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FILE NAME Brakes BRK DATE 2008 DOC BRK185 DOCUMENT DESCRIPTION Journal Article - Asbestos Fibre Concentrations in the Lungs of Brake Workers Ann Occup Hg pp 1-7 'The Author 2008 Published by Oxford University University Press on behalf of the British Occupational Hygiene Society dos 10 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 Objective To reanalyse data on the lung content of asbestos fibres among brake mechanics Methods I analysed data published by Butnor Roggli and colleagues on the lung content of chrysotile and tremolite asbestos fibres among brake mechanics and controls Statistics of the distributions were estimated by maximum likelihood to accommodate observations below the detection limit Mean concentrations were compared by the test bootstrap resampling and censored survival methods Results The mean concentrations of fibres were higher among the brake workers than the controls The concentration of tremolite fibres was higher than the concentration of chrysotile a pattern similar to that observed among Quebec chrysotile miners and millers Conclusions analysis of published data does not support the interpretation that in automotive brake repair workers with malignant mesothelioma asbestos content is within the normal range The alternative interpretation that brake mechanics have a greater than background burden of asbestos fibres attributable to occupational exposure to dusts from friction products manufactured from Canadian chrysotile appears more credible This asbestos burden might be associated with an increased risk of associated cancers Keywords asbestos brakes friction products lung fibre content INTRODUCTION Mesothelioma is a rare tumour strongly associated with exposure to asbestos During most of the 20th century asbestos was an important constituent of vehicular braking systems Paustenbach et al 2004 In 1973 the US Environmental Protection Agency reported that brake linings contained 33-73 asbestos by weight and estimated that 32 million kg of asbestos were worn away from brake linings each year Jacko and DuCharme 1973 Automotive and brake mechanics have occasionally been diagnosed with mesothelioma and the attributability of these tu- mours to asbestos exposure has become a contentious 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 lung cancer or mesothelioma among male automobile mechanics occupationally exposed to asbestos from brake repair Goodman et al 2004 concluded that employment as a motor vehicle mechanic does not increase the risk of developing mesothelioma I was asked by a defence law firm to examine the liter- ature 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 friction 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 subjects with mesothelioma published by Roggli et al 2002 Both sets of reviewers interpreted the data 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 mesothelioma 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 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 > um in 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 as a 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. I 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 L L : 8+ Concentration Concentration : Concentration 75 Concentration 75 Concentration : Concentration 7 Tremolite i Tremolite Tremolite oe i Tremolite of Logarithm 6 Logarithm | 6617711 6617711 1 vad a a aa s 1 bad a a 77 964055 4 83992 83992 fi 83992 83992 7 791222 791222 6 Logarithm 1 55 Logarithm j \ bed 55 t T T 6 65 7 Inverse Normal Grid lines are 10 25 50 75. 90 and 95 percentiles 7 75 347107 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 chrysotile 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 tremol 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 Cl Number of fibres tremolite > 2180 Number of fibres chrysotile > ... 2180 C2 C3 C4 C5 C6 C7 C8 C9 C10 CLI CL2 CL3 440 4630 720 1160 490 340 240 3280 2170 990 1770 210 440 660 720 580 490 340 120 2180 720 990 1770 100 CLA CL5 CL6 CL7 CL8 CL9 400 570 2540 470 760 890 400 570 2540 470 760 300 CL10 CL11 170 1000 170 1000 CL12 CL13 1310 960 650 960 CL14 CL15 CL16 CL17 CL18 CL19 790 430 510 370 600 600 790 430 510 370 600 600 Data are obtained from the publications of Butnor et al 2003 and Roggli et al 2002 of 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 51 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 detection 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 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 Case Frequncy Control ay T T T T 55 6 65 7 75 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 of7 Concentrations Concentrations Concentrations Concentrations Concentrations Concentrations Concentrations Concentrations Concentrations Concentrations Control Control Control Control bd e ry e e e e * e Concentrations Concentrations Concentrations e Concentrations Concentrations Concentrations oe Concentrations Concentrations e Concentrations Concentrations Case e Case -4 4 -4 Case - T- a 0 5 To 10 s e e r e e ~ an ins enemas ores 12 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 Concentrations Concentrations 15 Concentrations * Concentrations t e Concentrations Concentrations t Concentrations 5 e e a bd Concentrations . * Concentrations H e e . Concentrations * Control Control : Control ; - Concentrations i . e fi e e Ld . . es Concentrations | Concentrations 5 Concentrations : ; Concentrations Concentrations | Concentrations i Concentrations Case Case | of Case 47 0 i 7 7 T 10 7 e i. 7 20 Boostrap Draw Number fee ee ne a L8 L8 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