title: 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.
authors: a Unit for Laboratory Animal Medicine, University of Michigan , Ann Arbor , MI , USA .
authors: Ingrid L
authors: IL
authors: Bergin
authors: a Unit for Laboratory Animal Medicine, University of Michigan , Ann Arbor , MI , USA .
authors: Laura A
authors: LA
authors: Wilding
authors: b Toxicology Program, Department of Environmental Health Sciences, University of Michigan , Ann Arbor , MI , USA .
authors: Masako
authors: M
authors: Morishita
authors: a Unit for Laboratory Animal Medicine, University of Michigan , Ann Arbor , MI , USA .
authors: Kim
authors: K
authors: Walacavage
authors: b Toxicology Program, Department of Environmental Health Sciences, University of Michigan , Ann Arbor , MI , USA .|c Department of Chemistry , University of Michigan , Ann Arbor , MI , USA .
authors: Andrew P
authors: AP
authors: Ault
authors: b Toxicology Program, Department of Environmental Health Sciences, University of Michigan , Ann Arbor , MI , USA .
authors: Jessica L
authors: JL
authors: Axson
authors: b Toxicology Program, Department of Environmental Health Sciences, University of Michigan , Ann Arbor , MI , USA .
authors: Diana I
authors: DI
authors: Stark
authors: a Unit for Laboratory Animal Medicine, University of Michigan , Ann Arbor , MI , USA .
authors: Sara A
authors: SA
authors: Hashway
authors: d Malvern Instruments , Westborough , MA , USA .
authors: Sonja S
authors: SS
authors: Capracotta
authors: e Michigan Nanotechnology Institute for Medical and Biological Sciences, University of Michigan , Ann Arbor , MI , USA , and.
authors: Pascale R
authors: PR
authors: Leroueil
authors: b Toxicology Program, Department of Environmental Health Sciences, University of Michigan , Ann Arbor , MI , USA .
authors: Andrew D
authors: AD
authors: Maynard
authors: b Toxicology Program, Department of Environmental Health Sciences, University of Michigan , Ann Arbor , MI , USA .|f University of Michigan Risk Science Center, University of Michigan , Ann Arbor , MI , USA.
authors: Martin A
authors: MA
authors: Philbert
mesh_terms: D000085:Acetates / Q000493:pharmacokinetics / Q000633:toxicity; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D019343:Citric Acid / Q000737:chemistry / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D005243:Feces / Q000737:chemistry*; D007700:Kinetics; D008297:Male; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D051379:Mice; D023421:Models, Animal; D009929:Organ Size / Q000187:drug effects; D010316:Particle Size; D011145:Polyvinyls / Q000737:chemistry / Q000633:toxicity; D011759:Pyrrolidines / Q000737:chemistry / Q000633:toxicity; D012834:Silver / Q000032:analysis / Q000737:chemistry / Q000493:pharmacokinetics* / Q000633:toxicity*; D018030:Silver Compounds / Q000493:pharmacokinetics / Q000633:toxicity; D014018:Tissue Distribution
chemical_list: D000085:Acetates; D011145:Polyvinyls; D011759:Pyrrolidines; D018030:Silver Compounds; C505150:poly(N-vinylpyrrolidine); C103100:silver acetate; D019343:Citric Acid; D012834:Silver
keywords: ICP-OES; in vivo; mouse; nanomaterials; nanoparticle; nanotoxicology; silver; toxicology