Synthesis and genotoxicity of acetoxyoxirane, the epoxide of vinyl acetate.

  title={Synthesis and genotoxicity of acetoxyoxirane, the epoxide of vinyl acetate.},
  author={Patrice Simon and Bernd Epe and P M{\"u}tzel and Dietmar Schiffmann and Dieter Wild and H. Ottenw{\"a}lder and N. Fedtke and Hermann M. Bolt and Dietrich Henschler},
  journal={Journal of biochemical toxicology},
  volume={1 2},
Acetoxyoxirane, the epoxide of vinyl acetate and a potential reactive intermediate, was synthesized and characterized by 13C-nuclear magnetic resonance (13C-NMR) and mass spectroscopy. The compound induced lesions (endonuclease-sensitive and alkali-labile sites) in supercoiled PM2 DNA in vitro and was directly mutagenic toward Salmonella typhimurium TA100. The mutagenicity of the epoxide in phosphate buffer (pH 7.4, 37 degrees C) decreased, with an initial half-life of 2.8 minutes, and… Expand
Vinyl acetate monomer (VAM) genotoxicity profile: Relevance for carcinogenicity
  • R. Albertini
  • Chemistry, Medicine
  • Critical reviews in toxicology
  • 2013
A mode of action (MOA) is proposed for VAM’s site-of-contact carcinogenesis that incorporates the overall process of mutation induction that includes both background mutations due to endogenous AA and those resulting from exogenous exposures. Expand
Nonlinear responses for chromosome and gene level effects induced by vinyl acetate monomer and its metabolite, acetaldehyde in TK6 cells
Cytotoxicity paralleled genotoxicity demonstrating that a small degree of cytotoxicity occurred prior to increases in MN, and established 0.25 mM as a consistent concentration where genotoxic first occurred for both VAM and AA provided VAM is hydrolyzed to AA. Expand
Asymmetric sharpless epoxidation of divinylcarbinol. Erythro-D- and -L-4-pentenitols by hydrolysis of regioisomeric epoxy-4-pentenols☆☆☆
Abstract The asymmetric Sharpless epoxidation of divinylcarbinol (1), a secondary, achiral allylic alcohol, is described in detail. The epoxidation proceeds with high enantio-control andExpand
Degradation of vinyl acetate by soil, sewage, sludge, and the newly isolated aerobic bacterium V2
The key enzyme of the pathway is vinyl acetate esterase, which hydrolyzed the ester to acetate and vinyl alcohol, which produced ethanol and acetate, providing the basis for a convenient spectrophotometric test. Expand
Mode-of-action-based dosimeters for interspecies extrapolation of vinyl acetate inhalation risk.
Reduction in intracellular pH (pHi) is proposed as the dosimeter most closely linked to the earliest stages of vinyl acetate toxicity, and risk assessments that are based on protection of nasal epithelium from intrACEllular acidification will be protective of all subsequent pathological responses related to vinyl acetates exposure. Expand
Physiologically based modeling of vinyl acetate uptake, metabolism, and intracellular pH changes in the rat nasal cavity.
A physiologically based pharmacokinetic model was constructed to describe the deposition of VA in the nasal cavity of the rat and provide estimates of regional tissue exposure to VA, AAld, and AA and provides nasal dosimetry estimates needed to develop mechanistically based risk assessment approaches for human exposures to VA vapor. Expand
Vinyl acetate is used in the manufacture of many polymers. The Clean Air Act Amendments of 1990 require that an inhalation risk assessment be conducted to assess risks to human health from ambientExpand
Halogenated derivatives QSAR model using spectral moments to predict haloacetic acids (HAA) mutagenicity.
A QSAR model, able to describe more than 90% of the variance in the experimental activity, was developed with the use of the spectral moment descriptors, and provides better results than other linear descriptors models based on Geometrical, RDF, WHIM, eigenvalue-based indices, 2D-autocorrelation ones, and information descriptors. Expand
Zur Voraussagbarkeit toxikologischer Wirkungen: Kanzerogenität von Alkenen
Ungesattigte aliphatische Kohlenwasserstoffe (Alkene) werden im menschlichen und tierischen Organismus in Epoxide (Oxirane) umgesetzt, die krebserzeugende und erbgutverandernde Wirkungen haben konnen.


Vinyl carbamate as a promutagen and a more carcinogenic analog of ethyl carbamate.
The qualitatively similar, but much stronger, carcinogenic activity of vinyl carbamate as compared to that of ethyl carbamate suggests that the metabolic pathways of these two carbamates may converge in the formation of similar or identical electrophilic reactants that bind covalently to macromolecules in vivo and initiate carcinogenesis. Expand
Vinyl acetate, a structural analog of vinyl carbamate, fails to induce enzyme-altered foci in rat liver.
No foci were observed in Vinyl acetate-treated animals at the age of 14 weeks, consistent with investigations on metabolism and pharmacokinetics of vinyl acetate which show that this compound, after entering the organism, is immediately split by blood esterases and thus may not be available for epoxidation to an ultimately carcinogenic metabolite. Expand
DNA cross-links in human leucocytes treated with vinyl acetate and acetaldehyde in vitro.
It is demonstrated that both vinyl acetate and acetaldehyde induce DNA cross-links in human cells. Expand
Chromosome damage induced by vinyl acetate through in vitro formation of acetaldehyde in human lymphocytes and Chinese hamster ovary cells.
The results indicate that vinyl acetate induces chromosome damage in cell cultures through enzyme-mediated hydrolysis to acetaldehyde, and this effect was more pronounced in cultures of isolated lymphocytes than in whole-blood cultures. Expand
Mutagenicity of vinyl compounds in Salmonella typhimurium.
Eighteen compounds structurally related to the mutagenic carcinogen vinyl chloride have been tested for mutagenicity in five strains of Salmonella typhimurium. Acrolein, acrolein diethylacetal,Expand
Induction of morphological transformation and unscheduled DNA synthesis in Syrian hamster embryo fibroblasts by hexachlorobutadiene and its putative metabolite pentachlorobutenoic acid.
Comparative induction of unscheduled DNA synthesis (UDS) and morphological transformation in the same cell system (Syrian hamster embryo fibroblasts) are indicative of a genotoxic mechanism for the carcinogenic actions of HCBD and PCBA. Expand
Detection of different types of damage in alkylated DNA by means of human corrective endonuclease (correndonuclease).
  • N. Duker, G. Teebor
  • Biology, Medicine
  • Proceedings of the National Academy of Sciences of the United States of America
  • 1976
Double-stranded, covalently closed DNA from phage PM II was treated with methyl methanesulfonate, N-methyl-N-nitrosourea, beta-propiolactone, or diepoxybutane to introduce alkylated bases and alkali-labile sites into the DNA, indicating the presence of a second type of alkali -labile damage that is correndonuclease-insensitive. Expand
Vinyl acetate: DNA-binding assay in vivo.
No specific hepatic DNA adducts, known to occur after administration of labelled vinyl halides or vinyl carbamates, could be detected in hepatic tissues following administration of 14C-labelled vinyl acetate. Expand
Rat liver microsomal transformation of ethene to oxirane in vitro.
Rat liver microsomal monooxygenases transform ethene to oxirane, which has a distinctly lower alkylating potency than vinyloxirane towards the test reagent (p-nitrobenzyl)-pyridine, which may suggest a lower toxicity of e thene, compared with butadiene. Expand
Detection of carcinogens as mutagens in the Salmonella/microsome test: assay of 300 chemicals.
There is a high correlation between carcinogenicity and mutagenicity: 90% (156/174) of carcinogens are mutagenic in the test and despite the severe limitations inherent in defining non-carcinogenicity, few "non-Carcinogens" show any degree of mutageniability. Expand