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Biological Trace Element Research

, Volume 185, Issue 1, pp 124–134 | Cite as

Acute and Cumulative Effects of Unmodified 50-nm Nano-ZnO on Mice

  • Tao Kong
  • Shu-Hui Zhang
  • Ji-Liang Zhang
  • Xue-Qin Hao
  • Fan Yang
  • Cai Zhang
  • Zi-Jun Yang
  • Meng-Yu Zhang
  • Jie Wang
Article

Abstract

Nanometer zinc oxide (nano-ZnO) is widely used in diverse industrial and agricultural fields. Due to the extensive contact humans have with these particles, it is crucial to understand the potential effects that nano-ZnO have on human health. Currently, information related to the toxicity and mechanisms of nano-ZnO is limited. The aim of the present study was to investigate acute and cumulative toxic effects of 50-nm unmodified ZnO in mice. This investigation will seek to establish median lethal dose (LD50), a cumulative coefficient, and target organs. The acute and cumulative toxicity was investigated by Karber’s method and via a dose-increasing method, respectively. During the experiment, clinical signs, mortality, body weights, hematology, serum biochemistry, gross pathology, organ weight, and histopathology were examined. The LD50 was 5177-mg/kg·bw; the 95% confidence limits for the LD50 were 5116–5238-mg/kg·bw. It could be concluded that the liver, kidney, lung, and gastrointestinal tract were target organs for the 50-nm nano-ZnO acute oral treatment. The cumulative coefficient (K) was 1.9 which indicated that the cumulative toxicity was apparent. The results also indicated that the liver, kidney, lung, and pancrea were target organs for 50-nm nano-ZnO cumulative oral exposure and might be target organs for subchronic and chronic toxicity of oral administered 50-nm ZnO.

Keywords

Nanometer zinc oxide LD50 Acute toxicity Accumulation coefficient Cumulative toxicity Target organs 

Notes

Funding Information

This study was funded by the National Natural Science Foundation of China (Nos. 31402263 and 41301562).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Abbasalipourkabir R, Moradi H, Zarei S, Asadi S, Salehzadeh A, Ghafourikhosroshahi A, Mortazavi M, Ziamajidi N (2015) Toxicity of zinc oxide nanoparticles on adult male Wistar rats. Food Chem Toxicol 84:154–160.  https://doi.org/10.1016/j.fct.2015.08.019 CrossRefPubMedGoogle Scholar
  2. 2.
    Adamcakova-Dodd A, Stebounova LV, Kim JS, Vorrink SU, Ault AP, O’Shaughnessy PT (2014) Toxicity assessment of zinc oxide nanoparticles using sub-acute and sub-chronic murine inhalation models. Part Fibre Toxicol 11(1):15.  https://doi.org/10.1186/1743-8977-11-15 CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Ben-Slama I, Mrad I, Rihane N, Mir LEL, Sakly M, Amara S et al (2015) Sub-acute oral toxicity of zinc oxide nanoparticles in male rats. J Nanomed Nanotechnol 6(3):284Google Scholar
  4. 4.
    Cho WS, Kang BC, Lee JK, Jeong J, Che JH, Hyeok SS et al (2013) Comparative absorption, distribution, and excretion of titanium dioxide and zinc oxide nanoparticles after repeated oral administration. Part Fibre Toxicol. 10(1):9.  https://doi.org/10.1186/1743-8977-10-9 CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Colvin VL (2003) The potential environmental impact of engineered nanomaterials. Nat Biotechnol 21(10):1166–1170.  https://doi.org/10.1038/nbt875 CrossRefPubMedGoogle Scholar
  6. 6.
    Du XL, Shi Z, Peng ZC, Zhao CX, Zhang YM, Wang Z et al (2017) Acetoacetate induces hepatocytes apoptosis by the ROS-mediated MAPKs pathway in ketotic cows. J Cell Physiol 232(12):3296–3308.  https://doi.org/10.1002/jcp.25773 CrossRefPubMedGoogle Scholar
  7. 7.
    Esmaeillou M, Moharamnejad M, Hsankhani R, Tehrani AA, Maadi H (2013) Toxicity of ZnO nanoparticles in healthy adult mice. Environ Toxicol Pharmacol 35(1):67–71.  https://doi.org/10.1016/j.etap.2012.11.003 CrossRefPubMedGoogle Scholar
  8. 8.
    Feng XL, Wu JR, Lai X, Zhang YL, Wei LM, Liu J et al (2017) Prenatal exposure to nanosized zinc oxide in rats: neurotoxicity and postnatal impaired learning and memory ability. Nanomedicine (Lond) 12(7):777–795CrossRefGoogle Scholar
  9. 9.
    Ghosh M, Sinha S, Jothiramajayam M, Jana A, Nag A, Mukherjee A (2016) Cytogenoto- xicity and oxidative stress induced by zinc oxide nanoparticle in human lymphocyte cells in vitro and Swiss albino male mice in vivo. Food Chem Toxicol 97:286–296.  https://doi.org/10.1016/j.fct.2016.09.025 CrossRefPubMedGoogle Scholar
  10. 10.
    Heim J, Felder E, Tahir MN, Kaltbeitzel A, Heinrich UR, Brochhausen C et al (2015) Genotoxic effects of zinc oxide nanoparticles. Nano 7(19):8931–8938Google Scholar
  11. 11.
    Hong TK, Tripathy N, Son HJ, Ha KT, Jeong HS, Hahn YB (2013) A comprehensive in vitro and in vivo study of ZnO nanoparticles toxicity. J Mater Chem B 1(23):2985–2992.  https://doi.org/10.1039/c3tb20251h CrossRefGoogle Scholar
  12. 12.
    Hou W, Westerhoff P, Posner JD (2013) Biological accumulation of engineered nanomaterials: a review of current knowledge. Environ Sci: Processes Impacts 15(1):103–122Google Scholar
  13. 13.
    Hussain N, Jaitley V, Florence AT (2001) Recent advances in the understanding of uptake of microparticulates across the gastrointestinal lymphatics. Adv Drug Deliv Rev 50(1-2):107–142.  https://doi.org/10.1016/S0169-409X(01)00152-1 CrossRefPubMedGoogle Scholar
  14. 14.
    Jacobsen NR, Stoeger T, Van Den Brule S, Saber AT, Beyerle A, Vietti G et al (2015) Acute and subacute pulmonary toxicity and mortality in mice after intratracheal instillation of ZnO nanoparticles in three laboratories. Food Chem Toxicol 85:84–95.  https://doi.org/10.1016/j.fct.2015.08.008 CrossRefPubMedGoogle Scholar
  15. 15.
    Kaya H, Aydın F, Gürkan M, Yılmaz S, Ates M, Demir V, Arslan Z (2016) A comparative toxicity study between small and large size zinc oxide nanoparticles in tilapia (Oreochromis niloticus): organ pathologies, osmoregulatory responses and immunological parameters. Chemosphere 144:571–582.  https://doi.org/10.1016/j.chemosphere.2015.09.024 CrossRefPubMedGoogle Scholar
  16. 16.
    Kermanizadeh A, Jantzen K, Ward MB, Durhuus JA, Juel Rasmussen L, Loft S, Møller P (2017) Nanomaterial induced cell death in pulmonary and hepatic cells following exposure to three different metallic materials: the role of autophagy and apoptosis. Nanotoxicology 11(2):184–200.  https://doi.org/10.1080/17435390.2017.1279359 CrossRefPubMedGoogle Scholar
  17. 17.
    Ko JW, Hong ET, Lee IC, Park SH, Park J, Seong NW et al (2015) Evaluation of 2-week repeated oral dose toxicity of 100 nm zinc oxide nanoparticles in rats. Lab Anim Res 31(3):139–147.  https://doi.org/10.5625/lar.2015.31.3.139 CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Lee CM, Jeong HJ, Yun KN, Kim DW, Sohn MH, Lee JK, Jeong J, Lim ST (2012) Optical imaging to trace near infrared fluorescent zinc oxide nanoparticles following oral exposure. Int J Nanomedicine 7:3203–3209.  https://doi.org/10.2147/IJN.S32828 PubMedPubMedCentralGoogle Scholar
  19. 19.
    Li MZ, Huang JT, Tsai YH, Mao SY, Fu CM, Lien TF (2016) Nanosize of zinc oxide and the effects on zinc digestibility, growth performances, immune response and serum parameters of weanling piglets. Anim Sci J 87(11):1379–1385.  https://doi.org/10.1111/asj.12579 CrossRefPubMedGoogle Scholar
  20. 20.
    Mantecca P, Moschini E, Bonfanti P, Fascio U, Perelshtein I, Lipovsky A, Chirico G, Bacchetta R, del Giacco L, Colombo A, Gedanken A (2015) Toxicity evaluation of a new Zn-doped CuO nanocomposite with highly effective antibacterial properties. Toxicol Sci 146(1):16–30.  https://doi.org/10.1093/toxsci/kfv067 CrossRefPubMedGoogle Scholar
  21. 21.
    Mao SY, Lien TF (2017) Effects of nanosized zinc oxide and γ-polyglutamic acid on eggshell quality and serum parameters of aged laying hens. Arch Anim Nutr 71(5):373–383.  https://doi.org/10.1080/1745039X.2017.1355600 CrossRefPubMedGoogle Scholar
  22. 22.
    Oberdorster G, Oberdorster E, Oberdorster J (2005) Nanotoxicology: an emerging discipline evolving from studies of ultrafine particles. Environ Health Perspect 113(7):823–839.  https://doi.org/10.1289/ehp.7339 CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Osman IF, Baumgartner A, Cemeli E, Fletcher JN, Anderson D (2010) Genotoxicity and cytotoxicity of zinc oxide and titanium dioxide in HEp-2 cells. Nanomedicine (Lond) 5(8):1193–1203.  https://doi.org/10.2217/nnm.10.52 CrossRefGoogle Scholar
  24. 24.
    Park HS, Shin SS, Meang EH, Hong JS, Park J, Kim SH et al (2014) A 90-day study of subchronic oral toxicity of 20 nm, negatively charged zinc oxide nanoparticles in Sprague Dawley rats. Int J Nanomedicine 9(Suppl 2):79–92PubMedPubMedCentralGoogle Scholar
  25. 25.
    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 (2013) Rat pancreatitis produced by 13-week administration of zinc oxide nanoparticles: biopersistence of nanoparticles and possible solutions. J Appl Toxicol 33(10):1089–1096.  https://doi.org/10.1002/jat.2862 CrossRefPubMedGoogle Scholar
  26. 26.
    Setyawati MI, Tay CY, Leong DT (2015) Mechanistic investigation of the biological effects of SiO2, TiO2, and ZnO nanoparticles on intestinal cells. Small 11(28):3458–3468.  https://doi.org/10.1002/smll.201403232 CrossRefPubMedGoogle Scholar
  27. 27.
    Shalini D, Senthilkumar S, Rajaguru P (2017) Effect of size and shape on toxicity of zinc oxide (ZnO) nanomaterials in human peripheral blood lymphocytes. Toxicol Mech Methods 13:1–28Google Scholar
  28. 28.
    Sharma V, Singh SK, Anderson D, Tobin DJ, Dhawan A (2011) Zinc oxide nanoparticle induced genotoxicity in primary human epidermal keratinocytes. J Nanosci Nanotechnol 11(5):3782–3788.  https://doi.org/10.1166/jnn.2011.4250 CrossRefPubMedGoogle Scholar
  29. 29.
    Sharma V, Singh P, Pandey AK, Dhawan A (2012) Induction of oxidative stress, DNA damage and apoptosis in mouse liver after sub-acute oral exposure to zinc oxide nanoparticles. Mutat Res/Genet Toxicol Environ Mutagen 745(1-2):84–91.  https://doi.org/10.1016/j.mrgentox.2011.12.009 CrossRefGoogle Scholar
  30. 30.
    Sharma AK, Singh V, Gera R, Purohit MP, Ghosh D (2016) Zinc oxide nanoparticle induces microglial death by NADPH-oxidase-independent reactive oxygen species as well as energy depletion. Mol Neurobiol:1–14Google Scholar
  31. 31.
    Song Y, Li N, Gu J, Fu S, Peng Z, Zhao C, Zhang Y, Li X, Wang Z, Li X, Liu G (2016) β-Hydroxybutyrate induces bovine hepatocyte apoptosis via an ROS-p38 signaling pathway. J Dairy Sci 99(11):9184–9198.  https://doi.org/10.3168/jds.2016-11219 CrossRefPubMedGoogle Scholar
  32. 32.
    Theodorou IG, Ruenraroengsak P, Gow A, Schwander S, Zhang JJ, Chung KF, Tetley TD, Ryan MP, Porter AE (2016) Effect of pulmonary surfactant on the dissolution, stability and uptake of zinc oxide nanowires by human respiratory epithelial cells. Nanotoxicology 10(9):1351–1362.  https://doi.org/10.1080/17435390.2016.1214762 CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Uski O, Torvela T, Sippula O, Karhunen T, Koponen H, Peräniemi S, Jalava P, Happo M, Jokiniemi J, Hirvonen MR, Lähde A (2017) In vitro toxicological effects of zinc containing nanoparticles with different physico-chemical properties. Toxicol in Vitro 42:105–113CrossRefPubMedGoogle Scholar
  34. 34.
    Wang, B., Feng, W.Y., Wang, M., Wang, T.C., Gu,Y.Q., Zhu, M.T., 2008. Acute toxicological impact of nano- and submicro-scaled zinc oxide powder on healthy adult mice. J Nanopart Res 10, 263–276, 2, DOI:  https://doi.org/10.1007/s11051-007-9245-3
  35. 35.
    Wu C, Wen LX, Yuan H, Peng T (2008) Toxicity of nano zinc oxide in mice. Cereal Feed Industry (China) 5:38–39Google Scholar
  36. 36.
    Yan G, Huang Y, Bu Q, Lv L, Deng P, Zhou J, Wang Y, Yang Y, Liu Q, Cen X, Zhao Y (2012) Zinc oxide nanoparticles cause nephrotoxicity and kidney metabolism alterations in rats. J Environ Sci Health Part A Toxic/Hazard Subst Environ Eng 47(4):577–588.  https://doi.org/10.1080/10934529.2012.650576 CrossRefGoogle Scholar
  37. 37.
    Ye DX, Ma YY, Zhao W, Cao HM, Kong JL, Xiong HM, Möhwald H (2016) ZnO-based nanoplatforms for labeling and treatment of mouse tumors without detectable toxic side effects. ACS Nano 10(4):4294–4300.  https://doi.org/10.1021/acsnano.5b07846 CrossRefPubMedGoogle Scholar
  38. 38.
    .Zhao XS, Ren X, Zhu R, Luo ZY, Ren BX (2016) Zinc oxide nanoparticles induce oxidative DNA damage and ROS-triggered mitochondria-mediated apoptosis in zebrafish embryos. Aquat Toxicol 180:56–70.  https://doi.org/10.1016/j.aquatox.2016.09.013 CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.College of Animal Science and Veterinary MedicineHenan University of Science and TechnologyLuoyangPeople’s Republic of China
  2. 2.Environmental and Animal Products Safety Laboratory of Key Discipline in University of Henan ProvinceLuoyangPeople’s Republic of China
  3. 3.Library of Henan University of Science and TechnologyLuoyangPeople’s Republic of China

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