A 90-day study of sub-chronic oral toxicity of 20 nm positively charged zinc oxide nanoparticles in Sprague Dawley rats

Hark Soo Park, Seon Ju Kim, Taek Jin Lee, Geon Yong Kim, Eunho Meang, Jeong Sup Hong, Su Hyon Kim, Sang Bum Koh, Seung Guk Hong, 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 journalArticle

19 Citations (Scopus)

Abstract

Purpose: The study reported here was conducted to determine the systemic oral toxicity and to find the no-observed-adverse-effect level of 20 nm positively charged zinc oxide (ZnOSM20(+)) nanoparticles in Sprague Dawley rats for 90 days. Methods: For the 90-day toxicity study, the high dose was set as 500 mg per kg of body weight (mg/kg) and the middle and low dose were set to 250 mg/kg and 125 mg/kg, respectively. The rats were held for a 14-day recovery period after the last administration, to observe for the persistence or reduction of any toxic effects. A distributional study was also carried out for the systemic distribution of ZnOSM20(+) NPs. Results: No rats died during the test period. There were no significant clinical changes due to the test article during the experimental period in functional assessment, body weight, food and water consumption, ophthalmological testing, urine analysis, necropsy findings, or organ weights, but salivation was observed immediately after administration in both sexes. The total red blood cell count was increased, and hematocrit, albumin, mean cell volume, mean cell hemoglobin, and mean cell hemoglobin concentration were decreased significantly compared with control in both 500 mg/kg groups. Total protein and albumin levels were decreased significantly in both sexes in the 250 and 500 mg/kg groups. Histopathological studies revealed acinar cell apoptosis in the pancreas, inflammation and edema in stomach mucosa, and retinal atrophy of the eye in the 500 mg/kg group. Conclusion: There were significant parameter changes in terms of anemia in the hematological and blood chemical analyses in the 250 and 500 mg/kg groups. The significant toxic change was observed to be below 125 mg/kg, so the no-observed-adverse-effect level was not determined, but the lowest-observed-adverse-effect level was considered to be 125 mg/kg in both sexes and the target organs were found to be the pancreas, eye, and stomach.

Original languageEnglish
JournalInternational Journal of Nanomedicine
Volume9
DOIs
Publication statusPublished - 2014 Dec 15

Fingerprint

Zinc Oxide
Zinc oxide
Nanoparticles
Sprague Dawley Rats
Toxicity
Rats
No-Observed-Adverse-Effect Level
Erythrocyte Indices
Poisons
Hemoglobin
Blood Chemical Analysis
Pancreas
Albumins
Stomach
Hemoglobins
Blood
Functional assessment
Body Weight
Salivation
Erythrocyte Count

Keywords

  • No-observed-adverse-effect level
  • Oral-toxicity study
  • Positive charge
  • ZnO

ASJC Scopus subject areas

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

Cite this

A 90-day study of sub-chronic oral toxicity of 20 nm positively charged zinc oxide nanoparticles in Sprague Dawley rats. / Park, Hark Soo; Kim, Seon Ju; Lee, Taek Jin; Kim, Geon Yong; Meang, Eunho; Hong, Jeong Sup; Kim, Su Hyon; Koh, Sang Bum; Hong, Seung Guk; Sun, Yle Shik; Kang, Jin Seok; Kim, Yu Ri; Kim, Meyoung-Kon; Jeong, Jayoung; Lee, Jong Kwon; Son, Woo Chan; Park, Jae Hak.

In: International Journal of Nanomedicine, Vol. 9, 15.12.2014.

Research output: Contribution to journalArticle

Park, HS, Kim, SJ, Lee, TJ, Kim, GY, Meang, E, Hong, JS, Kim, SH, Koh, SB, Hong, SG, Sun, YS, Kang, JS, Kim, YR, Kim, M-K, Jeong, J, Lee, JK, Son, WC & Park, JH 2014, 'A 90-day study of sub-chronic oral toxicity of 20 nm positively charged zinc oxide nanoparticles in Sprague Dawley rats', International Journal of Nanomedicine, vol. 9. https://doi.org/10.2147/IJN.S57927
Park, Hark Soo ; Kim, Seon Ju ; Lee, Taek Jin ; Kim, Geon Yong ; Meang, Eunho ; Hong, Jeong Sup ; Kim, Su Hyon ; Koh, Sang Bum ; Hong, Seung Guk ; Sun, Yle Shik ; Kang, Jin Seok ; Kim, Yu Ri ; Kim, Meyoung-Kon ; Jeong, Jayoung ; Lee, Jong Kwon ; Son, Woo Chan ; Park, Jae Hak. / A 90-day study of sub-chronic oral toxicity of 20 nm positively charged zinc oxide nanoparticles in Sprague Dawley rats. In: International Journal of Nanomedicine. 2014 ; Vol. 9.
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AU - Meang, Eunho

AU - Hong, Jeong Sup

AU - Kim, Su Hyon

AU - Koh, Sang Bum

AU - Hong, Seung Guk

AU - Sun, Yle Shik

AU - Kang, Jin Seok

AU - Kim, Yu Ri

AU - Kim, Meyoung-Kon

AU - Jeong, Jayoung

AU - Lee, Jong Kwon

AU - Son, Woo Chan

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N2 - Purpose: The study reported here was conducted to determine the systemic oral toxicity and to find the no-observed-adverse-effect level of 20 nm positively charged zinc oxide (ZnOSM20(+)) nanoparticles in Sprague Dawley rats for 90 days. Methods: For the 90-day toxicity study, the high dose was set as 500 mg per kg of body weight (mg/kg) and the middle and low dose were set to 250 mg/kg and 125 mg/kg, respectively. The rats were held for a 14-day recovery period after the last administration, to observe for the persistence or reduction of any toxic effects. A distributional study was also carried out for the systemic distribution of ZnOSM20(+) NPs. Results: No rats died during the test period. There were no significant clinical changes due to the test article during the experimental period in functional assessment, body weight, food and water consumption, ophthalmological testing, urine analysis, necropsy findings, or organ weights, but salivation was observed immediately after administration in both sexes. The total red blood cell count was increased, and hematocrit, albumin, mean cell volume, mean cell hemoglobin, and mean cell hemoglobin concentration were decreased significantly compared with control in both 500 mg/kg groups. Total protein and albumin levels were decreased significantly in both sexes in the 250 and 500 mg/kg groups. Histopathological studies revealed acinar cell apoptosis in the pancreas, inflammation and edema in stomach mucosa, and retinal atrophy of the eye in the 500 mg/kg group. Conclusion: There were significant parameter changes in terms of anemia in the hematological and blood chemical analyses in the 250 and 500 mg/kg groups. The significant toxic change was observed to be below 125 mg/kg, so the no-observed-adverse-effect level was not determined, but the lowest-observed-adverse-effect level was considered to be 125 mg/kg in both sexes and the target organs were found to be the pancreas, eye, and stomach.

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KW - Positive charge

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