Bisphenol A and Orthodontic Materials

Theodore Eliades and George Eliades (eds.)Plastics in Dentistry and Estrogenicity2014A Guide to Safe Practice10.1007/978-3-642-29687-1_6

© Springer-Verlag Berlin Heidelberg 2014

6. Bisphenol A and Orthodontic Materials

Dimitrios Kloukos1 and Theodore Eliades 

Department of Orthodontics, University of Bern, Bern, Switzerland

Department of Orthodontics and Paediatric Dentistry, Center of Dental Medicine, University of Zurich, Zurich, Switzerland
Theodore Eliades
Orthodontic polymers, and their applications, have been instrumental in introducing aesthetics, innovation, and practicality into the orthodontic specialty. Such materials constitute a large class of components including plastic elements and auxiliaries such as adhesives, polycarbonate brackets, and aligners.

6.1 Introduction

Orthodontic polymers, and their applications, have been instrumental in introducing aesthetics, innovation, and practicality into the orthodontic specialty. Such materials constitute a large class of components including plastic elements and auxiliaries such as adhesives, polycarbonate brackets, and aligners.
The composition and configuration of these materials vary notably. Some of them are based on bisphenol A (BPA), which is used as a precursor of bisphenol A glycidyl dimethacrylate (Bis-GMA) or BPA dimethacrylate (Bis-DMA) during the production of many composite resins. The BPA structure assembles a bulk, stiff chain that offers low susceptibility to biodegradation as well as great rigidity and strength [1]. Although BPA is not used by itself as a raw material in composite resins, it is likely to be present as an impurity from the synthesis process [2, 3].
Since the 1960s, when the use of bisphenol A glycidyl dimethacrylate (Bis-GMA) began to flourish in dentistry, many studies have assessed the effects of dental composites on pulpal impairment [4] and their cytotoxic properties [57]. Nevertheless, the systemic health consequences of these chemicals, or their monomers, have not been thoroughly evaluated [8, 9].
Even though the patient may come in contact with significant amounts of unpolymerized monomers during the placement of composites, the release of uncured monomers after polymerization has been assumed to cause most of the unwanted effects [10]. In particular, BPA release from dental resins has attracted recent attention in the literature because of numerous experiments presenting adverse effects of BPA [2, 3, 11]. BPA has shown potential estrogenicity in a significant number of studies [12] and is described as an endocrine disruptor chemical (EDC), owing to its ability to bind and activate the human estrogen receptor, however with a capacity of 1,000–5,000 times less than the endogenous 17-b estradiol [13].
Moreover, BPA can interact with other endocrine receptors, as thyroid hormone receptors and peroxisome proliferator-activated receptor gamma [14]. BPA was classified as a reproductive toxic substance of category 3, a significant risk factor for human fertility [15]. The concern is not isolated only at the molecular level. A recently published review indicated that exposure to dental composite resins based on BPA derivatives may even impact psychosocial health in children. Increased levels and duration of exposure (5 years) to composite indicated higher levels of anxiety, depression, social stress, and interpersonal-relation problems in children [16].
The European Food Safety Authority published an initial risk assessment on BPA in 2006, based on a tolerable daily intake (TDI) of 50 μg/kg body weight/day [17]. Several scientists arguably disputed the use of TDI for risk assessments on EDCs, suggesting that the effects of EDCs are observed at very low doses, non-monotonic dose–response curves, as well as on effects occurring from very specific windows of exposure [18].
The uncertainty in the dental literature was initially provoked by a study published by Olea et al. [19] who reported elevated salivary levels of BPA in patients with dental sealants. Since then, the extensive implementation of new polymers has triggered the investigation of their long-term effects at subtoxic levels. The investigation of the biological properties of materials has deviated from various routine cytotoxicity assays, for example, DNA synthesis or MTT proliferation assay [20].
The orthodontic concerns originate from the fact that monomers equivalent to those used for dental sealants are also used for the construction of orthodontic polymeric adhesives, plastic polycarbonate brackets, and other polycarbonate-made appliances that might also be sources of BPA. However, the actual effects induced by the possible release of BPA are difficult to be assessed because the mode of application of the materials, the growth stage and age of the individual, and potential other environmental factors might alter the extrapolation of results.
The purpose of this chapter is to briefly summarize the limited evidence available on the topic, which is associated with (a) polymeric orthodontic adhesive resins, (b) plastic polycarbonate brackets, and (c) polymeric aligners and their relationship to the possibility of bisphenol A (BPA) release and the subsequent phenomena of estrogenicity. A recently published systematic review was utilized as basis [21] for providing the evidence discussed in this chapter.

6.2 Orthodontic Adhesives

Bonding of brackets to enamel has been an enduring critical issue in orthodontics research.
Biomechanical principles necessitated a relatively inelastic interface that would transfer a load applied to the bracket directly to the tooth or to its root. Furthermore, the engagement of an archwire to the bracket should not exceed the bond strength between bracket and tooth [22]. Based on these requirements a considerable volume of research was undertaken, aimed to find new materials and new perspectives in the province of orthodontic adhesives.
Orthodontic adhesive exposure to the oral environment involves three patterns:


The bracket peripheral margins
The average thickness of these margins is quantified as between 150 and 250 μm [23]. The effect of aging and leaching of the material throughout these margins and under oral conditions might not be that potent.

Bonded fixed lingual retainers
Fixed retainers have been used in orthodontics for many years. In both arches, mandibular and maxillary, they are routinely used for a prolonged period of time or even permanently. The use of these bonded retainers has been proven and well documented to be efficient in preventing relapse of the orthodontic treatment in most patients [24]. Two main types of fixed retainers are generally used: large-diameter wires, usually made of stainless steel, bonded only to the lingual surfaces of the canines, or small-diameter wires bonded to the lingual surfaces of all six anterior teeth.
For bonding both retainer types, specific orthodontic adhesives, mainly light-cured, are used. The adhesive in this case is used in a mode that involves full exposure of its surface to the oral environment. An extremely large surface-to-volume ratio of the applied adhesive is the main reason that increases its reactivity with the surrounding oral environment and facilitates aging and degradation, with volatile BPA release [25].

Removal of the brackets and cleaning up of the enamel surface
This procedure follows the completion of orthodontic treatment [26]. This standard technique involves grinding and removal of the adhesive layer that existed between the bracket and the tooth with rotating instruments at low or high speed. This process discharges three main fragments in the aerosol that is created: polymer matrix pieces, filler degradation by-products, and particles descending from the wear of the bur [27].
The potentially hazardous nature of this aerosol is double. Potential concerns deal with the respiratory health of the patient and the treatment-providing team, since the produced dust is capable of reaching the alveoli of the lungs [2729]. If we also take into consideration that the medical team is exposed on a long-term basis to this condition, we can easily assume the importance of these concerns.
Secondly, the particles attained from the presence of a double benzoyl ring in the released Bis-GMA monomers lead, as proclaimed, to the formation and release of bisphenol A (BPA) and hence to potentially disruptive hormonal action [3033].

6.3 Orthodontic Adhesives: In Vitro BPA Release

Published studies are contradictory with respect to the qualitative and quantitative parameters of elution and BPA release from adhesives, probably because of the varying methodologies that have been employed. Eliades et al. were the first to investigate the release of bisphenol A from orthodontic adhesives after their artificial accelerated aging with an in vitro study [34]. The results showed no indication of BPA identified for either type of adhesive across all time intervals used in the study, i.e., 1 day and 1, 3, and 5 weeks. Nevertheless the authors concluded that although the lack of BPA release was demonstrated in a particularly severe environment and under artificial accelerated aging conditions, these results should not be unquestionably extrapolated to real-life clinical conditions. The given reasons were three: Initially, the analysis of the adhesive extracts should be handled with caution, as far as it concerns the estrogenicity of polymers, because of the documented reactivity of BPA at very low levels [35]. In addition, the detection threshold level of the analytical apparatus used could be well above the potential BPA levels in the analyzed samples. Finally, intraoral aging, which is rather inconsistent with the extraoral reproductive aging, involves complex mechanical and chemical aging with the action of human enzymes, such as esterases, that induce degradation [36].
Similar protocol and techniques for assessing BPA release with the previous research were also used in a recent in vitro study of Sunitha et al. [37]. The scope of this study was to assess the BPA released from an orthodontic adhesive by varying the light cure tip distance and correlate it with the degree of conversion (DC). The degree of conversion of a resin composite material is the range of transformation of carbon double bonds (C═C) that exist in the monomer into carbon single bonds (C–C) to form polymers during the polymerization process. This has been found to significantly affect the physical [38, 39], mechanical [4042], and biological [43] properties of dental composites.
The outcomes of the study displayed that increase in light cure tip distance from the adhesive caused a decrease in the degree of conversion of the substance which, in turn, led to a greater BPA release.
The release of bisphenol A from an orthodontic adhesive used to bond lingual fixed retainers on the surface of teeth was also studied recently from Eliades et al. [25]. Eighteen recently extracted teeth, divided into three groups of six teeth each, were used for this study. A light-cured adhesive was bonded to a twist flex wire adjusted to the lingual surface of the teeth. Then the arches were immersed in double-distilled water for 10, 20, and 30 days. Thereafter, the concentration of BPA in the three eluents was investigated with gas chromatography–mass spectroscopy. The results certified measurable amounts of BPA that were identified for all groups, with the highest found in the immersion media of the 30 days groups: 2.9 mg/L. The control group, which consisted of teeth maintained in immersion media, showed BPA in the mean of 0.16 mg/L.

6.4 Orthodontic Adhesives: In Vitro Estrogenicity

The actual contribution of the above amounts of BPA to adolescents and adults remains indefinite, and it is not likely that it would have a direct effect, considering the age of the average orthodontic patient in the retention phase of the treatment, which may be well above 14 years of age. At such developmental stages, the action of BPA might not have the distinct effects reported for utero or early stages of life.
On the other hand, infants and children, examined on a pound-for-pound basis, have higher relative intakes of many widely detected environmental chemicals because they eat, drink, and breathe more than adults [44].
A recent statement of the US National Toxicology Program concluded that, along with high doses, BPA may show a diversity of effects at much lower ones [12]. A close example is that of phthalate esters, for instance, octaphenol, a substance added to plastics to make them more flexible, durable, and transparent. These plasticizers are capable of altering the uptake of dopamine by hypothalamic cells, at levels as low as 10 parts per trillion [45].
Therefore, there is unfortunately a large window of uncertainty on BPA potential estrogenicity, even if a precise and reliable quantitative estimation is attained. Moreover, there are about 20 different formations of bisphenol, and some of them share estrogenic action with BPA, such as Bis-DMA [30]. Therefore, the direct analysis of the estrogenic action of, artificial or not, aged adhesive eluents may be the method of choice for the inquiry about the potential estrogenic action of orthodontic polymers.
Appraisal of estrogenicity of orthodontic adhesive resins with in vitro studies has started to blossom mainly in the last 10 years. Eliades et al. assessed the estrogenic action of a chemically cured and a light-cured orthodontic adhesive resin [46]. The adhesives were bonded to 40 stainless steel brackets divided into two equal groups. The clinical handling of materials was reliably simulated. In total, three representative series of samples were prepared for each adhesive and bracket group. After immersion of the specimens in normal saline, samples of eluent were discharged from each group at 1 day and 1 week following incubation. The probable estrogenicity was measured by the effect of the eluents on the proliferation of cells. Estrogen-responsive MCF-7 breast cancer cells and estrogen-insensitive MB-231 human breast adenocarcinoma cells were used as active group and as control, respectively. The data from both cell lines indicated that no estrogenic activity was detected in the eluents from the resins tested.
Gioka et al. considered that whereas bulk, unimpaired orthodontic adhesive samples, used for the previous research, had not demonstrated estrogenic action, the biological features of their small-scale particles had not been assessed. One of the purposes of her study was to evaluate the estrogenicity of orthodontic adhesive particulates assembled by simulated debonding [26]. A chemically cured and a light-cured adhesive were included in the study. Specimens were prepared by simulating clinical bonding procedures. The adhesives prepared with this method were grounded in glass chambers with a high-speed handpiece. The collected amounts of the ground adhesives were immersed in saline for 1 month at 37 °C, replicating body temperature. Estrogenicity was assessed with estrogen-responsive cell line derived from human breast adenocarcinoma (MCF-7). Estradiol and bisphenol A as positive and saline as negative controls were also used. The proliferation rate of MCF-7 cells was clearly elevated, 160 and 128 %, compared to control for both chemically cured and light-cured adhesives, respectively. Both adhesives demonstrated therefore an estrogenic behavior. The possibility of irrelevant effects to estrogenicity interfering with proliferation was excluded as the estrogen-insensitive cell line MB-231 did not show any discrepancy in the experimental groups.

6.5 Orthodontic Adhesives: In Vivo BPA Release and Estrogenicity

The estrogenicity in eluents of tested adhesives with in vitro studies is usually measured by an established assay, for example, as seen before through the estimation of the proliferation of the estrogen-responsive cell line. These cells are known to express estrogen receptor-α (ERα), which is of paramount importance for the proliferative effect of estrogens. The typical method for measuring estrogenic action in vivo is the increase of mitotic indices of rodent epithelia [47]. This strategy may have, however, limited relevance to humans. That is because estrogenicity is diminished from rat hepatic microsomes in contrast with human liver [48]. Receptors for estrogens have been additionally identified in human gingival tissues, supplying evidence that this tissue can be a target organ for human sex hormones [49]. There are also indications of a sex hormone influence on the oral human epithelium reacting to chemical challenge [50]. It has been reported that the oral mucosa of premenopausal woman was appreciably more sensitive to sodium lauryl sulfate found in toothpastes than that of postmenopausal woman.
Up-to-date information about in vivo assessment of BPA released from orthodontic adhesives in humans has to do mainly with a recent study of Kang et al. [51]. This study assessed the changes in bisphenol A level in the saliva and urine before and after placing a lingual bonded retainer on the lower dentition of 22 volunteers. The samples were obtained immediately before placement of the retainer and 30 min, 1 day, 1 week, and 1 month after placement. The only significant level of BPA was detected in the saliva collected immediately after lingual retainer placement. Age and gender of the volunteers did not seem to affect the BPA level in the saliva or urine. The salivary BPA level (mean 5.04 ng/mL, levels ranging from 0.85 to 20.88 ng/mL) observed in the immediately collected sample was, as implied by the authors, far lower than the reference daily intake dose. Nevertheless, they concluded that, since some evidence of “low-dose effect” exists, clinicians should reduce the uncured layer of the material, using pumice surface prophylaxis of the adhesive.
The US human exposure limit and European Food Safety Authority have set the tolerable daily intake level of BPA to 50 μg/kg/day [17, 52]. The BPA released level from the lingual bonded retainer in this study was far below these doses. However and as already mentioned before, there is some controversy regarding the safe level of BPA exposure. Vom Saal and Hughes [53] proposed the need for a new risk assessment for BPA. They based this proposal on more than 100 in vivo and in vitro study results indicating that a BPA level far below 50 μg can cause modifications in the biological activities of cultured cells.
Finally, it should be also outlined that there are plenty reports of allergic dermatitis in dental personnel [5458], which can reasonably be attributed to released monomers from dental composite resins and, in our case, orthodontic adhesives. A smaller number of case reports of allergic responses in patients, which appear to be linked with the monomers, also exist. The last of these reports [59] described two cases of allergic contact dermatitis to bisphenol A glycidyl dimethacrylate (Bis-GMA) during the application of orthodontic fixed appliances. The authors concluded that these cases highlighted the importance for clinicians of two matters. Firstly, the importance of documenting which bonding agent the clinicians use rather than just recording “bonding upper and lower” and secondly, the conflict to the popular belief that dental adhesives are not eventually all the same, i.e., some have Bis-GMA, others do not.

6.6 Polycarbonate Brackets: In Vitro BPA Release

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Oct 30, 2015 | Posted by in General Dentistry | Comments Off on Bisphenol A and Orthodontic Materials
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