Skip to main content
Log in

Species differences in butadiene metabolism between mice and rats evaluated by inhalation pharmacokinetics

  • Original Investigations
  • Published:
Archives of Toxicology Aims and scope Submit manuscript

Abstract

Metabolism of 1,3-butadiene to 1,2-epoxybutene-3 in rats follows saturation kinetics. Comparative investigation of inhalation pharmacokinetics in mice also revealed a saturation pattern. For both species “linear” pharmacokinetics apply at exposure concentrations below 1000 ppm 1,3-butadiene; saturation of butadiene metabolism is observed at atmospheric concentrations of about 2000 ppm.

For mice metabolic clearance per kg body weight in the lower concentration range where first order metabolism applies was 7300ml×h−1 (rat: 4500 ml×h−1). Maximal metabolic elimination rate (Vmax) was 400 μmol×h−1 ×kg−1 (rat: 220 μmol ×h−1×kg−1). This shows that 1,3-butadiene is metabolized by mice at higher rates compared to rats.

Based on these investigations, the metabolic elimination rates of butadiene in both species were calculated for the exposure concentrations applied in two inhalation bioassays with rats and with mice. The results show that the higher rate of butadiene metabolism in mice when compared to rats may only in part be responsible for the considerable difference in the susceptibility of both species to butadiene-induced carcinogenesis.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Andersen ME (1981) Saturable metabolism and its relationship to toxicity. CRC Crit Rev Toxicol 10: 105–150

    Google Scholar 

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

    Google Scholar 

  • Bolt HM, Schmiedel G, Filser JG, Rolzhäuser HP, Lieser K, Wistuba D, Schurig V (1983) Biological activation of 1,3-butadiene to vinyl oxirane by rat liver microsomes and expiration of the reactive metabolite by exposed rats. J Cancer Res Clin Oncol 106: 112–116

    Google Scholar 

  • Bolt HM, Filser JG, Störmer 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 

  • Buchter A, Bolt HM, Filser JG, Goergens HW, Laib RJ, Bolt W (1978) Pharmakokinetik und Carcinogenese von Vinylchlorid. Arbeitsmedizinische Risikobeurteilung. Verh Dtsch Ges Arbeitsmed 18: 111–115

    Google Scholar 

  • Filser JG, Bolt HM (1979) Pharmacokinetics of halogenated ethylenes in rats. 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 

  • Filser JG, Bolt HM (1984) Inhalation pharmacokinetics based on gas uptake studies VI. Comparative evaluation of ethylene oxide and butadiene monoxide as exhaled reactive metabolites of ethylene and 1,3-butadiene in rats. Arch Toxicol 55:219–223

    Google Scholar 

  • Hazleton Laboratories Europe (1981) “1,3-butadiene. Inhalation teratogenicity study in the rat”, Final report and addendum No. 2788-522/3, Hazleton Labs., Harrowgate HG3 1 PY, England

    Google Scholar 

  • Huff JE, Melnick RL, Solleveld HA, Haseman JK, Powers M, Miller RA (1985) Multiple organ carcinogenicity of 1,3-butadiene in B6C3F1 mice after 60 weeks of inhalation exposure. Science 227: 548–549

    Google Scholar 

  • Kirk-Othmer Enzyclopedia of Chemical Technology (1979), Wiley, New York, ed. 3, vol. 4, pp 313–337

  • Malvoisin E, Lhoest G, Poncelet F, Roberfroid M, Mercier M (1979) Identification and quantitation of 1,2-epoxybutene-3 as the primary metabolite of 1,3-butadiene. J Chromatogr 178: 419–425

    Google Scholar 

  • Malvoisin E, Mercier M, Roberfroid M (1982) Enzymic hydration of butadiene monoxide and its importance in the metabolism of butadiene. Adv Exp Med Biol 38A: 437–444

    Google Scholar 

  • Malvoisin E, Roberfroid M (1982) Hepatic microsomal metabolism of 1,3-butadiene. Xenobiotica 12: 137–144

    Google Scholar 

  • Phalen RF (1983) Animal models. In: Inhalation studies formation and techniques, CRC Press Inc., Florida, pp 211–241

    Google Scholar 

  • Schmidt U, Loeser E (1985) Species differences in the formation of butadiene monoxide from 1,3-butadiene. Arch Toxicol 57:222–225

    Google Scholar 

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

    Google Scholar 

  • Van Duuren BL, Nelson N, Orris L, Palmes ED, Schmitt FL (1963) Carcinogenicity of epoxides, lactons and peroxy compounds. J Natl Cancer Inst 31: 41–55

    Google Scholar 

  • Walker CH (1978) Species differences in microsomal monooxygenase activity and their relationship to biological half-lives. Drug Metab Rev 7: 295–323

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kreiling, R., Laib, R.J., Filser, J.G. et al. Species differences in butadiene metabolism between mice and rats evaluated by inhalation pharmacokinetics. Arch Toxicol 58, 235–238 (1986). https://doi.org/10.1007/BF00297112

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00297112

Key words

Navigation