ADME: An essential component of the safety assessment of nanoscale food ingredients

Nanotechnology has the potential to transform the entire food industry by changing the way food is produced, processed, packaged, transported and consumed. 1 Nanomaterials are generally defined as those classes of materials that have one or more physical dimensions at the nanoscale— ranging from 1 to 100 nanometers. 2 At such a small scale, nanomaterials exhibit different physical and chemical properties than larger sized versions of the same substance. 3 Compared to larger sized particles, nanoparticles have vastly increased surface-to-volume and surface-to-mass ratios. Further, as the size of a particle approaches the nanoscale, quantum mechanical effects of subatomic particles may produce fundamental changes in atomic structure, physical and/or optical characteristics, shape, solubility, thermodynamics, agglomeration properties, surface charge, antigenicity and/or reactivity. These changes may impart unique biological properties to materials, resulting in altered absorption, distribution, metabolism or excretion (ADME) in the body. As the toxicity of a substance is dependent on its ADME, the toxicological profile of a nano-sized material may be entirely different from the same material in a larger scale version.

While the gastrointestinal (GI) tract contains a variety of protective mechanisms that prevent entry of potentially toxic substances into the cells lining the GI tract (e.g. stomach acid, mucus, tight junctions between epithelial cells, and lymphoid tissue), it is designed to let beneficial substances in through diffusion or active transport. One of the primary concerns regarding oral exposure of nanomaterials is increased potential for permeability through cell membranes or tight junctions between cells, resulting in increased absorption into the blood. Once in the bloodstream, the nanomaterial may readily distribute to, or accumulate in organs. Nanomaterials may persist in the body, due to increased stability or decreased solubility in blood or tissues. Further, they could gain access to organs (e.g. brain or placenta) that ordinarily block entry of the larger form of the same material or organs of the reticuloendothelial system (e.g. liver, thymus or spleen) that contain resident phagocytic cells. Depending on dose and surface properties, phagocytes could effectively clear nanomaterials or be activated to produce toxicity. Thus, nanoparticles may exhibit unique toxicities that are due to not only the dose, but also to any alte