Genotoxicity, biodistribution and toxic effects of silver nanoparticles after in vivo acute oral administration

Abstract In the last years, silver nanoparticle (AgNP) use is increased due to the presence in several consumer products, including cosmetics and food packaging, for their antimicrobial activities. Silver in its elemental form is authorised as food additive E174 and EFSA noted that approximately a 20% of AgNPs are released from confectionary pearls. Toxicological assessment of E174 performed by EFSA concluded that the available information was insufficient to assess the safety for consumers and one of the major issues was the in vivo genotoxic potential. Aim of the present study was to provide data on in vivo genotoxicity of AgNPs by Alkaline Comet Assay - according to the OECD Test Guideline (TG) 489 - and by Micronucleus Assay. AgNP dispersions (20 nm) were orally administered to male and female mice for three days at 50, 150, 300 mg/kg bw per day on the basis of the OECD TG 489. AgNP dispersions were fully characterized. Comet assay was performed on blood, liver, spleen, duodenum and kidney, and Micronucleus assay on spleen lymphocytes to evaluate the genotoxic potential. Biodistribution and histopathological assessment were performed. AgNPs accumulated in duodenum as first contact site and transferred to other target tissues; in liver and duodenum they were free in the cytoplasm or included in organelles but never in the nucleus, as detected by Transmission Electron Microscope analysis. No genotoxic or tissue damage was recorded by both assays in all the tested tissues. The in vivo genotoxicity data supported a more comprehensive risk assessment of AgNPs.