers also had elevated commercial amphiboles There are a number of limitations of the present study First of all the study is a case series of medicolegal cases and may not be representative of all individuals exposed to brake dust occupationally Secondly historical information obtained by patient interview is subject to the limitations of recall bias for events that occurred decades previously This may explain the absence of reported exposures to commercial amphiboles in our study Thirdly there is the possibility that long chrysotile fibers with diameters 0.15 ...mwere missed by the use of SEM at a screening magnification of 1000x However we think that this is unlikely since a number of investigators using the somewhat more sensitive transmission electron microscopy method have found no correlation between the concentration of chrysotile asbestos and the risk of mesothelioma in individuals exposed to both chrysotile and commercial amphibole fibers McDonald et al 1989 Churg and Vedal 1994 Rodelsperger et al 1999 A more troublesome issue is the possibility that chrysotile fibers might be able to interact with mesothelial cells induce neoplastic transformation and then be removed from lung leaving no trace of the initial excess fiber burden In this regard it should be noted that there is no disagreement regarding the greater persistence of the amphibole fibers compared to chrysotile nor is there disagreement regarding the greater potency of amphiboles for producing mesothelioma Furthermore experimental studies with Brake dust and mesothelioma 329 made mineral fibers indicate that it is the fibers that persist within the lung that cause fibrosis and neoplasia Hesterberg et al 1994 1995 1996 There are no studies in experimental animals indicating that chrysotile can cause disease and subsequently be completely cleared from the lungs Thus the andrun hypothesis for chrysotile is a flimsy one without any solid scientific support Lung burden analyses in automotive brake repair workers with MM in our series reflect tissue asbestos content within the normal range or elevated commer- cial amphiboles These findings combined with data from prior lung fiber analyses Langer and McCaughey 1982 Woitowitz and Rodelsperger 1994 industrial hygiene studies Hickish and Knight 1970 Lorimer et al 1976 Rohl et al 1976 Levine 1978 Rodelsperger et al 1986 Kauppinen and Korhonen 1987 Moore 1988 Roggli and Pratt 1988 and epidemiological reports Wong 2001 strongly suggest that friction product exposure such as that encountered by automotive mechanics is unlikely to contribute to the development of MM The presence of elevated commercial amphiboles in the lungs of some brake workers indicates that unrecognized asbestos exposure through other forms of employment plays a confounding role in the development of MM in this population Other cases have tissue asbestos contents indistinguishable from background controls and may be considered to be spontaneous or idiopathic REFERENCES Agudo 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