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 partialy 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 K(mapp) = 1.17 +/- 0.37 (mu-mol/l of tissue) and the corresponding atmospheric concentration at steady state was 560 ppm. The inhibition constant of styrene was found to be K(i) = 0.23 +/- 0.30 (mu-mol/l of tissue). The maximal metabolic rate for 1,3-butadiene was 230 +/- 10 (mu/kg/h).