Document RJqBRqnDjBKEDQ1VvvdBwMNqB

EN1C 184 pages 12.-- 181 pages | __ 271 pages IS.-- 786 pages IS -- 241 pages IS -- 243 pages IS.-- ,'2o pages , 32.-- '5" pages 3h.-- 2f'S pages ^ "* __ ^P^pages '<* pages U-- >: pages VI __ 2" paprs V4_ * pafe* i-- 1! ; ! 1 j ; ! j 1 ir --r<t 4 Nn Kf %, .i I IARC MONOGRAPHS ON THE EVALUATION OF THE CARCINOGENIC RISK OF CHEMICALS TO HUMANS Some Monomers, Plastics and Synthetic Elastomers, and Acrolein VOLUME 19 This publication represents the views and expert opinions of an IARC Working Group on the Evaluation of the Carcinogenic Risk of Chemicals to Humans which met in Lyon, 7-13 February 1978 February 1979 INTERNATIONAL AGENCY FOR RESEARCH ON CANCER v r ( . jt " -:' VINYL CHLORIDE AND POLYMERS 391 Simultaneous exposure to 1.75 %/m1 (671 ppm) vinyl chloride with 200 ppm vinylidene chloride prevented vinylidene chloride-induced hepatic injury in fasted male rats. However, pre-exposure to concentrations of vinyl chloride which depleted hepatic glutathione concentrations signifi cantly enhanced early acute hepatotoxic response to vinylidene chloride in fed rats (Jaeger et at., 1975a,b). Exposure of guinea-pigs to 260 g/m3 (100 000 ppm) vinyl chloride for 2 hours/day for 3 months resulted in marked growth disturbances and intense histopathological and histochemical lesions in the liver, kidneys, spleen and lungs. Interruption of the exposure resulted in a regenerative effect, denoting a certain degree of reversibility of the hepatorenal lesions. Large quantities of vitamin C reduced the gravity of the lesions caused by vinyl chloride (Prodan et at., 1975b). Mice were exposed to 130, 650 or 2600 mg/m3 (50, 250 or 1000 ppm) vinyl chloride for 6 hours/day on 5 days/week. The highest dose caused some acute deaths with toxic hepatitis and marked tubular necrosis in the renal cortex. From the 6th month of treatment, all mice became lethargic, lost weight quickly and died. Only a few mice exposed to 50 ppm survived for 12 months (Lee et at., 1977). The non-protein, free SH-groups of the liver are depleted in rats exposed to 390-5200 mg/m3 (150-2000 ppm) vinyl chloride for 1-7 hours, as a function both of concentration and duration of exposure (Watanabe et at., 1976a). Vinyl chloride and two of its presumed metabolites, chloroethylene oxide and chloroacetaldehyde, depressed DNA synthesis in rat liver in vivo (Border & Webster, 1977). Embryotoxicity and teratogenicity Pregnant CF-1 mice were exposed by inhalation to 130 and 1300 mg/m3 (50 and 500 ppm) vinyl chloride on days 6-15 of gestation, Sprague-Dawley rats to 1300 and 6500 mg/m3 (500 and 2500 ppm) on days 6-15 of gestation, and New Zealand rabbits to 1300 and 6500 mg/m3 (500 and 2500 ppm) on days 6-18 of gestation, for 7 hours/day, with or without simultaneous exposure to 15% ethanol in the drinking-water. A significantly increased incidence of several skeletal anomalies was observed in offspring of mice that received vinyl chloride plus ethanol (John et aZ.,/1.977; Schwetz et at., 1975). Absorption, distribution, excretion and metabolism The in vivo and in vitvo metabolism of vinyl chloride has been studied and reviewed (Antweiler, 1976; Bartsch 4 Montesano, 1975; Bonse & Henschler, 1976; Green 4 Hathway, 1975, 1977; Haley, 1975; Hefner etal., 1975; Malaveille et at., 1975; Milller 4 Norpoth, 1975; Mliller et at., 1976; Plugge & Safe, 1977; Watanabe 4 Gehring, 1976; Watanabe et at., 1976b,c). UCC 107228 ) 428 IARC MONOGRAPHS VOLUME 19 John, J.A.* Smith, F.A., Leong, B.K.J. & Schwetz, B.A. (1977) The effects of maternally inhaled vinyl chloride on embryonal and fetal develop ment in mice, rata, and rabbits. Toxicol, ppl. Pharmacol., 39, 497-513 jUhe, S. 4 Lange, C.-E. (1972) Sclerodermal skin changes, Raynaud's syndrome and acro-osteolyses in workers in the PVC-producing industry (Ger.). Dtsch. med. Wschr., 97, 1922-1923 Kappus, H., Bolt, H.M., Buchter, A. 4 Bolt, W. (1975) Rat liver microsomes catalyse covalent binding' of 11> C-vinyl chloride to macromolecules. Nature (Lond.), 257, 134-135 Kappus, H,, Bolt, H.M., Buchter, A. 4 Bolt, W. (1976) Liver microsomal uptake of ['`'Cjvinyl chloride and transformation to protein alkylating metabolites in vitro. Toxicol, appl. Pharmacol., 37, 461-471 Keplinger, M.L., Goode, J.VJ., Gordon, D.E. 4 Calandra, J.C. (1975) Interim results of exposure of rats, hamsters, and mice to vinyl chloride. Ann. NY Acad. Sci., 246, 219-224 Kogan, A.K. 4 Tugarinova, V.N. (1959) On the blastomogenic action of polyvinyl chloride (Russ.). Vop. Onkol., 5_, 540-545 Laib, R.J. 4 Bolt, H.M. (1977) Formation of imidazol derivatives of nucleic acid bases (DNA and RNA) by metabolites of vinyl chloride in vivo and in vitro (Abstract P 26). In: Proceedings of the 4th Meeting of the European Association for Cancer Research, Lyon, 1977, Lyon, University of Lyon, Faculty of Medicine, p. 84 Lange, C.-E., JUhe, S., Stein, G. 4 Veltman, G. (1974a) Vinyl chloride disease - a systemic sclerosis due to occupational exposure? (Ger.) Int, Arch. Arbeitsmed., 32, 1-32 Lange, C.-E., JUhe, S. 4 Veltman, G. (1974b) Appearance of angiosarcomas of the liver in two workers in the PVC production industry (Ger.). Dtsch. med. Wschr., 99, 1598-1599 Lange, C.-E., JUhe, S., Stein, G. 4 Veltman, G. (1975) Further results in polyvinyl chloride production workers. Ann. NY Acad. Sci., 246. 18-21 ---- Laramy, R.E, (1977) Analytical chemistry of vinyl chloride - a survey. American Laboratory, December, pp. 17-27 Lee, C.C., Bhandari, J.C., Winston, J.M., House, W.B., Peters, P.J., Dixon, R.L. 4 Woods, J.S. (1977) Inhalation toxicity of vinyl chloride and vinylidene chloride. Environ. Health Perspect.. 21. 25-32 ---- UCC 107229 lT 434 IARC MONOGRAPHS VOLUME 19 Rona, A. (1971) Instrumental investigation of adhesives used in the buil(j_ ing industry. In: Symposium on Synthetic Resins in Building Con- struction. Paper RILEM (Reunion Int. Lab. Essais Rech. Mater. Constr.t 1967, Vol, 2, pp. 464-471 [Chem. Abstr., 76. 100475w] Uj- Rosenkranz, S., Carr, H.S. & Rosenkranz, H.S. (1974) 2-Haloethanols: mutagenicity and reactivity with DNA. Mutat Res., 26, 367-370 Russell, F.E., Simmers, M.H., Hirst, A.E. & Pudenz, R.H, (1959) Tumours associated with embedded polymers. J. natl Cancer Inst., 23, 305-315 Safe Drinking Water Committee (1977) Drinking Water and Health, Washington DC, National Academy of Sciences, p. 794 Saggese, M.F., Wakeman, I.B. & Owens, F.V. (1976) PVC with no VCM. Modern Packaging, September, pp. 19-21, 62 Salmon, A.G. (1976) Cytochrome P-450 and the metabolism of vinyl chloride. Cancer Lett., 2_, 109-114 ( J Sarii, M., Kular, Z., Zorica, M. & Gelic, I. (1976) Malignant tumors of the liver and lungs in an area with a PVC industry. Environ. Health Perspect., 17, 189-192 Schwetz, B.A,, Leong, B.K.J., Smith, F.A., Balmer, M. & Gehring, P.J. (1975) Results of a vinyl chloride-teratology study in mice, rats, and rabbits (Abstract No. 29). Toxicol, appl. Pharmacol., 33, 134 Shackelford, W.M. & Keith, L.H. (1976) Frequency of Organic Compounds Identified in Water, EPA-600/4-76-062, Athens, Ga, US Environmental Protection Agency, pp. 129-130 Smith, P.M., Crossley, I.R. & Williams, D.M.J. (1976a) Portal hypertension in vinyl-chloride production workers. Lancet, ii, 602-604 i Smith, P.M., Williams, D.M.J. & Evans, D.M.D. (1976b) Hepatic angiosarcoma in a vinyl chloride worker. Bull. NY Acad. Med,, 52, 447-452 Smyth, H.F., Jr & Weil, C.S. (1966) Chronic oral toxicity to rats of a vinyl chloride-vinyl acetate copolymer. Toxicol, appl. Pharmacol., 9, 501-504 Sokol, W.N., Aelony, Y. & Beall, G.N. (1973) Meat-wrapper's asthma. A new syndrome? J. Am. med. Assoc.. 226, 639-641 ! i ' Spirtas, R. & Kaminski, R. (1978) Angiosarcoma of the liver in vinyl chloride/polyvinyl chloride workers. 1977 Update of the NIOSH Register. J. occup. Med., 20, 427-429