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2002-2003 Scientific Review - Toxicity of Titanium
source

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.

   1.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. 
   2.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. 
    3.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. 
    4.Ferreira ME, De Lourdes Pereira M, Garcia 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. 
    5.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. 
   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 cell proliferation 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 hip replacement. 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 genomic instability in primary human fibroblast cells.
                     Br J Cancer. 2003 Feb 24; 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 and particulate titanium dioxide on alveolar
       macrophages of Fischer 344 rats. 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 of Ti 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 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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