The short video from RIVM explains the ONTOX work on developing animal-free computational modeling to prevent human chemical-induced neural tube defects.
The Centre for Health Protection of the Dutch National Institute for Public Health and the Environment (RIVM) is part of the ONTOX consortium on behalf of the project partner Utrecht University. This video zooms on the RIVM’s development of a computational model for neural tube development, an aspect of human development that is especially vulnerable to chemical disruption:
The classical way of safety assessment relies heavily on the use of laboratory animals. However, humans may respond differently to toxic substances than animals.
Therefore, RIVM is working on a new approach for human safety assessment based on ontologies. Ontologies can be used to describe human biology and delineate the basis of adverse outcome pathway (AOPs) networks. AOPs characterize how chemical exposures may lead to adverse health effects and can help to select animal-free in vitro and in silico methods, comprehensively covering the network.
“Based on our knowledge of physiology and disease, we can actually describe what happens when a compound affects the system all the way to the disease that emerges which is at the end. We can describe this process in so-called adverse outcome pathways in which we describe all the different elements that lead from the initial event to the adverse outcome in the end.”
RIVM is working on a three-dimensional computational model of neural tube closure in the developing embryo using the ontology approach. This model can improve the prediction of human developmental toxicity.
“We have a detailed understanding of how the neural tube is formed in embryogenesis. This allows us to describe the ontology to extract the AOPs and to define what test systems we need to test the effects of compounds on the system. And this combined with in silico models will allow us to do a hazard and risk assessment of chemicals using this novel, human-based system,” explains Prof. Dr. Aldert Piersma, RIVM.