Subacute oral toxicity investigation of nanoparticulate and ionic silver in rats

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.