John Wiley & Sons, Ltd.

A physiologically‐based pharmacokinetic model for disposition of 2,3,7,8‐TCDD in fathead minnow and medaka

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A Physiologically‐Based Pharmacokinetic (PBPK) model was developed for the disposition of 2,3,7,8‐TCDD in two fish species, fathead minnow and medaka. The model was developed based on the empirical data on disposition of dioxins in fish tissues, as well as existing knowledge on the mechanisms of uptake, distribution, storage and elimination of dioxins in various species (other than fish). This study examined the applicability of mechanisms known to occur in other species for fish and concluded that the same mechanisms defined for disposition of 2,3,7,8‐TCDD in (mostly) rodents can be applicable for the two fish species examined as well. Parameter values for the model were selected and/or calibrated using available databases. Model compartments included the gill, kidney, liver and other richly‐perfused tissues, as well as fat and other slowly‐perfused tissues. The model was calibrated using two independent datasets for exposure of fathead minnow and medaka to 2,3,7,8‐TCDD in water. The initial values of the model parameters were selected from several sources, and calibrated to represent the two exposure datasets. With very few exceptions the estimated parameter values for the two species were comparable, and the final predictions were in strong agreement with the observations. The model developed in this study can therefore be used in the prediction of the body burden of 2,3,7,8‐TCDD in two fish species, fathead minnow and medaka. Uncertainty in the model prediction as a result of variability in input parameters is discussed for the parameters with the highest impacts on the model outcome. Environ Toxicol Chem © 2013 SETAC

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