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DOI: 10.17653/2374-9075.SS0006

Dental composites are actually the restoration of choice for most practitioners, due to their ease of handling and superior esthetics, and although their physical and mechanical properties have much improved, most of their components whether non-polymerized monomers, additives and fillers, have been shown to have definite toxicity, the most concerns in literature have been the release of Bisphenol A (BPA).1Needless to say that BPA exists already in various products used on daily basis, most significantly food containers; thus BPA concentration in saliva was found to be at least 0.07 ng/ml even before placement of resinous restorations of any kind.2,3

BPA itself is not used in dental composite resins, but it may be only found in dental resins as an impurity, 4,5the main reason is that moisture from saliva and salivary enzymes (esterase) inhibit its polymerization by causing hydrolysis of the second hydroxyl groups. On the other hand BPA derivatives are frequently used in dental resins; these derivatives are liquid monomers that polymerize into a solid after either chemical or light curing.4Among the mostly used are BPA glycidyldimethacrylate (bis-GMA), BPA dimethacrylate (bis-DMA) and BPA diglycidylether (BADGE) as well as BPA ethoxylatedimethacrylate (bis-EMA) and urethane-modified bis-GMA. The BPA derivative bis-DMA was found to hydrolyze into BPA; thus responsible for the Bisphenol A detected in extracts from certain composites, on the other hand, no studies have addressed the potential for other BPA derivatives used in dental materials to hydrolyze to BPA. 1,4,6Other potentially toxic methacrylate monomers including Hydroxyethylmethacrylate (HEMA) and Triethylene glycol dimethacrylate (TEGDMA) are commonly found in the composition of resin based dental materials.7

During the polymerization reactions, large chains are formed and crosslinking takes place, reducing the mobility of the monomers, and leading to entrapment of unreacted residual monomers. It was found that the degree of conversion varies depending on the resin-based material between 50 and 70%, 811the trapped uncured monomers can then leach out into the oral cavity. More leaching can take place due to further degradation of the resin composite, this usually takes place through mechanical swelling, water sorption and enzymatic degradation, as the degradation increase it results in more porosity and consequently more monomer leaching.8

The potential toxicity of these leached monomers can be either locally on the pulp and surrounding tissues, or systemic on the body as a whole. On the cellular level it was found that restorative materials containing resin are cytotoxic, especially after mixing, in the dental field this may lead to pulp irritation and gingival inflammation and retraction. Moreover, according to some reports elution could continue for up to 1 year after the initial polymerization.12Other studies discussed the probable synergistic effect of different monomers in increasing their toxicity toward pulp cells.13Another effect of monomer release from resin restorations could be in the form of favoring bacterial proliferation, especially the microorganisms implicated in caries formation, as with methacrylic acid (MA) and TEGDMA, therefore, contributing to the development of secondary caries.14

The systemic toxicity presents a more complicated problem, multiple toxilogical and epidemiologic studies have shown the noxious effects of BPA, for exampleepidemiological studies found that children with resin-based composites had worse psychosocial outcomes on some measures of neurodevelopment 5 years after placement,15 and that prenatal exposure to BPA was associated with chromosomal defects, other group of studies claimed that it is implicated in local and systemic allergic-related reactions.16 The French National Agency for Food Safety and Occupational and Environmental Health (ANSES) concluded that according to available scientific literature, BPA has recognized impacts on animal health and suspected impact on human health and recommended reducing the exposition to BPA for humans by substituting it with other components. Protective measures should specifically target infants and young children as well as pregnant and nursing women. 1,17

BPA has been shown to contribute to cancer development and progression through interaction with estrogen receptors α and β, leading to changes in cell proliferation, apoptosis, or migration. BPA has also been shown to be involved in multiple oncogenic signaling pathways. 18 BPA has also been shown to disrupt the thyroid hormone system at the gene expression level.19

From another perspective, the question whether to consider BPA and other monomers used in dental materials as a toxic substance or as endocrine disrupting chemicals with Nonmonotonic Dose Responses 20,21would have a huge impact on the relevance to human health of the “low-dose effects”,which can sometimes be 1000 times lower than the dose levels currently accepted by regulatory authorities as the No Observed Adverse Effect Level (NOAEL).

Under the EU chemicals policy REACH (Registration, Evaluation, Authorization and Restriction of Chemicals), manufacturers and importers are required to register their substances with the European Chemicals Agency (ECHA). For a substance manufactured or imported in a quantity ≥1 ton/year manufacturers must compile a Technical Dossier on the physico-chemical, human health and environmental properties of that substance. For a substance manufactured or imported in a quantity ≥10 tons/year, like BPA, a Chemical Safety Assessment must be carried out and documented in a Chemical Safety Report (CSR).

The leading manufacturers of BPA formed the BPA REACH Consortium and developed the registration dossier for BPA, based on the EU BPA Risk Assessment Report 2003, and updated 2008.

The BPA dossier was submitted to ECHA in August 2010 under the REACH regulation, “substances of very high concern” (SVHC) may be subject to “Authorization” in order to ensure that the risks from these substances are properly controlled.

In May 2010, The Polycarbonate/BisphenolAn industry group of PlasticsEuropeexaminedauthorizationunder REACHpublished a report which concluded that BPA does not meet the criteria of an SVHC under REACH. Following the regulation, authorization is not required for “intermediates”; that is substances that are converted during chemical processing. BPA is predominantly used as an intermediate in the manufacture of polycarbonate plastic and epoxy resin.

In November 2013, ECHA announced to request further data on BPA in the area of skin contact and environmental exposure, the BPA REACH Consortium accepted the request and is currently working to provide the additional input within the timeline by the end of 2015.

In March 2014, the Risk Assessment Committee supported an opinion proposing BPA as reprotoxic 1B. If adopted, enforcement will most likely not apply before early 2017. The classification will not affect compliance with food legislation: BPA can continue to be used in food contact applications for consumers.

Another part of the dilemma lies in the fact that the predetermined endpoints used in standard toxicological testing, have nothing to do with the modern technological methods that take in account endocrine disrupting compounds; that disrupt crucial cell-signaling pathways, and that cannot be detected by classical endpoint assays. 20,22The rodent studies reporting low-dose effects of BPA are claimed as irrelevant for the assessment of risks to human health by some groups because of different toxico kinetics between species.22 More accurate and sensitive methods are thus required to provide the necessary scientific data required by regulators to assess the safety features and the risk assessment of BPA.

With the evolution of new types of composite dental restorations, and the subsequentcontinueddevelopment of new resins and monomers, the main challenge that presents itself is to resolve the problems of shrinkage and secondary caries and at the same time preserve a good level of biocompatibility with dental tissues. In this work several studies dealing with BPA toxicity in dentistry were reviewed; we focused on the best methods developed to reduce BPA toxicity, whether through new ways to assess toxicity, development of new chemical compositions, the effect of type of cure and time, and finally the effect of various additions on increasing or decreasing the level of toxicity. The objective of this work is to give an overall view of the current situation, and to examine potential pathways that were tested to counter the probable harmful effects of PBA and other related substances in dental restorative resins.

Data Sources

A search was conducted for articles dealing with BPA toxicity and other related substances in dentistry dating for 5 years (January 2009), our study included all remarkable articles published between 2009 and 2014.The key words used were “Bisphenol” AND “toxicity” AND “dental composite”. The electronic databases searched were: PubMed and Science direct, in addition, more articles were included through manual search of selected journals.

Study selection

The number of studies obtained was 211, duplicates were removed, and searches were limited to publications in English (187). At each stage, the search strategy was validated by the authors. The abstracts of these articles were examined and of those identified, articles that did not discuss the toxicity of dental composites, or provide background information (review articles) were excluded (Figure. 01). The reference lists of these articles were searched to identify any other articles relevant to the subject. Articles found were classified according to the main themes: Toxicity assessment, Chemical composition, Type of cure and time, and Materials affecting toxicity.

Flow of information through the different phases of the search strategy

Toxicity Assessment

Assessment of dental material toxicity can be either through measurement of toxic components elution from the restorative material, through direct measurement of its toxic potential of the cells/tissues, or its ability to reach the pulp, gingival tissues and/or the systemic circulation.

Several methods exist for component release quantification from dental resin-based materials. The gravimetrical measurement of samples before and after extraction of components is the least expensive method.8 On the other hand to determine the individual release of separate compounds, sophisticated analytical methods should be used, (GC)sgas chromatography is more suitable for analysis of low molecular weight compounds, whereas (HPLC)High performance liquid chromatography and liquid chromatography (LC) are more applicable for analysis of high molecular weight compounds. Mass spectrometry (MS) gives information on the molecular mass of the compound and allows the detection and quantification of compounds based on their ionization, and computation of the mass-to-charge ratio. It can be used as a sophisticated detector in conjunction with one of the above mentioned analyses and allows detection of degradation products.8 Infrared spectroscopy and Fourier transform infrared spectroscopy are nowadays regarded as outdated, mainly because the interpretation of the spectrogram is difficult and not molecule-specific. It is worth noting that a great diversity exists between studies using these methods, mostly due to lack of standardization of the test methodology and the test set-up. 11,23,24

The actual toxicity assessment invitro on living cells is performed through cell culture. Franz and coworkers found that cell culture toxicity data are highly model dependent 25and that different ratios of specimen size to cell layer surface/volume of cell culture medium produced differences in cytotoxicity when the same material was tested.Their recommendations were that an internationally standardized protocol for specimen production is required to obtain comparable results between studies.26

Other investigators tried a different approach through studying the mobile secondary free radicals release by dental composites stored in hydrophilic media,27on the other hand Urcanet al.[28]used the xCELLigence system, a real-time and continuous monitoring system that allows label-free assessment of cell proliferation, viability and cytotoxicity to investigate cytotoxicity of the most common monomers/comonomers in dental resin composites.28 others still analyzed the degradation of a model dental composite leading eventually to the release phenomenon. 29,30

For screening new dental monomers,Pérez-Garrido et al.31 used a quantitative structure-activity correlation (QSAR) model that could distinguish mutagenic from non-mutagenic species in new developed dental materials, and identify the molecular features that most contribute to the mutagenic effects of these chemicals, so that their presence should be avoided in the design of new monomers.

New techniques like focused ultrasonic solid–liquid extraction or electron paramagnetic resonance spectroscopy are evolved to monitor BPA traces or hydroxyl radical release. 27,32Asimakopoulos et al.33 in their review discussed the problems related to control of contamination during sampling and handling of specimens, as well as data analysis and interpretation during the process of BPA biomonitoring, stressing the importance of implementing strict rules during sampling and handling of specimens before drawing final conclusions.

Researchers are in a continuous request for new methods for the toxicity assessment; some authors focused on the method sensitivity, others focused more on rapid or easy methods. Recently, Willershausen and co-workers used the Alamar blue assay to evaluate the in vitrobiocompatibility of a bioceramic root end material.34More recently, Attik and collaborators described a sensitive method for a dental composite cytotoxicity evaluation using time lapse confocal imaging.35

New approaches are being explored in order to obtain reliable information about material toxicity, especially with the advent of new composite resin materials, and the integration of monomers with new chemical formulas each day.

Chemical composition

BPA derivatives like BisGMA, BisEMA, EBPADMA and/or UDMA are mostly used for the development of dental composites, they allow for the development of restorative composites with better mechanical properties, rapid polymerization and low shrinkage. However, these monomers generally result in low methacrylate conversion, leaving significant amounts of unreacted monomers that would elute from the restoration over time.TEGDMA(not a BPA derivative)is mostly used in order to reduce viscosity, enabling larger percentage of filler to be incorporatedintothe resin matrix, for acquiring dental restorative composite with better mechanical properties.36

Miao found that in comparison to Bis-GMA/TEGDMA resin system, the composites containing EBPADMA exhibit greater compression strength, higher depth of cure, higher light transmission and lower volume shrinkage.37Moreover several studies found urethane-di, -tri, and -tetramethacrylates products had lower polymerization shrinkage and higher flexural strength properties compared to bis-GMA-based resins. Derivatives of urethane dimethacrylate are able to increase the molecular weight, reduce water sorption, and/or increase mechanical properties by incorporating aromatic or aliphatic groups.38 Yet on the other hand the urethane-based polymers absorb significantly more water than the aromatic-based materials, leading to passive and enzymatic hydrolytic degradation of the polymer matrix 39which not only change mechanical properties of urethane- based polymers, but also initiate the release of unbound monomers and degradation by-products. UDMA may also induce a broad spectrum of cyto- and genotoxic effects in human cells. 40,41

In recent times, with the arouse of public concerns about bisphenol toxicity, monomer development efforts shifted more toward bisphenol-A alternatives: Eliades et al.42 studied the formulation of benzoic ring-free, high molecular weight molecules to replace Bis-GMA.The toxicological and inflammatory potential of newly developed materials as silorane-based composites, sometimes present contradictory results. Wellner and co-workers 43 studied the release of 24 cytokines from human leukocytes and found that Filtek™ Silorane stimulates the leukocytes to a higher release of cytokines when compared to TetricEvo Flow, Indicating a higher sensitization potential for Silorane.At the same timeKrifka et al.44 found silorane-based composite resin to have no direct cytotoxicity, and only a very slight increase in ROS production.

Another example is the use of bile acids as starting materials to form multimethacrylate monomers, they showed reduced volume shrinkage and promising mechanical properties; but, exhibited extremely high viscosities (higher than BisGMA).36Polyhedraloligomericsilsesquioxanemethacrylates (POSS-MA) were found to improve the mechanical properties even in small amounts. In another report,dimethacrylates based on cycloaliphatic epoxides showed kinetics and mechanical properties comparable with those of BisGMA.45Another alternative to BisGMA were methacrylated beta-cyclodextrin derivatives found to exhibit flexural strength and volume shrinkage comparable with those of BisGMA/TEGDMA.46Previous work has also demonstrated that Toluene 2,4-diisocyanate (TDI) modified resinmatriceswere found to trap toxic resin monomers in the complicated resin structure leading to lesser cytotoxicity,47Poplawski et al.48 examined the cytotoxic and genotoxic effects ofglycidyl methacrylate (GMA), they warned against a potential long lasting exposure to this compound due to its broad spectrum of GMA genotoxicity, including DNA double-strand breaks.48Zanchi studied an experimental HEMA-free three-step adhesive system Bis-EMAs, (Bis-EMAs) he found that they have low ability to penetrate into wet demineralized dentin mainly because of their hydrophobicity. He postulated that it would be less toxic, but recommended cytotoxicity tests and long-term evaluation before arriving at that conclusion.49

Various studies classified monomers according to their degree of toxicity; D’Antòet al.50 found hydrophilic monomers such as HEMA less cytotoxic than the more hydrophobic monomers Bis-GMA, UDMA and TEGDMA, while other studies found BisG.MA as the most cytotoxic, followed by UDMA, HEMA and MMA,51Lin et al.52 found that while increasing the BisGMA content increased the mechanical properties, it reduced the conversion attained. And since its ultimate conversion is lower, it is therefore more likely to have a toxic effect,another group of studies found that BisGMA and UDMA were released from composite resins in much lower levels than toxic concentrations.53

Moreover several factors control the degree of toxicity of resin materials used in dentistry; Anand et al.54 found that unreacted double bonds in dental composites influence biocompatibility rather than its degree of conversion, and that the magnitude of double bonds depends on the polymerization and chemical composition, this affect biocompatibility especially if they possess lipophylic properties as previously pointed out by Durner et al.8 who correlated the lipophilicity of substances with their genotoxicity. Molecular weight also plays an important role concerning toxicity and pulp reactions that control monomer diffusion through dentin since the diffusion coefficient is inversely related to molecular weight.

The degree of elution of the released components depend on various factors,mainly the extent of the polymerization reaction (the 40 seconds usually used for the polymerization of resin composites seem insufficient to prevent a high release of monomers),55another factor is the size of the released components, as smaller molecules are eluted at a faster rate, finally the chemistry of the solvent and the action of pH on the extraction of components from polymerized and unpolymerized composite. Moreover, Durner et al.8 found that the degree of conversion of urethane dimethacrylate and bisphenol-Aglycidyldimethacrylate varies from different manufacturers.In another report, it was found that residual monomers and not breakdown products eluted only in small quantities during the first 90 days, but in high quantities thereafter.56

According to Lin et al.57 filler type/content has little effect on cell viability, while the degree of conversion, hydrophobicity and roughness had marked effect.Other components of resin based dental materials may indirectly contribute to the increase of toxicity

As an example, in a study by Curtis et al.58 it was found that larger surface area to volume ratio of the fillers present in the nanofilled materials as compared to conventional composite increased water uptake and resultant degradation of the filler/matrix interface.Another factor is the degree of dentin permeability, Porto and collaborators found that total-etch adhesives remove the smear layer and smear plugs, and widen the entry to the dentinal tubules, allowing for the permeation of solutes and solvents, thus increasing the risk of toxicity. Self-etching adhesives on the other hand do not completely remove the smear layer, and are considered safer because the resinous monomers cannot penetrate very deeply into the dentinal tubules.59

In perspective, there is limited commercial use of the new dimethacrylate derivatives, since theimprovement in overall properties as compared to the conventional BisGMA/TEGDMA based resins seems only moderate for the present time(Table1). It can be shown from the table that most commercial dental composites depend on their composition on the conventional BisGMA/TEGDMA formulation. Moreover it must be noted that while BPA and BPA derivatives are being put under scrutiny, studies show that new BPA free materials claimed to be safer sometimes are equally toxic. Thus Several studies state that TEGDMA, one of the main compounds leaching from polymerized resins is highly cytotoxic and moderately genotoxic. 53,6062In conclusion, while primary reports for new materials and additions seem mostly encouraging; sufficient in vitro and in vivo tests should be operated before drawing any conclusions, or commercial use of these materials.

Table. 01 Materials, manufacturer and chemical composition of the matrix

Material Manufacturer/batch Resin matrix
Adamant Cavifil Vivadent/E 52179 BisGMA, UDMA, TEGDMA
Arabesk Top VOCO/94816 BisGMA, UDMA, TEGDMA
Ariston pHc Vivadent/B21705 BisGMA, UDMA, TEGDMA
Beautifil Shofu/050143 BisGMA, TEGMA
Herculite XRV Kerr/909065 BisGMA, TEGMA
Charisma Heraeus Kulzer/10023 BisGMA, TEGMA
Clearfil ST Kuraray/00002A BisGMA, TEGMA
Point 4 Kerr/102A48 BisGMA, TEGMA
Kurary Clearfil Majesty Bis-GMA, TEGDMA
Venus Heraeus Kulzer/010022 BisGMA, TEGDMA
Esthet X Dentsply/0112121 BisGMA, BisEMA, TEGDMA
Brillant Coltene/IA350 BisGMA, BisEMA, TEGDMA
Synergy Duo Shade Coltene/IG079 BisGMA, BisEMA, TEGDMA
Prodigy Kerr/812898 BisGMA, TEGDMA, EBADM,UV-9
Tetric Vivadent/C16884 BisGMA; UDMA, TEGDMA
Tetric Ceram Ivoclar-Vivadent D00037 BisGMA, UDMA, TEGDMA
Z250 3M ESPE/20011016 BisGMA, UDMA, BisEMA
Filtek Silorane 3M ESPE/A-094 3,4-Epoxycyclohexylethylcyclo-polymethylsiloxane Bis-3,4-epoxycyclohexylethyl-phenylmethylsilane

Note: Composition as supplied by the manufacturers

Type of cure and duration

The curing mode plays an important role in controlling the degree of toxicity of dental restorative resins, chemical-cured materials were found to be more cytotoxic than the light-cured material.63Kopperud et al.64 demonstrated that reduced exposure time even with high intensity LEDs results in inferior curing depth and increased leaching of monomers.

On the other hand, the light-curing polymerization process with its different parameters whether light spectrum, power density, and polymerization time has a direct influence on the degree of polymerization of the composite, eventually leading to different releasing rates of BPA or unreacted BPA based monomer.65Santini et al.66 found that polywave LEDs significantly improved both the degree of conversion of materials which contain TPO initiator.Miletic et al.67 in their comparison of polywave and monowave LED light-curing unit (LCU), found polywave LED LCU more efficient in curing TPO -containing materials compared to CQ–amine only or the combined TPO and CQ–amine system.

Sigusch and collaborators65 found that the concentration of the released monomers UDMA and BIS-GMA in the composite varies with the light energy used, they also found that the size of the filler has an influence on the transmission of the curing light by the material, they recommended the use of high power density units to decrease the release of toxic substances; and that composites and light curing units should be harmonized with one another for achieving maximal biocompatibility. Durner et al.8 studied the various factors controlling the elution of substances from polymerized and non-polymerized dental restorative materials, they found that, the wavelength, wavelength-distribution and intensity of the light source, as well as the distance light source – dental material, the hardening time, the composition and the color of the dental material are all factors that control their degree of toxicity.

Materials affecting toxicity

In the various studies reviewed in this work, some materials were added to the dental restorative with the intention of decreasing its toxicity, while other materials were added only to improve the mechanical properties, decrease the polymerization shrinkage of dental restoratives, or for antibacterial effect, never the less these materials had an important effect on the toxicity of dental resins, mostly indirectly through their action on the polymerization reaction and the amount of monomers eluted from the dental restorative materials.

Morgan et al.[68] studied the potential protective effect of cinnamon against BPA-induced oxidative stress, on the other hand multiple studies examined the effect of adding antioxidants to counter the cytotoxicity of monomers.It was shown that N-acetyl cysteine (NAC) was able to prevent cell damage induced by all materials tested, incorporation of NAC into a dental resin has been shown to restore the suppressed viability and function of dental pulp cells or oral fibroblasts on the resin substrate to a biologically relevant degree, and to protect against BPA-induced cognitive dysfunctions and oxidative stress in rats. 50,6976It was found that NAC acts not only as a direct oxidant scavenger, but also improves the intracellular glutathione systems compromised by oxidative stress.72 Other studies, considered the action of chitosan in decreasing the risk associated with the use of UDMA.40

Not all additions have effect on the polymerization reaction, and the toxicity potential of resin materials; for example the incorporation of 2% proanthocyanidin into dental adhesives,77 or silane treatment modifications to increase the bond strength between composite resins and leucite reinforced feldspathic ceramic.78 Also the addition of synthetic antimicrobial polymers with their prolonged antimicrobial activities and non-toxic and non-irritant properties had no effect on the polymerization reaction, compared with ordinary low molecular weight antibacterial agents, which present some disadvantages, such as toxicity and short-term antimicrobial ability.79Several reports investigated the antibacterial and mechanically strong nano composites incorporating a quaternary ammonium dimethacrylate (QADM), nanoparticles of silver (NAg), and nanoparticles of amorphous calcium phosphate (NACP). They found that Ag has a low toxicity and good biocompatibility with human cells, and a long term antibacterial effect due to sustained silver ion release. 8082

On the other hand, someadditions had an effect on the curing reaction; silicone-based additives can accelerate or retard the reaction, depending on the presence or absence of DMA.83 While liquid Rubber (LR) though increased the mechanical properties lowered the crosslink density of 50/50 Bis- GMA/TEGDMA resin.84 Musanje et al.85 studied the optimal concentration of photo initiators, whether CQ or ethyl-4-dimethylaminobenzoate, needed for maximum polymerization, and sufficient depth of cure, that would consequently affect the amount of available free monomers to be leached. Polydorou86 studied the effect of bleaching on the elution of monomers from two modern composite materials, the bleaching agents tested reduced the amount of some of the monomers released from the two composite materials, and he concluded that the contact of bleaching agents with composite materials may not have any detrimental results for the human health.

To our knowledge, most of the materials added to the dental restoratives in an effort to reduce its toxic effects whether directly or indirectly have not yet been used in commercial composites, and albeit the initial success for these materials to combat toxicity; more studies need to be performed in vivo, and long lasting effects have yet to be considered.


The present systemic review aims to provide an exhaustive summary of current literature related to the potential cytotoxicity of BPA and other materials in dental restorative resins.

A controversy still exists about the actual risk of use of BPA and BPA derivatives in dental materials, and the degree of elution from dental restorations, and whether toxicity studies conducted on animals reflect their actual toxicity on humans.

It must be noted that while BPA and BPA derivatives are being put under scrutiny, studies show that new BPA free materials claimed to be safer; sometimes are equally toxic.

Any of the factors that affect the degree of convergence and the depth of cure of the dental resin havea direct effect on the degree of BPA toxicity and the degree of eluted toxic monomers.Several studies have shown that the simple act of gargling water for 30 seconds after application of the dental sealant or composite or washing the surface for 30 seconds with an air-water syringe while suctioning fluids and debris from the mouth, has been shown to decrease salivary BPA levels to nearly baseline, and pumice on a cotton ball or in a rotating rubber dental prophylaxis cup was highly effective in removal of residual monomer and eliminating absorption of bis-DMA, bis-GMA, and TEGDMA. 1,87

The development of dimethacrylate derivatives of BPA has been an active research area. Recent developments regarding public perceptions of bisphenol toxicity may have a strong influence on steering future monomer development efforts toward BPA alternatives.

Competing interests:

The authors declare that no competing interests.

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