The issue. The controversy about Bisphenol A (BPA) and its potential impact on health and human development received increased media attention in the past year. Headlines have linked BPA to heart disease, coronary artery disease, obesity, diabetes, and immune system and reproductive disorders.

BPA is a common component used to make polycarbonate plastic and epoxy resins. Polycarbonate plastics are found in countless everyday items such as food and beverage containers, eye glasses, cell phones, bike helmets, children’s toys, plastic tableware, some types of receipts, self-adhesive labels and a host of other consumer products. Epoxy resins are often used as protective coatings inside metal food cans. The primary source of exposure to BPA for most people is assumed to occur through the diet1 although industrial and household wastes released into the environment are other sources.

BPA, which has been used in consumer products since the 1960s, was used in the manufacture of some dental materials.2-4 Dental sealants were identified in 1996 as a source of very low-level BPA exposure5 and a recent study published in the Journal of the American Dental Association reports that “placement of resin-based composite restorations was associated with detectable increases in saliva of BPA and other study compounds within one hour after restoration placement and increased concentration of BPA in urine nine to 30 hours after restoration placement.”6

Some manufacturers of dental composites and sealants market their products as “BPA-free,” yet some studies have detected BPA in the saliva of patients within minutes following placement. BPA-free usually means that no BPA is added to the product, or that residual BPA is below the detection limit of the analytical method used to make the claim.

So, why would BPA appear in “BPA-free” dental materials?

Composite restorative materials are made from a mixture of ingredients where bisphenol A glycidyl methacrylate (bis-GMA) is the major component. BPA is a critical starting material used to manufacture bis-GMA and many other methacrylates used in sealants and bonding materials.

Looking at the structures of BPA and estradiol (Fig.1) you will find similar features between the two compounds that impart at least some ability for BPA to bind to mammalian estrogen receptors.5

Bis-GMA is an extremely viscous material making inclusion of polymerization initiators very difficult without adding modifiers to change its handling properties. An example of one of these modifiers is bisphenol A dimethacrylate (bis-DMA), which, when mixed with bis-GMA, reduces viscosity sufficiently to allow the addition of stabilizers and polymerization initiators resulting in a homogeneous mixture that is easily handled. BPA also is used to synthesize bis-DMA.

Materials containing bis-DMA can release very small quantities of BPA after coming in contact with salivary enzymes (esterases) (Fig.2).7

Several alternative aliphatic viscosity modifiers often are used instead of bis-DMA. One of these alternatives is TEGDMA, which is not synthesized from BPA, nor does it decompose to BPA (Fig 3).

Materials made with bis-GMA do not undergo esterase hydrolysis.7 Sealants, bonding agents and composite resins developed with bis-DMA and/or bis-GMA may contain trace amounts of BPA as a byproduct of the manufacturing process. Careful formulation during the manufacturing process for bis-GMA keeps the unreacted levels of BPA to a minimum, but some residual trace levels of BPA can remain. Manufacturers of materials containing dental resins do not manufacture bis-GMA themselves. Bulk bis-GMA is purchased from at least 22 worldwide suppliers of bis-GMA.8 Four suppliers are based in the United States, 11 in mainland China, three in Hong Kong, three in Germany and one in the United Kingdom. It is unknown how well residual levels of BPA are controlled among these manufacturers.

Polymerization of bis-GMA containing materials involves free-radical chemical reactions. Oxygen in the air interferes with this process causing incomplete polymerization at the bis-GMA/air interface. Thus, any newly placed restoration or sealant will have a thin surface layer of incompletely polymerized material, which is rapidly lost within hours post-placement. This could be the reason that the Kingman study6 detected higher levels of composite components (including BPA as well as bis-GMA) in saliva and urine after placement than before placement. However, as in other studies, component release became significantly reduced or undetectable within hours,6 and exposure to these substances seems to be acute, not chronic.

What level of BPA exposure produces harmful effects in humans?

This is a key question and the subject of active research today. A decade or more ago, several studies showed that clinical levels of BPA in various body fluids were transient and rapidly fell below the detection limit of 1.0 to 5.0 ng/mL (1.0 - 5.0 ppb) by the high pressure liquid chromatography (HPLC) methods used at that time. However, a proliferation of subsequent studies using more sensitive liquid chromatography/mass spectrometry (LCMS) analytical methods reduced BPA detection limits to 0.02 ng/mL (50 times lower). The more sensitive methods appeared capable of detecting BPA at significantly lower levels than the earlier methods. Furthermore, other studies implicated dental resins as a potential cause of harmful effects such as neurobehavioral disorders9 or obesity in children.10 In an apparent response to concerns surrounding potential harmful effects of dental resins, many dental resin manufacturers have stated that their product contains no detectable level of BPA. However, manufacturers often do not state the detection limit or the analytical method employed. Any dental material made with bis-GMA potentially can contain trace levels of BPA.

The fact that the presence of a perceived harmful material can be detected does not mean the material is harmful at that detection limit. More than 500 years ago, a German physician, Philippus von Hohenheim, better known as Peracelsus, stated:

“All substances are poisons; there is none which is not poison. The right dose differentiates a poison from a remedy.”11

In other words, the dose makes the poison. This is an extremely important concept that the dental professional always must be mindful of when evaluating studies or reports claiming that a toxic substance was found in a dental material.

Patients may be alarmed by media reports of environmental exposure to BPA from a multitude of common items, and the media reports usually mention dental materials in the same breath.

Acceptable BPA exposure limits are:

EPA:12 <0.05 mg/kg body weight/24 hours, which is the same as <50,000 ng/kg/day

Thus for a 70 kg man = 3.5 x 106 ng/day, and for a 10 kg child = 0.5 x 106 ng/day

The National Toxicology Program (NTP)17

suggested: 10,000 ng/kg/day

The recent Kingman study6 measured BPA concentrations in the saliva of study subjects before and after placement of a composite resin restoration. Salivary concentrations of BPA should represent the highest measurable indicator of BPA exposure from composite resin, since saliva is in direct contact with the resin. Salivary concentration should thus be a good indicator of exposure. Salivary BPA measured before placement accounts for any BPA exposure from pre-existing sources and serves as a baseline level. Subtracting the BPA concentrations following placement is an indicator of the amount of BPA originating directly from the composite.

Geometric means were calculated for three sampling periods post-placement: 0-1; 1-8; and 9-30 hours. The geometric mean average of BPA in saliva within the first hour of placement was 0.21 ng/mL. Following composite placement from one to 30 hours, BPA was not detected in saliva at levels above baseline.6 This indicates that BPA exposure from composite placement is very short and does not persist in saliva in detectable amounts after 60 minutes.

Therefore, these data suggest that the estimated oral BPA exposure from one composite resin restoration over 24 hours is 0.00875 ng/mL saliva/hour. A nanogram is one-millionth of a mg. If we assume average saliva production of 0.5 mL/minute or 30 mL/hour, and an average body weight of 70 kg for each study participant, then the BPA exposure following composite placement is about 6.3 ng/70 kg within the first hour. Since salivary BPA levels were not significantly different from pretreatment baseline levels after one hour and up to 30 hours post-treatment, the average adult daily dose of BPA from one composite resin restoration was 6.3 ng. Another study looked at BPA in saliva following sealant (no bis-DMA) placement in adults. Analysis found an average of 0.32 ng/mL of BPA in saliva immediately following treatment, and essentially no BPA was detected in saliva in excess of pretreatment levels one hour after placement of sealant on an average of six teeth.13

The above two clinical studies show that BPA exposure from current bis-GMA based composites and sealants is more than 500,000 times lower than the EPA acceptable daily exposure limit for adult humans. If the more conservative NTP exposure limit is used, then BPA exposure from one composite is more than 100,000 times lower. The margin of safety is several orders of magnitude lower than either exposure limit. Trace levels of BPA from dental resins do not appear to present a health hazard based on current exposure limits, especially when one considers that the exposure predominantly is acute only during the first hour post-treatment.

Urethane modified methacrylate restorative resins (UDMA) are available and are not manufactured from BPA (Fig. 4). However, their use as a bis-GMA resin alternative is limited because they do not develop equivalent stiffness and hardness characteristics as bis-GMA based restoratives.14 Consequently, use is restricted primarily to low-stress surfaces.

Some earlier studies in rodents suggested significant harmful reproductive effects from very low levels of BPA exposure, much lower than the EPA acceptable level, and may have raised concerns that similar exposure levels could have the same effect in humans. However, recent studies have challenged that notion by showing that primates metabolize ingested BPA differently from rodents. Newborn monkeys were found to have a high capacity for inactivating BPA in contrast to newborn rodents. Blood levels of equivalent BPA exposures were found to be 10-fold lower in rhesus monkeys than in rats and mice.15 Another study showed that people who ingested high levels of BPA in their diet did not show high levels of BPA in their blood, which supported findings in the primate studies.16

Despite an absence of documented adverse health risks related to these dental materials, some patients may be concerned. Nevertheless, the benefits of composite resin materials for restoring oral health and preventing caries is well established, while any health risks from their use is not. In 2007, the U.S. Department of Health and Human Services stated that, “Dental sealant exposure to bisphenol A occurs primarily with the use of dental sealants [containing] bisphenol A dimethacrylate. This exposure is considered an acute and infrequent event with little relevance to estimating general population exposures.”17 Furthermore, the medical community continues to support the use of resin-based dental materials based on their proven benefits and brevity of BPA exposure.18

(Editor’s note: A future issue of the ADA Professional Product Review will feature “An Evaluation of Bisphenol A found in Dental Materials,” in which we will report ADA Laboratory test results of BPA and bis-DMA levels from a variety of dental composites, sealants and bonding materials. Although these data will not use human subjects, they will give insight to the potential patient exposure levels of BPA from known amounts of product resin.)

ABBREVIATION KEY Bisphenol A (BPA): A chemical produced in large quantities for use primarily in the production of polycarbonate plastics and epoxy resins. Bis-GMA: Bisphenol A-glycidyl methacrylate. Bis-DMA: Bisphenol A-dimethacrylate. TEGDMA: Triethylene glycol dimethacrylate. UDMA: Urethane dimethacrylate.

BPA and Dental Materials: Addressing Patient Concerns

Here are some key points that can help you answer patient questions about BPA:

• According to manufacturers, BPA is not an added ingredient in dental composites or sealants currently on the market.

• The main ingredient in most commonly used composites and sealants is bis-GMA, which has been shown to be stable within the mouth and does not decompose to BPA over time.

• Trace amounts of BPA present in raw bis-GMA are a residue of its manufacturing process.

• Some products contain added bis-DMA as a bis-GMA viscosity modifier. Bis-DMA is known to decompose to BPA in the presence of salivary esterases (enzymes). However, many current dental resins severely limit or eliminate all bis-DMA from their formulations.

• Although trace levels of BPA can be detected in dental products containing bis-GMA, the potential exposure level is at least 100,000 times lower than current exposure limits.

• BPA exposure from dental materials likely lasts only a few hours after placement of a composite or sealant. Therefore, any BPA exposure is brief and transient.

• The preponderance of scientific data over the past 15 years indicates that the amount of BPA exposure from dental restoratives does not present a health hazard.

References

1. NTP-CERHR Monograph on the Potential human reproductive and development effects of bisphenol A. National Toxicology Program, U.S, Department of Health and Human Services. National Institutes of Health. NIH Publication No. 08-5994. 2008.

2. Bowen RL. Use of epoxy resins in restorative materials. J Dent Res; 1956;35:360-9.

3. Bowen RL. Properties of a silica-reinforced polymer for dental restorations. JADA 1963;66:57-64.

4. Bowen RL, inventor. Method of preparing a monomer having phenoxy and methacrylate groups linked by hydroxy glycerol groups. U.S. patent 3179623. April 1965.

5. Olea N., et al. Estrogenicity of resin-based composites and sealants used in dentistry. Envirnomental Health Perspectives, 1996. vol. 104, pgs. 298-305.

6. Kingman A, Hyman J, Masten SA, Jayaram B, Smith C, Eichmiller F, Arnold MC, Wong PA, Schaeffer JM, Solanki S, Dunn WJ. Bisphenol A and other compounds in human saliva and urine associated with the placement of composite restorations. JADA 2012;143(12):1292-302.

7. Atkinson JC, Diamond F, Eichmiller F, Selwitz R, Jones G. Stability of bisphenol A, triethylene-glycol dimethacrylate, and bisphenol A dimethacrylate in whole saliva. Dent Ma¬ter.;18(2):128-35.

8. Chemical Register for CAS 1595-94-2 (http://www.chembuyersguide.com/index.cfm?P=search). Accessed January 31, 2013.

9. Maserejian NN, Trachtenberg FL, Hauser R, McKinlay S, Shrader P, Tavares M, Bellinger DC. Dental composite restorations and psychosocial function in children. Pediatrics 2012. Aug;130(2):e328-38. doi: 10.1542/peds.2011-3374. Epub 2012 Jul 16.

10. Trasande L, Attina TM, Blustein J. Association between urinary bisphenol A concentration and obesity prevalence in children and adolescents. JAMA 2012. 19;308(11):1113-21.

11. Klassen CD. Casarett & Doull’s Toxicology, 5th edition. Chapter 1. McGraw-Hill, ISBN 0-07-105476-6.

12. US Environmental Protection Agency, Integrated Risk Information System: Bisphenol A (CASRN 80-05-7). http://epa.gov/iris/subst/0356.htm Accessed January 31, 2013.

13. Joskow R, Barr DB, Barr JR, Calafat AM, Needham LL, Rubin C. Exposure to bisphenol A from bis-glycidyl dimethacrylate-based dental sealants. JADA 2006, 137(3):353-62.

14. Lemon MT, Jones MS, Stansbury JW. Hydrogen bonding interactions in methacrylate monomers and polymers. J Biomed Mater Res A 2007.;83(3):734-46.

15. Doerge DR, Twaddle NC, Vanlandingham M, Fisher JW. 2011.Pharmacokinetics of bisphenol A in neonatal and adult CD-1 mice: inter-species comparisons with Sprague-Dawley rats and rhesus monkeys. Toxicol Lett.;207(3):298-305. doi: 10.1016/j.toxlet.2011.09.020. Epub 2011 Sep 29.

16. Teeguarden JG, Calafat AM, Ye X, Doerge DR, Churchwell MI, Gunawan R, Graham MK. 2011. Twenty-four hour human urine and serum profiles of bisphenol a during high-dietary expo¬sure. Toxicol Sci 2011. 123(1):48-57. doi: 10.1093/toxsci/kfr160. Epub 2011 June 24.

17. National Toxicology Program. Center for the Evaluation of Risks to Human Reproduction. Monograph on the Potential Human Reproductive and Developmental Effects of Bisphenol A. NIH Publication No. 08-5994, September 2008.

18. Fleisch AF, Sheffield PE, Chinn C, Edelstein BL, Landrigan PJ. Bisphenol A and related compounds in dental materials. Pediatrics 2010. 126(4):760-8. doi: 10.1542/peds.2009-2693. Epub 2010 Sep 6.