Understanding the Role of Nano-TiO₂ on the Toxicity of Pb on C. dubia through Modeling -- Is It Additive or Synergistic?

Nano-TiO2 can remarkably increase lead (Pb) toxicity in aquatic organisms. However, the mechanism of this toxicity, additive or synergistic, is not well understood. To explore this mechanism, we inspected the role of nano-Ti O2 in the toxicity of Pb on Ceriodaphnia dubia (C. dubia), a model water flea species typically used for ecotoxicity studies. The effect of algae, a diet for aquatic organisms, on the effect of this binary mixture was also investigated. A two-compartment toxicokinetic (TK)-toxicodynamic (TD) modeling approach was used to quantify the Pb toxicity under these complex conditions and to develop critical parameters for understanding the mechanism of toxicity. This two-compartment modeling approach adequately described the Pb accumulation in the gut and in the rest of the body tissue under different nano-TiO2 concentrations, with and without algae, and predicted the toxicity response of C. dubia. It indicated that increasing the nano-Ti O2 concentration reduced the Pb tolerance level and concurrently increased the killing rate constant of C. dubia. Therefore, nano-TiO2 synergistically enhanced Pb toxicity. Algae remarkably reduced the toxicity of this binary mixture through reducing the Pb transfer rate to the body tissue and the killing rate, although it did not affect the Pb tolerance level. This two-compartment modeling approach is useful in understanding the role of nanoparticles when assessing the overall toxicity of nanoparticles and other toxic elements in the environment