The purpose of this editorial is to present an update of the evidence on bisphenol A (BPA) in orthodontics by critically reviewing the available evidence, which often shows variable validity and derives from in-vitro, animal, simulated in-vivo, and in-vivo experimental configurations; clarify several misconceptions that are the results of false assumptions in the design of studies or limitations of instrumental analyses; and suggest ways to minimize the exposure of operator, staff, and patients to this molecule. The wording of the title implies that the therapeutic team including the clinician and chair-side staff should be given priority with regard to the implementation of means to shield them from BPA. This is because the operatory personnel are exposed repeatedly and for long periods of time to materials and processes that can result in BPA production compared with patients who participate only once in such scenarios.
BPA is a chemical produced in large quantities for use primarily in the production of polycarbonate plastics and epoxy resins, which have many applications in modern material items including food and drink packaging. The primary source of exposure to BPA for most people is through the diet. Whereas air, dust, and water (including through the skin when handling materials, or during bathing and swimming) are other possible sources of exposure, BPA in food and beverages accounts for the majority of daily human exposure. BPA can migrate into food from food and beverage containers with internal epoxy resin coatings and from consumer products made of polycarbonate plastic such as baby bottles, tableware, food containers, and water bottles. Leaching of BPA into packages and food carriers depends more on the temperature of the liquid than the age of the container—ie, more migration with higher temperatures.
Over the past decade, the effects of BPA on a wide array of tissues, organs, and systems have been established through in vitro and animal studies, as well as case analyses and observations in humans. Therefore, what was initially considered a topic of dispute among scientists, professional societies, and the industry has reached the status of an unequivocally defined thesis, with organizations at national and international legislative levels issuing relevant statements. These highlight the fact that BPA at levels as low as parts per billion are unconjugated, which means that they are not metabolized and thus are biologically active, and are detected in human blood and tissues.
BPA as endocrine disruptor
Xenoestrogenicity is a relatively recently described property of certain polymeric molecules such as BPA to express biologic effects similar to those induced by natural estrogens. The similar chemical structure of BPA to natural estrogen (17-beta estradiol) is the reason for this deviation of the hormonal homeostasis from the proper pathway.
The effects of endocrine disrupting compounds were identified in the early 1960s when the nests of bald eagles, which consumed prey contaminated with pesticides, were found to produce 3 to 4 times fewer eaglets than the corresponding numbers recorded in the 1930s. In spite of the early recognition of these effects, it took several decades for a substantial body of literature reporting biologic effects associated with these compounds to be accumulated, demonstrating the phenomena accompanying the exposure of organisms to BPA and including hormonal-related effects.
For a given exposure period and BPA quantity, the accumulation of BPA in the body may vary as functions of the developmental stage and the sex of the subject. Exposure of infants to the chemical leads to higher BPA body levels relative to those during adulthood, because of the absence of enzymes capable of metabolizing BPA to its biologically inert form. Also, a sexual dimorphism is implied by several studies, which have reported higher plasma BPA levels in male than in female fetuses even after correcting for a positive correlation between body weight and BPA concentration. Most importantly, there is extensive evidence that outcomes may not become apparent until long after BPA exposure during development has occurred. The issue of a very long latency for effects in utero to be observed is referred to as the developmental origins of adult health and disease hypothesis. These developmental effects are irreversible and can occur due to low-dose exposure during brief sensitive periods in development, even though no BPA is detected when the damage or disease is expressed.
The reader would understand the often contradicting conclusions of studies by considering the objective difficulty in reaching a definitive agreement with regard to levels of BPA released and potential effects; this is because the biologic action of BPA sets in at very low concentrations within the range of the detection threshold of the majority of standard analytical techniques. Specifically, substances such as octaphenol are capable of altering the uptake of dopamine by hypothalamic cells in animals at levels as low as 10 parts per trillion (or pg/L). Therefore, even if a precise and reliable quantitative estimation of BPA is obtained, there is still a large window of uncertainty on its potential estrogenicity.
The basic differences between the study of common toxicants or other hazardous materials and BPA relate to the fact that natural hormones such as 17-beta estradiol educe effects at concentrations far beneath the levels at which all hormone receptors become bound. This observation has given rise to a new perspective of toxicity. Once all receptors are occupied, a further increase in natural hormone levels does not result in an increased response. Conventional testing of substances for toxicologic impact assessment involves exposure to levels many times higher than those required for complete receptor binding. Thus, the lack of response to excessively high concentrations of effectors may be misinterpreted as lack of effect. Along with that, the effects of BPA on tissues follow a nonmonotonic curve pattern, which is characterized by intense reactivity at low levels and no response at high ones, respectively.
BPA and orthodontic polymeric materials
The broader dental composite polymer materials literature has indicated that a wide range of effects can be induced upon exposure of insufficiently polymerized material to the oral environment. In general, the degree of cure or carbon double-bond conversion of polymers may modulate the physical and mechanical properties of the material, especially solubility and degradation. This has a pivotal role in altering the biologic performance of the materials because a less densely formed network resulting from a decreased conversion of double bonds is associated with residual monomer leaching and release of substances that are constituent components of the polymer such as amines, polymerization initiators, and inhibitors, among others. Additives such as plasticizers, which are used for altering the brittleness of most polymers, include the phthalates, aromatic esters suspected to mimic hormones.
In dental materials, BPA is used as a raw material for formulation of Bis-GMA and polycarbonate products; as a general rule, the estrogenic action is confined to molecules with a double benzoic ring. The implication of BPA release from dental biomaterials was first reported in a study that assessed salivary BPA levels in patients with dental sealants. A considerable dispute exists on the actual release of BPA from sealants, since BPA release from sealants has not been confirmed in a large-scale study.
Orthodontic polymers considered in this section include resin adhesives and glass-ionomer modified adhesives (but not glass-ionomer cements) used for bonding brackets and fixed retainers, plastic brackets, elastomeric ligatures, and chains; protective wire sleeves; acrylic Hawley appliances; and thermo-formed retainers. A critical point in considering the potential implications of these materials in BPA release relates not only to their composition and manufacturing process but also to their application mode. For example, the application of orthodontic adhesives as bonding materials involves a sandwich (between bracket and enamel) material configuration, allowing only the peripheral margins of the material to be exposed to the oral cavity; this is vastly different from the use of adhesives in lingual fixed retainer bonding. In the latter scenario, the material approaches a 2-dimensional structure, with a large surface-to-volume ratio; therefore, exposure of the entire surface of the material to the oral environment takes place. This includes masticatory stresses, temperature variations, pH fluctuation, enzymatic degradation, and oral microbiota material challenges for periods of time many times greater than the duration of a typical orthodontic treatment. A BPA release assay may not constitute conclusive evidence in determining the potential of a material to give rise to BPA formation because of the threshold of chromatographic analyses used. Thus, the amount released could be undetected by the instrumental analysis.
As an empirical rule, the potential of BPA release is restricted to materials that contain BPA as a precursor during the manufacturing process. Obviously, any polymer without an aromatic ring in its structure is free of this concern; therefore, acrylic retainers and other linear carbon chain polymers have no known risk for BPA release. The materials that in most cases are manufactured with the use of BPA are polycarbonate brackets and Bis-GMA, although recently traces of the molecule were identified in thermo-formed aligners. Bis-GMA-based orthodontic adhesives were manufactured with BPA as a precursor; however, most manufacturers have reported that they have abandoned this process.
Systematic reviews on the subject showed that published studies are contradictory with respect to the qualitative and quantitative parameters of BPA release from adhesives and sealants, probably because of the varying methodologies that have been used. Results of 1 investigation showed no indication of BPA; another study demonstrated that an increase of the distance between the light-cure tip and the adhesive introduced a decrease in the degree of conversion of the polymer that led to greater BPA release, whereas the release of BPA from an orthodontic adhesive used to bond lingual fixed retainers indicated measurable amounts of BPA that were identified for all groups, with the highest found in the immersion media of the 30-day immersed group. In general, the in-vivo assessment of BPA release in biologic liquids indicates a broad variance along with a rise immediately after bonding of brackets or lingual fixed retainers.
On another class of orthodontic materials—polycarbonate esthetic brackets—it has been reported that during the synthesis of polycarbonates, nonreacting BPA probably remains inside the materials and is released when these are immersed in water or organic solvents resulting in a rate of BPA release increasing with time and temperature, although the issue has not been unequivocally determined with respect to the xenoestrogenicity of the appliances.
Lastly, there have been promising efforts for the development of orthodontic adhesives for use with lingual fixed retainers at the first stage, based on monomers without a BPA derivative or precursor during the synthesis, and with similar performance with respect to bond strength, degree of carbon double-bond conversion, hardness, oxygen inhibition, polymerization zone, and physical properties such as viscosity, with a widely used product.
For aligners, the evidence is contradictory, since BPA’s implication in the use of these products has not been conclusive at the cell culture or analytical level, with views such as their inert profile or BPA release supported by studies with different methodologic approaches.
BPA and orthodontic polymeric materials
The broader dental composite polymer materials literature has indicated that a wide range of effects can be induced upon exposure of insufficiently polymerized material to the oral environment. In general, the degree of cure or carbon double-bond conversion of polymers may modulate the physical and mechanical properties of the material, especially solubility and degradation. This has a pivotal role in altering the biologic performance of the materials because a less densely formed network resulting from a decreased conversion of double bonds is associated with residual monomer leaching and release of substances that are constituent components of the polymer such as amines, polymerization initiators, and inhibitors, among others. Additives such as plasticizers, which are used for altering the brittleness of most polymers, include the phthalates, aromatic esters suspected to mimic hormones.
In dental materials, BPA is used as a raw material for formulation of Bis-GMA and polycarbonate products; as a general rule, the estrogenic action is confined to molecules with a double benzoic ring. The implication of BPA release from dental biomaterials was first reported in a study that assessed salivary BPA levels in patients with dental sealants. A considerable dispute exists on the actual release of BPA from sealants, since BPA release from sealants has not been confirmed in a large-scale study.
Orthodontic polymers considered in this section include resin adhesives and glass-ionomer modified adhesives (but not glass-ionomer cements) used for bonding brackets and fixed retainers, plastic brackets, elastomeric ligatures, and chains; protective wire sleeves; acrylic Hawley appliances; and thermo-formed retainers. A critical point in considering the potential implications of these materials in BPA release relates not only to their composition and manufacturing process but also to their application mode. For example, the application of orthodontic adhesives as bonding materials involves a sandwich (between bracket and enamel) material configuration, allowing only the peripheral margins of the material to be exposed to the oral cavity; this is vastly different from the use of adhesives in lingual fixed retainer bonding. In the latter scenario, the material approaches a 2-dimensional structure, with a large surface-to-volume ratio; therefore, exposure of the entire surface of the material to the oral environment takes place. This includes masticatory stresses, temperature variations, pH fluctuation, enzymatic degradation, and oral microbiota material challenges for periods of time many times greater than the duration of a typical orthodontic treatment. A BPA release assay may not constitute conclusive evidence in determining the potential of a material to give rise to BPA formation because of the threshold of chromatographic analyses used. Thus, the amount released could be undetected by the instrumental analysis.
As an empirical rule, the potential of BPA release is restricted to materials that contain BPA as a precursor during the manufacturing process. Obviously, any polymer without an aromatic ring in its structure is free of this concern; therefore, acrylic retainers and other linear carbon chain polymers have no known risk for BPA release. The materials that in most cases are manufactured with the use of BPA are polycarbonate brackets and Bis-GMA, although recently traces of the molecule were identified in thermo-formed aligners. Bis-GMA-based orthodontic adhesives were manufactured with BPA as a precursor; however, most manufacturers have reported that they have abandoned this process.
Systematic reviews on the subject showed that published studies are contradictory with respect to the qualitative and quantitative parameters of BPA release from adhesives and sealants, probably because of the varying methodologies that have been used. Results of 1 investigation showed no indication of BPA; another study demonstrated that an increase of the distance between the light-cure tip and the adhesive introduced a decrease in the degree of conversion of the polymer that led to greater BPA release, whereas the release of BPA from an orthodontic adhesive used to bond lingual fixed retainers indicated measurable amounts of BPA that were identified for all groups, with the highest found in the immersion media of the 30-day immersed group. In general, the in-vivo assessment of BPA release in biologic liquids indicates a broad variance along with a rise immediately after bonding of brackets or lingual fixed retainers.
On another class of orthodontic materials—polycarbonate esthetic brackets—it has been reported that during the synthesis of polycarbonates, nonreacting BPA probably remains inside the materials and is released when these are immersed in water or organic solvents resulting in a rate of BPA release increasing with time and temperature, although the issue has not been unequivocally determined with respect to the xenoestrogenicity of the appliances.
Lastly, there have been promising efforts for the development of orthodontic adhesives for use with lingual fixed retainers at the first stage, based on monomers without a BPA derivative or precursor during the synthesis, and with similar performance with respect to bond strength, degree of carbon double-bond conversion, hardness, oxygen inhibition, polymerization zone, and physical properties such as viscosity, with a widely used product.
For aligners, the evidence is contradictory, since BPA’s implication in the use of these products has not been conclusive at the cell culture or analytical level, with views such as their inert profile or BPA release supported by studies with different methodologic approaches.
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