Twenty-first century challenges for in vitro neurotoxicity

Area of Science:

• Neuroscience
• Toxicology
• Cell Biology

Background:

• In vitro methodologies have significantly advanced human nerve cell biology understanding over 40 years.
• Application of these methods to neurotoxicity investigations faces challenges due to the nervous system's complexity.
• Alternative neural models are crucial for elucidating mechanisms of neurotoxicity.

Purpose of the Study:

• To review the development and current state of alternative neural models for neurotoxicity assessment.
• To discuss various available model systems and their applications.
• To highlight key neuronal endpoints and cytotoxic evaluations for assessing neurotoxicity.

Main Methods:

• Review of scientific literature on in vitro and alternative neural models.
• Analysis of tiered testing strategies for neurotoxicity screening.
• Discussion of advancements in molecular and stem cell biology relevant to neural tissue.

Main Results:

• Alternative neural models are currently most effective in determining mechanisms of nervous system perturbation.
• Tiered batteries of test models show encouraging data for neurotoxicity screening globally.
• Developments in molecular and stem cell biology offer future advancements.

Conclusions:

• Alternative neural models are essential for understanding neurotoxicity mechanisms in both adult and embryonic nervous systems.
• The integration of tiered testing strategies and novel biological advancements promises significant progress in the next decade.
• Continued research in neural alternatives is vital for accurate neurotoxicity assessment and ensuring neural health.