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Cited 31 time in webofscience Cited 30 time in scopus
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A 90-day study of subchronic oral toxicity of 20 nm, negatively charged zinc oxide nanoparticles in Sprague Dawley rats

Authors
Park, Hark-SooShin, Sung-SupMeang, Eun HoHong, Jeong-supPark, Jong-IlKim, Su-HyonKoh, Sang-BumLee, Seung-YoungJang, Dong-HyoukLee, Jong-YunSun, Yle-ShikKang, Jin SeokKim, Yu-RiKim, Meyoung-KonJeong, JayoungLee, Jong-KwonSon, Woo-ChanPark, Jae-Hak
Issue Date
15-Dec-2014
Publisher
DOVE MEDICAL PRESS LTD
Keywords
negative charge; oral toxicity study; rat; ZnO
Citation
INTERNATIONAL JOURNAL OF NANOMEDICINE, v.9, pp 79 - 92
Pages
14
Indexed
SCI
SCIE
SCOPUS
Journal Title
INTERNATIONAL JOURNAL OF NANOMEDICINE
Volume
9
Start Page
79
End Page
92
URI
https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/8635
DOI
10.2147/IJN.S57926
ISSN
1176-9114
1178-2013
Abstract
Purpose: The widespread use of nanoparticles (NPs) in industrial and biomedical applications has prompted growing concern regarding their potential toxicity and impact on human health. This study therefore investigated the subchronic, systemic oral toxicity and no-observed-adverse-effect level (NOAEL) of 20 nm, negatively charged zinc oxide (ZnOSM20(-)) NPs in Sprague Dawley rats for 90 days. Methods: The high-dose NP level was set at 500 mg/kg of bodyweight, and the mid-and low-dose levels were set at 250 and 125 mg/kg, respectively. The rats were observed during a 14-day recovery period after the last NP administration for the persistence or reduction of any adverse effects. Toxicokinetic and distribution studies were also conducted to determine the systemic distribution of the NPs. Results: No rats died during the test period. However, ZnOSM20(-) NPs (500 mg/kg) induced changes in the levels of anemia-related factors, prompted acinar cell apoptosis and ductular hyperplasia, stimulated periductular lymphoid cell infiltration and excessive salivation, and increased the numbers of regenerative acinar cells in the pancreas. In addition, stomach lesions were seen at 125, 250, and 500 mg/kg, and retinal atrophy was observed at 250 and 500 mg/kg. The Zn concentration was dose-dependently increased in the liver, kidney, intestines, and plasma, but not in other organs investigated. Conclusion: A ZnOSM20(-) NP NOAEL could not be established from the current results, but the lowest-observed-adverse-effect level was 125 mg/kg. Furthermore, the NPs were associated with a number of undesirable systemic actions. Thus, their use in humans must be approached with caution.
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