WP 5: ENP toxicokinetics and toxicodynamics

NERC, VUA, UOXF.DJ, UAVR, UNIPMN, IHPP, CU, UGOT

• Objectives

• Identify the internal fate of trackable particles in exposed organisms by combining time series exposures with detailed tissue and cellular morphology using qualitative and quantitative particle detection methods. (Main participants: UNIPMN, CU, UOXF.DJ, IPHH)
• Investigate the link between internalisation and toxicological effects in time series exposures, and use model prediction of toxicokinetic parameters to study the internal tissue distribution and form of ENPs (using analytical electron microscopy) to attribute causal effects to intact ENPs and dissolved free metal ions. (Main participants: VUA, NERC, UGOT, CU, UOXF.DJ)
• Investigate the suitability of existing biomarkers for major modes of action known to be linked to ENP toxicity (e.g. reactive oxygen species (ROS) generation, lysosomal responses) for identification of ENP exposure and early-stage effects. (Main participants: UNIPMN, UWC/NERC, VUA, CU)
• Utilise a toxicogenomic approach to investigate novel modes of action associated with ENP exposure when compared to effects attributable to the free metal ions in samples from organisms exposed at ion levels close to concentrations known to cause life-history effects. (Main participants: UNIPMN, CU, VUA)