Ingested engineered nanomaterials: state of science in nanotoxicity testing and future research needs.

We identified 5 clusters of factors deemed relevant to nanotoxicology of food-grade iENM: (i) using food-grade nanomaterials for toxicity testing; (ii) performing comprehensive physicochemical and morphological characterization of iENM in the dry state, (iii) establishing standard NP dispersions and their characterization in cell culture medium, (iv) employing realistic dose ranges and standardized in vitro dosimetry models, and (v) investigating dissolution kinetics and biotransformation behavior of iENM in synthetic media representative of the gastrointestinal (GI) tract fluids, including analyses in a fasted state and in the presence of a food matrix. We discussed how these factors, when not considered thoughtfully, could influence the results and generalizability of in vitro and in vivo testing. We conclude with a set of recommendations to guide future iENM toxicity studies and to develop/adopt more relevant in vitro model systems representative of in vivo animal and human iENM exposure scenarios.