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Evaluation of Maternal Toxicity in Rats Exposed to Multi-Wall Carbon Nanotubes during Pregnancy

  • Lim, Jeong-Hyeon (College of Veterinary Medicine, Chonnam National University) ;
  • Kim, Sung-Hwan (College of Veterinary Medicine, Chonnam National University) ;
  • Lee, In-Chul (College of Veterinary Medicine, Chonnam National University) ;
  • Moon, Chang-Jong (College of Veterinary Medicine, Chonnam National University) ;
  • Kim, Sung-Ho (College of Veterinary Medicine, Chonnam National University) ;
  • Shin, Dong-Ho (College of Veterinary Medicine, Chonnam National University) ;
  • Kim, Hyoung-Chin (Biomedical Mouse Resource Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Kim, Jong-Choon (College of Veterinary Medicine, Chonnam National University)
  • Received : 2011.01.10
  • Accepted : 2011.03.10
  • Published : 2011.01.01

Abstract

Objectives: The present study investigated the potential adverse effects of multi-wall carbon nanotubes (MWCNTs) on pregnant dams and embryonic development following maternal exposure in rats. Methods: MWCNTs were orally administered to pregnant rats from gestational day (GD) 6 through 19 at dose levels of 0, 8, 40, 200, and 1000 mg/kg/day. During the test period, clinical signs, mortality, body weights, food consumption, serum biochemistry, oxidant-antioxidant status, gross findings, organ weights, and Caesarean section findings were examined. Results: All animals survived to the end of the study. A decrease in thymus weight was observed in the highest dose group. However, maternal body weight, food consumption, serum biochemical parameters, and oxidant-antioxidant balance in the kidneys were not affected by treatment with MWCNTs. No treatment-related differences in gestational index, embryo-fetal mortality, or fetal and placental weights were observed between treated and control groups. Conclusions: The results show that 14-day repeated oral dosing of MWCNTs during pregnancy induces minimal maternal toxicity at 1000 mg/kg/day in rats. Under these experimental conditions, the no-observed-adverse-effect level of MWCNTs is considered to be 200 mg/kg/day for dams and 1000 mg/kg/day for embryonic development.

Keywords

References

  1. Lam CW, James JT, McCluskey R, Arepalli S, Hunter RL. A review of carbon nanotube toxicity and assessment of potential occupational and environmental health risks. Crit Rev Toxicol 2006; 36(3): 189-217. https://doi.org/10.1080/10408440600570233
  2. Nel A, Xia T, Madler L, Li N. Toxic potential of materials at the nanolevel. Science 2006; 311(5761): 622-627. https://doi.org/10.1126/science.1114397
  3. Firme CP 3rd, Bandaru PR. Toxicity issues in the application of carbon nanotubes to biological systems. Nanomedicine 2010; 6(2): 245-256. https://doi.org/10.1016/j.nano.2009.07.003
  4. Oberdorster G, Oberdorster E, Oberdorster J. Nanotoxicology: an emerging discipline evolving from studies of ultrafine particles. Environ Health Perspect 2005; 113(7): 823-839. https://doi.org/10.1289/ehp.7339
  5. Folkmann JK, Risom L, Jacobsen NR, Wallin H, Loft S, Moller P. Oxidatively damaged DNA in rats exposed by oral gavage to C60 fullerenes and single-walled carbon nanotubes. Environ Health Perspect 2009; 117(5): 703-708. https://doi.org/10.1289/ehp.11922
  6. Shvedova AA, Castranova V, Kisin ER, Schwegler-Berry D, Murray AR, Gandelsman VZ, et al. Exposure to carbon nanotube material: assessment of nanotube cytotoxicity using human keratinocytes cells. J Toxicol Environ Health A 2003; 66(20): 1909-1926. https://doi.org/10.1080/713853956
  7. Zhu L, Chang DW, Dai L, Hong Y. DNA damage induced by multiwalled carbon nanotubes in mouse embryonic stem cells. Nano Lett 2007; 7(12): 3592-3597. https://doi.org/10.1021/nl071303v
  8. Pacurari M, Yin XJ, Zhao J, Ding M, Leonard SS, Schwegler-Berry D, et al. Raw single-wall carbon nanotubes induce oxidative stress and activate MAPKs, AP-1, NF-kappaB, and Akt in normal and malignant human mesothelial cells. Environ Health Perspect 2008; 116(9): 1211-1217. https://doi.org/10.1289/ehp.10924
  9. Karlsson HL, Cronholm P, Gustafsson J, Moller L. Copper oxide nanoparticles are highly toxic: a comparison between metal oxide nanoparticles and carbon nanotubes. Chem Res Toxicol 2008; 21(9): 1726-1732. https://doi.org/10.1021/tx800064j
  10. Takagi A, Hirose A, Nishimura T, Fukumori N, Ogata A, Ohashi N, et al. Induction of mesothelioma in p53+/- mouse by intraperitoneal application of multi-wall carbon nanotube. J Toxicol Sci 2008; 33(1): 105-116. https://doi.org/10.2131/jts.33.105
  11. Kovacic P, Somanathan R. Mechanism of teratogenesis: electron transfer, reactive oxygen species, and antioxidants. Birth Defects Res C Embryo Today 2006; 78(4): 308-325. https://doi.org/10.1002/bdrc.20081
  12. Chung MK, Kim CY, Kim JC. Reproductive toxicity evaluation of a new camptothecin anticancer agent, CKD-602, in pregnant/lactating female rats and their offspring. Cancer Chemother Pharmacol 2007; 59(3): 383-395.
  13. Kim JS, Lee K, Lee YH, Cho HS, Kim KH, Choi KH, et al. Aspect ratio has no effect on genotoxicity of multi-wall carbon nanotubes. Arch Toxicol DOI 10.1007/s00204-010-0574-0.
  14. Chen HH, Yu C, Ueng TH, Chen S, Chen BJ, Huang KJ, et al. Acute and subacute toxicity study of water-soluble polyalkylsulfonated C60 in rats. Toxicol Pathol 1998; 26(1): 143-151. https://doi.org/10.1177/019262339802600117
  15. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with Folin phenol reagent. J Biol Chem 1951; 193(1): 265-275.
  16. Aebi H. Catalase in vitro. Methods Enzymol 1984; 105: 121-126.
  17. Carlberg I, Mannervik B. Reduction of 2,4,6-trinitrobenzene-sulfonate by glutathione reductase and the effect of NADP+ on the electron transfer, J Biol Chem 1986; 261(4): 1629-1635.
  18. Paglia DE, Valentine WN. Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 1967; 70(1): 158-169.
  19. Habig WH, Jakoby WB, Guthenberg C, Mannervik B, Vander Jagt DL. 2-Propylthiouracil does not replace glutathione for the glutathione transferases. J Biol Chem 1984; 259(12): 7409-7410.
  20. Moron MS, Depierre JW, Mannervik B. Levels of glutathione, glutathione reductase and glutathione-S-transferase activities in rat lung and liver. Biochem Biophys Acta 1979; 582(1): 67-78. https://doi.org/10.1016/0304-4165(79)90289-7
  21. Berton TR, Conti CJ, Mitchell DL, Aldaz CM, Lubet RA, Fischer SM. The effect of vitamin E acetate on ultraviolet-induced mouse skin carcinogenesis. Mol Carcinog 1998; 23(3): 175-184. https://doi.org/10.1002/(SICI)1098-2744(199811)23:3<175::AID-MC6>3.0.CO;2-B
  22. Lee JC, Shin IS, Ahn TH, Kim KH, Moon C, Kim SH, et al. Developmental toxic potential of 1,3-dichloro-2-propanol in Sprague-Dawley rats. Regul Toxicol Pharmacol 2009; 53(1): 63-69. https://doi.org/10.1016/j.yrtph.2008.11.001
  23. Muller J, Huaux F, Moreau N, Misson P, Heilier JF, Delos M, et al. Respiratory toxicity of multi-wall carbon nanotubes. Toxicol Appl Pharmacol 2005; 207(3): 221-231. https://doi.org/10.1016/j.taap.2005.01.008
  24. Pauluhn J. Subchronic 13-week inhalation exposure of rats to multiwalled carbon nanotubes: toxic effects are determined by density of agglomerate structures, not fibrillar structures. Toxicol Sci 2010; 113(1): 226-242. https://doi.org/10.1093/toxsci/kfp247
  25. Bottini M, Bruckner S, Nika K, Bottini N, Bellucci S, Magrini A, et al. Multi-walled carbon nanotubes induce T lymphocyte apoptosis. Toxicol Lett 2006; 160(2): 121-126. https://doi.org/10.1016/j.toxlet.2005.06.020
  26. Bottini M, Tautz L, Huynh H, Monosov E, Bottini N, Dawson MI, et al. Covalent decoration of multi-walled carbon nanotubes with silica nanoparticles. Chem Commun (Camb) 2005; (6): 758-760.
  27. Patlolla A, Knighten B, Tchounwou P. Multi-walled carbon nanotubes induce cytotoxicity, genotoxicity and apoptosis in normal human dermal fibroblast cells. Ethn Dis 2010; 20(1 Suppl 1): S1-65-72.
  28. Cui D, Tian F, Ozkan CS, Wang M, Gao H. Effect of single wall carbon nanotubes on human HEK293 cells. Toxicol Lett 2005; 155(1): 73-85. https://doi.org/10.1016/j.toxlet.2004.08.015
  29. Wirnitzer U, Herbold B, Voetz M, Ragot J. Studies on the in vitro genotoxicity of baytubes, agglomerates of engineered multi-walled carbon-nanotubes (MWCNT). Toxicol Lett 2009; 186(3): 160-165. https://doi.org/10.1016/j.toxlet.2008.11.024
  30. Di Sotto A, Chiaretti M, Carru GA, Bellucci S, Mazzanti G. Multi-walled carbon nanotubes: Lack of mutagenic activity in the bacterial reverse mutation assay. Toxicol Lett 2009; 184(3): 192-197. https://doi.org/10.1016/j.toxlet.2008.11.007
  31. Liang G, Yin L, Zhang J, Liu R, Zhang T, Ye B, et al. Effects of subchronic exposure to multi-walled carbon nanotubes on mice. J Toxicol Environ Health A 2010; 73(7): 463-470. https://doi.org/10.1080/15287390903523378
  32. Huczko A, Lange H, Calko E, Grubek-Jaworska H, Droszcz P. Physiological testing of carbon nanotubes: are they asbestos-like? Fullerene Sci Technol 2001; 9(2): 251-254. https://doi.org/10.1081/FST-100102973
  33. Mitchell LA, Gao J, Wal RV, Gigliotti A, Burchiel SW, McDonald JD. Pulmonary and systemic immune response to inhaled multiwalled carbon nanotubes. Toxicol Sci 2007; 100(1): 203-214. https://doi.org/10.1093/toxsci/kfm196
  34. Li JG, Li WX, Xu JY, Cai XQ, Liu RL, Li YJ, et al. Comparative study of pathological lesions induced by multiwalled carbon nanotubes in lungs of mice by intratracheal instillation and inhalation. Environ Toxicol 2007; 22(4): 415-421. https://doi.org/10.1002/tox.20270

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