Document q33N5VGwLaKJa4ZnZamr449VG

Vi.' i JO l. - 'JiJ iill J oynz U'vV IIULI VJ1W | rocyte membrane adenosit )'*,v _ . pan appeared. Total adenosine tripneaphst id maynoalunri-aGttvviad ATPoatl tM}*cuvn<eao( numan aryinroc ' branaa after incubation in vart< on* ol aromatic Hydrocarbons rapreaeolt tne mean ol fourtrtfl*.j parrmanta. ail made In trtpiioala. Total sdenocine triphoaetuii and msooesiuin-acttvaiee ATPose] >asa activities ot human erythrocyte Ti&rsnes alter incubation In vinous ] fionsot chlorinated aliphatic hydro, j Each ooiflt represents the mean of] >endent exeenmertts. all mace m tri- l. Total adenosine triphosphatase sno msanesiunv'sctlvatso ATPase ie> activities of rtvmen sfyinrocyte em&ranei after incubation >n venous rations of alcohols. Each point repre. irxi^ of (our ^dependent exoartill mode in tnpttcaia. Scotttf J 1Vork Environ Hr*il't* K (1988) 81--78 Effects of exposure to vinyl chloride An ueestment of th evidence by sir Richard Doll, FRS1 DOLL R. EfTcctf of exposure to vinyl chloride: An assetuneiu of the evidence, Scand J Work Environ fiea/iA 14(1998)61--78,11118 paper reviews the possible effects of vinyl chloride on tie mortality of oc- cupatioully exposed ton and (he cardoogenic cfTecu that mtgtK tie observed la the icaersi population as t resell ofenvironmental pollution with vinyl chloride. The rendu of foor studies fulQDing the criteria of providing substantia! makers of obicrvaiiOQS more than 2S years after first exposure and covering a period long enough for more than 10 4b of the woritert to faav been axpected to die constitute the tab for tha assessment of the occupational hazards. Other Kodlci provide oaly suppknraury Information. The dt> permit two coodudoos. first, men oecupuiooifly exposed to vinyl chloride have experienced a specific hazard of angiourcoaia of the liver. Second, any other ocaipattontl hazards that may have existed have been small. No positive evidsaes of a hazard of any oossaalignaat or asy type of caaoer other than anfloojcoma of the Uver has been found exempt possibly for a small hazard of lung cancer when exposure vu bciy. Mora definite eondudors aright be ietched if those who have studied exposed employees could present itdr results In appropriate and comparable wan. A very small risk of angiosarcoma p*y hove oosurrod as a result of riayi ddorideemapiag into the environment around plans* handling vfayt chloride la the pan, but the evidence Indicates that the currant risk to the general public (if any) must be aegUgibk. Key terms: angiosarcoma of the brer, cancer, lung ana, mortalcy, polyvinyl chloride, review, vinyl chloride monomer. For many years the inhalation of large amounts of vinyl chloride has been recognized as potentially haz ardous. Concentrations or the order of 10 000 ppm in the air induce unconsciousness and cardiac arrhyth mia, while prolonged exposure to concentrations an order of magnitude lower have been liable to cause a tpedfio pathological syndrome. This "vinyl chloride illness" has been characterized by four cardinal signs, namely, enlargement of Che fiver and spleen with a specific histological appearance, patchy infiltration of the skin resembling scleroderma, bony changes In the tips of the fingers described as acroosteolysis, and peripheral circulatory changes identical with the das sical picture of Raynaud's disease. These pathologi cal reactions may occur singly or together and may pos sibly be accompanied by other leas characteristic ef fects. The)1 can. however, be completely avoided if ex posure never exceeds the level of a few hundred paru per million, ie. the level to which exposures were generally reduced In the mid-1960s. One other serious effect has. however, been observed that may not be avoidable in the same relatively easy way, namely, the production of angiosarcoma of the iver. It must, indeed, be presumed that some risk of developing the disease will persist from exposure to imperial Cancer Rvccan.li Fund, Cancer Epidcmulogy arul Clinical Trials t-'nii. Raddiffe Infirmary. Oxford. United Kingdom. Kcprini request* 10: Sir A Doll, Imperial Cancer Research i end. University of Oxford. Git)ton Building. Ttie Raddiffe infirmary. Oxford 0X2 6KE, United Kingdom. doses that are eves lower than the corredt industrial levelsof3 ppm or less, as vinyl chloride has been shown to act as amutagen (25), aod it cannot be assumed that a threshold exists below which no carcinogenic risk persists. Moreover, the paatibOfcy has to be considered that vinyl chloride may cause some cancers other than angiosarcoma of the liver, partly because laboratory studies Have shown that it causes other cancers in animal experiments and partly because the Initial studies demonstrating the produaion oF angiosarcoma of the Uver In humans were inadequate In size to ex clude a material increase In the risk ofcues la cornown sites, such as the King and large bowel. Since no threshold dose can be postulated, It also follows thai some earners may have been produced in the general public bythe small amounts that have escaped into the general environment. Consideration also needs to be given to the possi bility that exposure to vinyl chloride over a long pe riod may have noxious effects on humans that cannot be seen easily in animal experiments (by, for example, producing chronic respiratory disease), and, as it is a mutagen, there is also a possibility that it may act as a teratogen and cause congenital malformations in offspring. In this review 1 have noi examined the possibility that vinyl chloride acts as a teratogen or that It causes mutations in germ cells, as there is too little serious evidence to justify inclusion. Reviews carried out for sections of the industry' by Downs er al (unpublished report to (he Society of Plastic Industries Inc in 1977) 61 c X co c-n co and by MacMahoa (unpublished report to u* cal Manufacturers Association la 1977) concluded Out the few reports of positive effects could act be sub* sure). These requirements do not introduce any new complexity, os both are, of course, also required Ifcor rect eonduriofts are to be drawn from the results of stantiued, tnd no additional evidence w found in the individual studies when they areexamined on their a similar later review by Barr (unpublished report to own. Air Products and Chemicals Inc In 1981). spirt from a report that embryos were absorbed and skeletal os sification was produced when pregnant rats were ex* posed to dosss appreciably tower than those that had been used by other workers without any such effects being observed. The report of absorbed embryos (34) ooukl oat be evaluated thoroughly, howsver, as the ex periment was inadequately described. I Have, therefore, examined only the possible effeos on the personal health of men occupationally exposed to vinyl diloride. other than those related to thdr reproductive capacity, and the carcinogenic effects that might con ceivably be observed In the general population as a result of dm widespread distribution of vinyl chloride as a pollutant. Sources of Information Four studies meet tbe aforementioned requirements, namely, two large national surveys, one reported by Jones (23) for tbe United Kingdom (UK) and the other by Environmental Health Associates (14) for the United States (US), and Studies of individual plants in Canada, reported by Theriault & AUard (46) and In Italy, reported (as apart of a national study) by Belli al (4). All tour include observations oa men more than 25 yean after their first exposure, and the ex pected number ofdeaths is, in each case, greater than ID ^tof (he total tuitaber ofemployees, a value indi cating a tong average period at risk. Earlier observa tions on UK tod US employe* (6.9, 12,16,20,36, 39,40,45, SO) havebeenjubjunwd Jo the national sur jCeupattanal hazards veys and now serveonly as sources ofhypotheses and of some detailed information not Included In the na Manystudies of workers exposed to vinyl chloride In the maaufactura of vinyl chloride monomer (VCM) and polyvinyl chloride (PVQ have been undertaken sinceit was first found tint vinyl chloride could cause cancer in animate (38,48) and man (10)* These Inves tigations have confirmed chat exposure causes a haz ard of angiosarcoma of the Kv and, in several In stances, have shown excess incidence or mortality rates that were conventionally statistically sigsificaat for otherdiseases. Conventional tests of statistical signifi cance are. however, designed to help answer tingle questions defined beforehand, and several findings that might be expected to occur by chance alone once in (say) 30 times must be expected to occur If dozens of rates are examined in each ofseveral sets ofindepen dent data- Scientists have, therefore, been faced with tional reports. Studies of German (49), Norwegian (22), Swedish (7), French (41. and unpublished report ofLaplanebe et al), Japanese (33,37), and some other Italian (4) workers provide some supplementary infor mation, but, in general, tire periods of observation have not been long enough for useful epidemiologic data to be obtained about diseases that are unlikely to occur withia 20 yean of first exposure, or they report only selected remits which are difficult to intopret, as only excess rates tend to have been selected. Studies of makers of PVC products have not been included, as tbs workers have had much less exposure to vinyl chloride than those employed in the manufac ture oT VCM Of PVC and any occupational hazard to which they may Imve been exposed is more likely to have been produced by PVC dust. the problem of deciding whether the excess rates that have been observed in individual studies are dueto oc US study. The study carried out by Environmental cupations! hazards or to the vagaries of chance. Health Associates (14) on behalf of the U$ Chemical This problem can be solved in part with an exami Manufacturers Association is the largest and most In nation of tbe results of a sumation of data from com formative investigation thus far undertaken. It cov parable studies, that Is. by a comparison of the sums of the numbers of deaths observed and expected in each study. This procedure does not require the as ered 10 173 men who had worked in 37 plants owned by 17 companies -- 1 214 men n II plants that produced only VCM. 6 848 men is IB plants that sumption that the exposures have been the same In cadi produced only PVC, 935 men in three plants that study any more than the same assumption is required produced both, and i 176 men in five plants that for each individual when the results ofeach study arc produced bomopolymert and copolymers, with or considered alooe. It does require however that each without VCM or PVC. exposed population hoi been observed over a period Twenty-two of (he plants were in tbe southern part when k* members were at risk of developing disease (if a genuine hazard existed) and chat in each study the reference population from which the expected num of tbe country, 14 were iu tbe northeastern or north central parts, and ooe was in the nest. Men were ioduded if they had been exposed to vinyl bers of deaths were derived was appropriate (that is. at the same risk of developing disease as the exposed population would have bcefl in the absence of expo chloride for at least a year before 21 Dccembo-1972 and had been employed is 1942 or subsequently (the first yar depending on tbe date the plant began making or using vinyl chloride and tin Eoonei records were deemed to was the later). Individuals whe Identified from company tecsoruieL Rada] characteristies were ki 97 Vt of whom were white, an the purpose of estimating th. deaths, that all 10 173 men w Follow-up data were obtain dalSecurity Administration re. died after 1979) from the Natl plants did not collaborate in th (9) earlier study, which had present Investigation, and the plants who were known to be 1972 were not followed any follow-up was attempted to 1982, whichever was thCcatlie of the men were successfully t uotraced were excluded from i which was usually the date wh* Almost half of the men (46 1 before 1955. A large proporti served more than 25 years afte tnanr cases for more than 30y< a long latency period might b Short-term workers had bt cohort, and most of the men ploymefit for many yean, two for 10 years or more and the a ptoyment betas 16 yean. Fifteen hundred and thirtyhave died. Is 1 439 cases, the tained from the death oertifical tained for the other 97 persot The numbers of deaths exp causes or groups of causes w plying the person-years at risk national rates for white males, age groups and five-year peri. , This important study is opt ttisms. which are unlikely to bffecu on the results. First, the [compiled by company person rcords without any independent sumption that all the employe K caused the expected deaths io underestimated, as the few biz to have had higher mortality reason forsupposing that the si **ie proportion of black etnplc xessariiy representative. Thfa itainiy was introduced by the E iai 7.3 5b of ihe employed- Two other criticisms are mo led number* of death* w. iption that the men wduk mortality rates as th< wl "D r~ <O.Tj\ to ttCO (1UU;UKD LBRY msmmmmimmm i^jyy-4/uyv I I IWJUIJP|JJU.IiU.u or using vinyl chloride and the earliest date that per. coftoel records were deemed to Be complete, whichever was the later). individuals who met these criteria were Identified from company records by compuiy per the whole country at tbe corresponding dates. The uie of national rote* it common practice in studies of in dustrial populations and tend* to result io an overestimation of the expected numbers of deaths to that sonnel. Racial characteristics were known only for 686 men, 97 4b of whom were white, and it was presumed, for the purpose of estimating the number of expected the employees appear to be unusually healthy. This "healthy worker offeet" is well known and has been taken Into account In my discussion of tbe results. A more saious objection to the use of national rates is deaths, that all 10 173 men were white. Follow-up data were obtained from plant and So* dal Security Administration records and (for men who died after 1979) from the National Death index. Five plants did not collaborate in the extension of Cooper's the way mortality varies from oae part of the country to another, due to differences la tbs prevalence of en vironmental and social factors unrelated to tbe occu pation of interot. li is, therefore, generally preferable to use itate (if dot county) rates. In place of national (9) earlier study, which had been subsumed In the rata. With 37 plants, however, it might be thought present investifaiioo. and the 93d employee* in these that their geographic distribution would be auitldentiy plans who were known to be alive on 31 December wide to make the u*e of national rates appropriate. 1972 were not followed any further. For the rest, Unfortunately 22 of the plants were located in tbe follow-up was attempted to death or 31 December 1982, whichever was rite earlier. On this basis 92.7 4s of the men were successfully traced. Those wbo were sooth, and a check would have been desirable to see whether their location could have caused any material distortion of the results. uatraced were excluded from the last date ofcontact, Second, ses were not obtained for 97 of the 1536 which was usually the date when employment ceased. deaths. This deficiency was allowed for in the calm- Almost halfof tbe men (46 W) were first employed ladenoftbe overallmortality bytbe ineUition ofdeaths before 1935. A Urge proportion was, therefore, ob served more than 23 years after fust exposure (and in many cases for more than 30 years) when diseases with a long latency period might be expected to be seen. due to unknown causa. It was not allowed for, how ever. (n the calculation of thetfseasc*petific mortality rata and will have caused the standardized mortality ratios to be underestimated by an average of 6-3 W. Short-term workers had been excluded from the For the present purpose, therefore, the numbers of . cohort, and most of the men had continued in as- deaths attributed to specific diseases have eadi been pksymem for many years, two-thirds bring onpioyed for to yean or more and the average duration of em ployment being 16 yean. multiplied by 1.0674 (100/(1--97/1536)] ood rounded off to the nearest Integer. Fifteen hundred and thirty-six men were found to UK.study. The study reported by Jones <25 and un hare died. In 1 439 cases, the cause of death was ob published} on behalfofthe British Health and Safety tained from the death certificate, but no ausc was ob Executive covered S 498 men who were employed for tained for the other 97 persons (6.3 ft). at least one year in jobs that Involved potential expo Tbe numbers of deaths expected from each of 38 sure to YCM for at lean 25 W of the work week and causes or groups or causes were obtained by multi who were first employed in the period 1940--1974. De plying the person-years at risk by the dlieue-tpcdfic tail) of the men were compiled from the personnel national rases for white males, for the corresponding records of nine chemical plants manufacturing or pely- age groups and five-year periods of the study. merttini vinyl chloride, and the vital status of the men This important study is open to three minor criti was determined at the end of 1984 from tbe records cisms. which are unlikdy to have had any material of the Notional Health Service Central Register. Five effects oo the results. First, the lists ofemployees were thousand four hundred and ninety-eight men were compiled by company personnel from company re traced (98.9 4%). Seven hundred and eighty deaths were cords without any independent check. Second, the as identified, and copies of the death certificates (coded sumption that ail the employees were white will have to the eighth revision of the International Classifica caused tbe expected deaths to have been very slightly tion of Diseases (ICO) If they occurred before 1979 underestimated, as the few black employees are likely and to the ninth revision if they occurred later] were to have had higher mortality rata and there Is no senl to the Investigators. reason for supposing that the small sample from which Several specific points about the study need to be ~ ihcproponionofWackemployeeswasetunutedwas necessarily representative. Third, on element ofuncer tainty was introduced by the failure to trace as many noted. First, national mortality rates for England and Wales were calculated for five-year age groups over quinquennial periods for 66 causes of death, and these as 7.3 * of the employes*. rata were used in the estimation of the numbers of Two other criticisms are more important. First, the deaths that might have been expected in the cohort by expected numbers ofdeaths were calculated on the as sumption that the men would have experienced the tame mortality rates as the white male population of multiplying them by the corresponding numbers of person-years under observation. Some difficulty which could have been related to the causa of death bring r~ c 63 coded according to the eighth and ninth revision* or presumed that the expected oumben of deaths m the the ICO was, however, experienced hi obtaining soft, first two exposure categories are Gkdy to have been able rates for aU causes of death, and rates for a rela overestimated. tively late period had to be used for estimating the number* of deaths iron many diseases that might have been expected to occur in earlier periods. For two categories the earliest available rales were 1960--1964, for one they were 1965--1969, for 24 they were 1970-- 1974, and for ooe they vere 1975--1979. CaiU&an study. The Canadian study (46) wte limited to employees of a single plant In Shawinigta, Quebec. The plant, which was situated Wi an industrial com plex, was opened in 1943. VCM and PVC were both made until the late 1960s, when the production of Second, an attempt was made io classify men ac VCM ceased, while the production of PVC continued. cording to whether they had high, intermediate. or low An attempt was made to trace all the production work exposure to VCM or PVC dust, and each man's em ers whose names appeared oa the union*' lists or the ployment history was recorded according to 12 job payrolls ofthe companies in the whole industrial com tides with advice from the plants concerned. The men plex, including the vinyl chloride plant, between 1 were then grouped according to whether exposure to January 1948 and 31 December 1972, ud contact was VCM was likely to have been high (group A), expo made with the worker or his next-of-kin la 1 611 out sure to PVC dust was likely to have been high with of 1 659 instances (97.1 ft). Detailed occupational and exposure to VCM low (group or exposure to VCM smoking histories wav obtained byquestionnaire, tad and PVC dust was intermediate and intermlnent 156 men who had been employed by the companies (group C). AU other men. who would generally have for less than five yean were excluded. The remaining i low exposure to both VCM and PVC dust, were men were categorized as (0 exposed to VCM If they ;ed as group D. Within afl the groups, exposure had worked oa the production of VCM Of PVC for /CM was likely to have been higher If it had begun at least five yean (451 men), (8) tmexposed to VCM before 1956. If they had worked rimQariy far lea than six months The study makes an Important contribution to the knowledge concerning the long-term effects of vinyl chloride. The use of national rata to calculate the ex pected numbers of deaths may be Justified on the grounds that the men were employed in nine plants, which were presumably distributed about the country, but no details of their location arc given. In general, mortifiiy rates tend to be higher in the parts of Britain where heavy industry is located than in other parts of (870 men), and (111) other man (134 la total). The lost group wo* excluded from the study. FoBow-up was closed on 31 December 1977. Copes of the death cer tificates were obtained, and the causa for aU who had died (59 exposed and 233 unexposed) were coded ac cording to the eighth revision of the ICD. Informa tion was also sought for histological or cytotogfcai con firmation of all the diagnoses for all the exposed men who had died of cancer. the country so that the expected numbers ofdeaths are The result* were examined to two ways. First, the more likely to be biased downwards than upwards; but mortalities of the exposed and unexposed men were whether this is so or not needs to be shown. compared after standardization far five-year periods The use of recent rates to cakelate expected num bers of deaths from many specific causes of death waa presumably necessary if the diseases were tobe studied individually and will have done no harm if the ind- ' dertee and rataliry of the diseases in question remained stable. U would haw been desirable, however, for (he disease* to have been specified so that the reader would know which were liable to be distorted. of thestudy and fivo-ytar age groups. Second, the mor tality of the exposed men was compared with that ex pected if the men had had the sex- and age-spedfk mortality rates recorded b Quebec far the year 1971. In both comparisons the causes of death used were those specified on the death certificate, and the addi tional pathological information was used later only for interpretation of the results. The system used to classify the men into four expo sure groups is the sort of syttem that is commonly used if precise measures of exposure are not available. It creates some difficulties in the statistical analysis if men Most of the exposed men were exposed for more than 10 years (75 ft), the average length of exposure was approximately 17 yean, and 44 ft were observed more than 25 yean after first exposure. move from one job to another and arc classed (as in this instance) a haring had high exposure (f they have ever had a particular type ofemployment (eg. ever been Although small, the study makes a useful contribu tion to (he overall results. The histological review of the cancer cases is particularly helpful It showed that anpioyed a &n autoclave worker). No evidence is pro all right cancers diagnosed as liver cancer (Including vided to show that the percon-years at risk before a two specified as hepatoma and one specified as angio man. entered the category have been subtracted and sarcoma) were angiosarcomas of the liver, as well a added to another exposure group before the numbers one that had been diagnosed as angiosarcoma of the of expected deaths were calculated. Movement from peritoneum. Two other coses of angiosarcoma of the one job to soother was said to have tended to be out liver were found to hove been certified as hfpal ic dr* of groups A and B into >, but even so it must be rho-jfs. It m abo helpful to have a comparison between .> companies as it shows that the i for oil nonmalignant diseases, a healthy worker effect and wg? recording of exposure (relative runt causes compared to that of 0.95). Oneaspect of the study has to ie, the use of provincial rates i calculate expected mortality s. period (1948 to 1977 inclusive), i to bunch up towards the end c vation to that the rates for lb have been fairly representative, 1 some distortion of the expected ike (and even the direction) of estimate. For most disease grou likely to have been large. Italian study. A study of all meduction ofvinyl chloride and PV was begun in 1983. All men w* employed Tor at least six month start up of the plant to the end stffl incomplete, but results are Is three plants (4), Two plant signing) began operation in (9 . thirty-seven men were employe to theother. AH butthree(from foDowedtothccndof 1984. Ext mated by multiplying the pern L corresponding national mortal' ^yeargge group and each fivg.ye )Thc total expected deaths in e jmore than 10 ft of the etnpto. tfU.4 and 12-8 ft). Clinical information was sou death ofall the 56 employees o( 1 died. Revised diagnoses, w tkparlson with the expected {deaths from cancers of the liv </ The Ravenna plant did not ;;1959. Six hundred and thirty-eif " but four w<re traced to th jWere found to have died. No m: - towed for more than 24 years. (0.9 ft o( the work force) were [ this plant have not. therefore, jUipal analyses, U may be not< fdemh was attributed to liver ct source. The Norwegian: rations on 454 men who hi : in Telemark where VCM I 1950 to 197J and PVC f: URL 735fta U2--10-^3 12:14 *25419 362 8842 HCQ HULP0R1) LbKY 006^027 ;d numbers of deaths ir lies are likely to have ai dy (461 was limited] iai jawinigan, Quebec.' d in an industrial com-l >. CM and PVC were both] >s, when the production art oduetion of PVC conilnued4 race all the production work-^ xl on the unions' lists or the; t in the whole industrial cam-; 1 chloride plant, between. I ember 1972, and contact was] r hts next-of-kin in 1 611 outl A). Detailed occupational and! buined by questionnaire, and] employed by the companies vere excluded. The remaining] (l) exposed to VCM if they] ductksn of VCM or PVC fort nett). (H) unexposed to VCM' llarly for less than sLx months: cr men (134 in toul). The last) the study. Follow-up was : 1977. Copies of the death cer- and the causes for alt who had 33 unexposed) were coded acevision of the ICD. Informs-j histological ot cytologies! coo-) gnoses for all the exposed men ` rr. {|J two ways. Firft, Ihe nr <nexposed men were r for five-year periods ar age groups. Second, the moricn was compared with that exi had the sex- and age-specific :d in Quebec for the year 1971. the causes of death used were death certificate, and the addlyrmation was used later only for results. ,d men were exposed for more the average length of exposure years, and 44 to were observed tier first exposure. ; study makes a useful contribuuhs. The histological review of ticuieriy helpful, it showed that nosed as liver cancer (including oma and one specified as angio.arcomas of the liver, as well as ignosed as angiosarcoma of the er cases of angiosarcoma of the ave been certified as hepatic dr ill to have a comparison between the exposed and "unexposed" employees of the same companies u (t shows that the low mortality observed for all nonmaUgnam diseases could be attributed to a healthy worker effect and was not due to bias in the recording of exposure (relative risk far ah nosmalign*nt causes compared to that ofthe `'trnexposed" men the study period. Every man was includod whose came was recorded In the company's personnel resistor and health department records who had ever been em ployed from the start of production to the end of 1969 and had worked for at least one year. The men wore followed from 1933 to 1979 Inclusive. Deaths and cases 0.93). One aspect ofthe study has to be criticised however, wc, the use of provincial rates for one year (1971) to of canoer were identified from the records of the Cen tral Bureau of Statistics and the national cancer regis try. No reference was made to any men being lost to calculate expected mortality spread over a 36-year period (1946 to 1977 Inclusive). Deaths will have tended to bunch up towards the end of the period of obser vation so that the rates for this particular year may follow-up, but h can be assumed thai the cumber Of not zero) was small, as all citizens have an ideality number which is used by both employers and central agendas. Fifty men were found to have died against have been fairly representative, but h must have caused tome distortion of(he expected numbers ofdeaths, the rise (and even the direction) of which Is impossible to estimate. For moat disease groups the distortion h un likely to have been Urge. 59.34 expected if |h sex-, age., and quinquenniumspedfic national mortality rates bad operated. Twentyone men were found to have devdoped 23 cancers against 20.16 cancm expected from the comparable national incidence rates, the use of which was justi fied by the finding that the Incidence in the county in Italian siudj. A study of all men employed in the pro duction ofvinyl chloride and PVCin aba Italian plants was begun in 1983. All men were included who were employed for at lean six months ai any time Iron the start up of the plant to the end of 1961. The study U still Incomplete, but results are now available for men in three plants (4). Two plants (in Ferrara and Ro- signana) began operation in 1933. Four hundred and thirty-seven men ware employed in one plant and 181 in theother. AS but three (from the Ferrara plant) were followed to tbe end of 1984. Expeaed detthr were esti mated by multiplying the person-years at risk by. the corresponding national mortality rates for och fiveyear age group and each five-year period ofthe study. Tbe total expected deaths in each cate amounted to more than 10 4b of the employees in the two plants 112.4 and 12.8 to). Clinical information was sought about the cause of death of all the 33 employees of the Ferrara plant who had died. Revised diagnoses, which were not used for comparison with tbe expected deaths, revealed four deaths from cancers of the liver in place of oac. The Ravenna plant did not begin operation until 1959. SLx hundred and thirty-eight moi were employed. All but four were traced to the end of 1983, and 17 were found to have died. No man could have beet) fol lowed for more than 24 yean, and only 25.1 deaths i3.9 to of the work force) were expected. The data for this plant have not. therefore, been used in the prin cipal analyses. It may be noted, however, that one 'death was attributed to liver cancer when 0.1 was ex pected. which the plant Was situated wu between 90 and 93 to of the rate of the country as a whole. One man who had been employed in FVC production devdoped an giosarcoma of the Uver. The observed and expected numbers of cases were given for cancers of the lung, colon, and thyroid, for melanomas, and for aJU can cers, but no expected numbers were given for other types of cancer. It Is evident that several.other types of cancer must havebeen in deficit, as there were right cases in all against 14.93 expected, and h is difficult (0 know what weight to give the excesses observed for the reported types of cancer,they seem likdy to have been reported specifically because the numbers were is excess of those expected. The authors noted that one further case of melanoma had occurred after the closure ofthe study and that one "Incipient case" was also known to them. The Genuan study (49) Induded the following three groups: (1) 7 021 men who had been exposed to VC in th* course of their employment in any of tbe 11 plants hi which VC and PVC had beat produced lo the Fedo'al Republic ofGermany, (U) 4 820 men who had been employed In seven chemical plants without having had any exposure to vinyl chloride, and (Hi) 4 007 men employed in two other plants where PVC was processed. Employees vere induded only if they were of German or Austrian nationality, and (hey were regarded as exposed to vinyl chloride if they were production workers or other skilled workers or laborers assigned regularly to the plants, but not If they were employed In them only occasionally. All the men were included from tbe time of opening of the plants to the end of 1974. and they were followed to the end of 1974. Many Of the men were therefore observed for only a few years aficr first employment, and only 14,36, and Other sources. The Norwegian study (22) provided ob servations on 434 men who had been employed in a plant in Telemark where VCM had been manufactured from 1950 to 1971 and PVC from 1950 to the end of 19 to, respectively, of the three groups were first em ployed before 1954 and were therefore capable of con tributing person-years at risk more than 20 years aficr firit employment, when an occupational hazard of can cer could be expected to be observed. 63 C JJ r-- CJ cn co Ol iix exposed group 93.2 ft were successfully fo{. lowed, and cause* of death were discovered for 92.8 ft TwoSwedish itiaomhave produced VCM and PVC, onesboe 1945 and theother since 1991, and employees of the 414 men discovered to have died. The propor ofthe first plant havebeen studied by fiyrecet ti (7j. tions for the other two groups were respectively 69.8 AH persons who hid ever been employed when expo and 88.7 fa for the unexposed and 91.1 and 86.9 Vs sure to VCM could occur were Kited from the per for (he PVC process workers. The failure to obtain sonnel files of tbe factory. Twenty-one wereexcluded causes of death for all the men who had died was allowed for la the subsequent analysts by the weight- lug of the numbers attributed to each cause by a sys tern which took account of the age group and odendar period in which death with an unknown causeoc curred. The expected numbers of deaths from each because they were fordgnoi who lefttbecountry after a short period ofemployment. The remaining 750 were followed toOetobw 1974. Expectednumbers ofdeaths were estimated by multiplying tbe person-years at risk by the corresponding age-spedfic mortality rates for the whole country, and the expected numbers of can cause was calculated by multlphiag die pereon-yttrs at risk by the a-. age-, and cause-specific mortality raxes for the Federal Republic of Germany. National cer cases from 1956 to 1991 inclusive (during which period all cancercases had beat registered nationally) were estimated by multiplying by the national age- data before 1968 used an Idiosyncratic classification system, and the 196$ rates had tobe used io multiply tH the person-year* at risk up to the and of 1968. For specific cancer incidence rates. la both instances, the raiei sued were those recorded in 1969. Fifty-eight deaths were found, but no figure was given for the ex subsequent yean (1969to 1974)theperson-yearsctrisk pected number. Detailed figures were given only for wetemultipliedbythe correqxwdmg ratesfor the same tbe numbersofdeaths and cases observed and expected for cancer of the lung and for ameers of tbe Kver and calendar year. epidemiologicstudies arcmomdifficult tocarryout ic Federal Republic of Oermany than fat North . -Genet, the United Kingdom, orScandinaviabecause the medical cause of death fa sot recorded publicly, and there is no central system which can be ttted for pancreas combined and for the earnben of deaths from brain cancer and three categories of cardiovas cular disease. Twomen known to haveangiosarcoma of the liver were certified as having died of Dver cancer or patterned* eaaotr, tod a third mas died tit checking whether an Individual Is t&ve or dead. In aagLoureoma of the Ever 17 months after the dose these ctfcuatfnnces, the German authors have made of the follow-up. valiant efforts to obtain reliable data, and the propor Two French Studies provide the results of a long term follow-up ofmeaemployed inoneplant(41) tad tions ofjnea In theexposed groups who weienot suc cessfully followed (6.8 ft) and the proportions of of a short<enn follow-up ofraea employed In 12 plants deaths for which the cause was not obtained (7.2 4k) (Lapland* et1, unpublished). The first provided ob were similar tothoseIn thestudy oftheEnvironmental servations on l 3H men exposed to vinyl chloride In the production of VCM and PVC and laselected an- Health Associates (14). Two defects, however, make the data less useful. First, no national mortality rates were available before calory operations from theopening oftheTftvaux plant In 1953 to the end of 1976 (41). Six other employees were excluded from the study because of lade of oc 1968. and the use of the 1968 rates to estimatethe num bers of deaths hi and before 1968 will have overcati* mated the numbers attributable to diseases that were becoming more prevalent or were being diagnosed cupational histories and 160 men because their vital status at the end ofthe study period was undetenttined. Twony-Gve men were found to havediedagainst 48.75 more often and underestimated those due to diseases that were becoming lest prevalent. Second, and more importantly. a large proportion of the men had been first employed lest than 10 years before the follow-up ended. Therefore the useful observations on the few men who had been exposed long enough to have had expected from contemporaneous sex- and age-specific national mortality rates <3.7 ft of the men at risk). One dealt was attributed to angiosarcoma of the liver, in a man who had been exposed for more than 15 years. The reported data are so incomplete and cover such a rdativriy short period from the opening of the plant much chance of developing an occupational disease w'uh a long latency period must have been swamped tftfll they add nothing of epidemiologic value to the results of the other studies, apart from the addition by amass of other observations that had little to con tribute. The expected deaths amounted to only 6.2 ft of a further case of angiosarcoma. Tbe second study provided observations oo l 100 of the exposed men. and there Is, therefore, Gttle to be gained, and something to be lost, by including the men aged 40 to 55 gears who. Is 1980, were exposed or had been exposed to vinyl dtioride fa> 12 plants, German data In the overview. It may be noted, how- which coortkured "rocsi of the French VCM polym -ver, that 12 deaths were attributed to cancer of the erisation plants** (Laplanche et 1, unpublished). Matty liver among the workers exposed to vinyl chloride against 0.9 expected and that smaller accesses were also observed among the auexpoted chemical workers (4 observed against l.l expected) and the FVC process workerr 0 deaihs agai/ut 0.8 expected). of the men were, or had been, employed at Tavtux and were presumably survivors or (he cohort studied by Pierre et si (41). The men were followed for five yean, and their morbidity and mortality were com pared with those observed for 1 ICO men of (he came -i rf ages (t2 years) who were empk but who bad never been expo; In both groups were interview formation was obtained abOi drinking habits, which were fo' two groups- The men in the ex first exposed for an average of: first been employed in the plan ousiy. Morbidity and mortality nually by the plant physJdan, v. 96 ft of tbe exposed men and ' One of the exposed men. but no developed at) angiosarcoma of t given separately for different - ployment, and h is impossible u of the finding that six of (he e> lung cancer against two of the well reflect a chance occurrence in ihc reference group, as the cancers in that group (2 out of' One exposed man developed a hematopoietic system against no none of the men in either grou* developed melanomas or can* roid. A Japanese study has repot pericnce of 4 524 men employs before 1965 In 25 Japanese pit during VCM or PVC between . xlve (37). The men were followt ^Twenty-eight percent of the me [than 20years after first employr !Served more (ban 26 years. Only tuniraced, and copies of the deal [tamed for all the 209 men who i jlslriat cohort). Individuals wei the job in which they had t : temtfnatioa of their loll i separately for the 2 S46 tn ' production and 1 978 as VCM production w this study Is continued fo mid provide useful addition; ita include too few ob [than 20 years after first exposui Luxe. They confirm the evident [cancer with six deaths among ^workers against 2.54 expected jwhile only one death wa* {Other workers against 1.62 exf . from liver cancer flrtion. ters was certified as due ti Iver, and at least one of the oil t due to the same cause. Lu . in excess (2 observed In PV< ted). No data were given t and hematopoietic syttc lid or thyroid, or for melai jrted by Masuda (33) for 3t T3 to oi 05 cr> 12: IV U'41'J 3S2 2 HCQ MULFOKU L5K.Y 'C produced VCM -find PVC, er since 1971, and employees ti studied by Byren el al (7). be** -mploycd when expoit tted from the per. -one wereexcluded ' *vno left the country after . The remaining 750 were Expected numbers ofdeaths lying the person-years as risk {.specific mortality nues for he expected numbers of can. 971 inclusive (during which vi been registered nationally) lpiylng by the national agerates. In both instances, the ecordcd in 1969. Fifty^ight io figure was given for the ex. 1 figures were given only far id cases observed and expected ad for cancers of the liver end 1 Tor the numbers of deaths three categories of cardiovasknown to have xugiosarooma ed at having died of liver can cer. and a third mu died of ver 17 months after the close provide the results of a longemployed in one plant (41) and jp ofmenemployed b> 12 plants bllshed). The first provided objn exposed to vinyl chloride io A and PVC and in selected anihr `ngof theTavaux plant lr Six other employees tc . , oecause of lack of ocod 160 men because their vital study period was undetermined, found to have died against 48.75 poraneous sex-and age-specific , (3.7 ft of the men at rtskl. One o angiosarcoma of the liver, In -xposed for more than 15 years. : so incomplete and cover such d from the opening of the plant : of epidemiologic value to the udies, apart from the addition lngiosarcoma. provided observations an l 100 an who, in 1980, were exposed to vinyl chloride in 12 plants, lOSt of the French VCVl polymlanche et at. unpublished). Many had been, employed at Tavaux survivors of the cohort studied The men were followed for five bidity and mortality were comrved for 1 10(1 men Of the same ages (2 years) who were employed in thetame plants ride workers has presumably been subsumed in Na but who had never been exposed to VCM. The men kamura's (37) later and larger study. in both groups were Interviewed penonatty, and in formation was obtained about their aaoklsj; and drinking habits, which were found to be similar la the Hazards of cancer iwo groups. The men In the exposed group had been The results of the four most useful studies are luted first exposed for an average of about 14 yean and had individually In tables l and 2, The overall result* for first been employed In the plant about 18 yean previ all causes, liver canccr.and three brood groups of con ously. Morbidity and mortality data wot recorded an ditions ore shown In table 3. and those for 10 type*, nually by the plant physician, who suocessfUBy traced orclasses, of eaneer ore presented In table 4. Data have 98 ft of the exposed men and 96 ft of the referents. not been reported foreach type of cancer in each study, One of (he exposed men, but none ofthose unexposed, and the sources of the data are. therefore, specified developed an angiosarcoma ofthefiver. Data were not separately for each type. Additional information ob given ccparately for different periods after first em tained from four other ks* mformaiivc studies (4,7, ployment, and it is Impossibleto assess the significance 22,49) Is given fat table 5 for seven types or classes of of the finding that six of the exposed men developed cancer. lung cancer against two of the referents, which max Table 3 show* that, opart from cancer of the liver, well reflect a chance occurrence of unusually few coses the overall mortality U what would be anticipated for In the reference group, as the proportion of all long an industry without any major hazard of accident or cancers in that group (2 Out of 15) wu unusually low. disease. In particular the standardized mortality ratio One exposed man developed a cancer of the lympho- (SMR) of 84 for diseases other than cancer la typical hematopoictic system against none ofthe referents, but of the ratios that are commonly observed for groups none of the men in either group were known to have of employed men. A tow SMR of thU order reflects developed melanomas or cancer of the brain or thy. the "healthy worker effect,'* which results from the rofcL A Japanese study has reported the mortality ex perience of 4 S24 men employed for at least one yeai selection process that inevitably excludes some of the least healthy members of the population from Indus trial employment. This effectdoes not, however, nor before 1965 m 25 Japanese plants which began pro. mally affect the mortality from cancer beyond tbal ob- - during VCM or PVC between 1949 and 1964 inclu served in the first few year* after the start of employ- sive (37). The men were followed to 31 October 1975. meat, and an SMR of 102 for cancers other than can- Twenty-eight percent of the men were observed more cer of the liver te compatible both with the absence of than 20 years after first employment, but none was ob hazard and with SMR values of 84 for other disease* served more than 26 years. Only 0.6 ft ofthe men were and 77 for accidents, poisonings, and violence. untraced, and copies of the death certificate were ob tained for all the 209 men who had died (4.6 ft ofthe initial cohort), individuals were classified according Angiosarcoma. Death certificates are an unreliable to the job In which they had been longest employed source of information about the histology of cancers at the lemUnaiton of their follow-up. and data were that cause death, but (here is no reason to suppose that riven separately for the 2 546 men classed as employed the excess mortality attributed to fiver cancer (or, in in PVC production and 1 978 others (including 900 classed as VCM production workers). (f this study U continued for another 10 years, it the US series, fiver and gallbladder cancer) Is not entire ly accounted for by the known hazard of angiosar coma. Fifteen of the 37 deaths1 attributed to cancers should provide useful additional informalion, taut the of the liver and gallbladderIn theUS series are known present data include too few observations on men more to have been due to angiosarcoma of the liver (14). than 20 years after first exposure to be of any material In the UK series, seven of the 11 deaths attributed to use. They confirm the evidence of a hazard of liver liver cancer, not specified as secondary, were known .`uncer with six deaths among the PVC production workers against 2.54 expected from national rates, uhitc only one such death was Observed among the to be angiosarcomas, and they all occurred in autodave workers against 0.38 expected liver cancers of all types <P< IC";) (25). In the Canadian series, histo other workers against 1.82 expected. One of the six .deaths from liver cancer among the PVC production workers was certified as due to angiosarcoma of the liver, and at least one of the other liver cancer deaths *as due io the same cause. Lung cancer deaths were not in excess (2 observed in PVC workers against 2.33 expected). No data were given for cancers of the lym phatic and hematopoietic systems, for cancer of the logical review showed that seven of the eight so-called liver cancers were angiosarcomas (one had been de scribed as an angiosarcoma on (he death certificate, two as hepatomas, and five as unspecified liver can cers). One so-called liver cancer death was found to have been due to cancer of the sigmoid colon, while one death attributed to angiosarcoma of the periio- braid or thyroid, or for melanomas. The mortality reported by Masuda (33) for 305 Japanese vinyl chlo- Increased to 39 in table I io take account of the 97 exin. deaths from tn unknown cause. 32 ^ c*j Co Tefale 1. Observed and expected cumber* o* Seethe from different cancer* i*PC<1*d In tti fear principal atudtea R. 14. 2& 46J.(0=obaafvtd number of deaths, Eaexpected numb* of daetha) Type or daai Of cancer IMtecr State* 0* E United Kingdom 0 Canada oE rt(y OE Buccal carry and pharynx Esophagus Btomaoh Large intestine Rectum liver Liver and gallbladder Pancreas Other dtgeilhe Larynx Lung Other reeoimioty Bone Skin (Mnmaiahcma Melanoma Prostate Tetda (Holder Kidney Othr wvt unspecified urinary Btain E^and central nervovs ayatam oho-and retlcufoearcoma jkln1* disease xamta vuttlple myeloma 1 Other lymphatic f Other An cancer* V 1136 T 1.07 It 19.01 21 26.79 30 SJ7 179 18.44a 118 11567 9 tit 2 161 6 738 ie 1560 & 848 is 808 25 12.78 12 768 3 6.45 14 1X64 8-37 46 4060 363 341.73 4 368 1 e 1464 28 2361 9 1364 11 104S 114 164 7 686 , 4 261 81 62.12 ,* 2 1.7* 12 069 2 168 14 100 3 4.10 3 469 4 6.19 2 043 4 238 3 2-80 7 .16 2 236 , 18 612 238 22160 0 064 # 4 0.14 ,. 638 Z 6.78 4 . 060 1 , 2 SO 167 068 1637 1 06 06 3 30 0 13 i 06 0 0> , 0.9 12 6.1 , 0 a'j W X7 a a 6 04 0 67 .. 9 4*6 90 21.1 * Ooaarved deaths multiplied by i6674 and roundad off to the neatest integer to aBow for beam* without discovered cause- TeW*2. Number* oi daaths from nonmefignani and a# causes reported in lha four prtrctotf studiaa (4, iA 25.461. (0observed number of deaths. E=expected number of death*) Unclad State* q* E Untied Kingdom 0E Canada 0E nary OE Benign and other unaoeeflad tviTW* Cerebrovascular disease lachemtc heart dlaee** Other circulatory dlaaaaa Bronchitis* Pneumonia Other reaptretewy disease CirrooM of (he liver Other dlgeauva dlaeaee Olaaaw of the genitourinary ayatem Otner disease* fiulcWe Accidents and other violence 4 969 75 81.93 21 897.73 .. zn 288 } 157 123.59 105 141 44 2263 38 19 16 3164 32.64 ] 40 44 l 61 * 87 6869 27 3962 11 2041 & . . 5 1j . 67 11669 43 76 49 82.78 130 173.19 1 so 25 3167 1 1 6 3.21 | 3.03 2s 6.40 2 10.58 19 $ 4 3 e i 08 274 a.o ti 2.7 70 Ofi 7-7 An nonmeBgnant causes 1183 136364 643 663 39 4.76 38 864 Ad ceuaes 1636 170837 780 B94 89 7167 69 773 See footnote to table 1, * Emphysema m data from the unttad State*- ___ include* two cases certified aa clnhoata of the liver which proved to be angtoeoreeme of the Irvor. tndudee one ease whh oauae unknown.. neum was found to have been due to angiosarcoma tritouted to cancer ofthe liver (for a total of four), but of the liver (46). In the Italian study, further evidence only one ofthe four was described as an angiosarcoma revealed that tiirce further deaths should have been at- (4). as Tabid*. Mortality Irer H< in* tow prtnctp* v number of d**tr>*. SK Cause of dcclh Cancer of th* fiver* Cancer of other alien Other diseases Aceldama, poisoning All causes * including canoere c Titna a Mooemy from various ca (Os observed number of death*, Type or ciaseof cancer Mouth andpftvyru Oigesdve ayatam (other than ilveo Respiratory system Lung Genitourinary syetem Melanoma firzln Thyroid Lymphatic and hematopotatie y*i Qtftar_________________ An other (nan of me liver a 1* United Slate* study (14). ? c i Table $. Mortality4 from variouo cr Bomber of deaths. = expected m. .Type or class ol cancer .Digestive system staxdutfing the ifveil ft Ra ct G <H O 36.C 233 ThyroiC Lymphatic and hemalcPoielle tystem 0(t*c (excluding me l*vfl Ah excluding the INer 2.1 163 .10.7 6T.I ?;.* Incidence and cases in ih Nor* Cancer of the Intestine only. * Cancer of the luno and brim on V.-: r lor Dver and gallbladder be attributed principally if n rt of angiosarcoma is obt : excess deaths with the ni rcom recorded in the I URL 13588 ^19x93 12:19 <<xr principal stw4(s <4, |4,2ji <naa . o!h 62i 5.78 (IMy 0 ea 11 0044 \a 5 34 1 0 121 i 04.1 0 0> j i 04 i 12 0.1 . 01 00.47 Jj IS! i 0> 1 040 147 G 0 0a4/ 1' 0.65 9 44 ' 16.37 90 21.1 daaitis without discovered cause. 0419 382 8842 HCQ HULFORD LBRY @1010/027 wwwwwe fjnrmuwwjf.Ty Teble x Monellly (Tomcancerof fhe Over and othereeuee* umonQ vinyl ctiiorids wor* In *9 plume In the lour principal cturfleC Combined <4,14,26,46). (OKeOserrotf number of deaths, s expected iwnibr of deuthe.&Mftnsrundardlxed mortality Q) Cauaeol deem Cancer of the liver* Ctfloaf ef other tlvee Other dlaeases Accidents, pouortnoa. and violence Alt eeueee 0 6$ 609 1847 228 3441 E 645 6W45 104449 285.15 274744 8MR 606 102 04 77 as * Indvdmo cancer* of tut Qi5bladder In the hum from Vie Veitad Slatei. Table 4. Mortality from venous cancers among vinyl eMoride worker* in 4fl pleats ui me four principal etudiee comWnaj. <0*obeerved number of deaths. Esoxpoead aumber of dastha, SMAsstoManlM mortality rattaf Typ or class of cancer OE SMR Source of Information* MeUtil MI pharynx Digstllve system (other then liver) Respiratory system Lum OenltCHjfinery system Melanoma Brain Thyroid Lymphatic and hematopoietic eyetem Other All diner than ef the Ivor 10 1647 125 19449 223 22826 211 21449 70 0241 2 144 20 1644 2 043 87 5047 83 6344 009 60645 100 1,2.3,4 81 1,2,21 87 1.2.3.4 60 1.2.4 111 1.13,4 * 2.4 140 1,2.3 2 112 1,21.4 131 1.2,3,4 1Q2 1,2,3,4 leUnited States study(t4),2Unrte4 Kingdom study pS),Canadian study (46). and 4eNUen study (4T studies(4,14.2S.4Q.(0 scbsefvod Canada - Italy OE > 3147 | 5 X21 | K 3.65 0 19 3 04 274 SO "" r 5.40 2 104$ 9 54.76 >9 7147 2 7.0 I 0.0 4 7.7 34 564 66 774 Table 9. Mortality* from vanou* cancan amona vinyl chloride woman: Supplementary evidence (4,7,22,40). (0* obetrved number of deaths, Eeexpected aumoarof rtaalnt, bMH- mandwdaaa mortaiay ritw) Type or clsea of cancer Federal Republic d Germany (11 (dents) 0E Norway G pfang oe Sweden ri piano 0e Italy (I plant! 0E Four countrtea combined (14 plants) 0 E SMR Dtoesifew system -excluding the Over) Lung Melanoma Bruin Thyroid Lymphatic end hemetoooietic system Other fexcledlng the Uw) All excluding the Rver 354 314 234 244 , 21 14 .* 194 7,7 10.7 244 674 86.7 3" 1r*4* 8 244 4 0.78 2 0.18 . 6 14.03 22 2ai 3 1.70 2 043 *. S< 2-11< 1 14 0 14 0 0.1 , 0 0.7 4 24 8 5,7 364 314 44 4.1 24 164 22.7 1104 3444 aoii 049 143 OM S.4 4143 11747 113 103 . 106 55 102 ' incidence and ceaat in tha Norwegian study. Cencar of uie tnteatlne only. : Canear of tha lung end bram only. URL 13589 i f the fiver tie liver (for a iota] of four}, but as described as SO angiosarcoma Further evidence that the excess mortality from Over cancer (or Hver and gallbladder cancer in the US senes) can be attributed principally if not wholly to the known hazard of angiosaxootn* is obtained in a comparison of (He excess deaths with the numbers of deaths from angiosarcomas recorded in the Register of Liver Angio sarcoma Cases (maintained on behalf of the Associa tion of nasties Manufacturers tn Europe by the Im perial Chemical Industry PLC) before the end of the follow-up period (Bennett, unpublished). Fifty-one ex cess liver cancers are recorded in the combined data, and 49 angiosarcoma are recorded in the Register for 69 URL 13S90 Tibia l Mortality from tuna mm In the eerie* from she Unitd sw(ii(14) md theUnited Kingdom<mq to ey eMfaotertaUo* relevant te*o nooupaMonw hiam. (0=06auvad number of death*. Ewexpebtod number of deatna, fiMRsaSandardtad mortality rata) cruractortattc* Category 1 O* E SMR Obeerved 20 yaara or more attar ftrwt mptoyrnem ft), other* CD Employed 10 yean or more tn the US (1). ether* In the US (2) Employee before 1M6 in the UK (1), other* Ir the UK Ever employed m autocl*** worker In theUKfl). other* In tne UK 11* 113JS TOO 66 6E4S 106 62 61.99 101 16 17-09 94 Category z o* E SMR 65 C43 *1 63 fB44 99 40JO 72 65 74*2 67 be seen than in other groups. This drcomitance k Illustrated by table 6, wtddi shows that the SMR values are ilightly higher for men observed 20 yean or more after fim exposure than for men observed earlier, for men employed before 1956 In the UK than for men lira employed after 1953 (when exposure levels we believed to have been lower), for men employed for longer than for shorter periods in the US, and for autoclave workers in the UK (among whom (he angio sarcoma eases have mostly occurred) than for other workers. The differences are all small or very small. They an, however, all la the same direction, and the probability that the rales should aQ be higher In the groups inwUch an occupational hazard k more like ly to be seen In each of the four pain of groups is I in 16. Additional information from other sources is given In table 5. A total of 30deaths (or esses) was observed, and this figure increases to 31-5 when allowance Is S ' Additional information fror | given In table 5. The small ex| Uuie further evidence of an ot one of the two deaths observe. occurred in a young m^n who! less than year when the dragthe excess death rate for brain I German study was less than chemical workers not exposed deaths after allowance for d > causes against 1.6 expected) anc PVC fabrication Industry (5.9 * for deaths from unknown cause Cancan ajlymphatic and hem ida that vinyl chloride might c phttic and hematopoietic iissu< the lymphatic tissue -- was su. AGaffey(45)and by WaxweQer tin numbers in paranttwsea deeionate the category, a Soe footnote to (able 1 tor observed deaths fci ins Us. made for the number Of deaths due to unidentified causes in the German study (S'*R becoming 103). In . studies, when they found, re* from lymphomas In the most b< the German study the SMR was higher for (he men against 2.54 expected and four devut periods for the three countries mod the two __*ijan piims* (hai are covered by (he forvey. None of ihc 120 cases yet reotfded Is the Regl*t vrere id men who were first exposed after 1969, and hods of the 46 men affected in North America were first exposed after 1964. AH may. therefore, have been exposed to cencentrattom of several hundred parts per siiUlofl. and many may have been exposed to eoocentradoos appreciably higher (unpublished report by Bair io Air Products and Chemicals lne in 1981). who had been exposed for 10 years or more than for those who had been exposed for shorter periods (l 11 against 79), and, In the Norwegian study, four of the five cases observed occurred fat men whom occupations were regarded as involving high exposure against 1.82 ofthe 2.34 expected. Both (beGerman and theSwediih studies derived the expected numbers of deaths from national mortality rates for a tingle year towards the end ofthe study period. The expected numbers of deaths ire Bkdy, therefore, to have been overestimated and the SMR values correspondingly underestimated the lymphatic and hematopoieti pected. There small excesses mi : If the laboratory findings had r. : suggesting that lymphomas wen tally In animals exposed to vir. ^tioa (29). The Ides that limila .cause lymphomas in humans, :ous consideration. The data fr that are summarized ir ippon for the hypothesis wh iphatic and hematopoietic ti$ Lung canctr. The ides that exposure to vinyl chloride might cause cancer of the ting was suggested by Mot ion etal in 1974(36), when they noted 13 cose* again an expected number of7.9 in a study of proportional mortality. The combined data shownin table 4 do not provide any support for the hypothesis, cither for res piratory cancer as a whale (SMR. 97) or for the speci fied dau for lung cancer in the US, the UK. and Italy (SMR 99). There are, however, consistently higher risks in the subgroups of men in the US and UK series, in which occupational hazards would be more likely to as the raqnalliy from lung cancer bad been rising throughout the period of observation. Brain cancer. The idea that vinyl chloride might cause brain cancer was also suggested by Monsan et a! (36) when they reported five cases against 1.2 expected. The combined data that are showo In table 4 provide some support for this hypothesis. The cases of Monson et al (36) were, however, observed In US workers and must be presumed to be included in the total reported by Environmental Health Associates (14); therefore they will have contributed a substantial proportion of ggether (57 deaths against 50.8* i very little more is obtained cancers ofthe lymphatic syst. t`i definition of ICO list nun 203 and 205 being used) t <(35 deaths against 29.40 expc aoreover, hardly altered if the ifley's initial report are subtra 1.36 expected, SMR 124). Little additional inforra&tio results of the German study {4' {study obtained an SMR of 2\< ' Twenty-nine were registered as occurring io (he United the toul In table 4. As a test of the hypothesis the data State* ocainct an excess of 33; only 20, however, were iden of Monson et al Ought, therefore, to be subtracted tifiable In both series, Inquiry has, a* yet. foiled to reveal information about the histology or the remuntoe 13 In the cohon study and the oripo of the nine extra deaths in the register. Nine deaths were registered as occurring in the from those in the table. Their investigation was not a cohort study, and their expected deaths do not cor respond exactly to those in table 4. If. however, the 1 United Kingdom against an exces* of nine, bu< one of Ihe observed and the expected eases are both subtracted registered cases was certified as due toa benign bemangtom* from the totals, twenty-four observed deaths remain and nos related to the liver (coda 227 In theeighth revision of the International Classification of Diseases). Tea cases were registered as occurring In Canada against an excess against approximately 18.3 expected, a difference which might eerily occur by chance <P one-h( of eight; two were recorded as bring la men who bad been 0,1)/* employed far five yean, and ii it possible that the actual duration had been slightly leu than five years with coa- sequeu exclusion from the Canadian cohort. One case was 4 If the study of Waxweiicr et al (SO) is regarded as the origin registered as occurring in one of the two Italian plants of the hypothesis, 26 deaths are left against 18.9* expected against an excess of less than One. (P one-oU!ed*=-0.07). on 15 observed deaths, h ilowance is made for the numt wi causes) against SMR va l unexposed group of chernica 3f PVC fabricators, it showed workers was present o i exposed for more than om ; was most marked for men t five years or more (10.7 dear number of deaths from tin: [0 expected. SMR 268. P one Janoma. An excess of roelaui egian workers by Heldaas .70..,,.____ ____ _____________________. _ ...........i-1--itfi i^'rtrU `it-/' arna1 oz-'ly/'j;} 1Z : Z1 MULb'OKU LbKY lan roups. This circumstance eh shows that the SMB. vah. m observed 20 years or mor for '"*n observed earlier, 35 e UK than for m< 55 exposure levels i, ,or men employed iods In the US. and fc UK (among whom the angle sily occurred) than for other! s are all small or very small. < n the same direction, and the. es should all be higher in the; ipational hazard (s more like-1 the four pairs of groups is l on from other sources is given^ deaths (or cases) was ohserved,j es to 31.5 when allowance la! or deaths due to unidentified ] tudy (SMR becoming 103). Ini SMR wax higher for the meal for 10 years or more than for] posed for shorter periods (11! : Norwegian study, four of the; itred in men whose occupations! ring high exposure against 1.82 loth the German and the Swed- r expected numbers of deaths j y rates for a single year towards | ,-riod. The expected numbers of fore, to have been overestimated orrcspondingly underestimated i lung cancer had been rising 1 o' 'rvtiion. il.. ,.yl chloride might cause suggested by Monson et al (3d) e cases against 12. expected. The e showain table4 provide some thesis. The cases of Monson et , observed in US workers and w included in the total reported :alth Associates (14); therefore uted a substantial proportion of a test of the hypothesis the data ht. therefore, to be subtracted le. Their investigation was not \eir expected deaths do not cor0 in table 4. If. however, the ccied cases jre both subtracted tv-four observed deaths remain ly >8.3 expected, a difference ccur by chance <P one-tailed = tier et al (501 is regarded as the origin Jeaihs arc left against id.94 expected Additional information from two other sources Is the possibility that vinyl chloride might have produced given In table 5. The tmall excess reported provides the disease. Four cuss were observed when 0.79 were little further evidence of an occupational hazard, as expected, and three ofdie four were in men whose oc one of the two deaths observed In the Swedish study cupations involved the highest exposures (against 0.31 occurred In a young man who had been employed for expected). At the time of the writing of their report, less than a year when the diagnosis was made, while adc further case had been detected with onset three the excess death rate for brain caacar observed In the yean after the closure of the itudy. Subsequent studies German study was loss than that observed among in other countries have, so far, reported only two chemical worker* not exposed to vinyl chloride (2*9 deaths against 2.0 expected. (See tables 1 and S.) deaths after allowance for deaths frost unknown causes against 1.6 expected) and among workers in the PVC fabrication Industry (5.9 deaths after allowance for deaths from unknown causes against 1,1 expected). THjmidcancer. Aa excess of thyroid cancer was also reported in the Norwegian study (22), In which two cases were observed against 0.16 expected. The inves Cancers oflymphatic and hematopoietic tissues. The idea that vinyl chloride might cause cancer ofthe lym phatic and hematopoietic tissues -- more specifically the lymphatic tissue -- was suggested by Tabenhaw A Gaffey (45)andby Woxwe&er et al (50) In cnocohort Studies, what they found, respectively, five deaths from lymphomas to the moot heavily exposed workers against 2.54 expeded end four deaths from eanoen of the lymphatic and hematopoietic tissues against 25 ex tigators werenot aware of uy other studies indicating an excess ofthis type ofcancer, and they drew no con clusion from their observation. Two of the three major studies that have been reported since the Norwegian observation was made gave no data for thyroid can cer; the third reported two deaths against 0.43 ex pected. (See table I.) One death from thyroid cancer, it may be noted, was reported in the US by Monson et tl (36). pected. These smstl excesses might have been ignored If the laboratory findings had not been interpreted as suggesting that lymphomas were produced experimen tally tit animals exposed to vinyl chloride by inhala tion (29). The idea that similar exposure might also cause lymphomas In human*, therefore, menu seri ous consideration. The data from the four principal studies that are summarized In table 4 provide Unle support for the hypothesis when all cancers of ihe lymphatic and hematopoietic tissues are considered to gether (5? deaths against 50.87 expected, SMR 112) and very 6ttle more Is obtained from theseparate data Concert ofthe digestive tract. Suggestions that vinyl chloride might cause cancers of the digestive tract in general have sometimes been made, but.they have not taken adequate account of ihe contribution of cancers of the Itvar to the total number of cancers Of the digestive system, particularly whai it is borne ia mind that Hhne liver cancers are likely to be-misdUgnosed as cancers of other organs. The combined data from the four principal studies shown in able 4 weigh heavily against the Idea tbit any such effect has been produced. for cancers ofthe lymphatic system fTabenhaw it Oaffey's definition of ICO Us naraben, eighth revision, 200--203 and 205 being used) that are shown io table I (35 deaths against 29.40 expected). The position Is, moreover, hardly altered if the data fat Tabcrshaw A Gaffey's initial report are subtracted (29 deaths against 23J6 expected, SMR 124), Little additional information Is provided by the results of tbe German study (49). (See table 5.) Thti ctudy obtained an SMR of 214 for exposed workers (based on 15 observed deaths, increased to 16.5 when allowance Is made for the number of deaths from un Other cancers. One ofthe remaining types, or classes, of cancer listed In table 4 shows a statistically signifi cant excess, namely, the heterogeneous group of "other cancers" (83 observed deaths against 65-24 ex pected, P two-aided <0.03). This excess is only mar ginally rigrrffiant and may be a chance observation. The most likely explanation Is, however, that a few angiosarcomas of the liver were not recognized and were diagnosed as secondary liver cancer or carci nomatosis, rite unknown, the number ofdeaths ht this category therefore being increased. known causes) against SMR values of 77 and 34 for an unexposed group of chemical workers and a group of PVC fabricators. It showed that the excess of (he -exposed workers was present only for men who had been exposed for more than one year and that this ex cess was most marked for men who had been exposed for five years or more (10.7 deaths after allowance for (hr number of deaths from unknown causes against 4.0 expected. SMR 268, P one-tailed <0.01). Hazards of nonmaligaanc disease No previous study has suggested that any noamalignarti cause of death other than cirrhosis of the liver would be likely to be increased as a result of exposure to vinyl chloride, and cirrhosis of the liver is presumed to be increased only because of the liver changes that were observed as part of the "vinyl chloride illness'* (24, 31, 33). Two other possibilities have, however, been raised, namely, the production of noamilignant Melanoma. An excess of melanoma was reported for respiratory disease, because of the changes in lung Norwegian workers by Heldaas et at (22), who raised function and radiographic appearances that have been 71 TcWtT. Mtninty l4tUaMIWltfdMM n cause* in the four principal etudtes oomMmO. (Oobserved number or daama, E&expected number of death*. SMRsBUnriardizad mortality ratio) Type Of disease 0 E 6MR Source of InforaiatIon* Bronchitis. emphysema* BO 6443 120 1.2 Oinar reaptratory disease 7t 12S.78 96 1.3 rooordedfor mn expoted to PVC dust (2, 26.27.44). and acute cardiac death, from analog; with the effect of other haloganated hydrocarbons (25) and the obtervation of an Increased mortality from myocardial Infarction in the few years foQowiag the cessation of exposure In the Swedish PVC processing Industry (35), Relevant figures for the numbers of deaths from these and other noomalignant causes that are obtainable from the four principal studies were given in table 2. and they have been summarized in table 7. All respiratory SitSMI 160 Z0042 tochertlc heart disease 7*7 686.73 Other circulatory UlSfB** 2SZ 26446 At circulatory disease* 1103 1 20946 Cbittoais of the liver 46 6626 Other disease 23a 966.07 60 1.13.4 90 14 06 14 81 1,2. a. 4 69 1.2.4 66 1,2,9.4 Clrritosls of the fiver. Three of the four principal studies gave separate figures for cirrhosis of the liver, none oT which showed to increased mortality (table 2); la combination they gave an $MR of 69 based on 46 deaths. The fourth study, which did not give sepa rate data for cirrhosis of the Ever, reported four deaths from all diseases of the digestive system combined All npnmaiignant disease AM external causa* 164T 164440 226 285.16 84 1,88* 77 12,3.4 against 3.85 expected and noted that the four Included two that-were certified as due to cirrhosis of ihe ttver. but aouaUy due toangiosarcoma (46). In the two sup 1 nonrastignant jueee AH causes 1773 219946 05 1.2. a. 4 2441 a 74743 89 12.9,4 plementary studies in which data were given for this disease, the SMR was 82 In one, based on 15.1 deaths after allowance for the number with unknown causes * i-umtsd State* atudy (14,2 Uftad Kingdom tttidy (H). StsCartadian study (46), and 4*itaftan study (4). * BroncWtte m tn tinned Kingdom study, emphysema In trip United Stats* study. * indudstoembfevaacular disease In the untied Kingdom vtti ttritan stutfes. (49), and 133 in the other, based on seven deaths (37). Nonmalisnant respiratorydisease. The data for nonmahgnam respiratory disease are confusingin that the total SMR from the combined data for tbe Tour prin cipal studies is 80 and Is tbe sortof figure that is com monly found in healthy industrial populations, yet the Table ft. Mortality from chronic obstructive lung disease* in the series Itemthe United States(U6) (14)and the United King dom {UK} <25} by chameisristlee ratavant to an occupational hazard. (0oba*fved number el death*. E asptaed numbar ct deaths, SMR * standardized mortality ratio) Data characteristic* Category 1 O 6 QMfl Category 2 o e earn Observed 20 years or more after nmt emplcymeAt In ihe vs (t). Others to the US (2} Employed 10 yean or more in the <JS (1). others m the US (2j Employed before 1866 to the UK (1), others tn the ok (2) Ever employed u an autodcra worker to 6UK 01 other* in me UK 30 16 26 6 164 160 104 147 90.17 66 646 46 11 7.0 157 25 120 206 10 1340 74 33 97-22 88 * Described aa emphysema in ina US study and a* bronchitis In Ihe United Kingdom study- * Tht number* In parentheses d^tgnat* the category. ' Men ever employed eaabegoer or drier, occupation* which would have causad the gr*v*et occupational exposure to polyvinyl ehlono* dust, experienced one death (tom bron chitis sgSnsl 4,96 xpiod US study recorded a substantially Increased mortality from emphysema (41 deaths and an SMR of 180 be fore any allowance was made for deaths from un known causes). No such excess was found in the UK. where 36 deaths from bronchitis gave an SMR of 82. International companions of chronic noaiualignani respiratory disease are complicated by the usage ofdif ferent terms to describe what it h now agreed is best called chronic obstructive lung (or pulmonary) disease, but which iu tbe past tended to be called emphysema in the US and chronic bronchitis in the United King dom. tt must, therefore, be presumed that the two categoric of '`emphysema" and `bronchitis" used re spectively in the two large national studies were meant to describe the same thing. One must assume, there fore, that the experiences m the two countries were vert different, despite the fact that both related to cahon> that bod very similar experiences of angiosarcoma ot the liver and so, presumably, fairly similar exposure* to vinyl chloride. Separate figures are shown in table 8, when Avail able. for (he mortality observed among men with dif ferent durations and intensities of exposure. Unlike the data Tor cancer of the lung that were shown in table 6, they provide no consistent evidence of a greater risl in the groups in which an occupational hazard would be expected to be concentrated, virotunenul Health Associates t to give any explanation for tt from emphysema, and they p* hardly be due to excess cigarette no overall excess for cancer of t however, that the excess is more by defidenciet in the other categ respiratory disease (pneumonia Other respiratory disease 14 de; the question arises whether ti could be a dassificatory an Health Associates (14) list all th< that they1were coded under IC in the out-of-date seventh revl* the coding of all deaths in the s"other respiratory disease not or included emphysema. Under tl emphysema that was associated be classified with bronchitis un to SQ2, and the possibility may t of the emphysana deaths shou' fat some category of respiratory number $27. Ifthis were the situ Tor both theexcess mortality fro grossly deficient mortality fror respiratory diseases. No excess mortality from "b> and asthma" was observed in it with 6.3 deaths observed a lumber of deaths from an un liovascular disease. Dam fc c) heart (which n ide the vast majority of ail c acute cardiac disease) were ; national studies, and they j i Increased mortality. The SM ip of diseases and of 91 for : recorded in (he four princ (the SMR values of healthy i I there is no suggestion of ar tfthe subsidiary analyses provk ^ Jn particular, there fc mortality within one |5floyment in the UK study ettl ^deaths, SMR 61) or for the mot tve workers (9 deaths. SMR A slight increase in ischemk ' was recorded for the expos i study (49), but it was less -* The deaths attributed to differm; euo end the corrc*ponding~SM section (or the US study an rual Health AuocUl<14) j 1 account for the number of > e. To take account of these t SMR values can both be o 7 .^1 VW O.d/ I'J/'JJ 1 to PVCdust (2. 26.27, from analog/ with the cff drocarbcns (25) and the J morality from myocar rs ing the ccnation 3\ essing industry (3 deaths from th uses that are obtain* studies were given in table unarized in table 7. Three of the four panel: ures for cirrhosis of the liver, an increased mortality (tab gave as SM R of 69 baifd udy, which did not give the liver, reported four deal: e digestive system combi d acted that the fourfodu u due to dirhosis of the liver, sarcoma (46). In the two su; rhich data were given for 2 in one, based on 15.1 deaths number with unknown can er. based on seven deaths (37) ory disease. The data for n Eiseate are confusing in that mbined data for the four pi is the sort of figure that is eo y industrial populations, yet 'bsiontiaUy increased mortality der ''d an SMR of ISO be- for deaths from uul . was found in the UK, bronchitis gave an SMR of 82.1 isons of chronic nonmalignant complicated by the usage of dlfbe what h is now agreed is tive lung (or pulmonary) disease, tended to be called emphysema! c bronchitis in the United King ore. be presumed that the two sema" and "bronchitis** used re. arge Rational studies were meant thing. One must assume, there<ces in the two countries were very, fact that both related to cohorts experiences of angiosarcoma o umably, fairly similar exposures MCO HULKOKl* LMWY -UIW'IR be expected to be concentrated. The authors of the En- be tinexposed chemical workers and the PVC fabri- \ ironmentd Health Associates report (14) were unable carora (SMR values of 127, 131, and 138 baaed oo 97-2. io give any explanation for the increased mortality 126.7, and 109,7 deaths, respectively, after allowance from emphysema, and they point out that it could for tbe number of deaths from unknown causes). hardly be due to excess cigarette smoking, ** there was no overall excess for cancer of the lung. It k striking, however, that the excess is more than compensated for Discussion by deftdenciea ki the other categories of nonmilignant Tbe information that has now been obtained about the respiratory disease (pneumonia 15 deaths,* SMR 47.0; long-tana health of men occupationally exposed to other respiratory disease 14 deaths, SMR 42.6), and vinyl chloride k massive tod compares favorably with rhe question arises whether the emphysema excess that available for any other occupational group. Two could be a clauifleatoiy artifact. Environmental facts are outstanding. First, the men have experienced Health Associates (14) list all the41 deaths which show a specific hazard of a type of cancer that is normally that they were coded under ICD dumber 527 which, in the out-of-date seventh revision that was used for the coding of all deaths in the study, was the code for extremely rare, namely, angiosarcomaof theliver. The rarity of this disease under other conditions made the detection of the hazard easy; but the long latency "otho- respiratory disease not otherwise dasaiflcd11 and period before the disease appears after first exposure included emphysema. Under that revision, however, (almost always more than 10 years and usually more emphysema that wi associated with brondritit should than 15 years) meant that a large number of meo had be dastified with bronchitis under ICD numbers 500 to 502, and the possibility may becnaddffwlthat some of the emphysema deaths should hive been rinrifled In rooie category of respiratory<&ce otherthaalGD number 527. If thIs were the situation, h could account for both the exesa mortality from emphysema and the grossly defidem mortality from other nonmalignant respiratory diseases. No excess mortality from "bronchitis, emphysema, and asthma"1 was observed In theOerman study (SMR 44 with 6.3 deaths observed after allowance for the number of deaths from an unknown cause) (49). been exposed before the hoard was detected and that It wiB still be many years before the extent of the prolection provided by the reduction In exposure in the I960* and that of the further reduction that followed the recognition of the hazard in 1974 are known. There b. unfortunately, no effective treatment for the dis ease, and the number ofcues lx reflected in the num ber of deaths. Some 50 deaths have occurred among tbe 16 740 men who were followed In tbe four prin cipal studies that have been reviewed in this report, so that approrimaldy I in 335 men have been affected. 2 7 of the deaths having been doe to this one cause. Eventually many more men must be expected to de velop the disease. One estimate (38) suggests that tbe Cardiovascular disease. Data for iscboulc (or artoiowlerotic) heart disease (which may be presumed to in clude the vast majority of all deaths certified as due to acute cardiac disease) were given only by the two big national studies, and they provide no evtdooe of an increased mortafity. The SMR values Of90 for this total may be Increased 10 times, but a more realistic estimate Is two to three timet (19). The second outstanding observation k that the mor tality of the exposed men, other than that due to angiosarcoma of the fiver, b typical of the normally healthy industrial worker -- that la not to sty that no group of diseases and of 91 for ifl cardiovascular dis ocher hazard exists, but that the effect of any other ease recorded in the four principal studies are typical of the SMR values of healthy industrial populations, and there is no suggestion of any occupational hazard in the subsidiary analyses provided by the two national qudies. In particular, there b no evidence of an in hazard is small. The missive data that ore oow available provide no reason for thinking that any hazard other than one of cancer bats been overlooked. It is. however, still dif ficult to dodde whether vinyl chloride produces a risk creased mortality within one month Of leaving em of developing cancer other than angiosarcoma of the ployment in the UK study either for afl workers (52 liver which might be smalt compared to the risks deaths. SMR 6t| or for the most heavily exposed auto clave workers <9 deaths, SMR 42). A slight increase in ischemic heart disease inortal- -it > was recorded for the exposed workers ta the Ger man study (49). but it was less than that recorded far produced by nonoocupationa! causes, but yet abso lutely almost as laige as die risk of developing the nor mally very rare angiosarcoma. One ofthe many hazards suggested can be dismissed, as there is no evidence to support it, namely, that of vinyl chloride os a cause of any cancer of the diges The deaths attributed to (Bftcnra groups ofrejpb-itofy dis eases and the con-eipondmgSMR values that art cited in .his section for the US study are as grvea by the Environ mental Health Associates (14) and have not been adjusted *o account for the rumba of deaths from an unknown caoM. To take account of these deaths, the observed deaths SMR values can both be multiplied by 14)474. tive tract other than angiosarcoma of the liver, Two hazards (of melanoma and cancer of the thyroid) Have been suggested only very recently, and few of cftc avail able studies have provided information about them. There is no good theoretics! reason or laboratory evi dence to suggest that either should be produced by 73 URL 13593 vinyl chloride, rad, in fight of present evidence, the simplest explanation U that the reported eueew are the chance effects that must be expected when many different types of tracer are studied in several different cidence of the disease varies moreover wkhin a coun try, and there must be doubts as (O whether the na tional experience provlda a sukable reference for men employed la plants that are not evenly distributed populations- So far as melanoma is concerned, it has about the country. In these circumstances one cannot to he remembered that the disease has become much exdude an occupational hazard unless it cm be shown more common in recent yean in Scandinavia (where that the mortafity of the exposed men Is Independent the excess was reported) due, h is believed, to the of the factor! that might be expected to influence it popularity of sunbathing and the increased oppor tunities for Scandinavians to travel to the warmer pars of Southern Europe and North Africa. The extern to If tome of it were occupational in origin, namely, the Intensity and duntkm ofexposure and the time since exposure began. It k not possible to examine these whicb this change may have affected the observation relationships in detail, as the reports do not provide In Norway needs to be examined. Two other bawds (oflymphoma and bnJn eencer) were suggested by the early results of some of the US allthenecessary iofamtadon. Such Information they do provide, which wassummarized la (able6, supports the Idea that exposure to vinyl chloride Involves a small studies. That vinyl chloride might produce a hazard of lymphoma was fam*ny supported by the prelimi nary rendu ofanimal studies, but thecomplete results hazard of lung cancer. Taken in conjunction with the knowledge that lung tumon have beenproduced in sev eral species of animalsexposed to viatf dilorkle by In of the many investigations that have been undertaken halation (29), It wouldseem that a small hazard of lung (see reference 29) do not suggest that lymphoma or any cancer probably did occur. The evidence is not. how other cancer of the hematopoietic system is liable to ever, strong enough to ooodude That it definitely did. produced. There k, however, some evidence that IfIt dkh the hazard waserident only for men whohad t tumors can be produced In ms (291* The hypoth- been employed for many yean at a time when expo that lymphomas and brain canoers aright be sures ofseveral hundredparts per mllSoti Of more were produced by vinyl chloride have been supported by the common, and any persisting risk can be only minute observation that both these types ofcancer have caused and Incapable of detection. death more often than might beexpected fitwa national The qaraioas that have been left anaoswered by lids mortality rates, bat the excesses observed In the com discussion might well be answered definitely if (I) alt bined data from the four principal studies In this re the exposed men could be fallowed to (aajfl the aid view an email and not statistically significant, rad the hypotheses remain unproved. The small exoea ofbrain cancer is particularly difficult to evaluate, as mortal- of 1984, <U) the investigator* could present their data in comparable ways, taking account of duration of employment and time since first employment and tty rates from this disease have changed rapidly over preseating data sepeiotdy for men first employed be time at methods of diagnosis have improved rad the fore (say) 1965 and between 1965 and 1974, rad (ill) suspicion of an occupational hazard (which was raised estimates could be made ofthe effect ofcorrecting the ia 197J) could have influenced the findings. What ex results for each group of employees for the locality In cess has occurred ha* been limited to the VS and Ger which they lived and worked. many, and the German findings carry Kttie weight, as die excess was found in each ofthe three occupational groups studied, irrespectiveof the chemicals to which they were exposed. The supplementary data from the German study Showing an increased mortality from Hazards to the general population As vinyl chloride has been proved so cause cancer ui lymphatic and hematopoietic cancers are more impres tive, particularly as the excess was the most marked for men who had been employed for il least five years. In these circumstances, judgment tntua still be sus pended until the data for each study are analyzed for each specific type of cancer, by intensity and duration of exposure, and by time since exposure begun. Thar remains the suggestion that vinyl chloride mail and is a mutagen in laboratory experiments, it most be presumed ibai even the minute doses that escaped into the general environment from production plants or (in the early days of manufacture) from pvC materials win have caused some risk orcancer to tin* general public. These risks must, however, have been very small, os &lr concentrations of vinyl chloride, even within a kilometer of plants handling vinyl chloride, might cause lung cancer. At fiat right, this possibil used to be (in or around 1975) of the order of 10 to ity is ruled oat by the SMR of 97 for the combined 40 ppb <1, 3,15), and this level Is about one-ten thou -taa for respiratory cancer for the four principal sandth of the concentration that has caused an occu udies. Lung cancer k, however, normally so com- pational hazard. It it obvious, therefore, that U would .non (accounting for about 8 of the expected deaths! be impossible to detect the risk ofany cancer that might that an increase in mortality that was half as impor be produced by vinyl chloride other than a risk of tant (numerically) as the increase in mortality from angiosarcoma of the liver, as it has proved so diffi angiosarcoma of the liver might easily be overlooked cult to detect aay other risk among men who were ex (OS V, confidence limits of the SMR 85--112). The in posed occupationally. The position with regard to an- giostreoma of the liver is differc; dully so rarethat, iatbeabtcnc to one of the known causes (vidioxide, and arsenic in pesticide annual incidence is on the order la these circumstances the disco la a man living dose to a factorride was used In the days before controlled may be regarded as j of the effect of environmental. Several surveys have been urn' whether any such cases hare occ and Etinder A Pershagea (13) s vicinity of plantshandling vinyl * and Swederftnd found none. In X al (11) found eight confirmed. $ to tborotrast or arsenic and cot ? with vinyl chloride." but they n f tioa of the patient's place of r ? (3) found 14 confirmed cases in tt-yew period, one of which w lived half a kilometer from a plant, rad. inNew York State c g Brady et al (5) found 19 cases g tributed to any known cause, five - pie living vrltinn a mile of plar using vinyl chloride. The overall i last two studies were not undulv jkroce of as many as six cases an jtioseto manufacturing plants Iscolleagues, moreover, corispa is with tnatdted referents an |fbe referents Eved equallydose to gsix neighborhood cases (one ir York State) cannot be sttrib loo with vinyl chloride, a* the disease had lived near * year*, respectively, before d id this period is loo short to al tency- The other four cases, h jfter 15 or more years of local rt ofthese cases strongly so ' the environment around pianos PVC roay have caused amini, public. Current concentrations around ^iloridc are certainly much (owe jptevioutly by the US Enviro ^jhgwicy. Recent British measure |gfow hundred meters of the VCM; values brio* the daily limit three of five plants, the readi 20 ppb (100 m outside the ppb (Just inside it) (47), al igj^ther values were recorded J?a |$*ted with putting one plant iot- gy- figure of M Ift*' cued by H been a misprint for 1.4 * iO ivt rraiinrtnscmrriliiti- r~ X Cj (.a CO -U \,.U VJ/'J3 12:27 Q419 362 8342 URL 13595 /vies moreover within a coug : doubts as to whether tbc is i suitable reference for i tat not evenly disuibuc Jt instances one caor ti unless it can be sb< xposed men is independr b tie expected to inftueacej ipatianal in origin, namely, i of exposure and the time iL not possible to examine the . as the reports da not provit wiloo. Such information as i summarized in table 6, supf to vinyl ehloride involves a t . Taken in conjunction with i (mom have been produced In: . exposed to vinyl chloride by ii seem that*small harard of U >ccur. The evidence is not, 0 conclude that it definitely dU, as evident only for men who I iany years at a lime when exi ed parts per millloa or more1 Tstsling risk can be only minut cciioo. nave been left unanswered byi ! be answered definitely if <i) Jd be followed to (lay) the tigators coaid present their . taking account of duration ne since first employment an< -ately for men first employed between 1965 and 1974, and (tit, ad' effect afcorrecting i t jyees for the locality ii 1 WVmvd. noral population s been proved to cause cancer in) cn in laboratory experiments, Its :hat even (he minute doses that] val environment from production) days of manufacture} from PVC j a used some risk of cancer to the' e risks must, however, have been icentraiions of vinyl chloride, even if plants handling vinyl chloride,: ound 1975} of the order of 10 to] d this level is about one-ten thou*] itraiion that has caused an occu-J - obvious, therefore, that it would ct the risk of any cancer that might] ivl chloride other than a risk ot e liver, as it has proved so diffiher risk among men who were cx-j y. The position with reaa.fd to gtos&rcoma of the iiw is different. This dueate is nor mally so rare that, in the abvncc of specificexposure to one of the known causes (vinyl chloride, thorium dioxide, and arsenic in pesticides and medicines), the annual inddove is oo the order of 1--2 10"1 (S, 8).* In these circumstances the discovery of even one case an accident m the other. According to any reasonable criterion the hazard to the general public (if there is any at all) must be negligible (42). No other hazard to the general population, other than a hazard of caneer, can reasonably be postulated. jn a man living close to a factory in which vinyl chlo ride was used in the days before exposure was tightly controlled may be regarded as presumptive evidence Summary of the effect of environmental pollution. This paper review! 0) the possible effects of vinyl Several surveys have been undertaken to determine chloride on the personal health of men exposed by a hether any such cases have occurred. Sarie et al (43) virtue of their occupation (other than the early effects nd Elinder 6t Parxhagea (13) sought for cases in the of the very high coocctmatioas to which men were ex vicinity of plants handling vinyl chloride In Yugoslavia posed when the industry was first developed--uncon- and Sweden and found none. In Holland Daldenip a sdousneas, etrdlac arrhythmia, and the characteristic al (l l) found eight confirmed cases not attributable "vinyl chloride Illness**) tad 00 the carcinogenic to thorotrast or arsenic tod could trace **ao contact offsets that might conceivably be observed in the gen with vinyl chloride,*1 but ihey mad no specific men* eral population as a result of the widespread distribu lion of the patient's place of residence. Baxter et al tion of vinyl chloride as a pollutant. The possibility (3) found 14 confirmed cases in Oreat Britain over a that vinyl chloride might act a* a teratogea or might 12-year period, one of which was in a man who bad cause mutations (a the germ cells bat not been exam lived half a kilometer from a PVC manufacturing ined, as the little evidence that has been adduced plant. od, In New York State over an 18-year period, relating to sodipossible effects has been reviewed else Brady et at (5) found 19 rases that could not be at whereand the eoodudaa was readiedthat no sudi ef tributed to any known cause, five ofwfckh were in peo fects hive been demonstrated. ple Evtng within a mile of plants manufacturing or Many groups of workers exposed to vinyl chloride using vinyl chloride. The overall incidence rate in these In the manufacture of VCM or PVC havrbeen studied last two studies were not unduly high, but the occur* since the carcinogenic potential of vinyl chloride wu rencc of as many as six cases among people living so first recognized. Some resnits have shown th occu close to manufaduring plants is surprising. Brady and pational exposure on cause angiosarcoma of (he Uver, hts colleagues, moreover, compared theirseries of pa and others have suggested'that ft may cause several tients with matched referents and found that oooc of the referents lived equally dose to a plant. Two ofthoc six neighborhood cases (one in England and one m other types of cancer as well. The actual situation can be determined only in an axamiudon of all the evideoea, especially the combined results of those studies New York Stile) cannot beattributed to environmental that include a substantial proportion of observations pollution with vinyl ehloride, as the mca who devel oo men more than 23 years after ibeir first exposure oped the dims* bad lived near the plants for six and and cover a long enough period for more than 10 7 right years, respectively, before developing (he disease, Of the employees to have been expected to die. and (his period is too short to allow for the necessary The resalu of four studies can be usefully combined latency. The other four cases, however, all occurred for this purpose. They are two national studies, one after 15 or more years of local residence, tad (be dis from (be US and the other from the UK, and two covery of these eases Strongly suggests that pollution studies of onployen in one plant In Canada and two of the environment around plants manufacturing VCM planu la Italy. The results of other studies from the or PVC may have caused a minute hazard to the gen Federal Republic of Germany, Norway, Sweden, Italy, eral piddle. France, and Japan can be used only to provide sup Current concentrations around plants handling vinyl plementary information. The many earlier reports of chloride are certainly much lower than (hose reported exposed workers in the US and the UK concern men previously by the US Environmental Protection covered more completely In the two recent national Agency. Recent British measurements made within a studies, and their results serve only as sources of hy few hundred meters ofthe VCM areas have given aver- potheses. -age values bdow (he daily limit of detection (5 ppb) Minor criticisms can be made of three of the four for three of five plants, the readings at the two others most useful studies. They do not seriously affect the bring 20 ppb (100 m outside the boundary fence) and value of the results, except that allowance has to be S.* ppb (ju^t inside it) (47), although substantially made for The failure to determine the cause of 6.3 higher values were recorded on two oaasxjns asso of the deaths recorded in the US study. Three of the ciated with putting one plant into Operation and with studies use national rates to estimate the numbers of deaths that might have bees expected to occur in the The figure of IA I0-* ced by Heath ct ai (21) seems to absence of any special occupational hazard, and the been tniiprirtt for t,4 10-?. founh (Canadian) uses rates for the province in which 75 the plant *11 situated. It must, therefore, be km In mind that the rales used may not have been wholly ap propriate for the localities in which the plants were situated. This circumstance U potentially important Tar the US study, which covered workers in 37 plants, 22 of which were situated In the southern part of the country. Theother lest informative studies are, for the most part, opes 10 more seriouscriticism, and the value of each set of results needs to be assessed seporatcly in relation to each disease. The combined results of the four principal studies show that theSMR values, reflecting the ratios between the numbers of deaths observed and those expected In the absence of an occupational hazard multiplied by 10Q, have been li) 77 for accidents end otherviolence, CD 84 for disuses other than cancer, and fifl) 102 for cancers other than cancer of the liver. All these results are what might be anticipated for an industry devoid tion Is the observation of an increased mortality from canons of the lymphatic and hematopoietic system* in the supplementary study from (he Federal Republic of Oermauy. Two types of cancer were reported to be in cxce*< (n the Norwegian study, namely, thyroid cancer and melanoma. The significance of this finding is difficuli to assess because very link information about the* cancers has been provided by other studies. Suggestions that vinyl Chloride might cause cancer*. Of the digestive tract have failed to account for the contribution of angiosarcoma of the Km. When this disease is excluded, (he mortality from digestive tract cancer decreaMt to below the average(SMR 82 for the four principal studies). A small excess mortality from the heterogeneous group of "other cancers" in the combined results of the four principal studies was statistically marginally, ' piratory diseases fSMR 46) in no consistent evidence that pbyiema or bronchitis was sp. and it scents possible that the v- US study was an artifact due ' tics w(th the use of the seventh Review' of the massive dab long-term health of men cci vinyl chloride leads to two cka men have experienced a specific extremely care angiosarcoma stately 1 in 335 of the men o tudiod died ofchc disease, ant the observed deaths were attrlb of time Ibc numbers of cases . .be expected to increase two ttbe mortality from all other c iof that of normally healthy inc URL 13596 of any specific occupational hazard. The low ratio for diseases other than cancer-reflects the "healthy worker effect," which results from the selection process that significant (63 deaths against 65.2$ expected, P<0.05t. Some of the excess was likely to have been due to the misclasrificatiod ofangiosarcomas as secondary can -^hazard has existed, its effect The data provide no reason ' ard other than one ofcancer 1 *acviuMy exdudes some of dm leu healthy members T die populatioa from Industrial employment and is compatible with a higher ratio for cancer, as the mor cers of the liver or carcinomatosis, site unknown. The following three nonnulignaat causes of death have required socialexamination: drthosls ofthe Uvcr is, however, still difficult to det ..tide produces snail risks ofcar |due to oonoocupaitanai cause* tality from cancer is not normally subject to such an because ofdamage to the fiver in "vinyl chloride ill. fiver, and, if so. whether, in t affect, apart from the first two or three yean tame- ness." myocardial infarction (from analogy with the dlately following the atart-of employment. effect of other hatogimted hydrocarbons and because ?COute almost as many deaths ? -Ivor. The mortality from cancer of the liver was nearly of some observations from Swedish PYC fabricator), seven timet that expected. Most ofthe 51 excess deaths and nounalgnant respiratory disease because of ' were known to be due to angiosarcoma, even though changes b lung function and the radiographic appear this diagnosis was not recorded on the death certifi ance of the lungs observed fa men exposed to pvc cate. The excess corresponds dosdy with the 49 deaths dart. Far from being raised, the mortality front cir due to angiosarcoma reported to the International rhosis of the liver was 1ms than expected In the three - RqgtacrofA&gtaMrcotssa Cases as occurring in wi principal studies and In oneofthetwo supplementary lt ployees of the pleats concerned daring the paiods studies which gave separate figures for the disease \ under observation. All the men who developed the dis- (SMR values of69, based on 46 deaths, and 82, based ^ auc were likely to have been exposed to coacmtrntlom on IS deaths), vriilie in the other supplementary study There is too little evidence eh. luggtttkm that vinyl chlot i or cancers of the thyroid thematopoietic cystoma. No : have been recorded point - )oal hazard, apart from th t ofthe lymphatic and hema* tan study reviewed, and ro tofchance effect that is oerta iy types ofcancer are exam of vinyl chioddc of severs! hundred parts per million the increase was trivial. ies. or more. Three other types of cancer which have been sug gested to occur as a result of exposure to vinyl chlo ride are cancers of thelung, brain, and lymphatic and hematopoietic systems. The combined data for the Data for myocardial infarction have not bc re ported separately. But myocardial infarction accounts for most of the deaths attributed to ischemic heart dis ease, andthere is no evidence that eitherischemic heart disease or cardiovascular disease as a whole was un lie lack of any increased m< (in the combined results of lb I docs not exclude the p> ; been a small occupations1 i disease, as geographic vari. mortality from respiratory cancer fail, at first sight, duly common (SMR values of 90 and 92, respective f-the disease throw doubt or to support the hypothesis regarding lung cancer (SMR 97). Higher ratios for hmg cancer have, however, been observed consistently in the subgroups In which the ly) or related to occupational exposure. The data for the third category of oonraalignant di- easc (itonmaltgnani respiratory disease) are confusing - onal rates for estimating th< s. The greater mortality In. kcutd be more likely to show a effect of an occupational hazard would be most like because the two large national studies give conflicting .c.h*a other groups suggests th* ly to be seeo (that Is. men employed for more than 10 results. The combined data for the four principal jbave existed. The evidence is, h yean, exposed to higher than average concentrations, studies show the low mortality that is commonly found or observed more than 20 years after first exposure). in healthy industrial populations <SM R 80). This fig . ^existence of a hazard has not ^.Clearer answers to some of t` In two of the supplementary studies U wee also noted that the mortality from lung cancer was specifically increased among the most heavily exposed workers. ure hides, however, an increased mortality from dironfc obstructive lung disease {SMR 120), which indudes emphysema and is due to a grossly increased posed in this review roig SjXrioui groups of investigatoi Results in more appropriate an The combined data show small excesses in the mor tality from cancers of the brais and of the lymphatic and hematopoietic systems. The excesses ore. however, not statistically significant, and there is nothing to sug gest that they are occupational in origin- An exeep- mortality attributed to emphysema in the US study (SMR 193). The corresponding mortality in the British study, which was preferentially described as due so bronchitis, was lest than expected (SMR 82), as wa* the mortality from pneumonia (SMR 50) and other re- As vinyl chloride is a mutfge. qu and a proved human c i that have escaped into th Uutanis must be prcsumcc My minute risks to the go OiVJ`.V03 12:30 ?S410 382 8342 HCO HULFORD LHRV (] 013^U27 i of an Increased mortality fr atlc and hematopoietic sys study from the Federal Repuf ;r -eported to be In exc d _ly, itiyroid cancer of this finding is diffie ,ttle Information about li >vidcd by other studies, nyi chloride might cause cane . have failed to aocount for >sarcoma of the liver. When i he mortality from digestive tn eiow the average (SMR 82 fori s). dreality from the heteroger cen" in the combined result! < jdies was statistically margit against 65.25 expected, F<0.( /as likely to have been due to1 angiosarcoma* as secondary carcinomatosis, tile unknown*] ee nonmalignam eauies of dt examination: cirrhosis of the 1 (O the liver in "vinyl chloride; nfarction (from analogy with coated hydrocarbons and beeav s from Swedish PVC fabricate respiratory disease because rtion and the radiographic apj ibservcd in men exposed to P^ ig raised, the mortality from /as less than expected in the If d in one of ihe two supplement s' *e figures for the (list 46 deaths, and 82, . . jthcr supplementary stud] ivial. dial infarction have not been lut myocardial infarction accour ihs attributed to ischemic heart dli ) evidence that either ischemic 1 ucular disease as a whole was ur R values of 90 and 92, respeetn ccupational exposure, third category of nanmalignant dU [ respiratory disease) art confusl ge national studies give eon dieting lined data for the four princif a- mortality that is commonly found al populations (SMR 80). This rig^ er, an increased mortality fror e lung disease (SMR 120), which tn-j i and is due to a grossly incrcas ed to emphysema in the US studj trresponding mortality in the Britisl preferentially described as due it s$ than expected (SMR 82). as wa pneumonia (SMR 50} and other re piratory diseases (SMR 46) in the US study. There is consistent evidence that tbe mortality from cm* physem* or bronchitis was specifically occupational, it jeema possible that the reported excess in the ijS study was an artifact due to nosologlcai dlfficul- risk could possibly be detected, other than one or angiosarcoma of the liver which is normally an ex tremely rare disease. Several surveys have sought evi dence of tbe existence of such an effect, and sugges tive evidence that such an effect may have occurred with ibe use of the seventh revision of tbe ICD. at n time when environmental pollution was much Review of the massive data now available on the greater than it b now has been found in one. ippgtterm health of men occupationally exposed to vinyl chloride leads to two dear conclusions. First the haveexperienced a spcdfic hazard of the normally Reterancaa fftrctndy rare angiosarcoma of the liver. Approxi mately 1 in 335 of the men exposed in the 49 plants <aidied died of the disease, and approximately 2 4% of dK observed deaths were attributed (oh. Inthe course e{ time the numbers of esses of angiosarcoma must ^ expected to Increase two to three time!. Second, the mortality from all other auses has been typical ofthat of normally healthy industrial workers. If any hazard has existed, its effect has been small. The data provide no reason to think that any baz* gti other than one of cancer has been overlooked, it b, however, still difficult to decide whether vinyl chlo ride produces small risks of cancer, compared to those due to aonoccupatiooal causes, at sitesother than the Over, and, if so, whether, io total, these risks might cause almost as many deaths as angiosarcoma of the gvef. There is too little evidence either to confirm or refute ihe suggestion that vinyl chloride might eautc mela noma or cancers of the thyroid, brain, and lymphatic tnd hematopoietic systems. None ofthe small excesses that have ben recorded point specifically to an occu pational hazard, apart from that attributable to can to* of the lymphatic and hematopoietic systems to the German study reviewed, and most are likely to be the jon of chance effect that b certain to be observed whn many types of cancer are examined in many different studies. The lack of any increased mortality from tong can* cer in tbe combined results of the four principal studies reviewed does not exclude the possibility that there may hive been a small occupational hazard of developing the disease, is geographic variations in the incidence of ihe disease throw doubt on the validity of using national cates for estimating (he expected numbersof deaths. Tbe greater mortality In groups of workers wbo would be more likely to show an occupational hazard than other groups suggests that a smell hazard may haw existed. The evidence is, however, weak, and the exigence of a hazard has not been proved. Clearer answers to some of Ihe questions that have bcert posed in this review might be obtained if the various groups of investigators could present their results in more appropriate and comparable ways. A.> vinyl chloride is a mutagen in laboratory experi ments and a proved human carcinogen, (he minute do<*> that have escaped into the general environment a* pollutants must be presumed to have caused com parably minute risks to the general public. No such I- Air Products aad Cheaiieila, loc. Comments on tbe pro posed standard for vinyl chloride. Letter to OR Goodwin, Environmental Protection Agency. Washingtoe. DC 23 September 1976. (Cited in an uopubtUbed report by &ut to Air Products and Chemicals. foe, in 19(1). 2. Basa ME. Tocfcata MS, Kennedy TP. Pulmonary function and respiratory symptoms In polyvinyl chlo ride fabrication woriurs. Am Rev Rapir DU 131(1985) 205--208. 3. Baxter PJ, Anthony PP, MazSween NM. Sdwuer PJ. Angiosarcoma of the Uver in Great Britain, 1963--73. Br Med J 2 (1977)919--921. 4. Belli S, BertuzJ PA, Comba P, Foa V, Maltoni C. Marina A. Picattn R, Rcgiaoai A, Vigocd MA. fodz- giae culls mortalIta del produttod dj PVC ia Italia: DUegoo delta studio e print! rituhod. Cancer !-- Cut Bn). rady J, Liberatore F. Hi/per P. OreenwtM F. Bur eau W, Deries TN. Bishop M, FoUw A, VUnt N. Aosjosareomaoftheliver An epidemiologic survey. J Natl Caoott last 39 (1977) 1383-1383. 6.Burner PA, Wood S. Elfler C. Suarez L, KUtaoc DJ. Mortality exptrimet of workore in n vinyl chloride monomer production pizza. J Occsp Med 21 (1979) 193-203. 7, Syren D, Enghaia G, Enghind A, Westerholm P. MorisBiy and cancer morbidity fa n group of Swedish VCM and PVC production worker*. Environ Health Penpea 17 (1976) 167-170. 8- Byren D, Holmberg fi. Two possible ease* ofangiosar coma of the Kvcr id a gtoap of Swedish vinyl chloride worker*. And NY Atd Si 246 (1973) 249--250. 9, Cooper WC. Epidemktogic sutdy of vinyl chloride vorfcm: Morally through December 3 L J972. Environ Health Perspecu 41 (1911) 101--106. 10. Cmch JL, Johnson MN. Angtatxrcom* of Uver in the Dianufsoure of polyvinyl chloride. J Occup Med 16 (1974) 130-131. II. Daldemp LM, Freni SC, Bmi O, Brondhunt FB. Anfiosarooeia of (he Hver. Lancet I (1976) 246. 12. Duck BW, Cvter JT, Coombcs EJ. Mortality study of worken b a polyvinylchloride production plant. Lancet 2(1975) U97-H99. 13. EGader CC. Pmahageo G. Pilot study concerning the mortality in NjuruncU Community. Swedish Nature Conservancy Board. 1971. (died in an unpublished repon by Ban to Air Products and Chemical*, toe. in 1981). 14. Environmental Health Assodaia. An update of an cpidemiotagicai studyof vinyl chloride workers 1942--82: Final reportto thChemical Manufacturer* Atwdadon. Environmental Kealdi Associates, Oakland, CA 19<6. U. Environmental Protection Agcnc>-. Standard support doounent sod environmental Impact statement: Emii- rioa standard for vinyl chloride. Environmental Protec tion Agency. Washington, DC 1975. (EPA 450/2-7J009). 14. Equitable Environmental Health. Epidemiological study of vinyl chloride worker*: Final report to Manufacturing Chemist! Association. RockriHc. MD 1978. 77 53 r~ oJ iO --J URL 13598 17. Falk H, Teiles NC, lshlk Kg, Tbomu US. Popper H. Epidemiology of thorotrast-induoad hepatic angiotarcoreat. Environ Rea II (1971) 63--73, 15. Flcchtncr i, Rcyea C, Rwuivifitu K, ct 1. Epidemi Mirttova E, Mihailova A, NeakO M. EmferiOUkrichou i wriiogano dcadige no virilkUsride. Kkll ZCnuo pa* 21 (1971)440. (Cited fat aa uepubBsbed report bv Bair to Air Products and Chemicals, Inc. In I96i). . ologic flexes nod reponc AagkHtroooia ofthe liver -- Wisconcta. Morb Mortal Widy Rep 25 (1976) 57--56. 19. FonnaaO, Bennett B, Stafford J,0ohR. Exposure to 35. Main I. MenuG, Hohnbtig B, Doftson S Kofanund L, Mooring R, Westerhdas P. Monalkyand cnc rates among wothen fat the Swedish PVC weaning induv vinyl chloride o& aogtaaattorn* of the liver A report el the register of case*. Br 3 lad Med <2 (1965) 750-- 7J3, 16. Foa AJ.CofiitfPP, Moctalhy experience ofworkers ex* poaed to vinyl chloride monomer In the manufacture of potyvtayt chloride la Great Britain. B 3 Ind Med 34 try. Environ Health Penpeer 41 (1961) !4$--13|. 36. Monson RIL Mat JM, Johnson HN. Pfoportioeal mortality unong viayhchloridevrortere. Lancet 2 <|974 397--398. 37. Nakamura K. A mortality studyofvinylchloride work- ersla Japan.Sangyo Ota DkuMZaaiW5(t9ai:tuppi, (1977) 1--10. 21. Heath GW, Falk HQr<oehJL Characteristics of cases of atifioiareoaatof theSverataoiti via)1 chloride work ers la the Uitittd State*. Ana NY Acad So 2*6 (197$) 231--236. 22. HridaaaSS, Langard SL,Andsrsen A Incidence ofop. cm among vtriri chloride end pdvvfayl chloride work er*. Br 3 Ud Mod 41 (1M4) 25--40. 49--57. 38. Nldtoboo WH. Hemtcbatur PK.Tbit D. Trends In oaih as moruBiy among workers h the syiuheUc polymeis Industry, la: (odustriaf haxardsofptatks and synthetw eUsdmers. Uis. New Yack. NY 1964, pp 65--78. 39. 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Scaad 1 Work Environ Health (la orate). 26. UUt R, A&dersM H. Miller A, Sclatoff 1. Pulmonary change*amongvinyl chloride polyraeritiiioa worker*. Chett 2 (I976)t fUppi. 299-205. 27. Lloyd MH,Gwdd S, Copland L, SouUrCA. Epldoiu- a atidy group. Royal Society, London 1983. 43. SaiM|Et>lm'Z>ZaricaM.GAcJ.MatifBaM(umoa af the liver god lungs la amt whh a PvC ladustry. Environ Health Perfect 17(1976) 119--191. 44. SoatarA.E|]ldeado(otfcrittadyoffmfiiratorydismvn is workers exposed topolyriliyf chloride dart."Thera* otagicalstudy ofhug fUactiou of workers at a factory ounufaeutrisg polyvinyl chloride. 0r i fed Mod 41 <198S) 328--333. 28. Maitooi C,ClUbcrti A. Qiimri L, Chfeco P- Vinyl chlo ride ctidnotexterist Current results *nd perspectives. Med Uv 65 (1974) 421 --444. 29. Mahon! C, Lcfcmiac O, CarettMgenklcy hioastays of vinyl chloride: Current resides. Ann NY Acad Sri 246 (1975) 193--218. 30. Mahofll C. Lefemloe O, COlberri A. Cotti O, Ctroetti D. 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Doumal spkaomegalJclivar dUeaae as evidenced by peri toneoscopy and gldd fiver biopsy among polyvinyl chloride production workers. Ann NY Acad Sri 246 (1975) 95--134. 31. MarsteUer Hi, Dfllbach WK Malkr R, JuheS, Lange CE. Rohaer HQ, Vritman Q. Chrouisch-toxische Lc* berschldeofeelArbeitm inder PVC'Produktlou. Dueh Med Woriteoschr 98 (1973) 2311--2314. 3) (1971) 516--519. 49. von Crriasr E. Xeial W, Weber H. VinjA-eUorid position and mortaUtlt deutsriter cheoucarbcitcr rorglriri} cur mortalitlt nichtexpoalerter chetniearbr1ter Md PVC-vervbritcr. 2lenr(aA)l Arbriltmcd At' britssch Prophj4 Ergoftoraif 21 (1912) 44--62. 50. Waxweiler RJ, Stringet W, Wajuncr JK, 3ws J. H, Carter C. Neoplastic risk among workers expo-^ to vinylchloride. Ana NY AcsdSd 271 (1974)40--^ 33, MuudaY. Loo* term mortality study of vinyl chloride andpolyvinyl chloridewertm ta a Japanese plant. Arch Iftd Hyg Toucol 30 (1979): suppl, 403--<109. Received for publication: 16 February1 1988 ORIGINAL ARTICLES r SCttfH J Work ELnviruit Heitih 14 ' Associations betvu exhaust and comb Results from a case-refer- by Jack Siomiafycki, PhD.1-2 Ron Dewar, MSc,1 Lesley Ri it9 SIEM1ATYCK1 J.GERIh between several rites of oa referent study in Moairea. refcrriii study provided in exhaust and combustion p cancer risk, in panicutar to Among the associations tt further investigation are !h gasoline ehaun and kidru adenocartiootna long esat combustion product* and Key terms: cartinogeoesis A large populaiion-based case *Uidy was carried out in Monir , Oupotional exposures as potontia ' 20 sires of cancer were ii r each partem, information wa * : exposure to about 300 sul juialytic strategy was to analyze `T M time to determine whether tl rkable cancer-exposure *u bis report examines the assc ; to our study and 10 types ?a products. These 10 "etc? s. Pour are exhaust prodi engines, with the dtsti oding on the engine fuel use fud, or propane. The other ai* the *`nonengine*' combus Swtances: coal, coke. wood. 1 dtstiaction heating oil oil), natural gas, and,pro ' c of products of the di/cct a yeocuidered separately from ih; *^propanc*burning ensifte). ^Epidemiology and Preventive Me itauu4e Arntand-frappier. Lavs ^CWnd*. ^PArtmou of Epidemiology and I ^^g4ty. Montreal, Quebec. Cana> hi of Occupational and Of Montreal. Moorre* : requests io- Or J Sinniaiyt 4ojvoto^ie et obJccinc fv< 531 boul dfs. Prair'*i. Lav /K7V IB7. n^frrtBfcttiaa, -r- '--""-WllVr-.I*t**<mi *iiv irwa-