Abstract
PURPOSE: 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 × 10(5) 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.