Effects of particle size and coating on toxicologic parameters, fecal elimination kinetics and tissue distribution of acutely ingested silver nanoparticles in a mouse model

Abstract

Consumer exposure to silver nanoparticles (AgNP) via ingestion can occur due to incorporation of AgNP into products such as food containers and dietary supplements. AgNP variations in size and coating may affect toxicity, elimination kinetics or tissue distribution. Here, we directly compared acute administration of AgNP of two differing coatings and sizes to mice, using doses of 0.1, 1 and 10 mg/kg body weight/day administered by oral gavage for 3 days. The maximal dose is equivalent to 2000× the EPA oral reference dose. Silver acetate at the same doses was used as ionic silver control. We found no toxicity and no significant tissue accumulation. Additionally, no toxicity was seen when AgNP were dosed concurrently with a broad-spectrum antibiotic. Between 70.5% and 98.6% of the administered silver dose was recovered in feces and particle size and coating differences did not significantly influence fecal silver. Peak fecal silver was detected between 6- and 9-h post-administration and <0.5% of the administered dose was cumulatively detected in liver, spleen, intestines or urine at 48 h. Although particle size and coating did not affect tissue accumulation, silver was detected in liver, spleen and kidney of mice administered ionic silver at marginally higher levels than those administered AgNP, suggesting that silver ion may be more bioavailable. Our results suggest that, irrespective of particle size and coating, acute oral exposure to AgNP at doses relevant to potential human exposure is associated with predominantly fecal elimination and is not associated with accumulation in tissue or toxicity.

• ICP-OES
• in vivo
• mouse
• nanomaterials
• nanoparticle
• nanotoxicology
• silver
• toxicology

Acknowledgements

We gratefully acknowledge Jennifer Fernandez, Mayu Uchihashi, Ian Speirs, C.J. Gasper, and the histology and technical services teams of the In Vivo Animal Core within the Unit for Laboratory Animal Medicine at the University of Michigan for their assistance in study conduct and sample collection. We additionally thank Frank Weber and the Analytical Chemistry Services Laboratory of RTI International for performing silver quantitation in tissues. The silver ENMs used in these studies were procured, characterized and supplied by NIEHS as part of NCNHIR consortium efforts.

Declaration of interest

The authors have no conflicts of interest to declare. This study was supported by the National Institute of Environmental Health Sciences of the National Institutes of Health under award number 1U01ES020128-01 as part of the NIEHS Centers for Nanotechnology Health Implications Research Consortium (NCNHIR). The article was reviewed by the NCNHIR consortium prior to submission, however, the content is solely the responsibility of the authors and does not represent the official views of the National Institutes of Health or the NCNHIR.

Supplementary material available online

Supplementary Tables 1-4.