Critical assessment of toxicological effects of ingested nanoparticles

Nanoparticles (NP) are being increasingly incorporated into foods and food packaging, however, our understanding of the biological interactions of such materials and their potential impact upon human health and disease lag far behind the technology itself. In response to this knowledge gap, many investigations are being directed toward assessment of toxicity induced by food-relevant NP in epithelial cells of the gastrointestinal (GI) tract, and pathophysiological responses to oral NP administration in vivo. Studies have focused upon various aspects of toxicity including cell death, inhibition of cell proliferation, oxidative stress, and organ injury and dysfunction, as well as other responses. While data generated by these studies have provided useful information, results have been at times inconsistent and in some cases contradictory. Herein we review the properties of food-relevant NP, including GI tract exposure, transport of NP, and immunogenicity. Then we critically review the major findings of a cross-section of studies of GI-related biological interactions of nanoscale silica (SiO2), titanium dioxide (TiO2), zinc oxide (ZnO), and silver (Ag), with particular focus upon the variation in results in the context of administered NP dosage, specific assay methods employed, uncertainties in NP physicochemical properties, and other factors that might influence experimental outcomes. We conclude with a series of recommendations for modification of the experimental approach toward greater consistency, and for addressing several important issues that have thus far been understudied.