Bisphenol A in dental
materials - existence and
biological effects
A literature review
Martina Löfroth
Marjan Ghasemimehr
Supervisor: Anders Falk
Department of Materials Science and Technology, Faculty of Odontology,
Malmö University
Bachelor thesis in Odontology (15 ECTS)
Dentistry Program
February, 2016
Malmö University
Faculty of Odontology
205 06 Malmö
Table of Contents
Abstract ................................................................................................................................................................................. 2
Introduction ........................................................................................................................................................................ 3
Materials and methods ................................................................................................................................................... 4
Results ................................................................................................................................................................................... 6
Studies showing no leakage of BPA ...................................................................................................................... 6
Studies showing leakage of BPA ............................................................................................................................ 7
Studies investigating Bisphenol A from dental materials and health................................................... 11
Discussion .......................................................................................................................................................................... 11
Conclusion ..................................................................................................................................................................... 13
Glossary............................................................................................................................................................................... 14
References .......................................................................................................................................................................... 15
1
Abstract
Objectives: Recently there has been uncertainties regarding the potential endocrine disrupting
effects of bisphenol A (BPA). This substance is a constituent in many different products such
as food containers and receipts which we frequently come in contact with. Resin based dental
filling materials are another source of exposure, although the amount and potential risks are
not clear based on the existing studies. The aim of this study is divided into two parts. The
first one is to identify which direct dental filling materials have the ability to leak BPA. The
second aim is to investigate if this leakage could lead to any adverse effects on health.
Methods: The database PubMed was the primary source for the literature search which was
completed with reference tracking. The selected articles were read in full text independently
by two viewers.
Results: A total of 23 articles were included of which 20 were used for the first aim (leakage)
and 3 for the second aim (health risks). The majority of studies, including all in vivo studies,
showed leakage of BPA from dental materials in various amounts and during different time
intervals. The findings showed a contradiction in results with regard to the connection
between dental materials and adverse health effects.
Conclusion: There is a leakage of BPA from some direct dental filling materials in oral
environment. A correlation between this leakage and possible adverse effects on health cannot
be dismissed and because of this there is a need for further studies, specifically long-term
studies.
Sammanfattning
Syfte: Den senaste tiden har det förekommit oklarheter angående potentiellt hormonstörande
effekter av Bisfenol A (BPA). Detta ämne är en beståndsdel i många olika produkter som vi
ofta kommer i kontakt med såsom matförpackningar och kvitton. Resinbaserade
tandfyllningsmaterial är en annan källa till exponering, men mängden och potentiell risk är
inte klarlagd baserat på befintliga studier. Syftet med denna studie har två delar. Det första är
att identifiera vilka direkta tandfyllningsmaterial som har förmåga att läcka BPA. Det andra
syftet är att undersöka om detta läckage skulle kunna leda till några negativa hälsoeffekter.
Metod: Databasen PubMed var den primära källan för litteratursökning, denna
kompletterades med ”reference tracking”. Utvalda artiklar lästes i fulltext självständigt av två
granskare.
Resultat: Totalt inkluderades 23 artiklar varav 20 användes för första syftet (läckage) och 3
för det andra syftet (hälsorisker). Majoriteten av studierna, inklusive alla in vivo-studier,
visade läckage av BPA från dentala material i olika mängder och under olika tidsintervall.
Resultaten var motsägande angående sambandet mellan dentala material och negativa
hälsoeffekter.
Slutsats: Det finns ett läckage av BPA från vissa direkta tandfyllningsmaterial i oral miljö.
Ett samband mellan detta läckage och eventuella negativa hälsoeffekter kan inte avfärdas och
på grund av detta finns det ett behov av ytterligare studier framför allt långtidsstudier.
2
Introduction
Among the many endocrine disrupting chemicals Bisphenol A (BPA) is currently at the
forefront of discussion. The substance was synthesised approximately 100 years ago and in
the 1930s it was identified as one of the first synthetic estrogens (1-4).
Since the 1950s BPA has been commercially used in the manufacture of polycarbonates and
epoxy resins which are used in a variety of commonly used products. Polycarbonates is a rigid
plastic used in toys, water bottles, eyeglass lenses and compact discs (CDs). Epoxy resins are
used in protective lining in cans, as strong adhesive and in dental sealants (4, 5). BPA is also a
constituent in thermal paper such as receipts and fax machine paper. The primary cause of
exposure to BPA is canned food due to leakage from the protective lining, this is followed by
thermal paper as the second largest source (6).
Due to its wide field of use we come in contact with this substance in our daily life possibly
without knowing it. More than 90% of the US population revealed detectable BPA in their
urine samples based on Centre for Disease Control and Prevention’s report (7), which
demonstrates this frequent exposure.
In the early 1990s, scientists discovered BPA leakage from polycarbonates which was the
starting point for further research regarding the possible adverse effects this may cause (4). In
1996 Olea et al. (8) reported a significant leakage of BPA from dental sealants to the saliva of
patients which led to increased concerns about the potential estrogenicity of dental materials
(3, 9).
Due to its structure, pure BPA is an estrogen-mimicking compound (xenoestrogen) which can
bind to estrogen receptors and potentially exert endocrine disrupting effects (2, 10). Exposure
to xenoestrogens can affect not only humans but also wildlife through disturbing their natural
processes, such as reproductive cycles and development (3).
The monomer Bisphenol A glycidyl dimetacrylate (Bis-GMA) is the most commonly used
BPA derivative in epoxy resin based dental composites (2). Bis-GMA is a monomer with
methyl methacrylate groups bound to hydroxyl groups of BPA. Another BPA derivative used
in dental materials is Bisphenol A dimethacrylate (Bis-DMA) which, in contrary to Bis-GMA,
hydrolyses into BPA by salivary esterase, this is due to structural differences between these
monomers (2, 11). Bis-DMA is rarely used in dental materials (12).
BPA itself does not have a functional role in dental composites, it exists as an impurity from
the incomplete manufacturing process or as a degradation product as per the process
described above (13).
Suppliers often have limited information about the specific composition of dental materials
listed in their safety data sheets (14). The European Parliaments regulations states that the
producers of dental materials are only obliged to declare toxic chemicals in concentrations of
0.1% - 1%. This concentration is dependent on the level of toxicity of the compound (12).
Dental materials can be marketed as “private labels” which means that the retailer put their
own brand on a product manufactured by another company. This makes it difficult for a
consumer (dentist) to track the manufacturing process and the actual content of the material
(15).
AH plus, the commonly used resin based root canal sealer, does list BPA as a component in
their safety data sheet but the amount is not specified (16). Therefore it is unclear if the
concentration is of a level sufficient to cause any adverse effects, if indeed a safe level even
exists.
3
Due to BPA being an endocrine disrupting chemical, its uses is regulated by several
organisations around the world for example European Food Safety Authority (EFSA) and
U.S. Food and Drug Administration (FDA). These organisations set restrictions for the use of
BPA based on the results from scientific studies by introducing a tolerable daily intake (TDI)
dose of BPA (17). The first safety standard was set in 1988 by Environmental Protection
Agency (EPA) at 50 µg/kg bodyweight (bw)/day (4). EFSA revised this TDI in January 2015
to a considerably lower and temporary level at 4 µg/kg bw/day, this shows a great uncertainty
regarding the adverse health effects of BPA. EFSA estimates that the combined dietary and
non-dietary exposure for adults is 1.449 µg/kg bw/day which is approximately 3 times lower
than the current temporary TDI (6).
The aims of this study is to find out which direct dental filling materials contain BPA and
their possible leakage of this substance. We also look at the possible adverse health effects
from these materials.
Our hypothesis for these aims are that BPA could be found in direct dental filling materials
such as resin composites and pit and fissure sealants. BPA leaks from these materials and in
combination with other sources of exposure it may increase the risk for adverse health effects.
Materials and methods
Search strategy
A review of current literature was made using the PubMed database. The literature search was
conducted 12th February 2015. “MeSH terms” and “free-text words” were used as search
terms. The used key words were: bisphenol A, bisphenol A epoxy resin, diglycidyl bisphenol
a ether, endocrine disruptors, estrogens, adverse effects, resin composites, pit and fissure.
Besides database searches, several studies were found by reference tracking.
Inclusion and exclusion criteria
Data from the primary search have been included only from studies published within the last
10 years. No publication date limit was used for the literature from the reference tracking.
Further inclusion criteria were studies which only analysed leakage (or synonyms thereof) of
BPA from an oral environment or in vitro and also health effects caused by this leakage.
Exclusion criteria were reviews and studies on rodents.
The direct dental filling materials included in this review are resin based composites and pit
and fissure sealants.
Other
A report by The Swedish National Board of Health and Welfare (Socialstyrelsen) was used as
support for detailed information in tables 1-3 (18). The layout of figure 1 is inspired by a
study from Papia et al. (19).
4
Search results
Resin composites - Potentially relevant publications: 21
Pit & fissure sealants - Potentially relevant publications: 17
Excluded on the basis of title: 11
Excluded on the basis of title: 7
Potentially relevant abstracts: 10
Potentially relevant abstracts: 10
Excluded onzkdsh
the basis of zkdsh
abstract
evaluation: 3
zkdsh
Excluded onzkdsh
the basis of abstract
evaluation: 2
Potentially relevant full text articles: 7
Potentially relevant full text articles: 8
zkdsh
zkdsh
Excluded on zkdsh
the basis of full-text
evaluation: 2
Excluded on the basis of full-text
zkdsh5
evaluation:
Original articles included: 5
Original articles included: 3
zkdsh
zkdsh
zkdsh Reference lists: 87
Excluded on the basis of
abstract evaluation: 31
zkdsh
Reference lists: 64
Excluded on the basis of
abstract evaluation: 33
zkdsh
zkdsh
Abstracts: 56
Abstracts: 31
zkdsh
zkdsh
Potentially relevant
full-text articles: 56
Excluded on the basis
full-text evaluation: 41
Potentially relevant
full-text articles: 31
zkdsh
zkdsh
zkdsh
Original studies
included: 15
zkdsh
zkdsh
Excluded on the basis
full-text evaluation: 31
zkdsh
Original studies
included: 5
Original studies
included: 3
Original studies
included: 0
zkdsh
Studies included: 3
Studies included: 20
zkdsh
zkdsh
zkdsh
zkdsh
zkdsh
Total number of studies included: 23
zkdsh
Figure 1. Literature search strategy for resin composites and pit zkdsh
and fissure sealants.
5
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Results
A total of 20 studies analysing the elution of BPA from resin composites and pit and fissure
sealant materials were selected for this review (8, 10, 20-37).
Studies showing no leakage of BPA
Hamid et al. (21) analysed 7 light cured pit and fissure sealants to identify the released
components using HPLC. Sealant filled extracted molars incubated in water were used in the
study. No detectable amount of BPA was found in any of the eluates. The authors also stated
that the present data does not prove the absence of BPA leakage, but if there was a release, it
was below the detection level.
Geurtsen et al. (22) investigated four types of light-curing pit and fissure sealants in order to
determine their composition and their cytotoxicity. The results showed that different
components of the material, such as co-monomers and initiating substances, leaked into
water. However no BPA, which is easy to detect by GC/MS, was found.
In their report, Koin et al. (23) studied the degradation of dental composites in vitro. They
stored a Bis-GMA coated surface in distilled water for 2 weeks. HPLC did not find any
detectable amounts of BPA but did find intact Bis-GMA and other BPA derivatives. It is
noted by the authors that due to the BPA content in these degradations products health
concerns might arise.
The water sorption and solubility of 6 resin composites were investigated by Ortengren et al.
(38). The testing was carried out using HPLC to analyse the eluted monomers after storage
with times ranging from 4h to 180 days. No detectable quantities of BPA was found during
the test period.
Table 1 – In vitro studies showing no leakage of BPA
Study
Method
Solvent
Time
DL
QL
DL:0.070.09 µg/ml
Material
A study of component release
from resin pit and fissure
sealants in vitro, Hamid et al.,
1997
HPLC
water
24h (several time
intervals were
tested)
Variability of cytotoxicity and
leaching of substances from
four light-curing pit and
fissure sealants, Geurtsen et
al., 1999
GC/MS
water
24h
-
Fissurit F, Helioseal
Visioseal, Delton Plus
ND
Analysis of the degradation of
a model dental composite,
Koin et al., 2008
HPLC,
LC/MS
water
2 weeks
-
Bis-GMA
ND
Water sorption and solubility
of dental composites and
identification of monomers
released in an aqueous
environment, Ortengren et al.,
2001
HPLC
water
4h
24h
7d
60d
180d
-
Alcaglass, C & B Cement
Sono-Cem, Targis, TPH Spectrum,
Vario-link II
ND
ND
ND
ND
ND
Concise, Ultraseal,, Prisma Shield,
Compules, Helioseal F, Delton
(Ash Dent GER), Delton J&J
ND: Not detected, DL: Detection limit, QL: Quantification limit, h: hour, d: day
6
Detectable amount of
BPA
ND
Studies showing leakage of BPA
In their in vivo study, Chung et al. (39) investigated the relationship between urinary BPA
concentrations and the presence of composite restorations or sealants in 496 South Korean
children. Urine samples were collected and analysed to measure the BPA concentration. The
results show that having many surfaces with composite fillings may increase the BPA
concentration in children.
Arenholt-Bindslev et al. (26) placed clinically appropriate amounts of either Delton LC or
Visio-sealed pit and fissure sealant in eight healthy male volunteers and measured BPA in
saliva samples collected from the subjects at various intervals. The authors found BPA only in
samples collected immediately after placement of Delton LC.
Fung et al. (10) applied dental sealant Delton LC on the teeth of 40 adults with no history of
fissure sealants or composite resin fillings. The results showed that BPA was only detectable
in some of the saliva samples collected at 1 and 3 hours. No detectable amounts of BPA in
blood samples suggest no or undetectable quantities of systemic circulation absorption.
Sasaki et al. (27) analysed the changes in salivary BPA concentration in connection to
placement of a composite filling in 21 subjects. Saliva samples were collected before and
immediately after placement, as well as after gargling with tepid water. All samples showed a
higher concentration of BPA immediately after filling placement compared to baseline but the
concentrations declined significantly after gargling. The authors concluded that efficient
gargling may reduce the risk of BPA exposure.
In a case-control study Han et al. (28) investigated the relationship between number of tooth
surfaces with sealant/resin fillings and amount of BPA in saliva. They collected saliva
samples from 124 children of which 50% formed the control group with no dental fillings and
the remaining 50% had more than four surfaces filled. Due to the positive correlation that was
discovered the authors suggest that there may be a connection between dental sealant/resin
fillings and salivary BPA levels.
Joskow et al. (29) measured the BPA concentration in saliva and urine after placement of
fissure sealants in 14 men. The fissure sealant materials used were Delton LC and Helioseal
F, the former showing a low level of BPA-exposure and the latter showing negligible
exposure. The authors mentioned that the collection of saliva samples likely reduced the
systemic absorption and with that the measured concentrations of BPA in urine.
The effects of pit and fissure sealant material on BPA levels in blood and saliva over time was
analysed by Zimmerman–Downs et al. (30). Saliva and serum samples of 30 randomly chosen
adults, with no previous fillings, were collected in various time intervals and divided into 2
groups, a low-dose and high-dose. The subjects were treated with either 1 occlusal sealant or
4 occlusal sealants, respectively. Results showed that BPA was detected in all of the
participants at baseline. The concentration of BPA however increased after applying the
sealants in both groups and the level peaked within 3 hours. No BPA was found in any serum
samples.
Olea et al. (8) also investigated the leakage of BPA and estrogenicity of dental sealants and
composites both in vivo and in vitro. 18 adults were selected and 12 dental fissure sealants
were applied on their molars. Saliva samples were collected one hour before and one hour
after treatment. BPA was identified in the post-treatment samples in varying amounts.
The components of uncured resin composites (Tetric, Charima and Pekalux) and fissure
sealants (Delton) were analysed in vitro at different pH levels. All of the materials showed a
leakage of BPA at pH 7.
7
Table 2 – In vivo studies showing leakage of BPA
Study
Method
Biologic
fluid
urine
Time
Dental composite
fillings and bisphenol
A among children: a
survey in South
Korea, Chung et al.,
2012
HPLC-ESI MS⁄
MS
Time-related
bisphenol-A content
and estrogenic activity
in saliva samples
collected in relation to
placement of fissure
sealants, ArenholtBindslev et al., 1999
HPLC
Pharmacokinetics of
bisphenol A released
from a dental sealant
Fung et al., 2000
HPLC
Saliva
Baseline
1h
3h
1d
3d
5d
Salivary bisphenol-A
levels detected by
ELISA after
restoration with
composite resin,
Sasaki et al., 2005
ELISA
Saliva
Salivary bisphenol-A
levels due to dental
sealant/resin: a casecontrol study in
Korean children, Han
et al., 2012
ELISA
saliva
Exposure to bisphenol
A from bis-glycidyl
dimethacrylate-based
dental sealants,
Joskow et al., 2006
Sensitive isotopedilution mass
spectrometry
saliva
DL
QL
-
-
Material
fissure sealant
material
composite filling
material and fissure
sealant material
saliva
0h
1h
24h
DL: 0.1 ppm
QL: 0.3 ppm
Delton LC
0.3-2.8ppm
ND
ND
Visio-Seal
ND
ND
ND
DL: 5ppb
(0.005ppm)
dental seal
Delton LC
ND
5.8-105.6 ppb
5.8-105.6 ppb
ND
ND
ND
Pre-treatment/
after treatment
-
Progress,
Palfique,
Toughwell,
Metafil Flo, Unifil
S, Beautifil, Xeno
CFII, Prodigy,
Clearfil ST
Mean detected :
32.1 ng/ml
Highest
detected : 60.1
ng/ml
-
-
existing dental
sealant or resin
0.0028.305µg/L
-
Delton LC and
Helioseal F
Mean value:
0.30 ng/ml
26.5 ng/ml
5.12 ng/ml
0h
1h
24h
pre-treatment
immediately after
1h
urine
pre-treatment
1h
24h
Bisphenol A blood
and saliva levels prior
to and after dental
sealant placement in
adults
Zimmerman-Downs et
al., 2010
ELISA
Saliva
Baseline
0.64 µg/g cr*
8.70 µg/g cr*
1.68 µg/g cr*
DL: 0.05µg/L
1-3h
Delton Pit and
fissure sealant-Light
Cure Opaque
24h
Estrogenicity of resinbased composites and
sealants used in
dentistry, Olea et al.,
1996
Detectable
amount of BPA
Highest mean
conc.: 9.13 μg/g
creatinine
Highest mean
conc.: 2.68μg/g
creatinine
HPLC, GC/MS
saliva
0.07-6.00 ng/ml
low-dose group:
3.98 ng/ml
high-dose group:
9.08 ng/ml
Return to baseline
1h pre-treatment
-
Delton Pit and
fissure sealant
1h post-treatment
ND-2123ng/ml
3300-30000 ng/ml
ND: Not detected, DL: Detection limit, QL: Quantification limit, Baseline = Pre-treatment: Before start of experiment, 1ppm: 1000ppm
*cr = creatinine, h: hour, d: day
Durner et al. (31) investigated how the leakage of BPA and other monomers from 3 dental
composites is affected by bleaching with Opalescence® Tooth Whitening System; PF 15% or
PF 35%. Polymerised composite specimens were bleached and thereafter stored in methanol
for 24h or 7 days. The results showed that bleaching with hydrogen peroxide increase the
elution of the monomers. Specimens bleached with PF 15% and thereafter stored for 24h
showed the highest leakage of BPA.
The following two studies analysed how leakage of BPA is affected by pH and came to the
same conclusion. Atkinson et al. (32) analysed the conversion rate of BPA, Bis-DMA and
8
TEGDMA in whole saliva stored at -20°c or -70°c. Solutions of the substances were added to
saliva samples collected from subjects with no previous dental sealants or composite
restorations and the mixtures were stored for various times. The authors also investigated the
stability of Bis-DMA mixed with whole saliva or water stored at 37°c. BPA was stable at all
times and temperatures, Bis-DMA on the other hand was highly unstable. After incubation for
4 months at -20°c almost all Bis-DMA was converted to BPA. All samples were stable at 70°c and only a slight decrease of Bis-DMA was detected in the water samples. Bis-DMA
samples stored at 37°c demonstrated a rapid and significant conversion to BPA, the Bis-DMA
concentration fell from 200 ng/ml to 21.8 ng/ml after 24h while the BPA concentration, which
was undetectable at baseline, rose to 100 ng/ml. The results also showed that a lower salivary
pH may decrease the leakage of BPA. Pulgar et al. (37) analysed BPA release from dental
composites and dental sealant at different pH (1, 7, 9 and 12). The dental materials were used
both in polymerized and non-polymerized form. The authors found BPA leakage from all
samples and it increased at more alkaline pH. Non polymerized Charisma composite showed
the maximal leakage amount of BPA (1.8 µg/mg).
Imai et al. (33) analysed leakage of BPA from a composite resin material in water and
methanol at 37°C. Each specimen was placed in water and observed at different time intervals
from 5 minutes up to seven days. Then they were transferred to methanol and observed again
for various time intervals, up to 28 days. The results showed that BPA elutes more rapidly in
both water and methanol solvents within 3 hours. The amount of eluted BPA in water became
constant after 7 days but when the material transferred into methanol the leakage increased.
In their in vitro study Manabe et al. (34) demonstrated that GC/MS is a reliable method for
detecting BPA in dental materials. This method was used to detect the elution of BPA from
uncured as well as cured dental bonding agents, dental sealants and dental composites. Three
pieces of polymerised dental sealants or composites were placed in phosphate buffered saline
for 24h and thereafter analysed using GC/MS. The authors concluded that these 3 materials
all leached BPA but in quantities far below the reported dose for xenestrogenicity in vivo.
Polydorou et al. (35) investigated the elution of BPA and other monomers from 3 dental
composites, a chemically cured, a photo-cured and a dual-cured. The cured samples were
stored in ethanol and the eluates were analysed after 24 hours, 7 days, 28 days and 1 year. No
BPA leached from the chemically cured material, a small amount of BPA leached from the
other samples, mainly from the dual cured composite. The results also showed a slight
increase of the eluted BPA with time.
In another in vitro study, leakage of BPA were investigated both from light cured (Ceram X
and Filtek Supreme XT) and chemically cured (Clearfil Core) composite material. Polydorou
et al. (40) compared the elution of BPA based on different curing- and incubation time. Only
one of the light cured composite materials (Ceram X) showed leakage of BPA and this
occurred in between day 1 and day 28 but not after 1 year. The curing time did not have a
significant effect of the amount leaked BPA.
G. Schmalz et al. (20) chemically analysed the BPA content of different monomers in fissure
sealant materials and their leakage of BPA under different hydrolytic conditions using HPLC.
They found no BPA release from Bis-GMA under any of the used conditions. They did
however find that the main proportion of Bis-DMA converted to BPA under the same
conditions so the authors conclusion is that BPA release is attributed to the Bis-DMA content
of the fissure sealant tested. The conversion was time related with a continuous increase in
conversion rate from Bis-DMA to BPA during a 24h period.
9
Table 3 – In vitro studies showing leakage of BPA
Study
Method
Solvent
Time
Effect of hydrogen
peroxide on the threedimensional polymer
network in
composites, Durner et
al., 2011
GC/MS
methanol
24h
DL
QL
-
Material
Tetric Flow
Tetric Ceram
Filtek^TM Supreme
XT
Stability of bisphenol
A, triethylene-glycol
dimethacrylate, and
bisphenol A
dimethacrylate in
whole saliva,
Atkinson et al., 2002
GC/MS,
HPLC
whole saliva
up to 4 month
Water
QL for
BPA:
1 ng/ml
BPA
BisDMA
TEGDMA
Detectable amount of
BPA
PF 15%
without/with bleaching:
2.09 µmol/l /14.49 µmol/
(4.78 µmol/l / 5.07
µmol/l*)
without /with bleaching:
1.82 µmol/l / 11.45µmol/l
(3.24 µmol/l / 7.66µmol/l
*)
without/with bleaching:
1.70 µmoL/l/12.41 µmol/l
(2.43 µmol/l / 4.62 µmol/l
*)
See text below
QL for
BisDMA:
10 ng/ml
QL for
TEGDMA:
500 ng/ml
Elution of bisphenol
A from composite
resin: a model
experiment Imai et
al., 2000
HPLC
water
methanol
up to 7d (in
water)
up to 28d (in
methanol)
-
Detection of
bisphenol-A in dental
materials by gas
chromatographymass spectrometry,
Manabe et al., 2000
GC/MS
phosphate
buffered saline
24h
-
Release of monomers
from different core
build-up materials
Polydorou et al.,
2009
LC-MS/MS
Ethanol
QL:
0.5µg/ml
24h
7d
28d
Long-term release of
monomers from
modern dentalcomposite materials,
Polydorou et al.,
2009
LC/MS
ethanol
Determination of
bisphenol A and
related aromatic
compounds released
from bis-GMA-based
composites and
sealants by high
performance liquid
chromatography.
Pulgar et al., 2000
GC/MS,
HPLC
Water
Bisphenol-A content
of resin monomers
and related
degradation products,
Schmalz et al., 1999
HPLC
saliva
Composite resin Z100
See text below
Silux Plus
Cured material
91.4 ng/g material
Concise
19.8 ng/g material
Teeth mate A
55.5 ng/g material
ClearfilTM Photo Core
Mean values
ND
1.92 µg/ml
6 µg/ml
24h
7d
28d
ClearfilTM DC Core
Automix
5.19 µg/ml
3.98 µg/ml
6.14 µg/ml
24h
7d
28d
24h to 1y
Clearfil®Core
Ceram X
ND
ND
ND
5.25µg/ml
Filtek Supreme XT
ND
Clearfil Core
ND
Charisma
Pekalux
Polofil
Silux-Plus
Z-100
Tetric
Brillant
Delton
pH 7, cured and uncured
1.4 µg/ml
0.6 µg/ml
2.8 µg/ml
16.5 µg/ml
0.3 µg/ml
12.9 µg/ml
ND
42.8 µg/ml
QL: 0,5
µg/ml
24h
DL:
0.20ppm
(0.20µg/ml),
QL:
0.23ppm
(0.23µg/ml)
DL: 1-104
ppm
0.3h-24h
0.3h
1h
2h
24h
Bis-GMA
Bis-DMA
Conversion rate:
<0.2% for all times
44.7%
73.4%
70.2%
81.4%
ND: Not detected, DL: Detection limit, QL: Quantification limit, PF = Potassium nitrate and fluoride, * = Detected amount after 7 days
h: hour, d: day, y: year
10
Studies investigating Bisphenol A from dental materials and health
Only 3 of the reviewed studies analysed the association between BPA release from dental
materials and its effect on health (1, 41, 42).
Maserejian et al. (1) compared physical development between children with amalgam or
composite fillings during 5 years. The subjects were randomly selected to receive filling
treatment with either one of these two materials. The authors measured changes in body mass
index (BMI), body fat percentage and height velocity. Their conclusion was that there were
no statistically significant correlations between composite or amalgam fillings and physical
development.
In another study Maserejian et al. (41) examined how and if resin based composite
restorations affects children's neurophysiological functions. The authors used a randomised
treatment plan placing either amalgam or composite fillings on the children's teeth.
Neurophysiological functions were followed up at 4 and 5 years after treatment by measuring
for instance intelligence, problem solving and memory. The results showed that greater
exposure to dental composites leads to small adverse effects however these results were
insignificant.
Maserejian et al. (42) analysed the association between Bis-GMA based composite fillings
and psychosocial functions in 534 children. Some of the eligibility criteria were no
psychosocial diagnosis, no amalgam fillings and ≥2 posterior teeth with occlusal caries in
need of treatment. The participants were randomly selected to be treated with either amalgam,
composite or compomer. After 5 years the children’s psychosocial function was followed-up.
The authors concluded that children with higher exposure to Bis-GMA based composites
showed impaired psychosocial functions for instance anxiety and depression. There were no
connection between these functions and the exposure to amalgam or compomer.
Discussion
In our primary literature search we decided to exclude articles older than 10 years in order to
collect the most up to date studies as well as limiting the scope. In the reference tracking
however several studies found were still relevant even though they did not meet the criteria
above. For instance a study by Olea et al. (8) that was referred to in a number of articles as
a starting point for further investigations of the leakage of BPA and was therefore included.
Leakage of BPA from dental materials have been analysed in different studies using different
methods with the majority showing a leakage of BPA of varying amounts. The studies that
showed no leakage were all performed in vitro (21-23, 38) and no in vivo studies could
confirm this result. This leads us to the conclusion that BPA does leak in an oral environment
which may be due to salivary enzymatic processes that could not be reconstructed in vitro.
The use of different methods as well as varying detection limits and quantification limits
complicates the comparison process. Only 9 studies have provided information about the used
detection- and quantification limits (10, 20, 21, 26, 30, 32, 35, 37, 40).
Some of the reviewed studies measured time dependent elution of BPA. Elution occurred in
higher amounts immediately after placement of the filling than at a later stage (10, 26, 29, 30,
33). Meanwhile the conversion rate from Bis-DMA to BPA increased continuously (20, 32).
Based on these findings it is important to take measures to reduce this initial elution through
thorough polishing of the filling and rinsing the mouth immediately after treatment. The “no
touch technique” should be applied to minimise the clinicians contact with uncured dental
materials in order to avoid possible allergic reactions. This technique may also indirectly
11
reduce the exposure risk of BPA in the clinical situation. The “no touch technique” as well as
the clinical recommendations are also recommended by Lars Ehrnford, associate professor in
odontology (13).
A study by Maserejian et al. is the only reviewed study showing a significant positive
correlation between BPA from dental composite restorations and adverse effects on health
(42). The other two studies did not find a connection. Three studies is not enough evidence to
conclude the effect of BPA leakage on health. EFSA also claims that there is need for further
studies on BPA and its effect on health (6).
EFSA published their first report on BPA and its risk characterisation from dietary exposure
in 2006 (6). This report gave rise to establishing the TDI for BPA at 50 µg/kg bw/day which
was based on several rodent studies showing adverse effects at considerably higher doses.
In 2010 EFSA concluded that there are uncertainties regarding the possible toxicological
effects of BPA due to a lack of scientific evidence. In late 2011 EFSA published a statement
(43) on the ANSES (French Agency for Food, Environmental and Occupational Health and
Safety) report on BPA (43, 44) due to a discrepancy with this and the 2010 EFSA report (45).
According to this statement the main reason for variance is that ANSES included non-dietary
sources in addition to dietary sources as opposed to EFSA who only included dietary sources.
EFSA however did state that there is need for further reviews of new studies to arrive at an
accurate conclusion.
In EFSA’s report from 2015 (6) the sources used for external non-dietary exposure were;
Thermal paper, air (inhalation), dust, toys (which may come into contact with the mouth) and
cosmetics. Dental materials were not included as potential source of BPA in this report and
therefore the results does not provide an accurate picture of the existing sources.
Due to all the uncertainty regarding the TDI of BPA the EU restricted the use of BPA in
infant feeding bottles in 2011 as a precautionary measure (46). Infants, children and women
of childbearing age are all considered as vulnerable groups for BPA exposure. One of the
factors of this is that in general infants consume a higher amount of food and drink per
bodyweight than adults, which in turn leads to a higher concentration of BPA. Some studies
analysed how BPA can affect the fetus through placental exchange and cause adverse effects
(47, 48) this is a reason for women of childbearing age, including pregnant women, to be
considered as vulnerable for this exposure.
As previously mentioned we are exposed to BPA from different sources in daily life. It can be
anything from receipts to canned food as well as dental materials. EFSA´s current opinion is
that BPA poses no health risks as the exposure levels are far below the TDI, however the
studies that these conclusions are based on does not consider dental materials as a source of
BPA exposure. There are possibly other unknown sources of BPA which has not been
included in these studies. Based on this we cannot be sure that our daily exposure is
significantly lower than the TDI. Hypothetically BPA in a lower dose could also be part of a
cocktail effect in combination with other endocrine disrupting chemicals that we are exposed
to. This includes a wide range of substances such as dichloro-diphenyl-trichloroethane (DDT)
synthetic insecticide, pharmaceuticals, dioxin and dioxin like compounds which might act
synergistic and lead to unpredictable adverse effects (49).
The current TDI level of BPA set by EFSA, 4 µg/kg bw/day, is temporary and up until
January 2015 it was 50 µg/kg bw/day. The new TDI is not final due to EFSA awaiting results
from an ongoing long term rodent study, this would show the level of uncertainty regarding
this subject. Due to this it is important to limit the exposure to BPA sources, specifically for
12
the vulnerable groups such as children and pregnant women (6). As previously discussed the
European Union (EU) has already taken measures to restrict the usage of BPA containing
materials in infant feeding bottles (46) meanwhile EFSA´s official statement (6) is that the
daily intake of BPA is far below the TDI.
Limiting a child’s exposure to BPA is a logical precaution. Fissure sealants which are
nowadays frequently used in a preventative way to reduce the risk of caries among children
may increase the exposure amount of BPA. Even though the studies showed a low risk of
BPA leakage from sealants it should still be a matter of concern due to them being in a risk
group. In regards to EFSA’s reasoning behind restricting the use of BPA in feeding bottles the
same argument could also be used. Considering all the uncertainties regarding exposure level
it may also be a legitimate measure to exclude pregnant women from getting composite
restorations unless it is urgent (2).
Considering that the main reason behind composite fillings is caries the best way to decrease
the possible BPA exposure from composites is to prevent the disease in the first place. In the
light of the current debate about the daily usage of fluoride from water and toothpaste etc. it is
important not to forget its major preventative effects on caries disease. Many studies show the
positive effects of fluoride in caries prevention (50) so it could be argued that the
recommended fluoride usage indirectly decreases the exposure to BPA due to less need for
composite fillings.
At the moment many of the studies regarding the endocrine disrupting properties of BPA are
conducted on rodents. Some of the studies showed that BPA exposure correlated with adverse
effects on reproductive, as well as non-reproductive systems, including neurobehavioral
development and endocrine system (51-57). However it is important to consider that the
source of BPA exposure in the studies was not dental materials, but pure BPA solvent, which
was administered subcutaneously, intragastrically or orally. According to the findings by
Taylor et al. the route of administration has no significant effect on plasma BPA levels (58),
based on this the route of administration should not be a reason to dismiss the results from
studies using a non-oral route.
Several factors including metabolism and exposure per kg bodyweight need to be taken into
consideration before drawing conclusions on human health based on results from animal
studies. Based on one study (52) the pharmacokinetics in women, female monkeys and mice
are similar, however the plasma concentration of BPA in rodents in these studies is much
higher than the equivalent concentration in humans.
Conclusion
Based on the results of the reviewed studies it can be determined whether or not the analysed
dental material contain and/or leak BPA. It would be valuable for the clinician to attain this
information by reading the safety data sheet. This is not the case however as the current
regulation policy set by the European Parliament does not require that companies fully
declare the content of their products (12). There may be reason to re-evaluate the regulations
to ensure that caregivers are aware of the exact content and possible risks of the materials.
There is a lack of studies analysing the association between BPA exposure from dental
materials and its adverse effects on human health. We cannot draw a conclusion about these
effects based on the reviewed studies.
13
Glossary
Chromatography: A chemical separation technique which use a stationary and mobile phase
to separate the different compounds.
Detection limits: The lowest amount of a substance that can be detected by a certain method.
Dioxin and dioxin like compounds: Toxic compounds which are by-products of different
industrial processes.
ELISA: Enzyme-Linked Immuno-Sorbent Assay. An analyse method that is used to detect
and quantify an antibody or an antigen. Specific antibodies adheres to their target substance,
for instance BPA, the antibodies are linked to an enzyme which in most cases will lead to a
colour change.
Electrospray ionisation (ESI): A method used in mass spectrometry to produce ions from
macromolecules using an electrospray.
Estrogenicity: The ability of a chemical to act like estrogen.
Gas chromatography (GC): A type of chromatography which use gas as a mobile phase.
High-performance liquid chromatography (HPLC): a modern name of liquid
chromatography (LC),
Liquid chromatography (LC): A type of chromatography which use liquid as a mobile
phase.
Mass spectrometry (MS): An analytical technique used for detection and quantification of a
compound using a mass spectrum.
Quantification limits: The lowest amount of a substance that can not only be detected but
accurately quantitatively determined by a certain method.
Tolerable Daily Intake (TDI): An estimation of the quantity of a contaminant to which we
are exposed to on a long term basis without resulting in any significant health risks.
Endocrine disrupting chemicals (EDC): Natural and synthetic compounds which can
interfere with body´s endocrine pathways mainly through interacting with hormone receptors
or transport proteins and lead to adverse reproductive, development, neurological and immune
effects. The adverse effects on wildlife that these chemicals may cause in some species
include reduced fertility as well as changes in immunity and behaviour. In humans EDC’s are
associated with declining sperm counts, genital malformations, certain hormone sensitive
types of cancer.
Xenoestrogen: An exogenic chemical with estrogenic effect in the body.
14
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18