Document 6R4vyZy65MkVDd5eeB4QqgaBR

Ann. ocaip. y*,, Vol 47, No. 4. pp. 325-330.2003 9 2003 Bfitffh Ottupsintwl Hygieas Society Published by Oxford University Press DOfc 10: l093/aflaby|/hscf04S Exposure to Brake Dust and Malignant Mesothelioma: A Study of 10 Cases with Mineral Fiber Analyses KELLY j. BUTNOR1, THOMAS A. SPORN2 and VICTOR L. ROGGLI2* 1University of Vermont Medical Center, Department ofPathology, Burlington, VT05405; 2Dttke University Medical Center, Department ofPathology, Box 3712, Durham, NC27710, USA Received 18 June 2002; is final form 27 January 2003 Objectives: A large number of workers in the USA are exposed to chiysotite asbestos through brake repair, yet only a few cases ofmalignant mesothelioma (MM) have been described In this population. Epidemiologic and industrial hygiene studies have foiled to demonstrate an increased risk ofMMin brake workers. We presentour 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 ail cases for which formalin-fixed or parafEtaernbedded lung tissue was available. j Results: Ten cases of MM in brake dust-exposed individuals were males aged 51-73 yr. Nine cases arose is the pleura and.one In the peritoneum. Although the median lung asbestos body count (19 AB/g) is at our, upper limit of normal (range 0-29 AB/g), half of the cases had levels within our normal range. In every case with elevated asbestos liber levels by SEM, excess commercial amphibole fibers were also detected. Elevated levels of chrysolite and non-commer cial amphibole fibers were detected only in cases that also had increased commerdai amphibole' fibers. Conclusions: Brake dust contains exceedingly low levels of respirable duysotiie, much of which consists of short fibers subject to rapid pulmonary clearance. Elevated lung levels of commercial amphlboles In some brake workers suggest that unrecognized exposure to these fibers plays a critical rote in the development of MM. Keywords: asbestos; auto repair; brake dust; chrysolite; fiber analysis; mechanic; mesothelioma; occupation; peritoneum; pleura c. 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, them is concern that brake repair workers are at increased risk for developing malignant meso thelioma (MM). Numerous studies have examined airborne asbestos fiber concentrations during brake maintenance operations, demonstrating measurable levels for considerable periods oftime 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; e-mail: ioggl002@mc.duke.edu (Hickish and Knight, 1970; Lorimer et ai, 1976; Rohl etaL, 1976; Levine, 1978; Rodelsperger etal, 1986; Kauppinen and Korhonen, 1987; Moore, 1988; Roggti 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 etal, 1989). Analyses of brake dust have shown that it contains <1 % asbestos, most ofwhich is short chrysotile fibers <1 pm in length, with much of the asbestos having beep 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 predom inantly on epidemiological studies, which have ALL-STATE LEGAL1 HWBUI0009031 326 K. J. Butnor, T. A. Spom and V. L. Roggli shown no increased risk of MM resulting from with gold. A JEOL JSM-6400 scanning electron exposure to automotive friction products (McDonald . microscope (JEOL, Peabody, MA) with a screen size and McDonald; 1980; Teta etal, 1983; Spirtas etal, of 22.7 x 17.3 cm was used to quantify uncoated 1985, 1994; Woitowite and Rodelsperger, 1994; fibers and AB at a screening magnification of lOOOx. Teschke et al, 1997; Agudo et al, 2000). A meta- Only fibers >5 pm in length with a length to width analysis of epidemiologic data concluded that the ratio of at least 3:1 and approximately parallel sides relative risk of MM in brake workers was 0.9, indi were counted. Fibers meeting these criteria were cating no excess risk above that expected in the quantified by examining 100 consecutive fields, with general population (Wong, 2001). a total area of -2.53 mm2, or until & 200 fiber count Studies correlating exposure with the actual was reached. The thinnest fibers we have observed at concentration of asbestos fibers in the lungs of brake this screening magnification are -0.15 pm in diam repair workers with MM are sparse (Langer and eter. The limit ofdetection is -400 fibers/g for a 0.3 g McCaughey, 1982; Woitowitz and Rodelsperger, 1994; Roggli el al, 2002). Most ofthese reports have included cases with substantial exposure to asbestos through other types of employment We describe our findings, including data Emm lung fiber analyses, in individuals with MM whose only known exposure to asbestos was to automotive friction materials. 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 deter mined by energy dispersive X-ray analysis. Asbestos ' fibers were classified as commercial amphiboles, specifically amosite + crocidolite (AC), non-com mercial amphiboles, including tremolite, anthophyl- MATERIALS AND METHODS Hie 10 cases selected for the current study were obtained from one of the'authors (VXJEL) consul tation files, which contain data on more than 1900 cases of MM. These cases were ail medico-legal consultations, which included five referred by plain tiffs and five by defendants of brake manufacturers. The diagnosis of MM was based on the gross distri bution of tumor, histologic appearance and the results of histocheraical and immunohistochemical studies using previously described criteria (Roggli et aL, 1992a). In all cases, die diagnosis of MM was made independent of asbestos exposure history, and tissue mineral fiber content Information regarding age, sex; lite and actinolite (TAA), or chryBOtile (Roggli et al., 1992b). Tissue concentrationof AC, TAA and chrysotile was calculated in each case using the proportion of each type of fiber and the total asbestos fiber con centration. Non-asbestos mineral fibers (NAMF) were classified according tp their morphology andXray 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 asbestosrelated disease at autopsy (Srebro et al, 1995). primary tumor site, occupation, smoking history and duration ofexposure was also obtained. Occupational ' RESULTS 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-fixed or paraffin-embedded lung parenchyma using thesodium hypochlorite digestion procedure, as previ ously described (Roggli et'aL, 1992b). Digested lung tissue was collected on 0.4 pm pore 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 ferru ginous 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/g), with a detection limit of -3 AB/g for a 0.3 g sample (Roggli, 1992b). For scanning electron microscopic (SEM) analysis, the filter was mounted on a carbon Ten cases of histologically confirmed MM in which tire only identified asbestos exposure was to brake dustwere 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 0) yr. Information regarding smoking was available in seven cases. AB seven smoked or were exsmokers. Hie length ofexposure to brake dust ranged from 7 to 40 (median 24) yr. AB patients had direct exposure to brake dust as automotive/brake 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 disc with colloidal graphite and then sputter-coated any case. 1 ) \ HWBUI0009032 J. j Brake dust and mesothelioma 327 Table 1. Demographic, pathologic and occupational information Case 1 2 3 4' 5 6 7 B 9 10 Age (yrVsex Timor type/site Occupation Smoking (pack-yr) 61/M E/PL Auto machinist 2;XS 58/M mi Stake mechanic 43 5S/M E/PL Brake mechanic 60 73/M B/PL Auto mechanic 20+ 51/M E/PE Brake repair. XS - 53/M D/PL Auto mechanic ND ND/M ND/PL Brake repair ND 66/M, B/PL Brake repair XS 71/M B/PL Auto repair 21; XS ND/M E/PL Brakeiine 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 . 34 No. B, triphasic; D, desmoplastic; E, epithelial; M, male; ND.'not determined; PE. peritoneal; PL, pleural; XS, ex-smoker. Table 2. Results of lung'tissue analysis. Case 1 2 3 4 5 6' 7 8 9 10 Median Reference cases* AB/g* 1490 25 ' 50 <5 , 24 13.4 9.1 2.6 560 14 19 3 (<0.2-22) AC* TAA* 3270 2180 4810 440 380 4630 <720 720 <580 1160 490 490 340- <340 120 240, 6000 3280 1440 2170 440 .940 <600 (<lOO-<2540) <600 (<170-2540) Guysodle1' NAMF* v 2180 9800 <440 - 1750 <660 660 <720 2880 <580 5780 <490 . 980 <340 340 <120 . 850 2180 6550 . 720 2890 <620 2320 <600 (<100-1000) <600(210-10160) AB, asbestos bodies; AC, commerdal amphiboles (amosite + crocidolite); NAME, non-asbestos mineral fiber, TAA, noncommeicial'amphiboles (tremolite anthophyllite + actmoiite). aAB/g, asbestos hodies/g wet lung by light microscopy. 'Total coated (AB) and untreated fibers SS psa (iength)/g wet lung as determined by scanning electron microscopy and'energy dispersive X-ray analysis. `Median values and range (in parentheses) for 20 cases with normal lungs at autopsy, no history of asbestos exposure or evidence ofasbestos-related disease (Srebro et cl. 1995). The results of the fiber analyses are summarized in Table 2. Hie median asbestos body count in brake dust-exposed individuals (19 AB/g) is at our upper limit of normal (range 0-20 AB/g) (Roggli et at, 1992b). In five of the 10 cases, the asbestos body content was within our normal range (cases 4, 6-8 and 10). Non-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 weremarginally elevated, but neither commercial amphi bole fibers nor chrysolite were detected and non commercial 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 non-commercial amphibole fibers also showed increased levels of commercial amphibole fibers. Pleura! plaques were present in four (cases 1,2,8 and 9). Commercial amphibole fibers were detected in all four of these cases and elevated in. three. Non asbestos 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 HWBUI0009033 328 K. 1. Butnor, T. A. Spora and V. L. Roggii of brake and clutch products (Greenberg and Darcy, 1992). Since the 1940s, the only form of asbestos used in automotive friction materials is chrysodle (Langer and McCaughey, 1982). Chiysotile 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 chrysolite liberated by various brake maintenance operations, such as `blowing out* brake surfaces and grinding brake shoes, is low (Lynch, 1968; Hicklsh mid 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/cm3 (National Institute'for Occupational Safety and Health, I980a,b; Cheng and O'Kelly, .1986; Rodelsperger et a!., 1986; Kauppinen and Korhonen, 1987). The low level of airborne chiysotile liberated during brake repair is consistent with the results of analyses of brake dust samples (Williams and Muhlbaier, 1982). Chiysotile fibers in unworn brake linings are entirely in a bonded or encapsulated -state. During braking, temperatures exceeding 70&-%QQC are reached. Much' of tire chiysotile Is broken down into forsterite, a non-asbestos anhydrous magnesium silicate'(Williams and Muhlbaier, 1982;'Wong, 2001). Of the small number ofresidua! intact chiyso tile fibers, most remain embedded in the plastic binding material. Less than 0.1--1% of the fibers in brake dust are free chiysotile, the majority of which are short fibers, <1 pm in length (Lynch, 1968; Hatch, 1970; Davis and Coniam, 1973; Williams and Muhlbaier, 1982; Wong, 2001). Of note, a consider ably higher concentration (2-^15%) of fine chrysodle has been detected in used brake linings (Rohl et ai., 1976). However, this material may not be representa tive of brake dust particles that become airborne (Williams and Muhlbaier, 1982). There has been considerable debate regarding the relative pathogenicity of chiysotile. Evidence from a number of studies on workers exposed'to chrysodle suggests that chrysodle asbestos poses a lower risk of MM than does amphibole asbestos (McDonald and McDonald, 1978; Wagner et aL, 1982; Churg et aLt 1984; McDonald et aL, 1984; Dunnigan, 1988; McDonald, 1988; Roggii and Pratt, 1988; Newhouse and Snllivan, 1989). The relative low potency for inducing MM has been ascribed to the low pulmon ary retention of chrysodle (Churg et aL, 1989; Mossman and Gee, 1989; Churg and Vedal, 1994). Fiber size also appears to play as 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 chiysotile fibers in brake dust are <1 pm In length (Williams and Muhl baier. 1982). A number of studies have examined workers with exposure to chiysotile through the mining and milling of asbestos. Non-commercial amphibole fibers arenatural contaminants of Canadian chrysotile. Lung fiber burden analyses performed many years after exposure show that non-commercial amphibole levels often exceed chrysotile concentrations (Churg and Wamock, 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 chiysotile fibers (1 pg/5 g wet lung), the overwhelming majority of which were <10 pm in 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 non-cotiunerciai amphibole fibers also had elevated commercial amphiboles. - There are a number of limitations-, of the present study. First ofall, the study is a case series of medico legal cases, and may not be representative of all indi viduals exposed, to brake dust- occupationally. Secondly, historical information obtained by patient interview is subject to the limitations ofrecall bias for events that occurred decades previously. This may explain the absence of reported exposures to commer cial amphiboles in our study. Thirdly, there is the possibility that long chiysotile fibers with diameters <0.15 pm were missed by the use of SEM at a screening magnification of lOOQx. However, we think that this is unlikely, since a number of investi gators using the somewhat more sensitive transmis sion electron microscopy method have found no correlation between the concentration of chrysotile asbestos and the risk of mesothelioma in individuals exposed to both chiysotile and commercial amphlbole fibers (McDonald et aL, 1989; Churg and Vedal, 1994; Rodelsperger etaL, 1999). A more troublesome issue is the possibility that chiysotile fibers might be able to interact with tnesothelial 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 meso thelioma. Furthermore, experimental studies with i \ -.J HWBUI0009034 Brake dust and mesothelioma 329 man-made mineral fibers indicate that it is the fibers Dunnigan I. (1988) Linking chrysotile asbestos with raeso- that persist within the lung that cause fibrosis mid neoplasia (Hesterberg et aL, 1994, 1995, 1996). There are no studies in experimental animals indicating ` thetioma. Am J had Med; 14:205-9. Greenberg GN, Darcy DJ. (1992) Occupational and environ mental exposure to asbestos, in Roggli VL, Greenberg SD, Pratt PC, editors. Pathology of asbestos-associated disease. thatchrysotile can cause disease and subsequently be Boston. MA: Little Brown, pp. 19-37. completely cleared from the lungs. Thus the `hit-andrun' hypothesis for chrysotile is a flimsy one without any solid scientific support. Hatch D. (1970) Possible alternatives to asbestos as a friction material. Ann Occup Hyg; 13:25-9. Hesterberg TW, Miller WC, Mast R, McConnell EE. Bernstein DM, Anderson K_ (1994) Relationship between lung bio Lung burden analyses in automotive brake repair persistence and biological effects of man-made vitreous workers with MM in our series reflect tissue asbestos fibers after chronic inhalation in rats. Environ Health content within the normal range or elevated commer cial atnphiboles. These findings, combined with data' from prior lung fiber analyses (Langer and Perspect; 102 (snppl. 5): 133-7, Hesterberg TW, Miller WC, Thevenaz P, Anderson R. (1995) Chronic inhalation studies of mart-made vitreous fibres: characterization of fibres in the exposure aerosol and lungs. McCaughey, 1982; Woitowitz and Rodelsperger, Ann Occup Hyg; 39: 637-53. 1994), industrial hygiene studies (Hicldsh and Knight,T970; Lorimer et aL, 1976; Rohl era/., 1976; Levine, 1978; Rodelsperger aL, 1986; Kaupputen and Korhonen, 1987; Moore, 1988; Roggli and Pratt, Hesterberg TW, Miller WC, Musselman RP, Kamstrup Q, Hamilton RD, Thevenaz P. (1996) Biopersistencs of man made vitreous fibers and crocidotite asbestos in the rat fung following inhalation. Fundam Appl Toxicol; 29:269-79. Hiekish DE, Knight KL. (1970) Exposure to asbestos during 1988) and epidemiological reports (Wong, 2001), brake maintenance. Ann Occup Hyg; 13:17-21. 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 atnphiboles in Hunchaiek M. (1990) Brake mechanics, asbestos, and disease risk. Am J-Forensic Med Pathol; 11:236-40. Hunchaiek M, Muscat J, Capotoito JV. (1989) Pleural meso thelioma in a brake mechanic. Br J Ind Med; 46:69-71. Jarvholm B, Brisman J. (1988) Asbestos associated tumors in the lungs of some brake workers indicates that unrec car mechanics. Br J Ind Med; 45:645-6. ognized asbestos exposure through other ferns of employment plays a confounding role in the develop ment of MM . in this population. .Other cases have Kauppinen T, Korhonen K. (1987) Exposure to asbestos during brake maintenance ofautomobile vehicles by different meth ods. Am Ind Hyg Assoc I; 48:499-504. -Langer AM, McCaughey WTB. 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