Advancing Toxicokinetic-Toxicodynamic Modeling To Assess Kinetic Bioavailability in Sediments.

Area of Science:

• Environmental Toxicology
• Ecotoxicology
• Aquatic Toxicology

Background:

• Traditional sediment risk assessments use fixed endpoints, missing dynamic exposure-effect interactions.
• Toxicokinetic-toxicodynamic (TKTD) models link exposure, internal dose, and effects but lack sediment application methods.
• High-quality kinetic data for sediment TKTD models is limited by tracing method availability.

Purpose of the Study:

• To develop a novel stable isotope tracing approach for sediment TKTD studies.
• To integrate bioaccumulation and toxicity in a sediment TKTD model for copper (Cu).
• To establish mechanistic bioavailability benchmarks for chronic risk assessment in estuarine ecosystems.

Main Methods:

• Pre-labeled clams (Ruditapes philippinarum) with stable ⁶⁵Cu in water before sediment exposure.
• Simultaneously tracked ⁶⁵Cu elimination and ambient Cu uptake in clams exposed to Cu-amended sediments.
• Developed a sediment TKTD model integrating bioaccumulation and clam survival across varying Cu bioavailability.

Main Results:

• Established a sediment TKTD model demonstrating species-specific Cu elimination and tolerance in clams.
• Identified a Michaelis-Menten relationship between Cu uptake and bioavailable Cu.
• Derived chronic thresholds: DGT-Cu based LC₅₀-chronic = 42 μg L^-1 and NEC_DGT = 34 μg L^-1.

Conclusions:

• Stable isotope tracing enables TKTD modeling in sediments, advancing process-based ecological risk assessment.
• The developed framework is transferable for evaluating contaminant bioavailability in estuarine environments.
• Mechanistic bioavailability benchmarks provide improved chronic thresholds for sediment risk management.