title: Subacute oral toxicity investigation of nanoparticulate and ionic silver in rats.
abstract: Subacute toxicity of 14 nm nanoparticulate silver (Ag-NP) stabilised with polyvinylpyrrolidone and ionic silver in the form of silver acetate (Ag-acetate) was investigated in four-week-old Wistar rats. Animals received orally by gavage the following: vehicle control (10 ♀, 6 ♂); Ag-NP at doses: 2.25 (8 ♀), 4.5 (8 ♀) or 9 mg/kg bw/day (10 ♀, 6 ♂); or Ag-acetate 9 mg silver/kg bw/day (8 ♀) for 28 days. Clinical, haematolological and biochemical parameters, organ weights, macro- and microscopic pathological changes were investigated. Caecal bacterial phyla and their silver resistance genes were quantified. For the Ag-NP groups, no toxicological effects were recorded. For Ag-acetate, lower body weight gain (day 4-7, 11-14, 14-16, P < 0.05; overall, day 1-28, P < 0.01), increased plasma alkaline phosphatase (P < 0.05), decreased plasma urea (P < 0.05) and lower absolute (P < 0.01) and relative (P < 0.05) thymus weight were recorded. In conclusion, these findings indicate toxicity of 9 mg/kg bw/day ionic silver but not of an equimolar Ag-NP dose. This is in accordance with previously reported data showing that oral Ag-acetate, in comparison with an equimolar dose of Ag-NP, resulted in higher silver plasma and organ concentrations.
authors.affiliation: Division of Toxicology and Risk Assessment, National Food Institute, Technical University of Denmark, Mørkhøj Bygade 19, 2860 Søborg, Denmark.
authors.forename: Niels
authors.initials: N
authors.lastname: Hadrup
authors.forename: Katrin
authors.initials: K
authors.lastname: Loeschner
authors.forename: Anders
authors.initials: A
authors.lastname: Bergström
authors.forename: Andrea
authors.initials: A
authors.lastname: Wilcks
authors.forename: Xueyun
authors.initials: X
authors.lastname: Gao
authors.forename: Ulla
authors.initials: U
authors.lastname: Vogel
authors.forename: Henrik L
authors.initials: HL
authors.lastname: Frandsen
authors.forename: Erik H
authors.initials: EH
authors.lastname: Larsen
authors.forename: Henrik R
authors.initials: HR
authors.lastname: Lam
authors.forename: Alicja
authors.initials: A
authors.lastname: Mortensen
mesh_terms: D000085:Acetates / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D000284:Administration, Oral; D000818:Animals; D019963:Clinical Chemistry Tests; D004305:Dose-Response Relationship, Drug; D005260:Female; D006403:Hematologic Tests; D007477:Ions; D008297:Male; D053768:Metal Nanoparticles / Q000633:toxicity* / Q000648:ultrastructure; D053761:Nanocomposites / Q000633:toxicity*; D019055:No-Observed-Adverse-Effect Level; D010316:Particle Size; D011205:Povidone / Q000493:pharmacokinetics / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D018030:Silver Compounds / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D013047:Specific Pathogen-Free Organisms; D018675:Toxicity Tests
chemical_list: D000085:Acetates; D007477:Ions; D018030:Silver Compounds; C103100:silver acetate; D011205:Povidone