Species differences in butadiene metabolism between mouse and rat.

Studies on inhalation pharmacokinetics of 1,3-butadiene were conducted in mice (B6C3F1) and rats (Sprague-Dawley) to investigate the considerable differences in the susceptibility of both species to butadiene-induced carcinogenesis. In rats and mice metabolism of 1,3-butadiene to 1,2-epoxybutene-3 follows saturation kinetics. "Linear" (first-order) pharmacokinetics apply at exposure concentrations below 1000 ppm 1,3-butadiene. Saturation of butadiene metabolism is observed at atmospheric concentrations of about 2000 ppm butadiene. In the lower concentration range where first-order metabolism applies, metabolic clearance of inhaled 1,3-butadiene per kg body weight was 7300 ml (gas volume) x hr-1 for mice and 4500 ml x hr-1 for rats. The calculated maximal metabolic elimination rates (Vmax - conditions) were 400 mumol x hr-1 x kg-1 for mice and 220 mumol x hr-1 x kg-1 for rats. This shows that 1,3-butadiene is metabolized by mice at about twice the rate of rats, under conditions of both low and high exposure concentrations.