Distribution and excretion of 2,2',4,4',5,5'-hexabromobiphenyl in rats and man: pharmacokinetic model predictions
Authors: Tuey, DB; Matthews, HB
Toxicology and Applied Pharmacology 53:420-431.
HERO ID: 4471079
A mathematical model was developed to describe the pharmacokinetics of 2,2′,4,4′,5,5′-hexabromobiphenyl . . .
A mathematical model was developed to describe the pharmacokinetics of 2,2′,4,4′,5,5′-hexabromobiphenyl (HBB) in rats and man. Rats were given single iv or multiple oral doses of [14C]HBB and tissue distribution and excretion data were obtained. A blood flow-limited physiological compartmental model was constructed and used to simulate the time course of HBB in rat tissues and excreta. Intestinal absorption of oral doses and reabsorption of HBB in bile could be accounted for by an effective permeability constant; a growing adipose tissue compartment was needed to properly describe the pharmacokinetics of HBB in growing rats. The model was then scaled to man by appropriately adjusting tissue volume, blood flow, and clearance and rate constant parameters. Human HBB tissue concentrations were predicted following an acute high-dose or a chronic low-dose exposure regimen, and the results compared to human data where available. As for the rat, adipose tissue had a significant effect on the HBB concentrations predicted in man. The estimated body burden t12 in man was 6.5 years. It appears that at least for this compound, past exposure and present and future human tissue concentrations can be estimated by extrapolating pharmacokinetic results obtained in the rat.