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.
Leavens
T L
TL
University of North Carolina, Chapel Hill 27599-7270, USA.
Bond
J A
JA
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