Advancing Toxicokinetic-Toxicodynamic Modeling To Assess Kinetic Bioavailability in Sediments

Traditional sediment risk assessments often rely on fixed-duration dose-response end points, which overlook how exposure conditions and organismal response interact over time. Toxicokinetic-toxicodynamic (TKTD) models address this by linking external exposure, internal concentration, and effects, but their application to sediments has been limited by the lack of suitable tracing methods to generate high-quality kinetic data. Here, we developed a novel stable isotope tracing approach tailored for sediment TKTD studies: prelabeling clams with stable ⁶⁵Cu in water prior to Cu-amended sediment exposure. By simultaneously tracking ⁶⁵Cu elimination and ambient Cu uptake, we successfully established a sediment TKTD model integrating bioaccumulation with toxicity, measured by clam survival across a wide range of Cu bioavailability driven by speciation differences. The model revealed that the clam Ruditapes philippinarum's Cu elimination and tolerance capability were consistent across exposure conditions, indicating species-specific physiological traits. Cu uptake followed a saturation-type Michaelis-Menten relationship with bioavailable Cu. From these kinetics, we derived mechanistic bioavailability benchmarks (DGT-Cu based LC₅₀-chronic = 42 μg L^-1 and no-effect concentration (NEC_DGT) = 34 μg L^-1) as chronic thresholds applicable to risk assessment. Overall, this study demonstrates TKTD modeling in sediments using stable isotope tracing, advancing process-based ecological risk assessments and providing a transferable framework for evaluating contaminant bioavailability in estuarine ecosystems.