Toxicity of 100 nm zinc oxide nanoparticles: A report of 90-day repeated oral administration in Sprague Dawley rats

Yu Ri Kim, Jong Il Park, Eun Jeong Lee, Sung Ha Park, Nak Won Seong, Jun Ho Kim, Geon Yong Kim, Eun Ho Meang, Jeong Sup Hong, Su Hyon Kim, Sang Bum Koh, Min Seok Kim, Cheol Su Kim, Soo Ki Kim, Sang Wook Son, Young Rok Seo, Boo Hyon Kang, Beom Seok Han, Seong Soo A An, Hyo In YunMeyoung-Kon Kim

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34 Citations (Scopus)

Abstract

Nanoparticles (NPs) are used commercially in health and fitness fields, but information about the toxicity and mechanisms underlying the toxic effects of NPs is still very limited. The aim of this study is to investigate the toxic effect(s) of 100 nm negatively (ZnOAE100[-]) or positively (ZnOAE100[+]) charged zinc oxide (ZnO) NPs administered by gavage in Sprague Dawley rats, to establish a no observed adverse effect level, and to identify target organ(s). After verification of the primary particle size, morphology, hydrodynamic size, and zeta potential of each test article, we performed a 90-day study according to Organisation for Economic Co-operation and Development test guideline 408. For the 90-day study, the high dose was set at 500 mg/kg and the middle and low doses were set at 125 mg/kg and 31.25 mg/kg, respectively. Both ZnO NPs had significant changes in hematological and blood biochemical analysis, which could correlate with anemia-related parameters, in the 500 mg/kg groups of both sexes. Histopathological examination showed significant adverse effects (by both test articles) in the stomach, pancreas, eye, and prostate gland tissues, but the particle charge did not affect the tendency or the degree of the lesions. We speculate that this inflammatory damage might result from continuous irritation caused by both test articles. Therefore, the target organs for both ZnOAE100(-) and ZnOAE100(+) are considered to be the stomach, pancreas, eye, and prostate gland. Also, the no observed adverse effect level for both test articles was identified as 31.25 mg/kg for both sexes, because the adverse effects were observed at all doses greater than 125 mg/kg.

Original languageEnglish
Pages (from-to)109-126
Number of pages18
JournalInternational Journal of Nanomedicine
Volume9
DOIs
Publication statusPublished - 2014 Dec 15

Keywords

  • 90-day oral dose toxicity
  • No observed adverse effect level
  • Surface charge
  • Zinc oxide nanoparticles

ASJC Scopus subject areas

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

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    Kim, Y. R., Park, J. I., Lee, E. J., Park, S. H., Seong, N. W., Kim, J. H., Kim, G. Y., Meang, E. H., Hong, J. S., Kim, S. H., Koh, S. B., Kim, M. S., Kim, C. S., Kim, S. K., Son, S. W., Seo, Y. R., Kang, B. H., Han, B. S., An, S. S. A., ... Kim, M-K. (2014). Toxicity of 100 nm zinc oxide nanoparticles: A report of 90-day repeated oral administration in Sprague Dawley rats. International Journal of Nanomedicine, 9, 109-126. https://doi.org/10.2147/IJN.S57928