SpringerLink
Log in

Metabolic Activation and Pharmacokinetics in Hazard Assessment of Halogenated Ethylenes

  • Conference paper
Industrial and Environmental Xenobiotics

Part of the book series: Proceedings in Life Sciences ((LIFE SCIENCES))

  • 70 Accesses

Abstract

Halogenated ethylenes play an important role in occupational and environmental medicine. Several attempts at toxicological evaluation of such compounds have been recently published (Maltoni 1977; Lee et al. 1978; Gehring et al. 1979; Kappus and Ottenwälder 1980; Henschler et al. 1980; Bolt 1980). The principal question is that of possible carcinogenicity. It is now clear that vinyl chloride (Maltoni 1977) and vinyl bromide (Bolt et al. 1979) are carcinogenic; some data also argue in favor of carcinogenicity of vinylidene chloride (Lee et al. 1978). Trichloroethylene (Henschler et al. 1980) and perchloroethylene (Bolt and Link 1980), according to present data, appear devoid of cancerogenic potency. These differences in biological behavior of such closely related compounds can only be explained on a biochemical basis (Bonse and Henschler 1976).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Similar content being viewed by others

References

  • Bartsch H, Malaveille C, Barbin A, Planche G (1979) Mutagenic and alkylating metabolites of haloethylenes, chlorobutadienes and dichlorobutenes produced by rodent or human liver tissue. Arch Toxicol 41: 249–277

    Article  PubMed  CAS  Google Scholar 

  • Bolt HM (1978) Pharmacokinetics of vinyl chloride. Gen Pharmacol 9: 91–95

    PubMed  CAS  Google Scholar 

  • Bolt HM (1980) Die toxikologische Beurteilung halogenierter Äthylene. Arbeitsmed Sozialmed Präventivmed 15: 49–53

    Google Scholar 

  • Bolt HM, Laib RJ (1980) Covalent binding of drug metabolites to DNA - a tool of predictive value? Arch Toxicol 46: 171–180

    Article  PubMed  CAS  Google Scholar 

  • Bolt HM, Link B (1980) Zur Toxikologie von Perchloräthylen. Verh Dtsch Ges Arbeitsmed 20: 463–470

    Google Scholar 

  • Bolt HM, Laib RJ, Stöckle G (1979) Formation of preneoplastic hepatocellular foci by vinyl bromide in newborn rats. Arch Toxicol 43: 83–84

    Article  PubMed  CAS  Google Scholar 

  • Bolt HM, Filser JG, Laib RJ, Ottenwälder H (1980) Binding kinetics of vinyl chloride and vinyl bromide at very low doses. Arch Toxicol Suppl 3: 129–142

    PubMed  CAS  Google Scholar 

  • Bolt HM, Laib RJ, Füser JG, Ottenwälder H, Buchter A (1981) Vinyl chloride and related compounds: mechanism of action on the liver. In: Chalmers TC, Berk PD (eds) Frontiers in liver disease. Thieme/Stratton, New York

    Google Scholar 

  • Bonse G, Henschler D (1976) Chemical reactivity, biotransformation, and toxicity of poly chlorinated aliphatic compounds. CRC Crit Rev Toxicol 5: 395–409

    Google Scholar 

  • Buchter A, Bolt HM, Filser JG, Goergens HW, Laib RJ, Bolt W (1978) Pharmakokinetik und Karzinogenese von Vinylchlorid-Arbeitsmedizinische Risikobeurteilung. Verh Dtsch Ges Arbeitsmed 18: 111–124

    Google Scholar 

  • Buchter A, Filser JG, Peter H, Bolt HM (1980) Pharmacokintics of vinyl chloride in Rhesus monkeys. Toxicol Lett 6: 33–36

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Filser JG, Bolt HM (1980) Characteristics of halo-ethylene-induced acetonemia in rats. Arch Toxicol 45: 109–116

    Article  PubMed  CAS  Google Scholar 

  • Gehring PJ, Watanabe PG, Park CN (1978) Resolution of dose-response toxicity data for chemicals requiring metabolic activation: example vinyl chloride. Toxicol Appl Pharmacol 44: 581–591

    Article  PubMed  CAS  Google Scholar 

  • Gehring PJ, Watanabe PG, Park CN (1979) Risk of angiosarcoma in workers exposed to vinyl chloride as predicted from studies in rats. Toxicol Appl Pharmacol 49: 15–21

    Article  PubMed  CAS  Google Scholar 

  • Green T, Hathway DE (1978) Interactions of vinyl chloride with rat liver DNA in vivo. Chem-Biol Interact 22: 211–224

    Article  PubMed  CAS  Google Scholar 

  • Hathway DE (1977) Comparative mammalian metabolism of vinyl chloride and vinylidene chloride in relation to oncogenic potential. Environ Health Perspect 21: 55–59

    Article  PubMed  CAS  Google Scholar 

  • Henschler D, Bonse G (1978) Metabolic activation of chlorinated ethylene derivatives. In: Advances in pharmacology and therapeutics. Proc 7th Int Congr Pharmacol, vol IX. Pergamon Press, Oxford UK, pp 123–130

    Google Scholar 

  • Henschler D, Romen W, Elsässer HM, Reichert D, Eder E, Radwan Z (1980) Carcinogenicity study of trichloroethylene by longterm inhalation in three animal species. Arch Toxicol 43: 237–248

    Article  PubMed  CAS  Google Scholar 

  • Jones BK, Hathway DE (1978) Differences in metabolism of vinylidene chloride between mice and rats. Br J Cancer 37: 411–417

    Article  PubMed  CAS  Google Scholar 

  • Kappus H, Ottenwälder H (1980) Toxische und kanzerogene Wirkungen von Vinylchlorid.-Stand der Forschung. Umwelthygiene 12: 86–113

    Google Scholar 

  • Laib RJ, Bolt HM (1977) Alkylation of RNA by vinyl chloride metabolites in vitro and in vivo: formation of l,N6-ethenoadenosine. Toxicology 8: 185–195

    Article  PubMed  CAS  Google Scholar 

  • Laib RJ, Bolt HM (1978) Formation of 3,N4-ethenocytidine moieties in RNA by vinyl chloride metabolites in vitro and in vivo. Arch Toxicol 39: 235–240

    Article  PubMed  CAS  Google Scholar 

  • Laib RJ, Bolt HM (1980) Die Quantifizierung präeoplastischer Leberareale in der experimentell-toxikologischen Beurteilung von Arbeitsstoffen. Verh Dtsch Ges Arbeitsnied 20: 537–548

    Google Scholar 

  • Laib RJ, Stöckle G, Bolt HM, Kunz W (1979) Vinyl chloride and trichloroethylene: comparison of alkylating effects of metabolites and induction of preneoplastic enzyme deficiencies in rat liver. J Cancer Res Clin Oncol 94: 139–147

    Article  PubMed  CAS  Google Scholar 

  • Lee CC, Bhandari JC, Winston JM, House WB, Dixon RL, Woods JS (1978) Carcinogenicity of vinyl chloride and vinylidene chloride. J Toxicol Environ Health 4: 15–30

    Article  PubMed  CAS  Google Scholar 

  • Malaveille C, Bartsch H, Barbin A, Camus AM, Montesano R, Croisy A, Jacquignon P (1975) Mutagenicity of vinyl chloride, chloroethylene oxide, chloroacetaldehyde and chloroethanol. Biochem Biophys Res Commun 63: 363–370

    Article  PubMed  CAS  Google Scholar 

  • Maltoni C (1977) Recent findings on the carcinogenicity of chlorinated olfefins. Environ Health Perspect 21: 1–5

    Article  PubMed  CAS  Google Scholar 

  • Osterman-Golkar S, Hultmark D, Segerbäck D, Calleman CJ, Göthe R, Ehrenberg L, Wachtmeister CA (1977) Biochem Biophys Res Commun 76: 259–266

    Article  CAS  Google Scholar 

  • Ottenwälder H, Bolt HM (1980) Metabolic activation of vinyl chloride and vinyl bromide by isolated hepatocytes and hepatic sinusoidal cells. J Environ Pathol Toxicol 4: 411–417

    PubMed  Google Scholar 

  • Ottenwälder H, Laib RJ, Bolt HM (1979) Alkylation of RNA by vinyl bromide metabolites in vitro and in vivo. Arch Toxicol 41: 279–286

    Article  PubMed  Google Scholar 

  • Schumann AM, Quast JF, Watanabe PG (1980) The pharmacokinetics and macromolecular interactions of perchloroethylene in mice and rats as related to oncogenicity. Toxicol Appl Pharmacol 55: 207–219

    Article  PubMed  CAS  Google Scholar 

  • Stöckle G, Liab RJ, Filser JG, Bolt HM (1979) Vinylidene fluoride: metabolism and induction of preneoplastic hepatic foci in relation to vinyl chloride. Toxicol Lett 3: 337–342

    Article  Google Scholar 

  • Watanabe PG, Young JD, Gehring PJ (1977) The importance of non-linear (dose-dependent) pharmacokinetics in hazard assessment. J Environ Pathol Toxicol 1: 163–179

    Google Scholar 

  • Zajdela F, Croisy A, Barbin A, Malaveille C, Tomatis L, Bartsch H (1980) Carcinogenicity of chloroethylene oxide after subcutaneous administration and in initiation-promotion experiments in mice. Cancer Res 40: 352–356

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Abteilung für Toxikologie, Pharmakologisches Institut, der Universität Mainz, Obere Zahlbacher Straße 67, 6500, Mainz 1, Germany

    R. J. Laib

Authors
  1. H. M. Bolt
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. G. Filser
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. R. J. Laib
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Institute of Hygiene and Epidemiology, Šrobárova 48, 10042, Prague 10, Czechoslovakia

    Ivan Gut M.D., Ph.D.  & Miroslav Cikrt M.D., Ph.D.  & 

  2. Faculté des études supérieures, Université de Montréal, C.P. 6128, Succ. A, H3C3J7, Montréal, Québec, Canada

    Gabriel L. Plaa Ph.D.

Rights and permissions

Reprints and permissions

Copyright information

© 1981 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Bolt, H.M., Filser, J.G., Laib, R.J. (1981). Metabolic Activation and Pharmacokinetics in Hazard Assessment of Halogenated Ethylenes. In: Gut, I., Cikrt, M., Plaa, G.L. (eds) Industrial and Environmental Xenobiotics. Proceedings in Life Sciences. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-68195-0_18

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-68195-0_18

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-68197-4

  • Online ISBN: 978-3-642-68195-0

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation