Lab Anim Res.  2015 Sep;31(3):139-147. 10.5625/lar.2015.31.3.139.

Evaluation of 2-week repeated oral dose toxicity of 100 nm zinc oxide nanoparticles in rats

Affiliations
  • 1College of Veterinary Medicine, Chonnam National University, Gwangju, Korea. toxkim@jnu.ac.kr
  • 2Health Care Institute, Korea Testing and Research Institute, Hwasun, Korea.
  • 3College of Veterinary Medicine, Chungnam National University, Daejon, Korea.

Abstract

The aim of this study was to verify subacute oral dose toxicity of positively charged 100 nm zinc oxide (ZnO(AE100[+])) nanoparticles (NPs) in Sprague-Dawley rats. ZnO(AE100[+]) NPs were administered to rats of each sex by gavage at 0, 500, 1,000, and 2,000 mg/kg/day for 14 days. During the study period, clinical signs, mortality, body weight, food consumption, hematology, serum biochemistry, gross pathology, organ weight, and histopathology were examined. Increased mortality and clinical signs, decreased body weight, feed consumption, hemoglobin (HB), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), platelet (PT), and lymphocyte (LYM) and increased white blood cells (WBCs), neutrophils (NEUs), alkaline phosphatase (ALP), and histopathological alterations in the spleen, stomach, and pancreas were observed at 2,000 mg/kg/day. Increased clinical signs, decreased body weight, feed consumption, HB, HCT, MCV, MCH, MCHC, and LYM and increased WBCs, NEUs, ALP, and histopathological alterations in the spleen, stomach, and pancreas were seen at 1,000 mg/kg/day. Increased clinical signs, decreased MCV and MCH and increased histopathological alterations in the stomach and pancreas were found at 500 mg/kg/day. These results suggest that the target organs were the spleen, stomach, and pancreas in rats. The no-observed-adverse-effect level was <500 mg/kg for both sexes.

Keyword

Zinc oxide nanoparticles; subacute toxicity; target organ; no-observed-adverse-effect level

MeSH Terms

Alkaline Phosphatase
Animals
Biochemistry
Blood Platelets
Body Weight
Erythrocyte Indices
Hematocrit
Hematology
Leukocytes
Lymphocytes
Mortality
Nanoparticles*
Neutrophils
No-Observed-Adverse-Effect Level
Organ Size
Pancreas
Pathology
Rats*
Rats, Sprague-Dawley
Spleen
Stomach
Zinc Oxide*
Zinc*
Alkaline Phosphatase
Zinc
Zinc Oxide

Reference

1. Kołodziejczak-Radzimska A, Jesionowski T. Zinc oxide-from synthesis to application: a review. Materials. 2014; 7:2833–2881.
Article
2. Becheri A, Durr M, Lo Nostro P, Baglioni P. Synthesis and characterization of zinc oxide nanoparticles: application to textiles as UV-absorbers. J Nanopart Res. 2008; 10:679–689.
Article
3. Lin CC, Lin WH, Li YY. Synthesis of ZnO nanowires and their applications as an ultraviolet photodetector. J Nanosci Nanotechnol. 2009; 9(5):2813–2819. PMID: 19452935.
Article
4. Osmond MJ, McCall MJ. Zinc oxide nanoparticles in modern sunscreens: an analysis of potential exposure and hazard. Nanotoxicology. 2010; 4(1):15–41. PMID: 20795900.
Article
5. Hong H, Wang F, Zhang Y, Graves SA, Eddine SB, Yang Y, Theuer CP, Nickles RJ, Wang X, Cai W. Red fluorescent zinc oxide nanoparticle: a novel platform for cancer targeting. ACS Appl Mater Interfaces. 2015; 7(5):3373–3381. PMID: 25607242.
Article
6. Wang B, Feng WY, Wang M, Wang TC, Gu YQ, Zhu MT, Ouyang H, Shi JW, Zhang F, Zhao YL, Zhao YL, Chai ZF, Wang HF, Wang J. Acute toxicological impact of nano- and submicroscaled zinc oxide powder on healthy adult mice. J Nanopart Res. 2008; 10(2):263–276.
Article
7. Adamcakova-Dodd A, Stebounova LV, Kim JS, Vorrink SU, Ault AP, O'Shaughnessy PT, Grassian VH, Thorne PS. Toxicity assessment of zinc oxide nanoparticles using sub-acute and subchronic murine inhalation models. Part Fibre Toxicol. 2014; 11:15. PMID: 24684892.
Article
8. Choi SJ, Lee J, Jeong J, Choy JH. Toxicity evaluation of inorganic nanoparticles: considerations and challenges. Mol Cell Toxicol. 2013; 9(3):205–210.
Article
9. Sharma V, Singh P, Pandey AK, Dhawan A. Induction of oxidative stress, DNA damage and apoptosis in mouse liver after sub-acute oral exposure to zinc oxide nanoparticles. Mutat Res. 2012; 745(1-2):84–91. PMID: 22198329.
Article
10. Yan G, Huang Y, Bu Q, Lv L, Deng P, Zhou J, Wang Y, Yang Y, Liu Q, Cen X, Zhao Y. Zinc oxide nanoparticles cause nephrotoxicity and kidney metabolism alterations in rats. J Environ Sci Health A Tox Hazard Subst Environ Eng. 2012; 47(4):577–588. PMID: 22375541.
Article
11. Surekha P, Kishore AS, Srinivas A, Selvam G, Goparaju A, Reddy PN, Murthy PB. Repeated dose dermal toxicity study of nano zinc oxide with Sprague-Dawley rats. Cutan Ocul Toxicol. 2012; 31(1):26–32. PMID: 21830917.
Article
12. Yang H, Liu C, Yang D, Zhang H, Xi Z. Comparative study of cytotoxicity, oxidative stress and genotoxicity induced by four typical nanomaterials: the role of particle size, shape and composition. J Appl Toxicol. 2009; 29(1):69–78. PMID: 18756589.
Article
13. Pasupuleti S, Alapati S, Ganapathy S, Anumolu G, Pully NR, Prakhya BM. Toxicity of zinc oxide nanoparticles through oral route. Toxicol Ind Health. 2012; 28(8):675–686. PMID: 22033421.
Article
14. Ho M, Wu KY, Chein HM, Chen LC, Cheng TJ. Pulmonary toxicity of inhaled nanoscale and fine zinc oxide particles: mass and surface area as an exposure metric. Inhal Toxicol. 2011; 23(14):947–956. PMID: 22122307.
Article
15. Kim KM, Kim TH, Kim HM, Kim HJ, Gwak GH, Paek SM, Oh JM. Colloidal behaviors of ZnO nanoparticles in various aqueous media. Toxicol Environ Health Sci. 2012; 4(2):121–131.
Article
16. Kim YR, Park JI, Lee EJ, Park SH, Seong NW, Kim JH, Kim GY, Meang EH, Hong JS, Kim SH, Koh SB, Kim MS, Kim CS, Kim SK, Son SW, Seo YR, Kang BH, Han BS, An SS, Yun HI, Kim MK. Toxicity of 100 nm zinc oxide nanoparticles: a report of 90-day repeated oral administration in Sprague Dawley rats. Int J Nanomedicine. 2014; 9(Suppl 2):109–126. PMID: 25565830.
17. Duffus JF. World Health Organization, Geneva, 1979, agreed terms on health effects evaluation and risk and hazard assessment of environmental agents. Internal report of a working group, (EHE/EHC/79.19) in glossary for chemists of terms used in Toxicology. Pure Appl Chem. 1993; 65:2003–2122.
18. Katsukawa H, Ninomiya Y. Capsaicin induces cystatin S-like substances in submandibular saliva of the rat. J Dent Res. 1999; 78(10):1609–1616. PMID: 10520965.
Article
19. Yu WJ, Chung MK, Chung YH, Kim HC, Kim SH, Lee IC, Kim JC. One-generation reproductive toxicity study of 2-methylbutane in Sprague-Dawley rats. Regul Toxicol Pharmacol. 2011; 60(1):136–143. PMID: 21419187.
Article
20. Yang YS, Lee SB, Choi SJ, Lee BS, Heo JD, Song CW, Kim HY, Kim JC, Lee K. Evaluation of subchronic inhalation toxicity of methylcyclopentane in rats. Food Chem Toxicol. 2014; 63:186–194. PMID: 24239891.
Article
21. Andersen H, Larsen S, Spliid H, Christensen ND. Multivariate statistical analysis of organ weights in toxicity studies. Toxicology. 1999; 136(23):67–77. PMID: 10514000.
Article
22. Bailey SA, Zidell RH, Perry RW. Relationships between organ weight and body/brain weight in the rat: what is the best analytical endpoint? Toxicol Pathol. 2004; 32(4):448–466. PMID: 15204968.
Article
23. Lewis RW, Billington R, Debryune E, Gamer A, Lang B, Carpanini F. Recognition of adverse and nonadverse effects in toxicity studies. Toxicol Pathol. 2002; 30(1):66–74. PMID: 11890477.
Article
24. Seok SH, Cho WS, Park JS, Na Y, Jang A, Kim H, Cho Y, Kim T, You JR, Ko S, Kang BC, Lee JK, Jeong J, Che JH. Rat pancreatitis produced by 13-week administration of zinc oxide nanoparticles: biopersistence of nanoparticles and possible solutions. J Appl Toxicol. 2013; 33(10):1089–1096. PMID: 23408656.
Article
25. Gross S, Keefer V, Newman AJ. The platelets in iron-deficiency anemia. I. The response of oral and parenteral iron. Pediatrics. 1964; 34(3):315–323. PMID: 14211098.
26. Boorman GA, Eustis SL, Elwell MR, Montgomery CA Jr, Mackenzie WF. Pathology of the Fischer Rat. Reference and Atlas. San Diego, USA: Academic Press;1990.
27. Greaves P. Histopathology of Preclinical Studies: Interpretation and Relevance in Drug Evaluation. New York, USA: Elsevier;1990.
28. Haschek WM, Rousseaux CG. Fundamentals of Toxicologic Pathology. San Diego, USA: Academic Press;1998.
29. Kim HY, Lee SB, Cho HW, Kang MG, Yang JS, Shin IS, Kim JC. Evaluation of 13-week inhalation toxicity of sec-butanethiol in rats. Food Chem Toxicol. 2009; 47(9):2294–2301. PMID: 19527766.
Article
Full Text Links
  • LAR
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr