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11 3. Personal Conclusions The Graph shows clearly the rather linear dose/effect relation at high exposure levels and demonstrates that the technological improvements in the mid 70's have eliminated the danger for exposed workers in VCM/PVc plants. At low exposure levels the concept of linearity does not seem to be supported by either epidemiological or metabolism data - unless we can clarify reasons for the choice between detoxifying and carcinogenic metabolic pathways of VCM. The "one molecule can kill"-theory is not supported by any facts.

12 BIBLIOGRAPHY 1. Filatova V.S. and Gronsberg E.S. "Hygienic working conditions in production of PVC resins and measures for improvement." Cig. Sanit. 1, 38-42 (1957) 2. Cordier J.M. et al. :"Acro-ost€olyse et lesions cutandes assocides chez deux ouvriers affectds au nettoyage d'autoclaves." Cah. Med. Trav., g, 3-39 (1966) 3. Suciu I., et al. :"Contributti la studint imbolnavirilor produce de chlorura de vinil." Med. Interna. 1,A, 967-78, (1963) 4. Viola P.L. :"Pathology of vinyl chloride". Med. lav. 174 (1970) 5. Viola P.L. et al. :"Oncogenic response of rat skin, lungs and bones to vinyl chloride." Cancer Res. 11„ 516-22, (1971) 6. Maltoni C. and M.A. Mehlman :"Archives of Research on Industrial Carcinogenesis." Princeton Scientific Publishers Vol. II (1984) 7. Maltoni C. et al. ."Vinyl chloride carcinogenesis current results and perspectives" Med. Lav. ¢5, 421 (1974). 8. Creech J.L. and Johnson M.N. :"Angiosarcoma of the liver in the manufacture of PVC." J. Occup. Med. 16, 150-151, (1974) 9. Barnes A.W. :"Vinyl chloride and the production of PVC" Proc. Roy. Soc. Med. §9, 277-281, (1976) 10. Norsk Hydro a.s. "PVC and the environment", Oslo, (1992) 11. Freiesleben W. "Responsibility of Chemical Industry in Occupational Health Risks." Proc. 4th International Medichem Conf., Haifa (1976) p. 180 12. ECETOC Techn. Report Nr. 31 "The mutagenicity and carcinogenicity of vinyl chloride : a historical review and assessment." Brussels, 1988, p. 7 13. N.tcholson, W.J. et al. :"Mortality experience of a cohort of vinyl chloride - PVC workers." Ann. N.Y. Acad. Sci. 246, 225-280, (1975) 14. Lahmann E. et al. :"Organisch-chemische Verunreinigungen in StSdtischer Luft". Bundesgesundheitsblatt 21, 75-76 (1978)

13 15. Ministerie van Volkshuisvesting, Ruimtelijke Ordering en Milieubeheer, NL (1984) 16. Til H.P. et al. :"Life-span oral carcinogenicity study of vinyl chloride in rats". TNO-CIVO report V 83.285/291099, Sept 1983 17. Barnes A.W. :°Institutional interactions in Problems of Occupational Health : An Industry View on the Lessons from Vinyl Chloride". Proceeding 4th Intern. Conf. Medichem, Sept. 1976, Haifa 18. Unpublished communication from APME's medical working group. March 1993. 19. Watanabe P.G. et al. ."Hepatic macromolecular binding following exposure to vinyl chloride." Toxicol. Appl. Pharmacol. 44, 571 (1978) 20. Gehring P.J. et al. :"Resolution of dose-response toxicty data for chemicals requiring metabolic activation." Toxicol. Appl. Pharmacol. 44, 581-591, (1978) 21. Buchter A. et al. :°Pharmakokinetik und Karziongenese von Vinylchlorid.° Verhandlung der Deutschen Geselischaft fur Arbeitsmedizin J&, 111-124, (1978) and Toxicol. Letters 6, 3-36 (1980) 22. Fornan D. et al. :"Expasute to vinyl chloride and angiosarocrte of the liver : a report of the register of cases: '-Brit. 8. Indust. Med. 42, 750.-753 (1985) N N O N ~ A Q1 ~ co 4a

, Exposure. levels DOSE/EFFECT RELATIONS FOR VCM 1992 m 20 mio t/a (ppm) ~I 400 Number oF ~~ =10 mio t/a cases/ Year ASI. (according to 'Q/ PVC production date of diagnosis) ', 300.-t- 15 Exposure levelsv 9 i Scale for 200 -i-10 100-i-5 C~tlE:~Iflt;:'EGi1Fta'7Eyl3•351172;:'7 min. latency lima Mortality predictions 1976 (Barnes) 8849b4Z0SZ