A Physiologically-Based Pharmaco-Kinetic Model for Disposition of Dioxins and Furans in Fish

A Physiologically Based Pharmacokinetic (PBPK) model was developed for the disposition of dioxins in various fish species. The model was developed based on available information on the mechanisms of uptake, distribution, storage and elimination of dioxins in various species (other than fish) and empirical data on disposition of dioxins in the fish tissues. Two versions of the model were implemented: one for exposure to dioxins in water through the gill and the other one for exposure through food. Model compartments included the gill, kidney, liver and other richly-perfused tissues, as well as fat and other slowly-perfused tissues. In the food exposure version, the gut was also included as a richly-perfused tissue. The water exposure model was calibrated using two independent data sets for exposure of fathead minnow and medaka to 2,3,7,8-TCDD in water. The estimated parameter values in the two data sets were comparable and the predictions agreed with the observations very well. The results were compared to those produced by the default methods (bioconcentration factors). Uncertainty in the model prediction as a result of variability in input parameters was also discussed for the parameters with the highest impacts on the model outcome. The predictions of the food pathway exposure model were compared to data for rainbow trout liver.