Document ZJwr9m2LoQDq5b7Bb89wrqOe0

R&S 107809 BIO-MEDICAL.RESEARCH " DOCUMENT DESCRIPTION FORM 63 Duplicate in all cards:--^ 68 69 ,, 76 00 CO 11)1 year as-1961- File number [Right justify [Numeric only] Author(s), as Last Name FS (No Punctuation) and coden for journal as JAMA preceeded by one blank space 1 20 21 40 41 /-' /'! t /(S-, '> 11 r L /// /r 7778 i (' Sub-Index Code 60 61 62 11 12 13 Title of Report; end with space-hyphen-hyphen-space. Follow with Index Terms > separated from each other with comma-space. Avoid other punctuation; do not abbreviate. . V* _ /. //, ,, , L.-_, -.-s-cSj /, , : .C,- ,' c C --t-t-.'-'r-. {'S 1 t-i i is*A' ' / 21 'i. 22 23 24 Source (Journal, Vol., Number, Pages, Date ) 61 62 31 32 Brief Summary 12 10 SUMMARY: 61 62 61 62 63 64 .V,U- yti Id J^X R&S 107810 000O(f/ CONSIDERATIONS IN THE DECISION OF THE SWEDISH OCCUPATIONAL STANDARD FOR VCM. Ms for report on panel "Internotionol differences in decision-making on environmcntol controls. Case study: Vinyl chloride." at the International Conference on the Public Health Control of Environmental Hazards, New York Academy of Sciences, June 29, I97Q. by DO HOLMBERG and ARNE WES TUN National Board of Occupational Safety and Health P.0. Box., S-100 26 STOCKHOLM, Sweden. Duckgrouml *- Pol/vinyl chloride (PVC) was first synthesized in the laboratory in Sweden during World War II. Vinyl chloride monomer (VCM) was made conventionol1y by adding hydrogen chloride to acetylene over a fixed bed catalyst containing mercury salt. At the end of the war, pilot plants were operating and market research was carried out by two Swedish companies. One of these, later named Kcma (lord or Kemu Nobel, started commercial production shortly after the war and is still manufacturing both VCM and PVC. VCM v/as considered a rather harmless gas in the fourties in Sweden, as well as elsewhere, and it may certainly he assumed that workers'exposure to VCM was badly controlled. Tire exposure showed probably a great variation from time to time and was generally very high during the first decade of production. Hygienic control was hampered by lack of good analytical techniques in that range of concentration which is of most interest from the hygienic point of view. However, it has been estimated that the exposure may have been several hundred ppm as a time-weighted average for an 0-hour work day. Occasionally 1000 ppm may hove been exceeded for hours and it happened that concentrations were around or above the lov/cr explosion limit. In the mid-sixties, the exposure was controlled to a highest level of 500 ppm according to recommendations from the authorities, the figure obviously emanating from the ACGIII TLV list. These recommendations were later decreased in steps down to 200 and 50 ppm (1972) partly due to the anxiety aroused by the reports on cases of acroosLcolysis. Actual exposure for most work places where VCM was handled in early 1974, when the great concern for VCM as a carcinogen arose, was around 30 ppm. R&S 107811 The situation for the workers cleaning autoclaves merits special attention. Although the reactors were ventilated before cleaners entered, these workers must have been heavily exposed. Compressed air gas masks were used from I960 and on, but for some years during the sixties the use of such masks was not mandatory. After directives from the aut horities they were generally used from about 1970 and on. The VCM exposed group of workers (population at risk) in - "'"the-whole PVC polymerization industry up to 1974 in Sweden may be approximated to be about 1000. Due to.rationalized production the work force today is around 250 for an annual production of about 150 000 tons PVC in a total of two plants. Most of this quantity is used by the fabricator industries in Sweden. The number of workers in the fabricator plants is today about 6000, as compared to a total labour force in the country of about 4 million. It may be appropriate at this point to remind of the organiza tion of the Swedish National Board of Occupational Safety and Health (MB05II). MB.0SII is comparable to the IJS authorities NIOSH and OSIIA, taken together and organized under the Ministry of Labour. The Board of NOOSH has eleven members only, two oT which arc civil servants, namely the president and the vice president of the Board, who are at the same time general director and vice director of NGOSH. Of the other members four come from the employees, three from the employers and two from the parliament. One employer represents the public employers (state and commune) and of the politicians one comes from the present political opposition party. Besides being ruled mainly by laymen NB0SII has good connec tions wi tli the interested main parties on the labour market. It should be pointed out furthermore, that all draft rules and regulation are thoroughly discussed with the labour R&S 107812 unions and employers primarily involved before brought up for final decision by the yenercil director or by the Board. The proposed standard for VCU was also treated in this participatory manner. R&S 107813 R&S 107814 Oiologicoi considcrolions . - llic es tabl i shiny of a permissible level of occupational exposure to VCM involves Ihcorclical difficulties as concerns the extrapolation from large doses to small doses within the same population studied (whether it is a mouse model or a group of occupationally exposed men). A'few extrapolation models ore at hand, as reviewed by Sclineiderman ct al (1), but no one can, on the present state of knowledge, tell which mathematical model is the true one to use for extrapolation from high doses to low doses for human dosc-rcsponsda la. Unfortuna tely, very few comparisons (2) of dose-response curves based upon animal and human studies for the same chemical can presently be made. By using dose-response data from Maltoni's experiment Schnciderman at al (1) extrapolated mouse data to the low dose range and found that 1 ppm VCM inhaled during 4 hours at day, 5 days a week for 52 weeks would probably cause less than one Swiss mouse having a liver hemangiosarcoma out of 10 000. Nov/, this extrapolation did only consider hemangiosarcoma of the liver, a tumour type which in fact v/as in minority (3,4) among the hemangiosorcomas in the mouse and more so when all tumour types are considered. Studies (5,6) on VCM exposed workers support the idea that ' VCM is a multipotential carcinogen also for human popula tions as it is for rodents. This means that extrapolations should ideally include all tumour types and not only liver hemangiosorcomas. In Maltoni's experiment (3) the Swiss mice inhaling 50 ppm did get a life exposure dose of 50 ppm x 4 hours x 5 days x 52 weeks = 52 000 ppm x hours. This is to be compared with the exposure for a PVC worker at a supposed TV/A level of 20 ppm giving u yearly dose of 20 pprn x 0 hours x 5 clays x 40 weeks = 30 400 ppm x hours. Added to that, the worker might be exposed to other chemicals, such as tobacco smoko, alcohol or drugs, compounds which moy contribute to the cancer risk. We don't know whether 1 ppm (jives o risk above or under 1 in 10 000 among occupationally exposed men. There were no dose data at hand for VCM exposure in the VCM and PVC producing industries. No extrapolation model can thus be applied to human datu. In many instances, witnesses dcclored that the victims of the VCM exposure occasionally have had high levels of exposure in their previous working history (7). It might, however, be thot high levels of exposure to a carcinogen for short time periods do involve a .proportionally smaller risk than low levels of exposure during a longer time. Dota obtained with polycyclic hydrocarbons (0) and with nitrosamines (?) seem to indicate that low levels are more effective than high levels, and this is discussed also for other carcinogenic agens (10). An important biological information at the time of the decision of having a low Swedish occupa l ional standard for VCM was that Maitoni (11) reported tumours in all tested species and particularly that 30 ppm, A hours a day, 5 days weekly for 52 weeks caused 2 % nephroblastomas. 2 % angio sarcomas and some other tumours in Swiss mice. The Swiss mouse might be regarded as being more sensitive towards VCM than the human, but a very important additional biological information relevant to the decision of the Swedish VCM standard was that liver tumour cases were reported to have occurred also among PVC fabricator work men (12). No dose data Tor previous exposures were at hand fo.r the PVC fabricators cither, but certainly most or even all the fabricator industries in Sweden have had an average level of less than 20and probably even much less than 10 ppm for many years. In that particular Swedish VCM and PVC production plant where two cases of liver hcmangiosarcomas were reported (13) in 197A, the total population at risk since 1945 was 771 individuals (7) giving a hemanyiosarcoma frequency of 0.26 % (2594/106). R&S 107815 Il should he added, that today tv a know of two additional eases in the saint; worker's population, c.g. a total of 4 cases (giving u frequency of 5188/10^). The number of liver hcmangiosorcoinas in the total population (0 millions) in Sweden is coses during the years 1958 through 1969 (13). The true form of the dose response curve at low doses of a carcinogen has been much discussed both before and after the VCM event in 1974. For mutagens (14) as well as for carcinogens (15), v/hich odd to an effect already appearing in the background ("noise"), the dose response curve is probably linear from zero dose and onwards. This would mean that there does not exist a safe level for exposure to a carcinogen. Gy lowering the dose, the risk is only diluted, and the problem is then to define a close giving a reasonable risk level. This level of exposure to a carcinogen we prefer to coll an accepted low risk level of exposure. In the acceptance of an accepted low risk level not only toxico logical information is important but so are also considcrations on technological feasibility and on political issues in a more general sense. It is to be recognized that we believe t Ha t a democratic involvement is reasonable in the acceptance of the low risk level. .* R&S 107816 T^icl^noloy i c_ol__c_on^ulo ra l l n s . - In the spring oT 19/1 il seemed inevitable, according lo the judgment accepted by N130SM to conclude that VCM is a potent animal ond human carcinogen. The first step made by NGOSH v/as to demand the PVC-produccr and also the PVC-f abr i ca to r s to control that exposure v/as not higher than 20 ppm as an 0 hours'TWA. This seemed possible to achieve by more stringent operation of the technical equipment and processes already in use. Although almost no measurements hod been made in the fabricator industry which transfer the PVC resin into moulded articles, floorings, coatings, films etc. it seemed certain that the general exposure among the fabricators was almost everywhere well below 20 ppm. Higher VCM concentrations over some hoppers for PVC-powder and in similar places could easily be reduced drastically. So the technological problem was mainly confined to the process industry. In the PVC-polymcrization industry 20 ppm was in the spring of 1974 believed to be the best achievable level in the immediate future. Therefore a tentative value on 20 ppm was set. In the autumn of 1974 more information was available. Taking into account the possibility that even very low exposures might carry some risk and taking into account the technical., and economic possibi1ities of eliminating exposure, NOOSH finally stated late in tloc autumn of 1974 that, tloc maximum permissible concentration (MPC) should be 1 ppm (0-hours TWA). However, the industry was given the whole year.of 1975 for adjustment to the standard. Current exposures were around 10 ppm TV/A or more at that time. The decision followed very much the same lines that had been drawn up in the U.S. and the 0$HA Standard for VCM was of course studied thoroughly. A possibility which was considered for a while was a stepwise decrease to the permissible level, but it seemed more suitable to give the industry a more definite figure at once and by that give them due time to plan and adjust their technology accordingly. The labour union representative at the PVC plant concerned urged Tor a zero value but was content with 1 ppm. Also the central trade union was in fervour of a stringent but not draconic move. 1 ppm seemed stringent and still possible to measure with satisfactory accuracy. Tbc technological considerations were based, amongst oilier tilings, on two facts. First it was known that the formal dehyde industry had long been operating in the few-ppm range and Lhc ethylene oxide industry at not very much higher levels (16). V/hat these industries could do, the VCM industry would also be able to achieve. Secondly, it was obvious - that VCM, earlier believed to be safe, hod been hitherto handled carelessly. The company Kama Nobel engaged in intenese work during 1975 in order to comply with the promulgated standard and it succeeded. The measures taken were many and some examples arc given below: 1. Thorough investigation of processes and process equipment was carried out in order to avoid ail major emissions of VCM. This included better gadgets in flanges, pump shafts etc, closing reject water systems and air outlets from pressurclcss toJ nks and vessels and a lot of similar measures. 2. Special ventilation was installed to catch every small emission at the source. Well designed hoods wore necessary in many places (17). 3. All PVC-products were, as far as possible, stripped of unpolymerized VCM before handled openly. '1. Special care was token that all PVC-crust from reactor cleaning is handled in closed systems. 5. New processes were installed in order to avoid crust formation. Iligh-pressurc cleaning of reactors was introduced. 6. Automation and remote control was installed. R&S 107818 7. Special pressure ventilation rooms were installed for autoclave operators. 0. General ventilation of a thoroughly designed type with jet-stream distribution of air Tlow was installed (16). 9. Special care was tal<cn that spent air was not recycled to work premises. 10. All work areas are continuously controlled with instruments. 11. Personal protective equipment, mainly respirators, but also protective clothing is thoroughly controlled. Respirators should be used as soon as VCM levels exceed a certain peak value. 12. Some processes and equipments arc not used any more. 13. All worker exposure is carefully monitored. It is to be noted that all these hygienic measures were possible by applying known technology only. True technological innovations were unnecessary. Present worker exposure is currently around 0,5 ppm or lower. Kema Nobel says the firm lias spent 20 million Swedish Crowns (around 4 million US dollars) on technical changes. This has added a cost of 1-2 million Swedish Crowns per year compared to the production cost at an air quality standard of 5-10 ppm. Kema Nord also claims that a longer adjustment period would have meant essential savings in the economical investment. However, the judgment of `.he situation is difficult even in re Irospective. It seems probable that the immaterial gain of the producer in restored confidence on behalf of the workers and the general public is worth much more than a portion of A million dollars. This sum should in its turn be soon in proportion to the profit per year of the company's PVC-divi5ion and seems then not to be a frightening fraction of money. The results of oil these endeavours con be seen in Table 1, which shows exposure at different time periods for different cathcgories of workers. Personal rnoniLors have been used and samples have been analysed chromatogrophical 1y. Also in the fabricator industry the situation is now satis factory. This is partly owing to the fact that the standard PVC resin produced and soiled by Kemu Moisei now contains less than 10 mgs oT VCM per kg of resin. Some qualities even come as low as below 3 mgs/kg. On tire other hand, some PVC resin products arc still on the market with as much as 1000-1500 mgs/kg of VCM. Thanks to special measures taken at the plants using this particular resin, the exposure to VCM today is well under 1 ppm among the fabricator industries loo. 3} R&S 107821 ------ -- -- JO & 0) O 2 N> RCFERL 'IS 1. Schnciderman, W.A., Mantel, N., and Drown, C.C.: From mouse to mein - or how to gel from the laboratory to Park Avenue and 57 th Street. Ann. tl.Y. Acad. Sci. 246, (1775), 237-248. 2. Cranmer, M.F.: Estimation of risks due to environmental co-cinogcncsis . Med. and Fed. Oncology 3, (1777), 167-190. 3. Male.. he value of predictive experimental bioassay in occupational and environmcntal carcinogenesis. An example: Vinyl chloride. Ambio, 4, (1975), 10-23. { . Ilolmberg, D., Kronevi, T., and Wincll, M.: The pathology of vinyl chloride exposed mice. Acta Vet. Scand. 17, (1976), 320-342. 5. Taber haw, J.R., and Guffey, W.R.: Mortality study oT workers in the manufacture of vinyl chloride and its polymers. J. Occup. Med. _1_6, ( 1974) ^9-MO. 6. Chiazze. 1 ll' -h0ls, V/.E., and Wong, 0.: Mortality among employ*. fabricators. J. Occup. Med. 19, ( 1977), 623-620. 7. Dyrdn, D., Engholm, G., Englund, A., and Westcrholm, P.: Dior tali ty and cancer morbidity in a group of Swedish VCM and PVC productions workers. Env. Health. Persp. 17, ( 1976), 167-170. 0. Payne, W.W., and lluepcr, W.C.; The carcinogenic effects of single and repeated doses of nzpyrene. Am. I nd. Hyg. Assoc. 2J_, ( 1760), 350-355 9. Druckrcy, II.: Quantitative aspects in chemical carcinogenesis. UICC l.lonocji aphs Scries R. Truhaut (Ed.), 7_, (1967), 60-78, Springer Vcrlag, Berlin. 10. Ehrcnbcrg, L., and Holmbcrg, 0.: Ex t rupo 1 u t i on of carcino genic risk from animal experiments to man. Env. Health Persp., 7_2_, ( 1978), 33-35. 11. Maltoni, C., and Lefcminc, G. : Carcinogenicity bioassoy of vinyl chloride*. Current results. N.Y. Acad. Sci.. 266, ( 1975), 195-210. 12. Anonymous: Angiosarcoma of the liver in vinyl chloride/polyvinyl chloride workers. J. Occup, Med. 1j6, (1974), C09. 13. Byren, D., and Holmbcrg, B.: Two possible cases of angio sarcoma of the liver in a group of Swedish vinyl chloride- polyvinyl chloride workers. Ann. N.Y. Acad. Sci. 24_6, (1975), 2-19-250. ; - i' 14. Ehrcnbcrg, L.: Genetic toxicity of environmental chemicals. Acta Biol. Jug. Ser. F. Genetica 6, ,1974), 367-390. R&S 107822 15. Crump, K.S., Hoel, D.G., Langley, C. ., and Pcto, R,: Fundamental carcinogenic process es nd their implications for lov/ dose risk assessment, Ca . Re- 36, ( 1976 ), 2973-2979. 16. Joyner, R.E.: Chronic toxicity of ctyione oxide. A sturly of human responses to long-term low-le-vcl exposures. Arch. Gnvironm. Health. 8, (1964), 700-710 17. England, A., and Holmbcrg, B,: Recent achievements and rescorch initiated in the Swedish plastics and rubber industry. Env. Health Persp. 17, (1976;, 237-239. Z8Z(H S9U P7C-'--'orkers'exposure to VU.i in ppm. Cc:upction Shift foreman Operator, genercl Operator, polymerisation Operator, treatment Stare worker Peaair man Service man C-`e~.iccIs preparations Cleaner VCM-chcrcer Packer House cleaner Engineers f-jnher or measurement: nvsrcce vciues: Quarter 2 Quarter 3 Quarter 4 Quarter 1 Quarter 2 Quarter 3-4 Year 1?74 1974 1974 1975 1975 1975 1975 S 14 11 8 44 18 25 7' 10 - 5 4,7 11,5 10,3 6,2 2,4 25,3 ?,5 12,4 8, 5 .13,0 4,0 3,5 5,4 1,4 5,3 3,4 2,3 0,4 2,2 4,0 1,7 3,0 13,3 2,4 2, 1 1,3 1, 1 1,9 1,4 0,8 0, 1 1,0 1,1 0,3 1,4 2,3 1,3 1,2 0,9 1,3 1,4 . 0,9 1,4 2,1 0,6 0,7 0,3 0,3 0,4 0,9 0,3 0,7 0,9 1,0 0,7 0,4 0,5 0,3 0,7 0,7 1,0 0,5 0,8 0,3 0,3 . 0,1 0,3 0,2 0, 2 0,3 0, 2 0,3 0,3 0,2 0,3 0,3 0,2 0,2 0,1 0, 3 0, 3 0,2 0, 2 0, 1 0,2 0, 1 0,2 0,3 0, 3 0, 1 0, 1 0,2 0,2 Ur*/ ; 4n 0,1 0,1 o, 2 0, 3 0, 1 0, 2 C, 3 0,2 0, 1 0, 1 20 71 32 40 45 40-45 52-50 57-5? 50 15,5 10,3 3,4 1,3 1, 1 .0, 9 0,3 0,2 0,2 ppn Figures are 8 hours TV.'A bcsed on personal dose measurements. Biogroplucol notes Holmbcrg, Bo, Ph.D.,, Associate Professor in Occupational Toxicology. Deportment of Occupotional Health, National Board of Occupational Safety and Health, Stockholm. Li xpe r imen Lol biologist, papers in experimental tumour research, the toxicology of organic solvents and vinyl chloride, occupational cancer epidemiology and on quantitative aspects on clTcmicolly induced cancer. R&S 107824 Westlin, Arne, Liny., Head of tlic Department of Supervision and inforccmcnt. National Board of Occupational Safely and Health, Stockholm. Graduated Royal Technical University, Stockholm, 1942. Occupied with industrial research and eh emicol engineering 1942-1956. PublicaLions on pulp chemistry, solvents, plastics, fuel chemistry, ole. From 1957 in occupa tional safety and health. Several publications in the field of occupational liygicnc. Notional Board of Occupational Safety and Health (NB05II), Stockholm, is a governmental body ui acr the Ministry of Laljour, although with a high degree aautonomy. It is tlic central and highest body for rcgulcrk..ng the work environment and is supervising and coordinating -.he regional and partly autonomous Factory Inspectorates. NUQSII consists of Llircc subdepartments, the department of Supervision and Enforcement, the department of occupational hca.'.n (a research dept) and an administrative department. Board of MGOSII consists mainly of laymen, employers and employees representatives and po1iticians.