How much do resin-based dental materials release? A meta-analytical approach

Abstract

Objectives

Resin-based dental materials are not inert in the oral environment, and may release components, initially due to incomplete polymerization, and later due to degradation. Since there are concerns regarding potential toxicity, more precise knowledge of the actual quantity of released eluates is necessary. However, due to a great variety in analytical methodology employed in different studies and in the presentation of the results, it is still unclear to which quantities of components a patient may be exposed. The objective of this meta-analytical study was to review the literature on the short- and long-term release of components from resin-based dental materials, and to determine how much (order of magnitude) of those components may leach out in the oral cavity.

Methods

Out of an initial set of 71 studies, 22 were included. In spite of the large statistical incertitude due to the great variety in methodology and lack of complete information (detection limits were seldom mentioned), a meta-analytical mean for the evaluated eluates was calculated. To relate the amount of potentially released material components with the size of restorations, the mean size of standard composite restorations was estimated using a 3D graphical program.

Results

While the release of monomers was analyzed in many studies, that of additives, such as initiators, inhibitors and stabilizers, was seldom investigated. Significantly more components were found to be released in organic than in water-based media. Resin-based dental materials might account for the total burden of orally ingested bisphenol A, but they may release even higher amounts of monomers, such as HEMA, TEGDMA, BisGMA and UDMA. Compared to these monomers, similar or even higher amounts of additives may elute, even though composites generally only contain very small amounts of additives. A positive correlation was found between the total quantity of released eluates and the volume of extraction solution.

Significance

There is a clear need for more accurate and standardized analytical research to determine the long-term release from resin-based materials. Several guidelines for standardization are proposed.

Introduction

In spite of 150 years’ worth of good clinical performance, the use of amalgam as a tooth filling material remains controversial. The most common allegations against amalgam are environmental pollution and possible hazardous health effects due to release and systemic uptake of mercury . The ongoing discussion about the safety of amalgam has also led to an increased focus on the safety of resin-based restorative materials . The use of resin-based materials in dentistry is nowadays ubiquitous, and during the past decades composite restorations have proved to be a satisfying alternative for amalgam to restore traumatized and decayed teeth .

Resin-based dental materials generally consist of a polymer matrix and inorganic filler particles that are attached to the resin matrix through a siloxane coupling . The most common resins used in dentistry are (meth)acrylates , but recently, new resin systems, such as ormocers (polysiloxane backbone with methacrylate sidebranches) and siloranes (silorane ringopening system) have been introduced .

Despite their growing popularity, there are concerns that resin-based materials may be toxic based on the fact that they may release components . Three main routes of systemic intake of chemical substances released by resin-based restorations have been postulated: the first through ingestion of released compounds in the gastro-intestinal tract, the second through diffusion to the pulp through the dentinal tubules , and the third via uptake of volatile components in the lungs . The last route is of special importance for the dental practitioner and the dental personnel, while the first and second route are more relevant for the patient.

Resin-based materials may release unpolymerized monomers, additives and filler components in the oral environment after placement of the restoration. Even though the patient may come into contact with large amounts of uncured monomers during the placement of the composite restoration, the release of unpolymerized monomers after polymerization causes most concerns in literature. Under clinical circumstances with a short curing time of usually not more than 40 s, and a temperature around 37 °C in the oral cavity, composites are never polymerized to a full extent as the propagation of the crosslinking reaction drastically reduces the mobility of the monomers . As a result, not only unbound substances, like additives, but also uncured monomers can leach out. Depending on the resin-based material, the degree of conversion can vary between 50 and 70% . The maximum degree of conversion is reached only after 24 h due to a post-cure process (‘in-the-dark’ polymerization), which signifies that the polymerization rate immediately after light-curing may be even lower (30–40%) . Filler leachability encompasses both release of complete filler particles after hydrolysis of the filler-matrix siloxane bond, and the release of filler components, such as SiO 2 , Ba, Sr, Na due to hydrolysis and ion-exchange mechanisms . Release of filler components has mainly been associated with progressive wear of composites; however little is known regarding possible health effects.

Intra-oral degradation processes may induce additional release of components from resin-based restorations . First, mechanical , hydrolytic and enzymatic degradation may result in chain scission and release of polymeric breakdown products in the form of monomeric or oligomeric molecules. Most of these degradation products have probably not yet been identified . Second, aging of composite materials may also lead to more porosities due to an interplay of mechanical swelling and water sorption and chemical/enzymatic degradation , and thus result in increased release of unpolymerized monomers that were initially trapped in the polymer network .

In literature, there are many indications that release of monomers and of some additives are potentially dangerous and might have compromising local or even systemic effects . Apart from the well-documented allergenicity of monomers , several ingredients have been shown to be cytotoxic , genotoxic and mutagenic , and toxic to the reproductive system . Besides the identification of hazards, risk assessment requires an accurate knowledge of the amounts of released compounds .

In spite of many analytical studies, the lack of standardized methodologies for quantification and of uniformity in presenting the results hinders correct interpretation of the quantities of released eluates. In other words, it is still unclear to what amount of specific components a patient may be exposed. This makes risk assessment of possible health hazards due to resin-based dental materials problematic. The objective of this study was to review peer-reviewed international literature on the unintended release of ingredients in the oral environment. Since there have been very few in vivo studies , only in vitro studies were included in this review. The quantities measured in studies that quantified the amount of released ingredients, were converted to a common unit. The main purpose was to gain knowledge on the total quantity of compounds that can be released by resin-based dental materials in the oral cavity.

Materials and methods

Search strategies

Using different online databases (PubMed, Web of Science and Embase), the international literature available until January 2010 was searched for papers that reported on the elution process of dental resin-based materials. The used keywords were: ‘resin-based’, ‘elution’, ‘eluate’, ‘dental composite’, ‘HPLC’, ‘LC’, ‘LC–MS’, ‘quantification’, ‘release’, ‘substances’, ‘ingredients’, ‘components’. Besides database searches, several papers (42%) were found by means of references in other papers.

Inclusion/exclusion criteria

Data have been included only from studies (1) in which the release of components was quantified in vitro by incubating a sample of resin-based material in a solvent for a certain period of time (at least 24 h), (2) in which there was no pre-incubation period (so that all possible eluates were quantified after polymerization of the sample) , and (3) in which the quantified data could be re-calculated to a molar quantity (mol) per volume or surface area of the tested specimens. Depending on the units used, this implied that the volume of the extraction solvent and the dimensions of the tested resin-based material needed to be mentioned. (4) In spite of the lack of standardization of the measurement intervals, most often researchers still measured the release after a 24-h time interval. It was therefore decided to include only papers that analyzed the released components after a 24-h or longer time interval. Studies that measured the release after several minutes were not included . (5) Papers in which a relative (semi-quantitative) quantification was performed, could not be included . (6) Studies in which released substances were measured in vivo , or in which the release and migration of components through the dentin were measured were also not included.

For those papers in which not all necessary information had been provided in the paper, attempts were made to obtain necessary information by contacting (email, letter) the corresponding author or co-authors. Papers with missing information that could not be recovered in this way, were not included. These inclusion criteria are listed in Table A1 .

Re-calculation of the average released quantity

Release data were expressed in a plethora of units (μg/ml, ppm, mmol/ml, mg/g, wt/wt%, μg/cm 2 ) ( Table 1 ). Therefore data were re-calculated and expressed in mol per volume of the resin sample and mol per surface area of the resin sample . The calculations are shown in Appendix calculations ). Since most researchers analyzed the incubation solution at 24 h, this was taken as a reference for comparison between the different studies included. For periods longer than 24 h, the total cumulative value of release for a compound was computed. The calculations can be found in Appendix A .

Table 1
Studies that met the inclusion criteria and could be included in the quantitative review.
Authors Title Journal Resin-based material Analytical method Units Quantified eluates Incubation medium
1 Al-Hiyasat AS, Darmani H, Milhem MM Cytotoxicity evaluation of dental resin composites and their flowable derivatives Clin Oral Investig 2005;9:21–5 Composite filling material HPLC μg/ml Bis-EMA
BisGMA
BPA
TEGDMA
UDMA
Culture medium without serum
2 Darmani H, Al-Hiyasat AS, Milhem MM Cytotoxicity of dental composites and their leached components Quintessence Int 2007;38:789–95 Composite filling material HPLC μg/ml BPA
BisGMA
TEGDMA
Bis-EMA
UDMA
Dulbelco’s modified eagles medium without serum
96% ethanol/water
3 Hamid A, Hume WR A study of component release from resin pit and fissure sealants in vitro Dent Mater 1997;13:98–102 Sealants HPLC nmol/mm 2
pmol/mm 2
TEGDMA
BisGMA
BPA
BHT
CQ
UDMA
TMA
HEMA
Distilled water
4 Imazato S, Horikawa D, Nishida M, Ebisu S Effects of monomers eluted from dental resin restoratives on osteoblast-like cells J Biomed Mater Res B: Appl Biomater 2009;88:378–86 Composite filling material
RM-GI cements
HPLC μg/ml TEGDMA
MMA
HEMA
Distilled water
5 Imazato S, Horikawa D, Ogata K, Kinomoto Y, Ebisu S Responses of MC3T3-E1 cells to three dental resin-based restorative materials, J Biomed Mater Res A 200615;76:765–72 Composite filling material
RM-GI cements
HPLC μg/ml BisGMA
TEGDMA
MMA
HEMA
Distilled water
6 Kawai K, Takaoka T Fluoride, hydrogen ion and HEMA release from light-cured GIC restoratives Am J Dent 2002;15:149–52 RM-GI HPLC μg/ml HEMA Distilled water
7 Manabe A, Kaneko S, Numazawa S, Itoh K, Inoue M, Hisamitsu H, Sasa R, Yoshida T Detection of bisphenol-A in dental materials by gas chromatography-mass spectrometry Dent Mater J 2000;19:75–86 Composite filling material
Sealants
GC/MS ng/mg BPA Phosphate buffer solution
8 Mazzaoui SA, Burrow MF, Tyas MJ, Rooney FR, Capon RJ Long-term quantification of the release of monomers from dental resin composites and a resin-modified glass ionomer cement J Biomed Mater Res 2002;63:299–305 Composite filling material
RM-GI
Electrospray ionization/MS mmol/mm 2 TEGDMA
HEMA
UDMA
BisGMA
BPA
BisDMA
Water
50% Ethanol/water
75% Ethanol/water
9 Michelsen VB, Moe G, Skalevik R, Jensen E, Lygre H Qualification of organic eluates from polymerized resin-based dental restorative materials by use of GC/MS J Chromotography B 2007;850:83–91 Composite filling material GC/MS μg/mm 2 HEMA
MEHQ
CQ
BHT
DMABEE
TEGDMA
TMPTMA
HMBP
TIN P
Ringer’s solution
100% Ethanol
10 Michelsen VB, Moe G, Strom MB, Jensen E, Lygre H Quantitative analysis of TEGDMA and HEMA eluted into saliva from two dental composites by use of GC/MS and tailor-made internal standards Dent Mater 2008;24:724–731 Composite filling material GC/MS μg/cm 2 HEMA
TEGDMA
Passive human saliva
11 Miletic V, Santini A, Trkulja I Quantification of monomer elution and carbon-carbon double bonds in dental adhesive systems using HPLC and micro-Raman spectroscopy J Dent 2009;37:177–184 Adhesives HPLC ppm/mg HEMA
TEGDMA
BisGMA
75% Ethanol/water
12 Moharamzadeh K, Van Noort R, Brook IM, Scutt AM HPLC analysis of components released from dental composites with different resin compositions using different extraction media J Mater Sci Mater Med 2007;18:133–7 Composite filling material HPLC mg/ml TEGDMA
BisGMA
UDMA
Water
Saline
Dulbelco’s modified eagle medium
Dulbelco’s modified eagle medium with serum
Artificial saliva
13 Nalçaci A, Ulusoy N, Atakol O Time-based elution of TEGDMA and BisGMA from resin composite cured with LED, QTH and high-intensity QTH lights Oper Dent 2006;31:197–203 Composite filling material HPLC ppm TEGDMA
BisGMA
HPLC-grade methanol
14 Ortengren U, Langer S, Göransson A, Lundgren T Influence of pH and time on organic substance release from a model dental composite: a fluorescence spectrophotometry and gas chromatography/mass spectrometry analysis Eur J Oral Sci 2004;112:530–7 Composite filling material Solid phase micro extraction/GC/MS μg/sample MA
MMA
HQ
EGDMA
TEGDMA
BPA
citrate-phosphate buffer (McIlvanes standard buffer solution)
15 Pelka M, Distler W, Petschelt A Elution parameters and HPLC-detection of single components from resin composite Clin Oral Investig 1999;3:194–200 Composite filling material HPLC nmol/ml TEGDMA
MA
TMA
BPA
BisGMA
CQ
Quantacure BEA
Irgacure 651
HMPB
BHT
Water
HCL
16 Polydorou O, Hammad M, König A, Hellwig E, Kümmerer K Release of monomers from different core build-up materials Dent Mater 2009;25:1090–5 Core composites HPLC–MS/MS μg/ml BisGMA
TEGDMA
UDMA1
UDMA2
BPA
75% Ethanol/water
17 Polydorou O, König A, Hellwig E, Kümmerer K Long-term release of monomers from modern dental-composite materials Eur J Oral Sci 2009;117:68–75 Composite filling material LC–MS/MS μg/ml BisGMA
TEGDMA
UDMA1
UDMA2
BPA
75% Ethanol/water
18 Polydorou O, Trittler R, Hellwig E, Kümmerer K Elution of monomers from two conventional dental composite materials Dent Mater 2007;23:1535–41 Composite filling material LC–MS/MS μg/ml BPA
BisGMA
UDMA
TEGDMA
75% Ethanol/water
19 Pulgar R, Olea-Serrano MF, Novillo-Fertrell A, Rivas A, Pazos P, Pedraza V, Navaquantitatives JM, Olea N Determination of bisphenol A and related aromatic compounds released from bis-GMA-based composites and sealants by high performance liquid chromatography Environ Health Perspect 2000;108:21–7 Composite filling material
Sealants
HPLC/GC–MS μg/ml BPA
EBPA
PBPA
BADGE
BisGMA
Bis-DMA
Water
20 Tabatabaee MH, Mahdavi H, Zandi S, Kharrazi MJ HPLC analysis of eluted monomers from two composite resins cured with LED and halogen curing lights J Biomed Mater Res B: Appl Biomater 2009;88:191–6 Composite filling material HPLC μg/l BisGMA
TEGDMA
Water
Passive human saliva
21 Yap AU, Han VT, Soh MS, Siow KS Elution of leachable components from composites after LED and halogen light irradiation Oper Dent 2004;29:448–53 Composite filling material HPLC ppm BisGMA
TEGDMA
Acetonitrile
22 Yap AU, Lee HK, Sabapathy R Release of methacrylic acid from dental composites Dent Mater 2000;16:172–9 CE (capillary electrophoresis) UV detector ppm MA Artificial saliva
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