Toxicological Research

Korean Society of Toxicology & Korea Environmental Mutagen Society (한국독성학회)
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The effects of 4-week inhalation exposure to titanium nitride on lungs of Sprague-Dawley rats

  • Yong‑Soon, Kim (Chemical Research Bureau, Occupational Safety and Health Research Institute, Korea Occupational Safety and Health Agency) ;
  • Eun‑Sang, Cho (Chemical Research Bureau, Occupational Safety and Health Research Institute, Korea Occupational Safety and Health Agency) ;
  • Chan‑Hyuck, Park (Eastern Seoul Area Office, Korea Occupational Safety and Health Agency) ;
  • Hyo‑Geun, Cha (Chemical Research Bureau, Occupational Safety and Health Research Institute, Korea Occupational Safety and Health Agency)
  • Received : 2022.09.12
  • Accepted : 2022.11.28
  • Published : 2023.01.15
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Abstract

Titanium nitride (TiN) is a ceramic material with physical properties such as extreme hardness, high decomposition temperature, defect structure, and gold-yellow color. TiN is generally considered non-toxic and safe; however, hazards have not been identified, especially in workers after inhalation exposure. Here, we conducted a four-week inhalation toxicity study of TiN using a nose-only inhalation exposure system in Sprague-Dawley rats. Rats were exposed to TiN for 4 weeks (6 h a day, 5 days per week) at target concentrations of 45, 90, and 180 mg/m3. Clinical signs, mean body weight changes, hematology, blood biochemistry, necropsy, organ weight, bronchoalveolar lavage fluid analysis, and histopathological findings were observed. Analytical concentrations of the low, middle, and high-concentration groups were 45.55 ± 3.18 mg/m3, 90.69 ± 7.30 mg/m3, and 183.87 ± 15.21 mg/m3, respectively. The mass median aerodynamic diameter (MMAD) for the low, middle, and high-concentration groups were 1.44 ±0.07 ㎛, 1.47 ± 0.18 ㎛, and 1.68 ± 0.16 ㎛, and the geometric standard deviation (GSD) was 2.24 ± 0.03, 2.31 ± 0.16, and 2.43 ± 0.11, respectively. No systemic adverse effects were observed after inhalation exposure to TiN; however, histopathological findings (increased phagocytic macrophages and alveolar/bronchiolar epithelial hyperplasia) and Bronchoalveolar Lavage Fluid (BALF) analysis (elevated lactate dehydrogenase and gamma-glutamyltransferase values) showed adverse effects on the lungs in the middle and high-concentration groups. Based on these results, the no observed adverse effect concentration (NOAEC) is suggested to be 45 mg/m3.

Keywords

Acknowledgement

This study was supported by the Korea Occupational Safety and Health Agency, Ministry of Labor, Republic of Korea, and Grant-in-Aid for Chemical Hazard Assessment.

References

  1. Van Hove RP, Sierevelt IN, Van Royen BJ, Nolte PA (2015) Titanium-nitride coating of orthopaedic implants: a review of the literature. BioMed Res Int 2015:485975. https://doi.org/10.1155/2015/485975
  2. Gobbi SJ, Gobbi VJ, Reinke G, Rocha Y (2019) Orthopedic implants: coating with TiN. Biomed J Sci Tech Res 16:11740-11742. https://doi.org/10.26717/BJSTR.2019.16.002786
  3. Mitsuo A, Uchida S, Nihira N, Iwaki M (1998) Improvement of high-temperature oxidation resistance of titanium nitride and titanium carbide films by aluminum ion implantation. Surf Coat Technol 103-104:98-103. https://doi.org/10.1016/S0257-8972(98)00380-6
  4. Kaliaraj GS, Ramadoss A, Sundaram M, Balasubramanian S, Muthirulandi J (2014) Studies of calcium-precipitating oral bacterial adhesion on TiN, TiO2 single layer, and TiN/TiO2 multilayer-coated 316L SS. J Mater Sci 49:7172-7180. https://doi.org/10.1007/s10853-014-8425-7
  5. Datta S, Das M, Balla VK, Bodhak S, Murugesan VK (2018) Mechanical, wear, corrosion and biological properties of arc deposited titanium nitride coatings. Surf Coat Technol 344:214-222. https://doi.org/10.1016/j.surfcoat.2018.03.019
  6. Karagkiozaki V, Logothetidis S, Kalfagiannis N, Lousinian S, Giannoglou G (2009) Atomic Force Microscopy probing platelet activation behavior on titanium nitride nanocoatings for biomedical applications. Nanomed Nanotechnol Biol Med 5:64-72. https://doi.org/10.1016/j.nano.2008.07.005
  7. European Food Safety Authority (2012) Scientific opinion on the Safety evaluation of the Substance, Titanium nitride, Nanoparticles, for Use in Food Contact materials. EFSA J 10:2641. https://doi.org/10.2903/j.efsa.2012.2641
  8. Santecchia E, Hamouda AMS, Musharavati F, Zalnezhad E, Cabibbo M, Spigarelli S (2015) Wear resistance investigation of titanium nitride-based coatings. Ceram Int 41:10349-10379. https://doi.org/10.1016/j.ceramint.2015.04.152
  9. Midtgard U, Jelnes JE (1991) Toxicology and occupational hazards of new materials and process in metal surface treatment, powder metallurgy, technical ceramics, and fiber-reinforced plastics. Scand J Work Environ Health 17:369-379. https://doi.org/10.5271/sjweh.1691
  10. Minchenko DO, Tsymbal DO, Yavorovsky OP, Solokha NV, Minchenko OH (2017) Expression of genes encoding IGFBPs, SNARK, CD36, and PECAM1 in the liver of mice treated with chromium disilicide and titanium nitride nanoparticles. Endocr Regul 51:84-95. https://doi.org/10.1515/enr-2017-0008
  11. Wang J, Liu K, Mo C, Minchenko OH, Zhang Y, Chen J, Hsiao C, Zhu Q, He Q (2022) Nano-titanium nitride causes developmental toxicity in zebrafish through oxidative stress. Drug Chem Toxicol 45:1660-1669. https://doi.org/10.1080/01480545.2020.1853765
  12. Organization for Economic Co-Operation and Development (OECD) (2018) Guidelines on the testing of chemicals, Sect. 4, Health effects test No. 412 28-day (subacute) inhalation toxicity study. OECD, Paris, France. https://doi.org/10.1787/20745788
  13. Organization for Economic Co-Operation and Development (OECD) (2018) Document on inhalation toxicity studies. Series on testing and assessment No. 39, 2nd edn. OECD, Paris, France. https://doi.org/10.1787/20745788
  14. Lee KP, Trochimowicz HJ, Reinhardt CF (1985) Pulmonary response of rats exposed to titanium dioxide (TiO2) by inhalation for two years. Toxicol Appl Pharmacol 79:179-192. https://doi.org/10.1016/0041-008x(85)90339-4
  15. National Institute for Occupational Safety and Health (NIOSH) (2011) Current intelligence bulletin 63, occupational exposure to titanium dioxide. DHHS (NIOSH) publication No. 2011-160. NIOSH, Atlanta, USA
  16. Alexander DJ, Collins CJ, Cooms DW, Gilkison IS, Hardy CJ, Healey G, Karantabias G, Johnson N, Karlsson A, Kilgour JD, 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
  17. Arika WM, Nyamai DW, Musila MN, Ngugi MP, Njagi ENM (2016) Hematological markers of in vivo toxicity. J Hematol Thrombo Dis 4:236. https://doi.org/10.4172/2329-8790.1000236
  18. Walter GL, Smith GS, Walker RM (2018) Chapter 29 Interpretation of clinical pathology results in non-clinical toxicology testing. Haschek and rousseaux's handbook of toxicologic pathology 3rd, pp 853-873. https://doi.org/10.1016/B978-0-12-415759-0.00029-7
  19. Koenig G, Seneff S (2015) Gamma-glutamyltransferase: a predictive biomarker of Cellular antioxidant inadequacy and disease risk. Disease Mark 2015:818570. https://doi.org/10.1155/2015/818570