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Quantifying Nanoplastic Toxicity Using Gold-Core Polystyrene Nanoparticles: In vivo Evaluation and Human Risk Extrapolation

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Researchers used gold-core polystyrene nanoparticles as a dual-detectable model to quantify nanoplastic toxicity in vivo, finding that chronic exposure induced intestinal accumulation and systemic toxicity, and used these data to extrapolate human health risk thresholds.

Polymers
Models
Study Type In vivo

Yingzi Cui,1,* Xiaohan Tong,1,* Jiawang Ding,2 Boqing Li,1 Wenke Wang,1 Chunlei Ma,1 Zhiqin Li,1 Ying Zhang1 1School of Basic Medical Sciences, Binzhou Medical University, Yantai, Shandong, People’s Republic of China; 2CAS Key Laboratory of Coastal Environmental Processes and Ecological Remediation, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai, Shandong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ying Zhang, School of Basic Medicine, Binzhou Medical University, 346 Guanhai Road, Yantai, Shandong, People’s Republic of China, Tel +86 535 6913209, Email zhangying@bzmc.edu.cn Boqing Li, School of Basic Medicine, Binzhou Medical University, 346 Guanhai Road, Yantai, Shandong, People’s Republic of China, Tel +86 535 6913069, Email liboqing@bzmc.edu.cnPurpose: Nanoplastics (NPs) are widespread environmental pollutants that pose risks to human health; however, risk thresholds for NPs accumulation in human tissues remain poorly defined. This study validates gold-core polystyrene nanoplastics (AuPS-NPs) as a quantifiable proxy for polystyrene nanoplastics (PS-NPs) to evaluate toxicity and bioaccumulation at environmentally relevant concentrations, with extrapolation to human health implications.Methods: AuPS-NPs were synthesized with a gold core and polystyrene shell, characterized by transmission electron microscopy (TEM) and quantified by inductively coupled plasma mass spectrometry (ICP-MS). In vitro, human gastric adenocarcinoma (AGS) and human colorectal adenocarcinoma (Caco-2) cells were exposed to AuPS-NPs or PS-NPs to assess cytotoxicity, reactive oxygen species generation, and mitochondrial membrane depolarization. In vivo, BALB/c mice were orally exposed to AuPS-NPs (1 and 10 mg/L) for 98 days, followed by evaluation of intestinal accumulation, body weight, organ indices, and biomarkers of inflammation, lipid metabolism, energy metabolism, and oxidative stress. A toxicokinetic–toxicodynamic (TK–TD) model was developed to simulate NPs accumulation, dose–response relationships, and human risk thresholds.Results: AuPS-NPs and PS-NPs showed comparable concentration-dependent cytotoxicity in vitro. In vivo, chronic AuPS-NP exposure caused intestinal accumulation, body weight reduction, increased organ indices, and biomarker perturbations including interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), triglycerides (TG), total cholesterol (T-CHO), adenosine triphosphate (ATP), lactate dehydrogenase (LDH), malondialdehyde (MDA), and superoxide dismutase (SOD). TK–TD modeling yielded a human intestinal toxicity threshold of 9.529 × 105 particles/kg, providing a particle-based reference for risk extrapolation.Conclusion: AuPS-NPs replicate PS-NPs toxicity and enable quantitative risk assessment. Chronic exposure may induce intestinal accumulation and systemic toxicity, underscoring the need for regulatory thresholds to mitigate nanoplastic risks. Keywords: polystyrene nanoplastics, toxicokinetics, toxicodynamics, human health risk assessment

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