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Metabolism and pharmacokinetics of vinyl acetate

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Abstract

The hydrolysis of vinyl acetate (formation of acetic acid) has been studied in vitro with rat liver and lung microsomes, rat and human plasma and purified esterases (such as acetylcholine esterase, butyrylcholine esterase, carboxyl esterase). Characterization of the kinetic parameters revealed that rat liver microsomes and purified carboxyl esterase (from porcine liver) displayed the highest activity.

In order to establish the rate of metabolism of vinyl acetate in vivo, rats were exposed in closed desiccator jar chambers, and gas uptake kinetics were studied. The decay of vinyl acetate was dose-dependent, indicating possible saturation of metabolic pathway(s). The maximal clearance (at lower concentrations) of vinyl acetate from the system (30 000 ml/h per kg body weight) was similar to the maximal ventilation rate in this species. This indicated that under conditions when metabolic enzymes are not saturated the metabolic rate is mainly determined by pulmonary uptake.

The exposure of rats to vinyl acetate resulted in a transient exhalation of significant amounts of acetaldehyde into the closed exposure system. This indicates the presence of this metabolic intermediate of vinyl acetate in the organism in vivo.

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References

  • Arndt R (1973) Isolierung und Charakterisierung von CarboxylEsterasen (E.C. 3.1.1.1) der Rattenleber, Diss., Kiel

  • Bolt HM, Filser JG, Buchter A (1981) Inhalation pharmacokinetics based on gas uptake studies. III. A pharmacokinetic assessment in man of “peak concentrations” of vinyl chloride. Arch Toxicol 48: 213–228

    Google Scholar 

  • Bolt HM, Laib RJ, Filser JG (1982) Reactive metabolites and carcinogenicity of halogenated ethylenes. Biochem Pharmacol 31: 1–4

    Google Scholar 

  • Bolt HM, Filser JG, Stornier F (1984) Inhalation pharmacokinetics based on gas uptake studies. V. Comparative pharmacokinetics of ethylene and 1,3-butadiene in rats. Arch Toxicol 55: 213–218

    Google Scholar 

  • Deutsche Forschungsgemeinschaft (1983): Vinylacetat. In: Henschler D (ed) Gesundheitsschädliche Arbeitsstoffe, toxikologisch-arbeitsmedizinische Begründungen von MAKWerten 9. Lieferung. Verlag Chemie, Weinheim

    Google Scholar 

  • Filser JG (1985) Habilitationsschrift, FB Medizin, Johannes-Gutenberg-Universität Mainz.

    Google Scholar 

  • Filser JG, Bolt HM (1979) Pharmacokinetics of halogenated ethylenes in the rat. Arch Toxicol 42: 123–136

    Google Scholar 

  • Filser JG, Bolt HM (1981) Inhalation pharmacokinetics based on gas uptake studies. I. Improvement of kinetic models. Arch Toxicol 47: 279–292

    Google Scholar 

  • Filser JG, Bolt HM (1983) Inhalation pharmacokinetics based on gas uptake studies. IV. The endogenous production of volatile compounds. Arch Toxicol 52: 123–133

    Google Scholar 

  • Guyton AC (1947) Respiratory volumes of laboratory animals. Am J Physiol 150: 70–77

    Google Scholar 

  • Jones RB, Mackrodt WC (1983) Structure-genotoxicity relationship for aliphatic epoxides. Biochem Pharmacol 32: 2359–2362

    Google Scholar 

  • Lijinski W, Reuber MD (1983) Chronic toxicity studies of vinyl acetate in Fischer rats. Toxicol Appl Pharmacol 63: 43–53

    Google Scholar 

  • Maltoni C (1977) Vinyl chloride carcinogenicity: an experimental model for carcinogenesis studies. In: Hiatt AM, Watson JD, Winsten JA (eds) The Origins of Cancer, vol A. Cold Spring Harbor Labarotory, New York, pp 119–164

    Google Scholar 

  • Mentlein R, Heymann E (1984) Hydrolysis of esterand amidetype drugs by the purified isoenzymes of nonspecific carboxylesterase from rat liver. Biochem Pharmacol 8: 1243–1248

    Google Scholar 

  • Norppa H, Tursi F, Mäki-Paakanen J, Järventaus J, Sorsa M (1983) Vinylacetate is a potent inducer of chromosome damage in mammalian cells. International seminar on methods of monitoring human exposure to carcinogenic and mutagenic agents. Espoo, Finland, IARC Scientific Publications (in press)

  • Remmer H, Greim H, Schenkman JB, Estabrook RW (1967) Methods for the evaluation of hepatic mixed-function oxidase levels and cytochrome P-450. Methods Enzymol 10: 703–708

    Google Scholar 

  • Siegers CP, Filser JG, Bolt HM (1978) Effect of dithiocarb on metabolism and covalent binding of carbon tetrachloride. Toxicol Appl Pharmacol 46: 709–716

    Google Scholar 

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Simon, P., Filser, J.G. & Bolt, H.M. Metabolism and pharmacokinetics of vinyl acetate. Arch Toxicol 57, 191–195 (1985). https://doi.org/10.1007/BF00290886

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  • DOI: https://doi.org/10.1007/BF00290886

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