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British Journal of Industrial Medicine 1989:46:180-187 Respiratory cancer in chrysotile textile and mining industries: exposure inferences from lung analysis P SEBASTIEN,1 J C McDONALD,1 A D McDONALD,1 B CASE.1 R HARLEY' From the School of Occupational Health.1 McGill University. Montreal. PQ H3A l A3. Canada, and Department of Pathology.2 Medical University of South Carolina. Charleston. SC 29425-0689. USA abstract In an attempt to explain the much greater risk of respiratory cancer at the same cumulative exposure in asbestos textile workers in Charleston, South Carolina, than in Quebec miners and millers, both exposed to chrysotile from the same source, 161 lung tissue samples taken at necropsy from dead cohort members were analysed by transmission electron microscopy. Altogether 1828 chrysotile and 3270 tremolite fibres were identified; in both cohorts tremolite predominated and fibre dimensions were closely similar. Lung fibre concentrations were analysed statistically (a) in 32 paired subjects matched for duration of employment and time from last employment to death and (b) in 136 subjects stratified by the same time variables. Both analyses indicated that the Quebec/ Charleston ratios for chrysotile fibre concentration in lung tissue were even higher than the corresponding ratios of estimated exposure intensity (mpcf). After allowance for the fact that regression analyses suggested that the proportion of tremolite in dust was probably 2 -5 times higher in Thetford Mines, Quebec, than in Charleston, the results from both matched pair and stratification analyses of tremolite fibre concentrations in lung were almost the same as for chrysotile. It is concluded that neither fibre dimensional differences nor errors in estimation of exposure can explain the higher risks oflung cancer observed in asbestos textile workers. The possible co-carcinogenic role of mineral oil used in the past in asbestos textile plants to control dust provides an alternative hypothesis deserving consideration. After many years of asbestos research, exposure response in man is still poorly understood. By combining factors such as fibre type, length, diameter, and numerical or gravimetric concentration, it is theoretically possible to construct several indices of exposure intensity, each of different biological relevance. Surface structure and chemistry should also be taken into account. Practically, however, informa tion on exposure intensity is at best limited to one index. Industrial hygienists currently measure the concentration of fibres with a length greater than 5 microns and a diameter greater than about 0-25 micron (f/ml). In the past, impinger methods were used to measure dust in million of particles per cubic foot (mpcf); in asbestos industries the particles were generally not fibrous or longer than 0-75 pm.' Quantitative studies of exposure response entail reconstruction of exposures in industries where condi tions and monitoring techniques have changed over the years and where the high and more important Accepted 15 February 1988 exposures of the past were seldom documented. This difficult exercise has been attempted in nine industrial populations.2 Among these were the chrysotile miners and millers of Quebec'4 and the chrysotile textile workers of Charleston, South Carolina.' Linear relations between excess mortality from respiratory cancer and cumulative exposure in these two popula tions (fig 1) illustrate the problem considered in the present report. In both cohorts cumulative exposures (mpcf.y) were calculated from impinger data, all that were available for the past. Cumulative exposures as high as 2000 mpcf.y were recorded in the Quebec cohort, 10 times higher overall than exposures in Charleston. Figure 1 shows that, for the same cumulative exposure, the risk of respiratory cancer was about 50 times higher in Charleston. These estimates of risk were essentially corroborated by independent studies in the Charleston plant4-* and in Quebec.' Studies in two other textile plants, one in the United States and another in the United Kingdom, gave similar results.1011 The large difference in risk between mining and 180 Fi. a teh> ex tein an fa* G in is as' thi as: O siti wa th* da' Ai sin en< ini fib de. Respiratory cancer in chrvsotile te xtile and mining industries, exposure inferences Jrom lung analysis 183 9004 203 400 600 800 3000 5200 Cumuiotiv* exposure (rrpct.y) Fig 1 Exposure response for respiratory cancer in Charleston chrysolite textile and Quebec mining industries.1 textile manufacture has never been explained. Three hypotheses have been suggested: the low reliability of exposure data, the presence of longer fibres in the textile industry, and the possibility of a co-carcinogen in textile plants. There are no data to confirm or refute any of these hypotheses. Fibre type could hardly be a factor since the chrysotile used by the plant in Charleston came mostly from the Quebec mines. Although lower dust concentrations were reported in the Charleston plant than in the mining industry, it is conceivable that textile workers who handled pure asbestos were more exposed to respirable fibres than the Quebec workers. Cumulative exposures to asbestos would then have been higher in the Charleston population and risk estimates in the two situations closer. The objective of the present study was to obtain better information on the exposure of the two cohorts. Intensity is the key question, since dates of employment and death were known precisely. Air measurements taken today are not informative, since conditions in both industries have changed enormously. It was thought that more relevant information could be obtained from examination of fibres retained in lung tissue taken at necropsy from dead cohort members. Collection of lung tissue The Charleston cohort comprised 2543 men, employed one month or more between 1938 and 1958. Death certificates were available for 95% of the 863 men who had died before 1 January 1978. From these certificates. 234 necropsies were identified. 117 in one of the 11 hospitals in Charleston and the rest in 47 other hospitals, mainly in the south east of the United States. All pathology departments in Charleston were visited. The directors of the 47 other departments were contacted by letter or by telephone. To find specimens from deaths after 31 December 1977, names of cohort members were sought in recent necropsy lists. By this means we obtained a total of 77 lung specimens, including 31 paraffin blocks. In five cases the amount of lung tissue in the paraffin block was insufficient, leaving 72 cases for analysis. The Quebec cohort comprised 10 939 men born between 1891 and 1920 and employed for at least one month. By 1976, 4547 deaths had occurred. Tissue collection was limited to two hospitals, one in Thetford Mines and the other in Sherbrooke, where two thirds ofthe necropsied cases had died. Altogether 302 necropsies from former workers were identified, 112 before and 190 after 31 December 1975. Lung specimens were obtained for 215, including 159 paraffin blocks. As all the selected cases were cohort members, information was readily available on work history, cumulative exposure (mpcf.y), and cause of death. All 72 lung specimens from Charleston were analysed but, because of limited resources, only a sample of those from Quebec, comprising cases from Thetford Mines where most of the chrysotile used in the Charleston plant had come from. The selection procedure was as follows: cases from both groups were distributed in six categories of cumulative exposure (table 1). To accommodate the much higher values in the mining industry, boundaries for Thetford were set at 10 times those in Charleston. Forty three per cent of the Table 1 Study subjects by cumulative dust exposure Cumulative exposure ca/egoris / 234 5 Charleston Thetford Charleston Thetford: available ThfJionJ: selected Charleston Thetford -3 -30 31 II 11 0-34 (37) 3-9 (3 0) -9 -90 Boundaries (mpcf.y"} -n - 81 -270 -810 - 243 -2430 Cases to 11 13 7 w 37 46 4! to 18 23 20 Geometric mean cumulative exposure (SD) 5 3 </'.)) 17-9 (f-2) 48 -6(1-4) I23(/-J) 50-5 (I-4) 177.0 (f-J) 515-0(14) I218(/J) Million of panicles per cubic foot.years. 6 - 729 -7290 0 7 7 -- 2923(1-2) HWBUI0006911 182 Table 2 Characteristics ofcases studied Age at first employment Age at death Years of employment Years of latency Years after employment Intensity of exposure to dust (mpcP) Million of particles per cubic foot Sebasiien, McDonald. McDonald. Case. Harley Charleston in 72) Median Mean fSD) 220 580 6-4 32-7 20-3 1-4 24-2 55-8 13 5 31 6 181 1-9 ( 6 2) ( 9 7) (143) ( 8 1) (13 2) ( 19) Thetford I rt - 89) Median Mean 230 68-0 360 46-6 8-0 10-9 23 8 67-5 32-6 44-2 11-6 195 ISO) ( 8 3) ( 9 7) (14 7) (10-61 (13-3) (21-0) " Charleston cases fell below 3 mpcf.y, the rest almost equally distributed between categories 2 to 5. Most cases in Thetford were in categories 3, 4, and 5, so a random sample of these was selected for analysis together with all cases in categories 1,2, and 6, yielding a total of 89. Characteristics of the two study groups are set out in table 2. First employment in both was during the period 1920-55 at a mean age of 24. Age at death was much higher in the Thetford series and duration of employment over twice as long. Mean intensity ofdust exposure (mpef) was 10 times higher in Thetford. In both industries the range of mpcf.y values for the necropsied group was similar to that of the cohorts from which they had come. In Charleston the distribu tion of mpcf.y values was also similar for necropsied cases and all deceased cohort members but in Thetford high values were overrepresented in necropsied cases. Table 3 shows the distributions by cause of death; diseases potentially related to asbestos were overrepresented in the Thetford group; better representativeness was achieved in Charleston. Analysis of retained fibres The 161 lung tissue specimens. 74 formalin fixed and 87 paraffin blocks, were analysed for fibres by transmission electron microscopy (TEM). Specimens were first prepared by digestion filtration techniques in a clean room using filtered chemicals and specially cleaned glassware. For formalin fixed specimens, the portion t0 be digested was cut, saturated in formalin for 10 minutes and weighed in a small covered plastic vial. Wet weight was converted into dry weight after measuring the lung density of an adjacent portion weighed wet and again after drying for two days in an oven at 62C. The wet portion was digested at room temperature for 60-90 minutes with fresh commercial bleach in a disposable Nalgene 100 ml centrifuge tube. The volume of bleach was adjusted to achieve the digest concentration of 1 mg dry weight/mi. A standard 15 ml aliquot was filtered through a membrane filter (Millipore stan dard. 0 45 jim, 25 mm). A spare filter was obtained in the same way. The Millipore filter was placed in a 50 ml glass bottle, the side with the filtration residue applied to the glass, and ashed overnight in a low temperature asher (100 Watts forward power, 10 cc O^/min). After ashing, bottles were completely filled with 50 ml of water. One hour later, the suspension was filtered through Nuclepore membrane filter (0-2 pm, 25 mm, shiny side up) and collected particles were transferred on to TEM grids (Cu, 200 mesh) using the classic technique of the replica in a carbon film.1*' Five grids were prepared from five randomly selected locations of the membrane. Paraffin blocks were first trimmed with cleaned disposable blades to remove excess paraffin and held for at least three days in hot xylene (64C) to melt and dissolve the wax. This operation was conducted in a specially designed dewaxing cell, containing a 75 ml glass syringe mounted on a metallic Millipore filter Table 3 Cause ofdeathfor cases in the study and deceased cohort members Respirator) holder for: removed a' plunger t standard, < * was dried , described # escaping f I adjusted p filter were filters pro TEM a electron t energy di analysis, holder ti 1 positions observed nominal: ` ing volta \ longer th Fibre t 4 ced micr EDS spe. used to type, rep disk and systemat Each t j from the 1 fibres w: specially mounter c The lent larger fi * using t\ diamete * the fibr t plicated bundles these, tl c Fibre d * categor blocks: ' Table 4 Causes ofdeath t /CD) Lung cancer (162-4) Mesothelioma* Gastrointestinal cancers (\ 50-4) Pneumoconiosis (523-4) Other Ail Variously coded.5 5 Charleston Necropsied cases 7 (9 7V.) 0 2 (28V.) 6 (8-3%) 57(79 2%) 72 Cohort members 66 (7-7%) I (0-01%) 24 (2-8V.) 21 (2-4%) 745 (86-9%) S57 Thetford Necropsied cases 22(24-7%) 4 (4 5%) 4 (4 5%) 11 (10 9%) 48 (53-9%) 89 Cohort members 250 (5-6%) 10 (002%) 242 (5-4%) 46 (1-0%) 3915(87-8%) 4463 9 % Chrysoii 9 Chari. Thetf. Tremoli Otari Thetf. To obi typeset HWBUI0006912 fHarley SDt I 8-3) , 9-7) (14-7) .106) . 13-3) i.'l-O) :ion to be (minutes. A el weight !g the lung and again The wet for 60-90 jKposable of bleach jiion of I ^uot was \irc stansumed in ,-j in a 50 a residue low 10 cc Tilled .spension me filter : particles <) mesh) t carbon jmJomly Jeaned nj held melt and ,\*tl in a i '5 ml -e filter Respiratory cancer in chrysolite textile and mining industries: exposure inferences from lung analysis 183 holder for filtration under pressure. The lung was then removed and the xylene, while still hot. pushed by the plunger through a membrane filter (Millipore standard, 0-8 pm. 25 mm). The dewaxed lung specimen was dried, weighed, digested, and prepared as described for the wet specimens. To correct for fibres escaping from the lung specimen during dewaxing, an adjusted portion of the xylene filter and the lung digest filter were ashed in the same bottle and the two pooled filters processed together. TEM analyses were made with a JEOL 100 CX electron microscope fitted with a PGT system IV energy dispersive spectrometer (EDS) for elemental analysis. Grids were inserted in a graphite sample holder tilted at 30 towards the EDS detector positioned as close as possible to the grid. They were observed in the transmission mode at * 10 000 nominal screen magnification under 80 kV accelerat ing voltage. All visible fibres (aspect ratio >3:1) longer than 5 pm were identified and sized. Fibre types were recognised on line by an experien ced microscopist from morphological features and EDS spectrum11; selected area electron diffraction was used to a limited extent. For each recognised fibre type, representative EDS spectrums were stored on disk and the fibres photographed. The same was done systematically for all fibres of unrecognised type. Each fibre was sized (length and diameter) directly from the screen. The projected diameter of the thinnest fibres was measured to the nearest 0-03 pm using a specially designed hemispherical eyepiece graticule mounted within the binocular lens of the microscope. The length of all fibres and the projected diameter of larger fibres were measured to the nearest 0-07 pm using two concentric circles (10 mm and 50 mm diameter) drawn on the fluorescent screen. As most of the fibres observed were isolated and without com plicated morphology, this was usually easy. A few bundles of chrysotile were observed however; for these, the diameter of the compact core was recorded. Fibre dimensions were reported in a matrix of 120 size categories designed to allow classification in three blocks: optic fibres, Stanton fibres, and short fibres as 600 700 (1! S > .*! i * *! 3........................ . . 3 U 600 Charleston Thetford 500 "TsT n'too , 1101 * (141 .1! 300 J61 1 * . 200 -- * (71 ' ' 1 1 ' (ill (15) (IS) 1i (21)!1 i 1 r-iHp-------- 2 " 1121 i*i (191 UJ.* 1 *ian 126) ; ,, i* ,, p too , --i- :-j-- (81 ibi; (171 '* . y.1231* **...*! (271 . a |A s.?--.%i2ji 100 200 300 400 500 600 700 tXrotion (months] Fig 2 Distribution ofsubjects by months ofemployment (duration) and months since last employment (cessation). defined by Sebastien.'4 For each fibre type, numerical concentrations of fibres longer than 5 pm per microgram of dried lung were reported. A sufficient number of grid openings was scanned to achieve a detection limit as low as 0-1 f/pg. Statistical analysis Our object was to extract information on intensity of past exposure to asbestos from lung retention measurements. We made the simple assumption that for a given fibre type, lung retention depended on duration of employment, mean intensity of exposure, and time since last employment (cessation). On this assumption, lung retention in cases with similar time characteristics, duration and cessation, should reflect mean intensity. Table 4 Sice distribution ofchrysotile and tremolite fibres in lung tissue Chrysotile: Charleston Thetford Tremolite: Charleston Thetford No of Percentage distribution length categories (pm) fibres sized* 5-8-8 0 8-0-128 12-8-205 20-5-32-4 32-4-52-4 226 72-6 16-4 6-2 3-6 13 371 670 21-6 8-1 2-2 08 175 760 17-7 40 11 H 405 78-8 17-3 3-7 -- 02 Mean length (pm) Mean diameter Stanton fibres'* (fan) (%) 7-9 (0-7) 8-3 (0-6) 7-4 (0-7) 6-9 (0-3) 0-10(002) 0-07 (001) 0-35 (004) 0 32 (002) 25-2 31 8 63 5-9 To obtain an equal contribution from each subject the distributions were established by taking into account only the first five fibres of each type seen. HWBUI0006913 184 Table 5 Concentrations offibres in lung tissue Sebastien, McDonald. McDonald. Case. Harley Resp TabU Fibres m tissue (nbipg) Chrysotile Ch 7m -01 -to -100 - 1000 -10000 Geometric mean (nb/jig) Geometric standard deviation 15 35 15 5 2 063 7-3 6 10 39 29 4 ! 5-3 7-7 Ch Charleston; Tm =*= Thelford Mines. Tremoiite Ch Tm 3! 17 7 038 7-5 \ 4 23 54 6 t 184 5-4 Amosite + crocuidiie Ch Tm 49 81 U3 64 3t Talcanthrophylliie Ch Tm 46 St 23 13 3 23 2 0 14 4-9 007 3-0 Oil 022 2-8 5-9 Other fibres Ch Tm 40 40 27 25 7 016 3-5 0-24 48 Each fibre type was treated separately and analyses made in two ways, by stratification and in matched pairs. In both methods lung retention of fibre and mean intensity ofdust exposure (mpcf) were compared between Charleston and Thetford in cases having similar duration and cessation. For the stratification analysis, cases were grouped in duration cessation cells as indicated in fig 2. For the paired analysis. Charles ton and Thetford cases were matched on both dura tion and cessation as closely as possible. Thirty two pairs were constituted which differed in duration and cessation by less than four years. Results Five main types of fibre were identified: chrysotile, tremoiite, amosite, crocidolite, and talc-anthophyllite; other fibre types included rutile, micas, iron, silica, and unidentified silicates. CHRYSOTILE A total of 1828 chrysotile fibres, including two bun dles, were analysed. Good quality EDS spectrums obtained from fibres larger than 0-2 ftm showed up to 50% magnesium leaching in almost all. There was some indication that the degree of the leaching was related to time between first employment and death. For chrysotile fibres of smaller diameter, EDS spec trums were not suitable for quantitative elemental analysis. Most of fibres were around 0 06 fim in diameter (table 4). Some slightly larger fibres were seen, especially in Charleston specimens. The longest fibre (62 pm) was found in a Thetford specimen. The length distributions in Charleston and Thetford were similar, although the proportion of very long fibres (>32-8 ptm) based on very small numbers (three or less) was higher in Charleston. Numerical concentra tions, over six orders of magnitude, were higher overall in Thetford (table 5). Results of the stratification analysis are reported in table 6. Twenty seven duration cessation cells were defined (fig 2) but in only 14 from which results are shown were there both Charleston and Thetford cases. In each of the 14 cells the median of mpcf values, lung concentrations ofchrysotile fibres and lung concentra tions of tremoiite fibres were reported for Thetford and Charleston. The chrysotile concentrations from Thetford exceeded those from Charleston in 12 of the 14 cells; the two exceptions were those with long duration and short cessation. The geometric mean ratios (Thetford/Charleston) were 6-70 for mpcf and 9-69 for chrysotile concentrations (table 6). The matched pair analysis is presented in table 7. For each pair, the ratios (Thetford/Charleston) of mpcf indices and of chrysotile concentrations were calculated; geometric means over the 32 pairs were closely similar (4-8 and 4-3). TREMOLITE Overall, tremoiite fibres were more numerous than chrysotile; a total of 3270 was analysed, all single fibres. Their diameters were generally sufficient for quantitative elemental analysis by EDS. Fibres in the specimens from Charleston and Thetford had similar elemental composition (fig 3). Size distributions (table 4) were almost the same in the two groups, but again the proportion of very long fibres was somewhat higher in Charleston. As for chrysotile, numerical concentrations were higher in Thetford; they did not exceed 10 f//jg in Charleston, whereas the highest concentration in Thetford was over 2700 f//tg. In the stratification analysis (table 6) median values were systematically lower in Charleston, especially in cells with short duration and long cessation. The geometric mean ratio was 23 00,3-4 times greater than the mpcf ratio (6-70). In the matched pair analysis (table 7) the geometric mean ratio was 12-3, 2-6 times greater than the mpcf ratio (4-8). As will be discussed below, however, there is reason to believe that the proportion of tremoiite in dust was substantially greater in Thetford than in Charleston. I 1 * Cell > 3 4 5 6 II i: 13 16 (7 19 :VoS '3 :5 Geom GM r. See f COM Non croci Chai Table 12 pa Pairs Mean duratiI mom -7r 9 18 46 62 68 99 110 149 190 290 292 306 312 314 351 352 355 378 389 391 404 411 420 427 431 443 449 467 471 480 500 Geon r HWBUI0006914 Respiratory cancer m chrysotile textile and mining industries: exposure inferencesfrom lung analysis Table 6 Median valuesfor exposure intensity (mpcfI and lungfibre concentrations in duration cessation cells Ifig 2) 185 Celt .Vo' Cessation (months; 3 500- 4 4005 3006 :oon 200- i: 100" 13 10016 SO0- 17 10019 < (00 20 <!00 22 <100 :3 <100 25 c 100 Geometric mean (GM) GM ratio Tm Ch *$ fig 2 for explanation. Duration (months; <100 <100 < too < too 100100200" 300400" too200300400500- No Tm Ch 3l 27 9 17 in 1t 1t 32 2? 23 22 i! 9 12 i 12 9 17 i 70 66 mpcf 7m Ch 3 86 50-87 i 43 0 70 4-29 Oil 102 1525 17 08 67-17 4 38 2562 11 09 12 30 1-33 2 71 2-2Q 105 0-27 210 1-23 1 29 1-29 1 93 1 34 0-50 2-83 i 70 7-30 109 6-70 Chrysotile tnbipg) Tm Ch 2-24 2-48 0-50 6-32 20-00 0 28 0-90 911 485-01 537-53 673 6-64 7-95 840 1 56 0 30 031 0-28 1 49 6 30 0-60 0-05 0-80 2-55 0-76 0 31 955 30-77 804 0-83 9-69 Tremolite tnb'pg> Tm Ch 4-49 31-12 1-40 11-58 1-60 014 1 30 41-10 10-18 45-44 16-49 39-90 27-07 29-60 0-05 005 005 0 to 1 49 005 0-90 i 87 063 090 4-05 11 19 4 20 10-81 0*47 23-00 COMMERCIAL AMPHIBOLES AND OTHER FIBRES Non-trivial concentrations {> OT f, <iig) ofamosite and crocidolite were measured in 32% of specimens from Charleston and 9% from Thetford. In Charleston Table 7 Lungfibre concentrations and exposure (mpcf) in 32 pairs matchedfor duration and cessation Pairs (n 32 > Mean duration i months) Mean cessation i months: 7 494 9 435 S8 558 46 366 62 255 68 435 99 399 no 112 149 32 190 98 290 169 29? 69 306 2 312 90 314 35 351 67 352 355 U 378 14 389 28 39! 53 404 14 4)2 6 420 204 427 " 72 431 l 443 6 449 102 467 88 471 30 480 8 500 13 Geometric mean Thetford'Charleston ratio Exposure (mpcf) Lungfibre concentration Chrysotile Tremotiie 0 12 13 0 153-0 041 0-66 21 0 2-5 100 49 2-4 6-9 2-7 71-0 0-69 1-7 0 30 23-0 0-53 12 0 159-0 16-0 580 003 130 3-8 21-0 3-3 6-8 27-0 19 2-5 18-0 4-8 69-0 8-2 1-2 1-3 63 0 005 7-0 32 840 u-o 630 650 0-43 1-5 2-0 116-0 260 4-3 4-8 336-0 1-5 0 59 --ISO 0 41 3-7 0-06 067 89-0 18 0 1-4 0-30 4-3 90-0 6(50 40 28 115-0 5-6 54 0 9-3 1680 126-0 70-0 12-0 100 180 1-5 45 8-7 94 107-0 196 0 62 2-0 0-67 110 3-1 190 040 2-7 84 0 096 7-9 22-0 12-4 commercial amphiboles were detected only in cases hired before 1940; no crocidolite was detected in cases hired after 1940. In Tbetford concentrations greater than 0 ! f/>g were measured in five cases. All were hired in the period 1928-36 and had been employed for many years (mean duration 39 9 years). Concentra tions of talc-anthophyllite and of other fibres were both slightly higher in Thetford (table 5). Discussion In the absence of an accepted model for lung retention of asbestos fibres comparison between the two groups was restricted to cases having similar time characteris tics of exposure (duration and cessation). In these circumstances it was assumed that retention would be proportional to mean intensity of exposure. This assumption, impossible to test without good environ mental data, may be questioned, especially for chrysotile. initially we thought it might be appropriate to use regression analysis to relate exposure intensity (mpcf) to lung fibre concentrations in the two series and to compare observed values in one with those expected by application of the regression equations from the other. Although the results obtained by this approach were similar to those from the matched pair and stratification analyses, we have not quoted them here because the underlying assumptions as to linearity did not seem justified. As discussed below, however, we used the regression equations to estimate the relative proportions of tremolite in the two plants. The representativeness of the two groups of necrop sies is also uncertain. The cases studied adequately covered the range of cumulative exposure (mpcf.y) in the two cohorts but asbestos related diseases were * 186 407. 207, 0 207. 407. Percentage of iremolite fibres Fig 3 Distributions ofelemental compositions ofIremolite fibres in lung tissue, determined by energy dispersive spectrometry using peak ratio method.'1 Numbers of Fe. Ca. Mg cations were calculated asfor 8 silicon atoms to allow comparison with idealformulafor iremolite. Ca. (Mg. Fej, (SifiJ(OH).. overrepresented in the Thetford series. As exclusion of such cases from the matched pair analysis yielded similar results, this bias was probably not important. The presence of longer fibres in the textile industry has often been proposed as the explanation of the higher risk in Charleston. Our study does not support this hypothesis; as the lung preferentially retains long fibres and our size selective analysis was orientated towards fibres longer than 5 pm. any difference in size distributions should have been picked up. The lung tissue analyses confirmed exposure to chrysolite but gave even stronger evidence of exposure to iremolite in both industrial groups. In all duration cessation cells, except that for short exposures in Charleston, the concentration of iremolite was higher than that of chrysolite. In the Thetford group iremolite represented 77% of all asbestos fibres analysed. As the proportion of tremolite in asbestos Sebassten. McDonald. McDonald. Case. Harley dust from the Thetford region has been estimated at around 1%.13 the respiratory system clearly treats tremolite differently from chrysotile. The explanation probably lies mainly in the more rapid clearance of chrysotile,14 the mechanism of which is unknown. Tremolite with the same elemental composition was found in lung tissue from Thetford and Charleston cases, implying a common source and suggesting that tremolite may accompany chrysotile from production into its industrial applications. Although these findings put in question the relative importance of tremolite and chrysotile in asbestos related pathology, they give no indication that tremolite was responsible for the higher risk of lung cancer in Charleston. In fact, both stratification and matched pair analyses indicate the reverse. In cells of short duration and long cessation (table 6) the tremolite retention was much higher in Thetford; even at longer durations a substantial difference remained. In the matched pair analysis (table 7) the mean tremolite ratio (Thetford/Charleston) was 12-4 w hereas the mean mpef ratio was only 4-8. We have no direct evidence, however, on the proportion of tremolite in dust at the two places. Linear regression analyses showed that the proportion of tremolite in pulmonary fibres was related to duration of employ ment and time since last employment. Equations relating proportion of tremolite (%T) to duration of employment in months (MD) and months since last employment (MC) were respectively: Charleston: (%T) = 0137 + 9-610'* (MD) + 5-2l0"(MC) Thetford: (%T) = 0-346 + 6-710" (MD) + 6-310" (MC) At zero values of MD and MC, these equations should reflect the proportion of tremolite among fibres deposited in the lung before modifications by solubility or clearance mechanisms. This suggests that the proportion of tremolite in dust was 2-5 times higher (346/137) in Thetford than in Charleston. Applying this correction to the mpef indices in the matched pair analysis yielded a mean ratio of exposure intensities of 12-0, a figure close to the 12-4 ratio for tremolite. Similar correction of the mpef index in the stratification analysis brought the value from 6-7 to 16-8 also fairly close to 23-0, the ratio for tremolite. In the matched pair analysis, the mean mpef ratio and the mean chrysotile ratios were similar. This implies that the midget impinger measurements adequately reflected exposure to chrysotile in both industries. Overall, the findings imply that exposures to asbestos were substantially higher in Thetford than in Charleston and even suggest that the impinger measurements adequately reflected exposure to both chrysotile and tremolite, provided that a 2 5 correction factor is applied to the latter. This conclusion is in .ip'mPLac h>r exp hue the'1 lev * ecu the 1 ` fact pra ma cor. pre Rei Pm 60.; Rei i 1 t 13 1I .1 4 5 46 e 4 ) HWBU10006916 Parley led g n1? * nee of nown. n was lesion g that iction lative >estos that lung i and 11s of i the even ined. mean 124 ve no n of ssion le in :>ioylions jn of last ons bres by that mes ton. the sure for the T! to alio Phis :nts Joth -ires nan .ger oth 4 ion in Respiratory cancer in chrysolite textile aiul mining industries xposure inferences from lung analysis 187 agreement with the fact that conversion factors (fee mpef) worked out by Dement el af and bv Gibbs and Lachance.' were similar in the two industries. The hypothesis of a systematic underestimation of exposures to asbestos in Charleston, which would have accounted for the difference in risk, must therefore be rejected and other explanations sought. The possible presence of co-carcinogens at the textile plant deserves consideration. During a 20 to 30 year period (1925-54), mineral oil was sprayed on to the asbestos stock to reduce dust concentrations and facilitate the process. Apparently, this was a common practice in the asbestos textile industry.'* Mineral oil may itself be carcinogenic'" and. in addition, it could conceivably enhance the action of cigarette smoke. At present, we see no way of testing this hypothesis. Requests for reprints to: Dr P Sebastien, Groupe Pneumopathies Professionnelles, GERCHAR. BP2. 60550 Verneuil en Halatte, France. References 1 Aver HE. Lynch JR. Fanne> JH. A comparison of impsnger and membrane filter techniques for evaluating air samples in asbestos plants. Ann V) AcadSci 1965:132:274-87. 2 McDonald JC. McDonald AD Epidemiology of asbestos-related lung cancer. In: Animann K. Hisner J. eds. Asbestos-related malignancy. Orlando, Florida: Grove & Stratton Inc. 1986: 57-79 3 McDonald JC. Liddell FDK, Gibbs GW. Eyssen GE. McDonald AD. Dust exposure and mortality mchrysotile mining 1910-75. BrJJnd Med 1980:37:11-24. 4 Liddell FDK. Thomas DC. Gibbs GW. McDonald JC. Fibre exposure and mortality from pneumoconiosis, respiratory and abdominal malignancies in chrysonic production in Quebec.. 1926-75. Ann Acad Med Singapore I984;l3(suppl):340--4. 5 McDonald AD. Fry JS. Woolley .AJ. McDonald JC. Dust exposure and mortality in an American chrysoule textile plant. 8r J ind Med 1983;40:361-7. 6 Dement JM. Hams Jr RL. Symons MJ. Shy CM. Estimates of dose-response for respiratory cancer among chrysotilc asbestos textile workers. Ann Occup / Ac \982:26 869--8" Dement JM. Harris Jr RL. Symons MJ. Shy CM. Exposure:* and mortality among chrysoule asbestos workers. Pan I: Exposure estimates. Am J Ind Med 1983:4:394-419. 8 Dement JM. Harns Jr RL. Symons MJ. Shy CM. Exposures and mortality among chrvsonlc asbestos workers. Pan II: Mor tality. Am J Ind Med 1983:4:421-33. 9 Nicholson WJ. SeiikoffU. Seidman H. et a!. Long term mortality experience in chrysoule miners and millers in Thetford Mines. Quebec. Ann \Y Acad Sci 1979;330:11-21. 10 McDonald AD. Fry JS. Woolley AJ. McDonald JC. Dust exposure and mortality in an American factory using chrysotilc, amosite. and croeidoliie in mainlv textile manufacture. Br J Ind Med 1983:40:368-74. I! Peto J. Doll R. Hermon C. Binns N. Clayton R. Goffe T. Relationship of mortality to measures of environmental asbes tos pollution in an asbestos textile factory. Ann Occup Hvg 1985:2*305-55. 12 Chat field EJ. Short mineral fibres in airborne dust. In: Proceedings of a symposium on short and thin mineral fibres. Identification, exposure and health effects. Solna: National Board of Occupational Safety and Health Research Department. 1983:9-81. 13 Sebastien P. Gaudichet A. Billon-Gaiiand MA. Janson X. Spcctrometrie X par dispersion d energie en microscopic electron* ique a transmission: application i la caractensation des fibres mineraies. Journal de Microscopie et de Spectroscopic Electronique 1980:5:83-97. 14 Sebastien P Measuring asbestos dust in the environment. In: Proceeding of a symposium on asbestos, its health risks, analysis, regulation and control. Pittsburgh: A PCA 1987:97-108. 15 Sebastien P. Plourde M. Robb R. Ross M. Ambiant air asbestos survey in Quebec mining towns. Part 2. Main study. Environment Canada. Ottawa 1986. (Report No: EPS, AP RQ-2E.) 1986. 16 Sebastien P. Begin R, Case BW, McDonaidd JC. Inhalation of chrysoule dust. In: Wagner JC. ed. Accomplishments in oncology. Philadelphia: JB Lippincott. 1986:19-29. 17 Gibbs GW. Lachance M. Dust exposure in the chrysotile asbestos mines and mills of Quebec. Arch Environ Health 1972:24: 189-97. 18 Laires A. Borba H. Rueff J, Golmes MI. Halpern M. Urinary mutagenicity in occupational exposure to mineral oils and iron oxide particles. Carcinogenesis 1982:3:1077-9. 19 International Agency for Research on Cancer. Monographs on the evaluation of the carcinogenic risk of chemicals to humans. Polynuclear aromatic compounds. Part 2. Carbon blacks, mineral oils and some nitroarenes. Lyon: IARC. 1984. HWBUI0006917