Toxicity of Titanium

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2002-2003 Scientific Review - Toxicity of Titanium Titanium has historically maintained the reputation of being an inert, and relatively biocompatible metal, suitable for use as both a medical and dental prosthesis. There are many articles supporting these beliefs, but more recently, there is scientific evidence that titanium, or its corrosion by-products, may cause harmful reactions after traveling through the circulatory, or lymphatic systems. These corrosion by-products can cause reactions in the blood, fibrotic tissue, and in the osteogenic cells. Wang (1) has shown that titanium particles can cause the osteogenic differentiation of human bone marrow, stroma-derived mesenchymal stem cells, to be suppressed. It also causes decreased cellular viability, proliferation, and inhibition of the extra cellular matrix mineralization. Decreased cellular viability is caused by apoptosis, and an increase in the level of tumor suppressor proteins. If

removal of an existing implant is being considered, the dental personnel should protect themselves from the inhalation of titanium particles. Bermudez (1) showed an increase in the inflammatory reactions within the lungs, such as increase in macrophage, and neutrophil numbers after long-term exposure. Rehn and Seiler (3) have shown that animals exposed to a single dose of titanium did not show any increase in the amount of inflammatory cells in their lungs, and animals exposed to quartz particles exhibited an increase in the amount of inflammatory responses (quartz particles are found in composites). Ferreira (4) looked at the short-term effects on the spleen after exposure to titanium. After 72 hours of exposure, the spleen showed alterations in morphology, and irregular features within the capsule and medulla. Namely the T4 and B cells. Alterations in the functioning of T and B cells will effect the functioning of the immune system. Titanium is found in

some root canal sealers, i.e.; AH26 and AH Plus. Miletic (5) found both materials to be cytotoxic at doses larger than 55.7 microg ml. Pulger (6) showed that AH26 did have an oestrogenic effect on breast cancer cells, and therefore recommended that endodontists be careful to avoid the leakage of sealer through the apex during root canal treatment. A case study reported by Munichor (7) found metallic particles inside an inguinal-pelvic mass adjacent to a total hip titanium replacement, and arthroplasty. The 72-year-old patient developed the right pelvic mass after the hip was replaced. A fine needle biopsy was performed, and the histopathology showed fibro connective tissue with chronic inflammation and marked lymph node sinus histiocytosis. Coen (8) has stated that particular debris from a titanium metal prosthesis induces genomic instability in primary human fibroblast cells. Wouldn't this also be true for titanium implants in the first molar region? Watanabe (9) placed macrophages in both a fibrous environment of titanium oxide, and particulate environment. The fibrous TiO (2) macrophages exhibited an increase in LDH release, no apoptosis, but a significant change in cellular vacuolars, and cell surface damage. The conclusion of the study was that titanium oxide toxicity was dependant on the shape of the material. These results were in accord with the work done by Kumazawa (10) who showed that cytotoxicity was dependant on the Titanium particle size, and that the smaller the size, the more toxic it is. Wilke (11) also showed the increase in LDH as a sign of increased inflammation when human bone marrow cells were incubated with titanium. The production of osteolytic mediators is responsible for the aseptic loosening of hip prosthesis. This would also be true of dental implants located in areas of high masticatory forces.In conclusion, titanium and its oxidizing by-products are not as inert and

biocompatible as once believed. Advances in research technology are showing changes to immune reaction cells in the blood, and the lungs. These findings should be taken into consideration when deciding whether or not to remove an implant on a particular patient. The dentist should also take precautions for their own safety when removing an implant, or when adjusting a titanium partial with a high-speed drill. Wang ML, Tuli R, Manner PA, Sharkey PF, Hall DJ, Tuan RS (2003) Direct and Indirect induction of apoptosis in human mesenchymal stem cells in response to titanium particles. Orthop Res. 2003 Jul; 21 (4): 697-707. Bermudez E, Mangum JB, Asgharian B, Wong BA, Reverdy EE, Janszen DB, Hext PM, Warheit DB, Everitt JI. Long-term pulmonary responses of three laboratory rodent species to sub chronic inhalation of pigmentary titanium dioxide particles. Toxicol Sci. 2002 Nov; 70(1): 86-97. Rehn B, Seiler F, Rehn S, Brunch J, Maier M. (2003)

Investigation on the inflammatory and genotoxic lung effects of two types of titanium dioxide: untreated and surface treated. Toxicol Appl Pharmacol. 2003 Jun. 1; 189 (2): 84-95. Ferreira ME, De Lourdes Pereira M, e Costa F, Sousa JP, de Carvalho GS. (2003) Comparative study of metallic biomaterials toxicity: a histochemical and immunohistochemical demonstration in mouse spleen. J Trace Elem Med Biol. 2003; 17(1): 45-9. Miletic I, Jukie S, Anic I, Zeljezic D, Garaj-Vrhovaz V, Osmak M. 2003. Examination of cytotoxicity and mutagenicity of AH26 and AH Plus sealers. Int Endod J. 2003 May; 36 (5): 330-5. Pulgar R, Segura-Egea JJ, Fernandez MF, Serna A, Olea N. 2002. The effect of AH26 and AH Plus on MCF-7 breast cancer cell proliferation in vitro. Int Endod J. 2002 Jun; 35(6): 551-6. Munichor M, Cohen H, Volpin G, Kerner H, Iancu TC 2003. Chromium-induced lymph node histocytic proliferation after hip replacement. A case report. Acta Cytol. 2003 Mar-Apr;

47(2): 270-4. Coen N, Kadhim MA, EG, Case CP, Mothersill, CE 2003. Particulate debris from a titanium metal prosthesis induces genomic instability in primary human fibroblast cells. Br J Cancer. 2003 Feb 24; 88(4): 548-52. Wantanabe M, Okada M, Kudo Y, Tonori Y, Niitsuya M, Sato T, Aizawa Y, Kotani M 2002. Differences in the effects of fibrous and particulate titanium dioxide on alveolar macrophages of Fischer 344 rats. J Toxicol Environ Health A. 2002 Aug 9; 65(15): 1047-60. Kumazawa R, Watari F, Takashi Y, Uo M, Totsku Y 2002. Effects of Ti ions and particles on neutrophil function and morphology. Biomaterials. 2002 Sep; 23(17): 3757-64. Wilke A, Endres S, Griss P, Herz U 2002. [Cytokine profile of a human bone marrow cell culture on exposure to titanium-aluminum-vanadium particles.] Z Orthop Ihre Grenzgeb. 2002 Jan-Feb; 140(1): 83-9. Copyright © 2002-2003, Holistic Dental Association

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