Toxicity of Titanium - Titanium is found in some root canal sealers

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http://www.holisticdental.org/titaniumtoxicity.html 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 medicaland dental prosthesis. There are many articles supporting thesebeliefs, but more recently, there is scientific evidence thattitanium, or its corrosion by-products, may cause harmful reactionsafter traveling through the circulatory, or lymphatic systems. Thesecorrosion by-products can cause reactions in the blood, fibrotictissue, and in the osteogenic cells. Wang (1) has shown that titanium particles can cause the osteogenicdifferentiation of human bone marrow, stroma-derived mesenchymal stemcells, to be suppressed. It also causes decreased cellular viability,proliferation, and inhibition of the extra cellular matrixmineralization. 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 dentalpersonnel should protect themselves from the inhalation of titaniumparticles. Bermudez (1) showed an increase in the inflammatoryreactions within the lungs, such as increase in macrophage, andneutrophil numbers after long-term exposure. Rehn and Seiler (3) haveshown that animals exposed to a single dose of titanium did not showany increase in the amount of inflammatory cells in their lungs, andanimals exposed to quartz particles exhibited an increase in theamount of inflammatory responses (quartz particles are found incomposites). Ferreira (4) looked at the short-term effects on the spleen afterexposure to titanium. After 72 hours of exposure, the spleen showedalterations in morphology, and irregular features within the capsuleand medulla. Namely the T4 and B cells. Alterations in the functioningof 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 than55.7 microg ml. Pulger (6) showed that AH26 did have an oestrogeniceffect on breast cancer cells, and therefore recommended thatendodontists be careful to avoid the leakage of sealer through theapex during root canal treatment. A case study reported by Munichor (7) found metallic particles insidean inguinal-pelvic mass adjacent to a total hip titanium replacement,and arthroplasty. The 72-year-old patient developed the right pelvicmass after the hip was replaced. A fine needle biopsy was performed,and the histopathology showed fibro connective tissue with chronicinflammation and marked lymph node sinus histiocytosis. Coen (8) has stated that particular debris from a titanium metalprosthesis induces genomic instability in primary human fibroblastcells. Wouldn't this also be true for titanium implants in the firstmolar region? Watanabe (9) placed macrophages in both a fibrous environment oftitanium oxide, and particulate environment. The fibrous TiO (2)macrophages exhibited an increase in LDH release, no apoptosis, but asignificant change in cellular vacuolars, and cell surface damage. Theconclusion of the study was that titanium oxide toxicity was dependanton the shape of the material. These results were in accord with the work done by Kumazawa (10) whoshowed 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 increasedinflammation when human bone marrow cells were incubated withtitanium. The production of osteolytic mediators is responsible forthe aseptic loosening of hip prosthesis. This would also be true ofdental implants located in areas of high masticatory forces.In conclusion, titanium and its oxidizing by-products are not as inertand biocompatible as once believed. Advances in research technologyare showing changes to immune reaction cells in the blood, and thelungs. These findings should be taken into consideration when decidingwhether or not to remove an implant on a particular patient. Thedentist should also take precautions for their own safety whenremoving an implant, or when adjusting a titanium partial with ahigh-speed drill. 1. Wang ML, Tuli R, Manner PA, Sharkey PF, Hall DJ, Tuan RS (2003)Direct and Indirect induction of apoptosis in human mesenchymal stemcells in response to titanium particles. Orthop Res. 2003 Jul; 21 (4):697-707. 2. Bermudez E, Mangum JB, Asgharian B, Wong BA, Reverdy EE, JanszenDB, Hext PM, Warheit DB, Everitt JI. Long-term pulmonary responses ofthree laboratory rodent species to sub chronic inhalation ofpigmentary titanium dioxide particles. Toxicol Sci. 2002 Nov; 70(1):86-97. 3. Rehn B, Seiler F, Rehn S, Brunch J, Maier M. (2003)Investigation on the inflammatory and genotoxic lung effects of twotypes of titanium dioxide: untreated and surface treated. Toxicol ApplPharmacol. 2003 Jun. 1; 189 (2): 84-95. 4. Ferreira ME, De Lourdes Pereira M, Garcia e Costa F, Sousa JP,de Carvalho GS. (2003) Comparative study of metallic biomaterialstoxicity: a histochemical and immunohistochemical demonstration inmouse spleen. J Trace Elem Med Biol. 2003; 17(1): 45-9. 5. Miletic I, Jukie S, Anic I, Zeljezic D, Garaj-Vrhovaz V, OsmakM. 2003. Examination of cytotoxicity and mutagenicity of AH26 and AHPlus sealers. Int Endod J. 2003 May; 36 (5): 330-5. 6. Pulgar R, Segura-Egea JJ, Fernandez MF, Serna A, Olea N. 2002.The effect of AH26 and AH Plus on MCF-7 breast cancer cellproliferation in vitro. Int Endod J. 2002 Jun; 35(6): 551-6. 7. Munichor M, Cohen H, Volpin G, Kerner H, Iancu TC 2003.Chromium-induced lymph node histocytic proliferation after hipreplacement. A case report. Acta Cytol. 2003 Mar-Apr; 47(2): 270-4. 8. Coen N, Kadhim MA, Wright EG, Case CP, Mothersill, CE 2003.Particulate debris from a titanium metal prosthesis induces genomicinstability in primary human fibroblast cells. Br J Cancer. 2003 Feb24; 88(4): 548-52. 9. Wantanabe M, Okada M, Kudo Y, Tonori Y, Niitsuya M, Sato T,Aizawa Y, Kotani M 2002. Differences in the effects of fibrous andparticulate titanium dioxide on alveolar macrophages of Fischer 344rats. J Toxicol Environ Health A. 2002 Aug 9; 65(15): 1047-60. 10. Kumazawa R, Watari F, Takashi Y, Uo M, Totsku Y 2002. Effects ofTi ions and particles on neutrophil function and morphology.Biomaterials. 2002 Sep; 23(17): 3757-64. 11. Wilke A, Endres S, Griss P, Herz U 2002. [Cytokine profile of ahuman bone marrow cell culture on exposure totitanium-aluminum-vanadium particles.] Z Orthop Ihre Grenzgeb. 2002Jan-Feb; 140(1): 83-9. 2002-2003, Holistic Dental Association