Deliverable 4.8 Report on the determination of uptake rate constants for physiologically based toxicokinetic modelling

Multicomponent and high-aspect ratio nanomaterials (MCNMs and HARNs) have various industrials applications. MCNMs and other chemical compounds containing ZnO are applied in sunscreens and cosmetic products and, therefore, are valuable substances. However, the potential toxic effect of these (nano)materials on various biological systems is uncertain. Differentiating between uptake of true metal NMs and that of released ions is essential to assess the actual role of these two metal forms in toxicity over time. Therefore, toxicokinetic experiments were conducted to assess the implications of ZnO containing NM and their components on earthworms in soil, daphnia in fresh water, and biofilm in sediment. These experiments comprised an uptake phase in which these organisms were exposed to a ZnO containing NM or one of its (ionic) components, after these organisms were transferred to a clean environment to depurate themselves from the NM or their components in the elimination phase. Earthworms exposed to the ZnO:Mn MCNM showed a rapid increase in Zn and Mn concentrations, followed by a rapid decline after transfer to clean soil. Earthworms exposed to MnCl2 showed increases and decreases in Mn concentration after exposure and transfer to clean soil that were similar to worms exposed to ZnO:Mn. Daphnids exposed to ZnO:Mn and ZnO also showed a rapid increase in Zn concentration, but a negligible decline after transfer to clean media. The Mn concentration in daphnids exposed to ZnO:Mn indicated a gradual increase and decline after exposure and transfer to clean media, respectively. Toxicokinetic one-compartment models were fitted to the earthworm and daphnid data and enable the estimation of uptake and elimination rate parameters along with the computation of the bioaccumulation factor. Moreover, in this deliverable a protocol to evaluate the toxicodynamics of ZnO and ZnO:Mn nanoparticles in biofilms is described, as well as the results obtained.