Document 3e9Egmg1KnXXpjV2qR8evwbR3

reaves 'dctlitU'i d Safctji non No '*teru`tin '< inuut ot NIOSH, itmptmt .iluution nvjttene i School AtUIC un M,;I IKUoyu ^ncc in Mratorv v'Ntimu* dv, BrJ British Journal of Industrial Medicine 1988;45:93-9? I I Increasing evidence of the rise of cancer in workers exposed to vinylchloride V B SMULEVICH.1 1 V FEDOTOVA.: VS FILATOVA5 From the All-Union Cancer Research Centre,' AMS USSR, Moscow, and Institute oj Occupational Medicines Gorky. USSR abstract The results ot'a cancer mortality study among workers employed in the production of vinylchloride and polyvinylchloride between 1939 and 1977 suggest a significant increase in deaths from malignancies of the lymphatic and haemopoieiic tissues. Mortality for tumours of the digestive organs, respiratory system, bone and connective tissues, brain, and skin are 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 300mg/mJ 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 of the plant, reaching levels of lOO-XOOmg/nr1.' This ex posure resulted in a high frequency of occupational toxic angioncuroses in the workers-5 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;m5. VC and PVC induced diseases in the workers pro ducing these agents were described later by several foreign authors.*'" Officially established MFCs of VC in the working zone in several countries before 1974 were as follows: United States--770mg.m5; Italy, France. Finland, and Yugoslavia--1300: East Germany--500: West Germany---260: and Rumania--100.7 In 1970 Viola published the results of his animal experiments that were aimed at reproducing the acroostcolysis observed in PVC workers. The animals de\clopcd tumours of the lung and skin and led the author to conclude that VC was carcinogenic.5 Many Acccpicd (Xiob^r I'JM other workers have confirmed that VC is carcinogenic to animals.9*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 900 times higher than in the general population.15 10 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 of 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 w ho had worked m 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 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.17 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.18 The results of the hygiene study of the occupational environment in VC production for the period 1953-66 were treated by methods of variational sta tistics with identification of average VC concen trations for particular workplaces. I`* 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/mJ: moderate level--VC concentrations 30-300 mg/m3: low level--concentrations <30mg/mJ. For the quantitative estimation of the "share" of VC and PVC in the total process of cancer devel opment in the workers of this industry the technique of factorial dispersion analysis30 was used. Results Between 1939 and 1977 2SS 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 brain. 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 clear from the analysis of working conditions at the plant there were three categories of workers based on the intensity of exposure to VC-PVC. The first group (highest exposure) consists of the workers of the major occupations (apparatus operators, filters) employed in producing VC by dehydrochlorination of dichlorethane in the Table I Observed number nt deaths Irani cancer ' Oh.r I and SMRs aj cancer in the cohnrt at I'C and P\'C workers Wen Suet ICO S. 1965 Oht All malignancies Oral cat uv and pharvnx Dmestivc oreans: Oesophagus Stomach Rectum Pancreas Liter Respiratorv nrcans: Ljr>n\ Trachea, bronchus, lun Hones and connective tissue Skin Hrcast Reproductive organs 1 nnars organs Hrain and nervous svsiem Leukaemia, jieukacmia Olher malignancies of lymphatic and haematopoietic tissue i4o^:oq 141-149 150-159 150 151 154 157 160-163 161 162 170-171 i7:-m 174 ISO-1X7 IXX-IKd 191-192 204-207 44 0 17 0 14 0 } 0 IX 1 17 1 tl 0 1 1 > X 200-20.1. :nx. 1 :<n SMR OH-2 74 H _ _K3-3 172-2 __ 141-7 100 0 I4< 3 166 7 __ _ 125-0 3H-5 do v 42X h 100 0 Women Ohs SMR id 153-S 0 __ X 121 2 i) ___ 7 142-9 1 1250 0-- 0 __ 0-- 0_ 0 -0 l looo o 0 2 71 4 0_ t 500 0 f>66'7 4 2000 0" Both fetes Obs SMR 63 106 6 0 25 S5 0 0 :i 84 -7 1 50-0 3 142 9 0 18 1 34 3 t 83 3 17 139 3 1 142 d 1 200 0 0 hi 3 i 34.5 4 153 X 5 500 0* 5 41K-7* Increa Table . Level of expo High Mcwjcr Low (/) 0 *5ienw O) CD medu the si begin ccrta realis Th sente PVC empl parai wher Th ployt ployi assist with 1 j Table j e.xpoi I VC le High Mode Low -7latov -red in logical .niable J-PVC com(table nours. i. and is and d. No were .1 canmale ! pan 's and r than s was I' the I haesa rking lories re to nsists raius VC the Increasing evidence of the rise of cancer in workers exposed to vinvlchloride Table 2 Observed deathsfrom cancer t Obs) and SMRs in subgroups of workers with various exposures to VC Level of exposure to VC Sites High All sues: Stomach Lung Lymphomas, leukaemias Moderate All sites: Stomach Lung Lymphomas, leukaemias Low All sites: Stomach Lung Lymphomas, leukaemias Significant at p <. 0 05. Men Obs :s 3 13 S 15 5 4 I 1 1 0 0 SMR 10L4 79 2 17|*| 3000 1071 1220 1290 166-7 31-3 33-3 -- Women Obs 12 5 0 4 5 -i 0 l * 0 0 1 SMR 444-4* 3X4-6* S-5` 40000- 113 6 133-3 -- 142-9 23-2 -- -- 333 3 Both sexes Obs SMR 40 132-0 13 114-0 13 163-3 7 636-4* 20 108-7 7 123-3 4 125-0 -> 153-8 3 29-1* 1 270 0 1 2000 95 medium of methyl alcohol and in producing PVC in the suspension who worked in these shops from the beginning of their employment up to 1959 (when certain improvements in working conditions were realised). The second group (moderate exposure) is repre sented by the workers in the new shops producing 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 with VC. The first and second occupational groups had a increased SMR for all cancers (table 2). More men in 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 cases of lung cancer noted. This supposes some effect of smoking, an essential factor in the development of lung cancer11 '*J 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 the lowest SMRs. Table 3 Observed deaths from cancer (Obs) and SMRs in various subgroups of workers by duration ol employment and exposure to VC ir/ciw Duration ol eotplavment (\ears) High 1^4 5-9 10-14 15-19 >-:o Moderate 0-4 5-9 10-14 15*19 *20 Low 0-4 5-9 10-14 15-19 :u Sicniticum jt p < 0 05. Men Ohs 13 5 \ a 3 0 1 0 I 0 0 0 0 SMR 113-2 104*2 90-9 131-8 66*7 mi-1 130 4 -- 166-7 47 fi -- -- -- -- Women Ohs SMR 1 68-5 5 714 3* 1 333-3* 4 1333-3* 1 5000 1 476 1 t 76*9 105-3 0 l 142 9 0_ 0-- ft 2S5-7 0-- Both sexes Obs SMR 19 108-1 10 131-8 3 120 0 6 428 6* > 1 17 6 12 100 0 4 1 III 5X-X 1 71 4 1 909 1 25 6 0-- 0-- t 250 0 ft R&S 001652 r 96 Smulevich. Fedotova. Filatova Thus there is a clear relation between cancer mor ering of the MAC in the USSR to 0-lmg/m1. tality and the level of VC exposure in the study co promotion of the hermiiic scaling of the equipment hort: the workers subjected to doses higher than used, and development of the non-stop technologies 30 mg/nr* have a higher risk of cancer than those with of VC production) will effectively serve to prevent the minimal contact with this compound. carcinogenic effects of VC on workers. Table 3 presents the distribution of deaths from cancer in the groups with different periods of References 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 1 Regnauit V. Composition of a chlorinated hydrocarbon (oil from oil-focmtn* gase$i, Justus Liebig's Annuls Chemistry 1835:14:22-33. 2 Filatova VS. Cronsberg ES. Sanitary and hygienic Ijbour condi (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. tions in production of polychiorvmyj tar and measures of their improvement, Ctgijena i sonttarqa l9S7:N'l:33-42.' 3 Smirnova NA. Clinical features of the professional toxic aneio* neuroses. In: Matertalv po voprosam gigieny truda t cltntkvprolesstonoltgch hiUezntf Gorkv I9$6:4-U52.# 4 Sucui J. Driman J, Vjl^skat M. Contribute la studiuc imbal- Discussion Our study has shown an increased cancer mortality in navmtor produsc de chlorurc de vinti. Med Intern 1963. 15,967- 7K. 5 Wilson RH. McCormick WE. Tatum CF, etui. Occupational acroosieolysis. JAMA 1967;20I'577-XI the workers employed in the production of VC and PVC. compared with the general population. An in creased frequency in malignancies of the digestive or gans. respiratory tract, brain, and lymphatic and 6 Juhc H. Lange CE. Sclerodermiaruce Haulfcrandecuncem Rcjnaud-Syndrom und Acroosteohson bet PVC-HerMellendcn Industry. Ditch Med H'aehnschr 1973.97.1922*3, Niknm VS. Rjabets VA. MPC of the noxious substances m the workshops air in the USSR and abroad. In: Snuehnve Rabotv haematopoietic tissues observed in this study is in ac cord with the results of similar studies of workers in VC-PVC plants in the United Kingdom. W Germany, France, United States, and other countries."1' Institute ohranv truth Vsesofuznogo Centralnogn Sovettt Proles* xtonahgch Sojuzor Moscow l973:&4'22-9.* X Viola PL, Carcinogenic effect of vmylchloride, In' Tenth inter* national Concer Congress. Houston. 1970. Vol 29, Houston: Medical Art Publishing Co. 1970. In our study no angiosarcomas were noted: these tumours arc considered hy some authors to be a specific occupational disease of VC workers.;J 30 The reason for this lack of angiosarcomas may be due to 9 Maltont C. Lefemine G, Vinyl chlondc carcinogenesis current results and perspective, Med Luv 1974.65,11-12. 10 Caputo A, Viola PL. Bigoin A. Oncogenic response of rat sktn. lungs and bones to vinyl chloride. Cancer Res l97l:3l:$lb-22. 11 Lee CC. Blandari GC. Winston JM. et of. Inhalation toxicitv ol the measures for limiting airborne levels at work which were introduced earlier than in other countries and to etfcctive protection (by relevant individual de vices) of workers in high exposure jobs. On the other vinvl chloride and vinvhdcne chloride. Cnvtnm Health Person 1977:21:25-35. 12 Multom C, Lefemine G. Ciliberty A. etui Carcinogenicity bio* j*uys of VC.M: a model of risk Jvwrssment on an experimental basis. Emtron Health Perspeit I9XI.4I 3-29, 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 (3 Slovbur NN\ Kurliundskv BA. Turuov VS. Towards the ratio* nale of the permissible vmylchloride contents in the working ione air. In: Teztsv dokladav ft I'semiuzhal tanterenen. Lenin grad: I979`28K.* M Kurhandskv BA, Stovbur NN. Turusov VS, Toward* the ques idea is to some extent confirmed by animal experiments11 with different doses of VC (3690. 266. 25. and 14 mg/nr1) where the lowering of adminis tered VC doses was accompanied by a change in the tion of hygienic reclamenution of vinyl chloride, (ttgtemt t Sunttartja |9Xl;3,74-X6 * 15 Creech JL. Johnson ML, Angiosarcoma of the liver in ihe manu facture ol PVC J Oitup \(ed 1976:16 150-- l 16 International Agency for Research on Cancer: Working group an ratio of liver malignancies, lymphomas and leu kaemias towards the production of the latter. The finding of significant increases in SMRs for lymphomas and leukaemias, especially among female vinyl chloride, Lyon: (ARC*. 1974 tint tech report N74 005.1 17 MaC.Mahon B. Pugh T, Ipscn J. The use at epu/emtolagic meihtnls m the Mudtes at tumtnteeuous diseases. Moscow Medif/ina, 1966, (Translated mm Russian,i IX Dvotrm VV, Analytical methods of the study in cancer epi 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 Ic'd of exposure agrees with experimental cudcncc on this subject.'* This gives hope that cur demiology research. In. C'hjkhn AV, ed Comer epidemiology in CMKA i nullifies, Moscow; Mcdilzma. 1979 19 Mcrkov AM, Poliakov I [ Sanitary \tatt\tn \ I cnmgratl1 Medlt/ina. 1974 * 2(1 Plohinsky NA tlioweiri Moscow, Moscow Stale Lnoersilv. 1970 ' 21 Scrcbrov At, Tobacco smoking and lune cancer .SVm* Med I97X.7 109-12. 22 Chaklin AV'. (jru/ute LA, Modern concepts about aetiology and pathogenesis ol lune cancer 1 <rr tint,"/ 19X2.2 3-9 * rent measures lor limiting VC exposure at work (low *ln Russian. Increa 23 Doll L'i 24 Butff l 25 Byre m* w 26 Fox te* P> V: A1 sh< mo (kr int dCC V:i 00 Br 0) 5U i o o in -4. the O) cn W o;u cm ent sht Jtova r mem ^gies u the f^ITI ntxtrv ..mdi: their Increusme evidence of die rise of cancer m workers exposed 10 vinylchloride y7 Doll R. Pilo R, The Cullies oi cancer. Oxford. New York: Oxford University Press. 1931. 24 Buffter PA. Wood S, Eifl*rr C, etui Mortality experience of the workers in a VCM production plant, J Occup \ted W79:l|;W5-2Q3. 25 Byrcn D. Engholm G. England A. etal. Mortality and cancer morbidity in a group of Swedish VCM and PVC production workers. Environ Health Perspect 1976;17:167-70. 16 Fo< AJ. Collier PF. Low mortality rates in industrial cohort stud ies due to selection tor work and survival in the industry Hr J f'rev Hoc Med 1976:30:225-30. 27 Monson RR. Peters JN. Johnson MN. Proportional mortality among VC workers. Lancet I974;ii:397-S. 23 Ott MG. Langner RR. Holder BB, Vinyl chloride exposure tn a controlled industrial environment. A long-term mortality ex perience in 594 employees. Arch Environ Health 1975;30:333-9, 29 Waxwetller RJ. Stringer W, Jones J, eiai Neoplastic risk among workers exposed to vinyl chloride. Ann NY Acad Set 1976: 271:40-3. 30 International Agency for Research on Cancer. Monographs on the evaluation of the carcinogenic rtsk of chemicals to humans. Vol 19. Lvon: (ARC 1979:377-133. iccm nden Vancouver style All manuscripts submitted to the Sr J Ind 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 wiih 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 ihe text by Arabic numerals above the line on each occasion the reference is cited (Manson1 confirmed other reports1In future refer ences io papers submitted to ihe Br J Ind Med should include: the names of all authors if (here arc six or less or, if there are more, the first three followed by ei al: the title of journal articles or book chapters; the titles of journals abbreviated according to the style of Index Medicus: and the first and final page numbers of the article or chapter. Examples of common forms of references arc: 1 International Steering Commute* of Medical Editors. Uni form requirements for manuscripts submitted to biomedical journal*. Br Med J 1979:1:532-5. 2 Soter NA. Washerman SI. Austen KF. Cold urticaria: release into the circulation of histamine and cosmo-phil chemouctic factor of anaphylaxis during coid challenge. /V F.n\*l J Med 1976:294.6X7-90. \ Weinstein L. Swart/. MN Pathogenic properties of invading micro-organisms. In: Sodcman WA Jr. Sodcman WA, cds. Pulhtdmitc phwitolotv rneehnniwi^ itf disease. Philadelphia. W H Saunders. 1974 457-72 R&S 001654