Particle coatings but not silver ions mediate genotoxicity of ingested silver nanoparticles in a mouse model

Incorporation of silver nanoparticles (AgNPs) in toothpaste, food containers, dietary supplements and other consumer products can result in oral exposure to AgNPs and/or silver ions (Ag⁺) released from the surface of AgNPs. To examine whether ingestion of AgNPs or Ag⁺ results in genotoxic damage and whether AgNP coatings modulate the effect, we exposed mice orally to 20 nm citrate-coated AgNPs, polyvinylpyrrolidone (PVP)-coated AgNPs, silver acetate or respective vehicles at a 4 mg/kg dose (equivalent to 800x the EPA reference dose for Ag) for 7 days. Genotoxicity was examined in the systemic circulation and bone marrow at 1, 7, and 14 days post-exposure. We found that citrate-coated AgNPs induced chromosomal damage in bone marrow and oxidative DNA damage and double strand breaks in peripheral blood. These damages persisted for at least 14 days after exposure termination. Because oxidative DNA damage and strand breaks are repaired rapidly, their presence after exposure cessation indicates that citrate-coated AgNPs persist in the body. In contrast, PVP-coated AgNPs and silver acetate did not induce DNA or chromosomal damage at any time point measured. To determine whether coating-dependent genotoxicity is related to different AgNP changes in the gastrointestinal tract, we examined AgNP behavior and fate in an in vitro gastrointestinal digestion model using UV-visible spectroscopy and DLS. Citrate-coated AgNPs were more susceptible to agglomeration than PVP-coated AgNPs in digestive juices with or without proteins. In summary, AgNPs but not Ag⁺ are genotoxic following oral ingestion. Nanoparticle coatings modulate gastrointestinal transformation and genotoxicity of AgNPs, where higher agglomeration of AgNPs in gastrointestinal juices is associated with higher genotoxicity in tissues. Since genotoxicity is a strong indicator of cancer risk, further long-term studies focusing on cancer are warranted.