title: In vivo distribution of nanosilver in the rat: The role of ions and de novo-formed secondary particles.
abstract: Silver nanoparticles are advertised as antimicrobial agents in a wide range of products. The majority of available studies suggest that silver nanoparticle toxicity is mainly caused by silver ions released from the particles. However, it remains challenging to distinguish between the effect of silver nanoparticles and silver ions. Here we used a combination of a short-term in vivo study in rats and an in silico-based toxicokinetic model to determine tissue distribution of administered ionic and nanoparticulate silver, and to estimate mixture ratios of the different silver species, namely primary nanoparticles, ions and secondary particles. Our data indicate that silver nanoparticles and silver ions are not or only marginally bioavailable after oral ingestion of a single, non-toxic dose. Experimental data on organ distribution after intravenous injection were accurately reflected by the predictions of the in silico model. Toxicokinetic modeling suggests systemic distribution of a major proportion of the injected ionic silver as de novo formed secondary nanoparticles, and the presence of such particles was proven by electron microscopy. The observation that silver ions form secondary particles, underlines the difficulties in distinguishing between particle- and ion-dependent effects of silver nanoparticles.
authors: BfR Federal Institute for Risk Assessment, Max-Dohrn-Str. 8-10, 10589 Berlin, Germany.
authors: Sabine
authors: S
authors: Juling
authors: Swiss Federal Institute of Technology (ETH) Zurich, 8093 Zurich, Switzerland.
authors: Gerald
authors: G
authors: Bachler
authors: Swiss Federal Institute of Technology (ETH) Zurich, 8093 Zurich, Switzerland.
authors: Natalie
authors: N
authors: von Götz
authors: BfR Federal Institute for Risk Assessment, Max-Dohrn-Str. 8-10, 10589 Berlin, Germany.
authors: Dajana
authors: D
authors: Lichtenstein
authors: BfR Federal Institute for Risk Assessment, Max-Dohrn-Str. 8-10, 10589 Berlin, Germany. Electronic address: Linda.Boehmert@bfr.bund.de.
authors: Linda
authors: L
authors: Böhmert
authors: BfR Federal Institute for Risk Assessment, Max-Dohrn-Str. 8-10, 10589 Berlin, Germany.
authors: Alicia
authors: A
authors: Niedzwiecka
authors: ZELMI, Technical University Berlin, Straße des 17. Juni 135, 10623 Berlin, Germany.
authors: Sören
authors: S
authors: Selve
authors: BfR Federal Institute for Risk Assessment, Max-Dohrn-Str. 8-10, 10589 Berlin, Germany.
authors: Albert
authors: A
authors: Braeuning
authors: BfR Federal Institute for Risk Assessment, Max-Dohrn-Str. 8-10, 10589 Berlin, Germany.
authors: Alfonso
authors: A
authors: Lampen
mesh_terms: D000818:Animals; D003198:Computer Simulation; D007477:Ions; D008297:Male; D053768:Metal Nanoparticles / Q000008:administration & dosage*; D008962:Models, Theoretical; D009928:Organ Specificity; D051381:Rats; D017208:Rats, Wistar; D012834:Silver / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: D007477:Ions; D012834:Silver
keywords: In vivo; Ion release; PBTK modeling; Silver nanoparticles; de novo particles