漫长的阴影：工程纳米材料慢性暴露、生物持久性与潜在健康风险的毒理学综述
The long shadow: a toxicological review of chronic exposure, biopersistence, and latent health risks of engineered nanomaterials.
摘要(中文译文)
工程纳米材料（ENMs）在工业和消费领域的广泛应用，引发了关于长期健康影响尚未解决的问题。现行监管框架针对传统化学品设计，未能充分应对纳米材料特有的挑战，尤其是生物持久性和多年组织蓄积问题。本综述通过分析持久性ENMs的生物动力学行为、病理学结局及方法学局限性，探讨慢性纳米毒性的机制基础。我们聚焦于慢性炎症驱动的三个病理学终点：由挫败性吞噬和炎症小体激活导致的肺纤维化和肝纤维化，炎症驱动的肿瘤微环境所促进的癌变，以及小胶质细胞激活后的神经退行性变。我们的分析表明，兼具高长径比、结晶结构、表面反应性和生物持久性的材料具有最大的致病潜力，而许多ENMs则可发生生物降解或被有效清除。我们识别出关键空白，包括对数千种材料变体进行终身生物测定不切实际、将实验剂量外推至现实暴露的剂量学挑战，以及缺乏将短期反应与长期结局相关联的已验证生物标志物。我们提出一个整合风险评估框架，结合不良结局通路分析、基于生理的药代动力学建模、新方法学方法以及安全设计原则，以实现预测性危害识别。该框架根据慢性风险的理化决定因素对材料进行分层，并提供与危害关注程度相称的分级测试策略，从而弥合机制性实验室发现与监管决策之间的差距。该方法支持对现有ENMs进行循证监管，同时能够对仍在开发中的材料进行安全性评价。
Abstract
The proliferation of engineered nanomaterials (ENMs) across industrial and consumer sectors raises unresolved questions about long-term health effects. Current regulatory frameworks, designed for conventional chemicals, inadequately address nanomaterial-specific challenges, particularly biopersistence and tissue accumulation over years. This review examines the mechanistic basis of chronic nanotoxicity by analyzing biokinetic behavior, pathological outcomes, and methodological limitations specific to persistent ENMs. We focus on three pathological endpoints driven by chronic inflammation: pulmonary and hepatic fibrosis from frustrated phagocytosis and inflammasome activation, carcinogenesis promoted by inflammation-driven tumor microenvironments, and neurodegeneration following microglial activation. Our analysis shows that materials combining high aspect ratios, crystalline structure, surface reactivity, and biological persistence present the greatest pathogenic potential, while many ENMs undergo biodegradation or efficient clearance. We identify critical gaps including the impracticality of lifetime bioassays for thousands of material variants, dosimetry challenges in translating experimental doses to realistic exposures, and the absence of validated biomarkers connecting short-term responses to long-term outcomes. We propose an integrated risk assessment framework that combines adverse outcome pathway analysis, physiologically-based pharmacokinetic modeling, new approach methodologies, and safe-by-design principles to enable predictive hazard identification. This framework bridges the gap between mechanistic laboratory findings and regulatory decision-making by stratifying materials according to physicochemical determinants of chronic risk and providing tiered testing strategies proportionate to hazard concern. This approach supports evidence-based regulation of existing ENMs while enabling safety evaluation of materials still in development.
如何引用
AMA
Yujian Fan, Jiaying Lyu, Xiaokai Guo, Caibin Zhang, Tianyang Huang, Xinyu Wang, et al. The long shadow: a toxicological review of chronic exposure, biopersistence, and latent health risks of engineered nanomaterials.. Journal of materials chemistry. B. 2026; doi:10.1039/d6tb00484a.
APA
Yujian Fan, Jiaying Lyu, Xiaokai Guo, Caibin Zhang, Tianyang Huang, Xinyu Wang, et al (2026). The long shadow: a toxicological review of chronic exposure, biopersistence, and latent health risks of engineered nanomaterials.. Journal of materials chemistry. B. https://doi.org/10.1039/d6tb00484a
GB/T 7714
Yujian Fan, Jiaying Lyu, Xiaokai Guo, Caibin Zhang, Tianyang Huang, Xinyu Wang, et al. The long shadow: a toxicological review of chronic exposure, biopersistence, and latent health risks of engineered nanomaterials.[J]. Journal of materials chemistry. B, 2026 doi:10.1039/d6tb00484a.
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