Neurotoxicity of Engineered Nanomaterials: Testing Considerations

Area of Science:

• Environmental toxicology
• Nanomaterial safety assessment
• Neuroscience

Background:

• Engineered nanomaterials (ENM) pose unique challenges in toxicological testing, particularly in neurotoxicology.
• Their complex physicochemical properties (size, surface area, composition, agglomeration, dissolution) complicate risk assessment.
• There's a growing demand for non-animal alternative testing methods in toxicology.

Purpose of the Study:

• To address the challenges in neurotoxicology testing of ENM.
• To highlight the scarcity of toxicokinetic data for ENM, hindering in vitro testing.
• To emphasize the need to incorporate indirect neurotoxic effects into advanced testing strategies.

Main Methods:

• Review of existing toxicological data and challenges in ENM neurotoxicity assessment.
• Analysis of in vivo studies indicating indirect neurotoxic and behavioral effects of ENM.
• Consideration of physicochemical properties and exposure routes influencing ENM toxicity.

Main Results:

• Scarcity of toxicokinetic data for ENM hampers dose selection for in vitro neurotoxicity testing.
• ENM can induce indirect neurotoxic and behavioral effects mediated by inflammatory responses in peripheral organs.
• Disturbance of the gut microbiome and intestinal mucus barrier by ENM can also lead to indirect neurotoxicity.

Conclusions:

• Advanced in vitro neurotoxicity testing methods must account for the complex properties of ENM.
• Indirect mechanisms of ENM neurotoxicity, including inflammation and gut microbiome alterations, need to be integrated into testing strategies.
• Developing non-animal alternative approaches for ENM neurotoxicity assessment is crucial.