The number of AgNP in vivo toxicological studies is still incredibly small, so generalized conclusions about the effects of AgNP exposure via food-relevant routes of exposure remains limited.
It is, for example, still unclear to what extent the biochemical pathways which facilitate processing of silver ions apply to AgNPs, to what extent AgNPs pass through the intestinal lining intact or are dissolved into silver ions in the highly acidic environment of the stomach, and to what extent AgNPs can pass through natural biological barriers such as the blood–brain barrier, the placenta or into breast milk.
It is also crucial to note that regardless of one’s interpretation of the available body of literature, there have been almost no attempts to study the cumulative effects of chronic AgNP exposure, and systematic investigations of the relationship between particle characteristics (size, shape, surface charge, etc.) and toxicity have yet to be performed.
Furthermore, while one study was able to demonstrate that silver nanoparticles dispersed within electrospun PVA nanowhiskers were cytotoxic to epidermal keratinocytes and fibroblasts, very little is known about how the toxicity of silver or AgNPs is altered when these species are dispersed within plastic coatings.
A review of in vitro and in vivo AgNP toxicological studies provides a more thorough analysis of this topic
---- In vitro toxicological studies have shown that AgNPs may not be benign to isolated mammalian cells.
Human lung fibroblasts and glioblastoma cells exposed to AgNPs exhibit reduced ATP content, increased ROS production, damaged mitochondria, DNA damage and chromosomal aberrations in a dose-dependent manner compared to controls, suggesting that AgNPs have the potential to be cytotoxic, genotoxic, antiproliferative and possibly carcinogenic.
AgNPs at low concentrations in vitro cause changes to the cell cycle progression of human hepatoma cells, whereas at higher concentrations AgNPs induced abnormal cellular morphology, cell shrinkage, and chromosomal damage to a much worse extent than that caused by similar Ag+ concentrations, indicating that the toxicity of AgNPs is not only caused by Ag cation release.
Exposure of spermatogonial mouse stem cells to 15 nm AgNPs at low (10 μg/mL) levels in vitro results in cellular morphological changes and mitochondrial damage, etc., and thus AgNPs may represent a threat to male reproductive health under some conditions.
AgNPs also exhibit cytotoxicity to rat liver cells mediated through oxidative stress (e.g., disrupted membrane potentials, ROS formation etc.) at far lower concentrations than particles composed of other metals and metal oxides [336]; AgNP size-dependent cytotoxicity caused by oxidative stress and ROS formation was also demonstrated for rat alveolar macrophages.
While at least one AgNP-based dermatological ointment has been demonstrated to be cytotoxic to human fibroblasts and skin/carcinoma cells, causing concentration-dependent morphological changes, signs of oxidative stress, lipid oxidation, DNA fragmentation/apoptosis and, at very high concentrations, necrosis, it has nevertheless been concluded that AgNPs were safe for skin contact at concentrations up to 6.25 μg/mL; however this dosage may be expected to be highly AgNP-size dependent, so the absolute usefulness of this mass-based dosage metric is debatable, particularly since the AgNP characteristics in this study were not disclosed.
Despite these reports of AgNP cytotoxicity, some other studies have arrived at contrary conclusions: one group of researchers found that epidermal cells are unaffected by antimicrobial-relevant concentrations of AgNPs and several groups have determined that AgNPs contained in LBL-assembled PNCs or bone-cements cause no observable toxic effects on human osteoblasts under the tested conditions