Description
The need to add whole organism models to fill the gaps in developmental neurotoxicity testing strategies.Systematic testing of DNT is not mandatory in international regulations for admission of pharmaceuticals or industrial chemicals. Animal studies are often time consuming and expensive to perform and not always human relevant. Therefore, there are many developments of new approach methodologies (NAMs) for DNT, which are currently mainly focused on cell-based assays. Although these assays are very relevant to investigate the molecular mechanisms of toxicity of a compound in human cells, these cell-based assays do often not represent all steps of the complex process leading to DNT. Validated models, such as whole organism models, with a multi-organ network of pathways that interact at the molecular, cellular and tissue level at very specific timepoints in a life cycle are currently missing. Consequently, these whole model organisms are being developed to screen for, and causally link, new molecular targets of DNT compounds and how these affect whole brain development and neurobehavioral endpoints. Given the practical and ethical restraints associated with vertebrate testing, lower animal models that qualify as 3 R (reduce, refine and replace) models, including the nematode, planarians, fruit flies and zebrafish will prove particularly valuable for unravelling toxicity pathways leading to DNT. Although not as complex as the human brain, these 3 R-models develop a complete functioning brain with numerous conserved neurodevelopmental processes resulting in a functioning brain including neurobehavior. Chemical disruption might affect this neurobehavior and underlying mechanisms of toxicity.
Goal
The goal of this special issue is to address the added value of whole organism models for DNT related testing strategies and IATAs and how these models can be an addition to the existing cell-based assays to better predict developmental neurotoxicity.
| Period | 2025 |
|---|---|
| Type of journal | Journal |
| ISSN | 2673-3080 |