Developing a feasible fast-track testing method for developmental neurotoxicity studies: alternative model for risk assessment of micro- and nanoplastics

Micro- and nanoplastics (MNPs) are widespread environmental pollutants that pose significant health risks. They originate from industrial processes, consumer products, and environmental degradation, inducing oxidative stress through cellular dysfunctions such as membrane interaction, internalization, mitochondrial damage, inflammation, metal ion leaching, and impaired antioxidant defense. Despite increasing evidence of their toxicity-particularly developmental neurotoxicity (DNT) and mitochondrial impairment-our understanding remains limited due to the high costs of animal studies, which reduce the overall size of experimental data. This underscores the urgent need for alternative test methods that are cost-effective, rapid, and translational. This review examines new approach methodologies (NAMs) for DNT assessment, addressing the ethical, financial, and translational limitations of animal models. NAMs integrate three complementary non-animal models that enhance conventional testing. First, zebrafish models provide organismal insights into behavioral and neurodevelopmental outcomes at minimal cost. Second, neuronal organoids replicate human-specific neurodevelopmental processes in a 3D system, offering mechanistic insights. Lastly, human cell lines enable high-throughput screening, integrating findings from zebrafish and organoid studies. Establishing a new paradigm for DNT testing is crucial for faster and more efficient toxicity and risk assessments, ultimately protecting public health. Standardizing and gaining regulatory acceptance for NAMs will improve predictive accuracy and broaden their application in environmental toxicology. Advancing these methodologies is essential to addressing the risks of MNP exposure while promoting ethical and sustainable research practices.