Bisphenol A and orthodontics: An update of evidence-based measures to minimize exposure for the orthodontic team and patients

Theodore Eliades · 2017 · 18 citationsRead the paper

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.1Howe S.R. Borodinsky L. Lyon S.R. Potential exposure to Bisphenol A from food contact use of epoxy coated cans.J Coatings Technol. 1998; 70: 69-74Crossref Google Scholar 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.2Ptak A. Wróbel A. Gregoraszczuk E.L. Effect of bisphenol-A on the expression of selected genes involved in cell cycle and apoptosis in the OVCAR-3 cell line.Toxicol Lett. 2011; 202: 30-35Crossref PubMed Scopus (62) Google Scholar, 3Nah W.H. Park M.J. Gye M.C. Effects of early prepubertal exposure to bisphenol A on the onset of puberty, ovarian weights, and estrous cycle in female mice.Clin Exp Reprod Med. 2011; 38: 75-81Crossref PubMed Scopus (97) Google Scholar, 4Jelnes J.E. Semen quality in workers producing reinforced plastic.Reprod Toxicol. 1988; 2: 209-212Crossref PubMed Scopus (42) Google Scholar 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.5Canadian Environmental Protection Act. Screening assessment for the challenge phenol, 4,4,-(1-methymethylidene)bis-(bisphneol A). Canada: Chemical Abstracts Service Registry Number 80-05-7; 2008.Google Scholar, 6European Chemicals BureauEuropean Union risk assessment report. CAS 80-05-7. 4,4'-isopropylidenediphenol (bisphenol A). Volume 37. European Commission, European Chemicals Bureau, Existing Substances, 2003Google Scholar, 7European Chemicals BureauEuropean Union risk assessment report draft: updated risk assessment of 4,4'-isopropylidenediphenol (bisphenol A) (CAS No. 80-05-7; EINECS No. 201-245-8). European Commission, European Chemicals Bureau, Existing Substances, 2008Google Scholar 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.8Bennetts L.E. De Iuliis G.N. Nixon B. Kime M. Zelski K. McVicar C.M. et al.Impact of estrogenic compounds on DNA integrity in human spermatozoa: evidence for cross-linking and redox cycling activities.Mutat Res. 2008; 641: 1-11Crossref PubMed Scopus (82) Google Scholar, 9Vom Saal F.S. Cooke P.S. Buchanan D.L. Palanza P. Thayer K.A. Nagel S.C. et al.A physiologically based approach to the study of bisphenol A and other estrogenic chemicals on the size of reproductive organs, daily sperm production, and behaviour.Toxicol Ind Health. 1998; 14: 239-260Crossref PubMed Scopus (664) Google Scholar 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.10Vom Saal F.S. Hughes C. An extensive new literature concerning low-dose effects of bisphenol a shows the need for a new risk assessment.Environ Health Perspect. 2005; 113: 926-933Crossref PubMed Scopus (941) Google Scholar 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.11Environmental estrogen endocrine disruptors. Available at: http://enhs.umn.edu/current/5200/estrogen/history.html. Accessed July 27, 2017.Google Scholar 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.12Welshons W.V. Thayer K.A. Judy B.M. Taylor J.A. Curran E.M. vom Saal F.S. Large effects from small exposures. I. Mechanisms for endocrine disrupting chemicals with estrogenic activity.Environ Health Perspect. 2003; 111: 994-1006Crossref PubMed Scopus (713) Google Scholar 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.12Welshons W.V. Thayer K.A. Judy B.M. Taylor J.A. Curran E.M. vom Saal F.S. Large effects from small exposures. I. Mechanisms for endocrine disrupting chemicals with estrogenic activity.Environ Health Perspect. 2003; 111: 994-1006Crossref PubMed Scopus (713) Google Scholar 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.13Kim Y.H. Kim C.S. Park S. Han S.Y. Pyo M.Y. Yang M. Gender differences in the levels of bisphenol A metabolites in urine.Biochem Biophys Res Commun. 2003; 312: 441-448Crossref PubMed Scopus (117) Google Scholar 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.14Wadhwa P.D. Buss C. Entringer S. Swanson J.M. Developmental origins of health and disease: brief history of the approach and current focus on epigenetic mechanisms.Semin Reprod Med. 2009; 27: 358-368Crossref PubMed Scopus (591) Google Scholar 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.15Eliades T. Fragen und Antworten zu Bisphenol A.IOK. 2013; 45: 51-56Google Scholar, 16Sifakakis I. Eliades T. Adverse reactions to orthodontic materials.Aust Dent J. 2017; 62: 20-28Crossref PubMed Scopus (24) Google Scholar 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).17Oehlmann J. Schulte-Oehlmann U. Tillmann M. Markert B. Effects of endocrine disruptors on Prosobranch snails (mollusca: gastropoda) in the laboratory. Part I: bisphenol a and octylphenol as xenoestrogens.Ecotoxicology. 2000; 9: 383-397Crossref PubMed Scopus (263) Google Scholar 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.18Welshons W.V. Nagel S.C. vom Saal F.S. Large effects from small exposures, III. Endocrine mechanisms mediating effects of bisphenol A at levels of human exposure.Endocrinology. 2006; 147: S56-69Crossref PubMed Scopus (826) Google Scholar 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.12Welshons W.V. Thayer K.A. Judy B.M. Taylor J.A. Curran E.M. vom Saal F.S. Large effects from small exposures. I. Mechanisms for endocrine disrupting chemicals with estrogenic activity.Environ Health Perspect. 2003; 111: 994-1006Crossref PubMed Scopus (713) Google Scholar 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.19Purushothaman D. Kailasam V. Chitharanjan A.B. Bisphenol A release from orthodontic adhesives and its correlation with the degree of conversion.Am J Orthod Dentofacial Orthop. 2015; 147: 29-36Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar 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.20Hannon P.R. Flaws J.A. The effects of phthalates on the ovary.Front Endocrinol (Lausanne). 2015; 6: 8Crossref PubMed Scopus (206) Google Scholar 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.21Olea N. Pulgar R. Olea-Serrano F. Rivas A. Novillo-Fertrell A. Pedraza V. et al.Estrogenicity of resin-based composites and sealant used in dentistry.Environ Health Perspect. 1996; 104: 298-305Crossref PubMed Scopus (878) Google Scholar 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.22Nathanson D. Lertpitayakun P. Lamkin M.S. Edalatpour M. Chou L.L. In vitro elution of leachable components from dental sealants.J Am Dent Assoc. 1997; 128: 1517-1523Abstract Full Text PDF PubMed Scopus (90) Google Scholar, 23Zampeli D. Papagiannoulis L. Eliades G. Pratsinis H. Kletsas D. Eliades T. In vitro estrogenicity of dental resin sealants.Pediatr Dent. 2012; 34: 312-316PubMed Google Scholar 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.24Eliades T. Hiskia A. Eliades G. Athanasiou A.E. Assessment of bisphenol-A release from orthodontic adhesives.Am J Orthod Dentofacial Orthop. 2007; 131: 72-75Abstract Full Text Full Text PDF PubMed Scopus (42) Google Scholar 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.25Kloukos D. Pandis N. Eliades T. In vivo bisphenol-a release from dental pit and fissure sealants: a systematic review.J Dent. 2013; 41: 659-667Abstract Full Text Full Text PDF PubMed Scopus (50) Google Scholar, 26Kloukos D. Pandis N. Eliades T. Bisphenol-A and residual monomer leaching from orthodontic adhesive resins and polycarbonate brackets: a systematic review.Am J Orthod Dentofacial Orthop. 2013; 143 (S104-12.e1-2)PubMed Google Scholar 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.27Eliades T. Voutsa D. Sifakakis I. Makou M. Katsaros C. Release of bisphenol-A from a light-cured adhesive bonded to lingual fixed retainers.Am J Orthod Dentofacial Orthop. 2011; 139: 192-195Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar, 28Kotyk M.W. Wiltshire W.A. An investigation into bisphenol-A leaching from orthodontic materials.Angle Orthod. 2014; 84: 516-520Crossref PubMed Scopus (28) Google Scholar, 29Moreira M.R. Matos L.G. de Souza I.D. Brigante T.A. Queiroz M.E. Romano F.L. et al.Bisphenol A release from orthodontic adhesives measured in vitro and in vivo with gas chromatography.Am J Orthod Dentofacial Orthop. 2017; 151: 477-483Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar, 30Halimi A. Benyahia H. Bahije L. Adli H. Azeroual M.F. Zaoui F. A systematic study of the release of bisphenol A by orthodontic materials and its biological effects.Int Orthod. 14: Scholar, Kim Kim J. Release of bisphenol A from resin composite used to bond orthodontic lingual retainers.Am J Orthod Dentofacial Orthop. 2011; Full Text Full Text PDF PubMed Scopus Google Scholar, C. Kailasam V. S. Chitharanjan A.B. Bisphenol A release from an orthodontic adhesive and its correlation with the degree of conversion on varying tip J Orthod Dentofacial Orthop. 2011; Full Text Full Text PDF PubMed Scopus Google Scholar In general, the in-vivo assessment of BPA release in biologic a with a rise after bonding of brackets or lingual fixed retainers. another of orthodontic has been reported that during the of BPA probably the materials and is released when these are immersed in water or resulting in a of BPA release with time and M. T. in the bisphenol A in a polycarbonate orthodontic bracket and its leaching in J. PubMed Scopus Google Scholar, K. K. K. H. F. and release of bisphenol A from polycarbonate dental J. 2000; PubMed Scopus Google Scholar although the issue has not been unequivocally with respect to the of the D. Eliades T. Katsaros C. Eliades G. effects of orthodontic brackets by of 2013; Full Text Full Text PDF PubMed Scopus Google Scholar there have been for the development of orthodontic adhesives for use with lingual fixed retainers at the first based on without a BPA or precursor during the and with similar performance with respect to bond degree of carbon double-bond polymerization and physical properties such as with a used A. Eliades T. F. N. of potential as a for Bis-GMA in orthodontic 2013; Full Text Full Text PDF PubMed Scopus Google Scholar, A. Eliades T. N. Eliades G. and testing of bisphenol adhesives for lingual fixed retainer J Orthod. 2017; PubMed Scopus Google Scholar, D. A. N. Eliades G. Eliades T. properties of orthodontic adhesives used for lingual fixed retainer 2017; Full Text Full Text PDF PubMed Scopus Google Scholar For the evidence is since implication in the use of these products has not been conclusive at the cell or analytical with such as their inert T. Pratsinis H. Athanasiou A.E. Eliades G. Kletsas D. and estrogenicity of J Orthod Dentofacial Orthop. 2009; Full Text Full Text PDF PubMed Scopus (38) Google Scholar or BPA H. Kailasam V. S. of salivary bisphenol A levels in patients and Hawley an in-vivo J Orthod Dentofacial Orthop. 2017; 151: Full Text Full Text PDF PubMed Scopus Google Scholar by studies with different The point in this issue is to present the evidence and its potential in the of The materials in from the body of the literature are Bis-GMA-based which are manufactured with BPA as a precursor; most of those materials are to be applications such as bonding materials for fixed retainers, the adhesive a surface relative to its to the constitute a BPA release case only if the adhesive is from the use of BPA. Also, during the stage the resin adhesive be with the produced also have an estrogenic C. Eliades T. S. Pratsinis H. Athanasiou A.E. Eliades G. et and in vitro estrogenicity of orthodontic adhesive produced by simulated 2009; Full Text Full Text PDF PubMed Scopus Google this is a hazardous for the and who are exposed to R. and qualitative of production during simulated orthodontic 2009; Full Text Full Text PDF PubMed Scopus Google Scholar, R. of produced during the of fixed orthodontic a of 4 J Orthod Dentofacial Orthop. 2008; Full Text Full Text PDF PubMed Scopus (30) Google Scholar and to a degree for the since the and staff may be exposed to this but the only to air, use of and and are for this as is the of as material as possible without the use of The most materials from the of potential polymers and only polycarbonate brackets as potential BPA should be not to all plastic with polycarbonate brackets because brackets may not be in this Therefore, from the wide array of orthodontic polymers, only 1 of materials could be considered a source of in the case of definitive BPA release, if the levels are within the range found in exposed to this through although there should be an to all sources of the amounts of BPA released may not a for the of the lack of evidence, however, patients most importantly, and the who in contact with products in the of during are to as should be used in to minimize exposure to patients and be given to the of orthodontic Thus, of general that are for in materials or other of workers by may have results and this a exposure contact per time per orthodontic materials is a and because of the there is no contact with materials the is to the staff of the with on the of the by and even if contact with resins BPA materials took the precise estimation of the BPA exposure is because the of BPA in the material is ways to patients most importantly, and staff from exposed to BPA include to lack of contact of patients and with BPA and relative to minimize exposure to this The of these takes into the evidence published to when studies orthodontic materials with BPA were Therefore, the evidence be considered as a because it has a validity that have a definitive Whereas the are based on evidence primarily from in-vivo studies, no are available on the of the other relative as a to minimize exposure of the involved in an orthodontic The first of BPA exposure, includes bonding with glass-ionomer and use of or brackets and Hawley of retainers. are polymers and have no known risk of leaching whereas for many other of polymers such as protective and with resins or conclusive evidence is The relative includes the use of orthodontic to the case of or adhesives BPA is not used as a precursor for the manufacturing of the this is to for the and it not to have critical since a study showed that by patients after the levels of BPA in their or to D. Sifakakis I. Voutsa D. I. Eliades G. Katsaros C. et and quantitative assessment associated with orthodontic bonding in 2015; Full Text Full Text PDF PubMed Scopus Google Scholar to to use to the release and a of the this in-vivo assessment showed that this no effect. most literature the first period after bonding as the time with the release, this implies that bonding is a critical in potential release. after bonding and a to this for may the initially higher salivary BPA to Along the use of brackets or plastic brackets until the evidence more conclusive on the actual in-vivo release of BPA from polycarbonate brackets is established that from materials, certain such as may in exposure to BPA during it is to that may exposure to BPA during For of as material as possible without is This can be by a bracket and an adhesive the application of during would result in a composite adhesive of A. S. Pandis N. Athanasiou A.E. Eliades T. The of orthodontic adhesive and bracket design in adhesive of Orthod. 2015; Full Text Full Text PDF Scopus Google Scholar In general, a of the bracket results in of the the from the to the thus a large of adhesive on the which in a and more process. adhesive is also by the of the however, the of may a

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