Document RJqM8bkJZpK8jXXQM9vkO3847

British Journal of Industrial Medicine 1988:45:93-97 increasing evidence of the rise of cancer in workers exposed to vinylchloride V8SMULEV1CH,' 1 V FEDOTOVA,5 V S FILATOVA5 fnm the All-Union Cancer Research Centre.' AMS USSR. Moscow, and Institute of Occupational Medicine.1 imky. USSR rfHACT The results of a cancer mortality study among workers employed in the production of myichloride and polyvinylchloride between 1939 and 1977 suggest a significant increase in deaths tom malignancies of the lymphatic and haemopoietic 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 to follow up period. The risk of cancer was highest among the workers exposed to concentrations jfVCof300mg/m5 and more who had worked at the plant for 15 to 19 years. The relatively high amber of leukaemias and lymphomas in the study group and the absence of liver angiosarcomas wobably reflects specific carcinogenic action of different doses of vinylchloride. Tit carcinogenicity of vinylchloride (VC) has been tsoied only recently although this compound was naihesised almost 150 years ago1 and its industrial xoduction in manv countries started in the late lls. Hie first clinical and hygiene study of the oeapatitmal setting and health of workers in plants xoducing VC and polyvinylchloride (PVC) was unfcnalttn in the USSR in the early 1950s. This study heavy air pollution with VC in the shops of t*plant, reaching levels of 100-800 mg/m5.5 This exiwirt resulted in a high frequency of occupational tme angioneuroses in the workers5 and led to the toshiivt limitation in the USSR (1957) of the VC rid in the working zone to a maximum permissible "Kentration (MPC) of 30mg/mJ. j 'Cand PVC induced diseases in the workers proj *>nng these agents were described later bv several ! TMgn authors-1'* Officially established MPCs of i 1 tfthe working zone in several countries before ! tV tttrt 35 follows: United States--770mg?m5: ! France. Finland, and Yugoslavia--1300; East ; 500; West Germany--200: and | ta>unia--100," | b 1970 \iola published the results of his animal `ivrimenis that were aimed at reproducing the acro^rolysis obser\eti in PVC workers. The animals dc'M'm tumours of the lung and skin and led the `'or to conclude that VC was carcinogenic *1 Many '^JOOc.obet 19X6 other workers have confirmed that VC is carcinogenic to animals.'"M 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.15 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. Fot 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 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 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." The numbers of person* years of observation for the entire cohort was 43216 (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.11 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.'9 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 <30mg/nv\ 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 analysis50 was used. Results Smulevich. Fedotova. FUaion Between 1939 and 1977 288 deaths were registered it the cohort, including 63 from cancer. Hisioiopa] confirmation of the diagnosis of cancer was availat* for 60% of the cases. As shown by the SMRs, the workers in VC-PVf plants have an increased cancer mortality by com. parison with the general population of the ettv <ubk 1). This was particularly noticeable for lung turnouts pancreas, bones and connective tissue, skm. anc brain. The observed mortality from leukaemias and lymphomas is significantly higher than expected No cases of angiosarcoma or other liver tumour u*k noted. For the male workers exposed to VC. the total tancer mortality was somewhat lower than tn the mak 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 tvas 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 workint conditions at the plant there were three categonr of workers based on the intensity of exposure tr VC-PVC. The first group (highest exposure) consist! of the workers of the major occupations (apparatus operators, fitters) employed in producing VC by dehydrochlonnatton of dichlorethane in the Table I Observed number ofdeaths from cancer tObst and SMRs of cancer in the cohort of VC and Pl'C workers Stirs icot. 06. All mahgnanoes Oral emu and pharynx Digestive organs. Oesophagus Stomach Rectum Pancreas Lver Respirator* organs' Larwu Trachea, bronchus, lung Bones and connective tissue Skin Breast Reproductive organs Unnarv organs Brain and nervou< #vstcm Leukaemia, uicukaemia Other malignancies ol'lvmphuiic anu haematopoietic tissue Significant at p < o (15 140-209 UUI49 1#0-159 ISO til IS IS" 100-16# 161 162 170-171 177-173 I'M IS0-1K7 IKS-1X0 iuuiv: 2<m-707 44 0 17 0 14 0 3 0 IK 1 17 l 0 0 1 1 a 3 200- 20X 111!.. 209 l SMR 98 2 - 74-8 83-3 -- 172 2 -- 141-7 100-0 145-3 166 7 -- -- 125-0 3X 5 90-9 42S-6 100-0 U'omen Ohs 19 0 8 0 7 1 0 0 0 0 0 0 l 0 A 0 A A 4 SMR 153-45 121 2 -- 142-9 125-0 -- -- -- __ -- 1000-0 -- 71-4 -- soo-o 666 7 2000 0- Bnifi sexes Ohs SMR 6? 106-6 0-- 25 85-G 0-- 21 84 7 1 500 \ 147-9 0-- IX 134 3 1 83-3 17 139 3 1 142-9 1 200-0 0-- 3 83-3 ) 34 5 4 153-S 5 5000- 5 VC6089 Mueastng evidence of the rise of cancer in workers exposed to vinylchloride Observed deathsfrom cancer (Obs) and SMRs tn subgroups of workers with various exposures to VC Urel Silts Hif* All DIM. Slomieh Uinf Lymphomas, leukaemias Madtnic All tiles Stomach Lung Lymphomas. leukaemias All met Sionuch Lung Lymphomas, leukaemias yrtirftcani at p < 0-05 Mtn Obs SMR 28 101A 8 792 13 1711 8 300-0 IS< 107-1 122-0 4 129-0 1 166-7 1 313 1 83-3 0 0-- Worn#i Obs SMR 12 444-J* 5 384-6- 0-- 4 4000-0* 5 1)3-6 2 133-3 0 --1 U2-9 A 282 0-- 0 --1 333-3 Both sexes Obs SMR 40 132-0 13 114-0 13 1688 7 636-4- 20 108 7 7 128-8 4 123-0 1S3-8 3 29)" 1 27-0 0 --1 200-0 95 zecim of methyl alcohol and m producing PVC in suspension who worked in these shops from the wanning of their employment up to 1959 (when main improvements m working conditions were isused). Tne second group (moderate exposure) is repre sented In' the workers in the new shops producing ?vc vuitb modem technology and those who were stpioved before 1971 in drying departments and ap- nraius operators in the polymerisation departments here PVC was produced with imported technology. Tot third group (low exposure) is composed of em>-.>>. of the new shops, the drying workers em|>ed between 197) and 1977 and laboratory lisants and other workers having minor contact >-= 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 cancer51 *33 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. - Observed deaths from cancer (Obs) and SMRs in various subgroups of workers by duration ofemployment and Sure io VC Duraunn of empinmitni hears) (M 5-9 10-14 15-19 >20 'r* ? 0-4 5-9 10-14 15-19 >20 0-4 V9 10-14 15-19 >20 mi p < 0-05 Men Qht 18 5 2 > 1 1) b \ 0 1 0 0 0 0 SMR 113 2 104: 90-9 181-8 66 7 mi 130 4 ___ 166 7 47-6 _ -- Homfn Ohs SMR 1 68 5 s 7I4-31 333 34 1333-3t 500-0 i 47-6 1 76-9 2 105 3 0-- ) 142-9 0 r_ 0 ___ 0 ___ *1 285-7 6-- Benh sexes Ohs SMR 19 108-1 10 181-8 3 120-0 6 428-6* 2 117-6 i: 100-0 4 111-1 2 588 1 71-4 l 90*9 1 25-6 0_ 0 ___ 2 250-0 0-- ii VC6090 96 Smuhvich. Fedotova. Filatova 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 30mg/inJ 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 ns action) on the nsk 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.24 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 10 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 experiments'4 with different doses of VC (3690. 266. 25. and I4mgfin3) 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 currem measures for limiting VC exposure at work (low- ering of the MAC in the USSR to Olmgun1 promotion of the hermitic sealing of the equipmeni used, and development of the non-stop technologies of VC production) will effectively serve to prevent thr carcinogenic effects of VC on workers References ) Regnauh V. Composition of chlorinated hydrocarbon toil fro* oiLforming gases). Justus Uehtp .< Annotes Chemmr. IF?5:I4 2 Filatova VS. Gronsberg ES. Samtaft and hygienic labour cone* lions in production of polyrhiorvtnyi j#r and measure* of thrr improvement Gtfttemi isonnorno I9$7;N1:JR^42 * .* Smirnova KA Clinical features of the professional ionc anppneurotes, In: Motertoh pe voprnsOm ftfiem truao i amik\ pt,+ It&stonehpch hoicznci Gnrki l9$6`44-52 * A Sucui J. Dnman J, Vaiiskai M Contnbuiti la ttudme tmb; navimoT proouse dr chlorure dr vim) Aled intern t$t` I5967-7S 5 Wilson RH. McCormick W. Tatum CF. etui Occupation^ acrootieolyiis. JAMA 1967:101 ;577-fil 6 Juhe H. Lange CE Scierodemiartigc Hautferandceungm Rejnaud`Syndroni und Acroosteohsnn bei PVC*Her*ieHendr Induitre Dtseh Met/ M orhnsrhr J 973:97:) 922-? 7 Nikitw VS. Rjabet* VA. MFC of iht noxious substances in ik workshops air m the USSR and abroad in Souchmr Aakv, Insnluia ohron\ trudo I sesojuzmtfo CentralnofO Sntfio Pride swnuitpeh SotuTot Matron 1973:84.*2-9 * R Viola PL. Carcinogenic effect of vinylchJondr In Tenth inti-* national Contv* Couprest. Houston. i9?(/ Vo! 29 Housiot Medny) An Publishing Co. 1970 9 Maltoni C. Lefemine G Vmyl chloride carcinogenesis curren results and perspective Med Lay 1974:65 11-12. 10 Caputo A. Viola FL. Bigom A Oncogenic response of rat sktr lungs and bones to vinyl chloride Conrer ftn i i Lee CC. Biandan GC. Winston JM. etui Inhalation loxtcm vtnvl chloride and vinvhdene chloride Environ Health Pe*p*< )977;21,25-35 12 Mahoni C. Lcfemine G. Cilibeny A, etui Carcinogenicity h*' asa v s of VCM: a mode) of risk assessment on an expenmenu basis Environ Health Pcrspeei !9M:4I'3-29 I? Stovbur N\. kurliandsky BA. Turuso\ VS Toward* the rai^ naie of the permiible xmylchlonde contents in the workirfc 20ne air In TfZi*\ dokltHinvfi I srxotuzhnl ronlerencn. Lewr prad 1979 2KK" 14 Kurhandkky BA. Stovbur KN. Turu>os VS Toward* the quo non ofhygiemc repiamentation of wnyl chloride. GtptenoiS# nornu 1981.3 74-XA 15 Creech JL. Johnson ML. Angiosarcoma of the liver in the mam faciure of PVC. J Oreup Med I07tj;)6 150-1 lb Iniemanonal Agency for Research on Cancer M orimp frivt"" vtnvl vMotide Lyon. lAR(\ 1974, tint tech report 17 Mac Mahon B. Pugh T. Ip*en J The use <if epuieotndopte in the studies u\ nonutfet wtu\ diseases Moscow Medunfu !9bh, (Translated into Russian.) IK Dvomn VV Analytical methods of the study in cancer rf demiolopy research In, Chuklin AV. ed Comer ppidemndK 1 ii CMF.A muntnes, Mowow: Mednzina. 1979 19 Merkov AM. Poiiykox LE Stmtior\ xtotts/trs Leningrad kir dii7ina. (974 2f) Plohmskx NA Btomeit\ Moscow Moscow State Lmvrron { 1970*' 21 Serebrov AI Tobjcco smoking and lunj: cancel 5 t I97S.7.I09-I2 22 Chakhn A\ . Grtt/utc LA Modern concept' ahoui adiology arc piithxitfcnesi' of hint camvr J npr Onkol I9K2.2 *-9* * In Russian VC6091 pmeosing evidence of the rise of cancer in workers exposed to vinylchloride 97 >1 run R. Poo R The causes of cancer. Oxford. Neu York: Oxford 198! j y letter PA. Wood S. Eifler C. rial Mortality experience of the Often in > VCM production plant. J Occup Mrd 1979^1:195-303. -t (ynn D. EnftvOlm C. Enpland A. riel. Mortality and cancer morbidity in a proup of Swedish VCM and PVC production orten nwon Health ftrspen t97fc:17; 167--70 ' > Fe> AJ. Collier PF. Low mortality met in industrial cohort (Ind ia due to (election for wort and survival in the industrv. fii J Prrr Sec Urd I9?6l30.::5-30, 17 Monton RR. Petert JN. Johnson MN Propontonal mortality amonp VC workers Loner: l974:n;J97-8. 28 Oil MG. Lanyner RR. Holder BB Vinyl chloride exposure in a controlled industrial environment. A tonf-ierm mortality ex perience in 594 employees. Arc* Lornon Health I97JJO:33.V9, 39 Viaxweiller RJ. Sinnpet W. Jones J. rial Neoplastic risk amonp workers exposed to vinvl chloride Am A')' Acad Sci 1976. 271 40-8 30 Inirmaitonal Apenry for Research on Cancer. Uonofraphs on ihr riahdimm nf the carcmofrmc risk vt rhrmirels to humans Vol 19 Lyon IARC. 1979.377-438 Vancouver style All manuscripts submit led to the Br J Ind Med should conform io 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 io accept articles prepared in accordance with the Vancouver style. The style (described in full in Br MedJ. 2d February 1979, p 522) is intended to standardise requirements for authors References should be numbered consecutively m the order in which ihev are first mentioned in ihr text by Arabic numerals above the line on each occasion the reference is cited (Manson1 confirmed other reports3'-'...). In future refer ences io papers submitted to the Br J Ind Med snould include the names of all authors if there are six or less or, if there are more, the first three followed by ei 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 Editor* Un* form requirement* for manuscript* submitted to biomedical journo Br Med J 1979;1:532-5 2 Soter Na. Wa**ernin SI, AuMtn KF, Cold urticaria. release into the circulation of hitumtnr and cosmo-phi) ehemotactic factor of anaphylaiu during cold challenge. A* Engl J Med 1976.294 hK7-90. 3 Weinstein 1.. Swart/ MN Pathogenic properue* of invading micro-orgjm*m* In Sodcman W'A Jr. Sodcman Wa eds Paihtdngu physiology nirrhanismj of diseuse Philadelphia. W' H Saunder*. 197a JS7-72