Session 2 Chair: Vladimir Lobaskin
Dr. Vladimir Lobaskin
Although the key to understanding toxicity is expected to be determined mostly by the chemistry of air or water pollutants, their biological action can be significantly modulated by multiple interactions in the environment and inside the organisms they enter. These interactions may change both the reactive properties of the toxicants and the way they are transported or disposed by the organisms. Therefore, for building predictive toxicological models one should address both intrinsic and system-dependent properties of toxicants. Modelling nanotoxicity is about predicting the risk due to the use of nanomaterials. Risk is defined as the probability that exposure to a hazard will lead to a negative consequence for the cell fate, or more simply, Risk = Hazard x Exposure. Hence modelling nanotoxicity is based on two types of models: Exposure models and Hazard models. Exposure models are intended to predict how nanomaterials evolve in the environment, including aggregation, and hence may harm human health and/or wildlife. On the other hand, hazard models are intended to predict what happens when nanomaterials come in contact with living cells and tissues. Hazard models can include materials modelling with the goal to determine nano-descriptors, which summarize the most relevant information about the nanomaterial, and interaction modelling to establish the relationships between the material properties and most significant biological endpoints, namely those specific biological events which are supposed to drive adverse effects. While statistical analysis often allows one to relate the physical and chemical descriptors of the materials to certain toxicity endpoints, the mechanisms of the toxic action are not always known.
The quantitative relations between the descriptors and the effect can only be deduced once we have a clear picture of all stages of interaction between the foreign agent and the biological tissue and of all stages of the systemic transport at the mechanistic level. The identification of molecular or nanomaterial properties responsible for the uptake or hazard can be facilitated by establishing the molecular initiating events in each adverse outcome pathway and by mechanistic modelling of the underlying processes. This effort is essential for creating sensible predictive schemes in toxicology. This session will address the ways to systematically describe the interactions at the nanobio interface, nanoparticle protein corona and toxicant transport across membranes.