• Delineation of the exposure-response causality chain of chronic copper toxicity to the zebra mussel, Dreissena polymorpha, with a TK-TD model based on concepts of biotic ligand model and subcellular metal partitioning model.

      Le, T T Yen; Milen, Nachev; Grabner, Daniel; Hendriks, A Jan; Peijnenburg, Willie J G M; Sures, Bernd (2021-08-18)
      A toxicokinetic-toxicodynamic model was constructed to delineate the exposure-response causality. The model could be used: to predict metal accumulation considering the influence of water chemistry and biotic ligand characteristics; to simulate the dynamics of subcellular partitioning considering metabolism, detoxification, and elimination; and to predict chronic toxicity as represented by biomarker responses from the concentration of metals in the fraction of potentially toxic metal. The model was calibrated with data generated from an experiment in which the Zebra mussel Dreissena polymorpha was exposed to Cu at nominal concentrations of 25 and 50 μg/L and with varied Na+ concentrations in water up to 4.0 mmol/L for 24 days. Data used in the calibration included physicochemical conditions of the exposure environment, Cu concentrations in subcellular fractions, and oxidative stress-induced responses, i.e. glutathione-S-transferase activity and lipid peroxidation. The model explained the dynamics of subcellular Cu partitioning and the effect mechanism reasonably well. With a low affinity constant for Na + binding to Cu2+ uptake sites, Na + had limited influence on Cu2+ uptake at low Na+ concentrations in water. Copper was taken up into the metabolically available pool (MAP) at a largely higher rate than into the cellular debris. Similar Cu concentrations were found in these two fractions at low exposure levels, which could be attributed to sequestration pathways (metabolism, detoxification, and elimination) in the MAP. However, such sequestration was inefficient as shown by similar Cu concentrations in detoxified fractions with increasing exposure level accompanied by the increasing Cu concentration in the MAP.
    • Modelling copper toxicokinetics in the zebra mussel, Dreissena polymorpha, under chronic exposures at various pH and sodium concentrations.

      Le, T T Yen; Grabner, Daniel; Nachev, Milen; Peijnenburg, Willi J G M; Hendriks, A Jan; Sures, Bernd (2020-12-11)
      The stenohaline zebra mussel, Dreissena polymorpha, is uniquely sensitive to the ionic composition of its aquatic environment. Waterborne copper (Cu) uptake and accumulation in zebra mussels were examined at various conditions in an environmentally relevant range in freshwater, i.e. Cu exposure levels (nominal concentrations of 25 and 50 μg/L), pH (5.8-8.3), and sodium (Na+) concentrations (up to 4.0 mM). Copper accumulation was simulated by a kinetic model covering two compartments, the gills and the remaining tissues. The Cu uptake rate constant decreased with decreasing pH from 8.3 down to 6.5, indicating interactions between H+ and Cu at uptake sites. The kinetic simulation showed dose-dependent effects of Na+ on Cu uptake. At 25 μg/L Cu, addition of Na+ at 0.5 mM significantly inhibited the Cu uptake rate, while no significant differences were found in the uptake rate upon further addition of Na+ up to a concentration of 4.0 mM. At 50 μg/L Cu, the Cu uptake rate was not influenced by Na+ addition. Calibration results exhibited dose-dependent elimination rates with more profound elimination with increasing exposure levels. With kinetic parameters calibrated at environmentally relevant conditions, in terms of pH and Na+ concentrations, the model performed well in predicting Cu accumulation based on independent data sets. Estimates of the Cu concentration in mussels were within a factor of 2 of the measurements. This demonstrates potential application of kinetic models that are calibrated in environmentally relevant freshwater conditions.