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International Agency for Research on Cancer (IARC) - Summaries & Evaluations

VINYL CHLORIDE
(Group 1)

For definition of Groups, see Preamble Evaluation.

Supplement 7: (1987) (p. 373)

CAS No.: 75-01-4
Chem. Abstr. Name: Chloroethene

A. Evidence for carcinogenicity to humans (sufficient)

Vinyl chloride has been associated with tumours of the liver, brain, lung and haematolymphopoietic system [ref: 1]. A large number of epidemiological studies [ref: 2-12] and case reports [ref: 13-25] have substantiated the causal association between vinyl chloride and angiosarcoma of the liver. Several studies also confirm that exposure to vinyl chloride causes other forms of cancer, i.e., hepatocellular carcinoma [ref: 13,19,23,26], brain tumours [ref: 11,27], lung tumours [ref: 12,28-30] and malignancies of the lymphatic and haematopoietic system [ref: 11,29,31]. Exposure to polyvinyl chloride dust was associated with an increased incidence of lung tumours in one study; the authors suggested that trapped vinyl chloride monomer was responsible [ref: 30]. Melanoma occurred in excess in one study [ref: 12] but has not been mentioned in others. Slightly elevated risks for gastric [ref: 29] and gastrointestinal cancer (other than liver cancer) [ref: 32] were indicated in some studies, but these were not confirmed in others.

B. Evidence for carcinogenicity to animals (sufficient)

Vinyl chloride administered orally or by inhalation to mice, rats and hamsters produced tumours in the mammary gland, lung, Zymbal gland and skin and angiosarcomas of the liver [ref: 1]. Similar findings were made in more recent studies [ref: 33-39]. In one, a combination of oral administration of ethanol and inhalation of vinyl chloride resulted in more liver tumours (including angiosarcomas) than after treatment with vinyl chloride alone [ref: 40].

C. Other relevant data

Chromosomal aberrations were induced in peripheral blood lymphocytes of workers exposed to vinyl chloride at levels of 5-500 ppm (13-1300 mg/m3). Two studies reported negative results for sister chromatid exchanges in exposed workers, while in another study a weakly positive response was found [ref: 41].

Vinyl chloride induced chromosomal aberrations, sister chromatid exchanges and micronuclei in rodents exposed in vivo but did not induce mutation in the mouse spot test or dominant lethal mutations in rats or mice. It alkylated DNA in several tissues of mice and rats exposed in vivo. Vinyl chloride induced sister chromatid exchanges in human lymphocytes in vitro. It induced mutation in Chinese hamster cells and unscheduled DNA synthesis in rat hepatocytes in vitro and induced transformation in BALB/c 3T3 cells and virus-infected Syrian hamster cells. It induced sex-linked recessive lethal mutations, but not aneuploidy, heritable translocations or dominant lethal mutations in Drosophila. It was mutagenic to plants and to Schizosaccharomyces pombe but not to other fungi; it induced gene conversion in yeast. It caused DNA damage and mutation in bacteria. Vinyl chloride bound covalently to isolated DNA in the presence of a metabolic system [ref: 41].

Overall evaluation

Vinyl chloride is carcinogenic to humans (Group 1).

For definition of the italicized terms, see Preamble Evaluation.

Also see previous evaluations: Vol. 7 (1974); Vol. 19 (1979)

References

1. IARC Monographs, 19, 377-438, 1979

2. Baxter, P.J., Anthony, P.P., MacSween, R.N.M. & Scheuer, P.J. (1977) Angiosarcoma of the liver in Great Britain. 1963-73. Br. med. J., ii, 919-921

3. Brady, J., Liberatore, F., Harper, P., Greenwald, P., Burnett, W., Davies, J.N.P., Bishop, M., Polan, A. & Viana, N. (1977) Angiosarcoma of the liver: an epidemiologic survey. J. natl Cancer Inst., 59, 1383-1385

4. Baxter, P.J., Anthony, P.P., MacSween, R.N.M. & Scheuer, P.J. (1980) Angiosarcoma of the liver: annual occurrence and aetiology in Great Britain. Br. J. ind. Med., 37, 213-221

5. Baxter, P.J. (1981) The British hepatic angiosarcoma register. Environ. Health Perspect., 41, 115-116

6. Falk, H., Herbert, J., Crowley, S., Ishak, K.G., Thomas, L.B., Popper, H. & Caldwell, G.G. (1981) Epidemiology of hepatic angiosarcoma in the United States, 1964-1974. Environ. Health Perspect., 41, 107-113

7. Thériault, G. & Allard, P. (1981) Cancer mortality of a group of Canadian workers exposed to vinyl chloride monomer. J. occup. Med., 23, 671-676

8. Vianna, N.J., Brady, J.A. & Cardamone, A.T. (1981) Epidemiology of angiosarcoma of liver in New York State. N.Y. State J. Med., 6, 895-899

9. Weber, H., Reinl, W. & Greiser, E. (1981) German investigations on morbidity and mortality of workers exposed to vinyl chloride. Environ. Health Perspect., 41, 95-99

10. Forman, D., Bennett, B., Stafford, J. & Doll, R. (1985) Exposure to vinyl chloride and angiosarcoma of the liver: a report of the register of cases. Br. J. ind. Med., 42, 750-753

11. von Greiser, E., Reinl, W. & Weber, H. (1982) Vinyl chloride exposure and mortality of German chemical workers in comparison to mortality of non-exposed chemical workers and PVC workers (Ger.). Zbl. Arbeitsmed., 32, 44-62

12. Heldaas, S.S., Langard, S.L. & Andersen, A. (1984) Incidence of cancer among vinyl chloride and polyvinyl chloride workers. Br. J. ind. Med., 41, 25-30

13. Gokel, J.M., Liebezeit, E. & Eder, M. (1976) Hemangiosarcoma and hepatocellular carcinoma of the liver following vinyl chloride exposure. A report of two cases. Virchows Arch. Pathol. Anat. Histol., 372, 195-203

14. Bonneton, G., Champetier, J., Fournet, J., Guidicelli, H., Legrand, J., Dupre, A., Hostein, M., Marty, F. & Pahn, M. (1977) Angiosarcoma of the liver and portal fibrosis in vinyl chloride workers. Two cases (Fr.). Nouv. Presse méd., 6, 735-742

15. Puech, A.-M., Fournet, A., Laulhere, L., Faure, J., Cau, G. & Mallion, J.-M. (1977) Study of hepatic lesions seen in 5 subjects exposed to vinyl chloride, including 3 cases of angiosarcoma of the liver (Fr.). Arch. Mal. prof., 38, 787-795

16. Réty, J., Lambert, R. & Pialat, J. (1981) Medical surveillance of persons exposed to occupational toxic compounds with late or carcinogenic effects. The 11th French case of angiosarcoma of the liver in a PVC worker (Fr.). Arch. Mal. prof., 42, 405-406

17. Pialat, J., Pasquier, B., Pahn, M. & Kopp, N. (1979) Hepatic lesions cuased by vinyl chloride monomer. Study of eight clinicopathological cases (Fr.). Arch. Anat. Cytol. pathol., 27, 361-375

18. Ghandur-Mnaymneh, L. & Gonzalez, M.S. (1981) Angiosarcoma of the penis with hepatic angiomas in a patient with low vinyl chloride exposure. Cancer, 47, 1318-1324

19. Koischwitz, D., Lelbach, W.K., Lackner, K. & Hermanutz, D. (1981) Angiosarcoma of the liver and hepatocellular carcinomas induced by vinyl chloride (Ger.). Fortschr. Rontgenstr., 134, 283-290

20. Vianna, N.J, Brady, J. & Harper, P. (1981) Angiosarcoma of the liver: a signal lesion of vinyl chloride exposure. Environ. Health Perspect., 41, 207-210

21. Chiappino, G., Bertazzi, P.A., Baroni, M. & Masini, T. (1982) Hepatic angiosarcoma from vinyl chloride. Report of a new Italian case. Med. Lav., 6, 555-563

22. Jones, D.B. & Smith, P.M. (1982) Progression of vinyl chloride induced hepatic fibrosis to angiosarcoma of the liver. Br. J. ind. Med., 39, 306-307

23. Evans, D.M.D., Williams, W.J. & Kung, I.T.M. (1983) Angiosarcoma and hepatocellular carcinoma in vinyl chloride workers. Histopathology, 7, 377-388

24. Maltoni, C., Clini, C., Vicini, F. & Masina, A. (1984) Two cases of liver angiosarcoma among polyvinyl chloride (PVC) extruders of an Italian factory producing PVC bags and other containers. Am. J. ind. Med., 5, 297-302

25. Louagie, Y.A., Gianello, P., Kestens, P.J., Bonbled, F. & Haot, J.G. (1984) Vinyl chloride induced hepatic angiosarcoma. Br. J. Surg., 71, 322-323

26. Langbein, G., Permanetter, W. & Dietz, A. (1983) Hepatocellular carcinoma after vinyl chloride exposure (Ger.). Dtsch. med. Wochenschr., 108, 741-745

27. Cooper, W.C. (1981) Epidemiologic study of vinyl chloride workers: Mortality through December 31, 1972. Environ. Health Perspect., 41, 101-106

28. Buffler, P.A., Wood, S., Eifler, C., Suarez, L. & Kilian, D.J. (1979) Mortality experience of workers in a vinyl chloride monomer production plant. J. occup. Med., 21, 195-203

29. Fedotova, I.V. (1983) The incidence of malignant tumors among workers engaged in the manufacture of vinyl chloride and polyvinyl chloride (Russ.). Gig. Tr. prof. Zabol., 4, 30-32

30. Waxweiler, R.J., Smith, A.H., Falk, H. & Tyroler, H.A. (1981) Excess lung cancer risk in a synthetic chemicals plant. Environ. Health Perspect., 41, 159-165

31. Filatova, V.S., Antonyuzhenko, V.A., Smulevich, V.B., Fedotova, I.V., Kryzhanovskaya, N.A., Bochkareva, T.V., Goryacheva, L.A. & Bulbulyan, N.A. (1982) Blastomogenic hazard of vinyl chloride (clinico-hygienic and epidemiologic study) (Russ.). Gig. Tr. prof. Zabol., 1, 28-31

32. Molina, G., Holmberg, B., Elofsson, S., Holmlund, L., Moosing, R. & Westerholm, P. (1981) Mortality and cancer rates among workers in the Swedish PVC processing industry. Environ. Health Perspect., 41, 145-151

33. Hong, C.B., Winston, J.M., Thornburg, L.P., Lee, C.C. & Woods, J.S. (1981) Follow-up study on the carcinogenicity of vinyl chloride and vinylidene chloride in rats and mice: tumor incidence and mortality subsequent to exposure. J. Toxicol. environ. Health, 7, 909-924

34. Feron, V.J., Hendriksen, C.F.M., Speek, A.J., Til, H.P. & Spit, B.J. (1981) Lifespan oral toxicity study of vinyl chloride in rats. Food Cosmet. Toxicol., 19, 317-333

35. Hehir, R.M., McNamara, B.P., McLaughlin, J., Jr, Willigan, D.A., Bierbower, G. & Hardisty, J.F. (1981) Cancer induction following single and multiple exposures to a constant amount of vinyl chloride monomer. Environ. Health Perspect., 41, 63-72

36. Maltoni, C., Lefemine, G., Ciliberti, A., Cotti, G. & Carretti, D. (1981) Carcinogenicity bioassays of vinyl chloride monomer: a model of risk assessment on an experimental basis. Environ. Health Perspect., 41, 3-29

37. Drew, R.T., Boorman, G.A., Haseman, J.K., McConnell, E.E., Busey, W.M. & Moore, J.A. (1983) The effect of age and exposure duration on cancer induction by a known carcinogen in rats, mice and hamsters. Toxicol. appl. Pharmacol., 68, 120-130

38. Suzuki, Y. (1983) Neoplastic effect of vinyl chloride in mouse lung - lower doses and short-term exposure. Environ. Res., 32, 91-103

39. Groth, D.H., Coate, W.B., Ulland, B.M. & Hornung, R.W. (1981) Effects of aging on the induction of angiosarcoma. Environ. Health Perspect., 41, 53-57

40. Radike, M.J., Stemmer, K.L. & Bingham, E. (1981) Effect of ethanol on vinyl chloride carcinogenesis. Environ. Health Perspect., 44, 59-62

41. IARC Monographs, Suppl. 6, 566-569, 1987

Synonyms


Last updated: 10 February 1998





















    See Also:
       Toxicological Abbreviations
       Vinyl Chloride (EHC 215, 1999)
       Vinyl Chloride (HSG 109, 1999)
       Vinyl chloride (ICSC)
       Vinyl chloride (WHO Food Additives Series 19)
       VINYL CHLORIDE (JECFA Evaluation)
       Vinyl chloride (PIM 558)
       Vinyl chloride (SIDS)