Toxicological Research

Korean Society of Toxicology & Korea Environmental Mutagen Society (한국독성학회)
권호 표지
DOI QR코드

DOI QR Code

Nasal and Pulmonary Toxicity of Titanium Dioxide Nanoparticles in Rats

  • Kwon, Soonjin (Inhalation Toxicology Center, Korea Institute of Toxicology Jeongeup Campus) ;
  • Yang, Young-Su (Inhalation Toxicology Center, Korea Institute of Toxicology Jeongeup Campus) ;
  • Yang, Hyo-Seon (Inhalation Toxicology Center, Korea Institute of Toxicology Jeongeup Campus) ;
  • Lee, Jinsoo (Inhalation Toxicology Center, Korea Institute of Toxicology Jeongeup Campus) ;
  • Kang, Min-Sung (Inhalation Toxicology Center, Korea Institute of Toxicology Jeongeup Campus) ;
  • Lee, Byoung-Seok (Toxicologic Phathology Center, Korea Institute of Toxicology) ;
  • Lee, Kyuhong (Inhalation Toxicology Center, Korea Institute of Toxicology Jeongeup Campus) ;
  • Song, Chang-Woo (Inhalation Toxicology Center, Korea Institute of Toxicology Jeongeup Campus)
  • Received : 2012.11.28
  • Accepted : 2012.12.03
  • Published : 2012.12.31
Download PDF
⟨ Previous Next ⟩

Abstract

In recent decades, titanium dioxide ($TiO_2$) nanoparticles have been used in various applications, including paints, coatings, and food. However, data are lacking on the toxicological aspects associated with their use. The aim of this study was to assess the inhalation toxicity of $TiO_2$ nanoparticles in rats by using inhalation exposure. Male Wistar rats were exposed to $TiO_2$ nanoparticles for 2 weeks (6 hr/day, 5 days/week) at a mean mass concentration of $11.39{\pm}0.31mg/m^3$. We performed time-course necropsies at 1, 7, and 15 days after exposure. Lung inflammation and injury were assessed on the basis of the total and individual cell counts in bronchoalveolar lavage fluid (BALF), and by biochemical assays, including an assay for lactate dehydrogenase (LDH). Furthermore, histopathological examination was performed to investigate the lungs and nasal cavity of rats. There were no statistically significant changes in the number of BALF cells, results of biochemical assays of BALF and serum, and results of cytokine analysis. However, we did observe histopathological changes in the nasal cavity tissue. Lesions were observed at post-exposure days 1 and 7, which resolved at post-exposure day 15. We also calculated the actual amounts of $TiO_2$ nanoparticles inhaled by the rats. The results showed that the degree of toxicity induced by $TiO_2$ nanoparticles correlated with the delivered quantities. In particular, exposure to small particles with a size of approximately 20 nm resulted in toxicity, even if the total particle number was relatively low.

Keywords

References

  1. Alexander, D.J., Collins, C.J., Coombs, D.W., Gilkison, I.S., Hardy, C.J., Healey, G., Karantabias, G., Johnson, N., Karlsson, A., Kilgour, J.D. and McDonald, P. (2008). Association of inhalation toxicologists (AIT) working party recommendation for standard delivered dose calculation and expression in non-clinical aerosol inhalation toxicology studies with pharmaceuticals. Inhal. Toxicol., 20, 1179-1189. https://doi.org/10.1080/08958370802207318
  2. Baan, R.A. (2007). Carcinogenic hazards from inhaled carbon black, titanium dioxide, and talc not containing asbestos or asbestiform fibers: Recent evaluations by an iarc monographs working group. Inhal. Toxicol., 19 Suppl 1, 213-228.
  3. Bermudez, E., Mangum, J.B., Asgharian, B., Wong, B.A., Reverdy, E.E., Janszen, D.B., Hext, P.M., Warheit, D.B. and Everitt, J.I. (2002). Long-term pulmonary responses of three laboratory rodent species to subchronic inhalation of pigmentary titanium dioxide particles. Toxicol. Sci., 70, 86-97. https://doi.org/10.1093/toxsci/70.1.86
  4. Bermudez, E., Mangum, J.B., Wong, B.A., Asgharian, B., Hext, P.M., Warheit, D.B. and Everitt, J.I. (2004). Pulmonary responses of mice, rats, and hamsters to subchronic inhalation of ultrafine titanium dioxide particles. Toxicol. Sci., 77, 347-357. https://doi.org/10.1093/toxsci/kfh019
  5. Cho, M., Chung, H., Choi, W. and Yoon, J. (2004). Linear correlation between inactivation of E. coli and OH radical concentration in $TiO_{2}$ photocatalytic disinfection. Water Res., 38, 1069- 1077. https://doi.org/10.1016/j.watres.2003.10.029
  6. Donaldson, K., Aitken, R., Tran, L., Stone, V., Duffin, R., Forrest, G. and Alexander, A. (2006). Carbon nanotubes: A review of their properties in relation to pulmonary toxicology and workplace safety. Toxicol. Sci., 92, 5-22. https://doi.org/10.1093/toxsci/kfj130
  7. Driscoll, K.E., Lindenschmidt, R.C., Maurer, J.K., Perkins, L., Perkins, M. and Higgins, J. (1991). Pulmonary response to inhaled silica or titanium dioxide. Toxicol. Appl. Pharmacol., 111, 201-210. https://doi.org/10.1016/0041-008X(91)90024-9
  8. Gurr, J.R., Wang, A.S., Chen, C.H. and Jan, K.Y. (2005). Ultrafine titanium dioxide particles in the absence of photoactivation can induce oxidative damage to human bronchial epithelial cells. Toxicology, 213, 66-73. https://doi.org/10.1016/j.tox.2005.05.007
  9. Hohr, D., Steinfartz, Y., Schinsm, R.P., Knaapen, A.M., Martra, G., Fubini, B. and Borm, P.J. (2002). The surface area rather than the surface coating determines the acute inflammatory response after instillation of fine and ultrafine $TiO_{2}$ in the rat. Int. J. Hyg. Environ. Health, 205, 239-244. https://doi.org/10.1078/1438-4639-00123
  10. unter, D.D. and Undem, B.J. (1999). Identification and substance P content of vagal afferent neurons innervating the epithelium of the guinea pig trachea. Am. J. Respir. Crit. Care Med., 159, 1943-1948. https://doi.org/10.1164/ajrccm.159.6.9808078
  11. Kreuter, J., Shamenkov, D., Petrov, V., Ramge, P., Cychutek, K., Koch-Brandt, C. and Alyautdin, R. (2002). Apolipoproteinmediated transport of nanoparticle-bound drugs across the blood-brain barrier. J. Drug Target., 10, 317-325. https://doi.org/10.1080/10611860290031877
  12. Kwon, J.T., Kim, H., Hwang, S.T., Yun, H.J., Kim, D.S., Choi, M.S., Han, D.Y., Kang, Y.W., Yun, T.J., Lee, J.K. and Cho, M.H. (2005). Inhalation Toxicology of nanoparticle. The Annual Report of KNTP, pp. 487-507.
  13. Lee, K.P., Trochinowicz, H.J. and Reinhardt, C.F. (1985). Pulmonary response of rats exposed to titanium dioxide ($TiO_{2}$) by inhalation for two years. Toxicol. Appl. Pharmacol., 79, 179-192. https://doi.org/10.1016/0041-008X(85)90339-4
  14. Lomer, M.C., Thompson, R.P. and Powell, J.J. (2002). Fine and ultrafine particles of the diet: influence on the mucosal immune response and association with Crohn's disease. Proc. Nutr. Soc., 61, 123-130. https://doi.org/10.1079/PNS2001134
  15. Ma-Hock, L., Burkhardt, S., Strauss, V., Gamer, A.O., Wiench, K., van Ravenzwaay, B. and Landsiedel, R. (2009). Development of a short-term inhalation test in the rat using nano-titanium dioxide as a model substance. Inhal.Toxicol., 21, 102-118. https://doi.org/10.1080/08958370802361057
  16. Nemmar, A., Melghit, K. and Ali, B.H. (2008). The acute proinflammatory and prothrombotic effects of pulmonary exposure to rutile $TiO_{2}$ nanorods in rats. Exp. Biol. Med. (Maywood), 233, 610-619. https://doi.org/10.3181/0706-RM-165
  17. Nordman, H. and Berlin, M. (1986). Titanium: in Handbook on the Toxicology of Metals, vol. II. (Friberg, L., Nordberg, G.F., Vouk, V.B. Ed.). Elsevier, Amsterdam, pp. 595-609.
  18. Oberdorster, G., Oberdörster, E. and Oberdörster, J. (2005). Nanotoxicology: An emerging discipline evolving from studies of ultrafine particles. Environ. Health Perspect., 113, 823-839. https://doi.org/10.1289/ehp.7339
  19. Oberdorster, G., Sharp, Z., Atudorei, V., Elder, A., Gelein, R., Kreyling, W. and Cox, C. (2004). Translocation of inhaled ultrafine particles to the brain. Inhal. Toxicol., 16, 437-445. https://doi.org/10.1080/08958370490439597
  20. Park, E.J., Yoon, J., Choi, K., Yi, J. and Park, K. (2009). Induction of chronic inflammation in mice treated with titanium dioxide nanoparticles by intratracheal instillation. Toxicology, 260, 37-46. https://doi.org/10.1016/j.tox.2009.03.005
  21. Sadrieh, N., Wokovich, A.M., Gopee, N.V., Zheng, J., Haines, D., Parmiter, D., Siitonen, P.H., Cozart, C.R., Patri, A.K., McNeil, S.E., Howard, P.C., Doub, W.H. and Buhse, L.F. (2010). Lack of significant dermal penetration of titanium dioxide from sunscreen formulations containing nano- and submicron-size $TiO_{2}$ particles. Toxicol. Sci., 115, 156-166. https://doi.org/10.1093/toxsci/kfq041
  22. Sager, T.M., Kommineni, C. and Castranova, V. (2008). Pulmonary response to intratracheal instillation of ultrafine versus fine titanium dioxide: role of particle surface area. Part. Fibre Toxicol., 5, 17. https://doi.org/10.1186/1743-8977-5-17
  23. Takenaka, S., Karg, E., Roth, C., Schulz, H., Ziesenis, A., Heinzmann, U., Schramel, P. and Heyder, J. (2001). Pulmonary and systemic distribution of inhaled ultrafine silver particles in rats. Environ. Health Perspect., 109 Suppl 4, 547-551. https://doi.org/10.1289/ehp.01109s4547
  24. Tin-Tin-Win-Shwe, Yamamoto, S., Ahmed, S., Kakeyama, M., Kobayashi, T. and Fujimaki, H. (2006). Brain cytokine and chemokine mRNA expression in mice induced by intranasal instillation with ultrafine carbon black. Toxicol. Lett., 163, 153-160. https://doi.org/10.1016/j.toxlet.2005.10.006
  25. Utell, M.J., Frampton, M.W., Zareba, W., Devlin, R.B. and Cascio, W.E. (2002). Cardiovascular effects associated with air pollution: potential mechanisms and methods of testing. Inhal. Toxicol., 14, 1231-1247. https://doi.org/10.1080/08958370290084881
  26. van Ravenzwaay, B., Landsiedel, R., Fabian, E., Burkhardt, S., Strauss, V. and Ma-Hock, L. (2009). Comparing fate and effects of three particles of different surface properties: Nano-$TiO_{2}$, pigmentary $TiO_{2}$ and quartz. Toxicol. Lett., 186, 152-159. https://doi.org/10.1016/j.toxlet.2008.11.020
  27. Wang, J., Chen, C., Liu, Y., Jiao, F., Li, W., Lao, F., Li, Y., Li, B., Ge, C., Zhou, G., Gao, Y., Zhao, Y. and Chai, Z. (2008). Potential neurological lesion after nasal instillation of $TiO_{2}$ nanoparticles in the anatase and rutile crystal phases. Toxicol. Lett., 183, 72-80. https://doi.org/10.1016/j.toxlet.2008.10.001
  28. Warheit, D.B., Laurence, B.R., Reed, K.L., Roach, D.H., Reynolds, G.A. and Webb, T.R. (2004). Comparative pulmonary toxicity assessment of single-wall carbon nanotubes in rats. Toxicol. Sci., 77, 117-125.
  29. Warheit, D.B., Webb, T.R., Sayes, C.M., Colvin, V.L. and Reed, K.L. (2006). Pulmonary instillation studies with nanoscale $TiO_{2}$ rods and dots in rats: Toxicity is not dependent upon particle size and surface area. Toxicol. Sci., 91, 227-236. https://doi.org/10.1093/toxsci/kfj140

Cited by

  1. A comparative study of the toxicological aspects of vanadium pentoxide and vanadium oxide nanoparticles vol.26, pp.13, 2014, https://doi.org/10.3109/08958378.2014.960106
  2. -Oligoaldaramide nanocomposites as efficient core-shell systems for wood preservation vol.132, pp.23, 2015, https://doi.org/10.1002/app.42047
  3. (nano) particles vol.73, pp.2, 2015, https://doi.org/10.1136/oemed-2015-103161
  4. production workers vol.11, pp.1, 2017, https://doi.org/10.1080/17435390.2016.1262921
  5. NPs) on the expression of mucin genes in human airway epithelial cells vol.29, pp.1, 2017, https://doi.org/10.1080/08958378.2016.1267282
  6. A 90-Day Inhalation Toxicity Study of Ethyl Formate in Rats vol.33, pp.4, 2017, https://doi.org/10.5487/TR.2017.33.4.333
  7. Influence of dispersion medium on nanomaterial-induced pulmonary inflammation and DNA strand breaks: investigation of carbon black, carbon nanotubes and three titanium dioxide nanoparticles vol.32, pp.6, 2017, https://doi.org/10.1093/mutage/gex042
  8. Markers of Oxidative Stress in the Exhaled Breath Condensate of Workers Handling Nanocomposites vol.8, pp.8, 2018, https://doi.org/10.3390/nano8080611
  9. Penetration, distribution and brain toxicity of titanium nanoparticles in rodents' body: a review vol.12, pp.6, 2018, https://doi.org/10.1049/iet-nbt.2017.0109