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WdSS;Z `SI MBS 3H11 (13AI303H AmBritain Jounut ot EpfdnaWogy Copyright 02001 ty ha Johns Hopkins Unhftity Bkxxtibtog School of Pubic HMhti All right* ruwnwd VW.184, No AfcfodhUS Cancer Mortality among Workers Exposed to Amphibole-free Chrysotile Asbestos Eiji Vano,' ZhtMng Wang,*1 2Xiao-Rong Wang,1*3 Mtan-Zheng Wang,* and Ya-Jia lan* . SA-501 The Issue of whether exposure to chiyeotltoasbestos alone, without contamination from amphiboie asbestos, causes Umg cancer and mesothelioma was Investigated in a 25-year longitudinal study (1972-1996) in Chongqln, China. The study cohort comprised 515 mala asbestos plant workers exposed to chrysotile only; the control cohort included 650 non-duet-expoeed workers. The results of analysis In which the proportional hazards model was used Indicated that mortality due to ail causes, all cancers, and king cancer was relatedto asbestos exposure; the relative risks, adjusted for age and smoHng, were 2.9, 4.3, and 6.6, respectively. Fiber concentrations in the raw material section mid the textile section of the plant were 7.6 and 4.5 fibsts/m), respectively. Because of differences between the study and control plants, the authors also compared various sections of the asbestos plant that had (Afferent levels of dust exposure.The adjusted relative risk of lung cancer was 8.1 for workers exposed to high versus low levels of asbestos. Two cases of malignant mesothelioma, one pleural and the other peritoneal, were found In the asbestos cohort These results suggest that heavy exposure to pure chrysotile asbestos atone, with negSgibte amphiboie contamination, can cause lung cancer and malignant mesothelioma in exposed workers. Am J Epftfomk)/200V,154:538-43. asbestos; longitudinal studies; lung neoplasms; mescthottoma; occupational exposure; smoking I Asbestos is a commercial group of natural mineral fibers that mainly comprises chrysotile and the amphiboie sub group of asbestos. The Commission of the European Communities recently adopted adirective (hat obliges mem ber states to prohibit the marketing and use of chrysotile asbestos, a directive similar to that previously applied to amphiboie blue asbestos crocidollte (1). Initial reports ofdie risk of lung cancer (2) and mesothelioma (3) among asbestos workers have been confirmed in subsequent occu pational studies (4,5). In some studies, however, workers exposed to only chrysotile asbestos have shown no increased, risk of lung cancer (6~8). As a consequence, researchers have implicated not chrysotile per se but a con taminant amphiboie fiber as die specific cause of lung can cer (9) and malignant mesothelioma(10,11). Another exten sive study ofa textile plant in which only chrysotile is used found a clearly increased Incidence oflung cancer (12). The reasons for the apparent discordance in the results might be Received lorpublication April 24,2000, and accepted for publica tion April *. 2001. Abbreviations: d, confidence interra); RR, relative risk. 1 Department of Hygiene and Public Health, Teikyo University School of Medicine, Tbtyo, Japan. 2Department of Occupational Medicine, West China University of Merfica) Sciences, Chengdu, China. 3 Department ot Environmental Health. Harvard School of Public Health. Boston, MA. Reprint requests to Professor Bji 'too. Department ot Hygiene and PubSc HeaBr, TWkyo University School of Medkrine, 2-11-1 Kaga, ftaboshMor, Tokyo, Japan 173-8805 (e-maS: eyanoOmed. telkyo-uacjp). due to a number of confounding factors, for example asbestos fiber type, job type, exposure duration, smoking effect, and epidemiologic methodology (13, 14). To stud) mortality due to lung cancer and mesothelioma in workerr exposed to chrysotile alone, we undertook a prospective cohort study in an asbestos plant in Chongqln, China, con trolling for several important confounding factors. Previous dust analysis bad shown that a virtually pure form oi chrysotile asbestos was used exclusively throughout the plant. MATERIALS AND METHODS A prospective, fixed cohort was established in the asbestos plant. The plant opened in 1939 and, since 1958, has greatly expanded both in size and variety of products; 6,000 tons of raw asbestos were used in 1996. In the 1970s, the products were classified into textiles, asbestos cement products, Diction materials, rubber products, and heatresistant materials. Only chrysotile asbestos obtained from two mines in Sichuan, China, has been used in the plant The amphiboie contamination in commercial chrysotile has been assessed by N. Kohyama (National Institute for Industrial Health, Kawasaki, Japan, personal communica tion, 2000). He used the X-ray diffraction analysis and ana lytical transmission electron microscopy method, which can detect amphiboie contamination of 0.001 percent or more. Hour commercial samples, derived from the two mines in Sichuan and used exclusively in the Choogqin chrysotile asbestos plant, were shown to contain less than 0.001 per cent oftremoBte fiber. 538 to. 5 SA ~r pit, dug ady rets live <MVOtli of the the >58. cts; 70s. lent eat* mm nfle for ica11Q. c*a ttiju pet- 'El'dBS 3WU muon CtwyeotHa and Lung Cancer 539 In spite of several attempts to improve the workplace environment in die Chocgqin phot, poor ventilation and improper personnel protection were still evident, and work place smoking was not prohibited No regular measurement of airborne fiber concentration had been instituted, but res pirable dost concentration was measured every 4 years. Records showed that the general dost concentration far exceeded the Chinese national standard of 2 mg/hr\ To determine the fiber exposure of winkers, airborne dost and fiber concentrations were measured Bum personal samplers that workers wore far 3 days in June 1999. Bor eachworker, triplicate measurements were performed, and as many as five workers in each asbestos plant section were monitored. In January 1972,754 workers were actively working in tfie asbestos plant; none had any signs of serious disease. Of this group, all 130 females and 109 males who by that time had worked there for less than 1 yearwere excluded. Finally, 515 area woe selected for the stndy cohort and were fol lowed op fix 25 years (from January 1,1972, to December 31, 1996). None of the workers employed after January 1, 1972, was included in the cohort (15). fn the plant, workers were grouped into seven major Job categories: office, asbestos cement, textile, maintenance, raw material, rear service, and rubber (friction) plate. An electronics manufacturing plant located in the suburbs of Chongqin, comparable--except for asbestos exposure-- in lams of socioeconomic, geographic, and working condi tions, was selected as a control. The original coatrol popu lation contained 1,239 workers, none of whom had any signs of malignant tumors. After we excluded 535 females, 28 workers who had worked there less than 1 year by January 1,1972, and 26 workers who bad been exposed to workplace dost, 650 male workers were finally selected for die control cohort They were followed concomitantly with the asbestos study cohort for 25 years. The vital status of every cohort member was determined annually by using the personnel records maintained at the plant Information was recorded oo death, leave, retirement, and development of a malignant tamer. Mortality records were kept itrtfae personnel section of the plant, and causes of death were also checked in the plant and in municipal hospitals. Thejobs of most of the workers in each plant were rela tively stable during the entire follow-up period. No major job changes occurred, but 20 asbestos workers aad 33 con trol group workers left the plants before retirement. The vital status of these workers was followed up by mterriewiag their dose friends or relatives. A majority ofthe cohort members retired during the fbllow-vp period, but they con tinued to live in company housing and come to the plant every month to receive their pension. Consequently, infor mation on the vital status ofthe workers whohadretired was alsorearfily obtained. Five control workers could not be fol lowed op. Those lost-to-fbUow-up workers were criminated from the analysis (16). When the two cohorts were compared, the relative risks of death from all causes, all cancers, aad hug cancer were calculated by using the Cox proportional hazards model (17); the starting time for each worker was set as the timeof AmJEpktomfof VW. 154, No. 6,2001 initial employment. Since there were significant differences in the age distribution and smoking habits between the twe cohorts, multivariate analyses ware used to calculate the adjusted relative risks. The three dependent variables ol death from all causes, all cancers, and lung cancer wen coded dichotamousiy and were analyzed separately in the calculations. Among the three independent variables asbestos exposure and smoking were coded dichotomoiuiy considering that die number of workers who had quit smok ing during the observation period was small (thee in tbr asbestos cohort and five in die control cohort). Age at liv starting time of observation (January 1, 1972) was uset directly in the calculations. For the cases of lung cancet those confirmed by pathologic examination were analyze* separately, lb examine the different rides for the leva wodrer job categories, the relative risk of lung cancer fo each category was calculated by using dummy variables. L addition, we compared the various sections of the asbesto plant for three groups of workers exposed to high, interne dine, and low levels of asbestos fibers. All calculation were performed by using PC-SAS, version 6.12 softwar (SAS Institute, Ino, Cary, North Carolina), and the statist) cal significance level was set at p < 0.Q5, unless otberwis noted. RESULTS Ittde 1 shows the geometric mean fiber anddust concec nations in the rrayor sections ofthe asbestos plant. In select ing particular workers to wear die personal sampler for dm and fibers, we fried to choose those who had the high exposure level in each section of the plant However, ih rerolls varied widely depending on the individual woriu and the type ofoperation performed. The highest fiber cor centration was fbtmd in the raw material section, especial! in the bagging operation. The second-highest fiber cancer nation was found in the textile section, where carding, spir ning, and weaving were performed. There was an apparei discordancebetween tire concentrations ofairborne dost an fibers. TABLE 1. Concanbatfon* offlborand duatfor worfeets in rnaior section* oftt* Chongqfa, CMne, asbestos plaid, by Job category, 1SO*- Jab ertijory Aar (NbnaAul (mgs)) Dost (OW (range)) Rffprnwtarfal Rubber ptafet Ibdte Mbiitoi cvmnt^ *5(53-?.S) 126(53-684) 24(26-3.1) 4.5(0,7-17.0) 0.1 &8 (B.1-12.3) 112(143-224) 2373 (176,0-3205) 224(183-36.3) 223 * OaomaMc moon (tangW taMtama to Bw weriuts aapoted ki cat tttMiloipMNCtfoni t !* w wtibarpkto aaefen, mrteo mo angapd naHy in duty* mfc* wdlvartovs nm OM* into a pH h a ana* room vritaaa varttefer t In to aabaaba camm McSon, u> amber et wmtoca la to dus anrfranowgUwaOTte--aoWrooowwtei ^mn ngg>d b durrptr i ! witeiM i >* i itm|* ire imwiteiiiiii w Yano ei ai. _'si 'd3s--3wn mum The basic characteristics and the proportions of death from major causes for the two cohorts are shown in table 2. Cancer was the leading cause of death in both cohorts. Fifty workers in the asbestos group developed malignant tumors, and long cancer was the moat common, followed by liver cancer <11 cases). Eleven control workers developed cancer (during the follow-up period), but the proportion of lung cancer was the same as that of liver cancer. Other types of cancers found in the asbestos plant were four gastnrintesti- TABLE2. Basle characteristics arid mortality of workers In the asbestos and control cohorts In Chongqin, Chino, followed up between January 1972 and December 1996 No. oi workers Average yearafUrth /Mange age at amptoyment (yean) Avanga nacf yea of ampfcymant Avaraga no. of yaara of obcenadon Total pervoo-yaa/x at observation of iirnolw No. of tola! deaths (% of total workers) MorteBy rate (par 1,000 pecaorvyaait) A* cancer* (%q< total drafts) Lung cancer (% ot al cancars) Nonmaftgnanl taeoltatoiy Naof caaaaof nwoomaSoma Aebnko* woriws Control workers 51$ 1930 29A 24.6 3X8 11,525 77.1 645 1937 2X8 2xa 34.3 15,871 50.4 132(25.6) 42 (US) 11.4 50(37.9) 22(44) 24 11 (28.1) 3(27) 38 9 2a nal, three esophageal, two laryngeal, and one each for can cer of the brain, kidney, bile duct, penis, thymus, and adre nils. Hie two cases of mesothelioma, one pleural and the other peritoneal, constituted 1.5 percent of total mortality ii the asbestos cohort from 11,525 person-years of observa tion. The second most frequent causes of death were respi ratoxy diseases in the asbestos cohort but cardiovascuta diseases in the control cohort. According to the analysis in which the Cbx proportiona hazards model was used, after adjustment for age at stud} entry and for smoking habits, the relative risk for the asso dation between a&estos exposure and lung cancer was 6.6 Asbestos exposure also was a risk factor for all causes o: death andall cancer deaths (table 3). When only the cases o: cancer confirmed pathologically were analyzed separately the adjusted relative risk for the relation between asbesto: exposure and all cancer deaths was still significant, and thr relative risk for die association with lung cancer was 1.9. When tiierisk of hmg cancer and other causes ofdeath foi each plant section was compared with that for the contra plant, the highest adjusted relative risk for lung cancer wai associated with the raw material section (relative risl (RR) 17.6,95 percent confidence interval (Cl): 4.5, 69.3.' followed by the textile section (RR = 9.8, 95 percent Cl 2.1,44.4). The relative risk for the maintenance section wat also elevated significantly (RR = 7.3, 95 percent Cl: 1.6 33.5). Despite the fact that the asbestos cement section anc the rubber plate section bad Ugh concentrations of dust, tin relative risks for Jung cancer were not significant (RR = 2.5,95 percent Cl: 0.4,15.5 and RR == 53,95 percent Cl 03, 51.2, respectively). There were no lung cancer cases among the office workers. TABLES. Adjusted relative rtek and 95% confidence interval* of death from all causes, all cancers, and lung cancer tn relation to age atatudy entry (1972). smoking, and wnptoymwit tn Uu Chongqln, China, asbaatoa plant Cauae of death and factor Arfustod RRM Al cases 9554 Ct* Fathotogicaly conflmud caaesf Adjusted RHg esxa _ AH causes - Agaf Srooldng Asbestos plant employment 1.06 0.97 237 1j04, 1.03 0-70,134 200,4.12 AO cancers Agel Smoking Asbestos ptant employment 1.05 1.89 429 1.02,1.08 0.93,3.67 2.17,8.46 0.94 1.95 3.33 0.91.0.98 0.80,4.77 1.39,7.96 Lung cancer Agl Smoking Asbestos plant emptoyment 1.07 3.03 634 1.02,1.12 0.90,10.2 1.92,23.0 CL92 4.B5 t.94 0.06,0.99 0.62,382 0.48,7.79 * Analyzed by using the Coot proportional hazante model. " t For the all cancers and lung cancercases, these whose disease was confirmed pathologically wsro analyzed separately. , 4 RR, rsfaVva risk; Cl, confidence interval 5 Adjusted RR obtained from muttfrartate analysis by using the Cox proportional hazards model. 1 Age at the lime of enfcy Into the cohort (1972) was used as a continuous variable in the calculation; smoking and asbestos exposure were cflchonmoua variables. Am J Epkiemtof Vol. 154, No. 6.2001 Mtt'l *l 'd3S 3WU 03M303H Chrysotile and Lung Cancer 541 The pleural mesothelioma case worked in die raw mate rial section and the peritoneal mesothelioma case in the textile section; both cases of disease were confirmed by pathologic examination. For the pleural case, the duration between first exposure and death was 13.8 years, while h was 21.8 years for the peritoneal case. Because of the possibility of uncontrolled differences between the two cohorts, a comparison was made within the asbestos cohort of groups for three levels of asbestos expo sure. Workers in the raw material and textile sections were always exposed to high levels of asbestos in poorly venti lated rooms. In contrast, the asbestos cement section was well ventilated. Office workers in die administration section were also included in the less-exposed group. Workers in the other sections with widely varying levels of asbestos were included in the intermediately exposed group. As the results indicate, although age and smoking prevalence were similar among die three groups, the incidence of lung cancer was much higher in the group exposed to high levels of asbestos (RR = 8.1) followed by the group exposed to intermediate levels (RR -- 3.6) (table 4), When we restricted the analysis to lung cancer confirmed pathologically, the age- and smok ing-adjusted relative risk comparing the groups exposed to high versus low levels of asbestos was 1.1 (95 percent Cl: Q.9.1.4); however; only a small number of cases had been finned pathologically (five in the high exposed group vs. ,,u in the low exposed group). Using the Cox model, we evaluated the interaction of smoking and of asbestos exposure with the occurrence of lung cancer. The results indicated that the relative risks of lung cancerby smoking, asbestos exposure, and both asbestos and smoking exposure, after adjustment for age, were 1.5, 3.4, and 12.6, respectively. Only the last one was significant (p " 0.014), suggesting the existence of an interaction between asbestos exposure and smoking, as has been noted previously (18). DISCUSSION For nearly a decade, die so-called amphibole hypothesis has generated an often-heated debate among scientists researching the hazards ofasbestos (19,20). The hypothesis postulates that chiysotile is far less carcinogenic than the amphibole* and featcases of mesothelioma observed among workers exposed to chrysotile can be explained by con founding exposure to contaminating amphibole asbestos. Fiber-type analysis ofthe lung tissue ofmesothelioma cases initiated fee hypothesis justifying the use of chrysotile but not amphiboles for industrial purposes (11, 21), and this view was further supported by epidemiologic studies of the mortality of chrysotile miners in Quebec, Canada <22,23). In these studies, contaminated tremoiite in chrysotile ore was suspected as fee primary pathogenic agent. However, a comparison with evidence obtained from a textile plant in Charleston, South Carolina, and from Quebec miners and millers felted to support the predicted higher incidence of lung cancer, caused by tremofite contamination, in the min ers and millers (24). likewise, the findings of the preceding studies on chrysotile-related lung cancer showed wide vari ability, with an associated risk negative to nearly equal feat for amphibole asbestos. However, such discordance is to be expected in the absence ofuniform and consistent protocols of epidemiologic study and because of the varying compo sition of different fiber types. Therefore, a study of workers TABLE i RHv* risk at lung carom; all cancers, and other cause* of daath among group* of wcrfcsre exposed to low, Intarmadtate, and high levels of asbestos In the Chongqln, China, asbestos plant between 1972 end 1098* Nad workers Age at employment (years) (mean (SDt)) No. of years ol employment (moan (SO)) Na of years of observation (mean ($0)) Na d smokers (%) Laval of mpoaure: asbestos plant secVon Low: office. asbestos cement imemwdMs: maintenance, rear service, rubber Plata High.raw material, textile 162 203 150 30.1 (7.6) 28.4(8.4) 30.1 (8.7) 24.4 (6.8) 25.5 (8.1) 23,5(6.6) 34.7 (7.2) 33.6 (7.7) 33.2 (7.7) 133 (821) 149(73A) 115(76.7) Total deaths (no. (%)) HR* (95% Cl) 39(24.1) 1.0 41 (20.2} 1.0 (0.7.1.8) 52(34.7) 1.5 (1-0,2.3) AH cancers (na {%)) Rfl*(95%CI) 13(8.0) 1.0 15(7.4) 1.2 (as. 25) 22(14.7) 2.1 (1.1,4.1) Lung cancer (na (%)) RR* (95% Cl) 2(1-2) 1.0 7(24) 3.6 (0.7,17.5) 13 (8.7) 8.1 {1.B, 36.1) * Data analyzed by using me Cox proportional hazards model, t SD. standard deviation. 4 Hetative risk (HR) and 95% confidence interval (Cl): age- and smoking-adjusted relative risk d workers amosad to high levels in the raw material and loctfa sections compared with workers exposed to low levels in the office and asbestos cement escVons. Am J Epidemiol Vol. 154, No. 6, 2001 542 Vtino et al. WISH *l *d3S 3WI1 Q3AI303H exposed specifically to an extremely pure Form of chrysotile might be expected to provide stronger evidence for the car cinogenic potency of chrysotile asbestos per sc. In our study, subjects were exposed to only amphibole-free chrysotile, and amphibole asbestos has never been used in the Choogqin plant. A well-recognized characteristic of asbestos-related lung cancer is its synergism with smoking (25). In our study cohorts, we confirmed the interaction of smoking and asbestos exposure with occurrence of lung cancer. We also found that the relative risk of lung cancer for smokers with out exposure to asbestos did not increase significantly. It has been recognized that; for smokers in China, the relative risk of developing lung cancer is lower than that reported in western countries. In a review of several cohort studies of male workers in China, die relative risk of lung cancer was found to vary between 2 and 4 (26-28). As the results indicate, we found no evidence in support of (he amphibole contaminant hypothesis. To the contrary, a strong potential for chrysotile asbestos alone to cause lung cancer and mesothelioma was suggested. In our study, several potential sources of bias could have ted to an overestimation of the effect of chrysotile exposure on lung cancer Fiber concentrations were measured for the first time by following an internationally approved proce dure (NIOSH procedure 7400; National Institute for Occupational Safety and Health, Cincinnati, Ohio). Nonetheless, fiber concentrations were probably much higher in the past because of poor industrial hygiene, thus introducing die possibility of overestimation of die effect In the past, workers also took asbestos home, extending their exposure. The diagnostic and record-keeping procedures in the study and control plants were similar. However, only a small proportion of malignant tumors were confirmed pathologically, which could have caused misclassificalion. Nevertheless, separate pathology-based analyses essentially confirmed our major findings, although die risk estimates woe reduced. Selection bias might have been introduced by excluding the five workers lost to follow-up. If all of these workers developed lung cancer after they left the control plant, lung cqpcer mortality in the control cohort would be markedly underestimated, which would also lead to an over estimation of the effect ofasbestos exposure. The likelihood that all five workers had lung cancer is small, because their actual reasons for leaving the plant were not related to any health problems. As for confounding bias, the average age and the preva lence of smoking were higher in the asbestos cohort, which required statistical adjustment Since there may have been unrecognized differences between die workers in the asbestos plant and those in the control plant, a comparison within the asbestos-exposed cohort was made. The relative risk of lung cancer we obtained from this comparison was even larger than die one from die original comparison. This finding suggests that the association between asbestos and lung cancer was not due to confounding by differences between the two cohorts. On the other hand, our measure of smoking was dichotomous, and, given the strong link between smoking and long cancer; it is possible that smok ing differences were not well controlled in either of the two cohorts or within cohort comparisons. With regard to mesothelioma, Stayner et aL (29) reviewed cohort studies of workers exposed to predominantly chrysotile asbestos and demonstrated that die overall propor tional mortality of mesotheliomawas 03 percent; in the pres ent study, mesothelioma accounted for 15 percent of the total deaths. Camus et al. detected no measurable excess risk oflung cancer amongwomen exposed to chrysotile asbestos (30) but, in the same study, found an excess risk ofmesothe lioma, with a proportional mortality of 05 percent (7 of 2542 deaths). Their estimate of average cumulative lifetime exposure to asbestos was 25 fiber-yeais/ml, far below the level determined in our study. It is generally recognized that the incidence of mesothelioma increases exponentially with follow-up time. Because the average observation time was only 33.8 years, and nearly (hree quarters of the asbestos weskers remained alive, the proportion of mesothelioma may yet increase further; In fact, in addition to the two cases we found, an asbestos worker's son developed mesothelioma only 8 years after he was employed by the asbestos plant. During bis childhood, this boy helped his family for several years by weaving asbestos by hand after school. However, because he was employed after die cohort started, this worker was not included in our study. A total of 139 workers with ashestosis were found in the asbestos cohort during the entire follow-up period. However, because 1/0 in the BLO classification (31) is not diagnosed as pneumoconiosis according to the Chinese stan dard, the total may be an underestimate. The proportional mortality of nonroalignant respiratory diseases, which include asbestosis, was also increased, but not significantly so, in the asbestos workers (29 vs. 21 percent). In conclusion, the present study demonstrates that exposure tonnermtaminated chrysotile asbestos only may be related to an increased risk of lung canoer to an extent comparable to that caused by mixed-type asbestos. In addition, it suggests that exposure to pure chrysotile can also cause mesothelioma. ACKNOWLEDGMENTS This study was supported in part by die Japan Foundation for Promotion of Sciences, the Sasakawa Foundation, and a grant-in-aid from the Ministry of Education. Science and Sports, Japan. Die authors thank Y. Konishi, manager of the Technical Research Section of the Japan Association for Working Environmental Measurement; R. Terayama for measuring the fiber concentration; andDr. N. Kohyama of the National Institute for Industrial Health for providing information about the composition of Chinese chrysotile. ' REFERENCES 1. Doll R. Mentality from lung cancer in asbestos workers. Br J IndMed 1955;12:81-6. Am J Epidemiol Vol. 154, No. 6,2001 Xl'dBS 3HU Q3AI3038 Chrysotile and Lung Cancer 543 L ^hmtan WD. Asbestosis and primary intrathoradc neo plasms. Ann NY Acad Sd 1965:132307-18. 3. SelikoffU, Hammond EL, SerdmanH. Modality experience of insulation workers in the US and Canada. Ann N Y Acad Sci 197933031-116. 1, Po J, Doll R, Herman C. et al. Relationship ofmortality to measures of environmental asbestos pollution in an asbestos textile factory. Ann Occup Hyg 198539:305-55. 5. McDonald AD, McDonald JC. Epidemiology ofasbestos-telaJed lung cancer. In: Antman K, Anister J, eds. Asbestos-related malignancy. Orlando, FL: Grunc & Stratton, 1987:57-79. 5. McDonald AD, Fry JS, Woolley FJr et al. Dust expoauie and mortality in an American chrysotile friction products plant. Br JIndMed 1984;41:151-7. 7. Morgan RW. Attitudes about asbestos and lung cancer. Am 1 Ind Med 1992;22:437-41. 3. Newhouse ML, Sullivan KR. A mortality study of workers manufacturing friction materials 1941-1986. Br J Ind Med 1989;46:176-9. 7. Hughes JM. Epidemiology of lung cancer in relation to asbestos exposure. In: Liddle D, Miller K, eds. Mioeral fibers and health. Boston, MA: CRC Ress, 1991:135-45. 3. Churg A, Wiggs B, Depaoli L, et aL Lung asbestos content in chrysotile workers with mesothelioma. Am Rev Respir Dis 1984;130:1042-5. 1. McDonald JC, Armstrong B, Case B, et al. Mesothelioma and asbestos fiber type. Evidence from lung tissue analyses. Cancer 1989:63:1544-7. 2. Dement JM, Harris RL Jr, Symons MJ, et al. Exposures and mortality among chrysotile asbestos workers. Fait II: mortal ity. Ami Ind Med 1983;4:421-33. 3. Neuberger M, Ktudi M. Individual asbestos exposure, smok- and mortality. Br J Ind Med 1990;47:615-20. f uskooen MS, Karjalainen A, Tbssavaiocn A, et al. Asbestos -ad cancer in Finland. Med Lav 1995;86:426-34. S. Checkoway H, Pearce N. Crawford-Brown DJ. Research methods in occupational epidemiology. New York, NY: Oxford University Press, 1989:103-10 6. UddellFDK, Hanley JA. Relations between asbestos exposure and lung cancer SMRs in occupational cohort studies. Br J bid Med 1985:42*389-96. 17. Klembaum DG. Survival analysis. New York, NY: SpringerVeriag, 1997:83-128. 18. Berry G, Newhouse ML, Antonis P Combinedeffect ofasbestos and smoking on mortality from lung cancerand mesothelioma in factory workers. Br J Ind Med 1985;42:12-18. 19. Mossman BT, Bignon J, Com M. et aL Asbestos: scientific developments and implications for public policy. Science 1990;247:294-301. 20. Landiigin PJ. The third wave of asbestos disease: exposure to asbestos in place. Public health control. Introduction. Ann N Y Acad Sci I991;643:xv-xvi. 21. McDonald JC, McDonald AD. The epidemiology of mesothe lioma in historical context. Eur Respir J 1996;9:1932-42. 22. McDonald AD, Case BW, Churg A, et al. Mesothelioma in Quebec chrysotile miners and millers: epidemiology and aeti ology. Ann Occup Hyg 1997;41:707-19. 23. Liddell FD, McDonald AD, McDonald JC. Dustexposure and lung cancer in Quebec chrysotile tubers and millers. Ann Occup Hyg 1998;42:7-20. 24. Scbistiea P, McDonald JC, McDonald AD, et al. Respiratory cancer in chrysotile textile and mining industries: exposure inference* from lung analysis. Br J Ind Med 1989;46:180-7. 25. Brown K. Asbestos related disorders. In: Parfces WR, ed. Occupational tang disorders, 3rd ed. Oxford, United Kingdom: Butterworth-Heineznanfl, 1994:479-84. 26. HouyuanY. A study a risk factors oflung cancer in rural area. Chin J Prcv Med 19963:65-70. 27. Zban H, Wang Z. Study of occupational long cancer In asbestos factory in China. Br J bid Med. 19930:1039-42. 28. Wwig Z, Wang M. Mortality of ooal mined' cohort study. Acte Acad Med Sichuan 1984;15:142-5. 29. Stayner LT, DanJcovic DA, Lemen RA. Occi^ational exposure to chrysotile asbestos and cancer risk: a review of the arnphibole hypothesis. Am J Public Health 1996;86:179-86. 30. Camus M, Siemiatycki J, Meek B. Non-occupational exposure to chrysotile asbestos and the risk of lung cancer. N Engl J Med 1998338:156S~71. 31. Guidelines for the use of R-0 international classification of radiographs of pneumoconioses. Rev ed. Geneva, Switzerland: Internationa] Labour Office. 1980. (Occupational Safety and Health series 22). r 4m J EpfdewSo! Vol. 154, No,6,2001