Abstract
The carcinogenicity of vinyl chloride for experimental animals when administered transplacentally is reviewed in comparison with known transplacental carcinogens, including those that, like vinyl chloride, are dependent on enzyme-mediated metabolic conversion to a reactive intermediate in maternal or fetal tissues. Vinyl chloride is converted by mixed-function oxidases to the reactive metabolite chlorooxirane, the carcinogenicity of which is also reviewed. Vinyl chloride is unequivocally a transplacental carcinogen for the rat. No evidence exists, however, to support the hypothesis that exposure of male rats to vinyl chloride or any other carcinogen confers an increased risk of tumor development on their progeny. Many structural analogs of vinyl chloride, i.e., substituted ethylenes, are also carcinogenic for adult animals, and can with confidence likewise be predicted to be effective transplacental carcinogens.
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- Alexandrov V. A. Blastomogenic effect of dimethylnitrosamine on pregnant rats and their offspring. Nature. 1968 Apr 20;218(5138):280–281. doi: 10.1038/218280a0. [DOI] [PubMed] [Google Scholar]
- Bartsch H., Malaveille C., Barbin A., Planche G. Mutagenic and alkylating metabolites of halo-ethylenes, chlorobutadienes and dichlorobutenes produced by rodent or human liver tissues. Evidence for oxirane formation by P450-linked microsomal mono-oxygenases. Arch Toxicol. 1979 Feb 23;41(4):249–277. doi: 10.1007/BF00296896. [DOI] [PubMed] [Google Scholar]
- Goerttler K., Loehrke H. Diaplacental carcinogenesis: initiation with the carcinogens dimethylbenzanthracene (DMBA) and urethane during fetal life and postnatal promotion with the phorbol ester TPA in a modified 2-stage Berenblum/Mottram experiment. Virchows Arch A Pathol Anat Histol. 1976 Nov 22;372(1):29–38. doi: 10.1007/BF00429714. [DOI] [PubMed] [Google Scholar]
- Ivankovic S., Druckrey H. Transplacentare Erzeugung maligner Tumoren des Nervensystems. I. Athyl-nitroso-harnstoff (ANH) an BD IX-Ratten. Z Krebsforsch. 1968;71(4):320–360. [PubMed] [Google Scholar]
- Lu A. Y., Levin W. The resolution and reconstitution of the liver microsomal hydroxylation system. Biochim Biophys Acta. 1974 Sep 16;344(2):205–240. doi: 10.1016/0304-4157(74)90004-5. [DOI] [PubMed] [Google Scholar]
- Lucier G. W., Lui E. M., Lamartiniere C. A. Metabolic activation/deactivation reactions during perinatal development. Environ Health Perspect. 1979 Apr;29:7–16. doi: 10.1289/ehp.79297. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Maltoni C. Occupational carcinogenesis. Predictive value of carcinogenesis bioassays. Ann N Y Acad Sci. 1976;271:431–443. doi: 10.1111/j.1749-6632.1976.tb23144.x. [DOI] [PubMed] [Google Scholar]
- Posner H. S., Falk H. L. Haloethylene-related compounds of industrial, environmental, and medical significance. Environ Health Perspect. 1977 Dec;21:293–326. doi: 10.1289/ehp.7721293. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rice J. M. Carcinogenesis: a late effect of irreversible toxic damage during development. Environ Health Perspect. 1976 Dec;18:133–139. doi: 10.1289/ehp.7618133. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Salmon A. G. Cytochrome P-450 and the metabolism of vinyl chloride. Cancer Lett. 1976 Nov;2(2):109–113. doi: 10.1016/s0304-3835(76)80019-5. [DOI] [PubMed] [Google Scholar]
- Simmon V. F., Baden J. M. Mutagenic activity of vinyl compounds and derived epoxides. Mutat Res. 1980 Jul;78(3):227–231. doi: 10.1016/0165-1218(80)90103-2. [DOI] [PubMed] [Google Scholar]
- Slaga T. J., Huberman E., DiGiovanni J., Gleason G., Harvey R. G. The importance of the "bay region" diol-epoxide in 7,12-dimethylbenz[a]anthracene skin tumor initiation and mutagenesis. Cancer Lett. 1979 Apr;6(4-5):213–220. doi: 10.1016/s0304-3835(79)80036-1. [DOI] [PubMed] [Google Scholar]
- Tomatis L. Prenatal exposure to chemical carcinogens and its effect on subsequent generations. Natl Cancer Inst Monogr. 1979 May;(51):159–184. [PubMed] [Google Scholar]
- Vesselinovitch S. D., Koka M., Rao K. V., Mihailovich N., Rice J. M. Prenatal multicarcinogenesis by ethylnitrosourea in mice. Cancer Res. 1977 Jun;37(6):1822–1828. [PubMed] [Google Scholar]
- Zajdela F., Croisy A., Barbin A., Malaveille C., Tomatis L., Bartsch H. Carcinogenicity of chloroethylene oxide, an ultimate reactive metabolite of vinyl chloride, and bis(chloromethyl)ether after subcutaneous administration and in initiation-promotion experiments in mice. Cancer Res. 1980 Feb;40(2):352–356. [PubMed] [Google Scholar]