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...

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Main Authors: Xian Wu, TinChung Leung, Dereje D. Jima, Majemite Iyangbe, John Bang
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-04-01
Series:Frontiers in Toxicology
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Online Access:https://www.frontiersin.org/articles/10.3389/ftox.2025.1567225/full
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author Xian Wu
TinChung Leung
TinChung Leung
Dereje D. Jima
Dereje D. Jima
Majemite Iyangbe
John Bang
John Bang
author_facet Xian Wu
TinChung Leung
TinChung Leung
Dereje D. Jima
Dereje D. Jima
Majemite Iyangbe
John Bang
John Bang
author_sort Xian Wu
collection DOAJ
description 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.
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spelling doaj-art-fbd136e4feb342e2bdf09d23e04fb57f2025-08-20T02:15:52ZengFrontiers Media S.A.Frontiers in Toxicology2673-30802025-04-01710.3389/ftox.2025.15672251567225Developing a feasible fast-track testing method for developmental neurotoxicity studies: alternative model for risk assessment of micro- and nanoplasticsXian Wu0TinChung Leung1TinChung Leung2Dereje D. Jima3Dereje D. Jima4Majemite Iyangbe5John Bang6John Bang7Department of Pharmacology and Toxicology, Brody School of Medicine, East Carolina University, Greenville, NC, United StatesThe Julius L. Chambers Biomedical and Biotechnology Research Institute, North Carolina Central University, Durham, NC, United StatesDepartment of Biological and Biomedical Sciences, College of Health and Sciences, North Carolina Central University, Durham, NC, United StatesCenter for Human Health and Environments, North Carolina State University, Raleigh, NC, United StatesBioinformatics Research Center, North Carolina State University, Raleigh, NC, United StatesIntergrated Bioscience, Ph.D. Program, North Carolina Central University, Durham, NC, United StatesDepartment of Environmental, Earth, and Geospatial Sciences, College of Health and Sciences, North Carolina Central University, Durham, NC, United StatesDepartment of Pharmaceutical Sciences, College of Health and Sciences, North Carolina Central University, Durham, NC, United StatesMicro- 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.https://www.frontiersin.org/articles/10.3389/ftox.2025.1567225/fullmicro-and nanoplasticsdevelopmental neurotoxicitymetabolismzebrafishorganoid
spellingShingle Xian Wu
TinChung Leung
TinChung Leung
Dereje D. Jima
Dereje D. Jima
Majemite Iyangbe
John Bang
John Bang
Developing a feasible fast-track testing method for developmental neurotoxicity studies: alternative model for risk assessment of micro- and nanoplastics
Frontiers in Toxicology
micro-and nanoplastics
developmental neurotoxicity
metabolism
zebrafish
organoid
title Developing a feasible fast-track testing method for developmental neurotoxicity studies: alternative model for risk assessment of micro- and nanoplastics
title_full Developing a feasible fast-track testing method for developmental neurotoxicity studies: alternative model for risk assessment of micro- and nanoplastics
title_fullStr Developing a feasible fast-track testing method for developmental neurotoxicity studies: alternative model for risk assessment of micro- and nanoplastics
title_full_unstemmed Developing a feasible fast-track testing method for developmental neurotoxicity studies: alternative model for risk assessment of micro- and nanoplastics
title_short Developing a feasible fast-track testing method for developmental neurotoxicity studies: alternative model for risk assessment of micro- and nanoplastics
title_sort developing a feasible fast track testing method for developmental neurotoxicity studies alternative model for risk assessment of micro and nanoplastics
topic micro-and nanoplastics
developmental neurotoxicity
metabolism
zebrafish
organoid
url https://www.frontiersin.org/articles/10.3389/ftox.2025.1567225/full
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