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EC number: 209-674-2 | CAS number: 590-19-2
The time-dependent decline of 1,3-butadiene in the closed system starting at initial concentrations of 10 to 5000 ppm showed that the curves for became flatter at higher concentrations indicating saturable elimination. Below about 1000ppm elimination was first order but at the higher concentrations saturation kinetics became apparent. Km and Vmax are shown below.
A constant equilibrium was achieved in both mice and rats after a distribution-dependent decline in the gas phase. The metabolism of 1,3-butadiene was inhibited by dithiocarb in both species.
1,3-Butadiene is exhaled after IP administration to mice. Kinetic parameters were then computed and calculated from the inhalation exposures and IP experiments. The pharmacokinetic model of Filser and Bolt fitted the kinetic behaviour of 1,3-butadiene. Metabolic elimination rates were then calculated. A comparison of the two species showed that metabolic elimination in mice is about twice that of rats under conditions of low and high exposure concentrations (mice: 7300 mL/h; rat: 4500 mL/h).
The table shows the pharmacokinetic parameters for 1,3-butadiene in rats and mice. The first order rate constants K21and Kel and co-efficient of static distribution (Keq) are similar in rats and mice. However, the maximum metabolic rate Vmax is higher and clearance (K12xV1) is 2-fold higher in mice than in rats. Therefore, under conditions of first order elimination, the steady-state concentration of 1,3-butadiene in mice is 2-fold higher than in rats.
Pharmacokinetc parameters for distribution and metabolism of 1,3-butadiene in rats and mice
The pharmacokinetics of 1,3-butadiene in mice after inhalation exposure of 10 to 5000 ppm (22-11063 mg/m3) in a closed system were investigated and compared with that of rats. Linear pharmacokinetics applied in both species at exposure concentrations below 1000 ppm, saturation of metabolism was observed at concentrations of about 2000 ppm. Metabolic clearance in the lower concentration range where first order metabolism applies was 7300 mL/h (rat) and 4500 mL/h (mice). Maximal metabolic elimination rate (Vmax) in mouse was 400 pmol/h/kg compared with 220 pmol/h/kg in rats. The results show that the higher rate of 1,3-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 1,3-butadiene -induced carcinogenesis.
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