Comparative toxicity of silicon dioxide, silver and iron oxide nanoparticles after repeated oral administration to rats.
Although silicon dioxide (SiO2), silver (Ag) and iron oxide (Fe2O3) nanoparticles are widely used in diverse applications from food to biomedicine, in vivo toxicities of these nanoparticles exposed via the oral route remain highly controversial. To examine the systemic toxicity of these nanoparticles, well-dispersed nanoparticles were orally administered to Sprague-Dawley rats daily over a 13-week period. Based on the results of an acute toxicity and a 14-day repeated toxicity study, 975.9, 1030.5 and 1000 mg kg(-1) were selected as the highest dose of the SiO2 , Ag and Fe2O3 nanoparticles, respectively, for the 13-week repeated oral toxicity study. The SiO2 and Fe2O3 nanoparticles did not induce dose-related changes in a number of parameters associated with the systemic toxicity up to 975.9 and 1000 mg kg(-1) , respectively, whereas the Ag nanoparticles resulted in increases in serum alkaline phosphatase and calcium as well as lymphocyte infiltration in liver and kidney, raising the possibility of liver and kidney toxicity induced by the Ag nanoparticles. Compared with the SiO2 and Fe2O3 nanoparticles showing no systemic distribution in all tissues tested, the Ag concentration in sampled blood and organs in the Ag nanoparticle-treated group significantly increased with a positive and/or dose-related trend, meaning that the systemic toxicity of the Ag nanoparticles, including liver and kidney toxicity, might be explained by extensive systemic distribution of Ag originating from the Ag nanoparticles. Our current results suggest that further study is required to identify that Ag detected outside the gastrointestinal tract were indeed a nanoparticle form or ionized form.
Department of Experimental Animal Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.
Jun-Won
JW
Yun
Seung-Hyun
SH
Kim
Ji-Ran
JR
You
Woo Ho
WH
Kim
Ja-June
JJ
Jang
Seung-Kee
SK
Min
Hee Chan
HC
Kim
Doo Hyun
DH
Chung
Jayoung
J
Jeong
Byeong-Cheol
BC
Kang
Jeong-Hwan
JH
Che
D000284:Administration, Oral; D000818:Animals; D001772:Blood Cell Count; D004305:Dose-Response Relationship, Drug; D005260:Female; D005290:Ferric Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D008297:Male; D053768:Metal Nanoparticles / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012822:Silicon Dioxide / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D018030:Silver Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D014018:Tissue Distribution
D005290:Ferric Compounds; D018030:Silver Compounds; C000499:ferric oxide; D012822:Silicon Dioxide
biodistribution; iron oxide; nanoparticle; silicon dioxide; silver; subchronic; toxicity