A physiologically based toxicokinetic model for the zebrafish Danio rerio

Area of Science:

• Environmental toxicology
• Pharmacokinetics and toxicokinetics
• Aquatic toxicology

Background:

• Zebrafish (Danio rerio) are crucial models for toxicological research, especially endocrine disruption.
• Toxicokinetic modeling can enhance the regulatory application of zebrafish-based in vivo and in vitro tests.

Purpose of the Study:

• To develop a physiologically based toxicokinetic (PBTK) model for zebrafish.
• To describe the uptake and disposition of organic chemicals in zebrafish.
• To evaluate existing models for predicting chemical-specific parameters.

Main Methods:

• The PBTK model integrates literature data, new experimental physiological information from zebrafish, and predicted chemical-specific parameters.
• Evaluated the relevance of predictive models for gill uptake and partition coefficients.
• Included confounding factors like body weight and temperature on ventilation rate.

Main Results:

• The PBTK model accurately predicted toxicokinetic data for six chemicals (88% within a factor of 5).
• Sensitivity analysis identified key parameters for effective modeling: 1-octanol/water partition coefficient, metabolism rate, and assimilation/partitioning parameters.

Conclusions:

• The developed PBTK model is a valuable tool for zebrafish toxicological studies.
• Precise determination of specific parameters is crucial for accurate toxicokinetic modeling in zebrafish.
• This model supports enhanced regulatory use of zebrafish in toxicological assessments.