Document RjjxZpk2ByXGeeqyB6yNk3dgB

t Greaves it facitmcs .inti Safety tepori No l American Manual of V, NtOSH, v Sampling 72~2J22f72 Evaluation 'utl Ingtene ard School HE. Acute Occup Mad luiemiafagu mi. presence of Respiratory non. csiimail study. BrJ a British Journal of industrial Medicine 1988;45:93-97 Increasing evidence of the rise of cancer in workers exposed to vinylchloride V B SMULEVICH,1 I V FEDOTOVA,3 V S FILATOVA3 From ihe All-Union Cancer Research Centre,1 AMS USSR. Moscow, and Institute of Occupational Medicine,1 Gorky. USSR abstract The results of 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 haemopoielic 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 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 of the plant, reaching levels of 100-800 mg/m3.2 This ex posure resulted in a high frequency of occupational toxic angioncuroscs 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 (MFC) of 30mg/m3. VC and PVC induced diseases in the workers pro ducing these agents were described later by several foreign authors.* ~fl Officially established MPCs of VC in the working zone in several countries before 1974 were as follows: United States--770mg/m3; Italy, France, Finland, and Yugoslavia--1300; East Germany--500; West Germany--260; and Rumania--100.3 In 1970 Viola published the results of his animal experiments that were aimed at reproducing the acroostcolysis observed in PVC workers. The animals de veloped tumours of the lung and skin and led the author to conclude that VC was carcinogenic.8 Many Aixcpioi 20 Otuiher text. 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 ol this dis ease in the exposed groups was 300 to 600 times higher than in the general population.1316 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 who had worked in a VC exposed joh 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 .s* BOR 006846 jliim othUi^HHb^tk 94 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 43216 (27059 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." 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/m3; low level--concentrations < 30 mg/m3. 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 analysis10 was used. Results Smutevich. Fedotova, Fiia Between 1939 and 1977 288 deaths were registerc the cohort, including 63 from cancer. Histolot confirmation of the diagnosis of cancer was avail for 60% of the cases. As shown by the SMRs, the workers in VC-I plants have an increased cancer mortality by c parison with the general population of the city (t I). This was particularly noticeable for lung tumc pancreas, bones and connective tissue, skin, brain. The observed mortality from leukaemias lymphomas is significantly higher than expected cases of angiosarcoma or other liver tumour noted. For the male workers exposed to VC, the total cer mortality was somewhat lower than in the i population of the city. The numbers of cases of i creatic cancer, lung cancer, tumours of the bones genitalia, and leukaemias, however, were higher i expected but not significantly so. The cancer mortality for the female workers greater than expected due to malignancies of stomach, rectum, skin, brain, and lymphatic and matopoietic tissues. The excess for leukaemias lymphomas was statistically significant. As was clear from the analysis of wor conditions at the plant there were three categi of workers based on the intensity of exposur. VC-PVC. The first group (highest exposure) con of the workers of the major occupations (appai operators, fitters) employed in producing by dehydrochlorination of dichlorethane in Table 1 Observed number ofdeathsfrom cancer (Obs) and SMRs ofcancer in the cohort of VC and PVC workers Men Sites /CD 4,1965 Obs All malignancies Oral cavity and pharynx Digestive organs Oesophagus 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, alcukuemiu Other malignancies of lymphatic and haematopoietic tissue 'Significant at p < 0 05. 140-209 141-149 150-159 150 151 154 157 160-163 161 162 170-171 172-173 174 180-1X7 188-189 191-192 204-207 44 0 17 0 14 0 3 0 18 1 17 1 0 0 1 l 2 3 1200-203.208. 209 SMR 98 2 -- 748 -- 83-3 -- 172-2 -- 141-7 100-0 145 3 166 7 -- -- 125 0 385 90-9 428-6 1000 Women Obs 19 0 8 0 7 \ 0 0 0 0 0 0 I 0 2 0 2 2 4 SMR 153-8 -- 121-2 -- 142-9 1250 -- -- -- -- -- -- 1000 0 -- 71 4 -- 500 0 666 7 2000-0* Both sexei Obs SMR 63 106 6 0-- 25 85-0 0-- 21 84 7 1 500 3 142-9 0-- 18 134 3 1 83 3 17 139 3 1 142 9 1 200-0 0-- 3 83 3 1 34 5 4 153 8 5 500 0* 5 4167* BOR 006847 Increasing evidence of the rise of cancer in workers exposed to vinylchloride Table 2 Observed deathsfront cancer (Obs) and SMRs in subgroups of workers with various exposures to VC ciW ; exposure to VC Sites High All sites: Stomach Lung Lymphomas, leukaemias Moderate All sites- Stomach Lung Lymphomas, leukaemias Low Alt sues. Stomach Lung Lymphomas, leukaemias 'Significant at p < 0 05. Men Obs 28 8 13 8 15 5 4 l l 1 0 0 SMR 101-4 792 171 1 3000 107 1 122 0 129-0 166-7 313 83-3 -- -- Women Obs 12 5 0 4 5 2 0 1 2 0 0 1 SMR 444 4* 384 6* -- 4000-0* 1136 133-3 -- 142-9 28-2 -- -- 333-3 Both sexes Ohs SMR 40 (32-0 13 114*0 13 168-8 7 636-4* 20 108 7 7 128 8 4 1250 2 153-8 3 29 1* 1 27-0 0-- 1 200-0 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 reprejnted by the workers in the new shops producing ;'VC 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 cancer21"13 that might enhance the carcinogenic influence of VC. Among the female workers exposed to the highest doses of VC, the SMRs arc 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. fable 3 Observed deathsfrom cancer (Ohs J and SMRs in various subgroups of workers by durdiion ofemployment and exposure to VC VC level Duration ofemployment (years) High <M 5-9 10-14 15-19 S 20 vloderate 0-4 5-9 10-14 15-19 ?20 Low 0--4 5-9 10-14 15-19 Ss20 at p < 0 05 Men Ohs 18 5 2 2 1 11 3 0 1 0 1 0 0 0 0 SMR 113 2 104 2 90-9 181 8 66-7 mi 130-4 -- 166*7 -- 47-6 -- -- -- " Women Ohs 1 5 1 4 1 1 l 2 0 1 0 0 0 2 0 SMR 68 5 7I4'3* 333-3* 1333-3* 500 0 476 769 105-3 -- 142-9 -- -- -- 285-7 Both sexes Obx SMR 19 108-1 10 181-8 3 120 0 6 428-6* 2 117-6 12 1000 4 111 1 2 58-8 1 714 1 909 1 25-6 0-- 0-- 2 250 0 0-- BOR 006848 96 Thus there is a clear relation between cancer mor tality and the level of VC exposure in the study co hort: the workers subjected to doses higher than 30 mg/m3 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%, 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.34"29 In our study no angiosarcomas were noted; these tumours are considered by some authors to be a specific occupational disease of VC workers.23 30 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 experiments1* with different doses of VC (3690, 266, 25, and 14 mg/m3) where the lowering of adminis tered VC doses was accompanied by a change in the 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 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.12 This gives hope that cur rent measures for limiting VC exposure at work (low Smulevich, Fedotova, File ering of the MAC in the USSR to 01 mg promotion of the hcrmitic scaling of the cquipi used, and development of the non-stop tcchnoli of VC production) will effectively serve to preven carcinogenic effects of VC on workers References 1 Rcgnaull V. Composition of a chlorinated hydrocarbon (oil oil-forming gases). Justus Liebigs Annates Chen 1835:14.22-38 2 Filalova VS, Gronsberg ES. Sanitary and hygienic labour i. lions in production of polychlorvinyl tar and measures ol improvement. Gigt/ena i .rantittri/a ! 95 ?.N1 IS 42 * 3 Smirnova NA Clinical features of the professional toxic .i neuroses In1 Material)- po voprtistim gigtenv truda i limit i fesstonaltgch hoteznej Gorkv 1950 44 52 * 4 Sucui J. Dnman J. Valaskai M. Comnbutii la studiuc u navintor produsc dc chlorure dc vinil Med Intern I 15.967-78 5 Wilson RH. McCormick WE. Tatum CF. etal Occup.li acroostcolysis. JAMA 1967;20l-577-81, 6 Juhe H, Lange CE Sclcrodermiaruge Haulfcrandccui Rejnaud-Syndrom und Acroosleolison bei PVC*Herstclh Induslre. Dtsch MetI tVochnsehr 1973:97'. 1922-3. 7 Nikitin VS, Rjabets VA. MPC of the noxious substances i workshops air in the USSR and abroad. In: Nauchnve R, Insliiuiu nhrany trutla I'sesojuznogo Centralnogn Sttvetu Pi stonatigeh Sojuzor Mascots- 1973;84:22-9.* 8 Viola PL. Carcinogenic effect of vinylchlonde. In Tenth I naInnull Cancer Congress. Houston, 19711. Vol 29. Hou Medical Art Publishing Co, 1970. 9 Maltoni C, Lefcmmc G, Vinyl chloride carcinogenesis cu results and perspective. Med Lav 1974:65' 11-12 10 Capulo A, Viola PL, Bigotti A Oncogenic response of ral lungs and bones lo vinyl chloride Cancer Rex 1971:311511 11 Lee CC. Blandan GC, Winston JM. etal. Inhalation loan. vinyl chloride and vinylidenc chloride. Environ Health Pa 1977:21:25-35. 12 Maltoni C. Lefemme G, Ciliherly A, etal Carcinogenicity assays of VCM1 a model of risk assessment on an cxpcrim basts Environ Health Perxpect 1981.41:3-29 13 Slovbur NN, Kurliandsky BA, Turusov VS. Towards the r nale of the permissible vinylchlonde contents in tlicwoi rone air. In: Tezisv ttoklmlov A t scsojuzhot cnnferetu n l< grad: 1979:288.* 14 Kurliandsky BA. Slovbur NN, Turusov VS. Towards the . lion of hygienic rcglamentation of vinyl chloride Gigtenn t itarija 19X1.3 74-86 * 15 Creech JL, Johnson ML Angiosarcoma of the liver in ihc n facture of PVC. J Occup Metl 1976:16:15(3-1. 16 International Agency for Research on Cancer II intiny C" vinyl chloride Lyon1 IARC, 1974. (Int lech report N74.li' 17 MacMahon B. Pugh T, Ipsen J. The use ol epulcintologtc me in the studies of ininiit/et ttottx discuses. Moscow Mcdu 1966. (Translated into Russian ) 18 Dvoinn VV. Analytical methods of (he study in cancer dcmiology research In: Chaklin AV. cd. (inner epidenn. in CMEA countries Moscow1 Medtt/ina. 1979 19 Merkov AM. Poliakov LE. Sontitirv statistics. Lainingr.id ditxina, 1974,* 20 Plohinsky NA. Biometry. Moscow Moscow Stale Urrivc: 1970* 21 Serehrnv Al Tobacco smoking and lung cancer ,5'r 1978.7:109-12.* 22 Chaklin AV. Gritrute LA, Modern concepts about acliologt pathogenesis or lung cancer. I npr Onknl 1982:2 1-9 * *ln Russian BOR 006849 4 Increasing evidence of the rise of cancer in workers exposed to vittylchbride 97 21 Doll R. Pclo R The causes of cancer Oxford. New York Oxford University Press, 1981 :4 Bufiler PA, Wood S, Eiftcr C. chit Mortalily experience of the workers m a VCM production plant J Ornip Ktvd 1979:21195-20^ 2* Hyren D, Engholm G, England A, etui. Mortality and cancer morbidity in a group of Swedish VCM and PVC production workers Environ Health Per.spcd 1976:17:167-70 26 Fox AJ. Collier PF. Low mortality rates in industrial cohort stud ies due to selection for work and survival in the industry Br J PrcvSoi Mi'd 1976,30 225-30 27 Monson RR, Peters JN. Johnson MN. Proportional mortality among VC workers. Lumet 1974;ii:397-8. 28 Ott MG, Langner RR. Holder BB. Vinyl chlonde exposure in a controlled industrial environment. A long-term mortality ex perience in 594 employees. Arch Environ Health 1975:30:333-9, 29 Waxwedler RJ, Stringer W. Jones J, era/. Neoplastic risk among workers exposed to vinyl chlonde. Ann NY Acad 5a 1976; 271,40-8 30 International Agency for Research on Cancer. Monographs i*n the evaluation of the carcinogenic ri\k of chemUah to humans Vol 19. Lyon; IARC. 1979:377-438 Vancouver style All manuscripts submitted to the Br 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 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 are first mentioned in the text by Arabic numerals above the line on each occasion the reference is cited (Manson1 confirmed other reports2"3..,). In future refer* cnees to papers submitlcd to the Br J lull Med should include, the names of all authors if there arc six or less or, if there are more, the first three followed by et at; 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 are: 1 International Steering Committee of Medical Editors. Uni* form requirements fur manuscripts submitted to biomedical journals Br Med J 1979;1:532-5 2 Sotcr NA. Wasserman SI, Austen KF. Cold urticaria: release into the circulation of histamine and eosino-pbil cherootuette factor of anaphylaxis during cold challenge. N Engl J Med 1976:294,687-90. 3 Weinstein L, Swart/ MN. Pathogenic properties of invading micro-organisms. In: Sodeman WA Jr, Sodcman WA. cds. Pathologic physiology' mechanism^ of disease. Philadelphia W H Saunders. 1974 457-72. BOR 006850