Pharmacokinetic model describing the disposition of butadiene and styrene in mice.
Coexposure to 1,3-butadiene (BD) and styrene occurs in the workplace of many polymer industries. The reactive epoxide metabolites of both compounds are responsible for their genotoxicity. A physiologically based pharmacokinetic (PBPK) model was developed to describe the simultaneous disposition of BD and styrene in mice coexposed by inhalation. A model with one oxidative pathway and competition between BD and styrene was compared with a model with two oxidation pathways for both BD and styrene. The different PBPK models were used to simulate the observed rate of BD metabolism and blood concentration of styrene from 8-h inhalation exposures of mice to mixtures of BD and styrene. The model with two oxidative pathways more accurately simulated the observed inhibition of BD uptake in coexposed mice.
University of North Carolina, Chapel Hill 27599-7270, USA.
T L
TL
Leavens
J A
JA
Bond
D000818:Animals; D002070:Butadienes / Q000493:pharmacokinetics*; D002273:Carcinogens / Q000493:pharmacokinetics*; D004347:Drug Interactions; D008297:Male; D051379:Mice; D008954:Models, Biological; D020058:Styrene; D013343:Styrenes / Q000493:pharmacokinetics*
D002070:Butadienes; D002273:Carcinogens; D013343:Styrenes; D020058:Styrene; C031763:1,3-butadiene