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Cancer Mortality of a Group of Canadian Workers Exposed to Vinyl Chloride Monomer RECEIVED AUG 25 1981 J. T. BARR SrS'.' C. Theriault, M.D, DrJ.H., and P. Allard, M.D,, MSc. The present study was undertaken to find out whether there was an excess of cancer mortality from cauies other than angiosarcoma of the liver among a group of workers heavily exposed to vinyl chloride monomer (VCM) The mortality of 451 workers exposed to VCM for more than five years was compared with that of 870 workers from the same company who had not been exposed to VCM. The relative risk for digestive cancer was significantly higher than 1 (6.25, confidence interval 2.69 to 14.52) in the ex posed group. The standardized mortality ratio (SMR) for digestive cancer was also higher (SMR 259.26 p < 0.01} than that of thegeneralpopulation. No other cancer was in excess. Since the exposed workers are kndwn to have hada cigarette smoking experience similar to that of those who were not exposed, it is concluded that the association be tween lung cancer and VCM exposure, if present is indeed rStnerjina.4 Several studies have demonstrated that vinyl chloride monomer (VCM) produces angiosarcoma of the liver among people exposed at work.1*' There is, however, much controversy about the capability of VCM to gener ate other types of cancer in man. One author,* using a proportional mortality ratio technique, described ex cesses of lung cancer (observed. 13; expected, 7.9; obs/exp 1.6) and brain cancer (observed, 5; expected, 1.2; obs/exp -4.2) in a group of 161 workers from two vinyl chloride plants.1 Another author.* who studied the mortality of a group of 1,294 American workers exposed to VCM, re ported excesses of lung cancer (observed. 11 expected, 7.5; SMR 194, p < 0.05) and brain cancer (observed, 3; ex pected, 0.6; SMR 498, p < 0.05) among men who had had From th Department of Social and Preventive Medicine School of Medicine, Laval Uravenhy. Sie-Foy. Quebec. Canada. C1X 7F4. This research was financed partly under Grant No. 760396 from the Conseii de la Recherche ert Sam* du Quebec. their first exposure more than 15 years before their death. While most authors have not been able to document a . significant excess of any other cancer in their studies, they have noted that such an excess may exist in order to better document the cancer mortality asso ciated with exposure to VCM. the present study of the workers of the Shawinigan vinyl chloride polymerization plant was undertaken. The main objectives of the study were (1) to compare ' mortality among vinyl chloride workers with the mortality of workers from a nearby industrial complex; and (2) to compare the mortality of the VCM workers with that of ' the general population. The Shawinigan vinyl chloride ' plant opened in 1943 as an independent company which ' produced both VCM and PVC (polyvinyl chloride) In 1958. it was merged into an industrial complex (to be used as the comparison group) of which it became the Cana dian Resins Division. In the late 1960s, the VCM produc tion ceased and only the polymerization process con tinued operation. In 1972, this division was sold and again became an independent plant Over the years, the VCM and PVC productions fluctuated. ,Jhe average annual work force at the plant was 225 men. In 1965, VCM pro duction was estimated at 90 million pounds and PVC at 60 million pounds.1' In 1977, PVC production was 22.3 million pounds." Since several episodes of unconscious ness amonu workers were reported, the level of VCM in the air at tne workplace is believed to have high during this period. Ten cases of angiosarcoma of the liver have been reported since then.' The industrial complex from which the comparison group was drawn comprises several divisions; a carbide division which produces calcium carbide and acetylene black; a chemicals division which produces several chem icals derived from acetylene-acetone, chloral, butanol, acetic acid, acetaldehyde, several acetates, solvents and resins; a stainless steel division which consisted of a small foundry and a division formed in 1957, which produced AP00003461 Fit 1. -- PepiiiatiM nrFw staty. - sulfuric acid, chlorine and cyanide. This complex started The men whose number of years of work for these i operations in 1927; some of its divisions opened at a later companies, as established through occupational histories, date; others dosed in the late 1960s or early 1970s. The did not exceed five were removed from the study. The re annual number of male workers averaged 1,000.'* maining population was then subdivided into three groups. The first group (known as the unexposed cohort) Methods consisted of men who stated they had not been involved Population Under Study. -- All production workers with the production of VCM or PVC, or both, for a period whose names appeared on tho union's lists or the com greater than five months. Tire second group (constituting panies payrolls ol the VC plant and the industrial complex the exposed cohort) comprised men who declared they between January 1,1943, and December 31,1972, consti had worked on the production of VCM-PVC~for more tuted the~population under study. Several methods (old thanrftvg years. Finally, she tnird group consisted of the addresses, telephone books, Quebec motor vehicles men whohad worked on the production of VCM-PVC for bureau, inquiries with fellow workers and families, a period of six months to five years. This group was ex searches in homes for retired persons) were used to trace cluded from analysis because it neither fulfilled the -. these men, 18% of whom were still working for the same definition of the exposed nor the unexposed cohort companies. Once identified, the worker himself or his Data Sources. -- The vital status of these men was next of kin (spouse, child or close relative) was questioned established as of December 31, 1977, Causes of death at home or at work by a trained interviewer. The ques were determined from death certificates. They were tions permitted the reconstruction of a detailed occupa coded according to the 8th revision (ICDA) by one of the tional history within and outside the companies under authors^ho was unaware at the time of the coding^to study. Questions were also asked regarding smoking f which group the man belonged. For cancer cases, a histohabits. For each deceased person believed to have been pathological confirmation was sought on autopsy, biopsy exposed to VCM, the occupational history was confirmed with the help of a fellow worker. or cytology reports contained in the medical files at the hospital. Information on Quebec's population and mor- AP00003462 Tibli 1. - Agi Distribution of thi Min in tm VCMExposed and Unixptsid Cohorts at ot Dicimbnr 31,1S77 (Dtcustd Exeludid). Ago 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-84 65-69 70-74 75 + Tottl . Expoctd No. K 0-- 0-- 1 0.3 23 7.1 75 t9.t 96 24.5 102 26.0 53 13.5 30 7.7 6 1.5 1 0.3 392 100.0 Unixpmd No. X 1 0.2 3 0.5 6 0.9 45 7.1 55 6.6 14 13.2 112 17.6 110 17.3 113 17.7 65 10.2 43 6.7 637 100.0 tality by cause, age and sex was secured from Statistics Canada for the year 1971. In order to ensure die validity of the results, only the causes of death which appeared on the death certificates were used in the comparisons. Statistical Analysis. -- The results were analyzed using the "man-years at risk" method as described by Hill." The number of person-years of observation was established for each five-year age group and for each five-year period between 1948 and 1977. The mortality in the exposed cohort was compared with that in the unexposed cohort according to the method of relative risk. The tests of significance used were those of Mantel, Haenszel'4 " and Miettinen.'*" The observed mortality was also compared with the mor tality expected from the population of the Province of Quebec according to the method of the standardized mortality ratio (SMRJ.'* The test of significance used was the one described by Bailar and Ederer." Quality Control Procedures. -- A thorough occupa tional history was developed for workers who were ex posed within the VC plant The questionnaires presented a detailed profile of the plant while specifying possible jobs within its major units. Before the beginning of the study, it was pre-tested with former employees. Interviewers who contacted the workers had received training by the same person and were supervised during the entire study. The completed questionnaires were re viewed weekly by one of the authors and missing infor mation was sought by telephone. Data entered in the computer were systematically checked against the origi nal questionnaires. Results As shown in Fig 1, the population under study originally comprised 1,659 workers. Of these, 48 men were untraceable, leaving the number in the study population at 1,611 tor 97.1 % of the original number). After the removal of trie lie men who had worked at the companies for a period not exceeding five years and the 134 men who had . been exposed to VCM for a perod extending from six months to five years, the exposed cohort comprised 451 men and the unexposed one. 870 men. In the exposed cohort, the proportion of men who responded to the : questionnaire for themselves was 84.396. In the unex posed cohort, this proportion was somewhat .lower at 68.296. The age distributions of the workers in the exposed and unexposed cohorts as of December 31,1977, reveals that workers in the unexposed cohort (Table 1) were somewhat older. Since the industrial complex had been in operation for several years when the VC plant opened, the finding of older people in the latter cohort was predictable. Table 2 shows the distribution of the exposed workers according to their length of exposure and their observa tion period (time between first employment and end of follow-up). Among these, 81 % (365 out of 451) had an ob- . servatlon period of 15 years or more. For 23% of them, the time elapsed between first exposure and the end of the follow-up period exceeded 29 years. The mean obser vation period for the exposed cohort was 22.6 years. Table 3 gives the diagnosis at death and the diagnosis after histopathological review of all the cancer cases found in the exposed group. On the death certificates, eight cancers of the liver were reported. The histopatho logical review rejected one of them as being a cancer of the sigmoidal flexure of the colon, but added another as an incorrectly diagnosed cancer of the peritoneal cavity. All eight cancers of the liver turned out to be angiosar coma of the liver. It is noted that two more angiosar comas of the liver were certified as cirrhosis on the death certificates and were considered as such throughout this study. Table 4 compares the mortality of the exposed workers with the mortality of the unexposed workers. The con fidence interval (95%) of the relative risk indicates that there is a significant excess of mortality due to cancers of the digestive system in the exposed group (RR 6.25, con fidence interval 2.69 to 14.52). There is no excess in the other causes of death. Table 5 shows the standardized mortality ratios (SMRs) for the exposed workers in comparison with the entire population of the Province of Quebec. The SMR for all causes is 83.02, thereby showing no excess of death in the exposed cohort Although the SMRs for all cancers, respi ratory system diseases and digestive system diseases ex- Tible 2. -- Oistributien if Expand Wnrkm by Lingth if Exptsuri and ObtirvitiM PirM. Exposure (Yoars) 5- 9 10-14 15-19 20-24 25-29 30+ Total Obiorvitlon ported (Yurt) 3-1 10-14 15-11 21-24 25-2! 30 + Total 30 26 7 40 2 4 111 -- 26 26 19 17 5 95 -- -- 17 35 11 3 79 -- -- -- 22 24 15 61 -- -- * -- -- 34 33 67 -- -- -- -- -- 33 36 30 56 50 116 96 103 451 AP00003463 Table 3. - Age at Death, Diagnosis an Death Certificate and Diagnosis on Histological Review ol the . 20 VCM-Exptsid Werittn Who Wed ei Cancer. _______ Casa , Number Baatb Certificate 1 Cancar oi th^rer Z 3 4 5- e' 7 3 9 10 11 12 13 H IS 16 17 13 19 20 Cancar of On Intutina CarchMni of the trachea Angiosarcoma of tlw peritoneal cavity Clncar of the lung Cencer of the liver Cancer of the liver Cencer M the prostate Angiosarcoma ol the liver Cancer of the pancreas Adenosarcoma of the Intestine Hepatoma Canetr ol the liver Cancar of the pancreas Chondrosarcoma Hspatoma Primary cancar of the liver Cencer of the digestive track Cancar el the biliary ducts Lymphoid leukemia HisWeeleaf Rtvisw Cancar at tha sigmoid flexure oi the colon Metastatic cancorcl the cote Carcinoma of the trachea Angiosarcoma ol the liver (no review) Angiosarcoma of the Over Angiosarcoma ol the liver Cancer of tha prostata Angiosarcoma at the Hvtr Epithelioma ol the head of the pancreas Adanosarcoma of the intestine Angiosarcoma of the liver Angiosarcoma el me liver Anaplastic epithelioma ol the pancreas Chondrosarcoma Angiosarcoma of the liver Angiosarcoma of the liver Cancar of the esewn Cancer ol tha head of the pancreas Lymphoid leukemia Agaet Death (Tears) 73 S3 SO 41 54 42 57 64 32 ' 40 53 S3 S3 59 43 43 53 52 54 43 Telal Expssure (Tsars) IS 16 IS 11 16 19 17 26 18 8 2S 24 22 29 7 22 5 26 12 21 Latsncy Period (Tears) 23 17 IS 11 * 16 19 23 29 23 13 28 24 23 30 10 22 12 26 12 21 ceed 100, they are not statistically significant On the other hand, deaths by accident and violence are significantly lower (p < 0.01). As for specific cancer deaths, a significant excess is noted for cancer of the digestive system only. This excess is accounted for exclusively by cancer oi the liver ta cases observed versus 0.14 expected. Smk 5,714.29)7No other cancers are in excess. The cancer mortality among the workers who were still alive 15 years after their first exposure shows the same . results as the mortality in the entire group, namely that only cancers of the digestive system are in excess in the exposed cohort (Table 6). Discussion Difficulties encountered in comparing the mortality of ! a group of workers with the mortality of a whole popula tion are well documented. They are termed: "healthy population selection effect." "survivor population effect"1* "ethnic/cultural/sodal characteristics." They are believed to underestimate the actual mortality of a group of workers and therefore to underscore the effects of thu risks to which these Individuals are being exposed at work. There are no easy ways to avoid such difficulties. One method would be to compare a group of workers with another group of workers with the same characteris tics except for the exposure to thu risk under study. The problems encountered in so doing are no easier. Although the group most similar to industrial workers is probably another group of industrial workers from the same town, it is almost impossible to think of a group of industrial r Tibia 4. -- Deaths Observed in the VCM-Expesed and Unexpessd Caherts, Age-Adjestsd Relative Risks and Confidence Intervals of the HeMra Risk. ! Cause el Death All cancers Mouth and pharynx (140-209) (140-149) Digestive (150-159) Respiratory (160-163) Bone, skin, connective (170-173) Urogenital (135-189) Eye. CNS Leukemia (190-192) (200-209) Other cancers Cardiovascular Respiratory (390-458) (460-519) Digestive (520*577) Accidents and violsnce (800-399) Others Total `Significant according to Miettintn's last" tOna causa unknown He. sf Cases Exposed Uaexpmd 20 52 02 14 9 2 20 22 17 02 14 06 25 124 S IS 4 12 2 . 15 2t 15 59 233 ttstsNve msk 1.44 -- 6.25 0.31 1.67 0.63 -- . 1.15 ~ 0.80 0.31 1.44 0.51 0.57 1.07 UK CaetMsaee Intersil ei the IlltaUve Risk 0.34- 2.61 -- 2.69-14.52* 0.03- 1.53 0.21-12.99 0.10- 7.10 -- 0.07-17.30 0.47- 1.36 0.44- 9.35 0.49- 4.25 0.21- 1.24 0.14. 2.39 0.79- 1.45 AP00003464 Table 5. - Obsorvod and Expected* Numbers of Deaths in the VCM-Expossd Cohort and Standsrdtzid Mortality Ratiee (SMRt). Ciusi af Oaalli AD cancers Mouth and pharynx Digaativa Respiratory Bona, skin, connective Urogenital Eyo, CNS , Leukemia Other cancers Cardiovascular Respiratory Oigeslivo Accidents and violence Others Total (140-209) (140-149) (150-159) (160-163) (170-173) (185-189) (190-192) (200-209) (390-458) (460-519) (5P0-577) (800-999) Observed 20 0. 14 2 2 1 0 1 0 25 ------- *- 4. 2 2t 59 Expected 16.37 0.64 5.40 5.78 Oil 1.33 0.60 1.87 0.54 31.67 3.21 3.85 , 10.58 5.40 71.07 SMR 122.17 -- 259.261 34.60 526.32 75.19 -- 59.88 -- 78.94 186.91 _ 103.90 18.90* 37.03 83.02* Expected numbers obtained tram 1971 males Quebec death rates applied to person-years In each age group tp<O.Ol' tone cause unknown workers not exposed to some kind of carcinogenic risks. In the present study, the authors decided to compare the cxi>osed workers with both the general population and a group of unexposed workers. It must be noted that among the unexposed workers, no causes of death were found to be in excess when their mortality was compared with that of the general population. The comparison of the mortality of'the exposed and the unexposed workers gave results similar to the one reached by the comparison with the general population. The number of cancer of the digestive system was signifi cantly higher in the exposed cohort No other cancer was in excess and there even seemed to be a deficit (not statis tically significant) in respiratory cancers. Considering the fact that animals experimentally ex- posed to VCM Have developed not only angiosarcomas of the liver but also malignant tumors of several organs (skin, lung, bone, Zimbal glands, kidneys, mammary glands}1*1121 and since several epidemiological studies on VCM-exposed workers have found an excess of lung cancer,14 the results of this study of heavily exposed men are surprising. Three questions can be raised. One concerriS the ascertainment of the population. In retrospec tive studies conducted from old company or union rec ords it sometimes happens that records of people who die or leave get lost These losses could account for the low cancer rates observed. But this is a remote possibility, since the approach followed was a historical-prospective retrospective one, which began with old lists of workers composed in 1948 and 1952 and fallowed almost every one through time, adding new workers as they first ap peared on more recent lists. This was done without knowl edge of exposure to VCM. A second reason for low lung cancer rates could be a > bias in the classification of persons as exposed or not ex-1 posed. The classification was made essentially on the basis of personal recollection for living persons and by family members with confirmation by co-workers for deceased persons. To minimize such bias, much attention had been given to the occupational history (with indica tion of the buildings the subject had worked in) and workers with VCM exposure shorter than five years were rejected. There remains the possibility that some of the men who died of liver cancer, had they lived longer, might have developed lung cancer. The small size of the population under study increased the probability of not detecting an excess that was actual ly present This was a case where "the number of person/ years at risk may be too small to detect an increased risk of cancer.21 It was particularly true for rare cancers such as cancer of the brain and cancer of the lymphatic system. Inasmuch as cancer of the lung was concerned, Y jJb Table 1. -- Relative Rieka and SMRs tar Cancer Deaths Anting Mae Having an Observation Perjed at 15 Years and Mart. Cincara Ail cancers Mouth and pharynx Digestiva Respiratory Bone, skin, connectivt Urogenital Eye. CHS Leukemia Other cancers p<0.0l* (140-209) (140-149) (150-159) (160-163) (170-173) (185-189) (190-192) (200-209) AetsUva He. Risk 15 1.30 0-- 11 5.68 2 0.35 0-- 1 0.82 0-- 1 0.59 0-- MS Confidence interval el ike Relative Riek 0.97- 1.74 2.72-11.58 0.25- 4.73 -- w -- SMR 129 -- 281* 47 _ -- -- AP00003465 \Sa) the situation was somewhat different. When one applies 7. Delorme f and Thdriault G Ten cases o< angiosarcoma ol the the Quebec lung cancer death rate after adjustment for livut in Sliuwimg.n, Quubwc. / Occup Mud 2U.JitS-.M0,1978. age to the exposed cohort the probability of finding an excess twice as high as in Quebec was 73%. This proba* 8. Morion R, Peters J. and Johnson M: Proportional morality among vinyl chloride workers. Lancet Z397-398.1974. 9. Waaweiler IK, Stringer W, and Wagner ||: Neoplastic risk among .laility would have been had the excess been three *1 2 w3o4rk5ers exposed to vinyl chloride. Arm NY Acad Sci 270:40-48.1974. . times as great in the exposed group.11 --, In view of the fact that the smoking experience of the , exposed workers was similaTto that ot the unexposed and : 1 considering that the subjects in this study are believed to J have been heavily exposed to VCM. it seems reasonable to conclude that the excess of lung cancer associated with VCM exposure. If present, is indeed rather small. 10. Special Report by the Editors: PVC aims tor a bigger share in - plastics. Can Chem Process l!5S!. in.-- 11. Coraeil das Sciences du Canada: Vue d'ensemble des dangers 1 de la conumlnation par ie chlorure de vinyle au Canada. Quebec: Science fSuppJJ ft-24.1977. 12. LaRochelle F: Shawinigan depuis 75 ans. Ateliers de I'imprimerie Publicity Piquet Enr.. 1976. pp 497-525. *- 13. Hill ID: Computing man yean at risk. Brl Prev Med 24:132-134. *19fl.------- --------- 14. Mantel N and Haenszal W: Statistical aspects of tha analysis of I The authors wish to espies* their gratitude, to the following who contributed to thh study* workers, union representatiuei and management fwoonne! of the comoanto Canadian Resets and Oinnicah-- Shawmiean Chemicals. B.f. <iAodrch JncTtttrClWM'WTIT^WWl'IlrfWl. Fabia. epidemiologists. and Dr. f. Delorme, pathologist, for thek heip awtrovice; the several hospitals com tacted; and the several persons who assisted with the collection of information and the writing of this article. data from retrospective studies of disease. / Natl Cancer Inst 22:710-748/1959. 15. Mantel N: Evaluation of survival daU and two rank order satis fies arising in its consideration. Cancer Chemcthet Hep 50:163-170. 1966. 16 Miettinan OS: SUndardiiation of risk ratios. Am / Epidemiol 96:383-388.1972. 17. Miettincn OS: Simple interval-estimation of risk ratio. Am / References Epidemiol 100:515-516,1974. 18. Caffey WR: A critique of the sundardized morality ratio. I Oc 1. Creech JL Jr end Johnson MN: Angiosarcoma of liver in the man- ' cup Med 3:157-160.1976. ufacture of polyvinyl chloride. / Occup Med 14:150-151,1974. 2. Tabershaw IR and Caffev WR: Mortality study of workers in the 19. Bailar )C and Ederer F: Significance factors for the ratio of a Poisson variable to its expectation. Biometrics _ manufacture of vinyl chloride and Its polymers. / Occup Med . 20. Foe A| and Collier PF: Low morality rat& in industrial cohort 14:509-518,1974. studies due to selection for work and survival in the industry. Br / Prev 3. Nicholson W|. Hammond EC Seidman H, et al: Mortality esperi- - Soe Med 30:225-230,1976. ence of a cohort of vinyl chloride polyvinyl workers. Ann NY Acad Sci 21. Viola PL: Cancerogenic Effect of Vinyl Chloride, Vol. 29, X Inter 246:225-230,1975. national Cancer Congress, Houston, 1970. 4. Duck BW. Carter IT. and Coombes E|: Morality study of workers in s polyvinyl-chloride production plant Lancet 2:1197-1199,1975. 5. Byren D, Engholm C, Englund A, and Westerholm P: Mortality 22. Viola PL, Bigotti A and Caputo A: Oncogenic response of rat skin, lungs and bones to vinyl chloride. Cencer Res 31:516-519.1971. 23. Maltoni C and Lefemine C: Cancerogenicity bio assays ot vinyl and cancer morbidity in a group of Swedish VCM and PVC production workers. Environ Health Perspect 17:167-170,1976. C. fox AJ and Collier PF. Mortality experience of workers exposed to chloride: Current results. Ann NY Acad Sci 246:195-216,1975. 24. Wagoner IK: Vinyl chloride and pulmonary cancer. I Env Pathol Toxicol 1:361-362.1978, vinyl chloride monomer in the manufacture of polyvinyl chloride in Creat Britain. Br 1 Ind Med 34:1-10. 1977. 25. Pell S, O'Berg MT, and Karrh B: Cancer epidemiologic surveil lance in the DuPont Company. I Occup Med 20.725-740.1978. 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Cancer Mortality of Canadian Workers Exposed to VCM: A Three Year Follow-up To the Editor: In a previous issue of JOM, we reported the results of a mortality study conducted in 1978 on a group of Canadian workers exposed to vinyl chloride monomer (JOM 23: 671-576, 1981). Liver cancers were found to be in excess, but neither brain nor lung cancers were higher than expected. Since the exposed workers were known to have a ciga rette smoking experience similar to those not exposed, it was concluded that the association between lung cancer and VCM exposure previously reported could be questioned. We would like to report the results of a three year follow-up of this study conducted in 1981. The methodology used was essen tially the same as In the 1978 study. The vital status was established through correspondence or by tele phone conversation with the men who constituted the first study population. The cause of death was certified from the death certificates. The assignment of the men into the exposed and unexposed cohort was done as pre viously, not considering the exposure during the last three years. Of the 1,310 men who constituted the origi nal study population, 38 could not be traced in the second study (11 in the exposed cohort, 27 in the unexposed one) leaving the new study population at 1,272 men. In the exposed cohort, 14 men died during the three year follow-up (three cancers: lung, stomach and larynx). Meanwhile, 66 men died in the unexposed cohort (10 cancers). Table 1 shows the deaths observed in the VCM-exposed and unexposed cohorts, age-adjusted relative risks, and con fidence intervals of the relative risk AP00003467 di of Jan. 31, 1981. The excess of mortality due to cancers of the diges tive system in the exposed group persisted (RR 3.10,confidence interval 1.61-5.96) whereas there is no excess in the other causes of death. Table 2 shows the standardized mortality ratios (SMR) for the ex posed workers in comparison with the entire population of the Province of Quebec. Again, a significant excess is noted for cancer of the digestive sys tem only. No other cancers are in excess. The expected numbers of lung cancers was 7.05, the number observed was three (SMR 42.55). Even though this foliow-up study covers an observa tion period three years longer than the previous one, the number of personyears of observation remained approxi mately the same due to loss to foliowup. Nevertheless, the lung cancer rates are still low and seem to negate its association with VCM exposure. Gllei Theriault, M.D., Or. Ph. Department de Medeclne Soclale et Preventive Universite Laval Cite Unlversitaire Quebec, Canada G1K 7P4 AOMA/AAOM New Address The address of the head quarters office of the American Occupational Medical Associa tion/American Academy of Oc cupational Medicine is now 2340 S. Arlington Heights Rd., Ar lington Heights, IL 60005; tele phone: 312/228-6850. Table 1 - Deaths Observed in the VCM Exposed and Unexposed Cohorts, Age-Adjustid Relative Risks and Confidence Intervals of the RR Cause of Death No. of Cases Exposed Unexposed Relative Risk 95% Confidence Interval of the Relativa Risk All cancers (140-209) Mouth and pharynx (140-149) Digestive (150-159) Respiratory (160-163) Bone, skin, connective (170-173) Urogenital (185-189) Eye, CNS (190-192) Leukemia (200-209) Others cancers Cardiovascular (390-458) Respiratory (460-519) Digestive (520-577) Accidents and violence (800*999) Others (3 age unknown) TOTAL 23 0 IS 4 2 1 0 1 0 30 7 4 z 7 73 64 1.01 1.00-1.02 2- - 14 3.10 1.61-5.96* 24 0.49 0.12-1.93 3 1.13 0.38 - 3.36 8 0.57 0.10-3.10 2-- - 4 1.15 0.07-26.13 7- - 150 0.72 0.49-1.05 21 1.97 0.51-7.65 12 1.27 0.29-5.49 15 0.83 0.08 - 1.0Z 37 0.94 0.69-1.27 299 0.92 0.80-1.09 p - 0.0S Table 2- Observed and Expected Numbers of Deaths in the VCM-Exposed Cohort end Standardized Mortality Ratios (SMR) Cause of Death Observed Expected SMR Alt cancers Mouth and pharynx Digestive Respiratory Bone, skin, connective Urogenital Eye, CNS Leukemia Others cancers Cardiovascular Respiratory Oigestive Accidents and violence Others TOTAL (140-209) (140-149) (150-159) (160-163) (170-173) (185-1891 (190-192) (200-209) - (390458) (460-519) (520-577) (800-999) 23 0 15 4 2 1 0 1 0 30 7 4 2. 7 73 21.47 0.81 7.17 7.69 0.50 1.90 0.57 2.07 0.71 41.83 4.38 4.83 11.69 6.85 91.09 107.13 0 209.21* 52.02 400.02 100.53 0.0 48.31 0.0 71.72 159.82 82.82 17.11** 102.19 80.14 * p < 0.05 * p < 0.01 Letters to the Editor 731 AP00003468 95: 109928W Follow-up ttudy on tho carcinogenicity of vinyl chloride and vinylidene chloride la rata and rale*: tumor inoidauco and mortality aubaoquant to exposure. Hong, C. B.; Winston, J. M.; Thornburg, L. P.: Leo, C. C.; Wood*, J. S. (Midwait Rat. Inst., Kansu City, MO USA), j. Toxicol. Environ. Health 1981, 7(6), 909-34 (Eng). Exposure of male and female mice to 60, 260, or 1000 ppm vinyl chloride (VC) (75-01-4] for 6 h/dy, S day/wk, for 1,3, or 6 mo resulted in increased no*, of deaths and increased moribundity at all dose levels during the exposure and poatexpoaur* periods, as compared with air-expoaed controls. Similar observations weri made with rats after 1, 3, 6, or 10 mo exposure to VC. Cumulative tumor incidence at Various organ sites also incraasad in both specie* during the pottexposure period in proportion to dose or duration of exposure at higher doe* level!. However, except for nummary gland tumor* in female mice, no significant increase in cumulative tumor incidence occurred in either epeciee at 50 ppm VC or 56 ppm oinylidene chloride (VDC) [75-35-4]. regardleea of duration of exposure. The** results suggest that exposure to vinyl halides at dose level* lower than those that elicit a significant increase in cancer incidence during the lifetime of the animal may, nonetheless, increase the risk of early death or moribundity from toxic pre- or subcarcinogenic effects. At dose levels higher than tho** consistent with the physiol, defense or repair capabilities of the cell, ultimate tumor incidence becomes proportionate to length of exposure and may rafleot the no. of carcinogenic events elicited during the exposure period.