title: Distribution, elimination, and toxicity of silver nanoparticles and silver ions in rats after 28-day oral exposure.
abstract: We report the results of a 28-day oral exposure study in rats, exposed to <20 nm noncoated, or <15 nm PVP-coated silver nanoparticles ([Ag] = 90 mg/kg body weight (bw)), or AgNO(3) ([Ag] = 9 mg/kg bw), or carrier solution only. Dissection was performed at day 29, and after a wash-out period of 1 or 8 weeks. Silver was present in all examined organs with the highest levels in the liver and spleen for all silver treatments. Silver concentrations in the organs were highly correlated to the amount of Ag(+) in the silver nanoparticle suspension, indicating that mainly Ag(+), and to a much lesser extent silver nanoparticles, passed the intestines in the silver nanoparticle exposed rats. In all groups silver was cleared from most organs after 8 weeks postdosing, but remarkably not from the brain and testis. Using single particle inductively coupled plasma mass spectrometry, silver nanoparticles were detected in silver nanoparticle exposed rats, but, remarkably also in AgNO(3) exposed rats, hereby demonstrating the formation of nanoparticles from Ag(+)in vivo that are probably composed of silver salts. Biochemical markers and antibody levels in blood, lymphocyte proliferation and cytokine release, and NK-cell activity did not reveal hepatotoxicity or immunotoxicity of the silver exposure. In conclusion, oral exposure to silver nanoparticles appears to be very similar to exposure to silver salts. However, the consequences of in vivo formation of silver nanoparticles, and of the long retention of silver in brain and testis should be considered in a risk assessment of silver nanoparticles.
authors.affiliation: RIKILT-Wageningen University & Research Centre, 6700 AE Wageningen, The Netherlands. meike.vanderzande@wur.nl
authors.forename: Meike
authors.initials: M
authors.lastname: van der Zande
authors.forename: Rob J
authors.initials: RJ
authors.lastname: Vandebriel
authors.forename: Elke
authors.initials: E
authors.lastname: Van Doren
authors.forename: Evelien
authors.initials: E
authors.lastname: Kramer
authors.forename: Zahira
authors.initials: Z
authors.lastname: Herrera Rivera
authors.forename: Cecilia S
authors.initials: CS
authors.lastname: Serrano-Rojero
authors.forename: Eric R
authors.initials: ER
authors.lastname: Gremmer
authors.forename: Jan
authors.initials: J
authors.lastname: Mast
authors.forename: Ruud J B
authors.initials: RJ
authors.lastname: Peters
authors.forename: Peter C H
authors.initials: PC
authors.lastname: Hollman
authors.forename: Peter J M
authors.initials: PJ
authors.lastname: Hendriksen
authors.forename: Hans J P
authors.initials: HJ
authors.lastname: Marvin
authors.forename: Ad A C M
authors.initials: AA
authors.lastname: Peijnenburg
authors.forename: Hans
authors.initials: H
authors.lastname: Bouwmeester
mesh_terms: D000284:Administration, Oral; D000818:Animals; D007477:Ions; D008297:Male; D008657:Metabolic Clearance Rate; D053768:Metal Nanoparticles / Q000008:administration & dosage / Q000737:chemistry* / Q000633:toxicity*; D009928:Organ Specificity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012834:Silver / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D014018:Tissue Distribution
chemical_list: D007477:Ions; D012834:Silver