Document 29D5RGgNxMrNDrB6nOgoKmjg

British Journal of Industrial Medicine 1988;45:93-97 <*r Increasing evidence of the rise of cancer in workers exposed to vinylchloride V B SMULEVJCH.1 I V FEDOTOVA.1 V S FILATOVA2 From tlw All-Union Cancer Research Centre.1 AMS USSR. Moscrne. and Institute of Occupational Medicine,1 Carkv. USSR s abstract The results of a cancer mortality study among workers employed in the production of vinylchloride and polyvinylchloride between 1939 and 19/7 suggest a significant increase in deaths from malignancies of the lymphatic and huemopoietic tissues. Mortality for tumours of the digestive Clf organs, respiratory system, bone and connective tissues, brain, and skin arc also greater than in the general population. There were no registered cases of liver angiosarcoma in the study cohort during the follow up period. The risk of cancer was highest among the workers exposed to concentrations of VC of 300 mg/m3 and more who had worked at the plant for 15 to 19 years. The relatively high number of leukaemias and lymphomas in the study group and the absence of liver angiosarcomas probably reflects specific carcinogenic action of different doses of vinylchloride. The carcinogenicity of vinylchloride (VC) has been studied only recently although this compound was synthesised almost 150 years ago1 and its industrial production in many countries started in the late 1930s. The first clinical and hygiene study of the oc cupational setting and health of workers in plants producing VC and polyvinylchloride (PVC) was un dertaken in the USSR in the early 1950s. This study showed heavy air pollution with VC in the shops or the plant, reaching levels of l00-800mg/m3.3 This ex posure resulted in a high frequency of occupational toxic angioneuroscs in the workers3 and led to ihc legislative limitation in (he USSR (1957) of the VC level in the working zone to a maximum permissible concentration (MPC) of 30mg/m3. VC and PVC induced diseases in the workers pro ducing these agents were described later by several foreign authors3"'' Officially established MPCs of VC in the working zone in several countries before 1974 were as follows: United States--770 mg/m3: Italy. France. Finland, and Yugoslavia--1300: East Germany--500: West Germany--260: and Rumania-- 100." In 1970 Viola published the results of his animal experiments that were aimed at reproducing the aeroostcolvsis observed in PVC workers. The animals de veloped tumours of the lung and skin and led the author to conclude that VC was carcinogenic.1' Many Accented 20 Ociulicr IVXA other workers have confirmed that VC is carcinogenic to animals.* '* In 1974 the first reports on cases of liver angiosarcoma among workers occupationally exposed to VC appeared. The frequency of this dis ease in the exposed groups was 300 to 600 times higher than in the general population.13 " The study presented here was aimed at evaluating ihc prevalence of malignant disease among workers employed between 1939 and 1977 in several Soviet enterprises producing VC and PVC. Materials and methods The base of, the study was one of the oldest Soviet chemical plants where VC and PVC have been pro duced lor various periods and under different tech nological patterns. The data on the specified workers were obtained from the registers of the administrative department and from attendance journals and lists of particular shops. For every member of the study cohort the fol lowing data were collected: specified occupation, du ration c.f employment in a VC exposed job. data and cause of death, and results of any postmortem study. The documents analysed were the death certificate, medical histories of disease, and necropsy protocols of those who had died from cancer. The cohort included all employees who had worked in a VC exposed job for al least one month as well as those who had changed their place of employment, were retired, left through ill health, or were dead. 93 NOTICE: THIS MATERIAL MAY BE PROTECTED BY COPYRIGHT LAW (TITLE 17 U.S. CODE) // BFG18645 94 Smulevich. Fedotova. Filatova Thus the study cohort consisted of 3232 workers Results (2195 men, 1037 women). The death rates in the cohort were determined by considering both the number of observed subjects jnd the period of observation.11 The numbers of person- Between 1939 and 1977 288 deaths were registered in the cohort, including 63 from cancer. Histological confirmation of the diagnosis of cancer was available years of observation for the entire cohort was 43216 for 60% of the cases. (27059 for men, 16 157 for women). As shown by the SMRs, the workers in VC-PVC The expected numbers of cases of cancer for the plants have an increased cancer mortality by com cohort were based on the mean death rates in the city parison with the general population of the city (table where the plant is located for the years 1959. 1969, I). This was particularly noticeable for lung tumours, and 1975 in the age group 15-74. The extent of risk pancreas, bones and connective tissue, skin, and was evaluated by means of standardised mortality ra brain! The observed mortality from leukaemias and tios (SMRs). The significance of the difference be lymphomas is significantly higher than expected. No tween the rates on the p level <0-05 was determined cases of angiosarcoma or other liver tumour were by the confidence limits of the variation of cancer fre noted. quency." For the male workers exposed to VC. the total can The results of the hygiene study of the occupational cer mortality was somewhat lower than in the male environment in VC production for the period population of the city. The numbers of cases of pan 1953-66 were treated by methods of variational sta creatic cancer, lung cancer, tumours of the bones and tistics with identification of average VC concen genitalia, and leukaemias, however, were higher than trations for particular workplaces." expected but not significantly so. The extent of VC influence on the workers resulting The cancer mortality for the female workers was from the average VC doses that they had been ex greater than expected due to malignancies of the posed to while working was estimated within the fol stomach, rectum, skin, brain, and lymphatic and hae lowing gradation: matopoietic tissues. The excess for leukaemias and high level--mean concentrations of VC lymphomas was statistically significant. >300 mg/m1; As was clear from the analysis of working moderate level--VC concentrations 30-300 mg/mJ; conditions at the plant there were three categories low level--concentrations <30 mg/m1. of workers based on the intensity of exposure to For the quantitative estimation of the 'sharc"'0f~ ` VC-PVC.' The first group (highest exposure) consists VC and PVC in the total process of cancer devel of the workers of the major occupations (apparatus opment in the workers of this industry the technique operators, fitters) employed in producing VC of factorial dispersion analysis10 was used. by dehydrochiorination of dichlorethane in the Tabic 1 Observed number ofdeaths from cancer (Ohsi and SMRs ofcancer in the cohort of VC and PVC workers Men Women Both sexes Sues 1CDS.IV65 Ohs Ail malignancies Oral cavity and pharynx Digestive organs: Oe*ophagu* Stomach Rectum Pancreas Liver Respiratory organs: Larynx Trachea, bronchus, lung Bones and connective tissue Skin Breast Reproductive organs Urinary organs Brain and nervous system Leukaemia, aieukacmia Other malignancies of lymphatic and haematopoietic uisuc 'Significant ai p < 0*05. 14(4209 Ul|49 150-159 150 151 154 15? 1W4I63 161 162 170-171 172-175 174 IKO-1K7 IKK-1X9 191-192 214-207 44 0 17 0 14 0 y 0 IK 1 17 1 0 0 l 1 y 201420.1.20X. 209 i SIUK 9*2 ... 74-K _ K3 3 _172! 141-7 1000 145-5 _166-7 _ 125-0 3K 5 90-9 42K *6 100-0 Ohs SMR 19 IJJ-S 0_ X 121-2 0 __ 7 142-9 l 125-0 0-- 0 0-- 0 ___ 0-- 0 __ 1 1000-0 0_ 71-4 0-- 2 500*0 666-7 4 2000-0* Ohs SMR 63 106-6 0-- 25 H5 0 0 *. -- 21 K4-7 1 500 3 142-9 0-- IK 134-3 l 83-3 17 1393 1 142-9 1 200-0 0-- 3 83-3 1 34 5 4 1538 5 500-0* 5 416-7* fncreasii Tabic 2 Use! of expaxur High Moderate Low 'Sigmiieai medium the susp beginnir certain realised, The s sented h PVC wi employe paratus where P The t! ployees ployed assistan wi'h VC 'I abic 3 exposure VC tevet High Moderate Low O *$ignmc; N Increasing evidence of the rise of cancer in workers exposed to vinylchloride 95 in cal Level ofexposure to IT Sites blc Atm Ohs SMR ' Wuttten Otu SMR Hath sexes Obi SMR High All sites: 28 101-4 12 444*4* 40 132-0 VC Stomach Lung 8 79-: 13 mi 5 3*46* 13 0-- 13 114-0 168-8 ru Lymphomas, leukaemias 8 300-0 4 4000-0* 7 636-4* ble r$, Moderate All sites: Stomach nd Lun| 15 107 I 5 122-0 4 129-0 5 113-6 20 1087 2 133-3 7 128 8 0 4 125-0 nd Lymphomas, leukaemias l 166-7 1 142-9 2 153 8 Vo Low All sues: 1 31-3 2 2S-2 3 29-1* 2re Stomach Lung 1 13 3 0 ___ 0-- 0-- 1 27-0 0-- Lymphomas, leukaemias 0 -- 1 333-3 1 200*0 m- aic "Significant at p < 0*05. ;n- nd an medium of methyl alcohol and in producing PVC in The first and second occupational groups had a the suspension who worked in these shops from the increased SMR for all cancers (table 2). More men in as he beginning of their employment up to 1959 (when certain improvements in working conditions were realised). these groups died than in the general male population from cancer of the stomach and lung and from leukaemias. It is of interest that only in the high and le nd The second group (moderate exposure) is repre moderate exposure groups of male workers were sented by the workers in the new shops producing cases of lung cancer noted. This supposes some effect ng cs PVC with modern technology and those who were of smoking, an essential factor in the development of employed before 1971 in drying departments and ap lung cancer21 ~21 that might enhance the carcinogenic to paratus operators in the polymerisation departments influence of VC. where PVC was produced with imported technology. Among the female workers exposed to the highest SIS The third group (low exposure) is composed of em doses of VC, the SMRs are high and significant for US C ployees of the new shops, the drying workers em malignancies of the stomach, and for leukaemias and ployed between 1971 and 1977 and laboratory lymphomas. assistants and other workers having minor contact The workers in the lowest exposure group also had with VC. the lowest SMRs. Table 3 Observed deaths from cancer (Ohs) and SMRs in various subgroups ofworkers by duration ofemployment and exposure to I 'C I'C level Duration o! employment 1 \emrx) High 0-4 5-9 10-14 15-19 >20 Moderate 0-4 5-9 10-14 15-19 >20 Lnu 0-4 5-9 10-14 15-19 >20 'Significant at p < 0 05. Aten Ohs 18 5 > 2 i n 3 0 1 0 1 0 0 0 0 SMR 113-2 104 2 90-9 181*8 66-7 til l 130-4 166-7 -- _47-6 _ - Women Ohs 1 5 I 4 l 1 1 2 0 l 0 0 0 2 0 SMR 68-3 714-3" 333-3* 1333-3* 500-0 47-6 76-9 _105-3 142-9 _ -- _ 2*5-7 -- Both sexes Otu SMR 19 108-1 10 181-8 3 120-0 6 428*6" 2 117-6 12 100-0 4 IIH 2 58-8 1 71-4 l 909 } 25-6 0-- 0-- 2 250-0 0 "** rv  few TW .dMTf.k 96 Thus there is a clear relation between cancer mor tality and the level of VC exposure in the :.tudy co hort* the workers subjected to doses higher than 30 mg/m1 have a higher risk of cancer than those with minimal contact with this compound. Tabic J presents the distribution of deaths from cancer in the groups with different periods of employment. The highest SMR is in the group having worked at the plant for 15-19 years. The treatment of the results by factorial dispersion technique for estimating the share of influence of VC (in dependence of level and duration of its action) on the risk of cancer have confirmed its significant role (5*8*/, p < 0*001) in the development of tumours among the exposed workers. Discussion Our study has shown an increased cancer mortality in the workers employed in the production of VC and PVC. compared with the general population. An in creased frequency in malignancies of the digestive or gans. respiratory tract, brain, and lymphatic and haematopoietic tissues observed in this study is in ac cord with the results of similar studies of workers in VC-PVC plants in the United Kingdom, W Germany. France. United States, and other countries. In our study no angiosarcomas were noted: these tumours are considered by some authors to be a specific occupational disease of VC workers.2110 The reason for this lack of angiosarcomas may be due to the measures for limiting airborne levels at work which were introduced earlier than in other countries and to effective protection (by relevant individual de vices) of workers in high exposure jobs. On the other hand, "it may reflect a certain specificity of action on the organism of various VC concentrations; higher doses lead to the development of liver angiosarcomas whereas moderate ones may aflccl other organs. This idea is to some extent confirmed by animal experiments'** with different doses of VC (3690. 266. 25. and 14 mg/m') where the lowering of adminis tered VC doses was accompanied hy a changc.in the ratio of liver malignancies, lymphomas and leu kaemias towards the production of the latter. The finding of sigmlicnnl increase.' in SMR.\ for lymphomas and leukaemias, especially among remale workers who usually have lower occupational ex posures to VC than male workers is noteworthy. This probably reflects a higher susceptibility of the women to the carcinogenic action of VC but this hypothesis needs further study. The relation between the carcinogenic action of VC and the level of exposure agrees with experimental evidence on this subject.11 This gives hope that cur rent measures for limiting VC exposure at work (low- Smulevich. Fedotova, Filatova ering of the MAC in the USSR to 01 mg/nr', promotion of the hcrmitic sealing of the equipment used, and development of the non-stop technologies of VC production) will effectively serve to prevent the carcinogenic effects of VC on workers. Relmnets 1 Rcgnault V. Comptwilion of a chlorinated hydrocarbon (oil from Miiwmotg gases} Ju\ln.\ l.n hif: Atuuiles ('heniiMry 1835;14:22-38. 2 Filatovs VS. Groiwberg ES. Sanitary and hygienic labour condi tion* in production of polychlorvinyl tar and measures of their improvement. 0igijem < uomttri/o |957;NI;JK-42.* 3 Smirnova NA. Clinical feature* of the professional toxic angt> neuroses. In: Maternity po rttprosam Rigieny truda i eiiniky pr*frnmmatigrh holezmy Corky 1956:44-52 * 4 Sucui i. Driman J. Vaiaskui M. Comrthutii la sludiue imbalnavihtor produce de chiorure de vmil. Med Intern 1963. 15*67-78. 5 Wilson RH. McCormick WE. Tatum CP. etai. Occupation.il acroocteofyiis. JAMA 1967;201:577-81. 6 Juhe H. Lange CE. Sclerodermianigc Hautferandeeungem Rejnsud-Syndrom und Acrootteolison bei PVC-WerstcIlendcn Indaaire. Disrh MetI Woehiuchr 1973:97:1922-3. 7 Nikitin VS. Rjabets VA. MPC of the noxious substances in the workshops air in the USSR and abroad. In: Nttuchrtw Rabo:y hulitmmnhronv irtnki V.ie.iatuznofn Cenirulnogn Soma Profe sumatigch Soju:or Musetm 1973:54:22-9.* 8 Viola PL. Carcinogenic effect of vmylchloridc. In: 7Vw//i Intermomma/ Ctmrvr Congress. Ihtuxltut. 1970. Vol 29. Houston: Medical An Publishing Co. 1970. 9 Maliom t\ Lcfeminc G. Vinyl chloride carcinogenesis current fowiu and perspective. Met! Lor 1974:6$: 11-12. 10 Caputo A. Viola PL. Bigotti A. Oncogenic response of rat skit:. lungs and hones to vinyl chloride. Conrer Res I971jl:5lfv22. 11 Lee CC. Blandart CC. Winston JM. etal. Inhalation toxicity of vinyl chloride and vmylidene chloride. Environ Health Perspet t 1977:21:25-35. 12 Matiom C. Lcfeminc G. Ciliherty A. etal. Carcinogenicity bio* assays oTVCM: a model of mk assessment on an experimental Hums. Kmetrtm Ileallit Perxfnft 1981:41:3-29 13 Stovhor NN. Kurliaodxky HA. Tunmtv VS. Toward*, (he ratlin natc of the permissible vmykrhlondc content* in the working rone air. In: Tetisv doklotlor 6 \seuijuzhoi ntnlcrrticti Lenin grad: 1979:288.* M Kurfaandsky BA. Stovhur NN. Turusov VS. Towards the ques tion of hygienic reglameniation of vinyl chloride. Cigteno t Son oorim 1981 J:74-K6* 15 Creech JL. Johnson ML. Angiosarcoma of the liver in the manu facture id PVC*. J Ot ntp Med 1976:16:1 SO- I. 16 ImcmaiKma! Agency for Research on Cancer: It Virkwij* group on nnvl thittettie. Lyon: IARC. 1974. (Im tech report N74/1KI5.) 17 MacMahon B. Pugh T. Ipsen J. '/he uxe of epulrtnuthtgiv metiuuh in ihr xtmlies of mminlevlnms tiiwtixcs Moscow Mcdti/iiu. J9M. (Jiamkmai iiiio Kuvunn.j IK Dvoinn VV. Analytical method* of the study in cancer epi demiology research. In: Chaklm AV, cd. Ctmtrr epidemiology mCMEA romonrs. Moscow; McUil/ina. !979. 19 Merkov AM. Poliakov l.li. Sonuory moii.mms. Leningrad: Meditnna. 1974.* 20 Plohmsky NA. Bkoneirv. Moscow: Moscow Slate University. 1970.* 21 Scrchrov Al. Tobacco smoking and lung cancer. Sor Med 1978:7:109-12.* 22 Chaktin AV. Grtuutc LA. Modern concept* about aetiology ami pathogenesis of lung cancer. I 'opr Onkol 19823:3-9.* In Russian. *1 In 23 24 trti(J6 02Z BFG18648 Increasing evidence of the rise of cancer in workers exposed to vi.:vlcMoride 23 DollR.PetoR The cause* of cancer .Oxford. New Vork: Oxford 21 M.*>on RR. Petcn JN. Johnson MN. Proportional mortality Univcrxiiv l*rcv*. I VS I iirong VC workers. Laurel !974:ii:397-8. 24 HnJlUr J'-V W,m| S. Iillti <\ *tul M.uulils expem-mv ol lIw 2S Oil M(. l-imgiwr KK. llokWr Mil. Vinyl chlonik exposure in a cs worker*. in a Vt'M production pUtii. J (/*rup Mc*t controlled industnal environment. A long-term mortality ex he I97V.2MVV20.V perience in 594 employees. Arth Environ Health 1975:30:333-9. 25 Bvrcn D. Engholm C. England A. etui. Mortality and cancer 29 War*eiller RJ. Stringer W. Jones J. el ai. Neoplastic risk among morbidity in a group of Swedish VCM and PVC production workers exposed to vinyl chloride. Am NY Acad Sci 1976; workers. Environ Health Pmpect 1976:17:167-70. 271:40--H. 2ft I ox AJ. Collier IM\ l.ow mortaliiy rale* in induMnal cohort Mud- W International Agency for Research on Cancer. Monographs an the ics due to >ciCLiion lor work and survival in the industry Hr J evaiaatom of the rorcint/genic risk of chemicals to humans. Vol ai63. Vancouver style All manuscripts submitted to the Br J Ind Med should conform to the uniform requirements for manuscripts submitted to biomedieal journals (known as the Vancouver style) The Br J Ind Med, together with many other international biomedical journals, has agreed to accept articles prepared in accordance with the Vancouver style. The style (described in full in Br Med J, 24 February 1979. p 532) is intended to standardise requirements for authors. References should he numbered consecutively in the order in which they arc first mentioned in ihc text by Arabic numerals above the line on each occasion the reference is cued (Manson1 confirmed other reports* *5...). 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