Document dYNXBnmOkQYrrBz07gDjgV3G6

Risk Analpls, Vol 24. No. 3,2004 Mesothelioma Among Brake Mechanics: An Expanded Analysis of a Case-Control Study Patrick A. Hesse!,1* M. Jane Teta,2 Michael Goodman,3 and Edmund Lau4 The US. Environmental Protection Agency has begun discussions to consider its assessment of asbestos toxicity related to mineral form and fiber size. Brake workers are typically exposed to short cbrysotfle fibers. To explore the mesothelioma risk among brake workers, considering otheroccupational exposuresto asbestos, data from astudy thatwas published previouslywere obtained and the analysis was extended. The National Cancer Institute provided data from a case-control study of mesothelioma. Because many participants with a history of brake work also had employment in other asbestos-related occupations, mesothelioma cases andcontrols wore compared for a history of brake work, controlling for employment in eight occupations with potential asbestos exposure. A stratified, analysis was also performed excluding those with any of the eight occupations. Possible interactions between brake work and other occu pational exposures related to risk ofmesothelioma wore also examined. The odds ratio (OR) for employment in brake installation or repair was 0.71 ($5% <3: 030-4-60) when controlled for insulation or shipbuilding. When a history of employment in 'any of the eight occupations with potential asbestos exposure was controlled, the OR was 0.82 (95% Cfc 036-1X0). ORs did not Increase with increasing duration of brake work. Exclusion of those with any of the eight exposures resulted in an OR of 0.62 (95% Cl: 0.01-4.71) for occupational brake work. There was no evidence of an interaction between brake work and other occupational expo sures. These latter analyses were based on small numbers of exposed cases. The results are consistent with tho existing literature indicating that brake work does not: increase the risk of mesothelioma and adds to the evidence that fiber type and size are important detenninants of mesothelioma risk. WOBJPSs Asbestos, auto mechanics, friction brake products, mesothelioma L INTRODUCTION would distinguish carcinogenic potency by fiber type, In February 2003, the U.S. Environmental Pro tection Agency (BRA) announced plans to evaluate an asbestos cancer risk assessment methodology that and size.*1* As noted in the announcement, the ex isting assessment has not changed since 1986 despite substantial improvements in asbestos measurement techniques and better understanding of how asbestos exposure contributes to disease. t Exponent, Wood Date, Ik, USA. i Exponent, Health Practice, New York, NY, USA. A large number of epidemiologic studies have been examined to address the comparative poten 3 Department of Epidemiology, Rollins School of Public Health, Emery University, Atlanta, GA, USA 4 Expoaem, Health Practice, Menlo Park, CA, USA * Address comspondenca to Patrick A. Hessel, PfaJEX, Expo nent, 185 Hansen <X Slo. 100, Wood Dele, It- 19l, USA; phessd@exponeat.com. cies ofchiysotile and the ampfciibole asbestos fibers. Animal studies have proved disappointing either be causethe routes ofexposure used in these studies (i&, peritoneal or intratracheal instillation) bypass clear ance mechanisms or because of the low sensitivity of t 547 0272-4B2/WMOCKWSiiOM 0 2004 Society totWsk teilpis HWBUI0011370 VV 548 the inhalation test model/5) Consideration of fiber length and diameter, however, has typically relied on experimental evidence (toxicology and lung bur den studies).14* Given the Agency's renewed interest in mineralogy and fiber size, studies of those ex posed primarily to short chrysotile fibers are espe cially relevant. Automotive brakes have historically been made from Merlon materials containing only the chrysotile form of asbestos. Motor vehicle mechanics who in stalled andrepaired brakes were exposed primarilyto shortchrysotilefibers withlow time-weighted average exposures and intermittent, higher, short-term expo sures during certain parts of tire process/5) Studies by the National Institute of Occupational Safety and Health in the late 1970s and early 1980s found timeweighted average exposures for mechanics to fibers greater than 5 fim in length and with at least a 3:1 aspect redo during brake jobs, ranging from 0.01 to 0.28 ffcc/6 7) Fiber size distribution analyses of these samples indicated a geometric mean length of 1.70 iim (range 0.24-10.0) and diameter of 0.15 /tm for airborne chrysotile asbestos fibers.W A number of studies have examined the associ ation between motor vehicle repair (m general) or brake work (in particular) and mesothelioma/"14) None of these have demonstrated a positive associ ation. A recent meta-analysis found that the relative risk of mesothelioma among auto mechanics was 0.90 (95% confidence interval (O): 0.66-1.23)/15) Addressing mesothelioma risk among brake workers is complicated by their frequent involvement in other occupations with potential asbestos expo sure. This was noted in a ease-control study by Spirtas et Thirty-three of the 208 cases (15.9%) and 72 of the 533 controls (13.5%) had worked on brakes. A risk estimate was not calculated because many brake workershad also worked inshipbuildingorinsulation. Thepurpose of^represent analysiswas to explore the relationshipbetween brake instaJlation/repair and mesothelioma in the data set originally described by Spirtas ef ri/16) after adjustment for employment ia occupations with known increased risk of mesothe lioma, and to determine whether these results sup port tiie proposed new methodology for asbestos risk assessment % METHODS 2,1. Previous Study The study of Spirtas et of/lfi) Included cases di agnosed from 1975 to 1980 and registered by the HesseJerel t Los Angeles County Cancer Surveillance Program, the New York State Cancer Registry (excluding New York City), and 39 large Veterans Administration (VA) hospitals. Of 720 eligible cases, next of kin of 536 (74%) were successfully interviewed. Patholog ical material was available to confirm the diagnosis for 426 (79%). Of these, 208 (49%) were accepted as definite or probable mesotheliomas. Controls for cases in New York State and Los Angeles County were selected from death certifi cates. Controls for cases from VA hospitals were se lected from those who had died and received med ical and financial benefits from the VA. Controls were Initially matched by date of birth, race, sex, year of death, and county of residence (for those in New York State and Los Angeles County) or hos pital (for those from the Veterans Administration) to the larger group of eases. Of the 687 eligible con trols, Interviews were completed with next of kin of 533 (79%). Because the number of controls who re sponded was much greater than the number of cases accepted as having definite or probable mesothe lioma, all controls with completed interviews were included and the analysis was unmatched. The same analytical approach was used for the present analysis. The interviews requested information about as bestos exposure in general, and specifically about in volvement in nine activities with potential asbestos exposure. These included brake lining installation or repair, furnace or boiler installation or repair, building demolition, plumbing or heating repair, in sulation, shipbuilding/ship demolition/shipyard work, elevator installation or repair, production of textiles, and production of paper products- For the first five activities, data were available on whether the activ ity was job related, nonjob related, or both job and nonjob related: All interviews were conducted with next of Ida and the interviewers assessed, subjectively, the qual ity ofthe occupational histories. Eighty-three percent of the interviews for cases and 90% for controls were rated as highly or generally reliable. Hie authors rec ognized the possible failure ofnext of km to recall all opportunities for asbestos exposure, especially in the distant past. Of thebrake workers, 32% did this as partoftheir job, 57% did it "on their own time," and 16% did both. For the present analysis, those who did brake work as part of theirjob and those who did both were consid ered occupationallyexposed. Cases and controlswere similarlydistributed for occupational and nonoccuparional brake work. HWBUI0011371 Mesothelioma Among Brake Mechanics 549 22. Present Analysis The electronic data and documentation were ob tained from the National Cancer Institute. Tb en sure that the data had been correctly converted, the first three tables in the original paper were recreate&<16) fbr (he most part, these tables could be re constructed exactly. Where changes werenoted, these resulted from the apparent clarification of missing data (Le., there were fewer missing values for age at death in the present data set compared to the previous report). The questionnaires of five cases and 12 controls had missing values for brake work. The occupational histories of four of the five rases were coded as questionable quality and one as unreliable. For the controls, six were questionable, three were gener ally reliable, and three were highly reliable. Those with missing responses were excluded from the anal, yses. This reduced the number of subjects classi fied as nonexposed relative to the original report, in which those with missing information were classified as nonexposed. There were no female brake workers, only two nonwhite females in the study group (both controls), and 16 nonwhite males (three cases and 13 controls). After esmssiawg the distributions of race and sex, and considering the ratings of the quality of the occupational histories and the types of brake work (occupational and nonoccupational), it was decided a priori that the most relevant analyses would come from: 1. white males, 2. with highly or generally reliable work histo ries, 3. with a nonmissing response for brake work, and 4. whose brake work was occupational. Of the 28 cases and 63 controls meeting the first three criteria, 12 cases tod 28 controls did occupa tional brake work (Tkble I). The remainder did it on their own time. The data were analyzed using unconditional lo gistic regression, controlling for age. For the initial analysis of all relevant variables and for the analy ses of shipbuilding and Insulation, age was entered as a continuous variable and large sample methods were used. For the analyses of subsets of brake work, age was categorized in five-year age groups (<40, 40-44,45-49,..., 85+) and exact methods were used. Categorization of age facilitated convergence of the Tbbte I. Numbers of Cases and Controls by Exposure Subset Subset Cases Controls All Those meeting selection criteria4 Brake worts None'' Nonoccupational Occupational <10 years' >10 years No shipbuilding or insulation None of eight listed activities4 203 147 119 16 12 5 6 2 1 S21 358 m 35 28 to 16 IS 9 "White males with highly or generally reliable work histories and nonmisiing response for brake work. *>Of these, 33 eases and 171 conuots were not exposed to say of the eight listed activities. "Length of occupational brake work was missing for one case and two controls. dThe eight activities included fiuaace or boiler installation or repair, buildingdemolition, plumbing orheating repair, insulation, thipbuilding/ship demolition/sbipyard work, elevator installation or repair, production of textiles, and production of paperproducts. model. Became smoking is not related to mesothe lioma, this was not controlled in the analysis (unlike the original report). Decisions regarding inclusions, exclusions, and analytical strategies were made before'nsk estimates were calculated. Tb examine the effect of exposure to brake work, three approaches for controlling the effects of other asbestos exposures were used. The first analysis in cluded all relevant terms in a single model. In this model, age was entered as a continuous variable and 0/1 variables were entered for absence or presence, respectively, of occupational brake work, nonoccupa tional brakework, shipbuilding, insulation, and anyof the remaining six activities. In this analysis, those with nonoccupational brake work and those with no brake work were coded as 0 (i.e., not exposed) for occu pational brake work. Those with occupational brake work and those with no brake Work were coded as 0 for nonoccupational brake work. To more clearly distinguish occupational and nonoccupational brake work, a second set of analy ses compared brake workers with nonbrake workers in separate analyses. For the analyses of any brake work, those with no history of brake work (occu pational or nonoccupational) were considered non exposed. For the analysis of nonoccupational brake work, those with no history of brake work were considered nonexposed and those with occupational brake work were excluded. For the analyses of oc cupational brake work, those with nonoccupational HWBUI0011372 sso Hesse! et aL Table O, Recession Coefficients (/3), Standard Errors (SE), Odds Ratios (OR), and 95% Confidante Intervals for Brake Work, Controlling for Age and Activities Potentially Entailing Asbestos Exposure Variable Age Occupational brake work Nonoccupational brake work Shipbuilding Insulation Other activities* P 0.011 --0.307 -0.184 1.798 1216 0.028 SB 0.009 0378 0332 0244 0218 0.199 Odds Ratio 1.01 0.74 033 6.04 338 1.03 95% Confidenee Interval 039-1.03 035-134 0.43-159 3.74-9.75 220-S.17 0.70-132 The other activities included furnace or boiler installation or repair, bonding demolition, plumbing or heating repair, elevator installation or repair, production of textiles, and production of paper products. brake work were excluded and those with no his tory ofbrakework were considered nonexposed.'Ihls analysis was repeated, Including a single variable for presence ofshipbuilding or insulation (~1) or absence of both exposures (=0). These were the two poten tially confounding occupational exposures noted by Spirtas etaLM Then the analysis was repeated, con trolling for work in any of the eight activities con sidered in the original report. A single variable for presence of any of these exposures (=1) or absence ofall ofthese exposures (=0) was eatercd.To evaluate the relationship with length of occupational exposure in these analyses, subjects were classified as having no occupationalbrake work,less than 10 years, or at least 10 years. The last approach dealt with the potential effects of asbestos exposures through exclusion. Cases and controls were compared for a history of occupational brake work, excluding those with any of the eight activities. To assess the potentialjoint effects of brake work and other exposures, interaction terms were entered into the multivariate models. In addition, odds ratios (ORs) were compared for workers in insulation and shipbuilding who either did or did not also have a history of brake work. 3. RESUITS The results of the full model demonstrated pos itive associations between mesothelioma and both shipbuilding and insulation (Table II). There was no association between mesothelioma and either occu pational or nonoccupational brake work, nor was there an association with the other six activities with potential asbestos exposure. Similarly, the analyses, that separated occupa tional and nonoccupational brake work found no as sociations (Table HI). The analysis by deration of employment showed no suggestion of increasing risk of mesothelioma with, increasing length of time em ployed in brake work. When the interactions between brake work and activities Involving potential asbestos exposurewere examined, there were no patterns sug gesting that brake work enhanced the risk associated with other asbestos exposures (data not presented). Whenparticipantswith any ofthe eightactivities were deleted from the analysis, the OR for occupational V-/ Thble HL Odds Ratios (OR) and 95% Confidence Intervals (95% Cl) for Association Between Brake Work and Mesothelioma Controlling for Age and Activities Potentially Entailing Asbestos Exposure Controlled for No activities Shlpbufltfingfinsulalion All eight activities4 Any Brake Work OR 95% Cl 1.03 039-1.75 0.74 0,42-130 0.82 0.46-1.41 Nonoccupational OR 95% a 0,99 0.48-1.96 0.74 034-133 0.79 037-1.61 Any OR 95% a 1.04 0.46-222 0.71 030-160 032 036-180 Occupational <10 years OR 95% a 132 039-3.97 0-99 027-322 1.03 030-322 alO years OR 95% a 0.86 026-2.41 033 0.15-160 0.68 021-1.98 The eight activities included furnace or boiler installation or repair, building demolition, plumbing or heating repair, insulation, stipbuMng&bip demolition/shipyard work, elevator installation or repair, production of textiles, and production of paper products. Nptr. Odds ratios and 95% confidence intervals based on exact methods. HWBUI0011373 Mesothelioma Among Brake Mechanics SSI Table IV, Age-Adjusted Odds Ratios (OR) and 95% Confidence tatenmjs (<2) for Insulation Workers and Shipbuilders by History Of Brake Work* 4 Group No History of Brake Work OR a History of Brake Work OR Cl Insulators 4.14 265-6.77 1.74 0.69-44$ Shipbuilders 5.16 2.94-903 4.36 06-14.8 Note:Brakework included bothoccupational and nonoccupadonal brake work. brake work was 0.62 (95% Cl: 0.01-4.71) based on one exposed case and rune exposed controls. The age-adjusted OR for insulation workers who had no historyof brake work was 4.14 (95% C 2.556.77),and for insulatorswho were also brake workers, the OR was 1.74 (95% CT: 0.69-4.46) (Thble IV). Fbr shipbuflderB with no employment as brake workers the OR was 5.16 (95% Cl: 2.94-9.23) and for ship builders with employment as brake workers, the OR was 436 (95% Ct 136-14.8). 4. DISCUSSION The present analysis focused on the question of the potential risk of mesothelioma associated with brhke work, while considering other activities involving potential asbestos exposures. The results were consistent with the available literature that demonstrates no apparent risk. The present analy sis used occupational histories evaluated as reliable by the interviewers. The results changed little and no conclusions differed when all respondents were In cluded, regardless of the quality of the work history. Siraflarly, including nonwhites had no discernable effect The study was limited by the relatively small numbers of brake workers, especially in the analy ses that excluded those with other potential asbestos exposures. The confidence intervals were reasonably narrowfor the overall analyses, but thoseforthe inter action terms were quite broad. In the stratified analy sis, only one case and nine controls with occupational brake work did not hold one of the otherjobs involv ing asbestos exposure. The original studyW excluded from the control group those who died from can cer and respiratory disease because the researchers felt that they might be related to asbestos exposure. If these diseases were positively associated with as bestos exposure in this population, the risk estimates for occupations with asbestos exposure may have been overestimated. The results indicated no excess risk of mesothe lioma among brake workers when the analyses were controlled for exposures in occupations with known risk of mesothelioma. Further, there was no evi dence of an exposure-response relationship between brake work and mesothelioma. This was evident in the analysis by duration of occupational brake work and the fact that the ORs for occupational brake work were indistinguishable from those for nonoccupational brake work. It is assumed that, on average, those with occupational brake work would have had higher exposures than those with nonoccupational brake work. These findings are consistent with no increase in risk of mesothelioma associated with short chrysorile fibres (<5 izm in length). There Is increasing evidence that such fibres may not be carcinogenic^*4,17* Expla nations for the observed results may include the fol lowing: (1) time-weighted average exposures axe low in this occupational group;*5,7* (2) most of the fibers are short;*6,7* (3) chiysotile asbestos is used almost exclusively;*17* (4) the fibers are embedded in resin; (5) much of the asbestos is transformed to foisteiite (a nonfibrous substance) during the braking process; and (6) only a small percent of "brake dust** is as bestos.*5* The findings for brake mechanics reinforce the caution that direct inferences from one occupa tional setting to another without consideration of the key determinants of risk are to be avoided.*18* ACKNOWLEDGMENTS The authors thank Dr. Aaron Blair from the Na tional Cancer Institute for providing the data. They also thank Dr- Robert Spirtas for helpful comments. The project was funded by Daimler Chrysler, Ford Motor Company, and General Motors Corporation. Drs. Hessel, Teta, and Goodman have provided sd-: eutific consulting sendees to these companies in the area offriction brakes. REFERENCES 1. United States Federal Register. (2003). Peer consultation workshop on a proposed asbestos cancer risk assessment Men/ Register, 66(24). 2. Hodgson, Jn & Dsrtott, A. (2000). The quantitative risk el mesothelioma and lung cancer in relation to asbestos tapesure. Annals ofOccupationalHygiene, 44, 565-601. 3. MuUe. H, & Pott, E (2000). Asbestos as referencematerial for fibre-induced cancer. International Arshines */ Oeatpedartedend Environmental Health, 7.3, $53-459, HWBUI0011374 552 Hessel staL 4. Berman, D. W., Crump, X. &, Chatfield, E, l, Davis jr, M. & Jones, A. D. (1995). lie sizes; shapes, and mineralogy of asbestos structures that induce Jung turnons or mesothelioma in AF/JHAJN nts following Inhalation. Risk Analysis, IS, 1SI195. 5. Rodelsperger, K., Jahn. H., BrfickehR, Manka, X, Faur.R. A WeiiewittrH.Jf. (1986). 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