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

IF 3.6 Q2 TOXICOLOGY
Frontiers in toxicology Pub Date : 2025-04-15 eCollection Date: 2025-01-01 DOI:10.3389/ftox.2025.1567225
Xian Wu, TinChung Leung, Dereje D Jima, Majemite Iyangbe, John Bang
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Abstract

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.

为发育性神经毒性研究开发一种可行的快速测试方法:微塑料和纳米塑料风险评估的替代模型。
微塑料和纳米塑料(MNPs)是广泛存在的环境污染物,对健康构成重大威胁。它们起源于工业过程、消费品和环境退化,通过细胞功能失调(如膜相互作用、内化、线粒体损伤、炎症、金属离子浸出和抗氧化防御受损)诱导氧化应激。尽管越来越多的证据表明它们的毒性-特别是发育神经毒性(DNT)和线粒体损伤-由于动物研究的高成本,这减少了实验数据的总体规模,我们的理解仍然有限。这强调了对具有成本效益、快速和可转换的替代测试方法的迫切需求。本综述探讨了用于DNT评估的新方法方法(NAMs),解决了动物模型的伦理、财务和翻译限制。NAMs整合了三种互补的非动物模型,增强了传统的测试。首先,斑马鱼模型以最小的成本提供了对行为和神经发育结果的有机见解。其次,神经元类器官在3D系统中复制人类特定的神经发育过程,提供机制见解。最后,人类细胞系可以进行高通量筛选,整合斑马鱼和类器官研究的结果。建立DNT测试的新范例对于更快、更有效地进行毒性和风险评估,最终保护公众健康至关重要。标准化和获得监管机构的认可将提高预测的准确性,并扩大其在环境毒理学中的应用。推进这些方法对于解决MNP暴露的风险,同时促进道德和可持续的研究实践至关重要。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
3.80
自引率
0.00%
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审稿时长
13 weeks
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