Compartmental analysis of benzo[a]pyrene toxicokinetics

A multicompartmental model to describe quantitatively the toxicokinetics of benzo[a]pyrene (B[a]P) was developed using SAAM (Simulation, Analysis and Modeling). [3H]-B[a]P dissolved in triethylene glycol was administered intratracheally to male Sprague-Dawley rats, and amounts of [3H] were quantified in various tissues at selected times up to 6 hr after administration. Elimination of [3H]-B[a]P and/or metabolites from lungs was biphasic, with half-times of 5.3 min. and 116 min. [3H]-B[a]P and/or metabolites were subsequently distributed primarily to liver and carcass (muscle, bones, fat, skin and associated blood). Carcass contained about 20% of administered [3H] at 6 hr after administration, and agreement between the model and experimental data required that the carcass be modeled as two compartments, one with rapid and one with slow exchange. Approximately 50% of the administered dose was excreted in feces in 6 hr and only 2% appeared in urine. Enterohepatic circulation was accounted for in the model. The model was then used to predict amounts of [3H]-B[a]P and/or metabolites which would be excreted into bile in animals with bile duct cannulas, and good agreement between the model and data was observed