Adverse Effects Associated with the Clinical Use of 4%TiF on Teeth Enamel

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 vitro^5,6 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.

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.

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

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

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

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