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ImlHunlr ttfettupu- i of Uii' [kMltt U.d. lUidvenhy h*ttd klfHCl. rMtphofdma IjlHdoA: eaten* JASA [vgl in, pen 1. land Welfare, 1WM /HctWt. Wafcrtr* [rm. INJH FuNi- ,--leflke mtrkin[ ftywtuxK IV7V. L^oa No "I*-1 b<>7. ^kwiforcancer of lAnwkanbull ikyUiia* eater*. ` "ciudict of the ___ me and Mfwc evaluation taped to ethylene [ifiH- Inlertility in H*l. teloccupa* itsuet tuppeeilion. ,___ jbffmmty. t95<h ]UAEducation and Wd* 74-615. IM74.I s. parts I and tkM-.JI-9.2l-*' Hritish Journal of Industrial Medicine I 9M4;d 1:25-30 Incidence of cancer among vinyl chloride and polyvinyl chloride worker^ S STORETVIib'l I IliLDA AS.* S L LANCiARD.' AND A ANDERSEN' From the Research ('enter,* Norsk Hydro a s Fahrikker. JW)t> 1`onyrann, telemark Sentrals- jttkehus,* Department of Occupational MetHeine. JVUO Vorsffntnn. and ( ancer Registry of Norway,* Mon tebello, Oslo 3, Norwuv. ^ -\ abstract The results of a follow up study of the incidence of cancer and the mortality in a cohort of 454 male workers producing vinyl chloride and polyvinyl chloride arc presented. The study population was restricted to employees with more than one year's work experience in the study plant between 1950 and 1969 and the cohort was followed up from 1953 to the end of 1979. Twenty three new cases of cancer were observed compared with 20-2 expected; one case of liver angiosarcoma was found. !:ivc cases of lung cancer were found (2*H expected) and four cases of malignant melanoma of the skin were observed (0*K expected). The possibility of a causal rela tionship between exposuree to vinyl chloride andy/thec jdicevvcelloopppmicent of mtadljiggnnaant melanomas is discussed. Since 1974 when Creech and Johnson presented their report,' human exposure to vinyl chloride (VCM) has been ussoeialed with the occurrence of angiosarcoma of the liver. Several studies have confirmed these.initial results as reviewed hy Spirtas and Kaminski.' In animal studies where V('M was given to mice. nils, and hamsters by different routes of administration neoplasms have also Ik'co induced in other organs/ ' **" Whether VCM has the potency to induce cancer in man in organs other than the liver has not yet been confirmed. I.ting cancer.4 ' brain tumours.4 * and cancer in the digestive system, primarily angiosarcoma of the liver.*** have been suggested to be in excess in workers produeing VCM and polyvinyl chloride (I*VC). and the prime purpose of the present investigation was to study the incidence of cancer in workers exposed to VCM. with special emphasis on cancers other than liver tumours. Material and method PLANT DESCRIPTION The study plant is located in the county of Telemark in south cast Norway. In addition to VCM and PVC the company produces fertilisers, magnesium, and chlorine in adjacent plant complexes. The produc Received 20 August l VS2 Accepted 14 October ! W2 tion of VCM and PVC was started in 1950. VCM was produced from acetylene in the room where the polymerisation reactors were located-. In 1967 the VCM production was partly altered, and cracking of elhylenedichloride (EDO was introduced as one of two production methods. The production of VCM was discontinued in 197 I after which time the plant was opcralcit as a polymerisation unit. Prom 1955 onwards VCM and I'VC were produced in separate rooms; table I shows the volume of VCM and PVC production and the mimt>cr of employees over time. STUDY POPULATION A list containing the names or employees who had started work before the end of 1974 and whose period of employment had exceeded one month was constructed from the personnel register provided by the plant. The health department of the company has kept the health records of ail present and previ ous workers employed from I94U und onwards. These records also contain some information on the place of work of each employee. By combining these Table I Annual vinyl eldoridr and polyvinyl chloride prodiiftion and ntrmher ofemployees in the study plant ll'iift promt IV50-55 1956-MI IVM-70 * 1971 V'Of tnmsl limn- 25<m 2.MRI- 5000 5IMHKMKHK) Nnnc I'Ve turns) No ofemployees 11)00- 251X1 45- 5t) 2500- 5000 45- V .SOtXt-.KHXMl 9tM20 .lOOOO-AOUtX) 120-130 25 0724001 BFG05038 T :<> two sources of information ;i list of mimes was eon* strutted whieh was presumed to he complete. The individual records contained the following informa- tiou on each worker: full name. dale of birth, iden- lily number. last known address, dates for beginning and terminating employment, departments in the plant at which each person had worked, and the duration of work in each department. Data were obtained for 1233 workers. It wax decided to restrict the analyses to mate workers win* had been employed for at least one year and who laid lirsi been employed at the plant before 1970. These limitations reduced the tfumher of subjects to 454. *' KSTIMATION OF t.M'OSKKF. As a' consequence of the leehnictil design of the plant and the process operation. the level of expos ure to VCM in the past must have been high hut no industrial hygiene survey had been performed before 1974. Mstimaics of the average atmospheric concentration in the past were bused on sporadic measurements that had been carried out with an "explosion-meter" which was graded from l)% to 10(1% of the estimated lower explosion limit; 1%. equivalent to 4th) ppm of VCM. Two sources of supplementary information for estimating the VCM concentration were used: interviews with workers, some or whom had heen employed in the plant since the start of production. and a suggested odour threshold of about 500 ppm VCM. Based on this information, vve have assumed that the VCM con centration was about 2000 ppm from 1950 to 1954, tilHHtt 10(10 ppm from 1955 to 1959. about 500 Ppm from I960 to 1967. and about 100 ppm front I96K to 1974. During autoclave cleaning the exposure level may have heen as high as 3000 ppm.1" Both emulsion I'VC am! suspension J5VV were produced. `Ihc surpltts monomer in the i>VC" leaving the man- {//chintu, LaugOrJ, and Andersen ufacturing plant before 1970 may have contained 5W ppm VCM or even higher concentrations." The plant was closed for reconstruction i> October 1974 and since J975 the VCM in the work Iing atmosphere has been monitored conlinuuuslj with automatic measuring devices, including alani systems that warn the workers during even mines [leakages. Since 1975 the VCM exposure level u the production units has been below I ppm most d the time. li- jon n.ASSIFU ATIONS l Jobs considered 10 have heen associated with hip VCM exposure include production, autoclave clean ing, maintenance, and lapping. Owing to the gre* amounts of surplus monomer in the PVC, one m) also assume that the exposure level in the packing unit may have been high until 1970. Those working in the development laboratory which contained small autoclaves in small rooms, in the control laboratory, and at processing in the customers' set vice laboratory, may also have been heavit) exposed, hut no information about VCM levels ii these working places is available. Nine differcN exposure categories were defined (tahtc 2), 1number of the workers having been employed h more than one exposure category. Membership of an exposure category was defined as that category* which the longest lime had been spent. If an indi vidual had been a production worker for some years and subsequently spent a greater number of years* a job that clearly entailed minimal exposure, hr t r r a b would by definition belong to a low exposure calej b ory. ... tt As the exposure level was high in (he early 1950s P* an attempt was also made to classify the jobs b ot determined by the exposure level, using the numbei in of "years of 5tH) ppm" exposure. The procedure w* th as follows: one year of production work in 1951. th ,lh us Table 2 Ohxentti tt>) and expected fKt deaths framtdl causes, and all new ernes ofameerin thestudypopulation except aon-tnchitiiutui akin cancer kijHtiiirr nurjufiri M "} Hivirn HI Vinyl ehtorkk (gwvlvk-m.-} Ii: Vinyl ehtnriJc {l-IX') n.% Ktxndi M*nrai*v IM IXttyvinvl dthvkk.' production IIS Auinetave (leaning IJ6 Maimenancr (17 fiK-iintitliyine OX ('uawntu service bhialry IN Vumws jobs 17 H IX 117 17 4.X vs 5v 5U All deaths <> t: 1 2-41 0 O.SU 4-.12 IV 16-42 5 >04 4 7-64 5 tt-44 7 H-77 7 7.HU tut: NC NC 0-46 Mb IM 052 (F5V tutu o-vx At! concert tt K n OKI I 0-2(1 U t-nv V >11) 1-11.1 T 2X7 5 2-V5 .1 >1)6 2 2-44 wt: NC NC NC 1*76 1-94 NO WV OVK 0-K2 Ptnon-Yton IV5J-7V ' IttH) VI2-0 230K-5 J0V-5 MIX-0 1742-5 1065-5 971-5 Total 454 50 5V-M OH4 25 ZOtb t-U *676*0 'Ml' -> Nut ratrubk'd. To of, mu 'fit j. --(im , Gin : Cm - r Ton fir. (i(n Grm NC lA 4 BFG05039 gi Andersen ^ kut contained (ions." ruction in in (he worknfmuously fcduding alarm ;tven minor ure level in Yppm most of ted with high atoclave cleanv io the great rVC. one may a the packing Those working thich contained in the control customers* serc been heavily VCM levels in . Nine different _ (table 2). a been employed in . Membership of ts that category in a jpent. If an inditer for some years, number of years at >nimal exposure, he I tow exposure caleg- lia the early 1950s, classify the jobs as l,using the number The procedure was i work in 1951. ljpopulation except hiddeiue ofiumrr ununiy vinyl thloridc tuhl polyvinyl chloride workers 27 when (he working atmnsphcic contained about poses and the expected number of deaths are based 2U0U ppm VCM on average. was classified as Tour on the national rates.. "500 ppm-ycars." The same type of work in 1961. when the atmosphere was about 500 ppm. would Results give one 500 ppm-ycar. This additional categorisa tion of exposure could he given for VC'M produc- Deaths from all causes and the number of new cases tiun, PVC production, autoclave cleaning, ntatnic- of cancer, excluding non-melanoma skin cancer, urc nance work, and PVC* packing. Ow ing to the surplus presented in table 2. The number of person-years at monomer in the resin, one year of packing I'VC risk is also shown together with a tabulation of the would give nhoiit one 500 ppm-year for each year nine different exposure categories. Among 454 men up to 1970, and it is even possible that this high level there were 50 deaths, from all causes (expected continued until 1974. In this wav high exposure for 59-3). short periods in workers categorised lv jobs will?*: During the 27 years of follow up. 23 new cases of low exposure level could he accounted Tor. >, cancer were found against 20*2 expected. The nine All workers were placed i/> an cv|xsure category H exposure categories have been combined into three before we had any knowledge of their state or health groups reflecting high, medium, and low exposure or diagnoses. (tabic 3): the increased incidence of cancer is accounted for almost entirely by the high exposure FOLLOW UP group. The main element of die method is to identify those There 'w*as only one liver angiosarcoma, recruited individuals who meet the criteria for membership of from exposure category 04, and this case has been the study population and to compare this population included in a previous survey.1 wiih a constructed Norwegian |xipuhilion whose age Table 3 presents the observed and expected distribution was identical with dial of the study figures for some malignant neoplasms of interest. group. (The method has been described in more |;ive cases of lung cancer were observed in the whole detail by Langhrd ft study population compared with 2*K expected. The Total mortality and cancer incidence from 1953 to `mean time Iviwccn first exposure and the time of the end of 1979 have Ivcn determined for the study diagnosis (latent period) in these live eases was 17-2 population. *llic Cancer Registry in Norway has years (range 3-26) (not shown in the table). Four of records of all new cases of cancer since 195.1 and has the live eases were in the high exposure group (1*82 access to information on all causes of dentil provided expected). hy the Central bureau of Statistics. This study is Four malignant melanomas of the skin were based on a comparison of observed and expected identified in the study population whereas only 0*8 total mortality and ineidenee of cancer for the was expected: three of the cases were observed in period 1953-79. To estimate .the expected numlvr the 'high exposure group (0*5 expected). The ' of cases of cancer, the national live year age specific tumours were located as follows: two on the trunk, ; incidence rales were used. According to the data of one in the face-neck area, and one on a foot. After ; the Cancer Registry, the rates of cancer ineidenee in the observation period one more case has been : the Telemark county arc between IMJI) and 0-95 of diagnosed in the medium exposure group; this was the national figures." Consequently, the more rob in the faec-neck area. We urc aware of one case of ust national rates could he used for reference pur incipient malignant melanoma located on the trunk Table 3 Broad ctiteyories ofnttrk mi/iiuu/u iv/wnurrfn'W. IJMnrnf ffit anil r*.r/rt*6i/ (FI deaths front all auises, cases ofcanerr (allsitesJ.colon >uneer tll`1> /5.tj, hnnuitiulnmrrr tICL) Iit2/lfi.l). tnuliymmt tttehmntnu ofthe skin (ICD IV0). and cancer ofthe thyroid viand IlCi) lWJ. For oork label, stv table 2 tjnoiuif tr.-tf* (iiaip I (itouft 2 Croup J Total No of tntrker* 297 107 90 494 AU.vta.n K7J/5.I ICO ln2Ht>.t ICO fto ICO IV4 it k ttk it i: itiE it E ihE tl t: WE it E ferion-yrar WJ-79 WE IK CWi 1*4 .1 .1 4*79 0-6 II * 2-44 ll-X 0 0-92 V3 0-34 NC 0-IK NC 4 0 1 I-K2 067 0-39 >.1 NC NC 3 t 0 U-51 9-9 0-IN NC IS Ml NC* 2 0 0 IS II 004 0-U2 IN-2 NC NC* 5727-0 1977*5 V7I-5 23 2016 II 3 1*44 2-1 5 2-H4 l-M 4 074 9*1 2 Olh 12*9 H676-0 *rruu|> I (high vinyl rtiKwkk.- evjvisunrl ** Wwk bhcKU|. 02. 04, 09.06. 07. (hup 2 I medium vinyl chtitrWic opHUU'l ** Wk labels OX OX. (iriMp 3 (ki* vinyl riiloriib.* cipKun`1 - W'ml. bihcl 04. NC Nrt okublcJ. CQQVZIQZ i|; RFHOSOdl Aih^'M*1 I. Indilanr ofamt t r uinmn; \ iti\ l ihluride iiiul po/rnVtW liilorule u tirkirs 2y ti*eiaiu>ma frv**Ml WJ-7 J7JTU i I246-.V W76-U jlKD I62/IA3). ,.p* txpoatre index tenon-ymrs I9}J-7V <V ,NC WM i vc :ww s } 354l>.' 125 *67frO I jfg cots ofeatuxti- 0 06 07 OH 09 r*rf.a Ji and diagnosed in 1977 from ihe medium ex|>usure group. `1'his case Iiun out been included in the study. Ihe latent period for the Tour cases occurring during Ihe follow up period wasH K years (range 2-2K)(mu sJiown in table .1). When Ihe Ivvn additional ease's were included the Intent period was id-1 years, Three cases of colonic cancer were observed in the high exposure group against 0-9 expected. Two cases of cancer in ihe thyroid gland were observed: .both were medullary carcinomas. Table 4 shows the relationship between the date of first employment in ihe plant and the incidence of all cancers and of some spoeilic tumour sites. We also related the expected chance (risk) of developing cancer to the estimated weighed level of exposure, the 500 ppm-ycar indicator, and these results arc shown in tabic 5. The highest risk ratios were found among those workers who were characterised by high exposure---that is. those accumulating more than live 500 ppm-ycars. We have no information about the VCM exposure level for the exposure categories 03 and OK (table 2). which are classified in table 5 under the "less than one*' index and which includes workers with less than one 300 ppm-yeur. It may be assumed, however, that some of these workers were exposed to VCM levels of about 500 ppm. Therefore, the correct exposure category for one of the two cases of lung cancer under ihe "less than one" index (table 5) could be the "one to five" index. The same may be true for the one malignant melanoma under the "less than one" index. The plant employment history of all workers in whom cancer hus been diagnosed and (he tumour sites, ranked according to K'D code (7th revision), ate presented in table ft. The year of first employ ment and the age when cancer was diagnosed are also included. The previously mentioned latent periods have been calculated from table 6. Discussion 1 4 15 ,,JCD 142116)(lui** * t>r`*ljN lHO(MlS(nftnl wtenuma ol tt r The present investigation has shown an increased incidence of malignant melanomas of the skin, lung canccT, colonic cancer, and thyroid cancer in VCM/ PVC workers. Our observation on lung cancers is in accordance with the results of several other studies but to our knowledge, an increased incidence of malignant melanomas in workers producing VCM/ PVC has not been shown before. 'I'hc present study is one on the incidence of cancer, by contrast with the other investigations which refer to deaths from cancer, if the percentage survival in diagnosed cases of malignant melanoma is high, studies on deaths (mm cancer may have masked a possible increased incidence of this tumour. Waxweiler et of observed 11 deaths from lung cancer, as compared with 5-7 expected, in VCM worker* with at least live years' exposure who also had been observed for 15 years or more after first exposure.* They also noted ;m unusual distribution in the histological lyjv of lung cancer. Of the eight histologically confirmed eases, live were classified us large ceil undifferentiated. In our study (wo of the cases of lung cancer were classified as oat cell car cinomas (small cell undifferentiated). Doth occurred in the high exposure group, and both patients had started work I'cfore 1959. As the numbers arc small. wto conclusions should be drawn, hut in-Norway,'4 as '}n other countries.'* only about 20% of all histologi cally classified lung tumour* arc listed ns oat cell or small cell carcinomas. Studies on populations occu pationally exposed to arsenic, asbestos, chromium VI. radiation from uranium, and cliloro- mcthylctlier" indicate that the proportion of oat cell lung cancers in these groups is much higher than expected, and this'suggests that attention should be paid to oat cell lung cancer in epidemiological studies on working/ populations. Uufller el al observed three deaths from lung cancer (0-6H expected) in a subgroup of VCM exposed workers with more than live years* exposure at high exposure level and a long observation period.1 Fox and Collier, on the other hand, could not show an increased risk of lung cancer in members of a cohort recruited from different plants.* They included all exposed workers, laid down no requirements for exposure minimum, and no minimum observation period was accounted for. In the present study the smoking habits of the members of cohort are not completely known. A smoking questionnaire survey in the plant in 1980 showed that 5,V*f. of the workers were smokers, by contrast with 42% in the male population in the whole country in the same year.'4 Consequently, it docs not seem likely that smoking us a confounding factor can explain the differences in the incidence of cancer.'4 Maltoni ei ul have indicated that VCM is a mullipotcnt carcinogen in mice, rats, and golden hams ters.1 They also showed skin tumours in golden ham sters. some of which were malignant melanomas. In a study of the kinetics and organ clistribulion of VCM in which rats were exposed to ,4C-VCM by inhalation. Duprat ei ul showed "a great deal of labelled molecules probably both VCM and its metabolites" in the skin after three hours.11 In a similar study Wuinuhc el al confirmed these results.'* None of these authors discussed the significance of the distribution of VCM to the skin, however. Malignant melanoma or the skin is believed to be associated with exposure to sunlight'* and few occu- m 0724005 BFG05042 \r .10 Ufhlons. iMiixAnl. mul AmU'nc* potions liavc been associated with the development 4*1 ilicv liimouis, Tcai gas {i*eli1om;icvrlophcmrte| itiul jhilycMitfinJiletl biphenyls"* me chcnucitlx Unit b:nv Ken su|>pcstcd as possible inducers. Ij) oof .study |x*|ul;nit>n one more case n( melanoma hits been JiapmiseU alter ilc closure nl the study and before the increased incidence id fufiMWf *'* known to us. Iliis additional ease considerably slieitpthvnx the association IviweeM c.\|xivuic to Vt'M mul (lie development <l mulipuam mekmrrmHS. As lJ>c medi cal services in the 'Iclcmurk county have been ol a htph ipinlily and ensile accessible, we do not believe that there lias Ivert imy bins due u* the presence of the occupational health service in the company. In tael, none ol ilk' lour eases was diagnosed by the occupational physicians. One <f the five subjects with skin cancer had survived until June llJH2. The incidence of malignant melanomas in the rurnt areas of 'telemark, county is xJiphtly higher Hum the naiMuial rate while the incidence in urban areas is faiily equal to the national rate." Alt subjects with skin cancer had lived in the urban area. We olwcrved two cancers of the thyroid gland (II-ih expected): With eases occurred in the high ex(>osrc jijoup ami were of the same histological lype. We are not awate o( other studies indicating an excess nl this type of cancer but as only two cases have K`eit observed. i conclusions mu Ih: drawn. In-a Canadian study on workers excised to VCM lot live years oi more Iheriault and Allard showed art excess d cancer in the digestive nMi'iit.' but the authors concluded (lull the excess is accounted lor exclusively by cancer of the'liver. In thc.prcxcilt study we lound ;i slight exeess of carreer of lire .colon. Matty or tlie other studies referred to inehide cancer of the liver in digestive cancers, and they conclude (bat the excess risk is due to tide hrmour. There are Tew re|Hrts on itccupaiinunlly induced cancer of the colon and reelunt although it has K-en indicated dial asbestos workers, textile workers, and steel workers base an increased risk Irom these diseases.Wat- nalv el uf in their kinetic study showed some taeeal elimination o( ,JC niter (be iniudaliott of but they discuss only urinary and pulmonary elimi nation in their paper." The results presented in the picscnt study, consi dered with oilier epidemiological studies, seem to Mip|vorl the view that VC*M may act ;tx a imilticar- eruiigen in man. 'litis is in accordance with observa- lions from animal studies.1 Some tf our imdings dir* fer from those picsetitcd by other workers, and will Ih* followed up later. The observation period is short lor some of the memlvers ol the cohort, and the study yioup is small. Nevertheless, the fact that (he excess ol dillcreiK cancers was seen in the pomp with ilu* 1'siimati`d ex|Hisitre level strenp- ibens the suggested association between VCM exposure and these lyjvcs of cancers, in particular the malignant nielanomns. We ibaiik the Plastic l>ivisimi of Norsk ) Jydroaxba JJ eiMi|H-tu<rnM diroiiplmiit the study. (> C Itbckmun'l critical vommculs were of preat help. We ttiauk Mr* P A I lor lor lirtpuistic help and Mrs U Damclxcn lor f typing the mamiscripl. Reference* ' C'n-cvh it . Ji4ius,i* MN. An|>>Ms.iKma nl liver in the manulaft..o- .4 p.lyOml chktride. .10.11 l*74;t6:l5M. ' Sputa* K. Kaminski K. Angamucoma mT lhe liver in vwjl OikttnV polvsinvl chloride workers. 1477 update iS tic _ NlOStl ictisnii/mr |97K;2lt:427-l. 1 M^liiwti 1 vk-iniiv G. titihcrii A. Cntti G, Carrcui D. Car* -utgr>m-ii> runaway* *4 nni vtiktridc monomer: "bhhJcI H risk irM-sxih-M on m experimental husis. linriran llnti IVopo-r IWI 41-..1 ;<J. *Mn'*xt HR, IVtcr* 1M. Miwm MN. |`Mpriional mood*) wHmif vintl.vlikMkk> wwirrs Ijtttrrt tVJr;#;.!*?**. * liilvislinw ih. Galley WR. Mnrtutiry study nl wtwkcf* in iW ' manwtactuic <! vinyl chloride ini it* polymer*. JOM |474-.lti-5u>i IH. lVnit-ik-r HI. Suinper W. Wagoner IK. Akw /. FtH U. Cwn f, Neoplastic tisk among wtHVvr* rtpacit m vinyl dikvik Ann SY H.*t M t l)7h:27l:4u-K. * Huiik-r I`A. Win*) S. l-iitcr ('. Stniri: L. KilUn l)t. Miwtst* i-sjH-iirrKV >4 workers in a vin>1 thUaWc mtxMtmcr ptiCvau pknit./rMt P7`J:2M>l5-2it2. I n* Af. t flier t*t;. Mttrlalily experience nf wtHkcncxtxwt* vinyl riiknitk- iiM>nmcr in the nwnulciutr of p4yvi*l cH1mk* in Cireat tliiisin. hr J hut KM 1177-34:1*10. - IlK'irantl G. Atbnl f. C'ams'r nvmnlrty if B ynmp ol (.'arattir hoitiers exisisctl u* vinyl chhiriUe moravmcr. Jtli l*i;J.Vf7l A. *' tkms-s A W. S'inyl chtorkle aist Oh* prducii<m <4 PVC. t'rocrrt ino af r Hnyul AnirtV */ Kfnliiinr |D7fi;W:f77-4l. " Kaisiatlt XI. per: heiltb implicBliorw and |<foduciHW trerri r.'nnriw 11ft)ih IVripert 117h;l7; IU7-1V " Iwiptil S. Awk'Ocn A*, (iflslb It. IrvcWicnct **( cancer anaw k'lriKkiiimiuM kwl h-uiMilinw worker*. Itr J JnJ Mrt I*iwi37:|l4.2t, "Cmk-ei Registry nl Nnr#}`. Incitichcr */ nwnvr In Ni iv?* (W: '!1h* NwvgiaR Cancvi .Society. " RvrIv ({. itvlianwii Aa. I jmpckrclt i Ninyc: cn xscrvikl havrtf HicftrepisieieK tttatetialc. liiuJif Nt* J^rgrf*r P>x::l02-4Hli4. " hVpwnn Oil. tVicrs JM. t*at ceB tong cancer in selected ocnif. . liorts: a v-aw-control sluily. JOSt l`l7K:2<t:7l.t^. "Awlvm It. Aspcvl* t confounding in nccupabotuf heat r|>tilent*<li>e>'. iownt J tVivk fjiiiruo ItntllU I17H;4:K5-S. *' Ihipiat I*, t-ahry Jl`, GrnOiski I). Magadur Jl_ Mcutv in industrial poisoning: Mood kiitclic* and tUvinl tin ol "(''VinvIcMnridc numiinKr (VCM). Aria IViarma honof pl77;4't.ppl |:|4-S. " Wqiaiiiilv |*G. McGoaran OR. Madrid HO. Orhrinf Pi. Fair px | vimf chloride tnlkwin; MhihtJoncipittrr ift rrlv 7- ho/ (/>/>/ rh*rme,^l \ 17hJ7:41-5g. ** Magnus K. tlahilx ol sun exposutc and risk of rruliju MH-larwHtu: an analysis of incidence rale* in Nivway IV 1**77 In- cohort. a>i, age ami primary tumor rile. Cm |MK|,4li:.t2-.tJ. ," Solv-i Al. t iwjvatrick '111. (ienetk and environmental lacto iulign.->Ml dh-Imiwki in man. J'rgmmt i'riJ |7l:MttU*N ' bnviin It. C`ohMcvtal caruvr--an occvpalitwal dbeiuc? i OivNhiniiiyr t17X;75:.t2t.t. ^ BFG05043 mated. (M In several cases, work histories la the - employment record* did not provide enough details to pinpoint ipecilic exposures. (4) Historical data on exposure levels were inadequate for the chemicals tmder investigation. Thus no quantification of ex/tosnre was possible. (5) Many of (lie workers were potentially exposed to a multitude ot thermcals, utid it was impossible to examine mortality by "pure" exposure. (6) For several conditions, the number of study subjects in some of the subgroups was smaller than desirable, and it was difficult to draw definitive conclusions. (7) Being a mortality study, the investigation nor only inherited all the problems associated with death certificates but also Suffered front lack ot in-depib clinks) information . (K) Employment other thnn thnt with the existing company was not considered. Nor was it feasible to include smoking history in the analysis, Despite these limitations, the study has identified several potential health problems in the cohort, We recom mend that this study be updated in the future. A longer observation period wifi not only increase the statistical power of the study but also establish any trend in mortality, it one exists, in (he cohort- We thank Professor (Irian MacMahon of Harvard University. Dr Philip Lnntlrtgin and Mr David llrnwii of the National Institute for Occupational Safety and Health, and Or Thomas H Milby of Environmental Health Associates for reviewing an earlier draft of this report and for making several constructive comments. This study was sponsored by Vvlsico) Chemical Corporation. Requests for reprints to: Dr Wong, Environmental Health Associates, 2150 Shavtuck Avenut, Suite 414. Berkeley. CA 94704. References tuauKil cKcnucak: *ilh t Uivuvchmi <! M>nla(Ua I iljuuiucM. Iisnbury i|kuI Hi*. V, Qiitb/i'aiiunx nfnerupt. riM e*ntti. CnW Sftttn tlaibui Ulantwij, till; JW-ll, Work) Health Ottmiuiwa, f<iitaia*ar clnuifieiHa* / Ob- rtut, 197V rr/iuoa. Gcwik: WHO, 1)7*. * Uonut HR. Andrvli el uUti-t tni f>tof-miior>l am. I tal>t)T. Cunputen *aW Uvittrjlttl Rattle* 1974:1:77$-); | (Aa updated venion el this pro|itm *n uuit in the ptuu [ iimjf.j i * Dolt K Krl'oifwClivr aiat pirtpecllvc ilu<ji<>. In: Wins L4, ti I Matital iutteyt a*d rJtnltof vtali. London: Otittrd Unlvctuj Prew, HM.Wr-7. * Mintcl N. Synthetic rcogipcctivc iluditi and (Minted tupi Btoinenki 197J;7*:47*-l*. * Manic) N, Htenitt) W. SiaihOtnl uptiW the snntjUt *t <lu> ItMUHcyotlnUwlottf SiUMI,MCI )9>*;il:7l*-4l 1 Mantel N. CSi-a)uwc tcili with one <Se|,te ot freedom: erica, i liens Of the Mamel-llaerUMt procedure. MU l4l;S*:*!-t00. * National Cuninw'iaiun on Oiahctes. Rrpori. Vat III. fan (. i NVaitimfloa: ptpatmeM ot HtM> RdvinMoo end Wellm, | I'iJS. (OltliW Putdienlion Nu (Mill) 7S-I02I. 1974.) I ' Nblic Health Service, National InttHutet uf llutlllt. ITiaScm I afata. (Compiled 1*77.) WtUiltiglWK Mill, 1*7*. (Mill fhbh i cation No JV-KM. 1*79.) * National llckrt,l.iM| and Uhud Initituie. krpotl o/rAr aeai,^ I t'-'af M Sum* Aerate rpidrmMnty Wathlopi,*): lt)t 1 National tmiilulei of Health, (Nil! publkatitilt Ho 79-S&41. j 1*79.) ` LoathSo Jti. R,iMai* SJ, Morriron AS. RIO laemo (or raacrrd tM lestla. H Uadi *ff IWiJttl 12-21 Amir li. Vokaat R. lilfrct id dietary elkyktie ahbromlde an M MM>. Hunt \VhS'.Wt'.**-ti. ,,, . Cdwords K, faction II, Tumi AH. Sludtestnlh sltylaimi eaten II. A ehcndcal iflleijvcUlnui ihrtHJtli nwulndic UihIki id *> aatl krlilily eflcos at clhykw deihancoif*onaie aad elhykat ikbriumdo. 4fm4em Pharmacol (97(hl*:l7Hl-9. * Wua( O. Ulidllan IIMO, Katun VS. kitieipectWe ciahtadaa (KModwtlv* performance ot wotUrt eapoud to cik)kat dibeomld*(CDP>./OM l*7*:ll:9t-lOb. "WUrftoo O, KrtoM. RM. MaaahaH S. Mdhy Til. lidemSir** auk ncsikhb vorters. Ltarrt I977#:l}5-M. Milhy Tit. Wkorion U. lirddentlnlnskal assetsmenr ol oeom llwiaay raUaed. chemkally iwluecd aperar count suppreuao iCM mojt.n-ti. Maw* TJ. McKay KW. W eanerr mmulky tf eoonly, f* 1969. Widiincn**-' Ikiuttnienl of I leatik education and < tau. |*7.(OU6W poWkMh* Nd(Nim14-4S. 1*74.) _ o Wane O. A piactkal |uWe foe non-epiikmhiloa'ais, Pam I m1 Si_____i/~r* _r Sultir lOShWS.il-*. 71-4. * Wrvnj O An uftalrnuolock llvJj ot <xStra pountUUy tipoaed Incidence of cancer among vinyl chloride and polyvinyl chloride workers s STORETVEDT HELDAAS,' S L LANCiARD,1 AND A ANDERSEN* tiniii the Research CenterNorsk Hydro as t'orsgnntn Fabrikkef, 3900 Portgnmn, 'felcmnrk Sinufllifilrhus,' Drpurfrrtrrif of Occupational Medicine, 3900 Pongruiin, and Cancer Registry of Nnru ay.1 Manithllv, Oslo 3, Noway. .oisttiAcr The results of a follow up study of the incidence of cancer and the mortality in n cohort uf 454 male workers producing vinyl chloride and polyvinyl chloride are presented. The Mtiily |ktpitlnlion was restricted to employees with more than one year's work experience in the study I>Um between 1950 and 1969 and (he cohort was followed up from 1953 to (he end of 1979. Iwenty three new cases of cancer were observed compared with 20-2 expected; one ease of liver xngiitsarcoinn was found. Five eases of lung cancer were found (2-8 expected) and four cases of malignant melanoma of tlw skin were observed (0-R expected), The possibility of a causal relittiutidiip between exposure to vinyl chloride and the development of malignant melanomas is tliwusscd. We p)74 when Creech nd Johnson presented linn of VCM and PVC was stance) in l')50 Vi'M their report,1 human exposure to vinyl chloride. was produced from acetylene in the rmin wficrc ilte (Vt'M) has been associated with ilte occurrence of polymerisation reactors were located In 19f>7 tin- jnyinsa/coina of Ilte liver. Several studies have VCM production was partly altered, and cracking; of confirmed these Initial results as reviewed by Spirtas elhylenedichloridc (GDC) was introduced as one nt *d Kaminski.* in animal studies where VCM was two production mctbnds. The production of VCM rcn to mlee, rnts, and hamsters by different mules was discontinued in 1971 after which time Hie plant of aduiiflisinuion neoplasms have also been induced was operated as a polymerisation unit. From 19.VS other organs.* mlwands VCM and PVC were produced in separate ^tether VCM has the potency to induce eatuxr rooms; table X shows the volume of VCM and PVC w man in organs other than the liver has mi yet production and the number of employees over time. 7i confirmed. Lung cancer,*-' brain tumours,*** ><td cancer in the digestive system, primarily STUDY POPULATION ui(itH4rcoma of the liver.''' have been suggested to A list containing the names of employees who h.ul t* in excess in workers producing VCM and started work before the cud of 1974 ttnd wImsc H)vinyl chloride (PVC). and the prime purpose of period of employment had exceeded one month n.i> (he prewni investigation was to study iltu incidence constructed from the personnel register provided by 4 Uncer in workers ci|ktscd in VCM, with special the plant. 'Ilte health department <>f the comp.iii) rmphasis on cancers other than liver Innnuirs. has kept the health records of all present and previ Vkteria) and method ous workers employed from >940 and oimtuK. These records also rnninin some information on tin- place of work of each employee, fly comtiining ili,-v >ant (}i-:scntmoH h>c study plant is loealed in lire county of Tclctii.iik o vittili cast Norway. In addition to VCM and I'VC Table I Annual I tttlnride and imlyx iiifl ehtorute prtHturdim mid numln r nfnnplnyesi in the tinrly iilimi un|i4iiy produces fertilisers, magnesium, and dikuiitL- in adjacent jduol complexes, 'tire priuliic- AufliU (9X2 v-irw rkii4:t full IVrtfS jv/huI tlUulnh-+sns |9bl-7(l : r'7t ITal fuu,,| ItMNS- 7Still j.stat. sm*t siaiv-.wtuMt rvc (.!) Vn ,|/, U, Iraki), ysta) .S'Mtamil..yiSaiaamm ytauat ijaaai 25 iinaMrt-iwMVia ***** Muta.;.^' tOOtZLQ?. `I sr 72^008 x%> -11-1 f|-|(TTir> i fTlTl Wlillltfniil*l'M>i'*'tfW<^1if<Wi`f1ffli Ml I'NO 1'M * |WHBh apiMmp |<e|* * ( dfe*. 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'alaidiuoa aq 01 pawmawl tnw q.-oq-A iji.iwiv I. I i 1 BFG 05045 M '"-'I..................................................... iihl ihapniwd in IV7V trout the medium exposure ill. . tin |/< It t'tm in lil.ili-111 in Win.- niifhifuli-i'tthe I'1""1 I...... Iliis cum has not been included in Ihc study. ........ .. <* */ uflr/i l*lVk i r*M * |>Mi J in i: iji >H Is4.ll 4S4 NC N.M . jkul.lv'J. AX twireei 11 K t 101 X Ml A ill } m: 2\ 111* 14 OIK OH M 14 14 0-H ICO I61II6J OK 1 till } 0*)4 a OS') i 0J1 i 3X4 (UK in 11 NC NC II HP 190 0 F. l fl 23 1 Oil ] IHV 0 fl 11 4 o? ``i VttUMS* on: 'nSi-19 HC NC ii-i NC JAIV-ll nun Uflii |!4(r3 3-1 salflu I lie latent period for the four caws occurring during ihc fallow up period was 8*8 yean (range 2-28) (not ih,.un in table 3). When Iltc two addiiiunal eases ere included Hie latent period was 13-1 years. three rases of colonic cancer were observed in ihc high exposure group against 0-9 expected. Two ow. of cancer in the thyroid gland were observed; |..ili were medullary carcinomas. table -I shows tlie relationship between the dale I UN employment in the plant and the incidence of \ >1! cancers and of some specific tumour sites. We f lUiictaifil the expected chance (risk) of developing I .il'k $ Ohsinnl ll*huul ei/wtof (K) inset nfttitteer, id! xiti*. n/Ulf cuiofl {ICO flJ}. s'fdie Jung (ICO 162116) \, ^ t tflii-r in Hie estimated weighed level of exposure, unilnuiMit iiii`Iii>iimiiii nj ihr skin tlCO 190), mul muerf i)f the ihy/oitl glmul (ICO 194), 6/ SOOppm-yrur t.tfivuitti<ubi in,' mh> ppm-ycar indicator, and these results are ,v.. ..I Mil Am'.,i.tiifn AtttMters ICO J.U ICO liVIU ICO t90 ICO 194 n (. mi: 0 c oik fl f. me o t on: o f. on: 4 7 (16 II H \ vio mi 14 V-Ul 1*4 l>51 NC Oil NC 0)4 2*1 101 Ml I 040 NC 0 1-44 M ) 0-2<4 NC 014 NC 03) 9-1 D M NC 3014 0 00) NC KWH'S 1104 33 ) 3S4Q-3 is 20*14 i i 144 2 1 014 131 *41*0 tViwn in (aide 3. Ilie highest risk ratios were found t.Mtg those workers who were characterised by s.|h opmurc--that is, those accumulating more thin Inc MHI ppm-ycars. We have no information iN*n the VCM exposure level for the exposure .iirf.uk-stl.l andQft (table 2), which are classified in iNe 5 under the "less than one" index and which vOuiW' workers with less than one SOU ppm-yvur. NC - N.k cAuOud. *l o cUkiMAcoI or-nurc leu ihcsccuci > . HM . Ii nixv In: assumed, however, that some of these were exposed to VCM levels of about 500 Iftn IIkcicfurc, the correct exposure category for .i( ihc' Iwtf cases of lung cancer under the "less * nc" imlex (table 5) could be the "one to Hs-c" I ul'lc h OiMrihniiin, I,K,,ert * Jnr.ihnn nu.ee nuegorie* mi....... .,/*< ' whom ttuu-ee hai'heen Mugnoteii (all raid rr unlcr tli/feintl enlcgories in yean ' I *-,ki '|hc smite may be true for the one malignant vIjiHinm tinder the "less than one" Index. _ I Ik plant employment history of alt workers in )' A/*# 4l'<t t Vutf offit*i tviij4<Jymrtu Yt* f tiidfamii ten ** i Fi^OiNff WfxriWfll Of 02 OJ 04 OS 06 of w <ts*m i-.-inccr lias been diagnosed and the tumour if i. ijnkc'd according io ICO code (7lh revision), tre presented in table 6. The year of first employ- l'W*i 1*144 I I1V*11441 t*ii: iisn.' - l*tO lilt IS) ||**IIMUII Il*V)11l IS) i)l |<)S(1 !')*; I1SS Il*VH4.nI 1*1)1 114433(01 1424194 OSH 1*1411 1I*`4114111 I *7)1 soil ms IW.1 143 |43 1)1 I la 1*452 ll**i52t |*,`H IUW IV.1T 1*1 (SKS Ivo tvu )U | wvnt jikI ihc age when cancer was diagnosed are h'l., iiu'luilcd. 'flic previously mentioned latent ' |r n-wls luvc Ix-cn calculated from table 6. Ihwusslnn' ' 1*h tkcvut investigation hul shown an increased ikk.b-iHV id niaiignnni melunomasof die skin, lung i ii,> i. colonic cancer, and thyroid cancer in VCM/ FM winkers. Our olwcrvation on lung cancers is in ..iidjmv with the results of several other studies '-i i" our knowledge, an increased incidcm'C of *Ml>fnjnl melanomas in workers producing VCM/ f' I hn not tsecn shown before. The present study ly/i i*n |V rvA I II I II Ik I*. I (u4'k,oi>vi|. It I) ISS id iIh* lubrfivpasSHgcsunifcver), IUJIAVIA.)(iMgand hi. Ill l.jiui-i ..I IIh* |M.4li>l. II II IT* Iw-uiv vxHClk. U.lj III |NKk< (ini|. ICO IVil (4(Aiil incliiunu >><<! II ,|,~ l> I I.JU.V! >H ikr iliyi.w.1 pLiikli with ih.* auwlvt* n ijHt >. Iin.-a dlivl Ikv c.kl ..I lUnervau.m (viwmI. ?. , > *<nc tin the incidence of cancer, l>y contrast with ihr oilier investigations wliidi refer to deaths fiotn nnrii. II t!|c percentage survival in diagimsed eases A malignant melanoma is high, studies on deaths tim cancer may have masked a possible increased I'VnIrnce of this tumour. IVaswcilcr cr itl observed 11 deaths from lung cancer, as compared with 5-7 cxisccicit, in VCM wurkers with at least five years' exposure who aKn Ikad been observed for 15 yean or more after lirst exposure.* They also noted an unusual (Jistribunon in the histological type of lung cancer. Of the eight histologically confirmed eases, five were classified as large cell undifferentiated, in our study two of ihc cases of lung cancer were classified as oat cell car cinomas (smalt cell undifferentiated). Doll) occurred in the high exposure group, and both patiems had started work before 1959. As the numbers are small, no conclusions should be drawn, but in Norway,** as in other countries,11 only about 20% of all hisiolop. colly classified lung tumours are listed as oa I cell or small cell carcinomas. Studies on populations occu pationally exposed to arsenic, asbestos, chromium VI, radiation from uranium, nnd chlnronielhylcther" indicate that the propnriioit of <*.h cell lung cancers in these groups is much higher than expected, and this suggests that aitunimn should he paid to oat cell lung cancer in epidemiological studies on working populuiiouv Buffer rr ol observed three deatiis from lung cunccr (0*68 expected) in a subgroup of VCM exposed workers with more than five years' exposure at high exposure level and a long observation period.' Fox and Cottier, on the other hand, could not show an increased risk of lung cancer in members of a cohort recruited from different plants.1 They included all exposed workers, laid down no rcquiremcnis for exposure minimum, and no minimum observation period was accounted for. In the present study the smoking hahiis of die members of cohort arc not completely known. A smoking questionnaire survey in the plant in 1980 showed (hat 53% of the workers were smokers, by eontrasl with 42% in the male population in tlu.whole country in the same year.'* Consequently, it does not teem likely that smoking as a confounding factor can explain the differences in the incidence of cancer.1* Maltoni el cl have indicated that VCM is a nuiltipoteni carcinogen in mice, rats, and golden hams. lers.'They also showed skin tumours in golden ham sters, some of which were malignant mctamwii.-iv In a study of the kinetics and organ disiribuiion of VCM in which rats were exposed to "C-VCM by inhalation, Dwprnl tt of showed "a great deal of labelled molecules probably both VCM and its metabolites" in the skin after three hours." In a similar study Wutnahc n ut cmifiimed ihi>v results.'* None of these authors discussed rlie significance of Ihc distribution of VCM >' ihc skm. however. Malignant melanoma of the skin is believed to he associated with exposure lo sunlight1* and few uuu- ..wwN awilHWPlOT9iMtW>WIWMttlWiM4an***m ................... .. ...... eootzzo BFG 05046 I ..Kn >u> have been associated with ihc development thens the suggested association between VCM <il these tumours. Tear gso (n-chloroacclnpticnom:) exposure and these types of cancers, in particular .mil ikilyehloniwlk'd biphenyls'* ire chemical* that the malignant melanomas. Occupational exposure to hydrazine and subsequentlime been suggested us possible inducers. In our We ihnnk the Plastic Division of Norsk Hydro as for Mini) (kipuhiuiii one more ease of melanoma has Iveii diugiuiscO after tin: closure of the sludy ami isjf.irc the increased ineiilcncu of tumour was known in un. litis additional cose considerably strengthens the association between exposure to VCM and the cooperation throughout live study. O C llftckman'i critical comments were of great help. We thank Mo P A Flor for linguinic help and Mrs U Daniclsen for typing (he manuscript. risk of cancer N WALD.' JILUAN OOREHAM,' R DOL1..' ANDJ BONSALU development of malignant melanomas. As the medi- Rtfercird From Iht ICRF Coactr hi'IJemiology and Chnleal Trials Unit,' University ofOrfont, Ratlcli/fe Infiniwrv. ul services in the Telemark county have been of a 1 Crutfc /U iutirun* MN. Anjioureeou at liver in the aiinulw- Otford, and Occupational Health Department,1FDC LimUtd, Haiaton, Cambridge, UK high quality and easily accessible, we do not believe that there has been any bias due to the presence of the occupational health service in the company. In fact, mute of the four cases was diagnosed by the occupational physicians. One of the live subjects twe ol polyvinyl calnri4c. RIM |9J4;|*:IJO-l. 1 Splnsi A. Ksmtnikl R. Aftflourcoms o( the liver In visp ddamk/pidyviityt ehlwUe wktrx 1*77 update ol (he NIOSM rt|iu<>. ION 1971,29:427-9. * Msltoni C. Uiwnlnc C, CUibtnl A. Cecil O. CeruilJ O, Or- tiftojerikiiy bioauayi ol vinyl chloride monomer: t modd d AiwiRACT Four hundred and twenty seven men with varying degrees of occupational exposure in hydraline, a weak animal carcinogen, were studied to see if they provided any evidence of carcinogenicity to man. The observed mortality was dose to that expected foe lung cancer, other .viiii skin cancer hod survived until June 1982. The incidence of malignant melanomas in the rural areas of Telemark county is slightly higher than the risk aiuuawM on so #ijrimnnll bads. Environ HmU cancers, and all other causes, irrespective of (he level of exposure. There were 49 deaths (61 -*t7 frrjpan I9II;4I:M9. j `Moniua HR. Retell JM. Johnson MR Rroponionsl monab) expected) from all causes including five deaths from lung cancer (6*65 expected). The results unoo| vloyt-eMorkle raker*. Lsatri I974;|i:)7-e. j thow that no obvious hazards associated with hydrazine exposure have yet appeared but because national rale, while Ihc incidence in urban areas is fairly equal to the national rate.'* All subjects with skin cancer had lived in the urban area, We observed two cancers of the thyroid gland 'Tsbenhsw IR, OaKey WR. MunsMy uwly ot Wilts in*.I msiMfseuue T vinyl chloride Md ill polymers. JOH I974;l*:)09-ll. * Wti.cikr Hi. Stringer W. W*|uncr IK. Jotwt 1. Filk It. Csrm c. NcOfUxnie iliX anklet willll npoK'' l* vinyl ehlnrid ol the small number of men studied they can only exdude gross hazards. I lyilra/foe (N,H.) is a colourless, fuming, oily liquid cancers, but 1,2-dimethyl hyihazinu did c-ni'i- (it th expected): both cases Occurred in the high exposure group and were of the siimc histological type. Wc arc mu aware of oilier siudics indicating an excess of this type of cancer hul as unly two eases have been observed, no conclusions can he drawn. In a Canadian study nn workers exposed to VCM lor live years or more Theriault and Allnrd showed an excess of cancer in the digestive system.* but the inithiirx concluded that the excess is accounted for exclusively by cancer of the liver. In ihc present siiiily we round u slight excess of cancer of the colon. Many of the other studies referred to include cancer AnnNY AaalSri 1074:471:40-0. * Baffler PA, Wood S. tidier C. SuX L Kihsn Ol. Mens!*) | Ciperlem.t ol rakers in s vinyl chloride iwMMtr r*ro**tu - Plain. iOU t97V:J|:IVS-70J. I * Pus AJ. Collier PF. Mnrtxlni eiferieiree at rakers etpoicd* vinyl chloride monomer In the tninulsaufc of p>4jrvp chloride in Grcrl 0,it tin. Hr J tad Urd 197734:1-10, TMrtauU O. Allard f: Camr monnlny of a |toup at Ci*A mkers cipnwd la vinyl chloride monomer. tUX 19tn;2J:*7M. - Buna AW. Vinyl chloride snd Ihe production of FVC hater* inyi nftht Hajat Soarif ofMwlirtiw I97A;49:277-It|. " Ktrutdl M. RVC: henllli Impdcilfom >nd pruduction Iren* nn>on lltahh 1`tttptri IV76:l7:107-15. " Lsnflid S. Artktsen An. Gylielh 0. Incidence of eseett iw*9 kuh an ammonia like odour. The cstimalcd loial mid production in 1981 was 30 000 tons. About 7)r of hydrazine is used is a chemical intermediate ia the.production of pesticides or plastic additives, ihMit.10% is,used In fine chemical manufacture (particularly In the production of isoniazid and illopurinol), and (he remaining proportion is used as s dcniygenating materia) for boiler-feed water and tt * propellant in rocketry. Hydrazine has been categorised by the tniern.v inmizI Agency for Research on Cancer as a weak rsirinogen' and by the American Conference of angiosarcomas of blood vessels and caccal ami hc|ia tic tumours.' ** Rats exposed for one year to hydrazine vapr.ur In inhalation in concentrations comparable to uccup.ilionatty exposed men (0-2S-S ppm), and then kepi for their normal lifespan, showed an increased inci dence of benign and microscopically malignant tumours in the nose, the incidence of which was dose dependent. Mice and hamsters similarly exposed showed an increased incidence of lung adenomas and of nasal polyps respectively." It seemed highly dcsirahlc, therefore, to sec id the liver in digestive cancers, and they conclude Dial ihc excess risk is doe to this tumour. There arc few reports on occupationally induced cancer of Ihc colon and rectum ullhmigh it Uni been indicated that asbestos workers, textile workers, und steel workers (crrnchreunium snd krrmlliaM rakelt. Ur J but IM 19X0.77:114-20. i< "Cancer Rejiury ot Nonvty. Inrijtnrr / ennrer In Rrwqj 1977-197*. Oita; The KuAveyisn Canur Sockiy, 1971. * Kvkk 0, Jidisntcn An. Un(cktdl I Nurge: cn mxnikl brnenp Ktrlircgiuenli nWlrrlsh. TMtiir Hat CnvemmcntuMndustdal Hygienists (ACGIN) as au industrial substance suspected of carcinogenic potential for man.1' The evidence is based largely nn the administration of hydrazine and Its sulphide ulis in rmlenti. whether tiwre was any evidence (tint hydrazine was carcinogenic to man and to sec wtuit had liappciwd la men who had been exposed to hydrazine vapour in Hie course of llieir work, even if ihc number available for study was small. A preliminary analysis have an increased risk from these diseases.1' Wat* mix' a nl in their kinetic study showed some faecal I9K7:ID2;4R(M. ,, i.. Mice given hydrazine sulphate hy mouth at up in Wvxmsn OU. Petcis )M. ttauvU la csfccr la selected llune a fSie owuriil slinly./fMf l`17*;79:79J-6. in*if( jl- f) tngrkgfday showed a dose related increase in (lie of men working at a hydrazine plant failed to succcm an excess risk of cancer associated with exposure to i elimination of "C after Ihc inhalation of "C-VCM, i* Aaelrna O. Ai(tell uh ou*vu.llii(i In nccupaiMnal head incidence of hepatoma, mostly "liepaltxcar- hydrazine." The follow up was incomplete, how tun they discuss only urinary and pulmonary elimi nation in their paper." The ccsull* presented in ihc present study, consi dered with other epidemiological studies, seem to epUemir*ny, JrW J IPm* ftrudmn 1971:4:87-9. [ "Dopial P. hal>ry IP. drsdiikl P. Msgaihir JL. Metsb*! approach In Indostrial pcdsnnlng: blood hinelia sad lion of "C-vinykhkirlde mommier (VCM). -Scan Mermw*; Tnifnd 1977:41. soppl 1:142-). u ,\ onnmai "* * Hydrazine, at doses around 25 mg/kg' 4>y. hat also been shown to cause myeloid leukaemia, reticulum cell sarcoma of the medias tinum, and pulmonary adenomas and lyni- ever. and as mortality was not analysed by cause no conducted a fresh study using the same cohort. The plant support the view that VCM may act us a multicar- " Wnlinahe PG. McOwonn CR. Madrid BO. Ochrln| PI. Fate* ptvimas.4** Rais fed 3-4-4 mgfday over a 68 week einogen in nmn. This is in accordance with observa tions from animal studies.' Some of our findings dif fer (font ili.isc presented by other workers, and will ("O vinyl ihhulda foUawwif inhalsihmcsposiu* In isiv Tm . kiJ April AMmintW I97J7:49-19. I * Matron , llahili ol ion and risk of mtlifw j melanoma: inalydi ot Incnlem* met In Norway ll (rood showed an increased incidence of lung (Jemimas and carcinomas, and an increased inci dence of liver tumours.* * At a (tetoty in the cast Midlands between l`J45 am] I97J about 700 tons of hydrazine were produced n year. The plant was in an enclosed building ttnd. .is be followed up l.ncr. The ubscrvaiiun period is short 1977 hy cnhoi. set, ate snd prihury llirnof die. Cam'. Oral administration of hydrazine sulphate to hatn- hydrazine was not considered to be more hazardous 'fur sirfoc of the members of the cohort, und the siuily group is small. Nevertheless, the lacl that the excess of liillerent cancel* wux seen in the group 19X1:41:2129-2). ' J Intel Al. FUrpairick TR. Genetic *M envirnnmenikl racior>< mi!<(>unl mclanmnn in mat. Pijpnmr CtH l979.S:*X-94. ' leniwHi II. Cidurcial cnrv.Tr--in uccupaiiimal diwncl C-* tm. however,.did not cause a significant excess of than ammonia, exhaust ventilation was run pmvitlcd. Hydrazine was kept in open tanks and hyd razine compounds were made from strong liyilr.miu- with Use highest estimated exposure level strcng- u.iemvioh-ey im;1S:lI1-S. solutions in open vessels, which were" heated m 070JrZLO *3 British Journal of Industrial Medicine 1984;41:328-333 fid /.a ft ?}/. Epidemiological study of the lung function of workers at a factory manufacturing polyvinylchloride M H LLOYD, S GAULD, L COPLAND AND C A SOUTAR From the Institute of Occupational Medicine, Edinburgh EH8 9SU, UK abstract A preliminary epidemiological study has been carried out to investigate a report that some men working in a factory manufacturing polyvinylchloride (PVQ had abnormally low values of the single breath diffusing capacity for carbon monoxide (Tlco). All 265 present and past employees of the PVC factory were studied, together with 219 men from the workforce of a nearby foundry. Each man's Tlco was measured and a smoking history and detailed occupa tional history obtained. The distribution of standardised TlCO results from all persons examined was symmetrical and did not indicate an unexpectedly high proportion of men with clinically important impairment of TlCO. The results of a case-control study showed that, having allowed for age, height, weight, and smoking habit, Tlco was associated with a history of working in the PVC factory before 1975 (when levels of vinylchloride monomers (VCM) were much higher than subsequently), and slightly associated with working in jobs where exposure to VCM was likely to have been highest. The men with low Tlco also tended to have smoked more heavily than controls. The relative importance of occupational factors and smoking in relation to low Tlco is not clear, but the results give some support to the hypothesis that work in the PVC factory before 1975 entailed exposure to a substance that caused impairment of lung function in a small number of men. The management and occupational physician of a factory making polyvinylchloride (PVC) had become concerned over an apparent excess in their workforce of men with impairment of the single breath transfer factor for carbon monoxide (Tlco). The present study was planned to determine whether there was such an excess of men with low values of TlCO in the workforce, and to make a preliminary assessment of whether low TlCO might be related to occupational factors. The factory had been in operation since 1969 and produced PVC powder from vinylchloride monomer gas (VCM). All men who had worked at the factory, whether or not they were currently employed there, were invited to participate in the study. A sample of men working in a nearby foundry were also invited to participate; they had been exposed to the same environmental conditions outside the workplace and were included in order to augment the number of men in the study who had not been exposed to poss ible hazards in the PVC factory. Received 28 February 1983 Accepted 9 May 1983 Methods SELECTION OF SURVEY POPULATION All 177 men currently employed at the PVC factory were invited to take part and attempts were made to trace and invite all the 263 former employees. At the foundry, the study was confined to 285 men selected randomly from the 1085 current male em ployees. The number of men at the foundry aged under 25 was limited to 15 to take account of a disproportionately large number of young men in the foundry population compared with the PVC workers and to provide a group of similar size to the 13 PVC workers of this age. Apart from this, selec tion did not take account of age. MEDICAL SURVEY The medical survey team visited the factories and recorded a full occupational history since leaving school for each man. Trained personnel using a questionnaire which was a modified version of the Medical Research Council questionnaire of respiratory symptoms' recorded details of each man's smoking history. Additional questions were related to age of starting smoking and the number of 328 s and aving ing a :>f the e of each were berof Epidemiological study of the lung function of workers at a factory manufacturing polyvinylchloride 329 cigarettes smoked during a man's maximum smok ing period. Measurements of single breath gas transfer factor for carbon monoxide were carried out on all men using the breathholding method2 based on the mod ified Krogh technique (transfer test B;PK Morgan Ltd, Chatham, Kent). The mean of two measure ments was used in the subsequent analysis. All PVC factory employees had forced expiratory volume in one second (FEV,) and forced vital capacity (FVC) measured using an electronic dry rolling seal spirometer (Ohio 800). The best of three technically satisfactory measurements was used for the analysis. Approval was not obtained for FEV, and FVC measurements in the foundry workers. METHODS OF ANALYSIS Analysis of data from the total survey population The data were studied initially by summary descrip tive statistics and by multiple linear regression analysis of lung function taking into account age, height, weight, and smoking habit. Men were assigned to one of three smoking categories; lifelong non-smoker, current smoker, and ex-smoker. The two smoking groups included smokers of pipes, cigars, and hand-rolled cigarettes but the majority smoked manufactured cigarettes. In the regression model used for both Ti_,co and FEV, different intercepts and age slopes were flowed for the three smoking groups, non-smokers, irrent smokers, and ex-smokers. This means that ihe estimated effects of age were not constrained to be the same necessarily in the three smoking habit groups. The relation between a man's observed and pre dicted lung function values was expressed as a stan dardised residual (SR). This is defined by the equa tion: (observed value--value predicted from fitted equation) (estimated standard deviation of the prediction) distribution of FEV, and Tlco SR values of the whole population was examined. Case-control study For each lung function variable, those men with the largest negative SR value were chosen as cases. Two groups of controls were selected randomly, firstly, from those men whose SRs were clustered around zero ("average" controls) and, secondly, from those with largest positive SRs ("healthiest" controls). ' groups were chosen because men with average cs may have included some whose lung function had been slightly affected by noxious influences, whereas those with very high values were least likely to have been affected by noxious influences but Table 1 Classification ofalt jobs ai PVC factory into six broad occupational groups. Broad occupational group Jobs included in group 1 All men working in reactors 1 and 2* 2 Dryer room B opcralorst 3 Dryer room Lead. A and A/B operators 4 Warehousemen, maintenance staff, laboratory staff, and drivers! 5 General staff who visit plant, such as shift supervisors and foremen 6 Management and office staff 'Men most likely to have been exposed to high concentrations of VCM in the past. tMen engaged in the bagging of PVC and probably exposed to higher concentrations of oust than other workers in the dryer buildings. tMen potentially exposed to all raw materials and products. might include men who were highly resistant to these influences. Cases were initially compared with the rest of the survey population in order to identify any systematic differences in age, smoking habit, and employment status. Then the occupational and smoking histories of cases and controls were examined and compared. Smoking histories were classified as they were for the total population, but additional information about the number of cigarettes smoked and the age of starting smoking was analysed in the case-control study. Broad occupational categories were defined for the PVC factory (table 1) and for the foundry, and the total number of years spent by cases and controls in each occupational category was calcu lated. Additional information was available for PVC employees in relation to exposure to emulsion polymer (which has a smaller particle size than sus pension polymer and which was manufactured at the factory between 1971 and 1974) and employment in the factory before 1975 when levels of VCM were much higher than the currently permitted levels.From the full occupational history the number of years spent in potentially "noxious" industries (such as coal, steel, chemicals, and a miscellaneous group of industries in which exposure to noxious com pounds might have occurred) was recorded. In the analysis Fisher's exact test, the chi-squared test for 2 x 2 contingency tables, and the chisquared test for linear trend were used where appropriate. Results A total of 488 men was seen, consisting of 165 cur rent PVC factory employees (93% of those who were asked to participate), 102 PVC former em ployees (39% of those invited), and 221 foundry employees (78% of those invited). Four men (two PVC and two foundry) were excluded from the BFG05048 330 so AS -3-2-10 1 2 3 SR wlue Fig 1 Number ofmen by ranges ofT^co standardised residuals. Tlco analysis because of incomplete data, and to the final analysis was based on 484 men. As FEV, and FVC measurements were not obtained from three PVC factory workers and all 221 foundrymen this analysis was based on 264 men. The distributions of standardised residual values of T^co and FEV, for the total survey population after allowing for age, height, weight, and smoking habit were fairly symmetrical and conformed approximately to Normal distributions (figs 1 and 2), although for FEV, there were slightly more extreme negative values than extreme positive val ues. SELECTION OF CASES AND CONTROLS A threshold SR value for Tlco of -- 1*5 supplied 31 men, a number that was considered large enough to form a study group. A control group of 31 men was selected randomly from those men with SR values between -0-25 and +075 inclusive (Tlco average controls). A second control group of 31 "extra heal thy" men was selected randomly from those with SR values in excess of +0*75 (Tlco healthiest con- Lloyd, Gauld, Copland, Soutar Table 2 Features ofTj^co cases, controls, and total survey population. Mean (and standard deviations) ofage, height, weight and T^co No of men TLCO groups Total Cases <3/) Controls Controls population (average) (healthiest) (494) (30 (30 Age (y): Mean (SD) Height (cm): Mean (SD) Weight (kg); Mean (SD) T.CO (mVrnir mm He); Mean (SD) 41-8 (10-2) 176-1 (7-1) 82-7 (13-3) 22-2 (4-1) 42-3 (125) 174-0 (6-6) 84-9 (18-5) 318 (2-9) 40.3 (11-3) 173-9 (5-6) 79-2 (9-5) 37-3 (4-3) 42-2 (11-9) 373.8 (7-0) 80-2 (12-6) 30-5 (5-9) trols). Similarly, 30 men with an FEV, SR value of less than --1*1 were selected as FEV, cases and two groups of controls (FEV, average controls and FEV, healthiest controls) were chosen from those men with SR value between -0-25 and +0-75 and in excess of +0*75 respectively. CLINICAL FEATURES OF CASES, CONTROLS, AND THE TOTAL POPULATION The general features of Tlco and FEV, cases, con trols, and the total population are shown in tables 2 and 3. The mean age of the Tlco case and control groups were similar. Observed Tlco and FEV, values of the cases were also expressed as a percentage of values pre dicted on the basis of Cotes' regression equation.7 Fifteen of the 31 Tlco cases had Tlco values below 70% of their predicted values; four were below 60%. Twelve of these 15 men were PVC workers and three were foundrymen. Nineteen of the 31 cases were from the PVC factory and four of these had evidence of airflow obstruction (FEV, < 80% and FEV/FVC < 70%); examination of forced expiratory flow-volume loops suggested that a further seven might have mild airflow obstruction. In the remaining eight the low Tlco appeared to be an isolated abnormality. Of the 30 FEV, cases, 13 had observed FEV, values below 80% of their predicted values and 10 of these men had FEV/FVC ratios below 70% sug gesting airflow obstruction. Seven of the FEV, cases also qualified for inclusion as Tlco cases. Fig 2 Number ofmen by ranges ofFEV, standardised residuals. OCCUPATIONAL HISTORIES Analysis of employment status showed that 19 of the Tlco cases worked or had worked at the PVC factory and 12 were foundrymen, but this difference could easily have arisen by chance. Most workers tutor trvey 'ighl. y lotion i 2 9) 8 0> 2 6) 5 9) ilue of id two i FEV, s men and in .AND s, conables 2 control e cases es nrej .J JS ir were -e PVC teen of four of tion of ted that ruction. edtobe d FEV, ; and 10 0% sug- at 19 of the PVC ifference workers Epidemiological study of the lung function of workers at a factory manufacturing polyvinylchloride 331 Table 3 Features ofFEV t cases, controls, and total survey population. Mean (and standard deviations) ofage, height, weight, T^CO, FEV, and FVC Table 5 Smoking habits ofT^co cases, controls, and total survey population. Number ofmen in each smoking category with percentages in parentheses No of men Cases (JO) TLCO groups Controls Controls (average) (healthiest) (JO) (30) Total survey population (264) Age (y): Mean (SD) Height (an): Mean (SD) Weight (kg): Mean (SD) FEV, (1): Mean (SD) FVC(I): Mean (SD) TiCO (rm/min mm Hg): Mean (SD) 43-3 (110) 176-0 (7-4) 82-2 (U-3) 2-7 (0-7) 4T (0-9) 29-1* (6-8)` 41-3 (12-5) 174-5 (6-6) 78-4 (10*1) 3-9 (0-7) 5-1 (0-8) 32-3 (6-0) `Value based on 29 observations. tValue based on 262 observations. 42-1 (120) 175-9 (8-0) 80 4 (11-5) 4-5 (0-8) 5-9 (0-9) 31-3 (6-5) 42-2 (11-8) 174-3 (7-1) 80-4 (12-3) 3-7 (0-9) 4-9 (1-0) 30-5t (6-l)t had worked in more than one type of job and in more than one broad occupational category during their employment with the companies. More cases than controls had worked in jobs in category 1 (on or near the reactors) at the PVC factory; 11 of 31 cases (35%) had worked in this category compared with 10 of 62 controls (16%) and this disproportion is significant at the 7% level (table 4). No suggestive differences were seen in the pattern of employment . of FEV, cases and controls. More cases than controls had worked at the PVC Cases Controls (average) Controls (healthiest) Total survey population Nonsmoker 3 (9-7) 4(12-9) 7 (22-6) 109(22-5) Current smoker 20 (64-5) 15 (48-4) 15 (48-4) 234 (48-4) Ex-smoker Total 8 (25-8) 12(38-7) 9 (29-0) 141 (29-1) 31 31 31 484 factory before 1 January 1975, when levels of vinylchloride were much higher than at present. Seven teen of the 19 TlCO cases who had worked at the PVC factory had been employed before 1975 whereas only five of the 15 healthiest controls and 11 of the 13 average controls had been. The differ ence between cases and healthiest controls was significant (p < 0*002), and the increase in the proportion of men with pre-1975 employment in the PVC factory for the three groups over healthiest controls, average controls, and cases was also statis tically significant (p < 0*001). Analysis of the dura tion of employment of men within different age groups showed that pre-1975 working was seen in both younger and older men. A similar analysis of FEV, cases and controls and foundry TlCO cases failed to show any significant differences in relation to working before 1975. These findings suggest that some factor or factors associated with working at the PVC factory before 1975 had caused impairment of TlCO in some men. There was no difference in the numbers of TlCO or FEV, cases and controls who had been exposed Table 4 Numbers ofmen who had spent some time in each occupational group. (Mean time (years) spent in each occupational group) No of Occupational groups / 2 3 4 5 6 78 9 10 11 12 13 Cases: PVC workers Foundrymen 19 12 11 11 4 4 2 _ (2-7) (0-6) (7-6) (90) (9-7) 1 (7-0) 4 (7-3) _ 2 (30) _5 (5-6) 5 7. (12*3) (4-0) _ 2 (3-2) j_ (1-4) 21 (U-4) (10) Average controls: PVC workers Foundrymen 13 18 4 71 5 1 (7-0) (0-7) (6-8) (6-0) U2-3) 35 1 9 1 5 1 (4-6) (16-1) (30-4) (9-4) (7-4) (10-6) (2-5) Healthiest controls: PVC workers Foundrymen IS 16 6 (3-0) 11 (1*0) 12 (10-R) (7-3) 2 (3-3) 1 (1-7) '-- -- 53 (13-4) (4-5) -- 3 (12-7) 2 (4-0) 6 (12*5) 1 (0-5) -- ---- 6-- <11*6) -- Note: Occupational groups 1-6 refer to PVC factory (see table 1) and 7-13 jobs at the foundry--that is. 7 work on or near the furnaces: 8 sand work and shot-blasting: 9 grinding and welding; 10 general jobs; 11 painting and dipping; 12 casting work; 13 fettling. 332 Lloyd, Gauld, Copland, Soutar PVC factory ^ Foundry 11 XI 10 20 30 40 >50 Coses No of cigarettes Fig 3 Number ofcigarettes smoked a day at weekends among current smoking Tjjco cases and healthiest controls. K616ff BB2Q>?1 Agefy) 0 WB <ti 5E 17 8 820>71 Age(y) Avenge controls Fig 4 (a) Age at start ofcigarette smoking among TjjCO cases and healthiest controls who were current smokers. (b) Age at start ofcigarette smoking among T^CO cases and average controls who were current smokers. to emulsion polymer at the PVC factory. No evidence was obtained that the observed dif ference between cases and controls could be explained on the basis of previous employment in industries other than the PVC factory or foundry. SMOKING HABITS OF CASES AND CONTROLS Whereas the procedure for selection of cases and controls had taken account of whether a man smoked, it was found that the T^co cases had tended to smoke more than controls. A slightly higher proportion of Tlco cases (65%) were cur rent cigarette smokers than either group of controls (on average 48%) (table 5), and more of these cases smoked 25 cigarettes or more at the weekend than the healthiest controls (fig 3). Weekday smoking fol lowed a similar but statistically insignificant pattern. The Tlco cases tended to have started smoking at an earlier age than controls (fig 4). Discussion Whereas exposure to PVC dust has been shown to be related to a mild reduction of lung function and chest x ray abnormalities,*5 less is known about the pulmonary effects of exposure to VCM. There have been some case reports of men exposed to VCM who had impairment of lung function, particularly Tlco,*' and changes in lung histology have been reported.6* The present study was designed as a preliminary examination of whether an undue number of men at this PVC factory had impaired Tlco, and whether such impairment was likely to be related to their occupation. We have found no evidence of a sub stantial excess of men with impairment of the Tlco, although low TlCO values were found in a few men, as might be expected in any large population of workers. After allowing for other factors,.however, those men with the lowest Tlco tended to have worked more often than would be expected at the PVC factory before 1975, a date before which con centrations of VCM were known to have been much higher than subsequently; these men also tended slightly to have worked in the jobs where the highest concentrations of VCM were found. This evidence gives some support to the hypothesis that work in the PVC factory entailed exposure to one or more substances that caused impairment of lung function in a small number of men. The most likely substance is VCM, on which suspicion has previously been cast by case reports of vinylchloride workers with impairment of gas trans fer factor, but in which proof of association has been lacking.67 It is also possible that exposure to respir able PVC dust may have contributed to the low gas transfer factors although there was little positive evidence for this in our study. PVC dust has been shown in other studies to be associated with impair ment of other aspects of lung function (though not the gas transfer factor) and slight chest x ray abnor malities.4 s There was little evidence to support, as an alterna tive hypothesis, the suggestion that the workforce recruited in the early years of production included an excess of men with poor respiratory health at the time of entry to the factory. The FEV,, a more sensi tive indication of the common types of chronic respiratory illness, was not found to be particularly adversely affected in men working in the factory before 1975. The selection of cases took into account whether a man smoked, but even after allowing for this, the cases with low TlCO tended to have smoked slightly more than the controls, and notably the age at which a man started to smoke appeared to be related to low Tlco. The relative contributions towards impairment of Tlco of smoking and of occupational factors are not dear from this study, but it is possible 725005 BFG05051 'ur nd .M ;r|y :en ary i at rter leir ,ubco, en, of Ver, ave (he onuch (led hest the .iled jsed r of hich is of ans->een spir- gas litive `-een irnot nor- :ma[force [uded it the tensiIronic iilariy ctory her a s, the ightly which ,ed to wards tional ssible (Epidemiological study of (he lung function of workers ai a factory manufacturing polyvinylchloride 333 that both were important. The men with the lowest TlCO values selected as cases were not all necessar ily suffering from lung disease but among them were 15 men whose Tlco was less than 70% of the value predicted by published normal values, a level which probably indicates the presence of disease. In eight of the 19 cases who had worked at the PVC factory the low Tlco was an isolated abnormality, a pattern unlikely to be the result of damage from smoking and which is usually associated with interstitial lung disease or disturbance of pulmonary perfusion. Reports of both animal and clinical studies give further support to the suggestion that exposure to VCM might have been an important causative factor. Animal studies have shown that exposure to high levels of VCM leads to pulmonary fibrosis, the changes being most severe in the animals which had been exposed for the longest time.* There have been isolated case reports of individuals with interstitial lung disease who had been employed in the man ufacture of PVC and who had, therefore, been exposed to VCM.*10 Hunter e/d/ described six such workers, three of whom had died from liver disease related to VCM exposure"; none of the six had respiratory symptoms, three had abnormal chest x ray films, and one an abnormal Tlco, but the lung histology from all six men showed a similar picture with , the presence of an inflammatory interstitial infiltrate. Diligent attempts were made to contact all men who had worked at the PVC factory but response .`.as low (39%). If the men not examined had included either an excess or deficiency of men with impaired gas transfer factor compared with the population examined then the analysis of the dis tribution of values among the population seen would be unrepresentative to that extent. We conclude that this preliminary study has shown no evidence that current working conditions in either factory have caused impairment of lung function but it does give some support to the hypothesis that work in the PVC factory before 1975 entailed exposure to a substance that caused impairment of lung function in a small number of men. Further work including clinical studies of affected men would be necessary to characterise this impairment and to explore more fully the relations with occupational and other factors. This study was carried out with the full cooperation of the management and workforce of Vinatex Limited to whom we are grateful for financial sup port. We thank the management and employees of the foundry for their generous cooperation in the study and the medical officers at Vinatex and British Steel for their help. We also thank. Dr A Seaton and Dr M Jacobson for their advice. Further details of the results of the work are recorded in Institute of Occupational Medicine report TM/82/4. References 1 Medical Research Council working party on research into chronic bronchitis. Report. London: Medical Research Coun cil. 1976. ' Meade F, Saunders MJ, Hyett F, Reynolds M, Pearl N, Cotes JE. Automatic measurement of lung function. Lancer l965;ii:573-5. 1 Cotes JE. Lung fimotion. Oxford: Blackwell Scientific Publica tions, 1979:369-85. * Soutar CA, Copland LH, Thoraley PE, era/. Epidemiological study of respiratory disease in workers exposed to polyvinyl chloride dust. Thorax 1980;35:644-52. 9 Maslrangelo G. Mantto M, M&icer G, if of. Polyvinyl chloride pneumoconiosis: epidemiological study of exposed workers. JOM 1979.21:540-2. * Darke CS. Vinyl chloride and the production of PVC Proceed ings ofthe Royal Society of Medicine 1976. ' Lange C. lube S, Stein G, Veltman G. Die sogenannie Vinykhlorid-Krankheit cine benifsbedingte Systemsklerose? international Archiv Arbeitzmtdilin 1974;32:1-32. ' Hunter AM, Wagner JC, Johnston N, Seaton A. Lung fibrosis in polyvinylchloride workers. Thorax 1981;36:711-2. * Prodan L. Sudu I, pislaru V, Uea E, Pasou L. Experimental chronic poisoning with vinyl chloride (monochloroethane). Ann NY Acad Sd 1975:246:159-63. * Amaud A. Pommier de Sand P, Garbe L, payan H, Qtarpin J. Polyvinyl chloride pneumoconiosis. Thorax 1978;33:19-25. 20725006 BFG05052 T