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FILE NAME Brakes BRK DATE 2011 DOC BRK218 DOCUMENT DESCRIPTION Journal Article - Asbestos Fiber Concentrations in the Lungs of Brake Repair Workers t Inhalation Toxicology 2011 23 681 688 '2011 Informa Healthcare USA Inc. ISSN 0895-8378 print 1091-7691 online DOI 08958378.2011.580472 08958378.2011.580472 RESEARCH ARTICLE informa healthcare 10/3/1 on Library University Brown by only use informaheltc.personal For from Downlade Toxicolgy Inhaltion Asbestos fiber concentrations in the lungs of brake repair workers commercial amphiboles levels are predictive of chrysotile levels Gary M. Marsh Ada O. Youk,,and Victor L. Roggli Department of Biostatistics Graduate School ofPublic Health Centerfor DukaBiostatistics and Epidemiology University ofPittsburgh Pittsburgh PA USA and 2Department of Pathology Duka University Medical Center Durham NC USA Abstract 2009 Objectives To investigate the impact of extreme data points in lung levels of commercial and commercial amphiboles high of association association association between tremolite as marker for chrysotile asbestos in brake repair workers with mesothelioma Methods We first identified potential potential outliers high po) whe! commercial amphiboles and tremolite among 15 br We brake repair work used sensitivity analysis and a commercial amphibole levels as a predictor of as We quantile reported duration duration employment employment employment repair employment worker predicted tremolite employment nd- rexts points was through levels of ronly known rexts was through through used for rexts data points and model used rexts to evaluate whether predicted lung rexts commercial amphiboles or amphiboles Results We found lung levels of amphiboles istically sensitivity analysis = 0.82 slope estimate value that 0.0001 Our data provide no e duration duration levels of tremolite or amphiboles amphiboles that amphiboles duration of tremolite tremolite levels via via call tas dictor regression slope estimate value tas tas repair worker was a predictor of lung Conclusions Our findings amphiboles that elevated levels of amphiboles arose elevated lung duration duration repair repair repair workers workers workers workers with with from concurrent SITUolite commercial amphibole and chrysotile asbestos in occupational settingthan than brake repair for SITUolite lungs are supported by five new cases The weight of role for the scientific of mesothelioma support a for exposure to brake dust and other friction products in of the development mesothelioma Keywords Asbestos amphibolestremolite chrysotile amosite crocidolite occupational diseases lung cancer mesothelioma robust regression sensitivity analysis Introduction Canadian chrysotile which accounted for the vast majority of chrysotile used in the United States in the manufacture of asbestos products is recognized to be contaminated with tremolite It has been suggested that tremolite might be a reasonably good biomarker for exposure to Canadian chrysotile as chrysotile tends to be degraded and removed from the lungs over time whereas amphiboles like tremolite are more biopersistent Churg 1988 Indeed analyses of lung tissue samples from Canadian chrysotile miners and millers have shown predominance of tremolite fibers Churg et al 1993 Furthermore mesothelioma occurrence among Canadian miners and millers correlates best with the degree of tremolite contamination in the various mines McDonald et al 1997 In 2002 Roggli et al reported the correlation between type of occupational asbestos exposure and asbestos fiber Addressfor Correspondence Gary M. Marsh Department of Biostatistics Graduate School of Public Health University of Pittsburgh Pittsburgh PA 15261 USA Tel 412-624-3032 Fax 412-624-9969 mail gmarsh@cobe.pitt.edu gmarsh@cobe.pitt.edu Received 19 February 2011 revised 05 April 2011 accepted 08 April 2011 681 RIGHTBLINK RIGHTBLINK RIGHTBLINK 10/3/1 on Library University University Brown by only use informaheltc.personal For from Downlade Toxicolgy Inhaltion 682 G.M. Marsh al lung burden levels for 1445 malignant mesothelioma cases Butnor et al 2003 reported results of lung fiber analysis for 10 malignant mesothelioma cases from Roggli et al 2002 whose only known exposure to asbestos was occupational contact with friction products e.g. brake dust as a brake repair worker Commercial amphiboles amosite or crocidolite asbestos were found in eight cases with excessive commercial amphibole fibers found in five of the cases The authors concluded that the presence of the elevated commercial amphiboles in the lungs of some of these cases suggested exposures other than occupational exposure to brake dust which contains small amounts 0.1-1 of mostly short < ...min length chrysotile asbes- tos fibers Lynch 1968 Hatch 1970 Davis and Coniam 1973 Williams and Muhlbaier 1982 Wong 2001 Finkelstein 2008 reported a reanalysis of the data in Butnor et al 2003 using an alternative computation for mean fiber concentration which resulted in mean con- centrations of commercial asbestos exposure principally tremolite with some actinolite and anthophyllite measured as a marker of chrysotile exposure that were higher than reported by Butnor et al 2003 In a letter to the editor Roggli et al 2009 considered this finding consistent with those of Butnor et al 2003 In response to the Roggli et al 2009 letter Finkelstein 2009 concluded from a regression analysis of the same 10 cases Butnor et al 2003 that levels of commercial amphiboles are not predictive of the levels of tremolite as a marker of chrysotile exposure thus implicating exposure to chrysotile fibers from friction products as a causative fac- tor for these mesothelioma cases We questioned the validity of Finkelstein's 2009 conclusion due to the observation in his Figure 1 of at least two extreme data points that were not appropriately weighted in the regression analysis The purpose of our _ reanalysis reported here was to investigate the robustness ofFinkelstein's 2009 findings with respect to the presence of these extreme points Our reanalysis also extends the work of Finkelstein 2009 by including amphibole and tremolite fiber concentration levels for five new cases of malignant mesothelioma from the Roggli et al case series whose only known asbestos exposure was occupational contact as a brake repair worker We also examined whether reported duration of employment as a brake repair worker was a predictor of lung levels of commercial amphiboles or tremolite Methods We abstracted from Butnor et al 2003 data on the levels of commercial amphibole fiber and tremolite fiber found in the lungs of 10 mesothelioma cases used in the Finkelstein 2008 2009 analyses The 10 cases from Butnor et al 2003 were selected on the basis of three criteria 1 having mesothelioma 2 only known asbestos exposure was occupational contact as a brake repair worker and 3 lung tissue was available for analysis In the process of preparing this manuscript we identified and corrected three errors in Butnor et al 2003 related to the lung fiber levels of two of the 10 cases Specifically for Case 2 the commercial amphiboles level changed from 4810 to 3940 for Case 3 commercial amphiboles changed from 380 to 970 and tremolite changed from 4630 to 4110 We also included lung levels of commercial amphibole and tremolite fibers for the five new mesothelioma cases from the Roggli et al series who were observed since the publication of Butnor et al 2003 and who met the same three inclusion criteria We also included information on reported duration of employment as a brake repair worker for all 15 cases Table 1 4000 'CCaassee 3 3000 TremoliteLevels 2000 C as1e0 L e 1000 Model 1 Case9 e e@ Case2 T 2000 4000 Commercial Amphibole Levels r 6000 Figure 1. The relationship between the levels of commercial amphibole fibers and tremolite fibers in the lungs of brake repair workers fitted simple linear regression model with 10 original data points Model 1 From Butnor et al 2003 and revised per Methods section Inhalation Toxicology RIGHTSLINKO RIGHTSLINKO RIGHTSLINKO 10/3/1 on Library University University Brown by only use informaheltc.personal For from Downlade Toxicolgy Inhaltion Fiber analyses and ascertainment of the diagnosis of mesothelioma in the five new cases were as described previously by Butnor et al 2003 and are summarized in Table 2 along with other relevant case information All were males with ages ranging from 40 to 70 years median 58 years Four were pleural mesotheliomas and one was peritoneal Four out of five were smokers or smokers The length of employment as a brake repair worker ranged from 5 to 32 years median 20 years As in previous analyses Roggli et al 2002 Butnor et al 2003 Finkelstein 2009 we substituted a value of 1/2 the detection limit for fiber levels below the limit of detection Cases with a less than < sign before the value are at the detection limit for that value For example as shown in Table 1 in Case 11 no asbestos fibers were Amphibole lung levels predict chrysotile levels 683 detected and the detection limit was 520. In Case 12 the asbestos body count is clearly elevated and a single cro- cidolite fiber was identified by SEM the detection limit was 810 for that case The detection limit varies from case to case because the amount of tissue available to analyze varied from case to case i.e. the weight of the sample For Case 15 one commercial amphibole fiber and one noncommercial amphibole fiber were identified Chrysotile was not detected Table 2 We recognized that 15 cases represent relatively small sample from which to infer whether tremolite levels are correlated with commercial amphibole levels or whether either level is correlated with duration of employment Moreover many data points for amphibole and tremolite levels were below the detection limit detects These Table 1. Lung levels of commercial amphiboles and tremolite and reported duration of employment for 15 mesothelioma cases whose only known exposure to asbestos was occupational contact as a brake repair worker Case 12316 Commercial amphiboles 3270 Tremolitec.d 2180 Duration of employment years 322 12316 3940 440 322 12316 970 4110 322 12316 720 used 360 12316 580 used 290 720 40 1160 11 6 490 490 7 7 340 340 used 170 15 & 120 240 40 ---- 6000 3280 17 10 1440 2170 257322 11b 520 used 260 520 used 260 257322 12b 810 810 used 405 257322 13b 480 used 240 480 used 240 257322 14b 390 used 195 390 used 195 257322 15b 490 490 257322 Data abstracted from Butnor et al 2003 and revised per Methods section New cases from Roggli case series Fibers per gram ofwet lung tissue for fibers 5 ...mor greater in length One the detection limit value used in analysis and shown in parentheses Table 2. Demographic pathologic and occupational information and results of lung tissue analysis for five new mesothelioma cases whose only known exposure to asbestos was occupational contact as a brake repair worker Case from Table 1 11 Age years sex 69 Tumor type Occupation BP1 clutch repair IH Smoking pack 1-1.5 ppd XS years Pleural plaque ND ABAB 7 Chrysotileb 520 12 70 EPI Auto mechanic Pipe many years ND 90 810 13 58 EP1 Auto mechanic NS ND 6.7 480 14 58 EPI Auto mechanic 1.5 ppd 45 years ND 29 390 15 40 EPe QC inspector 0.5 ppd 23 years ND 2 490 Median 58 Reference casesc -_ _- _ - _ - 7 490 _ 3 0.2-22 600 100-1000 B Biphasic E epithelial IH International Harvester M male ND not determined NS smoker Pe peritoneal Pl pleural ppd packs per day QC quality control XS smoker AB asbestos bodies NAMF asbestos mineral fiber 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 normal range tissue asbestos body counts and no evidence of asbestos disease Butnor et al 2003 '2011 Informa Healthcare USA Inc. 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Marsh et limitations notwithstanding these 15 cases represent all eligible cases from the Butnor et al 2003 and Roggli al case series Obtaining additional cases and using or developing methods that lower fiber detection levels were not practical options for our analysis We first attempted to replicate the Finkelstein 2009 results by fitting a simple linear regression on the 10 data points from Butnor et 2003 Second to assess whether commercial amphiboles are predictive oftremolite levels we performed a simple linear regression and used regres- sion diagnostics to locate any potential outliers high leverage or influential points using all 15 data points An outlier is defined as any point with a large residual difference between observed and fitted values value a high leverage point is an observation with an extreme value in one of the predictor variables and an influential point is one that substantially changes the estimates of the coef- ficients when removed A standardized residual is the residual divided by the estimate of its standard error Any standardized residual value over 2.0 is typically considered to be large A standard marker for high leverage is anything greater than k where is the number of predictors in the model and n is the sample size Criteria for a point to be considered a highly influential point is typically any value larger than n Chatterjee and Hadi 200W6e then sensita isenvsiititviyty analysibsy remov- ing any points that were considered to be extreme outliers high leverage or influential refitting the regression model and comparing these results to the model based on all 15 points We also fit a quantile regression model to account for the undue influence of the extreme points without omitting them as in the sensitivity analysis Unlike simple linear regression which is based on a least squared devi- ation criterion quantile regression minimizes the sum of absolute residuals using a linear absolute value function Because this function is symmetric minimizing the sum of absolute residuals ensures that the same number of observations occur above and below the median Because the quantile regression model estimates the relationship between a predictor variable and specific quantiles of the outcome variable rather than the mean of the outcome variable as in simple linear regression the parameter estimates are robust with respect to large outliers or influential points Koenker and Hallock 2001 Hao and Naiman 2007 Cameron and Travedi 2009 We also used simple linear regression and quantile regression to evaluate the relationship between duration of employment as a brake repair worker and lung levels of commercial amphiboles or tremolite All statistical models were fit using the Stata Statistical Software Release 11 StataCorp 2009 Results While data are not shown here we replicated exactly the simple linear regression results ofFinkelstein 2009 Using the revised data for Cases 2 and 3 we refit the simple linear regression model as shown in Model 1 and Figure 1 Tremolite level = 981.01 + 0.29 commercial amphiboles level Model ) As found using the original data commercial amphi- boles level was not a statistically significant predictor of tremolite r 0.43 slope estimate value = 0.21 and the R= 0.19 was low indicating a poor fit only 19 of the variance explained by Model 1 We refit the Finkelstein 2009 model using all 15 data points as shown in Model 2 and Figure 2 Tremolite level = 615.09 +0.38 +0.38 commercial amphiboles level Model 2 Unlike Model 1 commercial amphiboles level was a statistically significant predictor of tremolite r = 0.53 slope estimate value = 0.04 but the R= 0.28 was low indicating a poor fit only 28 of the variance explained by Model 2 Model 2 remains an inferior model because it does not properly account for extreme values In Models 1 and 2 Case 2 Case 3 and possibly Cases 9 and 10 appear as extreme points that could affect the fit- ted line Figures 1 and 2 We performed regression diagnostics to determine if these points were in fact causing undue influence to the fitted equation Table 3 shows the computed residuals standardized residuals leverage and influence statistics For these data the cutoff for high leverage is 0.40 and for a highly influential point it is 0.27 In Table 3 the highlighted values are those that exceed the typical cutoff values Case 3 is an outlier and an influential point Cases 2 and 10 also have the potential to be outliers as their residuals are much larger than the other residuals Case 2 is also an influential point Case 9 is a high leverage point We performed a sensitivity analysis by refitting the simple linear regression of tremolite versus commercial amphiboles with the three extreme points removed Cases 2 3 and 9 Case 10 was not removed because the cutoff was not exceeded for the standard- ized residual leverage and influence The fitted line without these three points is shown in Model 3 and Figure 2 Tremolite level = 257.49 +0.68 +0.68 commercial amphiboles level Model 3 The constant term in Model 3 is about 1/3 that of Model 2 and the slope estimate for commercial amphiboles increased almost fold Commercial amphibole con- centration is a now statistically significant predictor of tremolite 0.82 slope estimate value and the 0.68 68 of the variation is explained by this Model 3 Inhalation Toxicology 10/3/1 on Library University Brown by only use informaheltc.personal For from The fitted quantile regression model is shown in Model 4 and Figure 2 Tremolite level = 177.96 +0.52 +0.52 commercial amphiboles level Model 4 As revealed by the slope estimates and the fitted lines in Figure 2 Model 4 falls between the model using all 15 points Model 2 and the model with the three extreme points omitted Model 3 In our quantile regression model that properly accounts for extreme values without Table 3. Results of regression diagnostics residuals standardized residuals leverage and influence Standardized Case E CN Residuals 318.583 -1676.780 residuals 0.317 -1.745 Leverage 0.160 0.234 Influence 0.010 0.465 CN 3125.201 A 32.305 2,951 -0.031 0.069 0.087 0.322 0.0001 5a 434.374 0.415 0.090 0.008 6" -311.853 -0.296 0.081 0.004 1 -574.682 * -420.832 -0.548 -0.404 0.088 0.099 0.014 0.009 ---- 378.076 0.540 0.594 0.213 10 1006.066 0.949 0.067 0.032 11b -454.191 -0.434 0.091 0.009 12b -518.827 -0.491 0.072 0.009 13b -466.569 -0.446 0.092 0.010 14b -494.417 -0.473 0.095 0.012 15b -311.853 -0.296 0.081 0.004 Data abstracted from Butnor et al 2003 and revised per Methods section New cases from Roggli et al case series Amphibole lung levels predict chrysotile levels 685 omitting them Model 4 commercial amphibole concentration is a statistically significant predictor of tremolite concentration slope estimate value 0.0001 The correlation coefficient and Rare not shown for the quantile regression as no accepted method exists for calculating these statistics Figures 3 and 4 show the scatterplots of duration of employment lung levels oftremolite and commercial amphiboles respectively as well as the fitted lines based on the simple linear regression and quantile regression Each scatterplot reveals evidence of influential points The fitted quantile regression models are given by Tremolite level = 359.23 + 6.54 duration of employment Commercial amphiboles level = 517.58 3.94 duration of employment Neither model revealed any evidence that duration of employment as a brake repair worker was a predictor of lung fiber level slope estimate values for both models Discussion Regression diagnostics sensitivity analysis and quantile regression are rigorous accepted and commonly used analytical procedures to ensure that the fit of a particular statistical model is not overly influenced by one or few observations Koenker and Hallock 2001 Chatterjee and Hadi 2006 Hao and Naiman 2007 Cameron and Travedi 2009 Our use of these rigorous procedures clearly showed that four extreme data points Cases 2 3 9 and 10 led Finkelstein 2009 to conclude incorrectly Downlade 4000 3 @ Case J Toxiclogy 3000 1 Inhaltion Levels e Case 10 Tremolite 2000 L Case 2 0 T 0 T T 2000 4000 Commercial Amphibole Levels T 6000 Figure 2. The relationship between the levels of commercial amphibole fibers and tremolite fibers in the lungs of brake repair workers fitted simple linear regression model with all 15 data points Model 2 and omitting three extreme points Model 3 Also showing quantile regression model Model 4 From Butnor et al 2003 and revised per Methods section and including five new cases from Roggli et al case series '2011 Informa Healthcare USA Inc. RIGHTSRILGHTSLIINK N)K 10/03/11 10/03/11 10/03/1 Library University University University University by onlyonly informahealthcare.com personal informaheltcare.om personal For informahealthcare.com from from DownladeDownloaded Downloaded Toxicology ToxicolgyToxicology InhalationInhalation Inhaltion 686 G.M. Marsh that lung levels of commercial amphiboles are not predictive of the levels of tremolite as a marker ofchrysotile asbestos When we removed or properly accounted for _ these extreme observations using an appropriate regres- sion model we found that lung levels of commercial amphiboles area statistically significant predictor oflung levels of tremolite We performed several confirmatory analyses to determine if our results were sensitive to the method of data substitution or data analysis For example since quantile regression is only one of several statistical approaches for handling data sets that deviate from the usual assumptions of simple linear regression such as extreme observations and absence of homoscedasticity we fit two regression models as alternatives to Model 4 We also evaluated whether the results of Model 4 and the alternative models were sensitive to the method used 1/2 detectable level DL for substituting values for detectable lung levels of asbestos Finally we refit Models 2-4 using the original 10 data points reported by Finkelstein 2009 and revised per the Methods section The first alternative regression model considered was robust regression This model first removes points with an influence statistic greater than 1.0 none in our 4000 'Case 3 e Case 9 Levels Levels Tremolite 2000 4 Tremolite Tremolite Tremolite 1000 1000 ' + T 0 @ Case 10 Case 1 e Simple linear regression ae Quantile regression model eet -- -- SAID SNE MATTER SS _- e ee e T T T v 10 20 Duration 40 Duration of Employment Figure 3. The relationship between duration of employment as a brake repair worker and the levels of tremolite fibers in the lungs of brake repair workers fitted simple linear regression model with all 15 data points and quantile regression model 6000 Case 9 e Levels 4000 4000 fiCase 2 Amphibole e Case 1 Comercial2000 a ed ae oe aee taree eae ore am esas me ama san _ o. LU ) e e eg oe LU T LU T 10 20 40 Duration of Employment Figure 4. The relationship between duration of employment as a brake repair worker and the levels of commercial amphibole fibers in the lungs of brake repair workers fitted simple linear regression model with all 15 data points and quantile regression model Inhalation Toxicology RIGHTSLINK RIGHTSLINK ) 10/3/1 on Library University Brown by only use informaheltc.personal For from Downlade Toxicolgy Inhaltion analysis then performs a weighted least squares regres- sion using weights that give small or zero weight to points with large residuals Berk 1990 Chatterjee and Hadi 2006 In the second alternative regression model an unweighted least squares criterion simple linear regression was used to fit transformed values of tremolite and commercial amphibole lung levels Here the logarithmic transformation gives less weight to the extreme values Alternative methods considered for the substitution of detects were DL and 2DL as proposed by Sanford et al 1993 and discussed by Helsel 2006 2010 Although data are not shown here both alternative regression models considered led to similar fitted models that corroborated the central result of Model 4 that is lung levels of commercial amphiboles are a statistically significant predictor of lung levels of tremolite Moreover the choice of detect substitu- tion method had negligible impact on the based results of Model 4 and the two alternative regression models We also found similar results when Models 2-4 were refit using the 10 original data points revised per the Methods section Our finding that lung levels ofcommercial amphiboles predict lung levels of tremolite was supported by our related findings that reported duration of employment as a brake repair worker was not associated with lung levels of tremolite or commercial amphiboles That is one would expect lung levels of tremolite chrysotile to increase with increasing duration of employment only if there was an association between friction products and mesothelioma Also because automotive brakes in the United States include only the chrysotile form of asbestos one would not expect lung levels of commercial amphiboles to increase with increasing duration of employment as a brake repair worker This lack of correlation between exposure duration and lung levels of tremolite or commercial amphiboles is an important and heretofore unreported observation although the raw data were available in the original Butnor et al's 2003 work Thus our findings suggest that elevated lung levels of tremolite as a marker of chrysotile in the lungs of some brake repair workers with elevated levels of amphiboles arose from concurrent exposures to commercial amphibole and chrysotile asbestos in occupational settings other than brake repair work Regarding the study by Butnor et al 2003 some investigators have questioned the validity of using scanning electron microscopy SEM for the analysis of lung tissue samples Reanalyzing lung tissue from Case 1 of Butnor et al 2003 Dodson et al 2008 claimed that transmission electron microscopy TEM is the superior instrument As we have stated elsewhere this is a moot point because lung fiber burden studies ofmesothelioma using TEM have come to similar conclusions as studies using SEM Srebo et al 1995 Roggli and Vollmer 2008 Roggli et al 2008 Moreover studies from two laboratories employing TEM to analyze a smaller number of lung '2011 Informa Healthcare USA Inc. Amphibole lung levels predict chrysotile levels 687 tissue samples of brake mechanics with mesothelioma found similar results to those we reported Dodson et al 2005 2008 reported two cases of mesothelioma one in a brake mechanic and the other an auto machinist both of which had elevated levels of commercial amphiboles the auto machinist case was a reanalysis of Case 1 from Butnor et al 2003 In fact Hammar and Dodson have written elsewhere that the question as to whether automotive mechanics ... have an increased risk of malignant mesothelioma remains unresolved and contentious Hammar et al 2008 Furthermore Gordon and Dikman reported eight cases of mesothelioma in brake mechanics All eight had only chrysotile in their lung tissue samples and the chrysotile in each instance was within their reported background population range Gordon and Dikman 2009 Because the findings in these two TEM studies are the same as what we have reported either background levels of asbestos or elevated commercial amphiboles with or without elevated tremolite or chryso- tile there is no validity to the claim that TEM is superior to SEM for this purpose As noted in the study of Butnor et al 2003 and summarized here our reanalysis and extension of the work of Finkelstein 2009 has some underlying limitations First our reanalysis is based on a case series of 15 medico cases that may not be representative of all individuals exposed to friction products occupationally Also historical information obtained by patient interview is subject to recall bias for events occurring decades previously This may explain the absence of reported exposures to commercial amphiboles among the cases considered Additionally many data points for amphibole and tremolite levels associated with the 15 cases were below the detection limit detects As detects can complicate statistical analysis they reflect the very low levels of asbestos in lung tissue which in itself is indicative of a lack of a relationship between asbestos exposure and mesothelioma in brake repair workers Conclusions Finkelstein's 2009 finding that lung levels of commercial amphiboles are not predictive of the levels of tremolite asbestos chrysotile is invalid because the regression analysis did not properly account for extreme data points Our regression diagnostics sensitivity analysis quantile regression and evaluation of reported duration of employment as a brake repair worker suggest that elevated lung levels of tremolite chrysotile in the lungs of brake repair workers with elevated levels of amphi- boles arose from concurrent exposures to commercial amphibole and chrysotile asbestos in occupational settings other than brake repair work These findings are supported by the five additionally reported cases in the current study Despite suggestions to the contrary by Dodson et al 2008 and Finkelstein 2008 2009 the weight of the scientific evidence does not support a role RIGHTBLINK RIGHTBLINK RIGHTBLINK 10/3/1 on Library University Brown by only use informaheltc.personal For from Downlade Toxiclogy Inhaltion 688 G.M. Marsh et al for occupational exposure to brake dust and other friction products in the development of mesothelioma Declaration of interest Drs Marsh and Youk performed this work study and manuscript preparation as a private consulting activity for Honeywell International Inc. Dr. Marsh was on the Asbestos Panel of the Scientific Advisory Board of the US Environmental Protection Agency He provided expert testimony for defendants in three asbestos liti- gation cases including two involving friction products Dr. Marsh also provided epidemiological and biostatistical consultation for defendants including Honeywell International Inc. in cases involving friction products Dr. Youk a was statistical consultant and performed analyses in preparation for the trial of a defendant in an asbestos litigation case Dr. Roggli has served as an expert witness for both plaintiffs and defendants in asbestos litigation including Honeywell in cases involving friction products References Berk RA 1990. 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Asbestos fiber burden analysis of lung and lymph nodes in 100 cases of mesothelioma Am J Respir Crit Care Med A5892 Hammar SP Henderson DW Klebe S Dodson RF 2008. Neoplasms of the Pleura Chapter 43. In Dail and Hammar's Pulmonary Pathology 3rd edition Tomashefski JF Cagle PT Farver CF Fraire AE eds Springer New York pp 558-734 Hao L Naiman DQ 2007. Quantile Regression Thousand Oaks CA Sage Publications Hatch D. 1970. Possible alternatives to asbestos as a friction material Ann Occup Hyg 25-29 Helsel DR 2006. Fabricating data how substituting values for nondetects can ruin results and what can be done about it Chemosphere 2434-2439 Helsel D. 2010. Much ado about next to nothing incorporating nondetects in science Ann Occup Hyg 257 262 Koenker R Hallock KF 2001. Quantile regression J Econ Perspect 143-156 Lynch JR 1968. Brake lining decomposition products J Air Pollut Control Assoc 824-826 McDonald AD Case BW Churg A Dufresne A Gibbs GW S^'bastien P McDonald JC 1997. 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An objective replacement method for censored geochemical data Math Geol 59-80 Srebo SH Roggli VL Samsa GP 1995. Malignant mesothelioma associated with low pulmonary tissue asbestos burdens a light and scanning electron microscopic analysis of 18 cases Mod Pathol 614-621 StataCorp 2009. Stata Statistical Software Release 11. College Station TX StataCorp LP Williams RL Muhlbaier JL 1982. Asbestos brake emissions Environ Res 70-82 Wong O. 2001. Malignant mesothelioma and asbestos exposure among auto mechanics appraisal of scientific evidence Regul Toxicol Pharmacol 170-177 Inhalation Toxicology RIGHTSLINK RIGHTSLINK RIGHTSLINK