Document 5D2EbeDKdVEm9d57NXwbzJN6J

SD-32 (REV. 5-78) Shell Development Company Interoffice Memorandum FEBRUARY 23, 1984 --OV* -C-ooSSo*? ov-VC FROM:-.. . . V. L. KIRKLAND . TO: C. E. ROSS, D.O. SUBJECT: VINYL CHLORIDE (VC) - LIVER ANGIOSARCOMA REGISTRY A copy of the most recent update of the subject registry, which was received via CMA, is attached. As you will recall, the registry was maintained for many years by Dr. John Stafford of ICI. Following Dr. Stafford1s recent retirement, Dr. Brian Bennett, also of ICI, has assumed responsibility for continuing the registry. V. L. Kirkland VLK:sw Attachment ^ . cV-V \ Vs* cc: w/attachment S. R. Cowles, M.D. HS&E-IS (2) Tox Archives w/o attachment V. L. Sawin see 4-0907 CD r-*o c_o ro un CO TJ - CQ -n . o Co ZB ZO r- 9 m --i m CO m zc. co in < m ~~o rn -TD o <-> zo rn --i M-32 (REV. 5-76) OCo-C .. - Shell Oil Company Interoffice Memorandum FEBRUARY 7, 1984 FROM: TO: S. R. COWLES, M.D. --* file; . * :* SUBJECT: CMA-VCM MORTALITY STUDY UPDATE . ' **'**-**.' .... . -- - ~rn~n <r~i CD ' <-3 ; >o9 *cry - m tlmo ffo . . T 0 rrj A conference call on 3 February 1984 to discuss the EHA Phase II proposal for the VCM Mortality Study was arranged by Dr. Stack. Reason for this telephone conference was to allow Dr. Otto Wong, EHA to respond to comments submitted from participating companies regarding the Phase II proposal. DOW and Monsanto had submitted letters to CMA and Dr. Wong expressing reservations about the proposal, particularly the lack of detail regarding what hypotheses were to be tested by the study and what methods were to be used for analysis of the data. Dr. Wong has agreed to revise the proposal and submit an updated version to CMA and the participants in the conference call within the next week. Telephone approval to CMA will then be requested so that final approval can be rapidly obtained and the Phase II implementation can begin. <r. CnA Sally R. Cowles, M.D. SRC/sId cc: V ;*Kirkland R. E. Joyner C. E. Ross l 2 CN8403801 see 4-0908 CHEMICAL MANUFACTURERS ASSOCIATION V. .KrtfKLflNP To: VinyX Chloride Program Panel From: C. Stack d; October 18, 1984 Dr. Brian Bennett of ICI England recently visited the U.S. and met with Maury Johnson and myself. Dr. Bennett left materials which are enclosed. Included are comments on the Heldaas paper which appeared in the British Journal of Industrial Medicine. /rds Enclosures ce=n> ..n -o :o see 4-0912 Formerly Manufacturing Chemists Association--Serving the Chemical Industry Since 1872 2501 M Street. NW Washington, DC 20037 Telephone 202/887-1100 Telex 89617 (CMA WSH) PO Box No 6 Bessemer Road Welwyn Garden City Hertfordshire AL7 1HD Telephone Welwyn Garden 23400 (STD Code 07073) Telex 264251 From J Stafford Health & Environment Protection Imperial Chemical Industries PLC Petrochemicals and Plastics Division To Dr G M Paddle Dr K S Williamson Dr U G F Adams Dr B Bennett Dr J J O'Sullivan Dr A P Wright Dr J T Carter Dr P Mann Dr I Williams Dr D M J Williams Mr P N Anderson Mr J G Davies Mr A Moses Mr G Dupont Mr Per Rangnes Dr Heldaas Dr J P Tassignon Dr C Celia Dr T R Torkelson Tour ref Our ref JS/SEN/DSO-36 Tel ext 7535 Date 9 February 1983 VCM - MALIGNANT MELANOMAS \ Dr I F H Purchase has just drawn my attention to a very useful paper "Tumours in Control Hamsters, Rats & Mice: Literature Tabulation" by Sanford P Sher in the March 1982 number of "CRC Critical Reviews in Toxicology", pages 49 to 79. Melanomas and melanocytomas seem to occur spontaneously in hamsters and are not uncommon. Though they are mentioned in a number of the papers cited, the important,.'references would appear to be Fortner, J G \ Cancer Vol 10 page 1153 (1957) Fortner, J G Cancer Research Vol 21 page 1491 (1961) I have not read these papers but T shall obtain copies. In the 1961 Fortner paper, 4 melanomas were found in 94 male hamsters and 1 melanoma In 87 females. J Stafford uLL 4 - i'i 9 i_ 3 From G M Paddle To Dr B Bennett: Works Medical Adviser Hillhouse Works Imperial Chemicals Industries PLC Central Medical Group Alderley Park. Macclesfield Cheshire. SK10 4TJ Telephone : Alder-ley Edge (0625) 582332 Telex : 669095/669388 Copies.to Your ref BB/MO Our ref GMP/EJ Tel ext 248 Oate 27 Oct 1983 "INCIDENCE OF CANCER AMONG VC AND PVC WORKERS" HELDAAS et al Thank you for sending me a copy of the long-awaited paper by Heldaas et al. This paper cannot, of course, be evaluated without taking into account all the previous literature on VCM/PVC. It is just not reasonable to regard every 'significant1 finding in every new paper as an add-on effect of VCM/PVC. My immediate reaction is that this paper on its own is an unconvincing demonstration of excess risk for lung, colon, skin and thyroid; and that in the context of the evidence accumulated to date it is even less convincing. I do not doubt the thoroughness of the project, nor the honesty of the presentation, but I do think that the interpretation is rather naive. Detailed comments which you may use or ignore as you think fit are attached. G M Paddle 4 -r>q i a DETAILED COMMENTS .ON HELDAAS ET AL 1. ' The categorisation of jobs as high, medium and low exposure does not match the ICI pattern. Why are monomer production workers, maintenance workers and packaging/drying workers classified as high? 2. When the cases are classified by job, rather chan exposure level, there is little or no pattern to be seen in the records of the cancer cases. 3. Several of the key latent periods and exposure times are very short. 4. Table 6 does not seem to be accurate because the 23 cases listed include 2 not in. the 23 in Table 4. One case has both lung and thyroid but cannot have been analysed as both (or was it?) 5. Any study of this size will produce a mixture of cancer cases. Are the sites that are in excess more causatively plausible than those which must have been low? Why are the low ones not listed in fact? or G M Paddle 27 10 83 see 4-0915 Vj British Journal of Industrial} Medicine 1984-41 *'5-3(j Incidence of cancer among vinyl chloride and polyvinyl chloride) workers S STORETVEDTtHELDAASi1 S L^ANG^RD;1 AN A(ANDERSENQ From the Center/ ^Horsk Hydro a s P^orjgrunn--Fabrrkker^ 3900 .Porsgrunn, Tele-mark- Scrttrals- jukehus,'- Dvrpartintnt ofOccupational Mediant,-3-900-PofSgfwm, and CaAcer-Regisiry-of Nofyay,' hion- uMf^Osio J, Kitrwup. 9K'6 ca ..... _i?A14 abstract The results of a follow up study of the incidence of cancer and the mortality in a cohort of 454 male workers producing vinyl chloride and polyvinyl chloride are presented. The study population was restricted to employees with more than one year's work experience in the study . plant between 1950 and 1969 and the cohort was followed up from 1953 to the end of 1979. ^ Twenty three new cases of cancer were observed compared with 20-2 expected; one case of liver angiosarcoma was found. Five cases of lung cancer were found (2-8 expected) and four cases of malignant melanoma of the skin were observed (0-8 expected). The possibility of a causal rela tionship between exposure to vinyl chloride and the development of malignant melanomas is discussed. Since 1974 when Creech and Johnson presented their report,' human exposure to vinyl chloride (VCM) has been associated with the occurrence of angiosarcoma of the liver. Several studies have confirmed these initial results as reviewed by Spinas and Kaminski.2 In animal studies where VCM was given to mice. rats, and hamsters by different routes of administration neoplasms have also been induced in other organs.1 Whether VCM has the potency to induce cancer in man in organs other than the liver has not yet been confirmed. Lung cancer/"' brain tumours/"* and cancer in the digestive system, primarily angiosarcoma of the liver,1* have been suggested to be in excess in workers producing VCM and polyvinyl chloride (PVC), and the prime purpose of the present investigation was to study the incidence of cancer in workers exposed to VCM, with special emphasis on cancers other than liver tumours. Material and method PLANT DESCRIPTION The study plant is located in the county of Telemark in south east Norway. In addition to VCM and PVC the company produces fertilisers, magnesium, and chlorine in adjacent plant complexes. The produc Received 20 August 1982 Accepted 14 October 1982 tion of VCM and PVC was started in 1950. VCM was produced from acetylene in the room where the polymerisation reactors were located. In 1967 the VCM production was partly altered, and cracking of ethylenedichloride (EDC) was introduced as one of two production methods. The production of VCM was discontinued in 1971 after which time the plant was operated as a polymerisation unit. From 1955 onwards VCM and PVC were produced in separate rooms; table 1 shows the volume of VCM and PVC production and the number of employees over time. STUDY POPULATION A list containing the names of employees who had started work before the end of 1974 and whose period of employment had exceeded one month was constructed from the personnel register provided by the plant. The health department of the company has kept the health records of all present and previ ous workers employed from 1940 and onwards. These records also contain some information on the place of work of each employee. By combining these Table 1 Annual vinyl chloride and polyvinyl chloride production and number of employees in the smdy plant Work period VCAif (tons) 1950-33 1956-60 1961-70 a 1971 1000- 2500 1500- 5000 5000-30000 None PVC (tom) So of employers 1000- 2500 2500- 5000 5000-30000 30000-60000 45- 50 45- 90 90-130 120-130 25 4-! 26 Heldans, Lengbrd, and Andersen two sources of information a list of names was con- ufacturing plant before 1970 may have contained structed which was presumed to be complete. The 500ppm VCM or even higher concentrations." individual records contained the following informs- The plant was dosed for reconstruction in tion on each worker: full name, date of birth, iden- October 1974 and since 1975 the VCM in the work- tity numbeT, last known address, dates for beginning mg atmosphere has been monitored continuously and terminating employment, departments in the with automatic measuring devices, including alarm plant at which each person had worked, and the systems that want the workers during even minor duration of work in each department. Data were leakages. Since 1975 the VCM exposure level in obtained for 1233 workers. the production units has been below 1 ppm most of It was decided to restrict the analyses to male the lime. ' workers who had been employed for at least one year and who had first been employed at the plant JOB CLASSIFICATIONS before 1970. These limitations reduced the number Jobs considered to have been associated with high of subjects to 454. VCM exposure include production, autoclave clean- i tag, maintenance, and tapping. Owing to the great estimation OF EXPOSURE amounts of surplus monomer in the PVC, one may As a consequence of the technical design of the also assume that the exposure level in the packing plant and the process operation, the level of expos- unit may have been high until 1970. Those working ure to VCM in the past must have been high but no in the development laboratory which contained industrial hygiene survey had been performed small autoclaves in small rooms, in the control before 1974. Estimates of the gverage atmospheric laboratory, and at processing in the customers' ser- concentration in the past were "based on sporadic vice laboratory, may also have been heavily measurements that had been carried out with an exposed, but no information about VCM levels in "cxplosion-meier" which was graded from 0% to these working places is available. Nine different 100% of the estimated lower explosion limit; 1%, exposure categories were defined (table 2), a equivalent to 400 ppm of VCM. Two sources of number of the workers having been employed in supplementary information for estimating the VCM more than one exposure category. Membership of concentration were used: interviews with workers, an exposure category was defined as that category in some of whom had been employed in the plant since which the longest time had been spent. If an indi- the stan of production, and a suggested odouT vidual had been a production worker for some years, threshold of about 500 ppm VCM. Based on this and subsequently spent a greater number of years at information, we have assumed that the VCM con- a job that dearly entailed minimal exposure, he cemration was about 2000 ppm from 1950 to 1954, would by definition belong to a low exposure categ- about 1000 ppm from 1955 to 1959, about 500 ppm ory. from i960 to 1967, and about 100 ppm from 1968 As the exposure level was high in the early 1950s. to. 1974. During autoclave cleaning the exposure an attempt was also made to classify the jobs as level may have been as high as 3000 ppm.14 Both determined by the exposure level, using the number emulsion PVC and suspension PVC were produced, of "years of 500 ppm" exposure. The procedure was The surplus monomer in the PVC leaving the man- as follows: one year of production work in 1951. Table 2 Observed (O) and expected (E) deathsfrom all causes, and all new eases ofcancer in the study population except non-melanoma skin cancer Exposure categories No of workers 01 Vinyl chloride (acetylene) 02 Vinyl chloride (EDC) 03 Research laboratory 04 Polyvinvl chlonde production OS Autoclave cleaning 06 Maintenance 07 PacXin^drytng OS Customer* service laboratory 09 Various jobs Total 17 8 48 117 17 43 95 59 50 454 AH deaths O 1 2-41 0 0-50 2 4-32 19 16-42 5 3-04 4 7-64 5 6-44 7 8-77 7 7.80 50 59-34 O/E NC NC 0-46 116 1-64 0-52 0-59 0-80 0-98 0-84 A0 cancers O 0 0-81 1 0-20 Q 1-69 9 5-10 2 1-03 1 2-87 5 2-95 3 306 2 2-44 23 20-16 OlE NC NC NC 1-76 1-94 NC 1-69 0-98 0-82 1-14 Person-veers 1953-79 368-5 JlO-O 912-0 2308-5 309-5 868-0 1742-5 1065-5 971-5 8676-0 *NC Not calculated. ' .. * /, * 2 u p ti n n rr * u cc si l< b o FT ir d l" d i! p n h b i P t> ir ii i` j see Incidence of cancer among vinyl chloride and polyvinyl chloride workers 27 when. -the' working atmosphere contained about 2CJ0 ppm VCM on average, was classified as four *'500 ppm-ycars.'* The same type of work in 1961, vhen the atmosphere was about 500 ppm, would ivc one 500 ppm-year. This additional categorisa tion of exposure could be given for VCM produc tion. PVC production, autoclave cleaning, mainte nance work, and PVC packing. Owing to the surplus monomer in the resin, one year of packing PVC would give about one 500 ppm-year for each year up to 1970, and it is even possible that this high level continued until 1974. In this way high exposure for short periods in workers categorised by jobs with low exposure level could be accounted for. All workers were placed in an exposure category before we had any knowledge of their state of health or diagnoses. FOLLOW UP The main element of the method is to identify those individuals who meet the criteria for membership of the study population and to compare this population with a constructed Norwegian population whose age 'isiribution was identical with that of the study roup. (The method has been described in more detail by LangSrd ei al.n) Total mortality and cancer incidence from 1953 to the end of 1979 have been determined for the study population. The Cancer Registry in Norway has records of all new cases of cancer since J 953 and has access to information on all causes of death provided by the- Central Bureau of Statistics. This study is based on a comparison of observed and expected total mortality and incidence of cancer for the >eriod 1953-79. To estimate the expected number j{ cases of cancer, the national five year age specific incidence rates were used. According to the data of the Cancer Registry, the rates of cancer incidence in the Telemark county are between 0-90 and 0-95 of the national figures.11 Consequently, the more rob ust national rates could be used for reference pur poses and the expected number of deaths arc based on the national rates. Results Deaths from all causes and the number of new cases of cancer, excluding non-melanoma skin cancer, are presented in tabic 2. The number of person-years at risk is also shown together with a tabulation of the nine different exposure categories. Among 454 men there were 50 deaths from all causes (expected 59-3). During the 27 years of follow up, 23 new cases of cancer were found against 202 expected. The nine exposure categories have been combined into three groups reflecting high, medium, and low exposure (table 3); the increased incidence of cancer is . accounted for almost entirely by the high exposure group. There was only one liver angiosarcoma, recruited from exposure category 04, and this case has been included in a previous survey.1 Table 3 presents the observed and expected figures for some malignant neoplasms of interest. Five cases of lung cancer were observed in the whole study population compared with 2-8 expected. The mean time between first exposure and the time of diagnosis (latent period) in these five cases was 17-2 years (range 3-26) (not shown in the table). Four of the five cases were in the high exposure group (T82 expected). Four malignant melanomas of the skin were identified in the study population whereas only 0-8 was expected; three of the cases were observed in the high exposure group (0*5 expected). The tumours were located as follows: two on the trunk, one in the face-neck area, and one on a foot. After the observation period one more case has been diagnosed in the medium exposure group; this was in the face-neck area. We are aware of one case of incipient malignant melanoma located on the trunk '"able 3 Broad categories ofwork indicating exposure level. Observed (Of and expected () deaths from all causes, cases cancer (all sites), colon cancer (ICO 153), bronchial cancer (lCD 162/163). malignant melanoma of(he skin (JCD 190). and cancer of the thyroid gland (/CD 194). For work label, see table 2 Exposure te\et' Group 3 Total No of workers 29? 107 50 All cancers ICO 133 (CD 162/163 ICD 190 O / OtE O E OtE 0 OtE O * ICD 194 OtE O Person- 1933-75 OtE 18 12-96 1-4 3 3 4-75 0-6 0 2 2-44 0-8 0 0-92 3-3 4 0-34 NC 0 0-18 NC 1 1-82 2-2 3 0-67 NC 1 0-35 NC 0 0-51 3-9 2 0-18 NC 0 0-10 NC 0 0-11 18-2 5727-0 0-04 NC 1977-3 0-02 NC 971-3 23 20-16 1-1 3 M4 2-1 5 2-84 1-8 ' 4 ' 0-79 5-1 2 0-16 12-5 8676-0 'Group I (high vinyl chloride exposure) m Work labels 01. 02. 04. 05. 06. 07. Group 2 (medium vinyl chiondc exposure) " Work labels 03. 08. Group 3 {low vinyl chloride exposure) m Work label 09. SC Noi calculated. 28 Helda&s, Langbrd, and Andersen . Table 4 Observed (O)and expected (E) cases ofcancer (all sites), lung cancer (ICO 162(163). and malignant meianoma of the skin (ICD 190) in relation to time of fin/ employment in the plant Years of fra ffnplnyrrienl 1950-t 1955-9 1960-1 1965-9 Total So of workers 105 128 123 98 454 ' AO eoncers O 6 . 7-21 8 6-51 6 -403 3 2-12 23 - 20-16 O/E 0-8 1-2 1-4 1-4 0-8 1CD 1621103 O 2 1-01 2 0-94 0 039 l 0-29 5 2-84 ICD 190 O/E . O . 2-0 1 2-1 1 NC . 2 NC 0 0-23 025 019 0-12 1-8 4 - 079 O/E NC NC III NC M Person' yean 1933-79 2619-0 2717-0 2093-5 1246-5 8676-0 NC " Not calculated. Table 5 Observed (O) and expected (E) cases of cancer, ail sites, ofthe colon (ICD 133), of the lung (ICD 1621163), malignant melanoma of the skin (ICO 190). and cancer of the thyroid gland (ICD 194), by 500 ppm-year exposure index Nn of 300 ppm-years So of workers <1 1-5 >5 T.hi! 169 124 161 454 All cancers ICD 153 ICD 1621163 ICD 190 ICD 19* Person-years O O/E O O/E O E OlE O - O/E O E O/E 6 7-06 08 0 05) NC 2 3 3-10 1-0 1 021 NC 0 14 9-95 1-4 2 074 2-7 3 1-01 2-0 \ 029 NC 0 040 NC 0 016 NC 0 1-44 2-1 3 033 9-1 2 006 NC 3074-0 003 NC 2088-5 006 33-3. 35405 23 20-16 1-1 3 1-44 2 1 5 2-84 1-8 4 079 5 1 2 0 1 6 12-5 8676-0 NC " Not calculated. 'For classification of exposure for these cases see material and methods Table 6 Distribution of exposure categories among workers in tviiom cancer has been diagnosed (all cases ofcancer). Figures give duration ofexposure under different categories in years Aye when eoneer was diagnosed Time offirst employment Year of diagnosis ICD No* Exposure categories t 01 02 03 04 05 06 07 OS 09 63 67 62 67 55 56 63 67 58 54 56 70 26 45 38 451 40 4] 41i 66 62 33 55 1962 1964 1956 1962 1968 1950 1950 1952 1953 1938 1968 1930 1961 1952 1952 1933 1938 1961 1961 1964 1969 1957 1955 /'* ; ,/ 1979 1967 1972 1973 1977 1971 1963 1978 1977 1977 1971 1973 1967 1979 1957 1981 1960 1974 1977 1979 1972 i960 1966 131 151 153 153 153 155 162 162/177 162/194 162 162 177 178 181 190 190 190 190 190 190 193 194 199 2 11 5 II 22 3 7 11 2 14 4 2 3 6 4 5 6 10 10 29 IS 18 4 14 13 IS 3 2 MCD 15 J (stomach cancer). ICD 153 (colon cancer). ICD 155 (cancer of the biliary passages and liver). ICD 162/163 (lung and bronchial cancer). ICD 177 (cancer o( the prostate). ICD 178 (testis cancer). ICD 181 (bladder cancer). ICD 190 (malignanl melanoma of the skin). ICD 194 (cancer of the thyroid aland), t&aposurc categories corresponding wan the numbers in table 2. tThis case occurred after the end of observation period, ilneipiem case. i \ nc* . and grot The the ! sho\ wen T the case boO T of fi all c also cant the sho' amc high thar abo inch It r wor ppn one that indt mel T whe site: are mei also per. Dis canPV( acc-. bui mal PV< is o the can of i froi inc: v Incidence of cancer among vinyl chloride and potyvin l chloride workers 29 and diagno*eu'in 1977 from (he medium exposure cancer, as compared with 5-7 expected, in VCM group. This case has not been included in the study. workers with al least five years* exposure, who also The latent period for the four cases occurring during had been observed for 15 years or more after first : e follow up period was 8-8 years (range 2-28) (not exposure.* They also noted an unusual distribution iown in table 3). When the two additional cases in the histological type of lung cancer. Of the eight were included the latent period was 13-1 years. histologically confirmed cases, five were classified as Three cases of colonic cancer were observed in large cell undifferentiated. In our study two of the the high exposure group against 0*9 expected. Two cases of lung cancer were classified as oat cell car cases of cancer in the thyroid gland were observed; cinomas (small cell undifferentiated). Both occurred both were medullary carcinomas. in the high exposure group, and both patients had Table 4 shows the relationship between the date started work before 1959. As the numbers are small, of first employment in the plant and the incidence of no conclusions should be drawn, but in Norway,1* as Y all cancers and of some specific tumour sites. We in other countries.** only about 20% of all histologi- : also related the expected chance (risk) of developing cally classified lung tumours are listed as oat cell or cancer to the estimated weighed level of exposure, small cell carcinomas. Studies on populations occu the 500 ppm-year indicator, and these results are pationally exposed to arsenic, asbestos, chromium - shown in table 5. The highest risk ratios were found VI, radiation from uranium, and chloro^ among those workers who were characterised by methylether11 indicate that the proportion of oat high exposure--that is, those accumulating more cell lung cancers in these groups is much higher than five 500 ppm-years. We have no information than expected, and this suggests that attention about the VCM exposure level for the exposure should be paid to oat cell lung cancer in categories 03 and 08 (table 2). which arc classified in epidemiological studies on working populations. table 5 under the "less than one" index and which Buffler et al observed three deaths from lung cancer 'ncludes workers with less than one 500 ppm-year. (0-68 expected) in a subgroup of VCM exposed *t may be assumed, however, that some of these workers with more than five years' exposure at high workers were exposed to VCM levels of about 500 exposure level and a long observation period.' Fox ppm. Therefore, the correct exposure category for and Collier, on the other hand, could not show an one of the two cases of lung cancer under the "less increased risk of lung cancer in members of a cohort than one" index (table 5) could be the "one to five" recruited from different plants.4 They included all index. The same may be true for the one malignant exposed workers, laid down no requirements for melanoma under the "less than one" index. exposure minimum, and no minimum observation The plant employment history of all workers in period was accounted for. whom cancer has been diagnosed and the tumour In the present study the smoking habits of the sites, ranked according to ICD code (7th revision), members of cohort are not completely known. A tre presented in table 6. The year of first employ smoking questionnaire survey in the plant in 1980 ment and the age when cancer was diagnosed are showed that 53% of the workers were smokers, by also included. The previously mentioned latent contrast with 42% in the male population in the periods have been calculated from table 6. whole country in the same year.14 Consequently, it does not seem likely that smoking as a confounding Discussion factor can explain the differences in the incidence of cancer." The present investigation has shown an increased Maltoni et al have indicated that VCM is a mul- incidence of malignant melanomas of the skin, lung tipotent carcinogen in mice, rats, and golden hams anccr. colonic cancer, and thyroid cancer in VCM/ ters.' They also showed skin tumours in golden ham PVC workers. Our observation on lung cancers is in sters, some of which were malignant melanomas. In accordance with the results of several other studies a study of the kinetics and organ distribution of but to our knowledge, an increased incidence of VCM in which rats were exposed to "C-VCM by malignant melanomas in worker* producing VCMI inhalation. Duprat et al showed "a great deaf of PVC has not been shown before. The present study labelled molecules probably both VCM and its is one on the incidence of cancer, by contrast with metabolites'* in the skin after three hours." In a the other investigations which refer to deaths from similar study Watnabe a al confirmed these cancer. If the percentage survival in diagnosed cases results." None of these authors discussed the of malignant melanoma is high, studies on deaths significance of the distribution of VCM to the skin, from cancer may have masked a possible increased however. incidence of this tumour. Malignant melanoma of the skin is believed to be Waxweiler et al observed 11 deaths from lung associated with exposure to sunlight" and few occu- 30 - Heldaas, Lang&rd, and Andersen pations have been associated with the development thens the suggested association between VCM of these tumours. Tear gas (e-chloroaceiophenonc) exposure and these types of cancers, in particular - and polychlorinated biphenyls** are chemicals that the malignant melanomas. have been suggested as possible inducers. In our study population one more case of melanoma has been diagnosed after the closure of the study and before the increased incidence of tumour was known to us. This additional case considerably strengthens the association between exposure to VCM and the We thank the Plastic Division of Norsk Hydro a s for cooperation throughout the study. O C BSckman's critical comments were of great help. We thank Mrs P A Flor for linguistic help and Mrs U Danielsen for typing the manuscript. ' development of malignant melanomas. As the medi-cal services in the Telemark county have been of a `high quality and easily accessible, we do not believe References v * Creed) JL. Johnson MN. Angiosarcoma of Ever in the manufac ture of polyvinyl chloride. JOM 1974;16:150-1. . that there has been any bias due to the presence of * Spinas R. lUminki. R. Angiosarcoma of the liver h vinyl the occupational health service in the company. In . fact, none of the four cases was diagnosed by the occupational physicians. One of the five subjects chloride/polyvinyl dtloridc workers. 1977 update of the Ml OSH register. JOM 1978;20:427-9. * Mahoni C, Lefcmine C. Glibcrti A. Coni G. Carrctti O. Car* rinogenidty bioaasays of vinyl chloride monomer, a model of with skin cancer had survived until June 1982, The risk assessment on an experimental basis. Environ Health incidence of malignant melanomas in the rural areas of Telemark county is slightly higher than the national rate, while the incidence in urban areas is Perspea 1981;41:2-29. * Monson RR. Peters JM. Johnson MN. Proportional mortality among vinyl<hloride workers. Lancet 1974;n:397-8. * Tabenhaw 1R. Gaffey WR. Mortality study of workers in the fairly equal to the national rate.1* All subjects with manufacture of vinyl chloride and its polymers. JOM skin cancer had lived in the urban area. We observed two cancers of the thyroid gland (0-16 expected): both cases occurred in the high exposure group and were of the same histological 1974;16:509-18. * Waxweiler RJ. Stringer W. Wagoner JK. Jones J. Falk H. Carter G Neoplastic risk among workers exposed to vinyl chloride. Am NY Acad Set 1976:271:40-8. 1 Butter PA, Wood S. Eifter C. Suarez 1_ Kitian DJ. Mortality type. We arc not aware of other studies indicating an excess of this type of cancer but as only two cases have been observed, no conclusions can be drawn. experience of workers in a vinyl chloride monomer production plant. JOM 1979;21:195-202. * Fox AJ. Collier PF. Mortality experience of workers exposed to vinyl chloride monomer in the manufacture of polyvinyl In a Canadian study on workers exposed to VCM chloride in Great Britain. Br J Jnd Med 1977;54:1-10. for five years or more Theriault and Allard showed an excess of cancer in the digestive system,* but the authors concluded that the excess is accounted for * Thdnaulc G. Allard P. Cancer mortality of a group of Canadian workers exposed to vinyl chloride monomer. JOM 198103:671-6. ** Barnes AW. Vinyl chloride and the production of PVC. Proceed exclusively by cancer of the liver. In the present Study we found a slight excess of cancer of the colon. Many of the other studies referred to include cancer of the liver in digestive cancers, and they conclude ings of die Royal Society of Medidne 1976;69:277-81. " Karstad: M. PVC: health implications and production trends. Environ Health Pertpea 1976;17:107-15. u Langlrd S. Andersen Am, Gylseth B. Incidence of cancer among (crrochromium and ferroailicon workers. Br J Ind Med that the excess risk is due to this tumour. There are 198037:114-20. few reports on occupationally induced cancer of the colon and rectum although it has been indicated that asbestos workers, textile workers, and steel workers Cancer Registry of Norway. Incidence of cancer in Norway 1972-1976. Oslo: The Norwegian Cancer Sodety. 1978. ** Kvkle G. Johansen Aa. Lungetrefi i Norge: enovenikt basen pi Kreftregistereu materiak. Tidiskr Nor Laegrfoten have an increased risk from these diseases.11 Watnabe el al in their kinetic study showed some faecal elimination of ,4C after the inhalation of ,4C-VCM. but they discuss only urinary and pulmonary elimi 1982:102:480-4. '* Wcgman DH. Peters JM. Oat cell lung cancer in selected ocrupa* lions: a case-control study. JOM 197830:793-6. w Axelson O. Aspects on confounding in occupational health epidemiology. Scand J Work Environ Health 1978;4:85-9. nation in their paper.1* The results presented in,the present study, consi dered with other epidemiological studies, seem to support the view that VCM may act as a multicar ,T Duprat P, Fabry JP. Gradiski D. Magadur JL- Metabolic approach to industrial poisoning: blood kinetics and distribu tion of l4C-vinylchloride monomer (VCM). Acta Pharmacol Toxicol 1977:41. suppl 1:142-5. * Watanabc PG, McGowan GR. Madrid EO. Gehring PJ. Fate of cinogen in man. This ij in accordance with observa ['`C] vinyl chloride following inhalation exposure in rift. Tox tions from animal studies.* Some of our findings dif fer from those presented by other workers, and will be followed up later. The observation period is short icol Appl Pharmacol 197637:49--59. " Magnus K. Habits of sun exposure and risk of malignant melanoma: an analysis of incidence rates in Norway 1955"1977 by cohort, sex. age and primary rumor site. Cancer for some of the members of the cohort, and the study group is small. Nevertheless, the fact that the excess of different cancers was seen in the group with the highest estimated exposure level streng- 1981:48:2329-35. w Sober AJ. Fitzpatrick TB. Generic and environmental favors of malignant melanoma in man. Pigment Celt 1979:5:88-94. " Jansson B. Colorectal cancer--an occupational disease? Gas troenterology 1978:75:321--3. ri; - Ni Fid/ Ox; ab: hvt car car exj she of u.n wo 1 <P4 all>. ad as : 1 tier car Cc inc po: on 53l` ctn da' leu tin ph. pci adi dci i sic Re Ac