A biologically based toxicokinetic model for pyrene in rainbow trout

Area of Science:

• Environmental toxicology
• Aquatic toxicology
• Pharmacokinetics

Background:

• Polycyclic aromatic hydrocarbons (PAHs) like pyrene pose risks to aquatic ecosystems.
• Understanding the metabolic disposition of pyrene in fish is crucial for ecological risk assessment.
• Existing models may not fully capture the complex processes of pyrene uptake and elimination in fish.

Purpose of the Study:

• To develop a biologically based toxicokinetic model for pyrene in trout.
• To simulate the metabolic disposition and tissue distribution of pyrene.
• To validate the model against experimental data for improved predictive accuracy.

Main Methods:

• Development of a mass balance model with compartments for gills, liver, gut, kidney, carcass, and blood.
• Inclusion of parameters for protein binding, biotransformation (Michaelis-Menten kinetics), and blood flow.
• Determination of kinetic parameters from in vitro liver cell experiments.
• Validation using experimental data from trout of different body weights and dosages.

Main Results:

• The model accurately predicted pyrene concentrations in various trout tissues for up to 6 days.
• Nonsaturable and saturable clearance mechanisms in the liver and kidney were incorporated.
• Renal clearance was found to be similar to the glomerular filtration rate in trout.
• Model predictions showed adequate agreement with empirical data during validation.

Conclusions:

• The developed toxicokinetic model provides a robust tool for simulating pyrene disposition in trout.
• The model enhances our ability to predict pyrene exposure and accumulation in aquatic organisms.
• This biologically based approach offers valuable insights for environmental risk assessment of pyrene.