Yong Soon Kim^1,7, Moon Yong Song¹, Jung Duck Park², Kyung Seuk Song¹, Hyeon Ryol Ryu¹, Yong Hyun Chung³, Hee Kyung Chang⁴, Ji Hyun Lee⁸, Kyung Hui Oh⁵, Bruce J Kelman⁶, In Koo Hwang⁷, Il Je Yu^1,8*

¹Korea Environment & Merchandise Testing Institute, Incheon, Korea. ²College of Medicine, Chung-Ang University, Seoul, Korea. ³Chemcial Safety and Health Research Center, KOSHA, Daejeon, Korea. ⁴College of Medicine, Kosin University, Busan, Korea. ⁵Korea Agency for Technology and Standards, Gwacheon, Korea. ⁶Veritox, Inc., Seattle, USA. ⁷College of Veterinary Medicine, Seoul National University, Seoul, Korea. ⁸Fusion Technology Research Institute, Hoseo University, Asan, Korea.

^* Correspondence :Il Je Yu

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.