Human health risk assessment of nanoparticles through food consumption - occurrence, exposure, and toxicological...

Nanotechnology is increasingly embedded in agri-food systems through nano-enabled inputs, processing aids, and smart packaging, raising concerns about dietary exposure and human health. A structured Scopus search (2016-2025) identified 669 records on nanoparticles (NPs) in food and drinking water, of which 262 met the inclusion criteria. The most frequently reported NPs were TiO₂, Ag, ZnO and nano/microplastics, followed by SiO₂, CuO, CeO₂, nanoscale zero-valent iron (nZVI), Fe₂O₃, Ni, and graphene. Entry routes into the food chain were intentional use in foods and supplements, migration from food-contact materials, and environmental transfer into raw materials and commodities. Evidence from in vitro and in vivo studies consistently showed oxidative stress, inflammation, genotoxic signalling and epithelial-barrier alterations, with oral exposure in animals linked to hepatic, gastrointestinal, developmental, reproductive and neurobehavioral effects. Risk characterisation applied indices such as Estimated Daily Intake (EDI), Daily Intake of Metals (DIM), Hazard Quotient (HQ), Hazard Index (HI), Margin of Exposure (MOE), Benchmark Dose Lower confidence limit (BMDL)-based methods and Cancer Risk (CR), often combined with probabilistic Monte-Carlo modelling and nano-specific adjustments including ion-equivalent or bioaccessibility-corrected doses, in vitro-to-in vivo extrapolation (IVIVE), and Physiologically Based Pharmacokinetic or Toxicokinetic (PBPK/PBTK) models. Methodological gaps persist, notably a limited number-based EDI for NP entities, reliance on total element measurements, mismatched dose metrics between exposure and hazard Points-of-Departure (PoDs), and the lack of chronic, low-dose oral studies suitable for BMD modelling. Regulatory contrasts underline these challenges: E171 (food-grade TiO₂) is no longer considered safe in the European Union due to unresolved genotoxicity, while synthetic amorphous silica (E551) remains of no safety concern, supported by an oral NOAEL of ~1000 mg kg^-1 bw day^-1. To guide decision-making, a tiered oral-exposure framework is proposed that aligns dose metrics, standardises nano-characterisation using spICP-MS and AF4-ICP-MS, integrates INFOGEST-based bioaccessibility testing, and ensures transparent reporting of uncertainty and sensitivity.