title: Subchronic oral toxicity of silver nanoparticles.
abstract: BACKGROUND
  The antibacterial effect of silver nanoparticles has resulted in their extensive application in health, electronic, consumer, medicinal, pesticide, and home products; however, silver nanoparticles remain a controversial area of research with respect to their toxicity in biological and ecological systems.
  
  
  RESULTS
  This study tested the oral toxicity of silver nanoparticles (56 nm) over a period of 13 weeks (90 days) in F344 rats following Organization for Economic Cooperation and Development (OECD) test guideline 408 and Good Laboratory Practices (GLP). Five-week-old rats, weighing about 99 g for the males and 92 g for the females, were divided into four 4 groups (10 rats in each group): vehicle control, low-dose (30 mg/kg), middle-dose (125 mg/kg), and high-dose (500 mg/kg). After 90 days of exposure, clinical chemistry, hematology, histopathology, and silver distribution were studied. There was a significant decrease (P < 0.05) in the body weight of male rats after 4 weeks of exposure, although there were no significant changes in food or water consumption during the study period. Significant dose-dependent changes were found in alkaline phosphatase and cholesterol for the male and female rats, indicating that exposure to more than 125 mg/kg of silver nanoparticles may result in slight liver damage. Histopathologic examination revealed a higher incidence of bile-duct hyperplasia, with or without necrosis, fibrosis, and/or pigmentation, in treated animals. There was also a dose-dependent accumulation of silver in all tissues examined. A gender-related difference in the accumulation of silver was noted in the kidneys, with a twofold increase in female kidneys compared to male kidneys.
  
  
  CONCLUSIONS
  The target organ for the silver nanoparticles was found to be the liver in both the male and female rats. A NOAEL (no observable adverse effect level) of 30 mg/kg and LOAEL (lowest observable adverse effect level) of 125 mg/kg are suggested from the present study.
authors.affiliation: Korea Environment & Merchandise Testing Institute, Incheon, Korea.
authors.forename: Yong Soon
authors.initials: YS
authors.lastname: Kim
authors.forename: Moon Yong
authors.initials: MY
authors.lastname: Song
authors.forename: Jung Duck
authors.initials: JD
authors.lastname: Park
authors.forename: Kyung Seuk
authors.initials: KS
authors.lastname: Song
authors.forename: Hyeon Ryol
authors.initials: HR
authors.lastname: Ryu
authors.forename: Yong Hyun
authors.initials: YH
authors.lastname: Chung
authors.forename: Hee Kyung
authors.initials: HK
authors.lastname: Chang
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Lee
authors.forename: Kyung Hui
authors.initials: KH
authors.lastname: Oh
authors.forename: Bruce J
authors.initials: BJ
authors.lastname: Kelman
authors.forename: In Koo
authors.initials: IK
authors.lastname: Hwang
authors.forename: Il Je
authors.initials: IJ
authors.lastname: Yu
mesh_terms: D000818:Animals; D001652:Bile Ducts / Q000187:drug effects / Q000473:pathology; D001835:Body Weight / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D005260:Female; D007668:Kidney / Q000378:metabolism; D008297:Male; D053768:Metal Nanoparticles / Q000633:toxicity*; D019055:No-Observed-Adverse-Effect Level; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D012834:Silver / Q000493:pharmacokinetics / Q000633:toxicity*; D014018:Tissue Distribution
chemical_list: D012834:Silver