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.

Rapid Kinetics of Size and pH-Dependent Dissolution and Aggregation of Silver Nanoparticles in Simulated Gastric Fluid

“…36 This along with the current study implies that there are limited opportunities for Ag + of the AgNP to interact with gut lining epithelium or with luminal bacteria, because it will form AgCl within the salt and acidic conditions of the human stomach. Thus, by improving our understanding of silver nanoparticle physical processes and evolution, fundamental understanding can be obtained regarding observed biological responses to AgNPs.…”

Low molecular weight chitosan-coated silver nanoparticles are effective for the treatment of MRSA-infected wounds

“…1,7,9,33,34 In addition, it has been reported that the ALT and AST levels in mice serum rose significantly after 2 days of oral intake of 20 μg/g AgNPs with a size of 35-45 nm. 9 Intriguingly, in the current study, we found that after 11 days of application, the liver silver content in the mice treated with LMWC-AgNPs was significantly lower than that in the mice treated with uncoated-AgNPs or PVP-AgNPs.…”

“…[19][20][21] The cytotoxicity of AgNPs could be influenced by particle size, surface-stabilizing agents, pH, and some other factors. 1,5,7,[22][23][24] The surface-stabilizing coating is one of the most important factors for protecting cell viability from AgNPs. [25][26][27] Previous studies have shown that chitosan has a very good biocompatibility and antibacterial properties.…”

“…5,6 Moreover, AgNPs can be absorbed into the bloodstream via different routes of administration, leading to deposition of silver in many organs, including the liver and spleen, and potential organ damage after a certain amount of accumulation. 1,[7][8][9] Therefore, in the actual application process, protecting their antibacterial properties while reducing their absorption and toxicity in the body has become a very important challenge. Previous studies have shown that different surface stabilizers have distinct impacts on AgNP cytotoxicity.…”

Acute systemic exposure to silver-based nanoparticles induces hepatotoxicity and NLRP3-dependent inflammation

“…Moreover, it is not known whether NP-induced cytotoxicity is solely a reflection of their remarkable ability to penetrate through cellular membranes, causing damage to various organelles, or is mediated through a physiological process of recognition by cellular sensors leading to an inflammatory reaction. Apparently conflicting data showing lack of any toxicity J U S T A C C E P T E D following oral gavage of AgNP was also recently reported (22), highlighting the need for further studies to refine our understanding of this important public health issue.…”