An Adverse Outcome Pathway for food nanomaterial-induced intestinal barrier disruption

Ingestion of nanomaterials (NMs) poses potential risks to intestinal health, yet the underlying mechanisms remain elusive. Despite growing concern, a comprehensive understanding of how NMs disrupt the intestinal barrier is lacking also due to limited and inconsistent data.In this study, we constructed an Adverse Outcome Pathway (AOP) based on biological plausibility and existing knowledge of NM-induced hepatic effects. Subsequently, we systematically evaluated the available evidence for a panel of six NMs commonly used in the food industry: ZnO, CuO, FeO, SiO2, Ag, and nanocellulose. Our proposed AOP (AOP530) outlines a pathway from NM uptake and lysosomal disruption to mitochondrial dysfunction, culminating in cell injury, death, and intestinal barrier compromise. We found substantial evidence supporting NM uptake by intestinal cells and intestinal barrier disruption for Ag, CuO, and SiO2 NMs. However, evidence for FeO and ZnO was more limited. Notably, data on lysosomal disruption and mitochondrial dysfunction were scarce for all NMs studied. Nanocellulose showed no evidence of toxicity or involvement in AOP530. By systematically evaluating the evidence supporting our proposed AOP, we identified critical knowledge gaps and inconsistencies in the existing dataset. The heterogeneity of study designs, including variations in stressors, biological models, and endpoint assessments, hindered data integration and interpretation. To enhance the safety evaluation of food-related NMs, standardized methodologies and a concerted effort to generate mechanistic data are imperative

STANCO Deborah;  LIPSA Dorelia;  BOGNI Alessia;  BREMER-HOFFMANN Susanne;  CLERBAUX Laure-Alix; 

2025-01-22

FRONTIERS MEDIA SA

JRC138999

2673-3080 (online),   

https://www.frontiersin.org/journals/toxicology/articles/10.3389/ftox.2024.1474397,    https://publications.jrc.ec.europa.eu/repository/handle/JRC138999,   

10.3389/ftox.2024.1474397 (online),