Subchronic oral toxicity of silver nanoparticles.
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.
Kim
Yong Soon
YS
Korea Environment & Merchandise Testing Institute, Incheon, Korea.
Song
Moon Yong
MY
Park
Jung Duck
JD
Song
Kyung Seuk
KS
Ryu
Hyeon Ryol
HR
Chung
Yong Hyun
YH
Chang
Hee Kyung
HK
Lee
Ji Hyun
JH
Oh
Kyung Hui
KH
Kelman
Bruce J
BJ
Hwang
In Koo
IK
Yu
Il Je
IJ
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
D012834:Silver