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

A two-compartment pharmacokinetic model was formulated to predict absorptio n, elimination, and tissue burden of toxaphene in rats. The model was const ructed based on the database of Crowder and Dindal (Bull. Environ. Contain. Toxicol. 12, 320-327, 1974) and included six tissue compartments: blood, b rain, liver, muscle, fat, and carcass. The pharmacokinetically based dosime try indicated that absorption of toxaphene was fast in fat, whole body, car cass, 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 wa s 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 an d Hillstrand (J. Environ. Sci. Health B 17, 635-648, 1982) on toxaphene abs orption and elimination in pregnant rats. Validity of the model was confirm ed by the close agreement between the predicted and observed tissue burdens of toxaphene in target tissues. Disposition of toxaphene via feces was a d ominant excretory pathway while urinary excretion was a minor elimination r oute in male rats. However, for pregnant rats, excretion of toxaphene both in urine and feces were of similar magnitude. These characteristics of elim ination are valuable for understanding the metabolism of toxaphene in pregn ant rats. The model serves as a starting point for a quantitative, mechanis m-based understanding of the processes that influence the pharmacokinetics of toxaphene in mammalian systems. (C) 2000 Academic Press.