Species Differences in Butadiene Metabolism Between Mice and Rats Evaluated by Inhalation Pharmacokinetics

Overview

Journal Arch Toxicol

Specialty Toxicology

Date 1986 Apr 1

PMID 3718226

Citations 20

Authors

R Kreiling

R J Laib

J G Filser

H M Bolt

Affiliations

Soon will be listed here.

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 7300 ml X h-1 (rat: 4500 ml X h-1. Maximal metabolic elimination rate (Vmax) was 400 mumol X h-1 X kg-1 (rat: 220 mumol X h-1 X 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.

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References

Filser J, Bolt H . Inhalation pharmacokinetics based on gas uptake studies. I. Improvement of kinetic models. Arch Toxicol. 1981; 47(4):279-92. DOI: 10.1007/BF00332394. View

Filser J, Bolt H . Pharmacokinetics of halogenated ethylenes in rats. Arch Toxicol. 1979; 42(2):123-36. DOI: 10.1007/BF00316492. View

Filser J, Bolt H . Inhalation pharmacokinetics based on gas uptake studies. IV. The endogenous production of volatile compounds. Arch Toxicol. 1983; 52(2):123-33. DOI: 10.1007/BF00354772. View

Huff J, Melnick R, Solleveld H, Haseman J, Powers M, Miller R . Multiple organ carcinogenicity of 1,3-butadiene in B6C3F1 mice after 60 weeks of inhalation exposure. Science. 1985; 227(4686):548-9. DOI: 10.1126/science.3966163. View

VANDUUREN B, Nelson N, Orris L, PALMES E, SCHMITT F . CARCINOGENICITY OF EPOXIDES, LACTONES, AND PEROXY COMPOUNDS. J Natl Cancer Inst. 1963; 31:41-55. View

Bolt H, Filser J, Stormer F . Inhalation pharmacokinetics based on gas uptake studies. V. Comparative pharmacokinetics of ethylene and 1,3-butadiene in rats. Arch Toxicol. 1984; 55(4):213-8. DOI: 10.1007/BF00341013. View

Schumann A, Quast J, Watanabe P . The pharmacokinetics and macromolecular interactions of perchloroethylene in mice and rats as related to oncogenicity. Toxicol Appl Pharmacol. 1980; 55(2):207-19. DOI: 10.1016/0041-008x(80)90082-4. View

Malvoisin E, Mercier M, Roberfroid M . Enzymatic hydration of butadiene monoxide and its importance in the metabolism of butadiene. Adv Exp Med Biol. 1981; 136 Pt A:437-44. DOI: 10.1007/978-1-4757-0674-1_32. View

Walker C . Species differences in microsomal monooxygenase activity and their relationship to biological half-lives. Drug Metab Rev. 1978; 7(2):295-323. DOI: 10.3109/03602537808993770. View

10.

Bolt H, Schmiedel G, Filser J, Rolzhauser H, Lieser K, Wistuba D . 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. 1983; 106(2):112-6. DOI: 10.1007/BF00395388. View

11.

Schmidt U, Loeser E . Species differences in the formation of butadiene monoxide from 1,3-butadiene. Arch Toxicol. 1985; 57(4):222-5. DOI: 10.1007/BF00324781. View

12.

Filser J, Bolt H . 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. 1984; 55(4):219-23. DOI: 10.1007/BF00341014. View

13.

Malvoisin E, Roberfroid M . Hepatic microsomal metabolism of 1,3-butadiene. Xenobiotica. 1982; 12(2):137-44. DOI: 10.3109/00498258209046787. View

14.

Andersen M . Saturable metabolism and its relationship to toxicity. Crit Rev Toxicol. 1981; 9(2):105-50. DOI: 10.3109/10408448109059563. View