Document gDE7Y09v1d3bvbvvdq7X7BeBG

m im Om Tt .*( i British .. .luritul of Industrial Medicine 1988;45:93-97 0y> <*r Increasingw- evidence of the rise of cancer in workers exposed to vinylchloride * V B SMULEVICH,' I V FEDOTOVA,2 V S FILATOVA2 n ir Front the All-Union Cancer Research Centre,1 AMS USSR. Moscow, and Institute of Occupational Medicine} Gorky. USSR >1 ic 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 .1/ from malignancies of the lymphatic and haemopoietic tissues. Mortality for tumours of the digestive of 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 rv the follow up period. The risk of cancer was highest among the workers exposed to concentrations rj of VC of 300mg/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 ago' 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 of the plant, reaching levels of 100-800mg/mThis ex posure resulted in a high frequency of occupational toxic ancioncuroscs in the workers3 and led to the legislative limitation in the USSR (1957) of the VC level in the working zone to a maximum permissible concentration (MPC) of 30mg/mJ. VC and PVC induced diseases in the workers pro ducing these agents were described later by several foreign authors.4'" Officially established MPCs of VC in the working /.one in several countries before 1974 were as follows; United Stales--770 mg/mJ; 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 acrooslcolysis observed in PVC workers. The animals de veloped tumours of the lung and skin and led the author to conclude that VC was carcinogenic." Many Accented 20 October IVXb other workers have confirmed that VC is carcinogenic to animals '" 14 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 limes higher than in the general population.1516 The study presented here was aimed at evaluating the 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 for 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 <.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 histones 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 at 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) l:n&c,o T 94 Smulevich, Fedotova, Filatova Thus the study cohort consisted of 3232 workers (2195 men, 1037 women). The death rates in the cohort were determined by considering both the number of observed subjects and the period of observation.11 The numbers of personyears of observation for the entire cohort was 43 216 (27 059 for men, 16 157 for women). The expected numbers of cases of cancer for the cohort were based on the mean death rates in the city where the plant is located for the years 1959, 1969, and 1975 in the age group 15-74. The extent of risk was evaluated by means of standardised mortality ra tios (SMRs). The significance of the difference be tween the rates on the p level <0-05 was determined by the confidence limits of the variation of cancer fre quency.1* The results of the hygiene study of the occupational environment in VC production for the period 1953-66 were treated by methods of variational r'.alistics with identification of average VC concen trations for particular workplaces.1* The extent of VC influence on the workers resulting from the average VC doses that they had been ex posed to while working was estimated within the fol lowing gradation: high level--mean concentrations of VC > 300 mg/m3; moderate level--VC concentrations 30-300 mg/mJ; low level--concentrations <30 mg/mJ. For the quantitative estimation `of the ''sharc" 3f~ VC and PVC in the total process of cancer devel opment in the workers of this industry the technique of factorial dispersion analysis*0 was used. Results Between 1939 and 1977 288 deaths were registered in the cohort, including 63 from cancer. Histological confirmation of the diagnosis of cancer was available for 60% of the cases. As shown by the SMRs, the workers in VC-PVC plants have an increased cancer mortality by com parison with the general population of the city (table I). This was particularly noticeable for lung tumours, pancreas, bones and connective tissue, skin, and braini The observed mortality from leukaemias and lymphomas is significantly higher than expected. No cases of angiosarcoma or other liver tumour were noted. For the male workers exposed to VC. the total can cer mortality was somewhat lower than in the male population of the city. The numbers of cases of pan creatic cancer, lung cancer, tumours of the bones and genitalia, and leukaemias, however, were higher than expected but not significantly so. The cancer mortality for the female workers was greater than expected due to malignancies of the stomach, rectum, skin, brain, and lymphatic and hae matopoietic tissues. The excess for leukaemias and lymphomas was statistically significant. As was dear from the analysis of working conditions at the plant there were three categories of workers based on the intensity of exposure to VOPVC.' The first group (highest exposure) consists of the workers of the major occupations (apparatus operators, fillers) employed in producing VC by dehydrochlorination of dichlorethane in the Table 1 Observed number ofdeaths from cancer t Ohs) and SMRs ufcancer in the cohort of VC and PVC workers Meti Sues icd . ms Ohs All malignancies Oral cavity and pharvnx Digestive organs: Oesophagus Stomach Rectum Pancreas Liver Respiratory organs: Larvnx Trachea, bronchus, lung Bones and connective tissue Skm Breast Reproductive organs Urmurv organs Brain and nervous svstem Leukaemia, ateukaemm Other malignancies of lymphatic and haemaiopoietic tissue 'Significant ui p < 0 05. 140*209 141-149 150-159 ISO 151 154 157 lM63 161 if,: 170-171 172-173 174 ISO-1X7 IKK-JK9 i9i-i9: :iu-:o7 44 0 t7 0 14 0 3 0 IX 1 17 1 0 0 1 l A y ;oo-:ox 20*. i w SMR 9X 2 --. 74X *-- *yy _ 172 2 -- 141-7 1000 145-3 166-7 -- 125*0 y*s 90*9 42X-6 100 0 Women Ohs 19 0 X 0 7 l 0 0 0 0 0 0 1 0 0 2 2 4 SMR 153-8 -- 121-2 -- 142*9 125 0 -- -- -- -- -- -- 10000 -- 71*4 -- 5000 666-7 2000-0* - Both sexes Obs SMR 63 1066 0-- 25 850 0-- 21 K4 7 1 500 3 142-9 0-- IK 134 3 1 83*3 17 139 3 1 142-9 ! 200-0 0-- 3 53-3 1 34 5 4 153-8 5 500-0' 5 416-7* Increasii Table 2 Level of exposw High Moderate Low c Sigmticai medium the susr beginmr certain realised. The s stntcd t* PVC wi. employe p^ratus where P The t! ployees ployed assisian' with VC 'I able 3 exposure VC level High Moderate Low Signmc. N  UM&W .*. Increasing evidence of the rise of cancer in workers exposed to vinylchloride Table 2 Observed deathsfrom cancer (Ohs) and SMRs m subgroups of workers with various exposures to VC 95 in cai Level blc of exposure la IT Sites Men Ohs SMR Wcmten Ohs SMR Both sexes Obs SMR High All sites: 2* 101*4 12 444*4* 40 132 0 VC Stomach Lung 8 79 2 13 mi 5 284*6* 13 0-- 13 114*0 168-8 m- Lymphomas, leukaemias 8 3000 4 4000-0* 7 636-4* bic rs, Moderate All sites: Stomach 13 1071 5 122 0 5 113*6 20 108 7 2 133 3 7 1288 nd Lung 4 1290 0 4 125-0 nd Lymphomas, leukaemias 1 1667 1 142*9 2 153-8 Low :rc All sues: i 31 3 Stomach 1 S3-3 Lung 0-- Lymphomas, leukaemias 0 -- 2 28-2 0-- 0-- 1 333-3 3 29-1* 1 27-0 0-- 1 200*0 ale '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 le nd beginning of their employment up to 1959 (when certain improvements in working conditions were realised). The second group (moderate exposure) is repre 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 moderate exposure groups of male workers were sented by the workers in the new shops producing eases of lung cancer noted. This supposes some effect ng :es to sts us C he PVC with modern technology and those who were employed before 1971 in drying departments and ap paratus operators in the polymerisation departments where PVC was produced with imported technology. The third group (low exposure) is composed of em ployees of the new shops, the drying workers em ployed between 1971 and 1977 and laboratory assistants and other workers having minor contact of smoking, an essential factor in the development of lung cancer21'23 that might enhance the carcinogenic influence of VC. Among the female workers exposed to the highest doses of VC, the SMRs are high and significant for malignancies of the stomach, and for leukaemias and lymphomas. 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 of workers by duration of employment and exposure tti I' C A/m VC level burtuianot employment (years) Ohs High 0-4 5-9 10-14 15-19 *20 Moderate Lou 0-4 5-9 10-14 15-19 *20 0-4 5-9 10-14 15-19 >20 'Significant at p < 0 05. is 5 : 2 t 11 3 0 I 0 l 0 0 0 0 SMR 113*2 104-2 909 181-8 66*7 III! 130 4 ___ 166*7 -- 47-fi ___ _ - H'omen Ohs 1 5 1 4 1 1 1 2 0 ! 0 0 0 2 0 SMR 68 5 714-3* 333 3* 1333-3* 5000 47*6 76-9 105*3 ___ 142-9 _ -- 285-7 -- Both sexes Obs SMR 19 108-1 10 181-8 3 120-0 6 428-6* 2 117-6 12 100-0 4 111 -1 2 58-8 1 71-4 1 90-9 ! 25-6 0-- 0-- 2 250-0 0-- i)06CZZ  iw 96 Thus there is a clear relation between career mor tality and the level of VC exposure in the uudy 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. Table 3 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*/4, 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 affect other organs. This idea is to some extent confirmed by animal experiments14 with dilTcrcnt doses of VC (3690. 266. 25. and 14 mg/m') where the lowering of adminis tered VC doses was accompanied by a changc.in the ratio of liver malignancies, lymphomas and leu kaemias towards the production of the latter. The finding of significant increases in SMKs lor lymphomas and leukaemias, especially among femaleworkers 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 cring of the MAC in the USSR to 01 mg/m', promotion of the hcrmitic scaling 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. References 1 kegnauh V. Composition of a chlorinated hydrocarbon (oil from iHi-Uwimug gases) Justus Liehtg's .1 otudes ( Itcnttsn v 1X35:14:22-38. 2 Filatova VS. Gronsberg ES. Sanitary and hygienic labour conjiIhnw m production of polychlorvinyl tar and measure* of ihetr improvement. Gigijenu t sundurtja l957;NI:3K-42" 3 Smirnova NA. Clinical features of the professional toxic angt.v ncvrina. In: Mutenttf) pa voprmam figteny iruda i cloak v pr>>(ruumuligrii hoieznej Gorky 1956 44-52 * 4 Sucui J. Oriman J, Vataskai M. Contribute la sludiuc tmbulnavimor produsc de chlorurc dc vmii. Med Intern 1963. 15:967-78. 5 Wilson RH. McCormick WE. Tatum C!\ <*//. Occupation.ii jcruusicolyus. JAMA 1967;201:577--K1 6 Juhe H. Lange CE. Sderodermiarligc Hautfcrindeeungcm Repuud-Syndrom und Acroosteolison bet PVC-Herstellendcn Indimrc. Distil Med Wothnschr 1973:97:1922-3. 7 Nikitin VS. Rjabeu VA. MPC of the noxious substances in the workshop* air m the USSR and abroad. In: Nauchnye Raha:y fnstnuta ohranv truth Vsesa/uznago Centrulnogo Soveta Profc.*suuudtgch Sojuznr Moscon 1973:84.22-9." K Viola PL. Carcinogenic effect of vmylchloridc. In; Tenth inter* mnumuf Comer Congress. Houston, 19711. Vol 29. Houston Medical Art Publishing Co. 1970. 9Malioni 0. Lcfcminc G. Vinyl chloride carcinogenesis current results and perspective. Med Lav 1974:65:11-12. 10 Caputo A. Viola PL. Bigotti A. Oncogenic response of rat ski;:. lungs and bones to vinyl chloride. Citmrr Res 1971:31:516-22. 11 Lee CC. Blandan GC. Winston JM. eta/. Inhalation toxicity of vinyl chloride and vinylidene chloride. Environ Health Perspen 1977;21:25-35. 12 Malioni C. Lcfcminc G. Cilibcny A. etui. Carcinogenicity bioassay* of VCM: a model of nsk assessment on an experimental basis. harirtut Health Perspeet 19X1:41:3-29 13 Siovhur NN. Kurliandsky HA. Turusov VS. Towards Jhe ratio nale of the permissible vinylchiohde contents in the working zone air. In: Tezisvthtklut/ov 6 Vsexojuzlud canfermrii. Lenin grad: 1979:288 * 14 Kurliandsky 8A. Siovhur NN'. Turusov VS. Towards the quev non of hygienic reglamcntaiion of vinyl chloride. Gigtemt t Son north 19KI J:74-X6." 15 Crccch JL Johnson ML. Angiosarcoma of the liver in the manu facture ill PVC*. J Orrup Met! 1976; I 6. 150- I. 16 International Agency for Research on C`ancer: ttWAme group on vutvt thloruU I .yon: IAR(`. 1974. (hit icch report N74/(H)5.) 17 MacMahon H. Pugh T. Ipscn J. The use of epuk-tnudogu methods at (hr studin of mmot/enonts thwosex Moscow MuIiI/iiki. 1966. (ItansUiietl inlo Russian.I IS Dvoirin VV Analytical method* of the study in cancer epi demiology research. In: Chakhn AV. cd. Cancer epidemiology to CMC.A rtHunnes. Moscow: Mcdn/mj. 1979. 19 Mcrkov AM. Poliakov l.l;. Sanitary sianstirs. Leningrad: Medit/ma. I$74.* 20 Plohinsky NA. Eitanetry. Moscow: Moscow Stale Uimcrsm. 1970.* 21 Serehrov Al. Tobacco smoking and lung cancer. Sov Med 1978;7:109-12.* 22 Chakhn AV. Ghizute LA- Modem concepts about aetiology and pat hogencsis of lung cancer. Topr Onktd 1982;2:3-9 * "In Russian. In VW)<5LrZZ I 9 tft tte *. h Vfl Inc reasing evidence of flic rise of cancer in workers exposed to vi.tyfchioride 97 23 Doll R. Pent R The uium.** of canter. Oxford. New York:Oxford 27 M>*ion RR. Peter* JN. Johnson MN. Proportional mortality nt Umvcrviiv l*ro>v I MS 1 N litilHei P\. VVmnl S. I illoi C . ciut MmtaliU experience ! I he urong VC workers. Lancet l974:ii:397-8. :s On Mli. iiin^ner KK. Holder llll. Vinyl chluiuic exposure in a cs workers. m .t V't'M production plain. J Umif* Mai controlled industrial environment. A longterm monality ex* he I979.2IIV5-20.V pencncc in 594 employees. Arch Environ Health 1975:30:333-9. 25 Byren D. Gnpholm G. England A. eiul. Mortality and cancer 29 Watweiller RJ. Stringer W. Jones J. etui. Neoplastic nsk among morbidity in a group of Swedish VCM and PVC production workers exposed to vinyl chlondo. Ann NY Acad Set 1976; workers Environ Health Persptet 1976.17:167-70, Z7L40-K. 26 I ok AJ. (. oilier l*l: Low iiHirtalny rates in mduMriiilcohori Mud- 30 Imcmaiiona! Agency for Research on Cancer. Mtumjtrapiuan the ics due to selection lor work and survival in the industry Hr J evaluation a( the ctirctnttgenic risk of chemicals to humans. VoJ Ptex Sm Met 1976:30:225-30. 19. Lyon: IARC. I979.377-43X. Ji. alhV Vancouver style All manuscripts submitted to the Br J !nd Med should conform to the uniform requirements for manuscripts submitted to biomedical 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 be numbered consecutively in the order in which they arc first mentioned in the text by Arabic numerals above the line on each occasion the reference is cited (Manson1 conlirmcd other rcpons:"5...). In future refer ences to papers submitted to the Hr J hid Med should include: the names of all authors if there arc six or less or. if there arc more, the first three followed by et at: the title of journal articles or book chapters: the lilies of journals abbreviated according to the style of Index Mediciu', and the first and final page numbers of the article or chapter. Examples of common forms of references are: 1 International Steering Commute* of Medical Editors. Uni* form requirements for manuscripts submitted Co biomedical journals. Br Med J l97V:l:5J2-5. 2 Surer NA. Wassermar SI. Austen KF. Cold uriicana: release olio lire etrvulation of histamine and eminn-phil chcnio* tt-eiie factor of anaphylaus during cold challenge. Id Engl J Med IC76.294.fiX7.90. 1 Weinstein U. Swan/ MN. Falhngcnie properties of invading ntieriynirganisms. In: Sodeman WA Jr. Sodeman WA. cds Pathologic physiology: mechanising id disease. Philadelphia. W H Saunders. 1974 4S7-72. T