A 90-day study of subchronic oral toxicity of 20 nm, negatively charged zinc oxide nanoparticles in Sprague Dawley rats

Hark Soo Park, Sung Sup Shin, Eun Ho Meang, Jeong Sup Hong, Jong Il Park, Su Hyon Kim, Sang Bum Koh, Seung Young Lee, Dong Hyouk Jang, Jong Yun Lee, Yle Shik Sun, Jin Seok Kang, Yu Ri Kim, Meyoung Kon Kim, Jayoung Jeong, Jong Kwon Lee, Woo Chan Son, Jae Hak Park

Research output: Contribution to journalArticlepeer-review

30 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)79-92
Number of pages14
JournalInternational Journal of Nanomedicine
Publication statusPublished - 2014 Dec 15
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2014 Park et al.


  • Negative charge
  • Oral toxicity study
  • Rat
  • ZnO

ASJC Scopus subject areas

  • Biophysics
  • Bioengineering
  • Biomaterials
  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry


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