A pharmacokinetic model for predicting absorption, elimination, and tissue burden of toxaphene in rats

A two-compartment pharmacokinetic model was formulated to predict absorption, elimination, and tissue burden of toxaphene in rats. The model was constructed based on the database of Crowder and Dindal (Bull. Environ. Contam. Toxicol. 12, 320-327, 1974) and included six tissue compartments: blood, brain, liver, muscle, fat, and carcass. The pharmacokinetically based dosimetry indicated that absorption of toxaphene was fast in fat, whole body, carcass, and blood, relatively slow in liver and muscle, and slow in brain. In contrast, the elimination rate was rapid in whole body, muscle, and blood, moderate in carcass and brain, and slow in liver and fat. Tissue burden was highest in fat, whole body, and blood, intermediate in liver, and lowest in brain. The model performance was evaluated by the data set of Pollock and Hillstrand (J. Environ. Sci. Health B 17, 635-648, 1982) on toxaphene absorption and elimination in pregnant rats. Validity of the model was confirmed by the close agreement between the predicted and observed tissue burdens of toxaphene in target tissues. Disposition of toxaphene via feces was a dominant excretory pathway while urinary excretion was a minor elimination route in male rats. However, for pregnant rats, excretion of toxaphene both in urine and feces were of similar magnitude. These characteristics of elimination are valuable for understanding the metabolism of toxaphene in pregnant rats. The model serves as a starting point for a quantitative, mechanism-based understanding of the processes that influence the pharmacokinetics of toxaphene in mammalian systems.