Bisphenol A in dental materials
Fact file
Statement:
Current evidence suggests that only a
very small and specific group of dental
materials is susceptible to the release
BPA, and then in only very small
amounts. The majority of resin based
dental materials appears not to release
BPA, which should alleviate concerns
regarding potential health risks.
What is bisphenol A?
Bisphenol A (BPA) is a chemical used
primarily for the production of polycarbonate
plastics and epoxy resins. Some 3 billion
kilos of BPA are produced worldwide and
the use of this chemical is so ubiquitous
that it has been detected in the urine of 93
per cent of the population over 6 years of
age (Welshons et al., 2006; Calafat et al.,
2005). A recent study found that BPA was
present in the saliva of all patients in the
study group prior to the placement of a
sealant and ranged from 0.07 to 6 ng/ml at
baseline (Zimmerman et al., 2010).
A major source of BPA is believed to be
polycarbonate water bottles (Hoa et al.,
2008). For example, Nalgene water
bottles were made with BPA until recently.
These are being replaced voluntarily by
bottles that are BPA-free. Other sources of
polycarbonate are food and drink
packaging, including infant bottles, toddler
sipping cups, tableware, and food
containers. Epoxy resins, which use BPA in
their manufacturing process, are used to
line metal products such as food cans,
bottle tops and water supply pipes.
The highest estimated daily intake
(exposure) for humans is:
less than 14.7 g/kg body weight
(bw)/day for children
less than 1.5 g/kg bw/day for adults.
(Source:
http://www.medicinenet.com/plastic/page4.h
tm#bisphenol.)
Why is BPA a concern?
BPA is one of a family of endocrine-
disrupting chemicals (EDCs) and exposure
to BPA and its potential effects on human
health are receiving increasing attention, as
studies on laboratory animals have shown
that BPA can cause genetic damage. BPA
stimulates cell proliferation and induces
expression of oestrogen-responsive genes
in vitro, albeit with a relatively low potency.
In vivo, BPA increases prolactin release and
stimulates uterine, vaginal and mammary
growth and differentiation. BPA shares
similarities in structure, metabolism and
action with diethylstilbestrol (DES), a known
human teratogen and carcinogen (Ben-
Jonathan and Steinmetz, 1998).
Studies on laboratory rodents have shown
that high doses of BPA during pregnancy
and lactation can reduce survival, birth
weight and growth of offspring early in life,
and delay the onset of puberty (Richter et
al., 2007). BPA has also been linked to
cancer, diabetes, and obesity in animals.
However, the doses given were
considerably higher than the estimated
human exposures shown above, being in
the range of milligrams rather than
micrograms:
delayed puberty: greater than 50 mg/kg
bw/day
growth retardation: greater than 300
mg/kg bw/day
survival: greater than 500 mg/kg bw/day.
This led the American Chemistry Council to
state that, "consumers would have to eat
more than 500 pounds of food and
beverages in contact with polycarbonate
plastic or epoxy resins every day of their
lives to exceed exposure levels determined
to be safe by the European Food Safety
Authority and the US Environmental
Protection Agency". (See:
http://factsaboutbpa.org/what-are-the-bpa-
myths.)
February 2011
What are the recommended safe levels
of BPA?
There is much confusion about the effects
of BPA on the human body, and the
greatest challenge seems to be in
presenting irrefutable evidence that it is, in
fact, harmless even at low levels.
Correlations have been made between
higher exposures to BPA in human adults
and higher risks of heart attack and Type II
diabetes. However, as long as adult
exposures to BPA do not exceed
acceptable levels, then there seems to be
no impetus for change. (See:
http://www.bisphenol-
a.org/about/faq.html#j.)
In its risk assessment on BPA, published in
January 2007, the European Foods
Standards Agency (EFSA) set a Tolerable
Daily Intake (TDI) of 0.05 mg/kg body
weight (bw) for BPA. The TDI is an estimate
of the amount of a substance, as a function
of body weight, that can be ingested daily
over a lifetime without appreciable risk. The
EFSA has said that intakes of BPA through
food and drink were well below the TDI,
even for infants and children. A recent
review (July 2010) by the EFSA, in which
some 800 publications were considered
(see:
http://www.efsa.europa.eu/en/ceftopics/topic
/bisphenol.htm), has for now decided that
the EFSA will maintain the TDI for BPA at
0.05 mg/kg bw per day. However, some
argue that this TDI is still some way above
levels reported to have an effect in animals
(Ginsberg and Rice, 2009), whereas the
EFSA maintains that the TDI for BPA is
some 200 times greater than that
associated with adverse events reported in
some rodent studies (Vandenberg et al.,
2007).
The recommendations expressed by the
EFSA are based on the concept of a toxic
dose response, such that there is a toxic
level and as long as this is not exceeded
the product is safe. This relies on a
monotonic dose-response curve, in which
more of the chemical leads to a greater
effect. Thus, by using a substantial safety
factor, a recommended safe level (TDI) can
be assumed. Endocrinologists have
challenged this, in that very low doses that
are outside the physiological range can
produce quite different effects compared
with what would be seen within the
physiologically relevant dose range,
especially during the critical periods of
perinatal development (Myers et al., 2009a,
Myers et al., 2009b). Thus endocrinologists
make the case that non-monotonicity is a
feature of edogenous hormones,
hormonally active drugs and environmental
chemicals with hormonal activity such as
BPA and phthalates. Sderholm and
Mariotti (1999), and more recently
Welshons et al. (2006), have asked for a
reassessment of the risks associated with
current estimates of a safe daily exposure
level for BPA. Myers et al., (2009a) go so
far as to suggest that what is required is for
regulatory decision makers to
fundamentally change the paradigm
commonly used to assess the risk to human
health posed by chemicals.
BPA release from dental materials
From the perspective of the safety of dental
materials, it is necessary to assess the
contribution of dental materials to the
overall body burden of BPA, and whether or
not individual patients could be affected by
exposure to dental materials that contain
BPA or BPA-based compounds.
Concerns have been expressed about the
possible exposure of patients to BPA from
dental materials, in particular some fissure
sealants. Bisphenol glycidyldimethacrylate
(Bis-GMA) is one of the most commonly
used monomers for both anterior and
posterior resin restorative materials, fissure
sealants and a range of other dental
products. Bis-GMA is derived from the
reaction of bisphenol A and
glycidyldimethacrylate. This resin is
commonly referred to as Bowens resin,
after its inventor. There are also several
composites that use a urethane
dimethacrylate resin (UDMA) rather than
Bis-GMA. Bis-GMA and urethane
dimethacrylate monomers are highly
viscous fluids because of their high
molecular weights; the addition of even a
small amount of filler would produce a
composite with a stiffness that is excessive
for clinical use. To overcome this problem,
low viscosity monomers known as viscosity
controllers are added, such as methyl
methacrylate (MMA), ethyleneglycol
dimethacrylate (EDMA), triethyleneglycol
dimethacrylate (TEGDMA) and bisphenol
dimethacrylate (Bis-DMA). Thus, dental
materials containing Bis-GMA or Bis-DMA
could provide a potential source of BPA.
It has been shown that BPA may be
released from some resin composite
restorative materials and fissure sealants
(Olea et al., 1996). However, Hamid et al.
(1997) and Nathanson et al. (1997) found
no release of Bisphenol A from any of the
sealants they tested. If BPA is found to be
released from dental restorative materials
then this may be for one of two reasons.
The release may be due to residual BPA
being present in the resin as part of the
production process of Bis-GMA, i.e. as a
contaminant. Manabe et al., (2000) reported
that some unpolymerised materials may be
contaminated with BPA, but they went on to
say that the amount released from dental
materials is less than 1/1000 of the dose
required for xenoestrogenicity in vivo.
Alternatively, the release of BPA may be a
consequence of hydrolytic or enzymatic
breakdown of the polymer with time in the
oral environment. For example, BPA has
been found to be released from Delton LC
Opaque pit and fissure sealant (Joskow
et al., 2006), which is believed to be due to
the breakdown of Bis-DMA (Schmaltz et al.,
1999). Saliva levels of BPA reached a peak
level of 9.08 ng/ml, compared with a
baseline of up to 6ng/ml, whereas the blood
serum did not contain BPA at any stage in
the investigation and BPA levels returned to
baseline levels within 24 hours (Zimmerman
et al., 2010). This confirms the earlier work
of Joskow et al., (2006), who also showed
that the raised levels of BPA were transient.
BPA has also been detected as being
released from ScotchBond Multipurpose
(3M/ESPE) and Delton sealant (Mazzaoui
et al., 2002), and from Ceram X
(Polydorou et al., 2009a). However, in
another study, Polydorou et al. (2009b)
were unable to detect BPA release from
Clearfil Core (Kuraray), but did find up to
15 g/ml of BPA being released from
Clearfil DC Core Automix. Kopperud et al.
(2010) examined a range of orthodontic
base plate materials and found no BPA in
the eluates. However, the situation
becomes more confusing when account is
taken of the elution conditions used in the
studies for the detection of BPA. In one
study, Polydorou et al. (2009a) were unable
to detect any release of BPA from Filtek
Supreme XT, but when the resin composite
was exposed to a bleaching regime BPA
was detected as being eluted for Filtek
Supreme XT (Polydorou et al. (2009c).
Is BPA release from dental materials a
matter of concern?
It would appear that BPA is released from
only a small number of resin-based dental
materials. Thus the contribution of dental
materials to the overall body/environmental
burden of BPA is very small indeed. Also,
where BPA release has been detected, the
amounts involved have been very low and
well within the TDI of 0.05mg/kg bw/day set
by the EFSA. This has led the ADA to state,
The ADA believes any concern about
potential BPA exposure from dental
sealants or composites is unwarranted at
this time. When compared with other
sources of BPA, these dental materials
pose significantly lower exposure
concerns. (Source:
http://www.ada.org/2989.aspx?currentTab=1
.) A systematic review of pit and fissure
sealants (Azarpazhooh, 2008) also states
that, The evidence suggests that patients
are not at risk for exposure to BPA from the
use of dental sealants. However, this
recommendation is primarily based on the
toxic effects of BPA.
Expert opinion currently suggests that BPA
doses from dental materials are low and
well within the safe exposure limits.
Nevertheless, research should continue to
determine whether human exposure to very
low physiological levels of BPA associated
with certain dental materials can cause
adverse oestrogenic effects.
 References:
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Prepared by Professor Richard van Noort, BSc, DPhil, DSc

Academic Unit of Restorative Dentistry, School of Clinical Dentistry, University of Sheffield

Any views or opinions expressed in this document are those of the author and do not represent the views of the University of Sheffield.
Table 1: Dental materials that have been tested for the release of BPA

Material Manufacturer BPA detected BPA not detected Ref

Delton Dentsply Trubyte  Nathanson

Concise 3M/ESPE  Nathanson

Helioseal Ivoclar  Nathanson

Prisma Shield Dentsply Caulk  Nathanson

Seal-Rite I Pulpdent Corp  Nathanson

Seal-Rite II Pulpdent Corp  Nathanson

Defender Henry Schein  Nathanson

Delton LC Opaque Dentsply  Joskow

Scotchbond Multipurpose 3M/ESPE  Mazzaoui

Delton Dentsply  Mazzaoui

Filtek Supreme XT 3M/ESPE  Polydorou

Ceram X Dentsply  Polydorou

Clearfill Core Kuraray  Polydorou

Clearfill Photo Core Kuraray  Polydorou

Clearfill DC Core automix Kuraray  Polydorou

Filtek Silorane 3M/ESPE  Kopperud

J.M. Poly Crown (polycarbonate) Nissin Co., Japan  Takahashi