Resin Dental Sealants and Bisphenol A Oral Exposure
Summary
Background
Release of BPA from Dental Sealants
Potential Exposure and Margin of
Safety
Conclusions
References
 Summary
Dental sealants and composites play a significant role
in preventing tooth decay and in maintaining dental
health. Dental sealants are an important tool in preventing
dental caries by providing a protective barrier on the
teeth, particularly when used during a child's formative
years. Dental composites are mainly used to fabricate
tooth colored fillings and veneers as well as in the
cementation of crowns. In addition to their functional
and aesthetic properties, composites provide an alternative
to mercury amalgam.
In 1996, Nicolas Olea and coworkers at the University
of Granada in Spain reported detectable levels of bisphenol
A (BPA) in the saliva of patients treated with dental
sealants, suggesting that children receiving this treatment
could be exposed to the chemical. These findings and
the subsequent clinical recommendations made by the
authors, stimulated public concern about this dental
treatment. Subsequent studies, culminating with that
of Eric Fung and coworkers, indicate that while extremely
low levels of BPA can be detected in the saliva of individuals
treated with selected dental resins in the hours immediately
following application, no BPA was detected in the blood
stream.
A review of key studies on dental resins containing
BPA-based materials reveals that the highest reported
acute oral exposure to BPA is more than 50,000 times
lower than levels shown to cause acute oral toxicity
in animal studies. Although repeated exposure to BPA
from dental resins is not expected to occur, the highest
reported acute oral exposure is also below the maximum
acceptable or "reference" dose for BPA, which
is set for repeated exposure over a lifetime. Consequently,
exposure to BPA from dental resins for both adults and
children is minimal and poses no known risk to human
health.
For additional information, see the statement from
the American
Dental Association and a summary of a study from
the Journal
of the American Dental Association.
Background
Dental composites are complex mixtures of materials
that generally consist of an organic resin matrix, reinforcing
inorganic filler and a silane-coupling agent, which
connects the filler and the resin matrix. Sometimes
known as "white filling" or "synthetic
porcelain", composites are commonly used as a tooth-colored
restorative material, for example in the fabrication
of fillings and veneers, and the cementation of crowns.
Composites without the filler and coupling agent are
commonly used as sealants, which effectively isolate
pits and fissures to help prevent caries in adults and
children.
Composite resins are formulated from a mixture of monomers
and are most commonly based on bisphenol A glycidyl
methacrylate, usually abbreviated as bis-GMA and sometimes
known as Bowen's monomer after it's inventor. Because
of the new treatment options made available, bis-GMA
based composites are considered to be one of the most
significant innovations of modern dentistry.
In addition to bis-GMA, composite resins generally
include other monomers to modify the properties of the
resin, for example bisphenol A dimethacrylate (bis-DMA),
ethylene glycol dimethacrylate (EGDMA) and triethylene
glycol dimethacrylate (TEGDMA). Although several key
components of composite resins are derived from BPA,
there is no known use of BPA itself in composite resins.
Composites and sealants are provided and applied in
the form of a paste or viscous liquid, which is then
cured or hardened after application by polymerization
of the resin with a UV or visible light treatment. In
addition to monomers and fillers, composites also may
contain initiators, to promote polymerization from light
treatment, and stabilizers, to maximize storage of the
uncured resin and stability of the cured resin. (Soderholm
and Mariotti, 1999; Guertsen, 1998).
Dental
Sealant Release
Is Bisphenol A Released
from Dental Composites and Sealants?
Several researchers have studied whether BPA leaches
from cured dental composites or sealants. In 1996, Nicolas
Olea and coworkers at the University of Granada (Spain)
and Tufts University in Boston, MA applied a commercially
available sealant to twelve molars each of eighteen
men and women, using about 50 mg of sealant per person.
Saliva samples were collected one hour prior to and
one hour after application. After treatment, all saliva
samples were reported to contain BPA in amounts ranging
from 90 to 931 µg (3.3 to 30 ppm). (Olea et
al, 1996)
In a similar study, Arenholt-Bindslev and coworkers
applied two commercially available sealants to four
molars of four men per sealant. Saliva samples were
collected before and immediately after application,
as well as one and twenty-four hours after application.
The only saliva samples reported to contain BPA were
those collected immediately after application of one
of the sealants, which was the same sealant studied
by Olea. The level of BPA reported ranged from 0.3 to
2.8 ppm, which is approximately 10 times lower than
the amount of BPA reported by Olea. No BPA was found
in the saliva samples collected at one and twenty-four
hours after application of this sealant or in any of
the saliva samples collected after application of the
other sealant, with a 0.1 ppm limit of detection. (Arenholt-Bindslev
et al, 1999)
In a third larger study, Fung and coworkers at the
University of Nebraska applied the same sealant studied
by Olea and Arenholt-Bindslev to the teeth of eighteen
men and twenty-two women. Half of the subjects received
8 mg of sealant applied to one tooth while the other
half received 32 mg of sealant applied to four teeth.
Both saliva and blood samples were collected before
application of the sealant as well as at intervals of
one, three and twenty-four hours, and three and five
days after application. Some, but not all, of the saliva
samples collected at one and three hours after application
were found to contain BPA in the range of 5.8 to 105.6
ppb. No BPA was found in saliva samples collected after
twenty-four hours or in any of the blood samples, in
both cases with a detection limit of 5 ppb. The maximum
level of BPA detected was more than 250 times lower
than the maximum amount reported by Olea. (Fung et
al, 2000)
Based on the data reported in the three studies involving
application of sealant to teeth, it appears that low
levels of BPA may be released from certain sealants,
although only during a short time period immediately
after application of the sealant. Further, no detectable
levels of BPA have been found in blood after application
of a sealant that releases low levels of BPA into saliva.
Although a wide range of BPA levels have been reported
in saliva, the validity of the high levels reported
by Olea has been questioned. The analytical method used
by Olea may not have been capable of distinguishing
between BPA and TEGDMA, which is known to be a predominant
component released from dental sealants but not reported
at all by Olea. The maximum amount of BPA that could
reasonably be released from the dental sealant has been
estimated to be less than the lowest level reported
by Olea. Consequently, TEGDMA may have been misidentified
as BPA in the Olea study (Atkinson et al, 2002).
Additional complicating factors may have been the excessively
large amount of sealant applied per subject in the Olea
study, potentially resulting in incomplete polymerization
and higher leachability (Fung et al, 2000).
The validity of the lower levels of BPA reported by
Fung and Arenholt-Bindslev is supported by in vitro
leachability studies on cured dental sealants. Nathanson
and coworkers at Boston University tested the leachability
of seven dental sealants that were cured in glass dishes.
None of the seven sealants showed detectable amounts
of BPA after extracting with ethanol with a detection
limit of 0.0001 µg BPA/mg sealant (Nathanson et
al, 1997). Similarly, Hamid and Hume tested the
leachability in water of seven dental sealants that
were applied to extracted teeth or stainless steel molds
and cured. None of the seven sealants showed detectable
amounts of BPA (Hamid and Hume, 1997). In a later study
from Olea's laboratory, samples of composites and sealants
polymerized in glass dishes were extracted with water
of varying pH for twenty-four hours. Low levels of BPA
(< 1 µg BPA/mg sealant) were reported for these
materials (Pulgar et al, 2000). Although these
studies may not be fully predictive of sealant leachability
in vivo, since they do not consider potentially
important factors such as mastication or the effect
of salivary enzymes, they do suggest that high levels
of BPA are not expected.
What is the Source of
BPA in Dental Sealants?
Dental sealants typically contain monomers that are
derived from BPA, such as bis-GMA and bis-DMA, but there
is no known use of BPA itself in dental sealants. Since
it is known that these monomers may leach from dental
sealants, the stability of the monomers has been studied
under a variety of conditions, including in saliva,
to determine if they may hydrolyze to form BPA. Bis-GMA,
the base monomer for many composite resins, has been
found to be stable to various hydrolytic conditions
(Schmalz et al, 1999). However, two researchers
have reported that bis-DMA is hydrolyzed to BPA, which
likely accounts for the BPA detected in extracts from
certain sealants (Schmalz et al, 1999; Atkinson
et al, 2002).
Potential
Exposure and Margin of Safety
The highest amount of BPA reported in saliva by Olea,
931 µg, forms the basis for the calculation of
potential exposure and margin of safety. This quantity
was reported in saliva after the application of one
brand of dental sealant in one individual in a single
study. Further studies by other researchers have reported
much lower levels of BPA and have suggested that BPA
may have been misidentified in the Olea study due to
interferences in the analytical method. In addition,
no detectable amounts of BPA were found in the blood,
indicating that while some BPA may leach into saliva,
systemic exposure does not occur.
Assumptions:
- 931 µg (0.931 mg) of BPA in saliva. This is
a very conservative assumption since it is the highest
value found in the literature. This value is still
the highest even if one assumes that 100% of bis-DMA
converts to BPA.
- Average weight of a child is 25 kg (55 pounds).
- Exposure subsides in the hours immediately following
application. No BPA was detected in samples after
three hours.
Since exposure to BPA from dental sealants occurs only
in a short time period immediately after the sealant
is applied, and dental sealants are applied only very
infrequently, safety is most appropriately evaluated
as an acute exposure event. In laboratory animals, BPA
has been found to have very low acute oral toxicity,
with LD50 values greater than 2000 milligrams per kilogram
of body weight.
In comparison, the potential exposure to BPA from use
of dental sealants on a child of average weight, based
on the assumptions above, is 0.037 milligrams per kilogram
of body weight. This exposure level is more than 50,000
times lower than the LD50 values that have been reported
for BPA. As noted, actual exposure to BPA from dental
sealants is most likely well below the highest reported
value, which further increases the margin of safety.
These assumptions also indicate that exposure to BPA
is less than the maximum acceptable or "reference"
dose of 0.05 milligrams per kilogram of body weight
per day (US EPA, 1993). The EPA reference dose is set
for a lifelong daily intake of a substance and includes
a considerable safety margin for sensitive stages of
life such as childhood. Although exposure to BPA from
dental sealants would not occur daily for a lifetime,
this comparison further indicates that even the worst-case
exposure to BPA from dental sealants represents no harm.
The reference dose for BPA has recently been confirmed
by a three-generation study in rats (Tyl et al, 2002),
which found no adverse effects on reproduction from
BPA at doses of 50 milligrams per kilogram body weight
per day and lower. The US EPA calculated the reference
dose by dividing the Lowest-Observed-Adverse-Effect-Level
(LOAEL, 50 milligrams per kilogram body weight per day)
from an earlier chronic toxicity study by an uncertainty
factor of 1000. Applying that same uncertainty factor
to the No-Observed-Adverse-Effect-Level (NOAEL, 50 milligrams
per kilogram body weight per day) from the Tyl study
confirms the safety of the reference dose, 0.05 milligrams
BPA per kilogram body weight per day. Since the maximum
estimate of BPA exposure from dental sealants is less
than the reference dose, human exposure to BPA from
dental sealants is minimal and poses no known health
risk.
Conclusions
Small amounts of BPA may leach from dental sealants
immediately after application of the sealants to teeth.
No BPA has been detected in blood samples, indicating
that there is no detectable systemic exposure to BPA
from dental sealants.
- The source of BPA that leaches from dental sealants
is likely to be from hydrolysis of bis-DMA, a common
monomer used in dental resin formulations.
- When evaluated as an acute exposure event, the highest
level of BPA reported in saliva from dental sealants
is more than 50,000 times lower than the LD50 values
that have been reported for BPA.
- Although BPA exposure from dental sealants does
not occur daily throughout a lifetime, the highest
level of BPA reported is also below the maximum acceptable
or "reference" dose for BPA of 0.05 mg/kg
body weight/day.
- A recent three-generation study has confirmed the
safety of the maximum acceptable or "reference"
dose for BPA of 0.05 mg/kg body weight/ day.
- Consequently, human exposure to BPA from dental
resins is minimal and poses no known health risk.
References
Atkinson, J. C., F. Diamond, F. Eichmiller, R. Selwitz,
and G. Jones, 2002, "Stability of bisphenol A,
triethylene-glycol dimethyacrylate, and bisphenol A
dimethyacrylate in whole saliva", Dental Materials,
vol. 18, pages 128-135.
Arenholt-Bindslev D., V. Breinholt, G. Schmalz, and
A. Preiss, 1998, "Time-related bisphenol A content
and estrogenic activity in saliva samples collected
in relation to placement of dental fissures", Journal
of Dental Research, 77(B): 692 (abstract 481).
EPA (U.S. Environmental Protection Agency), Bisphenol
A, CASRN 80-05-7, IRIS, Integrated Risk Information
System, on-line, 1993. Available on the Internet at
http://www.epa.gov/iriswebp/iris/subst/0356.htm.
Fung, E. Y. K., N. O. Ewoldsen, H. S. St. Germain Jr.,
D. B. Marx, C. Miaw, C. Siew, H. Chou, S. E. Grunniger,
and D. M. Meyer, 2000, "Pharmacookinetics of Bisphenol
A Released from a Dental Sealant", Journal of
the American Dental Association, vol. 131, pages
51-58.
Guertsen W., 1998, "Substances released from dental
resin composites and glass ionomer cements", European
Journal of Oral Sciences, vol. 106, pages 687-695.
Hamid A and W. R. Hume, 1997, "A study of component
release from resin pit and fissure sealants in vitro",
Dental Materials Journal, vol. 13, pages 98-102.
Nathanson D., P. Lertpitayakun, M. Lamkin, M. Edalatpour,
and L. Chou, 1997, "In vitro elution of leachable
components from dental sealants", Journal of
the American Dental Association, vol. 128, pages
1517-1523.
Olea N., R. Pulgar., P. Perez, F. Olean-Serrano, A.
Rivas, A. Novillo-Fertell, V. Pedraza, A. M. Soto and
C. Sonnenschein, 1996, "Estrogenicity of resin-based
composites and sealants used in dentistry", Environmental
Health Perspectives, vol. 104, pages 298-305.
Pulgar R., M. F. Olea-Serrano, A. Novillo-Fertrell,
A. Rivas, P. Pazos, V. Pedraza, J. Navajas, and N. Olea,
2000, "Determination of bisphenol A and related
aromatic compounds released from Bis-GMA-based composites
and sealants by highperformance liquid chromatography",
Environmental Health Perspectives, vol. 108,
pages 21-28.
Schmalz G., A. Preiss, and D. Arenholt-Bindslev, 1998,
"Bisphenol A content of resin monomers and degradation
products", Journal of Dental Research, 77(B):
823 (abstract 1536).
Soderholm K., and A. Mariotti, 1999, "Bis-GMA
Based Resins in Dentistry: Are They Safe?", Journal
of the American Dental Association, vol. 130, pages
201-209.
Tyl, R. W., C. B. Myers, M. C. Marr, B. F. Thomas,
A. R. Keimowitz, D. R. Brine, M. M. Veselica, P. A.
Fail, T. Y. Chang, J. C. Seely, R. L. Joiner, J. H.
Butala, S. S. Dimond, S. Z. Cagen, R. N. Shiotsuka,
G. D. Stropp, and J. M. Waechter, 2002, "Three-Generation
Reproductive Toxicity Study of Dietary Bisphenol A in
CD Sprague-Dawley Rats," Toxicological Sciences,
vol. 68, pages 121-146.
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