093 | Beyond biodegradability: assessing the toxicological footprint of polylactic acid nanoplastics on zebrafish gastrointestinal tract development

Polylactic Acid (PLA) is widely promoted as a sustainable and biocompatible alternative to petroleum-based plastics, but its degradation into nanoplastics (NPs) presents emerging environmental and toxicological challenges. In environmental contexts, PLA-NPs contribute to the so-called "plastic soup" in marine and terrestrial ecosystems, where they can adsorb and transport heavy metals or persistent organic pollutants. In animal models, exposure to these particles through ingestion or inhalation has been associated with oxidative stress, inflammatory responses, and metabolic disruptions. Consequently, their potential implications for human health remains a critical concern, as preliminary studies suggest that PLA-NPs can translocate through the intestinal epithelium and the blood-brain barrier, potentially inducing cellular toxicity and long-term systemic effects [1-2]. This study highlights the necessity of re-evaluating the "green" profile of PLA, emphasizing that biodegradability does not inherently equate to biological safety when fragmented at the nanoscale. To address these concerns, the present study investigates the primary exposure route—ingestion—using an in vivo zebrafish (Danio rerio) model to assess toxic effects on developing organs, with a primary focus on the gastrointestinal tract. Our results demonstrate that PLA-NPs bioaccumulate in zebrafish in a time- and concentration-dependent manner, with significant localization in the gut. Furthermore, exposure to PLA-NPs resulted in altered intestinal barrier permeability and compromised mucus layer morphology. In conclusion, the size of PLA-NPs significantly influences the rate of internalization and their capacity to bypass or disrupt biological barriers, probably triggering systemic toxic effects across different organ systems.The experiments were conducted as part of the PRIN project “Plastic Contamination by Poly(Lactic Acid) (PLASTAMINATION): organ lesions and underlying molecular mechanisms”, MUR, PRIN-PNRR2022 CODE NUMBER: P2022AA47Y-CUP: B53D23032060001.