FDI review of the scientific evidences on BPA in Restorative Materials

This review of the literature will be continuously updated by FDI and is only a support document to the Policy statement.
Only the Policy statement on Bisphenol-A in Dental Restorative and Preventive Materials
was approved by General Assembly in 2013.

Bisphenol-A (BPA) is an endocrine active synthetic substance and thus has attracted considerable attention in the public and in the scientific community as an endocrine disrupting chemical (EDC). It may be released from a large variety of materials of daily use, e.g. from polycarbonate based food containers, and plastic bottles. In this context, the BPA exposure of the general population from certain resin based dental restorative materials including resin fissure sealants has been highlighted [1].

Indeed, BPA is part of the molecules (e.g. Bis-GMA and Bis-DMA) which are very often used in dentistry like resin based materials for fillings, fissure sealants, luting materials, crown built-ups and bondings of brackets and orthodontic bands [2, 3]. BPA may be also used during the production process of the above mentioned materials and thus the final product may be contaminated with BPA.

Bisphenol-A (BPA) was claimed to be released from resin based materials [4, 5] with more BPA being eluted in the polymerized state of the composite resin than in the unpolymerized. These data, however, were heavily questioned. The fact that from unpolymerized samples fewer substances are released than from polymerized ones is in contradiction to other reports (see below). Furthermore, a large number of other authors who studied BPA release using a large variety of test methods and materials could not detect BPA with the exception of a Bis-DMA containing sealant [1, 6]. Because of the contradictory results, the analytical methods used [4, 5] were questioned [1, 6, 7, 8, 9].

However, it was consistently shown that materials containing Bis-DMA released BPA immediately after application into saliva, but to a much lesser extent than in the report cited above and 24 hours after placement BPA concentration in saliva of these patients was down to the level before [2, 10].  In the same study, a Bis-GMA-based pit and fissure sealant that contained no primary BPA contamination was not found to release BPA into saliva. BPA release from Bis-DMA containing sealants have been reported by other authors [e.g. 11]. BPA could not be detected in the blood samples, and urine content of BPA was most elevated in patients after Bis-DMA material application one hour after placement and then decreased after 24 hours.

It was shown that Bis-DMA is cleaved hydrolytically under alcaline conditions, enzymatically using porcine esterases and in contact with human saliva and BPA could be detected, but this is not the case with Bis-GMA [2]. It can be concluded that Bis-DMA is initially eluted from Bis-DMA-containing pit and fissure sealants, which is then degraded to BPA in saliva. BPA degradation from Bis-GMA could not been shown under the given analytical conditions [2].

In another clinical study on 172 patients it was shown, that placement of resin-based composite restorations was associated with increases of BPA in saliva for a short time but in urine for about 30 hours [14].

As BPA is used during the production process of Bis-GMA, and therefore BPA impurities in Bis-GMA resins may be possible. These have been estimated [7, 8] to be at maximum 10µg/g unpolymerized resin. Experimental addition of 100 µg/g of BPA to a composite resin resulted in a BPA release being less fast than for TEGDMA, and over ten years 12% (water) or 53% (methanol) BPA from the original BPA content of the resin was calculated to be released. From 1 g of this resin within 10 years patients may be exposed to minute amounts of 4 (water) or (methanol) 16ng/day [8].

In vitro grinding studies under simulated conditions revealed a sample which was eluted in saline for one month at 37°C. MCF-7 cells were exposed to these extracts and increased growth rate indicated estrogenic activity. Clinical relevance is, however, still unclear; but the authors mention that dental personnel may be exposed several times per day to such aerosols [15].

In another study the effects of leached components from a resin-based dental composite on female mouse fertility was investigated. The results revealed a significant reduction of pregnancies: 54,5 % vs 100 % (control). The authors conclude, that TEGDMA was the major leached component followed by BPA [16].

Summarizing the data it can be stated that patients may only be exposed to minute amounts of BPA from Bis-GMA resins due to possible impurities. From materials containing Bis-DMA, BPA exposure for patients could consistently be found, but mainly during the first 24 hours after placement. The consequence of the dust derived from composite grinding is unclear.

All estimates on the biological role of BPA in general and the relative importance of BPA from dental materials depend on a number of variables; e.g. the sensitivity and validity of the analytical methods used for BPA determination in different body fluids [13]. Furthermore, the relevance of biological endpoints to be used for risk assessment is still under discussion. Therefore, the literature and position statements from national and international competent authorities need meticulously be followed. 

References

1. Fleisch AF, Sheffield PE, Chinn C, Edelstein BL, Landrigan PJ. Bisphenol A and related compounds in dental materials. Pediatrics 2010 Oct;126(4):760-8.
2. Schmalz G, Preiss A, Arenholt-Bindslev D. Bisphenol-A content of resin monomers and related degradation products. Clin Oral Investig 1999 Sep;3(3):114-9.
3. Tarumi H, Imazato S, Narimatsu M, Matsuo M, Ebisu S. Estrogenicity of fissure sealants and adhesive resins determined by reporter gene assay. J Dent Res 2000 Nov;79(11):1838-43.
4. Olea N., Pulgar R., Perez P., Olea-Serrano F., Rivas A., Novillo Fertrell A., Pedraza V., Soto A. M., Sonnenschein C.: Estrogenicity of resin based composites and sealants used in dentistry. Environ Health Perspect 104, 298 – 305 (1996).
5. Pulgar R., Olea-Serrano M. F., Novillo-Fertrell A., Rivas A., Pazos P., PedrazaV., Navajas J. M., Olea N.: Determination of bisphenol A and related aromatic compounds released from BisDMA-based composites and sealants by high performance liquid chromatography. Environ Health perspect 108, 21-27 (2000).
6. Schmalz G., Arenholt-Bindslev D.: Biocompatibility of dental materials. Springer, Berlin, Heidelberg (2009).
7. Imai, Y., Comments on “Determination of Bisphenol A and Related Aromatic Compounds Released from Bis-GMA-Based Composites and Sealants by High Performance Liquid Chromatography”. Environmental Health Perspectives, 108 (12), 545 (2000)
8. Imai, Y and Komabayashi, T., Elution of Bisphenol A from Composite Resin: A Model Experiment. Dental Materials Journal 19 (2): 133-138, 2000
9. Myers DE.  Hutz RJ.  Current status of potential bisphenol toxicity in dentistry. [Review] General Dentistry.  59(4):262-5, 2011
10. Arenholt-Bindslev D., Breinholt V., Preiss A., Schmalz G.: Time-related bisphenol-A content and estrogenic activity in saliva samples collected in relation to placement of fissure sealants. Clin Oral Investig 3, 120 – 125 (1999).
11. Joskow R., Barr D. B., Barr J. R., Calafat A. M., Needham L. L., Rubin C.: Exposure to bisphenol A from bis-glycidyl dimethacrylate-based dental sealants. J Am Dent Assoc 137, 353 – 362 (2006).
12. Gioka C, Eliades T, Zinelis S, Pratsinis H, Athanasiou AE, Eliades G, et al. Characterization and in vitro estrogenicity of orthodontic adhesive particulates produced by simulated debonding. Dent Mater 2009 Mar;25(3):376-82.
13. Dekant W, Volkel W. Human exposure to bisphenol A by biomonitoring: methods, results and assessment of environmental exposures. Toxicol Appl Pharmacol 2008 Apr 1;228(1):114-34.
14. 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): 1292-1302.
15. Van Landuyt KL, Yoshihara K, Geebelen B, Peumans M, Godderis L, Hoet P, Van Meerbeek B: Should we be concerned about composite (nano-)dust? Dental Materials 28 (2012) 1162-1170.
16. Al-Hiyasat AS, Darmani H, Elbetieha AH. Leached components from dental composites and their effects on fertility of female mice. Eur J Oral Sci 2004; 112: 267-272.

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