title: Differential Effects of Silver Nanoparticles and Silver Ions on Tissue Accumulation, Distribution, and Toxicity in the Sprague Dawley Rat Following Daily Oral Gavage Administration for 13 Weeks.
abstract: There are concerns within the regulatory and research communities regarding the health impact associated with consumer exposure to silver nanoparticles (AgNPs). This study evaluated particulate and ionic forms of silver and particle size for differences in silver accumulation, distribution, morphology, and toxicity when administered daily by oral gavage to Sprague Dawley rats for 13 weeks. Test materials and dose formulations were characterized by transmission electron microscopy (TEM), dynamic light scattering, and inductively coupled mass spectrometry (ICP-MS). Seven-week-old rats (10 rats per sex per group) were randomly assigned to treatments: AgNP (10, 75, and 110 nm) at 9, 18, and 36 mg/kg body weight (bw); silver acetate (AgOAc) at 100, 200, and 400 mg/kg bw; and controls (2 mM sodium citrate (CIT) or water). At termination, complete necropsies were conducted, histopathology, hematology, serum chemistry, micronuclei, and reproductive system analyses were performed, and silver accumulations and distributions were determined. Rats exposed to AgNP did not show significant changes in body weights or intakes of feed and water relative to controls, and blood, reproductive system, and genetic tests were similar to controls. Differences in the distributional pattern and morphology of silver deposits were observed by TEM: AgNP appeared predominantly within cells, while AgOAc had an affinity for extracellular membranes. Significant dose-dependent and AgNP size-dependent accumulations were detected in tissues by ICP-MS. In addition, sex differences in silver accumulations were noted for a number of tissues and organs, with accumulations being significantly higher in female rats, especially in the kidney, liver, jejunum, and colon.
authors.affiliation: Division of Biochemical Toxicology, mary.boudreau@fda.hhs.gov.
authors.forename: Mary D
authors.initials: MD
authors.lastname: Boudreau
authors.affiliation: Division of Biochemical Toxicology.
authors.forename: Mohammed S
authors.initials: MS
authors.lastname: Imam
authors.affiliation: NCTR-ORA Nanotechnology Core Facility, and.
authors.forename: Angel M
authors.initials: AM
authors.lastname: Paredes
authors.affiliation: Division of Biochemical Toxicology.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Bryant
authors.affiliation: NCTR-ORA Nanotechnology Core Facility, and.
authors.forename: Candice K
authors.initials: CK
authors.lastname: Cunningham
authors.affiliation: Bioinformatics and Biostatistics Division, National Center for Toxicological Research, Food and Drug Administration, Jefferson, Arkansas; and.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Felton
authors.affiliation: NCTR-ORA Nanotechnology Core Facility, and.
authors.forename: Margie Y
authors.initials: MY
authors.lastname: Jones
authors.affiliation: Toxicologic Pathology Associates, Jefferson Laboratories, Jefferson, Arkansas.
authors.forename: Kelly J
authors.initials: KJ
authors.lastname: Davis
authors.affiliation: Toxicologic Pathology Associates, Jefferson Laboratories, Jefferson, Arkansas.
authors.forename: Greg R
authors.initials: GR
authors.lastname: Olson
mesh_terms: D000284:Administration, Oral; D000818:Animals; D004305:Dose-Response Relationship, Drug; D000067493:Dynamic Light Scattering; D005260:Female; D007477:Ions; D008297:Male; D053768:Metal Nanoparticles / Q000633:toxicity*; D046529:Microscopy, Electron, Transmission; D010316:Particle Size; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics; D012834:Silver / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity*; D013054:Spectrophotometry, Atomic; D013499:Surface Properties; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D007477:Ions; D012834:Silver
keywords: accumulation; distribution; exposure assessment; in vivo; nanoparticle; oral administration; rodent; silver; silver acetate; transmission electron microscopy