Document NerD4O0NRQKmVynbRgZOpmwbg

FILE NAME Brakes BRK DATE 2008 DOC BRK186 DOCUMENT DESCRIPTION Journal Article -Asbestos Fibre Concentrations in the Lungs of Brake Workers vem y Ann Occup Hyg PF 1-7 'The Author 2008 Published by Oxford University Press on behalf of the British Occupational Hygiene Society doi 10.1093 men036 Asbestos Fibre Concentrations in the Lungs of Brake Workers Another Look MURRAY M. FINKELSTEIN Family Medicine Centre Mount Sinai Hospital 60 Murray Street 4th Floor Toronto Ontario Canada M5T 3L9 Received 28 November 2007 in final form 29 April 2008 content of asbestos fibres among brake mechanics Objective To reanalyse data on the lung Butnor Roggli and colleagues on the lung content Methods I analysed data published by mechanics and controls Statistics of the of chrysotile and tremolite asbestmosafxiibrmeus mamloinkeglibhroaokdeto accommodate observations below the and distributions were esticmoantceedntbryations were comparedcompared by the test bootstrap resampling detection limit Mean censored survival methods the brake workers than the Results The mean concentrattrieomnosliotfe ffiibbrreess wwearsehhiigghheerrtahamnonthge concentration of chrysotile controls The concentratioobnsoefrved among Quebec chrysotile miners and millers a pattern similar to that data does not support the interpretation that in auto- Conclusions analysis of published asbestos content is within the nor- motive brake repair workers with malignant mesothelioma mechanics have a greater than mal range The alternative interpretation that brake to dusts from fric- background burden of asbestos fibrCeasnaatdtiriabnutcahbrlyesottoiolcecuappapteiaornsalmeoxrpeoscurreedible This asbestos tion products manufacturedwfirtohman increased risk of associated cancers burden might be associated Keywords asbestos brakes friction products lung fibre content INTRODUCTION Mesothelioma is a rare tumour strongly associated to asbestos During most of the 20th with exposure asbestos was an important constituent of vecentury hicular braking systems Paustenbach et al 2004 In 1973 the US Environmental Protection Agency reported that brake linings contained 33-73 asbes- tos by weight and estimated that 32 million kg of as- bestos were worn away from brake linings each year and DuCharme 1973 Automotive and brake Jacko with mechanics have occasionally been diagnosed mesothelioma and the attributability of these tu- has become a contentious mours to asbestos exposure legal issue in the US A number of reviews have been published by authors working for lawyers or involved with litigation Lemen 2004 concluded that even the so called controlled use of asbestos containing brakes poses a health risk to workers users and their families Laden et al 2004 concluded that the ev- idence did not support an increase in risk of either *Author to whom correspondence should be addressed Tel + 1-416-326-7879 fax 1-416-326-7761 mail murray.finkelstein@utoronto.ca murray.finkelstein@utoronto.ca lung cancer or mesothelioma among male automobile mechanics occupationally exposed to asbestos from brake repair Goodman et al 2004 concluded that as a motor vehicle mechanic does not employment increase the risk of developing mesothelioma I was asked by a defence law firm to examine the literature on mesothelioma and friction materials Follow- ing review and discussion I was not asked to prepare a written report Other than this instance I have had no involvement with materials litigation During my reading I noticed that both Laden et al 2004 and Goodman et al 2004 referred to a study of the analysis of asbestos fibres in the lungs of sub- with mesothelioma published by Roggli et al jects the data 2002 Both sets of reviewers interpreted as being consistent with the opinion that brake dust is unlikely to cause mesothelioma Individual data for 10 cases from this series of subjects with meso- thelioma were published in 2003 Butnor et al 2003 Commenting on these data Butnor et al write Lung burden analyses in automotive brake repair workers with malignant mesothelioma in our series reflect asbestos content within the normal range or elevated commercial amphiboles I have examined 1 of7 2 of7 M. M. Finkelstein the brake worker data reported in Butnor et al 2003 and the data for 19 control subjects without occupational asbestos exposure published by Roggli et al 2002 from the same laboratory I believe that a different interpretation of these data is credible and my analysis and interpretation are presented below METHODS The data used in this study were abstracted from published reports The study subjects were selected by Roggli and Butnor from the consultation files of Victor Roggli Butnor et al 2003 The control subjects were a convenience sample of subjects without occupational asbestos exposure Roggli et al 2002 The counting methodology was described by Butnor et al 2003 Fibre analyses were performed on formalin or embedded lung parenchyma using the sodium hypochlorite digestion procedure described Roggli et al 2004 Digested lung tissue was collected on 0.4 ...mpore size Nuclepore filters For scanning electron microscopic SEM analysis the filter was mounted on a carbon disc with colloidal graphite and then sputter with gold Only fibres 5 ...min length with a length to width ratio of at least 3 and approximately parallel sides were counted Fibres meeting these criteria were quantified by examining 100 consecutive fields with a total area of 2.53 mmor until a 200 fibre count was reached The limit of detection is 400 fibres for a 0.3 g sample For cases in which no asbestos fibres were detected the value was reported as less than the detection limit for that case The chemical composition of fibres was determined by energy dis- persive ray analysis Asbestos fibres were classified as commercial amphiboles specifically amosite + crocidolite AC commercial amphiboles including tremolite anthophyllite and actinolite TAA or chrysotile Roggli et al 1992b I have made several assumptions in the analysis and interpretation of the Roggli and Butnor data These are 1. I assume that most of the friction material products used in the North American market during the 20th century would have been manufactured using chrysotile from the mines of Quebec Virta 2000 2. Quebec chrysotile is known to be contaminated with fibrous tremolite McDonald and McDonald 1997 I assume that both chrysotile and tremolite fibres would be constituents of respirable brake dust 3. Roggli and Butnor report counts of non- commercial amphiboles including TAA a as sin- gle group According to Roggli et al 1993 the vast majority of these fibres had the typical composition of Mg which is the chemical signature for tremolite I have presumed that TAA is predominantly tremolite 4. assume that counts of asbestos fibres would be lognormally distributed in the lungs of both case and control subjects in the Roggli series This assumption is confirmed by the Shapiro test of normality on the transformed data for the tremolite content of the lungs of both the cases P > 0.75 and controls P > 0.87 Figure 1 shows for the control series the fit of the tremolite data above the detection limit to the lognormal distribution There were too few subjects 5.271367 4 1 84 Concentration Concentration Concentration Concentration 7.5 Concentration Concentration Concentration Concentration Tremolite Tremolite Tremolite Tremolite | Tremolite 6.5 Tremolite of of Logarithm 6 Logarithm Logarithm Logarithm Logarithm Logarithm 5.5 Logarithm T 5.5 6.617711 i t 1 T T i 6 6.5 7 Inverse Normal Grid lines are 5 10 25 50 75 90 and 95 percentiles 7.964055 i L 7.83992 . 7.83992 7.83992 7.83992 be 791222 791222 i 791222 791222 6 F 7.5 r 347107 347107 7 347107 347107 5 Fig 1. The fit of the observed tremolite data to a lognormal distribution Lung asbestos content of brake workers 3 of7 with counts above the detection limit to examine in detail the statistical distribution of the chryso- tile fibres tions Case or control status was used as the independent variable in the survival regression model and the distribution of the survival times that is the lung fibre concentrations was taken to be lognormal One important feature of the fibre count data in the Roggli and Butnor publications is that many observations particularly for chrysotile were below the detection limit of the analytical method Roggli and colleagues dealt with this issue by presenting the median as the summary of the data distribution Comparison of point estimates of the median without consideration of its sampling distribution is not an optimal method for comparing distributions between two series of subjects It is possible however to estimate the parameters mean and standard deviation of the distributions using the method of maximum likelihood ML and to make quantitative comparisons of the distributions of fibre concentrations among the case and control subjects In 2001 a colleague and I published a methodology implemented in spreadsheet software to perform the ML calculations Finkelstein and Verma 2001 The ML method was used here to compute the parameters of the distributions of the counts of tremolite and chrys- otile fibres in the lungs of the case and control subjects assuming that the distributions were lognormal It is of interest to compare the distributions of fibre concentrations in the lungs of cases and controls The standard method would be to use a test to compare the estimated means of the logarithmic distributions However because of the data points below the detection limit it is not clear what are the correct degrees of freedom to be used in the test The standard method was thus supplemented here by two other methods In the second method the means of the logtransformed distributions among mesothelioma and control subjects were compared using the bootstrap method Davison and Hinkley 1997 Thirty bootstrap samples were drawn from each of the case and control series and the ML method was used to compute estimates of the means of the log- transformed data for each series The difference be- tween the means of the case and control series was then calculated for each bootstrap sample The third method was that of censored survival analysis In this method we conceive of each fibre concentration data point as analogous to a length of survival in a hypothetical survival analysis Observations below the detection limit are treated as left censored that is in the survival framework they are thought to have occurred at an unknown time before entry to the study where the time of entry is here the analytic detection limit The program INTCENS Griffin 2005 written for the Stata statistical software package StataCorp 2005 was used to perform the regression calcula- RESULTS Table 1 shows the individual counts fibres per gram wet lung tissue of uncoated tremolite and chrysotile fibres 5...min length for the 10 brake workers and 19 control subjects abstracted from the papers of Butnor et al 2003 and Roggli et al 2002 Table 2 shows the means and standard devia- tions of the distributions of fibre counts from the lungs of brake workers and control subjects computed by the method of ML The concentrations of both chrysotile and tremolite were higher in the lungs Table 1. Tremolite and chrysotile asbestos fibre counts > ...min length per gram wet lung in the lung tissues of brake workers n = 10 labelled C and control subjects n = 19 labelled CL Subject number Number of fibres tremolite > ... Number of fibres chrysotile >> ... C1 2180 2180 C2 440 C3 4630 440 660 C4 720 720 C5 1160 580 C6 490 490 C7 C8 C9 C10 340 240 3280 2170 340 120 2180 720 CLI 990 990 CL2 1770 1770 CL3 210 100 CLA CL5 CL6 400 570 2540 400 570 2540 CL7 CL8 470 760 470 760 CL9 890 300 CLIO 170 170 CL11 1000 1000 CL12 1310 650 CL13 960 960 CL14 790 790 CL15 430 430 CL16 CL17 CL18 CL19 510 370 600 600 510 370 600 600 Data are obtained from the publications of Butnor et al 2003 and Roggli et al 2002 4 of7 M. M. Finkelstein of the brake workers than in the lungs of the control subjects Comparison of the fibre concentrations in the lungs of case and control subjects The test comparison The test of the hypothesis that the concentration of chrysotile was greater in the lungs of the brake workers than in the lungs of the control subjects had a value = 0.13 The test of the hypothesis that the concentration of tremolite was greater in the lungs of the brake workers than in the lungs of the control subjects had a value = 0.023 Comparisons by the bootstrap method In the bootstrap comparisons I drew 30 bootstrap samples among the cases and controls For each bootstrap sample I computed the ML estimate of the mean of the transformed data and subtracted the estimate of the mean log concentration for the controls from that of the estimate of the mean log concentra- Table 2. Means and standard deviations of the distributions of logarithmically transformed fibre counts in the lungs of brake workers and control subjects Brake workers n = 10 Control subjects n = 19 Chrysotile Mean standard deviation of logarithmically transformed data 5.1 1.9 4.3 1.4 Tremolite Mean standard deviation of logarithmically transformed data 6.9 1.1 6.0 1.0 Statistics are computed by the method of ML tion for the cases Because only a few of the chrysotile measurements exceeded the limit of detection among the 30 bootstrap draws for chrysotile were five three case draws two control draws in which none of the data points were greater than the detec- tion limit In those instances the ML method did not converge to a positive value and those draws were omitted from the control comparisons Figure 2 shows the distributions of the means of the transformed tremolite fibre concentrations for the 30 bootstrap draws among the case and control subjects For each bootstrap draw the mean con- centration among the controls was subtracted from that of the case subjects Figure 3 shows for chrysotile the results of the subtraction of the estimates of the mean concentrations for the controls from those of the cases for each of the 25 bootstrap samples In 14 of 25 bootstrap samples the mean concentration was higher among the cases and in 11 the mean concentration was higher among the controls This small difference in proportions is consistent with no significant differences between the chrysotile concentrations among the case and control subjects Figure 4 shows the results of the same computation for the 30 bootstrap draws for the tremolite counts In all 30 bootstrap samples the mean concentration was higher among the cases than among the controls This difference in proportions is consistent with a sig- nificant difference between the mean tremolite con- centrations among the case and control subjects Comparisons by censored survival analy- sis The test of the hypothesis that the concentrations of chrysotile were greater in the lungs of the cases than in the lungs of the controls had a value = 0.095 The test of the hypothesis that the concentrations of tremolite 15 10 g Frequency Frequency Frequency 0 Frequency Frequency 15 Frequency Frequency Frequency 10 4 40 4 Case CoCnonttrrooll 5.5 6 6.5 ? 75 Mean LogConcentration Tremolite Fibres Graphs by CaseControl Fig 2. Comparison for brake workers and controls of the distributions of estimated means from 30 bootstrap results using tremolite data as source Lung asbestos content of brake workers 5 of7 Concetrais Control - Concetrais Case T T 10 15 20 25 Boostrap Draw Number Fig 3. For chrysotile the results of the subtraction of the estimates of the mean concentrations for the controls from those of the cases for each of 25 bootstrap samples 1.5 Concetrais Control - Concetrais Case T T 10 20 30 Boostrap Draw Number Fig 4. For tremolite the results of the subtraction of the estimates of the mean concentrations for the controls from those of the cases for each of 30 bootstrap samples were greater in the lungs of the cases than in the lungs of the controls had a value = 0.017 The three comparison methods were thus in agreement the mean of the concentrations of tremolite but not of chrysotile was significantly higher in the lungs of the cases than the lungs of the control subjects DISCUSSION Measurements of asbestos fibre counts in the lungs of 10 brake workers were reported by Butnor et al 2003 and data for a series of 19 control subjects were reported by Roggli et al 2002 After analysing their data Butnor et al wrote lung burden analyses in automotive brake repair workers with malignant mesothelioma in our series reflect asbestos content within the normal range or elevated commer- cial amphiboles I believe that another interpretation of these data is credible Table 2 showed that using the method of ML to deal with observations below the analytical detection limit the mean concentrations of both chrysotile and 6 of7 M. M. Finkelstein tremolite fibres were higher among the brake workers than among the control subjects Three methods of comparison were in agreement that the mean of the concentrations of tremolite but not of chryso- tile was significantly higher in the lungs of the cases than the lungs of the control subjects While the point estimate of the concentration of chrysotile in the lungs of the case subjects was higher than that in the control subjects the difference in means did not achieve statistical significance for chrysotile However there were only 10 case and 19 control subjects and the statistical power of the test was conse- quently very low the power to detect a significant difference in means at the % level was only 22 The asbestos utilized in the manufacture of the friction products used in the North American market during much of the 20th century came from the mines of Quebec It is well known that these ores were contaminated with fibrous tremolite and some authors have postulated that the incidence of mesothelioma and of lung cancer resulting from exposure to commercial chrysotile is mainly attributable to low but varying levels of tremolite fibres McDonald and McDonald 1997 Butnor and Roggli classified the commercial amphiboles that they counted as TAA However the vast majority of these fibres had the typical composition of Mg which is the chemical signature for tremolite Roggli et al 1993 I have thus presumed that TAA is predominantly tremolite Tremolite fibres were present in the lungs of both the cases and controls in the Roggli series In fact the mean concentration of tremolite fibres was higher than the mean concentration of chrysotile in the lungs of both the cases and controls How could it be possible for the concentrations of a minor contaminant to be higher than the concentrations of the principal commercial fibre Does this exonerate occupational exposure to brake dust as the source of the fibres In 1999 a colleague and I published the results of an analysis of the asbestos fibre content of the lungs of 72 Quebec chrysotile miners and millers and of 49 control subjects measured using analytical transmission electron microscopy Finkelstein and Dufresne 1999 We concluded that tremolite fibres persisted in lung tissue with a very long half but chrysotile fibres were cleared from lung tissue with a clearance rate that varied inversely with the length of the chrysotile fibres For chrysotile fibres 10 ...min length the clearance time was estimated to be ~ years and the clearance time was ~ years for fibres 5-10 ...min length I have returned to that data set and computed the mean concentrations of fibres in the lungs of the Quebec chrysotile miners and millers and the control subjects The results are presented in Table 3. We have the result that among the Quebec chrysotile miners and millers the lung concentrations of fibres of the contaminant tremolite were higher than the concentrations of the principal fibre chrysotile This is the same pattern that was seen in the lungs of the brake mechanics occupationally exposed to dusts of Quebec chrysotile Since chrysotile is cleared from the lungs of brake workers tremolite is arguably a better marker of exposure to Quebec chrysotile than is chrysotile itself CONCLUSIONS Further examination of the lung fibre data obtained by Butnor and Roggli data show that the 10 brake workers with mesothelioma had higher mean concentrations of tremolite and chrysotile fibres in their lungs than did the control subjects without occupational asbestos exposure The pattern of higher tremolite than of chrysotile concentrations is consistent with occupational exposure to dusts of Quebec commercial chrysotile The alternative interpretation of the data of Butnor and Roggli is thus that automotive mechanics have elevated concentrations of asbestos fibres in their lungs consistent with occupational exposure to commercial chrysotile I believe that this interpretation is more strongly supported by the data than is the interpretation proposed by the authors One must be cautious in generalizing these observations based as they are on data from only 10 subjects with mesothelioma and 19 control subjects While the dust exposures of automotive mechanics are likely to have been less than those experienced by chrysotile miners and millers it has been esti- mated that 1 million American workers are involved in installing and repairing clutch facings and brake shoes Huncharek 1990 In this circumstance even a mild increase in risk might have produced cases of Table 3. Means and standard deviations of the logarithms base 10 of asbestos fibre concentrations fibres > ...min length in the lungs of Quebec chrysotile miners and millers n - 72 and of control subjects n = 49 Miners and millers Controls Chrysotile 5 to 10 ...in length 2.97 1.00 2950 f mg dry lung tissue 1.71 0.46 65 f mg dry lung tissue Tremolite 5 to 10 ...in length 3.39 0.70 4300 f mg dry lung tissue 1.85 0.57 100 f mg dry lung tissue Chrysotile 10 ...in length 2.58 0.86 900 f mg dry lung tissue 1.64 0.40 50 f mg dry lung tissue Tremolite 10 ...in length 2.71 0.65 850 f mgfl dry lung tissue 1.66 0.33 50 f mg dry lung tissue Arithmetic mean concentrations are presented in square brackets Lung asbestos content of brake workers 7 of7 associated cancer among workers in this trade Acknowledgements thank editor David Bartley for helpful discussions REFERENCES Butnor KJ Sporn TA Roggli VL 2003 Exposure to brake dust and malignant mesothelioma a study of 10 cases with mineral fiber analyses Ann Occup Hyg 47 325-30 Davison AC Hinkley DV 1997 Bootstrap methods and their application Cambridge Cambridge University Press Finkelstein MM Dufresne A. 1999 Inferences on the kinetics of asbestos deposition and clearance among chrysotile miners and millers Am J Ind Med 35. 401-12 Finkelstein MM Verma DK 2001 Exposure estimation in the presence of nondetectable values another look Am Ind Hyg Assoc J 62 195-8 Goodman M Teta MJ Hessel PA et al 2004 Mesothelioma and lung cancer among motor vehicle mechanics a metaanalysis Ann Occup Hyg 48 309-26 Griffin J. 2005 Intcens Available at http.//ideas.repec.org/c/ s453501.html Accessed 16 June 2008 Huncharek M. 1990 Brake mechanics asbestos and disease risk Am J Forensic Med Pathol 11 236-40 Jacko MG DuCharme RT 1973 Emissions Measurements from Brake and Clutch Linings from Selected Sources 6804-0020 US EPA Washington DC Laden F Stampfer MJ Walker AM 2004 Lung cancer and mesothelioma among male automobile mechanics a review Rev Environ Health 19. 39-61 Lemen RA 2004 Asbestos in brakes exposure and risk of disease Am J Ind Med 45. 229-37 McDonald JC McDonald AD 1997 Chrysotile tremolite and carcinogenicity Ann Occup Hyg 41 699 705 Paustenbach DJ Finley BL Lu ET et al 2004 Environmental and occupational health hazards associated with the presence of asbestos in brake linings and pads 1900 to present a state review J Toxicol Environ Health B Crit Rev 7 25-80 Roggh VL Pratt PC Brody AR 1993 Asbestos fiber type in malignant mesothelioma an analytical scanning electron microscopic study of 94 cases Am J Ind Med 23 605-14 Roggli VL Sharma A Butnor KJ et al 2002 Malignant mesothelioma and occupational exposure to asbestos a clinicopathological correlation of 1445 cases Ultrastruct Pathol 26 55-65 Roggli VL Oury TD Sporn TA 2004 Pathology of asbestosassociated diseases New York Springer StataCorp LP 2005 Stata statistical software College Station TX Version 9.1 Virta RL 2000 Asbestos Mineral Yearbook US Geological Survey Washington DC