Document DGYJJw0zVnnxYzGp64YzrmJra

t 1 354 British Journal of Industrial Mediant 1992;49:134-137 Exposure to vinyl chloride monomer: results of a cohort study after a seven year follow up Agnes Laplanche, Fran?oise Ciavel-Chapelon, Jean-Claude Comassot, Claudine Lanouziere, and the French VCM group (see end) Exposure Table 1 1 Non-expot, Exposed si: Exposed < Exposed ? Twoavbir 1Ad)mted i Abstract In 1980 a prospective cohort study of exposed and non-exposed subjects was initiated in France by the Instirut National de la Santi et de la Recherche Medicale (INSHRM U2S7) in collaboration with occupational physicians from the companies involved. The aim was to evaluate the association between mortality and cancer morbidity and occupational exposure to vinyl chloride monomer (VCM). A total of 1100 subjects exposed to VCM and 1100 nonexposed controls matched for age (to two years), plant, and physician were followed up for seven years (299 and 202 person years for exposed subjects and controls respectively) for vital status and health and occupational state. Forty deaths occurred among exposed and 43 among non-exposed subjects (relative risk (RR) = 1*0; 95% confidence interval (99% Cl) 0*6-1 *5). Forty eight and 32 cases of cancer were reported among exposed and non-exposed subjects, respectively (RR ** 1*3; 95% Cl 0*82*1). Three cases of angiosarcoma of the liver occurred in the exposed group. Eight cases of lung cancer occurred among exposed subjects and six among non-exposed subjects. Fourteen cases of Raynaud's disease were found among exposed and one among non-exposed subjects and the difference was significant. One hundred and twenty three and 93 cases of cardio vascular disease (Raynaud's disease excluded) occurred in the exposed and non-exposed Dcpartemeot de Biostatistique et d'Epideiniologie, lnstitut Gustave Roussy, 94805 Villejuif, France A Laplanche Unite de Recherche 287 1NSERM, lnstitut Gustave Roussy, 94805 Villejuif, France F CJavel-Chapelon Medecine du travail, ATOCHEM, 69191 St-Fons, France J-C Contassot Medecine du travail, Solvay et Cic, 39500 Tavaux, France C Lanouziere groups respectively (RR 1*4; 95% Cl TO-1-8); this difference was mainly due to hypertension. The test for an increasing risk with increased exposure was significant. The percentages of diseases of the respiratory system did not differ between the two groups (RR = 1*1; 95% Cl 0-7-1-8). In 1980, s prospective cohort study of workers exposed to vinyl chloride monomer (VCM) and nonexposed workers was initiated by the lnstitut National de la Same et de la Recherche Medicale (INSERM U 287) in collaboration with occupational physicians from the different companies involved in France. The main purpose of this study was to evaluate the association between mortality and mor bidity (especially malignant tumours) and occupational exposure to VCM. This paper presents the health characteristics of the cohort after a seven year follow up. Materials and methods The design of the study has been described previously.1 Briefly, the exposed group consisted of 40 to 55 year old employees exposed to VCM at the time of inclusion in 1980-1 or previously. Controls were employees who had never been exposed to VCM. Each control was matched to one exposed subject for age (to two years), plant, and physician, Interviews for initial data collection were conducted by the physician of each plant over a one year period. Data collected comprised the following information: identification, employment history' (the entire work history was coded), occupational category, dates of exposure to VCM, and medical history as well as smoking and drinking habits. The subjects were followed up yearly for seven years from the time of inclusion until December 1988 for vital status and health and occupational state. Causes of death as well as pathological findings were coded according to the 9th revision of the International Classification of Diseases (ICD-9). Subjects who had terminated V ;* .* T " ^ jf jj j; j. f* ^ y j VC6194 V a*1 Table 2 All cause, Canee: Greulau Smoots Trauma, Alcohol Others Unknou their err, retired) \ Relati* with nor. (all cauS' ease (Ra disease, the srud> ing that * (cominu worker ( state, (m resiaenct history other di; orex-sm duration ethyli c t alcohol t glasses), to wheth or more Table 5 year folio Non-expo Exposed a Exposed Exposed ; Nine sut tSee footr -S); ion. iscd s of .ffer Cl kers ^03UTUZ s 10 Tiorand SDI5 even ibed .d of : the :rol$ d to osed C1ZT-. :ctfd DOC. :ior*: vork es of ]] 5 .vere ie of we1! > Lie r. of Slid Exposure to vinyl chloride monomer: results of a cohort study after a seven yearfollow up 135 Table 3 Relation between exposure to vinyl chloride and deaths during the seven yearfollow up txeths dunng follow up Yei In rn S3) Non-exposed Exposed after > 976 Exposed < 10 y before 1976 Exposed > 10 y before 1976 43 4 is 21 +Two subjects were tost to follow up. tAdjusted for iniuft) chvsctensues defined in Materials tod io(Wdi. Ne (t - 21)1) 1056 68 405 566 RR5 (95% Cl) 1-0 1-04 (0-3--3 2) 0-94 (0-5-1 -7) 0-99 (0-6-1 -7) Table 2 Couses of death during the seven year fallots up Expend U0p9j Controls (3099; years before 1976, or exposed after 1976. The data were verified using the FIGAS system5 and analysed with the GLIM package.5 All cause* Cancer Circulatory svsiem Suicide* Traumas Alcohol Others Unknown 40 20 9 2 2 3 3 5 41 22 To 4 0 3 0 4 their employment (resigned, been transferred, or retired) were followed up by each physician by mail. Relative risks (RRs) among exposed compared with non-exposed subjects, are presented for death (all causes), malignant tumour, cardiovascular dis ease (Raynaud's disease excluded), and pulmonary disease. Subjects with a disease at the beginning of the study were excluded from comparisons concern ing that disease. Relative risks were adjusted for age (continuous), duration of activity as a blue collar worker (continuous), foreign origin (yes/no), marital state, (married, single, widowed, divorced), place of residence (urban or rural), paternal or maternal history1 of cancer, cardiovascular, respiratory, or other disease, smoking habits (non-smoker, current or ex-smoker, number of daily cigarettes, (< or 20) duration (< or >25 years)), subject considered ethylic by the plant physician (yes,/no), and weekly alcohol consumption (<14, 14-56, 57-112, >112 glasses). Relative risks were also expressed according to whether the workers were exposed to VCM for 10 or more years before 1976, exposed for less than 10 Results The study population included 1100 exposed and 1100 controls in 12 plants, and has been described elsewhere.14 The follow up of the two groups was similar. In 1990 the number of person years was 8299 and 8202 and the number of subjects lost to follow up were 2% and 1% in the exposed and non-exposed groups respectively. MORTALITY During the seven year follow up, 40 and 43 deaths were reported in the exposed and non-exposed groups, respectively (RR = 1 '0; 95% Cl 0-6-1 -5). Table 1 gives the RRs according to the different levels of exposure. None of the risks differed significantly from unity. Table 2 presents the main causes of death. MORBIDITY Exposure to VCM increased the risk of malignant tumour (1CD-9 140-208) slightly but not sig nificantly (RR = 1-3; 95% Cl 0-8-2-1). Table 3 shows the relation between the different categories of exposure to VCM and the occurrence of malignant tumour. Table 4 presents the distribution of the 70 sites of malignant tumours. Three cases of angio sarcoma of the liver occurred in the exposed group, but no cases of skin melanoma or malignant brain TabU 3 Relation between exposure to vinyl chloride and occurence of malignant tumours (/CO-9 J40-208) during the seven yearfollow up Malignant tumours* Yes In 70) No (n - 2119) RRK 95% Cl) Non-exposed Exposed afier 1976 Exposed < 10 v before 1976 Exposed > 10 y before 1976 32 1061 10 3 69 1-4 (0-4--4-9) J4 404 1 -2 (0-6-2-4) 21 585 1-3 (0-7-2-3) 'Nine subjects had a malignant tumour ar entry to the study (three among exposed subjects and six among controls). 7 See footnote to table 1. VC6195 o 136 Laplonche, Clavel-Chapeion, Contassot, Lanouxiete Table 4 Types and numbers of malignant tumours found during the seven year follow up _________ _____ Exposed (10991 Controls U099) All sites (ICD-9 140-208) Lip mouth pharynx (140-149) Digestive orpins (150-159): Oesophagus Stomach Small intestine Colon rectum Liver angiosarcoma Liver Pancreas Digestive non-specific Larynx (161) Lung (162) Bone (170) Connective tissue (171) Melanoma of skin (172) Other skin (173) Testis penis 086-1B7) Bladder kidney (186-189) Endocrine (194) Lymphohematopoietic (200-208) Secondary (196-198) Primary silt uncertain (199) 38 1 ii i 2 ] 5 3 3 0 0 2 8 1 1 0 5 1 2 i 1 1 1 32* 5 12 1 1 0 6 0 0 2 2 2 6 1 0 1 ] 1 3 0 2 0 2 Subject! without malignant tumours at initial examination (No of subjects at nth): exposed 1096, controls 1095. *Tht total exceeds 32 at fout subjects exhibited two primary oncers. tumour. Fourteen lung cancer cases were reported, eight in the exposed and six in the non-exposed group. One case of lymphoma was seen in the exposed and two cases in the non-exposed group. The risk associated with the onset of diseases of the circulatory system (Raynaud's disease excluded) (ICD-9 390-459) was significantly higher than unity (RR = 1-4; 95% Cl 1-0-1-8; p < 0-05). Moreover, an increased exposure to VCM was significantly (p = 0-02) associated with increased incidence of cardiovascular diseases (table 5). One hundred and twenty three and 93 cases of diseases of the cir culatory system were noted in the exposed group and controls respectively. Table 6 presents the types of cardiovascular diseases. Fourteen cases of Raynaud's disease were seen in the exposed and one in the nonexposed group (p < 0-01). The occurrence of diseases of the respiratory system (1CD-9 460-519) did not differ between the two groups (RR = M; 95% Cl 0-7-1-8). None of Table 6 Type of cardiovascular disease (Raynaud's disease excludedI found during the seven yearfoliate up Exposed 0099! Controls 0099) No of subiecu at risk* Circulatory system (390--459) Hypertension (401-405) Corunarv insufficiency (4)0-4) 4) Mvwardisl infarction (410) Cerebral visculsr disorders (430-43B) Arteriosclerosis of limbs (4476,4479,4402) Other circulatory disorders 933 123t 55 30 21 E 9 27 955 93T 34 28 16 10 15 'Subjects without s circulstory disease at iht initial examination. tTht total exceeds 123 and 93 at tome subjects exhibited two or more circulatory diseases. the risks significantly differed from unity when dif ferent degrees of exposure were considered (table 7). Discussion In our study, no relation was found for the occurrence of malignant tumour or respiratory dis eases and exposure, whereas an increased risk of cardiovascular diseases was seen in the group exposed to VCM compared with the non-exposed group. With respect to cancer, the risk of angiosarcoma of the liver has been well documented since 1974. This was confirmed in our study although only three cases were found. During the same period 14 cases of angiosarcoma of the liver were registered in France. This discrepancy can be explained by the limited size of our cohort as well as the selection of the plants and exposed group. Our results showing a lack of relation between exposure to VCM and other cancers agree with others." The IARC study,* which pooled data from Great Britain, Italy, Norway and Sweden totalling 222 746 person years, did not show any positive evidence that a particular malignant disease was a hazard either. Our findings for the control group are in agreement with French statistics of incidence of cancer* in the same age groups, as 32 cases of malignant tumours were observed, corresponding to an annual incidence rate of 390 per 100 000. Table 5 Relation between exposure to vinyl chloride and occurrence of cardiovascular disease (except Raynaud's disease) (ICD-9 39Q-4S9) during the seven yearfollow up Cardiovascular distant* Yet (n - 216) No (n - 1672) RR1 (9SK Cl) Non-exposed Exposed after 1976 Exposed < 10 y before 1976 Exposed 10 y before 1976 93 862 10 7 63 0-8 (0-4-1-9) 46 327 1-3 (0-9-1-9) 70 420 1-5 (11-21) Three hundred and ten subjects hid a cardiovascular ditease ai entry in the study (166 among exposed and 144 among controls). TSee footnote to table 1. Exposure Table 7 sevenyeo Non-expo Exposed a Exposed Exposed : One hun tSee footr An respiratand pol study, : disease \ exposed maligna exposur By ar bydroca infarcti' publish increase In our cardiov. noticed, was ay abnorm (0 a var; venous lack of explana; tension thisrela that inc Raynau exposed estimate The dii disease ; worker t phenorr. estimati To st VCM, before ; exposur tation Measur workshc of expopared v duratioi before t years be high ex; Exposure to vinyl chloride monomer: results 0/ a cohort study after a tevenyearjolioa up 137 Table 7 Relation between exposure to vinyl chloride and occurrence of pulmonary disease (1CD~9 460-519) during the seven yearfollow up period Pulmonary diseases* Yu (n - 12) Ne In m 191S) RR1 (9551 Cl) Non-ex posed xpo*ed liter 1976 Exposed < 10 y before 1976 Expoied * 10 v before 1976 37 952 1-0 8 61 1-3 (0-5-3-5) 18 381 1 2 (0-6-21) 19 524 10 (0-6-1-9) 'One hundred end ninety eight tubieeti hid 1 pulmoniry diteut it entry to the trudv (88 imong expoied ind 110 imong contrail). tSee footnote to table 1. An increased occurrence of non-malignant hazards related to the exposure to VCM. Apan from respiratory disease as a result of exposure 10 VCM these diseases, the evidence indicates that the risks and polyvinyl chloride dust has been cited. In our associated with exposure to VCM, in terms of both study, morbidity- from non-malignant respiratory mortality and as morbidity, are probably negligible. disease was not different among the exposed and nonexposed group. Also the incidence of death from nonmalignant respiratory' disease was not affected by exposure to VCM in two other recent studies.*1 By analogy with the effect of other halogenated hydrocarbons, an increased risk of myocardial French VCM group: Drs Aubrun, Barrat, Baylac, Bellec, Paris, Quelin, Rambaud, and Richard (Rhone-Poulenc); Drs Bennech, Cestin, Favre, Leveque, Lussato, Puech, Rery, and Ruty (ATOCHEM). infarction has been suspected* with, however, little Requests for reprints to: Dr Agnes Laplanche, published evidence. One study111 showed a slight Departement de Biostatistique et d'Bpidemiologie, sea increase in mortality due to ischaemic heart disease. Institut Gustave Roussy, Rue Camille Desmoulins, In our study, although a linear increase in risk of 94805 Villejuif Cedex, France. 2 of cardiovascular diseases with increased exposure was noticed, no association with myocardial infarction } Laplanche A, Gavel F, Contassot JC, Lanouziere C, Exposure to vinv) chloride monomer: report on a cohort study, Br J Ind was apparent. The increase in cardiovascular Med 1987;44:711-5. of abnormalities is mainly due to hypertension but also 2 Wartelle M, Kramar A, Jan P, */ ol. PJGAS. an interactive statistical database management system. In: Proceeding oj the to a variety of other circulatory problems including second international taorkshop on statistical database manage^ venous disorders, arythmia, and valvopathy. This lack of precision makes it difficult to provide an men*. Los Altos, CA:J 983;] 24-32. 3 Baker RJ, Nelder JA, The GUM system, release 3,77. Oxford: Numerical Algorithm Group press, 1985. !l E^ 3 explanation for our positive result. The excess hyper tension could be explained by the shift work," but this relation has never been found, not even in a study that included 15 000 workers." With respect to Raynaud's disease, 14 cases were seen among the exposed workers (0-2%); this rate is lower than that estimated for the general population--namely. 4%.1! 4 Gavel F, Laplanche A, Contassot JP, Lanouziere C. Exposure to vinyl chloride monomer: Report on a 7-year follow-up cohort study. In: 23rd International Congress on Occupational Health. Montreal, Canada: M Cusson, 22-26 September 1990. (abstract 278.) 5 Simonato L, L'Abbe K.A, Andersen A, ts oh A collaborative study of cancer incidence and mortality among vinv) chloride workers. Stand J Work Environ Health 1991;17:159-69. 6 Doll R. Effects of exposure to vinyl chloride. An assessment of evidence. Stand J Work Environ Health 1988;] 4:61-76. The difference can be explained because (1) the disease affects women more than men, (2) a healthy worker effect may exist, and (3) the cases ofRaynaud's phenomenon have perhaps been included in the estimation for the general population. 7 Jones R, Smith D, Thomas P. A mortality study of vinyl chloride monomer workers employed in the United Kingdom in 19401974. Stand J Work Environ Health 19BS;14:J 53--60. 6 Wu W, Sieenltnd K, Brown D, Wells V, Jones J, Schulte T,etah Cohort and case-control analyses of workers exposed to vinyl chloride: an update. J Ottup Med 1989;31:518-23. 9Benhamou E, Laplanche A, Wartelle M, Faivre j, Gignoux M, To study the effect of the degree of exposure to VCM, we decided to take into account exposure Menegoz F, Robillard J, Schaffer P, Schraub $, Flamant R. Incidence des canters en France, 1976*1982. Paris: editions INSERM, 1990. before and after 1976. This was the year when exposure to VCM was reduced due to the implemen tation of the 1975 French legislation.14 Measurements of exposure on workers, or in the workshops themselves, were not available and doses 10 Grciscr E, Rein! W, Weber H. Vmylchlorid-cxposition und mortalitat deutscher chemiearbeitcr im vergleich *ur mor* tahtat nichtexponicrter ehemiearbciier und PVC*verarbciter. Praphybxe und Ergonomic ] 982;32:44-62. 11 De Gaudemans R, Monzie A, Battisieila P, Sichc JP, Mallion JM. Pression arrerielle et activite* de travail pone. Archive* des Maladies Prafessionnelles l9B8'f49:5-9, of exposure before 1976 were extremely high com pared with doses after 1976." For these reasons, the 12 Perroud D. Travail posts, tension ortiriellc, corpulence et tabagitme. Lyon: these de Mcdccine, 1983. 13 Bayle O, Consoli SM, Baudm M, Vayssairat M, Fietsinger JN, duration of exposure to VCM was only considered before this date and periods of less or more than 10 years before 1976 were taken as thresholds of low or high exposure. Housset E, Phenomene de Raynaud idiopathique et secondaire. La Pretse Midicolt 1990;19:741-5. 14 Reglement d'administration publjque relatif aux mesures de protection des travailleurs centre les risque* presentes par le chlorure de vinyle monomere. Journal Officiel, Decret n 80-203 du 12 mars 1960. In conclusion, angiosarcoma of the liver and Raynaud's phenomenon seem to be the major 15 Contassot JC. Chlorate de vinyle. Paris: Encyclopedic MedicoChinirgicale, 9-1990. Accepted 8 July 1991 __ VC6197