Impact of nanoplastics on thyroid function: Unraveling cellular biokinetics, molecular mechanisms and human risk assessment.

Nanoplastics (NP) have emerged as a significant environmental and health concern with endocrine disrupting potential that remain largely unknown. This study investigates the effects of Polystyrene NP (PSNP) on thyroid disruption using thyroid-derived cell lines, focusing on cellular biokinetics, distribution, alteration of redox balance and impact on thyroid hormone (TH)-related gene and protein expression and function. PSNP were rapidly internalized in a cell-type-dependent manner and localized in lysosomes and the endoplasmic reticulum with limited clearance. They led to time and concentration-dependent alterations in key thyroid hormone-related transcripts (e.g. NIS, MCT8), without overt cytotoxicity. Toxicity data were used to calculate a benchmark dose (BMD5) for NIS gene (Slc5a5) inhibition at 11 particles/cell (0.21 µg/mL), suggesting a robust point of departure for thyroid bioactivity. Our study demonstrates that PSNP elevated ROS levels, reduced cellular iodide uptake, disrupted TH homeostasis and could contribute to thyroid diseases such as hypothyroidism and impaired neurodevelopment. Moreover, we have identified PSNP as endocrine disruptors (thyroid modality), supporting their urgent consideration in regulatory actions given the recent detection of similar particles in human tissues. Our study provides novel insights into the potential molecular impacts of NP on thyroid physiology, and it highlights the importance of integrating New Approach Methodologies for risk assessment of NP.