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Physiologically based modeling of hepatic and gastrointestinal biotransformation in fish
Nichols, J., L. Saunders, AND F. Gobas. Physiologically based modeling of hepatic and gastrointestinal biotransformation in fish. SETAC North America, Orlando, FL, November 06 - 10, 2016.
In fish, as in mammals, the liver generally viewed as the principal site of chemical biotransformation. For waterborne exposures, such as those conducted in support of standardized BCF testing, the effects of hepatic metabolism on chemical accumulation can be simulated using relatively simple models which assume, as a first approximation, that the liver operates on chemicals inblood, and that the blood is fully equilibrated with the rest of the animal. Such models may be inadequate, however, when biotransformation occurs elsewhere in the organism (e.g., gills or gut). This is particularly true when the diet is the primary route of exposure, as may be expected for hydrophobic chemicals in a natural setting, or when the organism is purposefully dosed in this manner (e.g., as part of recently developed dietary testing protocols). Here we use physiologically based toxicokinetic (PBTK) models to simulate how biotransformation occurrning in the liver and gut, alone or in combination, could be expected to impact chemical accumulation occurring as a result of wateronly, diet-only, and combined water and dietary exposures. Of specialinterest was the desire to develop the simplest model capable of adequately representing these processes. To support this effort we developed a set of scaling factors needed to extrapolate in vitro activity in gut subcellular fractions to the intact tissue. The modeled results indicate the need to represent the liver and gut as tissues operating in series against a fraction of the total cardiac output. Failure to model these processes correctly could result in underestimation of either tissue's true impact on chemical accumulation, particularly when the model is used to solve for apparent rates of activity based on measured chemical residues in the organism or apparent dietary assimilation efficiencies.