Uptake and depuration of Ag nanoparticles versus Ag ions by zebrafish through dietary exposure: characterization of Ag nanoparticle formation and dissolution in vivo and toxicokinetic modeling

The uptake and depuration of silver nanoparticles (AgNPs) vs. Ag⁺ by zebrafish (Danio rerio) were investigated using a range of analyses including single-particle ICP-MS (spICP-MS), high resolution-TEM imaging with crystal and elemental characterization of the extracted particles, and toxicokinetic modeling. We showed for the first time that AgNPs upon uptake were partially transformed into dissolved Ag and that reversely Ag⁺ was converted to Ag₂S and zerovalent AgNPs. The dissolution progressively resulted in smaller sized AgNPs in vivo. Regardless of initial Ag forms in exposure, both particulate and dissolved Ag were involved in the uptake and depuration of Ag by zebrafish. This obviously explained similar toxicokinetic profiles observed for AgNP vs. Ag⁺ exposure. A one-compartment toxicokinetic model could describe the mass concentration-based body burden data better (R² > 0.93) than the number concentration data (R² = 0.83). The observed dynamic particle fate processes such as dissolution and neo-formation of AgNPs discovered could not be totally captured by the traditionally mass concentration-based toxicokinetic model. Thus, the study highlights the dynamic biological fates of AgNPs in zebrafish that can influence the mass concentration-based vs. number concentration-based toxicokinetic behaviors.