A biologically based toxicokinetic model for pyrene in rainbow trout.

A biologically based toxicokinetic model was developed to stimulate the metabolic disposition of pyrene in trout with an average body weight of 450 g and dosed with a single bolus injection of the chemical (10 mg/kg). The model consists of a membrane-limited muscle compartment and six flow-limited compartments including the gills, liver, gut, kidney, carcass, and blood. The compartments are represented by mass balance equations including terms for the binding of pyrene to tissue and blood proteins, biotransformation, penetration rate into the muscle, blood flow rate, tissue mass, etc. The model also provides for nonsaturable and saturable clearances of pyrene by the liver and kidney. Michaelis-Menten constants for pyrene metabolism (Km, Vmax) were determined from in vitro experiments using isolated liver cells. Renal clearance of pyrene was very close to the glomerulus filtration rate of trout. Solution of the system of equations yielded the time courses of pyrene concentration in the tissues. Predicted concentrations of pyrene in the gills, liver, gut, kidney, muscle, and blood were consistent with experimental observations for at least 6 days. The model was validated by comparing the model predicted and experimental results of trout weighing 285 g and dosed with a single intraarterial dose (3 mg/kg) of pyrene. The predicted pyrene concentrations also were in adequate agreement with the empirical data.