Uptake, distribution and elimination of chemicals in fish - Which physiological parameters are the most relevant for toxicokinetics?

Bioconcentration and toxicity studies are regularly conducted for the risk assessment of chemicals. If such tests yield different results for different fish species, this can either be due to differences in toxicokinetics or to differences in toxicodynamics. Here we investigate which physiological parameters could cause major differences in the toxicokinetics in fish. To this end it is important to distinguish physiological parameters that affect the sorption capacity of the fish from those that affect kinetic processes. Variability in the lipid content of a fish is the most influential parameter for the sorption capacity of fish and therefore most relevant for the total concentration in fish under steady-state conditions when metabolism is not relevant. In terms of kinetics, ventilation rate, uptake efficiency from food and metabolism are the most influential factors. While ventilation rate can roughly be estimated from allometric scaling equations, little general information is available on the uptake efficiency from food. The metabolism rate constant appears to be the single most influential toxicokinetic factor. This information cannot be estimated but must be determined experimentally, preferably from in vitro experiments.

Modelling oral up-take of hydrophobic and super-hydrophobic chemicals in fish.

We have extended a recently published toxicokinetic model for fish (TK-fish) towards the oral up-take of contaminants. Validation with hydrophobic chemicals revealed that diffusive transport through aqueous boundary layers in the gastro-intestinal tract and in the blood is the limiting process. This process can only be modelled correctly if facilitated transport by albumin or bile micelles through these boundary layers is accounted for. In a case study we have investigated the up-take of a super hydrophobic chemical, Dechlorane Plus. Our results suggest that there is no indication of a hydrophobicity or size cut-off in the bioconcentration of this chemical. Based on an extremely high, but mechanistically sound facilitation factor we received model results in good agreement with experimental values from the literature. The results also indicate that established experimental procedures for BCF determination cannot cover the very slow up-take and clearance kinetics that are to be expected for such a chemical.

A toxicokinetic model for fish including multiphase sorption features.

In the scientific field of physiologically based toxicokinetic modeling the complexity of the model used depends on the complexity of the problem to be handled, leading to a broad range of existing models from simple 1-box models to complex multicompartment models. Most of these models work with lumped parameters, for example, an uptake efficiency parameter that can only be obtained with a fit of experimental data. The authors' goal was a model that is completely based on well-defined physiological and physicochemical parameters. Lumped parameters fitted on training data sets would limit the model's applicability. This would enable a new view on process understanding for uptake, distribution, and elimination procedures. Eventual goals are a better localization of chemicals within the organism itself, and to set the stage for future extensions toward ionic compounds and active transport across membranes. The model evaluation reported in the present study has shown that uptake, clearance, and bioaccumulation data for nonpolar chemicals are well predicted. Environ Toxicol Chem 2017;36:1538-1546. © 2016 SETAC.