May 2011
Volume 32, Issue 4

Adverse Effects Associated with the Clinical Use of 4% TiF4 on Teeth Enamel: Case Report

Rafael de Lima Pedro, DDS; Luciana Pomarico, DDS, PhD; Michele Villardi, DDS; and Lucianne Cople Maia, DDS, PhD


Titanium tetrafluoride (TiF4) has been studied in dentistry as a promissory alternative for prevention and treatment of carious lesions. However, there are few in vivo studies concerning the consequences of its use on tooth enamel. The goal of this study was to report the effects of a 4% TiF4 application on the remineralization of an incipient carious lesion of a permanent tooth. This research found an unexpected clinical outcome. A patient with active white spots had two of these lesions treated with 4% TiF4 associated with fluoridated dentifrice and another lesion treated with fluoridated dentifrice only, thus the remineralization of the two kinds of treatment administered could be observed and compared. An extrinsic pigment appeared in the regions that received the TiF4 treatment, which was partially removed by professional prophylaxis. Also, regular recidivists of this pigmentation in the review consultations were noted. The authors concluded that although the use of 4% TiF4 was effective in treating incipient carious lesions on enamel, it was also responsible for an undesired pigmented layer on the tooth to which it was applied.

Beyond the varied fluoridated materials used in dentistry, titanium tetrafluoride (TiF4) deserves attention. This compound has the common properties of fluorides, and researchers are exploring its role in carious lesion prevention,1-3 fissure sealing,4 and tooth erosion prevention in in vitro5,6 and in situ studies.7 Research is also exploring its use for microinfiltration prevention in tooth restoration8 and hypersensitivity treatment.9 However, when compared to other fluoridated products TiF4 demonstrates additional, specific particularities, such as the formation of a titanium dioxide (TiO2) layer, which is tough, hydrophobic,10 and resistant in acidic environments.4

Nevertheless, there are insufficient in vivo studies concerning the consequences of TiF4-containing products affecting tooth enamel. Thus, the goals of this study were to report the effects of a 4% TiF4 application on the remineralization of an incipient carious lesion of a permanent tooth and to show the results of a backscattered scanning electron (BSE) analysis that was performed on the primary tooth. The clinical outcome was unexpected.

Case Report

A 9-year-old patient visited a pediatric dentistry clinic of a public university for treatment. The medical history and extraoral examination did not provide any relevant facts. The intraoral examination revealed incipient enamel carious lesions on teeth Nos. 8 and 9 (Figure 1) and the left primary canine. A 4% TiF4 water solution was used by inherent isolation on tooth No. 9 and the primary canine. The solution was used with a Microbrush® (Microbrush International, www.microbrush.com) for 1 minute on the demineralized enamel surface. The only recommendation to the patient was to begin tooth brushing 12 hours after the consultation.

Tooth No. 8 was treated with fluoridated dentifrice with monofluorophosphate brushing and toothbrush only. The patient received oral hygiene and tooth brushing recommendations. After 1 month, a new evaluation of the incipient carious lesions was made. Regardless of the kind of treatment administered, tooth remineralization with lesion reduction occurred in all three cases. However, on the teeth that received one application of 4% TiF4 for 1 minute, an extrinsic yellowish pigmentation had appeared (Figure 2).

The pigmented region received professional prophylaxis, thus partially eradicating this stain. However, the reappearance of this stain was observed in the follow-up consultation at 1 year (Figure 3). Another prophylaxis treatment was performed, and again partial eradication of the extrinsic pigmentation was observed (Figure 4). The patient was accompanied by an adult in review consultations to control this unexpected outcome.

To determine the presence of titanium and/or any other substances, the left primary canine that had been exfoliated 6 months following the initial application was scanned with an electron microscope (JEOL JSM 5310, JEOL USA, www.jeolusa.com) (Figure 5) for a BSE analysis (Figure 6). The BSE consists of high-energy electrons originating in the electron beam that are reflected, or backscattered, out of the specimen interaction volume by elastic scattering interactions with specimen atoms. Because heavy elements (high atomic number) backscatter electrons better than light elements (low atomic number), they appear brighter on the image. BSE is used to detect contrasts between areas with different chemical compositions.11 The presence of titanium on the pigmented region (Figure 7) was visible, as was fluorine and oxygen.


Dental pigmentations are included in chief dentistry complaints.12,13 These pigments can be intrinsically caused by dental pathologies or environmental factors.12 However, they may also be extrinsically caused by factors such as diet (tea, coffee, or red wine), medicine (chlorhexidine), or metal salts (iron or tin).14,15 McDonald et al16 reported that the appearance of pigments was also caused by the use of stannous fluoride.

In this report, yellowish pigmentation occurred after a single application of TiF4 solution. According to Mundorff et al,17 after an application of this product, precipitates other than calcium fluoride (CaF2) are formed with a glaze-like layer. One hypothesis is that the interaction between TiF4 and the proteins on the tooth’s surface influence the incorporation of fluorine and change the constitution of this glaze,17 resulting in this unexpected stain. As in this case, there was no food restriction; the patient’s diet also may have been responsible for this glaze’s pigmentation. Another hypothesis relates to the titanium reaction of phosphate groups on the tooth’s surface with the oxygen atoms, forming a stable titanium dioxide.3,18 This component formed after the application of TiF4 is tough, hydrophobic,10 and resistant in acidic environments.4 This differentiates TiF4 from other fluoridated products; however, the true clinical effects are unclear.

Büyükylmaz et al4 found signs of this glaze after the TiF4 application on the enamel surface in furrow and deciduous molar cracks, remaining stable for as long as 12 months. Other researchers noted similar findings.6,17 Van Rijkom et al5 observed the presence of a macroscopic white layer on the enamel. The stable layer that was formed could explain the varied recurrences found in the present case.

BSE analysis has been shown to be reliable for study of the mineralized state of calcified tissues and especially bone.19,20 To the authors’ knowledge, BSE analysis has never been used for titanium and fluorine analysis. In this study, BSE analysis indicated a higher presence of titanium in the pigmented region than the other areas of the primary tooth, even 6 months after TiF4 application. Also, fluorine and oxygen were identified, as was the confirmation of other compounds such as titanium dioxide.

McDonald et al16 reported that professional prophylaxis with pumice was sufficient for removal of the extrinsic pigmentation, as was also observed in this report. However, the depth of this pigmentation is another aspect that must be considered. Chevitarese et al21 quantified a depth of 3.25-µm TiF4 penetration in enamel. According to these authors, professional prophylaxis usually removes 10.7 µm of enamel. Nevertheless, as various pigmentation recurrences were observed in this case, their causes, according to Büyükylmaz et al,4 could be related to a deeper TiF4 tooth enamel penetration.

Regarding a combination of two fluoridated products, Maia et al22 concluded that the interaction of varnish and fluoridated dentifrice is responsible for intensifying fluoride penetration in tooth enamel as well as a greater remineralization of the carious lesions. In the present case, the TiF4 interaction with fluoridated toothpaste could also be responsible for the intensification of tooth enamel incorporation of titanium or for the change of compounds formed, which, according to Büyükylmaz et al,4 could be the cause of the pigmentation, although similar reports have not been described.

The 4% TiF4 concentration used in this study was also employed in other research.4,15 This high concentration could partially explain the undesired effect. However, further research is needed to determine the minimal safe TiF4 concentration to achieve the desired outcome without the unwanted effects.

Other studies have also suggested testing new formulations, such as titanium fluoride,23 and different therapeutic methods with the current research agent to maximize its properties and minimize its unexpected effects.


In vivo use of TiF4 4% is efficient in incipient enamel carious lesion treatments and also responsible for formation of a pigmented layer on the tooth to which it is applied.


1. Büyükyilmaz T, Ogaard B, Duschner H, et al. The caries-preventive effect of titanium tetrafluoride on root surfaces in situ as evaluated by microradiography and confocal laser scanning microscopy. Adv Dent Res. 1997;11(4):448-452.

2. Morais AP, Souza IP, Chevitarese O. An in situ study of human enamel after titanium tetrafluoride application. Pesq Odontol Bras. 2000;14(2):137-143.

3. Schlueter N, Ganss C, Mueller U, Klimek J. Effect of titanium tetrafluoride and sodium fluoride on erosion progression in enamel and dentine in vitro. Caries Res. 2007;41(2):141-145.

4. Büyükyilmaz T, Sen BH, Ogaard B. Retention of titanium tetrafluoride (TiF4), used as fissure sealant on human deciduous molars. Acta Odontol Scand. 1997;55(2):73-78.

5. van Rijkom H, Ruben J, Vieria A, et al. Erosion-inhibiting effect of sodium fluoride and titanium tetrafluoride treatment in vitro. Eur J Oral Sci. 2003;111(3)253-257.

6. Hove L, Holme B, Ogaard B, et al. The protective effect of TiF4, SnF2 and NaF on erosion of enamel by hydrochloric acid in vitro measured by white light interferometry. Caries Res. 2006;40(5)440-443.

7. Magalhães AC, Comar LP, Rios D, et al. Effect of a 4% titanium tetrafluoride (TiF4) varnish on demineralisation and remineralisation of bovine enamel in vitro. J Dent. 2008;36(2):158-162.

8. Castro RAL, Chevitarese O, Souza IPR. Action of titanium tetrafluoride on occlusal human enamel in situ. Fluoride. 2003;36(4):252-262.

9. Charvat J, R Söremark R, Li J, Vacek J. Titaniumtetrafluoride for treatment of hypersensitive dentine. Swed Dent J. 1995;19(1-2):41-46.

10. Büyükyilmaz T, Ogaard B, Rølla G. The resistance of titanium tetrafluoride-treated human enamel to strong hydrochloric acid. Eur J Oral Sci. 1997;105(5 pt 2)473-477.

11. Goldstein J, Newbury DE, Joy DC, et al. Scanning Electron Microscopy and X-ray Microanalysis. New York, NY: Plenum Press; 1981.

12. Walsh TF, Rawlinson A,Wildgoose D. et al. Clinical evaluation of the stain removing ability of a whitening dentifrice and stain controlling system. J Dent. 2005;33(5):413-418.

13. Goyal CR, Sharma NC, Qaqish JG, et al. Efficacy of a novel brush head in the comparison of two power toothbrushes on removal of plaque and naturally occurring extrinsic stain. J Dent. 2005;33(suppl 1):37-43.

14. Joiner A. Tooth colour: a review of the literature. J Dent. 2004;32(suppl 1):3-12.

15. Joiner A. Review of the extrinsic stain removal and enamel/dentine abrasion by a calcium carbonate and perlite containing whitening toothpaste. Int Dent J. 2006;56(4):175-180.

16. McDonald RE, Avery DR, Dean JA. Dentistry for the Child and Adolescent. 8th ed. Philadelphia, PA: Mosby; 2004.

17. Mundorff SA, Little MF, Bibby BG. Enamel dissolution. II. Action of titanium tetrafluoride. J Dent Res. 1972;51(6)1567-1571.

18. Tveit AB, Klinge B, Tötdal B, Selvig KA. Long-term retention of TiF4 and SnF2 after topical application to dentin in dogs. Scand J Dent Res. 1988;96(6):536-540.

19. Roschger P, Plenk H Jr, Klaushofer K, Eschberger J. A new scanning electron microscopy approach to the quantification of bone mineral distribution: backscattered electron image grey-levels correlated to the calcium K alpha-line intensities. Scanning Microsc. 1995;9(1):75-88.

20. Bloebaum RD, Skedros JG, Vajda EG, et al. Determining mineral content variations in bone using backscattered electron imaging. Bone. 1997;20(5):485-490.

21. Chevitarese AB, Chevitarese O, Chevitarese LM, Dutra PB. Titanium penetration in human enamel after TiF4 application. J Clin Pediatr Dent. 2004;28(3):253-256.

22. Maia LC, de Souza IP, Cury JA. Effect of a combination of fluoride dentifrice and varnish on enamel surface rehardening and fluoride uptake in vitro. Eur J Oral Sci. 2003;111(1):68-72.

23. Exterkate RA, Ten Cate JM. Effects of a new titanium fluoride derivative on enamel de- and remineralization. Eur J Oral Sci. 2007;115(2):143-147.

About the Authors

Rafael de Lima Pedro, DDS
Postgraduate Student
Department of Pediatric Dentistry and Orthodontics
School of Dentistry
Federal University of Rio de Janeiro

Luciana Pomarico, DDS, PhD
Associate Professor
Department of Pediatric Dentistry
School of Dentistry
Federal Fluminense University

Michele Villardi, DDS
Postgraduate Student,
Department of Pediatric Dentistry and Orthodontics,
School of Dentistry
Federal University of Rio de Janeiro

Lucianne Cople Maia, DDS, PhD
Associate Professor
Department of Pediatric Dentistry and Orthodontics
School of Dentistry
Federal University of Rio de Janeiro

© 2021 AEGIS Communications | Privacy Policy