title: Distribution of silver in rats following 28 days of repeated oral exposure to silver nanoparticles or silver acetate.
abstract: BACKGROUND
  The study investigated the distribution of silver after 28 days repeated oral administration of silver nanoparticles (AgNPs) and silver acetate (AgAc) to rats. Oral administration is a relevant route of exposure because of the use of silver nanoparticles in products related to food and food contact materials.
  
  
  RESULTS
  AgNPs were synthesized with a size distribution of 14 ± 4 nm in diameter (90% of the nanoparticle volume) and stabilized in aqueous suspension by the polymer polyvinylpyrrolidone (PVP). The AgNPs remained stable throughout the duration of the 28-day oral toxicity study in rats. The organ distribution pattern of silver following administration of AgNPs and AgAc was similar. However the absolute silver concentrations in tissues were lower following oral exposure to AgNPs. This was in agreement with an indication of a higher fecal excretion following administration of AgNPs. Besides the intestinal system, the largest silver concentrations were detected in the liver and kidneys. Silver was also found in the lungs and brain. Autometallographic (AMG) staining revealed a similar cellular localization of silver in ileum, liver, and kidney tissue in rats exposed to AgNPs or AgAc. Using transmission electron microscopy (TEM), nanosized granules were detected in the ileum of animals exposed to AgNPs or AgAc and were mainly located in the basal lamina of the ileal epithelium and in lysosomes of macrophages within the lamina propria. Using energy dispersive x-ray spectroscopy it was shown that the granules in lysosomes consisted of silver, selenium, and sulfur for both AgNP and AgAc exposed rats. The diameter of the deposited granules was in the same size range as that of the administered AgNPs. No silver granules were detected by TEM in the liver.
  
  
  CONCLUSIONS
  The results of the present study demonstrate that the organ distribution of silver was similar when AgNPs or AgAc were administered orally to rats. The presence of silver granules containing selenium and sulfur in the intestinal wall of rats exposed to either of the silver forms suggests a common mechanism of their formation. Additional studies however, are needed to gain further insight into the underlying mechanisms of the granule formation, and to clarify whether AgNPs dissolve in the gastrointestinal system and/or become absorbed and translocate as intact nanoparticles to organs and tissues.
authors.affiliation: Division of Food Chemistry, National Food Institute, Technical University of Denmark, Søborg, Denmark. kals@food.dtu.dk
authors.forename: Katrin
authors.initials: K
authors.lastname: Loeschner
authors.forename: Niels
authors.initials: N
authors.lastname: Hadrup
authors.forename: Klaus
authors.initials: K
authors.lastname: Qvortrup
authors.forename: Agnete
authors.initials: A
authors.lastname: Larsen
authors.forename: Xueyun
authors.initials: X
authors.lastname: Gao
authors.forename: Ulla
authors.initials: U
authors.lastname: Vogel
authors.forename: Alicja
authors.initials: A
authors.lastname: Mortensen
authors.forename: Henrik Rye
authors.initials: HR
authors.lastname: Lam
authors.forename: Erik H
authors.initials: EH
authors.lastname: Larsen
mesh_terms: D000085:Acetates / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism*; D000284:Administration, Oral; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007082:Ileum / Q000378:metabolism / Q000648:ultrastructure; D008422:Materials Testing; D053768:Metal Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D010316:Particle Size; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012834:Silver / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism*; D018030:Silver Compounds / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D000085:Acetates; D018030:Silver Compounds; C103100:silver acetate; D012834:Silver