The need to add whole organism models to reduce uncertainties in developmental neurotoxicity testing strategies

There is growing evidence of an association between exposure to toxic compounds and developmental neurotoxicity (DNT). Despite this, systematic DNT testing of chemicals to understand how they impact brain development is not mandatory in international regulations for the approval of pharmaceuticals or industrial chemicals. Traditional animal studies, while informative, are often time-consuming, expensive, and not always directly relevant to human biology. Recent advancements have focused on new approach methodologies (NAMs), particularly cell-based assays, to investigate the molecular mechanisms of toxicity. However, these assays often fail to capture the complexity of DNT, which involves multiple interacting pathways at the molecular, cellular, and tissue levels. Consequently, there is a growing need for validated whole organism models that can provide a more comprehensive understanding of DNT and its impact on brain development and neurobehavioral outcomes. Alternative animal models, such as nematodes, planarians, fruit flies, and zebrafish, offer promising alternatives due to their ethical and practical advantages, as well as their ability to develop functioning brains with conserved neurodevelopmental processes.

This Research Topic aims to explore the added value of whole organism models in DNT testing strategies and integrated approaches to testing and assessment (IATAs). The primary objective is to evaluate how these models can complement existing cell-based assays to provide a more accurate prediction of developmental neurotoxicity. Specific questions to be addressed include the utility of these models in measuring DNT, their relevance to endocrine disruption mechanisms, and their current status and future development needs. Additionally, the research will investigate the protocols and endpoints used in these models, their applicability domains, and their potential regulatory uses.

To gather further insights into the boundaries of this research, we welcome articles addressing, but not limited to, the following themes:
- Utilization of whole organism models to measure DNT in both environmental and human hazard contexts.
- Exploration of the link between DNT and endocrine disruption mechanisms.
- Current status and developmental needs of whole organism models for DNT testing.
- Detailed protocols and endpoints relevant to DNT and their significance.
- Applicability domains of these models, including present and absent processes and mechanisms.
- Regulatory implications and future steps for incorporating these models into regulatory frameworks.

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Data Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• ... View all formats

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Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Data Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Policy and Practice Reviews
• Policy Brief
• Review
• Study Protocol
• Systematic Review

Keywords: neurotoxicology, model organisms, developmental neurotoxicity, whole organism models, New Approach Methodologies (NAM), brain, screening, 3Rs, neurobehaviour

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.