Pharmacokinetic interaction between 1,3-butadiene and styrene in Sprague-Dawley rats.
Gas uptake studies were carried out to evaluate kinetic interactions between 1,3-butadiene and styrene in Sprague-Dawley rats. The animals were co-exposed by inhalation to a mixture of 1,3-butadiene between 20 and 6000 ppm (v/v) and styrene between 0 and 500 ppm. The data demonstrate that metabolism of 1,3-butadiene was partially inhibited by styrene. The inhibition was competitive at atmospheric concentrations of styrene up to 90 ppm. Higher concentrations of styrene resulted in a small additional inhibition only. The apparent Michaelis-Menten constant for 1,3-butadiene, related to the average concentration in the organism of the animals, was Kmapp = 1.17 +/- 0.37 (mumol/l of tissue) and the corresponding atmospheric concentration at steady state was 560 ppm. The inhibition constant of styrene was found to be Ki = 0.23 +/- 0.30 (mumol/l of tissue). The maximal metabolic rate for 1,3-butadiene was 230 +/- 10 (mu/kg/h).
Laib
R J
RJ
Institut für Arbeitsphysiologie, Universität Dortmund, Federal Republic of Germany.
Tucholski
M
M
Filser
J G
JG
Csanády
G A
GA
D000388:Air / Q000032:analysis; D000818:Animals; D002070:Butadienes / Q000032:analysis / Q000493:pharmacokinetics*; D002849:Chromatography, Gas; D004347:Drug Interactions; D007700:Kinetics; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D020058:Styrene; D013343:Styrenes / Q000032:analysis / Q000493:pharmacokinetics*
D002070:Butadienes; D013343:Styrenes; D020058:Styrene; C031763:1,3-butadiene