Chloroethylene oxide

Castro CE, DM Riebeth, NO Belser (1992a) Biodehalogenation the metabolism of vinyl chloride by Methylosinus trichosporium OB-3b. A sequential oxidative andreductive pathway through chloroethylene oxide. Environ Toxicol Chem 11 749-755. 

Huberman E, Bartsch H, Sachs L Mutation induction in Chinese hamster V79 cells by two vinyl chloride metabolites, chloroethylene oxide and 2-chloroacetaldehyde. Int J Cancer 16(4) 639-644, 1975... 

Gwinner, L.M., Laib, R.J., Filser, J.G. Bolt, H.M. (1983) Evidence of chloroethylene oxide being the reactive metabolite of vinyl chloride towards DNA comparative studies with 2,2 -dichlorodiethylether. Carcinogenesis, 4, 1482-1486... 

Zajdela F, Croisy A, Barbin A, et al. 1980. 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 40 352-356. 

Storage of vinyl chloride is limited by the rapid metabolism and subsequent excretion. Vinyl chloride is biotransformed by cytochrome P450-mixed function oxidase systems (CYP 2E1), with the two primary metabolites being chloroethylene oxide and chloroacetaldehyde. These materials are further converted to chloroethanol and monochloroacetic acid. Metabolites are primarily excreted in urine. When rats were exposed to vinyl chloride at 100 ppm for 5 h, 70% of the absorbed dose was excreted as urinary metabolites within 24 h. The half-life for urinary excretion in rats was 4h. With an increase in dose via either inhalation or ingestion, the proportion exhaled increased and urinary and fecal elimination decreased. 

Vinyl chloride is also a human and animal carcinogen associated with an increased incidence of hepatic angiosarcoma. Chloroethylene oxide, chloroacetaldehyde, and monochloroacetic acid all react covalently with DNA and RNA. This alkylation results in highly effective base-pair substitutions that can lead to neoplastic transformation. These reactive metabolites might also interact with chromosomes causing clasto-genic effects. 

Chiang SY, Swenberg JA, Weisman WH, Skopek TR (1997) Mutagenicity of vinyl chloride and its reactive metabolites, chloroethylene oxide and chloroacetaldehyde, in a metabolically competent human B-lymphoblastoid line. Carcinogenesis, 18 31-36. 

Zajdela, F. et al., Carcinogenicity of chloroethylene oxide, an ultimate reactive metabolite of... 

Chlorobiphenyl, 136 A -(2-Chloroethyl)dibenzylamine, 206 Chloroethylene oxide, 225 Chlorofluorocarbon, 325... 

Chloroethylene oxide as the reactive toxic intermediate in the biotransformation of vinyl chloride [296]... 

ZiEF and Schramm (1964) have shown that chloroethylene oxide spontaneously rearranges to chloroacetaldehyde. 

Pre-treatment of rats with phenobarbitone, which is known to increase the P450 content of microsomal enzymes, increased the mutagenic response to vinyl chloride monomer in vitro (Bartsch etal. 1975). In an aqueous solution at pH 7.4 and 37 °C the epoxy compound had a half-Ufe of 1.6 min, and its rate of hydrolysis followed a first order kinetic. Chloroethylene oxide, but not 2-chloroacetaldehyde, showed a strong alkylating activity as determined by its reaction with 4-(p-nitrobenzyl)pyridine (Malaveille etal. 1975). 2-Chloroacetaldehyde is a chemically reactive and toxic compound (Lawrence et al. 1972), and is covalently bound to cellular nucleophiles. It reacts at pH 3.5-4.5 and 37 °C with adenosine or cytidine to give fluorescent products, which have been characterised as 3- 3-D-ribofuranosyl-imidazo-(2,l-i)pur-ine or 5,5-dihydro-5-dihydro-5-oxo-5- 3-D-ribofu-... 

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