Document 4QV292vgvV0j5rX0gvXZJLO1G

RECEIVED JUL 5 1977 jrTrBTmw-- ! British Journal/ Industrial Mcdictnc,9T1, 34, 1*10 i Mortality experience of workers exposed to vinyl chloride monomer in the manufacture of polyvinyl chloride in Great Britain A. J. FOX* AND P. F. COLLIER Office ofPapulation Censuses and Sttrvtys, St Catherines House, 10 Kingsway, London WC2B 6JP and Health and Safety >v/.'i, Employment Medical Advisory Service (EMAS) abstcact Identification particular* were obtained Tor over 7000 men who were at tome time between 1940 and 1974 exposed to vinyl chloride monomer in the manufacture of polyvinyl chloride. Approximately 99% or these men have been traced and their mortality experience studied. The overall standardised mortality ratio, 75-4, shows a significant reduction comparer' with the national rates, Fcer eases ofiivcr cancer were found. Two of these have been confirmed b; a panel of liver pathologists as angiosarcoma und two as not angiosarcoma. There is no evidence to support the hypothesis that cancers other than those of the liver are associated with exposure to vinyl chloride monomer. The two cases of angiosarcoma were found in men who had been exposed to high con centrations of the monomer although the second man died only eight years after first exposure. The industry In Great Britain has expanded considerably since the second world war with over 50% of men having entered within the lost decade. Conclusions drawn -about the effect of vinyl chloride monomer on the mortality experience of men in this industry must consequently be tempered by the reservation that the full impact may not yet be in evidence. In 1974 three cases of angiosarcoma of the liver in workers at a plant manufacturing polyvinyl chloride (PVO In the United States of America were re ported (Creech and Johnson, IS1*). Further .nvestlgatlon by the firm led to the identification of two furlhe- uses vro had died some yean pre viously (Biock, 1974). A programme of medical surveillance at the plant (Mukk rt at., 1974) resulted in the identification of two caws of angiosarcoma of the liver among cunt or workers (Falk rr at., 1914). The rarity of this tumour may be judged from the Incidence or reported cases: for the USA 20 to IS eases a year (British Medical Journal. 1974) and for England and Wales tome three to four euses a year (Baxter and. Fox, 197S). Previously the only agents reported as associated with the development of angiosarcoma of the liver were arsenic (Regelson a* df., 1955) and thorolrdst I MacMuhon tt a/- 1947). live Ant ease of angiosarcoma of the liver in a man known to havu been exposed ro vinyl chloride monomer (VCM) in the manufacture of PVC in Fetmcriy with EMAS Uotivcd Tot publication 19 April 1976 Acnpicd for publication 16 June 1976 Great Britain was reported by Lee and Harry (1974). The man had been a process worker for 20 years and he died in 1972 aged 71 years. At this time 19 cases of angiosarcoma in workers who had been exposed to VCM in the manufacture of PVC had been reported throughout (he world. Alt these men had been ex posed to extremely high concentrations of VCM usually at autoclave `pot' cleaners. By 1975 some 32 cases had been reported all ofwhich won in men who had been associated with the manufacture of PVC (Lloyd, 1975). These included a second British patient who had been exposed for Tour years and died aged 37 years only eight year* after dm expo sure. Early report* of epWemtotogipal studies in the USA have been given by Monson tt at. (1974). Tabcrshaw and GatTrcy (1974), Falk et at, <1974), Makk tt el. <1974). and Nicholson tt al. (1975). The Employment Medical Advisory Service (EMAS), with the assistance of company medical representa tives and the support M the unions, co-ordinated a prospective mortality study covering the manu facturing industry in Great Britain. The objectives of this study were to present a general picture of the mortality experience of workers engaged in the in- AP00007005 2... A. J. Fox and P. F. Collier dustry in Great Britain and to relate this to factors all death certificates for people In the study popula auch a* tea, age, year or entry Into the industry, tion who died before 1968 (the year the 8ih Revision length of time exposed, and exposure levels. war introduced). Dcalh rates calculated for 1951, 1961, and annually after 1966 were applied to the Method* ptrson-ycars-nt-rWk for 1940-55, 1956-65, and The ttudy covert all worker* who may have been exposed to VCM through having been employed in this industry in Great Britain. All new entrants are being added to the population annually. Only four companies manufacture PVC and they have kept , most of their personnel records at least since these processes were Introduced. The companies were asked to supply EMAS with the names, sox, address (date at which pertinent), date or birth, year of entry into the indusiry, year of departure, job resulting in annually after 1966, At 1974 death rates were not available, 1973 death rates were applied to 1974 penon-ycars-at-rlsk. A comparison between ob served and expected values It made by assuming a Poisson distribution with mean equal to the ex pected value. Pearson and Hartley (1962) give the probabilities of individual term* of the Poisson dis tribution. For a iretn greater than 15-0 the normal (gausstan) approximation to the Poisson distribution has been assumed. highest exposure, and maximum level ofexposure for cadi person who had entered their employment. Results As full job histories-were not readily available for the population as a whole, it was decided to record the activity in which the maximum exposure was likely to have occurred and to follow-up individual cases, such as those dying with the mention of liver disease on their death certificate, to obtafn a more complete job history. Mo measurement of the levels ofexposure experienced by people employed before the mid-1960s was available. Estimates were made hjr the companies using the definitions t High -- greater than 200 parts per Medium million -- between 25 and 200 parts per million . Time weighted average Low -- below 25 parts per million Constant -- most of the rime Intermittent -- occasionally. THEPOPUtATION These results cover the period between 1940 and 1974. Information relating to the deaths in people who entered in 1975 is not inch-Jed nor it the fact that some people left during 1975. This information was made available during 1975 and will therefore be added to future analyses. Complete information on 7717 workers was obtained from the companies participating in the study. This was forwarded to the OPCS who notified EMAS or those whom they had traced together with the findings. Table ] shows that 15 workers, only l-t% of the initio) population, had net been traced at the time of analysis. This figure includes 59 workers at one factory for whom identi fying information was scanty. Another 72 workers (0-9%) who were traced were excluded because of Inadequate information on their work history in the industry. A total of 409 deaths were recorded, 393 men and 16 women, and 148 workers emigrated before 1975. Two who emigrated returned during 1975 to live in Great Britain and will be included in Alt data provided by the companies wore sub- ftnure analyses. Mile deaths have been studied in aequemly re-checked by them once they had been detail, hut because so few women art Involved In this computerised. Throughout this analysis and dis industry their deaths art summarised in Appendix 1. cussion it is ax-tumed that the information given Appendix 2 gives the deaths in 1940-74 notified to EMAS is accurate. It it also necessary to assume since the analysis. nw persons not 'rtduded In this analysis, either Figure I shows the number br men employed In because they were not identified or because ade the industry each year from 1970 onwards and the quate data were not available, do not constitute a number who had been previously employed. The hired sample. work force in 1974 represents some 53% or men ever The number of deaths observed is compared with employed in the industry, reflecting the rapid growth that expected using sex and age standardised death sinee in inception. Table 2 shows that approximately fates for England and Wales. Five-year age groups 12% of men were exposed to high levels, almost all have been used for ages between 15 and 74 years. to constant high luvcls. The newness of the Industry The Office of Population Censuses and Surveys it rcfltvicvi by the fact that only 8% of the workers (OPCS) provided death rates in accordance with the have been employed in the industry for more than 20 iHitraatlonal Clottijleaikm of Discaxet (8th Rcvi- years. Of ihcsc, only 34 men had been exposed to Sion) for the certified causes ofinterest and re-codcd constant high levels. AP00007006 Mortality nytrirwf ofwcrktrs expoted so tittyl chloride monomer TWc 1 Summary ofthe number ofpersons Identified, traced, andflatted by the Office ofPopulation Canutes and Snrtfja affording to factory Aamlwr Umtifiti XNMNt Urn W-- a tieso S (l* 4 (1P* j (-- ie ii*j II <19411 13 <|Mfl ij turn fp||| popHlfettM mi 1100 1140 41 449 3149 m %w TSOI a 34 s n T 31 1* n _1 09 tit *KH DmiIii Ka him and women. rlitelula m p*mm 9*4 abroad who tiu beta trHjdcd from Ihc study, yow In ohkh wn than 5U peapk *tf in grrMtiDptoyowni. ktiuto tpWwiUrn J 9 37 34 a -- S3 (0-1 JO 1940-74 U 1u42 4 3 us a 1 409 ntjrflttiM* ifMr 13 34 _34 M 1 10 141 3 Flf, 1 Nwutor eftmn At tht (ndutrry and (hr tout natttbrr %to tod hfi thr industry far rack jrar ttnet /W. OVERALL MORTALITY" PATTERN Table 3 shows that only 393 deaths hav* been re corded as compared with 521-22 expected and the standardised mortality ratio (SMR) is 75-4. The SMR for eaneers as a group is hither than this whereas the SMR for circulatory disease is approxi mately the tome and that for respiratory disease, digestive disease, accidents, and suicides is below the overall SMR. It i> difficult to Identify anttosarcoma of the liver from death certificates (Baxter and Fox, 1975). Soma eases wilt be classified as primary liver cancers {!CD no. 135). some as secondary or un specified liver cancer UCD no. 197.7 or 197.S), and others may be In other categories (for example /CD no. 227). Only one death was certified as being caused by primary liver cancer compared with 0-71 expected. There were how-ver three deaths, nearly 2) times the expected number, irt these other categories. Histories for these four people are sum marised in Table 4. Slides for microscopical analysis obtained from these cases ware referred with no Table 2 Lr-'Is ofexposure oad tcwftks ofexposure for men Included lit the survey 3hKl(^ Crnnem tMimismt r* IMot low nkh JA4m Uw M lOvlf 304 TIC30 au H2 24 7>l (IOS50 tom too m t IT 91 243 114 H 11 1412 (IPOSO 12M (1*130 IK (HfA lilt 1094 3701(774*0 210 351 130 303 SU(9430 2IITC9JT0 ltt7GI*250 7409 [JMJ0 CMMddt f<ntoTDialini, ffllvrmtaml * Cxtaknully, High * > 300 part* per mBItoii. ^ HnJiw* m 300 parts ptr viilUmt > jv > XI puu per mflHon. } Tim# nlphltR iwi|s. lew <Sl^fiifirpijtfaw. J AP00007007 3 technology European Chemical New*. October 14, 1977 UK study reveals extent of VCM-related cancer risk the first comprehensive re-evaluation of data on the UK incidence of angio sarcoma of the liver, believed to have been responsible, worldwide, for over iS deaths of workers in the PVC in dustry, has concluded that the associa tion between the disease and the PVC industry could be less than was origin ally thought. Although only preliminary, the report from the UK's Health and Safety Executive, suggests that between 1963 and 1973only one death could be confidently associated with workplace exposure to VCM. It also failed to show any geographical link between the incidence of the disease and the .location of PVC plants, nor .any firm evidence that there was any risk, of contracting the disease through exposure in PVC fabrication plants. The report refers to the one worker whose death was attributable to VCM exposure us having been exposed "to levels of VCM exceeding 200 parts per million for over 20 years". Organized by the HSE's Dr. Peter Baxter and three other medical ex perts, the study involved the examina tion of histological data, where it was available, relating to 47 deaths which had been previously attributed to angiosarcoma. In only 37 of these cases nr such evidence available, but Of those the cause of death could oniy be confirmed as being due to angiosar coma in Meases. Occupational histories of 12 of these revealed, besides the one PVC worker already referred to, only one other death which could be associ ated with PVC--a glass fibre worker who died at the age of 56, but who had (previously worked in a rubber factory which also produced PVC coated fabrics. There was no evidence to [suggest that he had worked in that sec tion of the plant, however. The authors describe the findings as "generally reassuring" in that angio sarcoma incidence is so low. and that there are grounds to hope that the chemical will turn out to be less o( a cancer risk than was originally sup posed when the US epidemiological findings were first announced in 1974. But they say that there remains a possibility that angiosarcoma may be associated with VCM at low exposure "so a Close watch on the occurrence of this tumour should be maintained". The work was carried out in parallel with other studies, as yet incomplete, in other industrialized countries since 1974. So far 21 angiosarcoma deaths have been attributed to exposure to VCM in the USA. the next highest national incidence being West Germany, with 11 deaths. Osha pushes controversial control plan the US Occupational Safety and Health Administration is to go ahead with its controversial plan to classify all poten tial industrial carcinogens into four broad categories and to regulate them accordingly. Although criticized by the Society of Plastics Industry, the plan is said by Osha to be necessary to-cope with the high incidence of cancer which is aid to be attributable to environmental factors. The SPI calls the move a rush to enforce judgement "on the basis of limited scientific knowledge of car cinogens". The new plan is expected to put about 100 substances into the first category of confirmed carcinogens which OSH A says it will conlrol by issuing "emergency temporary stan dards" similar to those already issued for VCM and acrylonitrile. The agency says that it will put inlo `category one' all those substance* which have been shown to be carcino genic in man or in two animal tests Carried out wills mammals. It would include nsheslos, VCM. cote oven emissions, arsenic, benzene, kepone and beryllium. The seeond category would include "suspected carcinogens", substances for which there is evidence from other animal species or tests, and this is ex pected to include about 203-300 sub stances. The third category, which would contuin substances for which there i* in sufficient data to confirm a fink with cancer. Osha expects to contain about i 500 substances. All these compounds and those con tained in "category four" (which could belong to the other three if they were found to be present in the workplace) would be expected to total about 2 000 substances, according to Osha. A US National Cancer Institute study published earlier this month reported a higher incidence of deaths due to can cers of (he lung, nasal cavity and sinuses of the skin, among the population in states with petroleum refining industries, than among the population in other states. In brief D The Coca-Cola company, having lost the opportunity of further exploiting acrylonitrile-based botllcs, has been holding discussions wish three chemi cal companies over possible contracts for the supply of bottles based on poly ethylene tcrephlhalate. One company, Sewell Plastics, has already signed a contract with Coca-Cola on the bottles, while those with Amoco Chemical and Continental Diversified Industries are still under discussion. The New Zealand government has initiated a study into the feasibility of using methanol as blending agent for gasoline (as a motor fuel) up to con centrations at high as 20 per cent. It has its eye on the future exploitation of natural gas which will soon be available from fields offshore near the country's North Island, Oxirane to manufacture TBA gasoline additive oxirane has applied to the local auth orities in Botick. near Rotterdam, for permission to construct a 260 000 ton/ year plant for the production of tertiarybutyl alcohol, following a previous application to expand its propylene oxide manufacturing capacity at the site, Oxirane intends to market the tertiary butyl alcohol production as a fuel addi tive to increase the octane of low-grade gasoline. The company completed tests with the compound in its employees' can last year and is optimistic about the market potential. Since the original application, mude in 1974, Oxirane has lowered the size of the proposed propylene oxide expansion from the original 180 000 to 100000 ton/year. The authorities had demanded that pressurized storage facilities should be replaced by cryogenic facilities. Both plants would start production around 1980. Mitsubishi licence for KTI kti has been Earned a non-cxclusivc licence to use the ground flare slack technology developed jointly by Mitsu bishi Petrochemical Engineering and Hitachi Shipbuilding and Engineering. The licencing agreement, which covers. Europe and runs, for a period of III years, represents the first export of this, technology. Developed in W72. the ground flare Muck in said fo be non-pi>flutin^. Unlike conventional flare Mucks used to burn oit ga* and often criticized because cl (he visible flame, noi&e ami smoke, the Japanese ground flare slack dimimi 1cn smokcand greatly reduces noise. AP00007008 4 A. J. Fox and F. F. Collier Table J Observed amt expected deaths, for 1940 to 1914. for ell nan torered by tht survey, oeeordlnt to certified tator ofdeotk ` tw tfd**tk (ICD* ,) mM74 **rrNd A* Cltwi CWtr TMemacH (1SJ) Pftnwy umr f Br (tJJ) Center efliAB(|t>3-J49) CMittff of train (If 1) Other liwf MMcn (I0T.7, III). *K) Lymphufc and furmainpolcuc iHstm (JOO-JO?) Satoerin*,. fuaniionsl, and meubollc dMM Dttcataa of CirCWUiot) tyitems (3904Jt) tehumk bun Uiuma (4(0~14) efraipiratory t>uem (440-519} fsVUWtil (CV0-4IJ) Dtoivci cT4tniivi (5XM1T) Uw 4i<au (370-S> Accidents lEMO-WI) Ividdci (E950-9W) All deciha (1-999) IIS 1M-77 H 13-M 1 frtl U *I2J t Hi i 0 >01 4 4-n im 2Mlt m t|4 41 ATO* U M7 a IIM I 24* 30 1-93 1 |tf H) jiin *AI dcaihi haw been cedrd Mcordini 10 the trrtcrrmiie/mt Cl*t*ifl**thm Utitvifi, Ith JltvJiion, SktX 907 1-3 I4M AM H* uu 99-9 HI 709 01 C3-4 704 97-4 JM H-l *$7 75-4 Tabled Deaths due to liver earner Artery w. A#tf /t4rj Certified mti* fde*tk I 27/10/till IW1/II70 Aicii<t;afeifM3M ef Uvnrf end omtnwm a W4/I90I 21/SI/ISM HMKiaftfSeeftJeiheHoa1* flTU*tf*s Y**r xw 1MI 194* i ttwifll 4/5/ln UfldifffrinlTettd eercfnpm* ofUvcrt, prtmaijr it awifii 34(13/1974 Cfrinwwftoilt; aeiywMjrpnii. +f Urn"; hepatic cirrhotfi CctiAtntfel to pmd of hjttopatKstofhu u #u to cnitotaiwroi or Uvcr. tCoftfemd to PtMl or hdwoNiboiotttU li net 4v* ( ottewcow ofHwr. 1951 1W rr to* (94* IMJ 190 1*14 tspnarr Wf Unnimm Uvr/lflttf- nutr mltMnt Mi|ti;caniiani AulsxUn 4oIpPt4fAit4o1f) Mcdtam/tMir- Promt miucftt operator WthfcowinM Fplyriianf Tfebk 5 06jcnW and *jcpett*ddtafJti and tHSndurdUed mortality ruth far alt deuthi betwte* 1940 Md /PW aecordin? W fattory ^brTofy edi Mimri dretht Iprriri dre/ti JJWJt 2 a 4 ti li ia la TMxl elilpn 71 13 in 4 2 in i J Ml M'*7 3M1 1*117 It at 171-90 1H1 12142 UK 1H 40 77*1 IM ao-4 434 JM 1W details of Iheir work history to a panel of liver pathologists (Baxter, 1976). A diagnosis of primary angiosarcoma of the lirer was confirmed in two of them and the remaining two were confirmed as nor being due to angiosarcoma. INDIVIDUAL *ACTORY imtllKCI Table S shows that significantly fewer deaths were observed for men employed in factories 3.10, and 13 than would be expected from the numbers employed and their ages, in factory JO. 59 workers could not be traced and a furlhcr 36 were excluded from the analysis because ofinadequate exposure information. Of these 36, three have died. The proportion of persons from this factory not traced is to much higher than for the other factories that it may include a disproportionately high number of deaths. Some early records for factory 3 were not accessible and these may also Include a high proportion of deaths. The factories with the highest number of expected deaths (factories 2, 4, and II) had similar $MRs (SSJ, g*-0, and 86 5 respectively). The low number of expected deaths for factory 13 relative to the number employed is a reflection of its expansion during recent years. Three of the liver cancer deaths occurred in AP000070I MMby enpevtcwce of workers exposed to vinyl chloride monomtr s McMqrlifter tM((Table 4). Thii issignificantly in atoesi of the expected 0*13 (r < 0 01). The number of death* attributed to cancer, 21 Observed, i* marginally in excess of the expected 20-71, whereat the number from rireuhiory disease 1* below that expected (37 observed. 40 27 expected*. Factory 4 hews a similar pattern with 41 observed cancers compered with 39-26 expected and 60 deaths at tributed to circulatory discate compared with 73-58 xpnr iril. at does factory i I with 44 observed can cers, 43-14 expected, and 71 circulatory disease deaths compared with 800S expected. While these dilferenees are not statistically significant they indi cate that in the three factories with the highest ex pected number of deaths, the SMR tor cancer deaths was in excess of the SMR for all deaths and that for deatlis associaied w ith circulatory disease. Little further information wat gained by analysing deaths by certified cause separately fet rich faeiory. Therefore in the following analysis ail data have been combined. mortality by year entering the IKSUCTRY Table (. by comparing cohorts who entered the in dustry in different quinquennia, shows that the ratio ofobserved to expected deaths is tower for those men who entered the Industry recently. Figure 2 shows this to be the ease for cancer and circulatory disease. The opposite trend i* shown for accidents. Although the downward slope with succeeding year of entry is seen bi Fig. 3 and Tabic 7 to be due to more recent cohorts having lower SMRs than earlier cohorts, the SMR for each cohort is seen to rise the longer the cohort is followcd-up (Table 8), The SMRs increase from 40-5 for the first five yesrs of foilow-up, to 85-1 for between 13 and 20 years of follow-up, to ICS-5 for 30 to 33 years of follow-up. MORTALITY by EXPOSURE LEVEL The overall SMR in Tabic 9 is seen to be lowest in the group with the highest exposure. 67-8, and highest fat the group with the lowest exposure. 78-0. The SMR for liver cancer was however hi|hesl in the group aspossd So the highest concentration of VCM. The two liver cancers In this group were both angiosarcomas whereas the liver cancers in the low and medium exposure groups were not (Table 4). The only other high SMR in Table 9 is for brain cancer in IK* high exposure group. This results from one ease being observed whereas 0-36 were ex pected. There is ne indication of a dose-response relationship for cancer as a group, lung cancer, or diseases of the circulatory system and only a slight indication for diseases of the respiratory system where the SMR is increased Tram 59-7 to 64-4 to 69-1 with successive rises in exposure group; and only a Slight and probably meaningless increase for diseases of the respiratory system. The SMR (Table 10) for thoie men who experi enced constant exposures to VCM, 33-3, is signifi cantly below that for men who experienced only intermittent exposures. 84-1. The SMR for liver cancer is however higher in the fonner group. The two angiosarcoma deaths were men who had experi enced constant exposure (Table 4). This table indi cates an excess of lung cancers in men constantly exposed (17 observed, 13-72 expected, r > 0-05) which arises from men exposed constantly to medium concentrations (13 observed, 7-73 expected, v > 0-05). This group also had a slightly raised bron chitis rate (6 observed. 4-56 expected, a > 0-05). In Table 11 cohorts based on men not in the in dustry but who were alive IS yean after tntry are subdivided according to the length of time spent in the industry, Fifi'-'n-year survivors are considered In order to eliminate the biases that occur in a simple comparison with length of exposure. These arise because a nun exposed for IS years cannot have died before he completed this exposure, whereas a man who was exposed for lets than five years may have died within five years of entering the Industry. The mortality experience of the four cohorts con sidered In Table II, men who entered between 1940 and 1944, between 1943 and 1949. between 1930 and 1934, and between 1953 and 1939 have been studied for 16 yean. 11 years, six years, and one year respectively. Although there is a slight drop in the SMR in relation to the length of exposure for the 1940-44 cohort, there Is an overall tendency for the Tabled Analysts ofobservedcod expected deaths hy year ofentry dltAtfrtf ms-4* 19S0-U lUflrll OhiMif iSad SM* s* ici-ss w Ml 12117 an n IJMi U 4mda la awa aba mill Srfwe iMean aM MiM la tea ate. H44 mi tUQ44 M Of iMMt ** 414 1970*74 ISM JM AP00007010 * A. J. Fox end F. F. Collier TaWc 7 Observed and expecteddeathsfratu alltames tmdSMKs aeeordlnf la year ofdeathfor cohorts basedan year eftttsry to the Industry Yemef rsettfibttk tataea jmmi mmi imn 1*4041 An :> ; 1HMV IMM0 im-H ft* 0M4 *0 i\ns NM U *n d >** 49 74-34 ,}|4I 42 94*4 1,YOO-J 49-71 1,V79J * 14*4 ,1*9-1- tit CMrta i im kfco (nun* Mon 1*0 HI tut ladutM la ihh (Mis FI|. 2 Standardised mortality ratlot far alt dretks, all tanctn, dhtases ofelrenlatary Itytltm, and aeeHeuts related t* Mr year/Cx/r/ Into Industry. Table I OtutnW WtJcpecttJ deaths in ninth* to fettgtk oftftw cft soften Mas MtenJbUo Ifdtft* *ftif** (pm) M 9* 1fr|4 ll>1* 3u*4a4* 3*44 V* UtiM la Mbit. frttht OMtkS 4AM 34 40-92 90 IH4 ire S 09*97 40*9 102-22 ts-i *0 94 012M*10 0T44--T1 90 SIS 104-1 h4 tfturcd Mfec* IMO in mc liwMid to tofe Phnilrm Flf. ) Standardised mortality ratios for deathsfrom nit AKf accordhtg tc year ofdeath for cohorts baud an year ifentry bn* Industry. SMR le Increase with increased exposure. The iota! SMIl Increases front 100-6 for those exposed for four yean or lest, to 104-7 for those exposed for the to nine years, to 113-3 for those exposed for 10 to 14 yean. Tbit industry has grown approximately tanfold alnee the second world war (Fig. I >. It is nearly.twice as large ai it was only 10 yean ago. The environ' mental condition* in the manufacturing processes are also known to have altered since men were first employed in the Industry In the early 1940*. The main factors effecting the exposure levels were firstly, in the mid'iixtie* the discovery that exposure to high concentrations of VCM can cause acro-osieolysU end Raynaud-like phenomena which have since been Classified under the heading vinyl chloride disease; and secondly, in 1974 the discovery that men ex posed to high concentrations of VCM hid in in. creased ride ofdying from angiosarcoma of the liver. These changes in the tire of Industry and exposure mean that more then half of the people who have ever been exposed to VCM in the manufacture of PVC in Great Britain are currently employed In the Industry; approximately 73% of men who have been employed in the industry have been employed for less thin 10 years; only 6% have been employed for 20 years or longer; approximately half the persons who hive been exposed to VCM have been intermh- AP0000701I Mortality experience ofworker! exposed to tlnyl chloride monomer 7 IMtof Observedoat/expecteddeaths according to whether exposure mu thought to be high, medium, or low Alanevt UWWM tMfaimr rain nimr Mmimi rsKcubietr nttu* r^irr fmpirimy mum All tfiMJ* srs 0teemed Expnwt SMU f N* 9*S S I3 I3*4 2 Mi 1 PM stt-i 1> t*n 711 1 434 #9 1 ti Mil *71 Mm Si 1 JJ WM M Si IM Cmm* SM* *M* 477 ho l-M ItfrJ* SMS 2441* III 13*9 M2 Ml MS IPf ittt OMtreed tryetna tkt* f> INI 93*1 1 Pfl ltt'3 SMI SOT 1 IM 99* 41 IM'SI 77-7 IS sou *97 23*10 IIP MirtC<<-->Ui im k wmm to trfctm farfaltd MUM rfinpMuM unuarM. Table 10 Observed mid expected death according to whether exposure wet cotulant or Intermittent Gmmtfdntk -- ttwamr ttfftflMBCir Inis nnerr Dimw of tlrcubnofy irwtn Wu--t fmptaitiry mum AS StM CmttmM Otmrtd 2 17 1 M II it Cxftr/rt JP*70 ' 0-34 13 73 l<2 tbn 140-94 IM* IPS 3104 104*1 104 *14 *17 fM /jMmtrjmr Chttvrl `M a at i 144 >1 303 CcpwW 747 4*11 3*43 Ml tMJT 49-37 140-15 IwiuSw SMtl ta t wM f*t whom m tetUM MW rnpoMnnsnMrM. SMir 9H 1*01 tu -- *74 411 4-1 Table II Observed and expecteddeath in relation to the length ofexposure andyear ofentry far in * were oHh IS yean after they entered tmifiMri ' dJyeeet Obtuwd Sue 1 JVtff Mwiii SMX CtpretM Qtonwrf tkt* tvtrN mp h <DhiI in 1MPT4 IP4M9 (QmMm t-vfvM'K ! 1*4 UT4) 1990.54 (Dmito 0turrWi| li 19C9-74) 1K5-99 hkCB mwrtna hi 1974) 31 32-01 JO to 1 HI m M 3447 i 97 41 13 Iti II-5S r Ml u Wt| 4 MS 112 f-97 *-IJ * Im t'JT IM vn 1st 479 7* Mil sttt 3MC feoe ' UH tcntly exposed; and only 10*' ofthose whohave been constantly exposed, have been exposed to high con* centraliont.Thui relatively few persons have been ex posed for a lone lime to high Icvcli of vinyl chloride monomer and even In cate* In which men have compiled 30 years or service, because their service has only recently been completed, the follow-up period is too short to evaluate the carcinogenic effect of YCM. SELECTION AND SURVIVAL IN THE INDUSTRY This population comprises menwho at one time since 1940 were fit enough to obtain a Job in the plastics industry. Because in general people entering em ployment are healthy their expected mortality rate should be lower titan that observed for the popula tion as a whole with whom comparison is made. Table 6, in which the population wai subdivided into cohorts according to year of entry into the industry, AP000070 I. At ft Fix andf. F. Collier ihowt that the cohort! of men who entered more cerebral neuroblastomas and pulmonary adenomas. recently had lower overall mortality ratio* than Tabcrshaw and Gaffrey (1974) confirmed the clinical thoae men who entered long ago. Figure 2 show* suggestions by Creech and Johnson (1974) that there that aimilar associations are obKrvcd for caneen was strong epidemiological evidence that exposure to and fbr circulatory discutc. Figure 3 confirm* VCM caused angiosarcoma of the liver in humans. that this association between SMR and year ofentry Their study also indicated an excess ofcancer or the into the industry It not a function of the cohort but respiratory system and brain although this was not b related to the length of time that it hat been statistically significant. Nicholson et at. (1973) also pursued and therefore to the length or time slnee the confirmed that exposures to vinyl chloride monomer individual entered the industry. Table 8 shows that it am cause liver cancer in humans. Although they may take 20 to 30 yean for this effect to disappear. observed three angiosarcomas of the liver and one At this population comprises all men who have brain cancer no deaths were due to lun* cancer. teen identified as.having worked with VCM since Comparisons between the findings in ^reat Britain the industry began in Great Britain in the early and those in the USA ere limited because of the 1940s, it includes men who have spent short periods differing experiences in the two countries. Ifwe apply In the Indus!, y as well as those who hive had longer the some population definition as employed by exposures, in any evaluation of the role duration of Tabcrshaw and Gaffrey (1974), we find 33! deaths exposure plays in a model of cause and effect it b observed and 462-29 expected. This gives an SMR. of necessary to accoum for differences in character- 72 compared with one of 73 found by Tabcrshaw and fstics between those subjects who stay a long time in Gaffrey (1974). Men in the high exposure group have the Industry and those who leave. Most of the'latter an SMR of 59-4 compared with one of 71-7 in the leave for reasons unrelated to health, but there are medium exposure group and 73-3 in thr low exposure some who will leave because ihty are not fit enough group. An unexplained trend similar to this wa to continue working or because they consider the job noted by Tabcrshaw and Gaffrey f 1974), We believe to be afretting their health. It is difficult to separate the trend is due to selection and survival in the in this effect, die survivor effect, from the healthy dustry and to the length of follow-up. Using the population selection efTeci describe < above. They were some' population definition as Tabcrshaw and both clearly described by Ogle <1833) but have not Gaffhey we would have found two liver cancer been matured. The 13-year survival effect for this deaths, one of which would have been due 1o angio population has been estimated by separating those sarcoma. persons alive 13 years after entering the industry Nicholson and co-workers in their study ofall men Into these working and those not working in the III' in one plant with greater than five years* exposure dimry after the IS years. The mortality patterns followed-up to years from first employment, ob after these IS years were then compared. The SMR served 24 deaths compared with 19-0 expected, and for men not in the industry, 103"4. was approximately nine cancers compared with 3-9 expected. Included In ' 50*,) higher than for those still in the industry, 74-0. these nine cancers were three angiosarcomas. The tn i separate report we have considered at greater last two columns in Table 11 show what might be length the Implications of these effects ind the effect termed a high risk group In that these are people who of the period of follow-up on the interpretation or have experienced between five and 14 years' expo, occupational mortality studies (Fox and Collier, tore and have left the industry. They are studied here 1976); they arc ofmajor importance in the interpreta 15 years after first employment. In this group tion of these data. 43 deaths were observed compared with 4403 ex pected. For cancer 13 were observed compared with Other stadia* 1J'4S expected and for hmg cancer six observed complied with 4-66 expected, ft should be em Some hypotheses concerning the effects on nun of phasised that none of the cases of liver cancer occur exposure to VCM have been proposed as a result of red in this high risk group. From Table 4 it can be the animal experiments conducted by Mahoni and deduced that a study in Great Britain similar to that Leremlni (1973) and ihe epidemiological studies con conducted by Nicholson tl at. 119751 would hivt ducted by, for example, Tabcrshaw and Geffrey identified one angiosarcoma and one other primary (1974) and Nicholson ei cl. 41975). Mahoni and liver cancer. befcmtnt (t975> have suggested that vinyl chloride monomer produced tumours in the three animal Genera! assumptions and Hmhatlou species studied: rats, mice, and hamsters. Liver angiosarcomas were observed in all three species. In Certain environmental factors are known to affect addition other tumours that occurred included man's longevity.-Some of these have been associated AP00007013 Mortality rxyerltiKt ofworkert expoeed u vbiyf chloride monomer with particular came* of death such u cigarette amoking wish king cancer, heart disease, and hronchkk. Other association* such at those between octal class and area of residence with cancers and bronchitis have not been fully explained. Epidemi ology docs not provide the immediate answer be came the cause and effect models arc complex and individual susceptibility confuses the tone. In this particular study no account has been taken of these other factors. We hate assumed that the social class, amoklna. and geographical distributions are similar to Ant for the national population with which comparison b made. The mortality study provides a relatively crude epidemiological technique for evaluating the risk to health in the group under study. It cannot account foe all the factors that may be relevant to the hypo theses that hate been tested and its power is limited with respect to the detection of harards Which pro duce smalt excesses of mortality. Such studies can confirm relationships between exposures to specific chemicals and th; subsequent development or un common tumours such as mesotheliomas, bladder caucus, and liver tumours. Unless the chemical con sidered b a powerful carcinogen these studies are less rensitivt when studying common causes of death. Conclusions It b not yet possible to evaluate the overalt impact of exposures to VCM on this population of workers but bearing in mind reservations discussed above two conclusions can be drawn at this stage. The first relates to whether or not there is evidence that exposure of men to VCM in Great Britain in the manufacture of PVC caused earner. We have Observed four livet cancers, two of which were sub sequently confirmed as angiosarcomas, significantly more'than would have been expected. All these cancers occurred between 1970 and 1974 and similar experiences have been reported in the USA and in ' animal experiments. We therefore conclude that VCM it probably a carcinogen causing liver cancer in workers exposed to it. Although In this study there Js Jltil# relationship with length of exposure, the 'angiosarcomas were associated with exposures to verj high concentrations of VCM. Ths mound conclusion relates to whether VCM causes cancers other than those of the liver. W find no evidence to support this suggestion. Only two brain cancers were observed and there is little indica tion of an excess of lung cancers. The SMft for cancer as a group is consistently higher than for all deaths but because of population selection factors this is difficult to evaluate. The effect of VCM on the mortality experience of workers exposed will only become clear after con tinuing this study for a further 10 yean at least. Although the rectntly adopted hygiene standards may in future be shown to have a residual risk asso ciated with them, men who entered the industry in recent years should bo at lower risk than those who were exposed at a time when conditions were less controlled. No study such es (his could have been conducted without Uie assistance and co-operation of the in dustry end unions Involved. Dr S. Gauvaln was In volved with the planning of this project and an early draft or this report was discussed with Dr M. Greenberg Dr A. M. Adtlstcin, and , Dr F. J. Baxter to all of whom we are grateful. The EMAS Survey Control Section administered the survey, individual companies' identified people who bad worked in this industry, end the Office of Population Censuses and Surveys obtained and coded ill death certificates. MMsm Baxter, t. J. (1976). Epidemiological uudtH or FVC manu facturers and fabricators, and primary angiosarcoma ofthe liver. ftfmdlqt of th* Jteyel Society of Medicine, 47, tti-tn. banter, r. I, and Pox. A J. ft9Tn, Angiosarcoma of the Iwasth cartHied caitat ofdata 1963*73. Lanen, i, 27a. lock, J, b. (1974). Angiosarcoma Of IhC liver following vinyl chloride exposure. Jaarnal of the Amerkon Medico/ Asiotimlos. 229,22-54. British Medical Journal <1974), Editorial. Itlilth Medkol Journal, I, 390-591. Creoch. J, I.- and Johnson. M. N. (1974). Angiosarcoma of tbs liver In the manufucr'ire of potyvlnyt chloride. Journal tfOeenpcihmot Mnlklif ft, 150-151. Felt. H., Creech. I. L., Heath, C. W,, Johnson. M. N.. and bey, M, (1974). Hepatic diseases amoeg workers or a vinyl chforldk poiimeriiarion plant. Journal of the American hfedkalAreoeMita, 2J0. 594), Pea, A. 2., and Collier. P. F. (137*1. Low mortality rale* In industrial cohort studies due to selection for work and survival la the industry, trklih Journal of freetaikt and Social Medklae. 30, 275-1)0. Lee. 7. i_ end Harry, D. $. (1974). Angiosarcoma of she liver in a vinyl chloride worker, takrr, I. I.Mt-1311- Lloyd. 2. W. 11975). Angiosarcoma of die liver in vinyl chloride, polyvinyl chloride workert. Journal of OeetpaHanoi Uedklnr, 17, J15-U4. MecMahon. ft. ,. Murphy, A. and Bales, M. I. (1947). Badotheliil cctl sarcoma of User endowing thorotrust injectiona. Amerkon Journal of AsrIWery. U, 515-611. Mulct, L. Creech. I. L.. Whelan. J. 0,, and Johnson. M. N, (1974). Liver damage and angiosarcoma in vinyl chloride workers. Journal tf the Aeitricen Mejkal AnsaetoUan, 250, *4-41, Malloni, C. amt Lefcmini. Q. {1975V Carcinogenicity bioassayitofvinyl chloride, current result*. Annals ofHem York Academy of Jriorri, 246, 135*211. Moaton. K, k, Pcicrs, J. M , end Johnson, M, N. (1974). Proportional mortality among vinyl-chtorhk worker*. Lancer, 2,397-291. AP00007014 M> A. J. Fox am! P. F. CaNtr Hkholwn, W. J. E, Hemmodd, E. C,, Milnun, H,, and MM, I. i. f 19751. Mnrtelhy iipiriin of a nliod ef vinyl chloride--polyvinyl chloride worken. Amh ef Ktm Yerk AenJrmy at Selrmr.% 14*, Slt-llS. OfJa, W. (IMSy. Lalt la (lie kcfhiiir General on the mortality In iha reyluraiion districts of tnjland and Wales diirinf the ten yean llll-KX Supplrmtta la Mr MSth Annuel Aepart of At Xeprjtrar Gtnrrot ef Mirth' Death amt Harriett* to EnfhmJ, p. juili. NltlM, E> I-, and Hanley, H. O- 0**2}. Miomnrlce Table? fee Stattnttton?, trol. t. Cembrldge University Prtu: iiwdofti Rejclscn, W, Kim, U.. Ospine. and Holland, J. f. OKI). Itaemaneie-aedolhelul aareoma at liver from , - .chronic arsenic inioxicadon by Foskr'i solution. Center, . 11 114 912 Tebershaav. I. R,. end Calkey. W. R. (19741. Moruiity study of workers in the manufacture of vinyl chloride and ill pdymen. Jaanal ef Oteepatlentil MtiUcinr, IS, 509,311. Appendix I Deathj in women fifUD ft*. JhttV**** 3 2.IU90J a IMlfM X ' 2J.tH> * lOiiriM 2 I7.10.JI7* a 17.7.1147 i. 13.tl.IM2 a 21.1.1*11 a 17.7.1194 X I.T.IIM 2 19.5.1909 4 3.10,11*0 4 12J.I914 4 9.10.1194 4 m.iifi 4 7.1,1994 Maiaijr euae toilette. 22J.I9U O.IHI Pkim I2.io.ioa 214.1*10 1.3.1971 3.7.1974 1J.I1M U.I0JM2 M. 15.111*47 7.11*71 U.I3M MMtU 215.1944 CdrfCM'fM M KDmA hw.wm ' 4U9 4mt4m fJM 43/9 440J. 7134 4m, 29)0 jw. ejoe. 4o 4409,4m JS79 M/f 45410119 4240,410*. *140 Mia, mt JVM, 7134,4300 29014271.4110 Yam J9m4 1*44 m2 IM 1945 1940 Ml IM4 1944 1942 041 1945 IMS 1941 1941 1*4* 1*42 tMF kl) IMS IMS 1*42 IMS 1*44 1*42 IMS 194J 1M1 1*41 IM9 1945 1941 u* 1940 1944 mw* Mi m Mcdlum/fmaaJiuh MtdhiOf'lMcrmdutm Mxiiim/biar. Preccu verkar Prow* vatkar Mwioko *WM WOdk*f PtcciM worker Fro*#!* wwkrr Mete* wvrktr htfUil 0<ku two) verkat Froom workrr Mcdkmi/Jntnv fmoa worlur HlhttflC ItwMtnnliuH nm ttlntiil WAdoTrwknelr* with AHljtM ktoniny attendat AMlrtled mnplo Worker irtth admit* Appendix 2 DtdfJu in J940*?4 Motlfitd sf/tc* erafyift Anayas btHtfbkt* Am 44mj6 eftowh ICD eete 4 I5.ll.190t 25.1.1*41 . JJM.4U0.4J39 ai.i2.im MJ.I9J5 010 4 IJ.tatMt 51.11943 4NtOo 7*24 l IMH97) 4/Of, I3 ' It |Uita4f 174*73 4309 II 1J.IV0T 13.4.1*72 mi, 4270,4341 5170 ii 15.10.1900 2e.IO.IMd nil, 4501051 4109 II uiim 119.1944 JJO&4JOO 11 tft.itot MIW* 4340 Mniiyeiaiiilttln, Yam jflnrf Yam kft mi 1**4 1224 1240 Mliitn I9T1 . Ntohnean iro 1*13 19M 1*11 1911 1911 1900 1917 I9CT fgwrr AM* M LowJIaimnAmi tffttftKaua tobeenr Madkim/late- MltBITMIM wlnm etoblaw Mtolum/nnsuru btaalrWtn InOv/lRitrmUttflt Stcurlty/ftmtM M6ftiai/coftUMt 9acoai>J*uio Modicm/tater* Fttuc nthmi lOvJlMtnotllfiil OrinMr hbVtanJliiira Fkwr mtoaot Lewflaumluni Ftoniit emntor JUN 14 1877. R. N WHEELErf JR. AP00007015