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REVIEW
Undesirable and adverse effects of tooth-whitening products:
a review
Michel Goldberg &Martin Grootveld &Edward Lynch
Received: 6 February 2009 /Accepted: 8 June 2009 / Published online: 20 June 2009
#Springer-Verlag 2009
Abstract Hydrogen peroxide (H
2
O
2
) is a powerful oxidis-
ing agent. It gives rise to agents known to be effective
bleaching agents. The mechanisms of bleaching involve the
degradation of the extracellular matrix and oxidation of
chromophores located within enamel and dentin. However,
H
2
O
2
produces also local undesirable effects on tooth
structures and oral mucosa. In clinical conditions, the daily
low-level doses used to produce tooth whitening never
generate general acute and sub-acute toxic effects. Geno-
toxicity and carcinogenicity only occur at concentrations
that are never reached during dental treatments. Some
transient adverse effects have been reported on the oral
mucosa and the digestive tract if the product is swallowed.
Local effects may occur on the oral mucosa and dental
tissues during whitening, namely, pulp sensitivity, cervical
resorption, release of selected components of dental
restorative materials, and alteration of the enamel surface.
Most of the local effects are dependent of the technique and
concentration of the product so far used, but as the results
of bleaching obtained are not stable, repeated treatments
add to the adverse effects. The informed decision to
administer or not and the control of bleaching effects
should stand in the hand of dental surgeons and certainly
not as it appears at present, as cosmetics sold without any
restriction despite the potential health hazards of peroxides.
Keywords Tooth whitening .Hydrogen peroxide .
Cytotoxic effects .Genotoxicity .Carcinogenicity .
Resorptions .Hypersensitivity .Enamel surface
Introductory remarks
Genetic diseases such as dentinogenesis imperfecta,or
dentine dysplasia or some forms of amelogenesis imper-
fecta, some acquired foetal and post-natal pathologies
occurring during tooth formation such as medical diseases
(i.e., icterus, congenital erythropoietic porphyria, chole-
stasis, and renal diseases), treatments with tetracycline, or
chronic ingestion of fluoride during childhood, may
induce unacceptable levels of intrinsic tooth staining that
should be included in the list of handicaps. In such cases,
there is a real need for bleaching, mostly for psychological
reasons and also for an improved social life of the patient
[19,22,49]. Bleaching procedures are effective and
certainly less destructive than any full or partial prosthetic
restoration.
However, there is currently a wide range of bleaching
techniques used for aesthetic reasons, and in many cases,
such treatments are not necessary. As a consequence, the
wide diffusion of whitening methods have to be
controlled because it is well known that there is no
therapy without high or small risks. When these methods
are used correctly, there are only minor consequences
and, therefore, a clinical tolerability. In contrast, abuses
approach the limits of risks and this should be taken into
Clin Oral Invest (2010) 14:1–10
DOI 10.1007/s00784-009-0302-4
M. Goldberg (*)
EA2496, Faculté de Chirurgie Dentaire,
Université Paris Descartes,
1, rue Maurice Arnoux,
92120 Montrouge, France
e-mail: mgoldod@aol.com
e-mail: michel.goldberg@parisdescartes.fr
M. Grootveld
Department of Applied Science, London South Bank University,
London, UK
E. Lynch
School of Dentistry, Queen’s University,
Belfast, Ireland
consideration or better documented prior to taking a
clinical decision.
Tooth-whitening treatments are carried out either at
the chair-side by dental surgeons (‘in-office’)orby
‘staff-supervised in-office bleaching’,oras‘at-home’
dentist-supervised treatments, or bleaching devices are
sold over-the-counter (OTC) to patients and may be used
without any control of dental practitioners [11,19]. Each
method is effective for most staining but needs different
periods of time to obtain the expected result. When strips
are used as typical OTC treatments, 31.85 cycles of
15 min are necessary to obtain some whitening; whereas,
at-home dentist-supervised bleaching needs 7.15 cycles
and in-office treatment needs 3.15 cycles [11].
In many countries, no final decision has yet been taken
by state agencies for sanitary security to classify the
bleaching agents as medical devices or cosmetic products,
or both, depending on the final concentration of the gel.
Whatever the decision will be in this matter, up to now, the
active compounds are, in general, the same although the
doses administered can differ substantially. Between 1918
[1] and the 1990s [66], sporadically, a few publications
reported that bleaching could be obtained clinically, but
most studies were published in the last 20 years [9,69].
Bleaching effects are mostly based on the effects of
carbamide peroxide, releasing about 33% of their content
as hydrogen peroxide (H
2
O
2
). H
2
O
2
can act as a powerful
oxidising agent and can give rise to agents known to be
effective bleaching agents (i.e., its corresponding mono-
anion (HO
2
−
) and hydroxyl radical (OH)). In addition,
carbamide peroxide also releases urea, which is rapidly
decomposed into carbon dioxide and ammonia [22,41].
Chemical reaction of the two reagents with the organic
extracellular matrix components (ECM), including pig-
ments or chromophores, constitutes the chemical basis of
tooth whitening.
It is well documented that urea degrades the organic
matrix located in the enamel [8,31,32]. The organic matrix
constitutes 0.6% in weight and 4% in volume of the total
human adult enamel. Urea and ammonium ions (NH
4
)
+
act
on the hydrogen bounds that are crucial regarding the
secondary, tertiary, and quaternary structures of matrix
proteins. After the initial alteration, the degraded proteins
are further split into small peptides, released, and finally
eliminated from the mature enamel [8,31,32,41,57]. The
same applies to most non-collagenous dentin matrix
components. The empty minute spaces that are rendered
accessible by urea allow the diffusion of hydrogen peroxide
throughout the whole thickness of enamel up to the
dentino-enamel junction (DEJ).
Bleaching agents cross the DEJ and interact in the
subjacent dentin with the chromophores, pigments, and ions
that are now recognised to be responsible for tooth staining.
The removal of ECM is not homogeneous. In enamel, it is
mostly detectable in some rods and not apparently
associated with inter-rods [31,32]. The removal of matrix
components is associated with the loss of some hydroxy-
apatite crystals, bound at specific areas where there is a
local accumulation of matrix components. Consequently,
minute craters form at the enamel surface as a reaction to an
efficient peroxide treatment [24,60,62,93]. The balance
between the need for treatment that is judged necessary by
the practitioner and the risk induced by the therapy has to
reach a valuable equilibrium. It is clear that many efforts of
the industry were carried out in order to minimise the
noxious effects of bleaching products. However, there is
clearly a compromise between efficiency and safety that
cannot be ignored [11,19].
Adverse effects of bleaching agents have been reported
after the treatment of non-vital teeth [69]. When applied to
vital teeth, tooth sensitivities, the alteration of enamel
surfaces, and the consequences arising from the release of
some components of restorative materials have been
reported [22] and are important phenomena to consider.
The effects on the oral mucosa are controversial and depend
on the technique that has been employed. It is also the case
that the effects of bleaching agents on the digestive tracts of
both animals and humans have to be considered in detail.
The conclusions of in vitro and animal studies should be
adapted to the human situation. Finally, general toxicity,
genotoxicity, and carcinogenicity are also important con-
siderations that have to be taken into account in the frame
of safety or tolerability [57,82,85].
A review of the potential effects of bleaching agents is
not facile, largely because of the many divergent reports
that have been published on a range of important aspects
of this area. There are multiple reasons for these
conflicting reports. In some cases, what has been
published arises more from the marketing and advertise-
ment of products rather than that from unbiased scientific
investigations, and it is not always a simple process to
decide what has to be kept on the list of reputable
references. In many cases, however, diverging published
data are mostly attributable to differences between the
concentrations of the bleaching reagent that was used,
the reagent itself, and even the carrier, which may also
play an important role in the reaction (or lack of it). In
any case, taking into account the many excellent reports
that are available, it is necessary to consider the limit
above which there is a risk of undesirable side effects.
An excellent review article has been published in 2003,
and we have to acknowledge that it constitutes one of the
major references in the field [22]. However, since the last
6–7 years, new experimental results were obtained and
new products were put on the market. These additional
data are incorporated in this review.
2 Clin Oral Invest (2010) 14:1–10
General and local toxic effects of hydrogen peroxide
Allergic sensitivity
No allergic sensitivity has yet been reported for carbamide
or hydrogen peroxides, or for alternative peroxo-adducts, in
contrast to the acute and sub-acute effects that are well
documented.
Acute cytotoxic effects
Acute cytotoxic effects appear at doses over 5 g/kg/day for
a product containing 10% (w/w) carbamide peroxide [44,
88]. This corresponds to a 0.3 to 1.8 mg/kg (body weight)/
day H
2
O
2
. Force-feeding rats directly into the stomach with
5, 15, and 50 mg of carbamide peroxide/kilogramme, or its
equivalent in tooth-whitening products, induce dose-
dependent ulcerations of the mucosa, easily detectable 1 h
after feedings; however, these heal after 24 h. This reaction
is not observed for doses lower than 15 mg/kg. The gel
associated with peroxides in a commercially available
product seems to enhance the toxic effects. No adverse
effect has been detected in the kidney or liver [21].
From these data, assuming a threshold of toxicity of
15 mg of carbamide peroxide/kilogramme and a security
factor of 100, it is apparent that at a carbamide peroxide
concentration of 10 mg (equivalent to 3.6% (w/v)H
2
O
2
),
we are at the limit of systemic effects for a 70-kg man [21].
In this context, it has been reported that a 16-month-old
child died after ingestion of a 3% (w/v)H
2
O
2
solution.
However, this accident was at the lowest doses so far
reported. From the available data, we can conclude that the
everyday doses used during whitening procedures is close
to a level where adverse systemic effects might occur.
Sub-acute toxic effects
There are no effects or, at least, no reported effects in
humans. In animals, the daily critical doses should be
lower than 30 mg/kg/day for the rat and 26 mg/kg/day
for the mouse.
After topical application to humans, °OH radical
derived from electron transfer to H
2
O
2
can, in principle,
induce lipid peroxidation, and also DNA alteration
followed by cell lysis and death [41,57]. Anti-oxidants
and iron chelators may prevent such reactions, the former
by scavenging °OH or lipid peroxyl radicals (LOO°), the
latter by complexing Fe(II) and attenuating its ability to
participate in Fenton-type reactions. The enzyme catalase
inhibits these reactions via its capacity to directly consume
H
2
O
2
; whereas, the lipid-soluble antioxidant vitamin E
(α-tocopherol) blocks such damage by scavenging LOO°
radicals [57,82].
H
2
O
2
induces squamous metaplasia on tracheal explants
at concentrations of 50–100 μmol/l; whereas, cytotoxic
effects appear at a concentration ≥500 μmol/l [71]. At
700 μmol/l, H
2
O
2
induces embryonic fibroblast necrosis;
whereas, at 150 μmol/l, apoptotic effects are induced [34].
In another report, it is shown that when 35% (w/v)
carbamide peroxide is used, the percentage of viable cells
is decreased to 60% in comparison with control cells
(FM3A cell line). This value falls down to 43% with a 20%
(w/w) carbamide peroxide gel. The level of toxicity is 50
and 40 μg/ml, respectively. An extrapolation to a 70-kg
individual suggests that in order to remain below the risk
doses and avoid any toxic effects, the daily dose used
should be ≤10 mg carbamide peroxide, or its 3.3 mg H
2
O
2
equivalent [7].
Genotoxicity and carcinogenicity
International Agency on Research on Cancer data [44] do not
refer to any mutation or cancer risk attributable to profes-
sional exposure. However, in animal models, adenoma and
duodenum carcinoma have been detected experimentally
after oral administration of H
2
O
2
. In the mouse, hyperplasia
appears in the gastric mucosa in 20–42% and duodenum
hyperplasia in 40–62% of the experimental animals 8 weeks
subsequent to the ingestion of 0.10% or 0.40% (w/v)H
2
O
2
solutions. These reactions are more substantial in the
duodenum than the stomach. In addition to gastric mucosal
ulcerations after force-feeding with 15 mg/kg carbamide
peroxide, adenoma and carcinoma were observed. This
pathological transformation seems to be strain-dependent
and linked specifically to the catalase activity of the different
groups of mice [45–47]. Critical analysis of the experimental
situation leads to conclude that hydrogen peroxide is not a
carcinogenic thread, at least for the digestive tract [23].
It seems unlikely that H
2
O
2
may induce cutaneous cancers
[13,52]. In the oral cavity, repeated applications of 30%
(w/w)H
2
O
2
produce hyperkeratosis, hyperplasia, and dyspla-
sia with weak intensity after 22 weeks [71,89]However,no
tumours were detectable with H
2
O
2
alone. This is not the case
when a carcinogenetic agent is co-administered with H
2
O
2
[89]. However, it is documented that H
2
O
2
inhibits gap
junctional intercellular communication in glutathione-
sufficient but not in glutathione-deficient cells, and an
aberrant intercellular junctional communication has been
implicated in tumour promotion, neuropathy, and teratogen-
esis. This sheds light on potential dangers and on some
genetic aspects of the reaction [87].
H
2
O
2
has been shown to be mutagenic in a number of
strains including Salmonella typhimurium and Escherichia
coli [2]. In some cell cultures, H
2
O
2
treatment induces
DNA strand breakage and is mutagenic, especially toward
cells from the L5178Y murine lymphoma subline. For
Clin Oral Invest (2010) 14:1–10 3
example, at 37°C, LY-R are 3.6 times more sensitive to the
killing effects than LY-S cells; whereas, at 4°C, they were
11 times more sensitive [53]. Mutagenicity has also been
reported in V79 Chinese hamster cells, and the reaction is
concentration dependent. Ziegler-Skylakakis and Andrae
[94] concluded from their investigations that at a solution
level of 4 mM H
2
O
2
, the mutation frequency increased
sixfold above the controls, and the extent of survival was
reduced by 50%. DNA fragmentation has also been
observed in human lymphocyte cultures and epithelial cells
of the respiratory tract.
Following the use of hydrogen peroxide at a concentra-
tion of (10 μmol/L), Timblin et al. [84] observed the
overexpression of the proto-oncogen c-jun, a process which
leads to cell proliferation.
It should be added that despite all the potential risks
inherent with the use of peroxides, up to now there is no
report of human cases where carcinogenic effects are
actually established [23,57]. However, two recent publica-
tions pointed out that hydrogen peroxide used in long-term
treatment and at a high concentration might act as a
promoter of oral mucosal damage and, moreover, have
genotoxic and carcinogenic effects [65,85].
Local effects of bleaching agents on dental tissues
and oral mucosa
The whitening effects of hydrogen peroxide on teeth
and oral mucosa are well documented [11,18,49,55,
67]. However, in a limited number of cases, undesirable
effects such as hypersensitivity (2.62–3.38%) and gingival
irritation (0.23–0.85%) have been reported [11,54].
Changes in enamel microhardness, micromorphological
defects due to demineralization, and effects on restorative
materials have also been reported [17,24,43,60,62,64,
68,77,80,81,90–93].
Effects on non-vital teeth (internal and/or external treatment):
internal and external resorptions
Some time after a root canal treatment, the colour of the
treated tooth changes and gradually becomes unaesthetic
[74]. This is very often the case for incisors after a local
trauma. Darker or brown-grey teeth may be subjected to a
whitening treatment that removes less dental tissue than
the preparation of a jacket crown or a veneer. In most
studies, however, no adverse reaction has been observed
after such treatments. Indeed, no resorption was detected
in a series of 100 and 250 patients, respectively, that have
been treated and recalled for a follow-up [6,42]. However,
external resorptions have also been reported in a further
series of patients. About 7% of the teeth displayed
resorptions in 58 cases, monitored during an 8-year period
[26]. The frequency of resorption is certainly dependent
on the bleaching method that has been utilised. A mixture
of sodium perborate and 3% hydrogen peroxide was
shown to induce delayed outer resorptions, which
appeared 12 years after the treatment. Heating the
bleaching solution enhances the number of resorptions
that are induced [69].
Exactly why such external resorptions are occurring is
poorly understood. They seem to be dependent on the pH,
the trauma, and the heating procedure that was used. They
appear a few years after the bleaching treatment, and we
are still unable to control them. The origin of the
pathology could be an enhancement of bacterial penetra-
tion inside dentine tubules [40]. This invading pathway
may be also related to some structural defects or patholog-
ical alterations of the cementum that favour such bacterial
penetration [74]. Apparently, no correlation was found
between the mechanism of action of sodium perborate and
the adhesive properties of macrophages. It seems that these
cells do not play a role in the resorption process [48].
Tissue permeability in the cervical area of the tooth may be
implicated in the initiation of such resorptions. However,
there is no predictable evidence from clinical examination
that such lesions will form. Therefore, before taking the
decision to administer a whitening treatment on non-vital
teeth, it is important to consider that resorption may be
induced. The final outcome of such cervical resorption is
the fracture of the crown, when the lesion reaches a certain
volume. This, unfortunately, leads to a residual root that
cannot be employed for a prosthetic device and, hence, has
to be extracted.
Effects of external treatments on vital teeth
Post-treatment hypersensitivity and pulp alteration
When a 10% (w/w) carbamide peroxide treatment is
conducted, between 15% and 65% of the patients receiving
it display sensitivities of the treated teeth within the next
4 days [38,54,78], far less for other authors (2.62–3.38%)
depending on the bleaching product and the concentration
used [11]. The sensitivity is higher with H
2
O
2
combined with
the thermo-catalytic enhancement at some point following
the chair-side treatments [69]. This sensitivity may last up to
39 days and, in some cases, is so painful that it leads to
treatment interruption. It is well documented that H
2
O
2
diffuses throughout the enamel layer and dentine, even in
vital teeth. In vitro studies demonstrate peroxide penetration
into the pulp with most bleaching agents and methods,
including whitening strips that presumably would excerpt
mild effects [28–30]. This phenomenon results from both the
osmotic and vascular pressures [35]. The physiopathological
4 Clin Oral Invest (2010) 14:1–10
mechanisms of sensitivity or pain are however not fully
understood. Nerve endings are undetectable in enamel.
Contemporarily, it is well documented that nerve endings
are present in the inner dentin in an area near the
periphery of the pulp (150 μm thick), visualised either by
radioautography [15] or by immunocytochemistry [58]. The
absence of nerve endings in the outer dentine and at the DEJ
clearly does not assist us in interpreting the phenomenon.
The hydrodynamic hypothesis developed by Brännström
[14] may apply here, i.e., backward and forward movement
of the “dentinal lymph”may be transmitted to odontoblast
processes located inside tubules and then to cell bodies
where a direct anatomical link occurs between odontoblasts
and nerve endings in what is known as the sub-odontoblastic
plexus. Bleaching agents containing H
2
O
2
in high concen-
tration may favour bacterial penetration through dentinal
tubules [40]. In view of the mild irritative process,
reactionary dentine is formed which gradually reduces the
hypersensitivity. Alternatively, there is peritubular dentine
formation after such stimulation, resulting in an eventual
reduction of diameter of the lumen of the tubules. The two
processes may be interdependent.
Diverging results have been published with respect to
the consequences of the influence of whitening treatments
on pulp. According to Seale et al. [79], a 35% (w/v)
hydrogen peroxide gel used for 30 min induces severe pulp
reactions in dog teeth. The odontoblast layer is reduced and
even disappears in the area facing the treated part of the
tooth. The predentine is missing. Inflammatory cells are
present at the pulp surface, and internal resorbing processes
may be observed 4 days after the treatment. The inflam-
matory reaction is present for a period of 15 days, together
with the dilation of blood vessels, vascular thrombus, and
haemorrhages. Fortunately, these alterations disappear after
2 months. Another report reveals translocation of odonto-
blast nuclei in dentinal tubules in 32% to 53% of treated
human teeth, without any pulp reaction [20]. The differ-
ences between these two reports do not appear to be
ascribable to compositional differences between the two
bleaching agents which were used, since they both
contained 35% (w/w)H
2
O
2
coupled with thermal enhance-
ment. A more recent study provides evidence for a
moderate reaction with 10% (w/w) carbamide peroxide
[5]. Moreover, it should be noted that bleaching methods
induce an increase of endogenous pulp peroxide (mean
value, 0.44 mM). However, this was 3,000 less than that
which can induce acute pulp damages arising from enzyme
release [50]. In any case, tooth sensitivity resumes
gradually, without any long-term adverse effects.
Sensitivity can be prevented or decreased by treating the
teeth 30 min prior to whitening by desensitising agents
containing 3% potassium nitrate and 0.11% per weight
fluoride [56].
Alteration of enamel surface: consequences on bacterial
plaque adhesion and cariogenicity
In this area, reports on the effects of whitening gels are also
divergent. Some researchers have reported either no effect
on or only minor changes to the enamel surface or the
subsurface [18,37,50,51,64,90–92]. In contrast, others
have shown moderate to severe enamel surface modifica-
tions [24,27,60,62,80,93]. Again, it is difficult to have a
clear-cut idea on the actual situation. The divergent results
that were obtained are mainly attributable to differences in
the protocols, the chemicals that were used and their
concentrations, and also may be influenced by the method
used to visualise the effects. In some case, the reliability of
the results is related also to the scientific independency of
the researcher and is also apparently linked to the scientific
quality of the journal where the report is published.
Although some authors have pointed out that tooth
bleaching with selected commercial H
2
O
2
or carbamide
peroxide do not produce modifications in surface morphol-
ogy [81–83], another group of reports found that bleaching
agents create some enamel porosity [21,54,56,84]. For
example, Ruse et al. [77] have shown that in bleached
enamel, the calcium/phosphate ratio is altered by a 35%
H
2
O
2
treatment. According to Seghi and Denry [80],
enamel treated with a 10% (w/w) carbamide peroxide gel
displays a reduction in apparent fracture toughness (ca.
30%), with no significant changes in surface hardness. Data
acquired indicate small but significant decreases in abrasion
resistance. To explain these findings, the authors hypoth-
esised that the chemical action of H
2
O
2
induced an
alteration of the organic matrix of enamel. Differences
between these published reports may arise from a variation
in the concentration of chemical bleaching agents, e.g., a
concentration of 35% (w/w) carbamide peroxide (11–12%
H
2
O
2
) affects the structure of enamel; whereas, 10% or
16% (w/w) have no effect [68]. From the published
literature, it could be concluded that bleaching treatments
induce changes in surface roughness and consequently
influence the formation of supra- and sub-gingival plaque
[70]. Therefore, the adhesion of Streptococcus mutans to
enamel is increased [43]. This is also the case for
Streptococcus sobrinus, but not for Actinomyces viscosus
[63]. Such undesirable effect may have some implication on
future developments regarding the carious decay. However,
to the best of our knowledge, it should be recognised that
up to now, there are no clinical report available on the
potential development of caries from a broad series of
whitening treatments. However, it may be assumed that
with the development of such methods, we may face such
consequences in the near future.
An investigation performed with the atomic force
microscope revealed that commercial bleaching agents as
Clin Oral Invest (2010) 14:1–10 5
well as a 30% (w/v)H
2
O
2
solution enhanced groves present
at the surface of enamel and also act on its inner structure
[39]. Hence, it may be concluded that most bleaching
agents (even those containing 10% (w/v) carbamide
peroxide), induce slight to moderate alterations of the
enamel surface and a decreased enamel microhardness,
variations between the bleaching agents employed were
clearly notable [73]. These microlesions are of much lesser
importance than those arising from etching with phosphoric
acid. From some reports, it appears that minor defects are
also induced in the subsurface. These defects might
interfere with the adhesive properties of restorative materials.
After some time, the porosities are gradually reduced. In view
of enamel abrasion, and also as a result of ion re-precipitation
controlled by some salivary proteins and/or by the bacterial
plaque, calcium-phosphate precipitation occurs inside the
porous enamel, a phenomenon that leads eventually to re-
hardening and furthermore contributes to a return to the
normal situation.
Therefore, the concept that “in-office”bleaching is a
non-destructive cosmetic procedure should be reconsidered,
and this apply also to the other whitening procedures. It
should be considered that enamel demineralization is an
undesirable effect resulting from bleaching agents, related
to their concentration and to the time necessary to obtain
teeth whitening. Along this line, strips may have less
destructive effects, although peroxide release in saliva is
higher by using some strips in comparison with trays
charged with gels [36]. Remineralization due to saliva may
restore gradually the mineral charge of enamel surfaces, but
the specific organic matrix is definitively degraded, and this
alteration may interfere with enamel repair. Attempts to
reduce the loss of mineral and the formation of micro-
defects on enamel surface were carried out with fluoride-
containing bleaching agents shown to induce less enamel
surface demineralization and altered microhardness [17].
Effects of tooth-whitening peroxides on the oral and gastric
mucosa
When the dental surgeon at the chair-side applies H
2
O
2
or
alternative peroxo-adducts, there is a clinical control of the
risk factor for developing gingival irritation. This is not
always the case with nightguard, i.e., dentist-prescribed
home-applied bleaching methods. The situation may be
even worse when patients without any control of a dental
surgeon are using whitening methods. Carefully adapted
trays are mandatory if the dental practitioner wishes to
prevent or suppress gingival irritations.
H
2
O
2
, together with lauroyl and benzoyl peroxides, all
represent compounds with the potential to generate free
radical species. They are not carcinogenic when applied
topically to the mouse skin, but they are potent skin
irritants. Notable modifications induced by peroxides in
skin are epidermal hyperplasia and the induction of dark
keratinocytes: 15% or 30% (w/v)H
2
O
2
gave rise to an
extensive epidermolysis, inflammation, and vascular injury
in rodents. This was found to be followed by a rapid
regeneration and epidermal hyperplasia [52]. After topical
application of 10% (w/v) carbamide peroxide, an increase in
the quantity of cells located in the basal layer of the oral
mucosa revealed by proliferating cell nuclear antigen
(PCNA) staining was noted [3]. However, by immunode-
tection of cyclin D and p16 (representing a proliferation
marker and a negative regulator of cell proliferation,
respectively, the alteration of which are considered as
markers of an initial cancer formation), studies carried out
on the oral mucosa failed to indicate any significant
alteration [33]. In contrast, using the PCNA as a marker,
the same researchers have shown a transient proliferation
after topical application of carbamide peroxide to the basal
and suprabasal epithelial oral border [3]. Therefore, the
controversy is not yet solved.
In fact, temporary burnings of the tissue arising from
H
2
O
2
have been reported. In the hamster pouch, severe
inflammatory processes are now well identified. During
the treatment of periodontal diseases, the bacteriostatic
properties of H
2
O
2
have been widely used, and in this
context, cell lysis has been reported at a concentration as
low as 1% [61].
Carefully adapted plastic trays or nightguards may
reduce the amount of whitening agent that is expelled onto
the oral mucosa when the patient overfills the tray. Strips
and painted lacquers reduce the risk. The ingestion of
bleaching gel may produce gastric pain, although the
repeated ingestion of peroxide-containing gels does not
seem to have severe consequences.
Effects on restorative materials: the release of mercury
and silver from amalgams and adverse effects
on the adhesive properties and on the margin
of composites fillings
Bleaching agents have well-established effects on dental
fillings [4,10]. After treatment of silver amalgam with a
gel containing 10% (w/w) carbamide peroxide, an increased
level of mercury and silver was found near the surface of
silver amalgam; whereas, tin and copper levels therein were
diminished [75,76]. In vitro, carbamide peroxide favours the
release of mercury from silver amalgams. However, in vivo,
the reaction is limited by the dental biofilm [83]. Mercury
can be released up to 80 h after whitening treatment [72].
Such effects have been reported exclusively for silver
amalgam fillings. These effects are not clinically detectable
but have been reported from in vitro studies for other
materials used in restorative dentistry. There are nowadays
6 Clin Oral Invest (2010) 14:1–10
convincing evidences that bleaching agents may influence
bacterial adhesion, modify the surface roughness of
polyacid-modified resin-based composites and resin-
modified glass ionomer cements (see for review [10]).
The interfacial fracture toughness of dentin/resin composite
adhesive is affected, with significant reductions observed at
16% and 21% (w/w) carbamide peroxide concentrations,
after 42 h [25]. The marginal leakage of resin composite
restorations is increased after bleaching with 10% (w/w)
carbamide peroxide, but not amalgam restorations [86].
Penetration of the pulp chamber by bleaching agents is
common with resin-modified glass ionomer cement fillings;
whereas, the lowest pulpal peroxide penetration is detected
with the resin composite materials [28]. A 6% (w/w)H
2
O
2
does not cause significant surface dissolution of glass
ionomer, but the authors did not investigate the dentin-glass
ionomer cement (GIC) interface [59].
Altogether, these data suggest that whitening treatments
may induce alterations of the restorative material itself,
impairs the conversion of dental adhesives after dentin
whitening, or modify the interface between the biomaterial
and dentine to the detriment of adhesive properties [10,16].
Moreover, if the restorative material is present in the
bleached surfaces, a significant reduction in the resin
composite shear bond strength can be observed [12,81].
The long-term effects of such methods are questionable
in terms of public health costs, especially when they are
used without the control of a dental surgeon.
Stability of tooth-whitening treatments and acquired
exogenous staining
It is now well established that bleaching methods are
efficient. After a few days or appointments at the chair-side,
teeth lost one or two colour divisions on a tooth shade
device, and patients are generally satisfied from the gain
that is obtained. However, after some time, the initial
staining colour returns, or in view of dental enamel
permeability, a renewed level of exogenous staining agents
penetrates and diffuses throughout enamel and even reaches
dentine [19]. This is the case for tobacco smoke, tea, coffee,
jams, and many other potential staining agents. As long as
dental surgeons control the process, it is not an acute
problem. However, when identified by the patient, the
staining instability may lead to uncontrolled multiple
treatments and, hence, the repeated re-exposure of enamel
and gingiva to peroxo derivatives. It is also clear that the
patient’s conception of white teeth is mentally mediated and
related more to social and sexual concepts rather than to a
reality, but the end-point will be that some individuals will
unnecessarily over-use whitening devices. As a conse-
quence, demineralisations and local severe structural alter-
ations may occur as a long-term effect of repeated
bleaching, and sub-toxic or toxic doses may be inadver-
tently attained. The percentage of such patients is not
known at present. Another open question is that on
treatment with 10% to 15% (w/w) carbamide peroxide,
efficient whitening results are easily and rapidly obtained.
To be equivalent to a process involving 10–15% (w/w)
carbamide peroxide for 2 weeks, a treatment conducted
with a lower concentration such as 5% (w/w) should be
performable for ca. 3 weeks. Although in the latter
treatment the dose of peroxide is lowered, the time required
to reach a whitening effect is of course extended.
Consequently, lower doses will involve longer treatments,
although it could be argued that noxious effects may be
similar [11,55].
Finally, in order to match the colour of previously
placed restorative material with the shade obtained after
bleaching on natural teeth, fillings have to be replaced.
Because tooth whitening is not stable, the colour of the
fillings differs gradually from the frontal teeth and they
need again to be renewed [19]. We reach here the limits
of what can be acceptable between a dentistry primarily
oriented on cosmetology and the biomedical clinical
practise.
Conclusions
Despite the rather contradictory conclusions arising from an
analysis of the literature, it appears that the chemical
mechanisms of bleaching agent actions involve alteration
or destruction of the enamel organic matrix, a phenomenon
that allows the diffusion of peroxides throughout enamel
toward dentin where the chromophores are oxidatively
decolourised. From an analysis of the available data, we can
conclude that
1. Bleaching causes small defects at the surface and
subsurface of enamel.
2. Dentin permeability is probably modified and, as a
consequence, post-treatment transient tooth sensitivity
is observed in many cases.
3. The effects on pulp are more controversial and may be
inconsistent. Nevertheless, chronic treatment with
peroxides may be not safe, and this could be the case
when such treatments are carried out in the absence of
a sufficient level of control by dental surgeons.
4. Effects observed regarding dental restorations are well
recognised, there is a release of mercury from
amalgam fillings, and bleaching methods alter the
interface between dental tissues and glass ionomer
cements or resin composites.
5. The bleaching of non-vital teeth may induce resorp-
tion in the cervical area in an unpredictable manner.
Clin Oral Invest (2010) 14:1–10 7
6. The long-term effect of bleaching on the development
of carious decay has not yet been demonstrated but
cannot be ignored.
7. Gingival lesions appear in relation to the uncontrolled
applications of whitening gels. Again, the cellular and
tissular mechanisms of peroxide damage are well
elucidated, and again there is a critical requirement for
qualified control in order to avoid long-term gingival
tissue damage.
8. The ingestion of peroxide may occur when poorly
adapted trays are employed.
9. At the doses that are administered, it is clear that up
until now, there is no indication of any effects in terms
of general toxicity, genotoxicity, and carcinogenicity
in human. Therefore, there is a clinical tolerability. It
is also clear that below a 3.6% (w/w)H
2
O
2
concen-
tration (10% (w/w) carbamide peroxide), there is
apparently no toxic or sub-toxic risk.
10. Taking into account the possibility that chronic treat-
ments might be applied as cosmetic products that are
sold OTC, the higher concentrations utilised should
perhaps be revised.
Altogether, all these local effects have to be taken into
consideration prior to deciding if a whitening treatment is
necessary or, for that matter, safe. Potential patients should
be warned. There is a balance between the effects that may
or may not appear and the real need for bleaching. In many
cases, it seems rather an artificial cosmetic fashion
requirement than a deserving cause. Finally, the informed
and appropriate decision to administer or not, and the
control of bleaching effects should stand in the hand of
dental surgeons (or at least be under their control), and
certainly not as it appears at present, as cosmetics sold
without any restriction despite the potential health hazards
of peroxides.
Conflicts of interest We have no conflict of interest.
References
1. Abbot C (1918) Bleaching of discolored teeth by means of
30% perhydrol and electric light rays. J Allied Dent Soc
13:259
2. Abu-Sharkra A, Zeiger E (1990) Effects of salmonella genotypes
and testing protocols on H
2
O
2
-induced mutation. Mutagenesis
5:469–471
3. Albuquerque RC, Gomez RS, Dutra RA, Vasconcellos WA,
Gomez RS, Gomez MV (2002) Effects of a 10% carbamide
peroxide bleaching agent on rat oral epithelium proliferation. Braz
Dent J 13:162–165
4. Al-Salehi SK (2009) Effects of bleaching on mercury ion release
from dental amalgam. J Dent Res 88:239–243
5. Anderson DG, Chiego DJ, Glickman GN, McCauley LK (1999)
Clinical assessment of the effects of 10% carbamide peroxide gel
on human pulp tissue. J Endod 25:247–250
6. Anitua E, Zabalegui B, Gil J, Gascon F (1990) Internal bleaching
of severe tetracycline discoloration: four year clinical evaluation.
Quintessence Int 21:783–788
7. Aren G (2003) In vitro effects of bleaching agents on FM3A cell
line. Quintessence Int 34:361–365
8. Arends J, Jongebloed WL, Schuthof J (1984) Interaction of urea
and human enamel. Caries Res 18:17–24
9. Attin T, Paquè F, Ajam F, Lennon M (2003) Review of the current
status of tooth whitening with the walking bleach technique. Int
Endod J 36:313–329
10. Attin T, Hanning C, Wiegand A, Attin R (2004) Effects of
bleaching on restorative materials and restorations—a systematic
review. Dent Mater 20:852–861
11. Aushill TM, Hellwig E, Schmidale S, Sculean A, Arweiler NB
(2005) Efficacity, side effects and patients’acceptance of different
bleaching techniques (OTC, in-office, at-home). Oper Dent
30:156–163
12. Ben-Amar A, Liberman R, Gorfil C, Bernstein Y (1995) Effect of
mouthguard bleaching on enamel surface. Am J Dent 8:29–32
13. Bock FG, Myers HK, Fox HW (1975) Cocarcinogenic activity of
peroxy compounds. J Natl Cancer Inst 55:1359–1361
14. Brännström M (1968) Physio-pathological aspects of dentinal and
pulpal response to irritants. In: Symons NBB (ed) Dentine and
pulp. University of Dundee, Dundee, pp 231–246
15. Byers M, Dong WK (1983) Autoradiographic location of
sensory nerve endings in dentin of monkey teeth. Anat Rec
205:441–454
16. Cadenaro M, Breschi L, Antonioili F, Mazzoni A, Di Lenarda R
(2006) Influence of whitening on the degree of conversion of
dental adhesives on dentin. Eur J Oral Sci 114:257–262
17. Chen HP, Chang CH, Chuang SF, Yang JY (2008) Effect of
fluoride containing bleaching agents on enamel surface properties.
J Dent 36:718–725
18. Chiesara E, Dayan AD, Duschner H, Maier H, White DJ (2002)
The safety of tooth whitening, Chap. 4. Blackwell Munksgaard,
Oxford, pp 31–39
19. Christensen GJ (2005) Are snow-white teeth really so desirable?
JADA 136:933–935
20. Cohen SC, Chase C (1979) Human pulpal response to bleaching
procedures on vital teeth. J Endod 5:134–138
21. Dahl JE, Becher R (1995) Acute toxicity of carbamide peroxide
and a commercially available tooth-bleaching agent in rats. J Dent
Res 74:710–714
22. Dahl JE, Pallesen U (2003) Tooth bleaching—a critical review of
the biological aspects. Crit Rev Oral Biol Med 14:292–304
23. Desesso JM, Lavin AL, Hsia SM, Mavis RD (2000) Assessment
of the carcinogenicity associated with oral exposures to hydrogen
peroxide. Food Chem Toxicol 38:1021–1041
24. Efeoglu N, Wood DJ, Efeoglu C (2007) Thirty-five percent
carbamide peroxide application causes in vitro demineralization of
enamel. Dent Mater 23:900–904
25. Far C, Ruse ND (2003) Effect of bleaching on fracture toughness
of composite-dentin bonds. J Adhes Dent 5:175–182
26. Friedman S, Rotstein I, Libfelt H, Stabholz A, Heiling I (1988)
Incidence of external root resorption and esthetic results in 58
bleached pulpless teeth. Endod Dent Traumatol 4:23–26
27. Fu B, Hoth-Hannig W, Hannig M (2007) Topic of micro-
morphologic alterations: effects of dental bleaching on micro
and nano-morphological alterations of the enamel surface. Am J
Dent 20:35–40
28. Gökay O, Yilmaz F, Akin S, Tunçbilek M, Ertan R (2000)
Penetration of the pulp chamber by bleaching agents in teeth
restored with various restorative materials. J Endod 26:92–94
8 Clin Oral Invest (2010) 14:1–10
29. Gökay O, Müjdeci A, Algin E (2004) Peroxide penetration into
the pulp from whitening strips. J Endod 30:887–889
30. Gökay O, Müjdeci A, Algin E (2005) In vitro peroxide
penetration into the pulp chamber from newer bleaching products.
Int Endod J 38:516–520
31. Goldberg M, Arends J, Jongebloed W, Schuthof J, Septier D
(1983) Action of urea solutions on human enamel surfaces. Caries
Res 17:106–112
32. Goldberg M, Arends J, Jongebloed WL, Schuthof J, Septier D,
Apap M (1984) Action of urea solutions on unerupted and erupted
teeth: an investigation on late maturation of human enamel.
Gerodontology 3:191–195
33. Gomez RS, de Castro Albuquerque R, Dutra RA, Vasconcellos
WA, Reis DA, Gomez RS, Gomez MV (2002) Effects of a
bleaching agent containing 35% carbamide peroxide on the
immunolocalization of cyclin D and p16. J Oral Rehabil
29:906–909
34. Guénal I, Sidoti-de Fraisse C, Gaumer S, Mignotte B (1997) Bcl-2
and Hsp27 act as different levels to suppress programmed cell
death. Oncogene 15:347–360
35. Hanks CT, Fat JC, Wataha JC, Corcoran JF (1993) Cytotoxicity
and dentin permeability of carbamide peroxide and hydrogen
peroxide vital bleaching materials, in vitro. J Dent Res 72:931–
938
36. Hannig C, Zech R, Henze E, Dorr-Tolui R, Attin T (2003)
Determination of peroxides in saliva—kinetics of peroxide release
into saliva during home-bleaching with Whitestrips and Vivastyle.
Arch Oral Biol 48:559–566
37. Haywood VB, Houck VM, Heymann HO (1991) Nightguard vital
bleaching: effects of various solutions on enamel surface texture
and color. Quintessence Int 22:775–782
38. Haywood VB, Leonard RH, Nelson CF, Brunson WD (1994)
Effectiveness, side effects and long term status of nightguard vital
bleaching. J Am Dent Assoc 125:1219–1226
39. Hegedüs C, Bistey T, Flora-Nagy E, Keszthelyi G, Jenci A (1999)
An atomic force microscopy study on the effect of bleaching
agents on enamel surface. J Dent 27:509–515
40. Heling I, Parson A, Rotstein I (1995) Effect of bleaching agents
on dentin permeability to Streptococcus faecalis. J Endod 21:540–
542
41. Hermans N, Cos P, Maes L, De Bruyne T, Vanden Berghe D,
Vlietinck AJ et al (2007) Challenges and pitfalls in antioxidant
research. Curr Med Chem 14:417–430
42. Holmstrup G, Palm AM, Lambjerg-Hansen H (1988) Bleaching of
discoloured root-filled teeth. Endod Dent Traumatol 4:197–201
43. Hosoya N, Honda K, Lino F, Arai T (2003) Changes in enamel
surface roughness and adhesion of Streptococcus mutans to
enamel after vital bleaching. J Dent 31:543–548
44. International Agency on Research on Cancer (1999) Hydrogen
peroxide. Monographs on the evaluation of carcinogenic risks to
humans—re-evalaution of some organic chemicals, hydrazine and
hydrogen paroxide, vol 71. IARC, Lyon, pp 671–689
45. Ito A, Watanabe H, Naito M, Naito Y (1981) Induction of
duodenal tumors in mice by oral administration of hydrogen
peroxide. Gann 72:174–175
46. Ito A, Naito M, Naito Y, Watanabe H (1982) Induction and
characterization of gastro-duodenal lesions in mice given
continuous oral administration of hydrogen peroxide. Gann
73:315–322
47. Ito A, Watanabe H, Naito M, Naito Y, Kawashima K (1984)
Correlation between induction of duodenal tumor by hydrogen
peroxide and catalase activity in mice. Gann 75:17–21
48. Jimmenez Rubio A, Segura JJ (1998) The effect of the bleaching
agent sodium perborate on macrophage adhesion in vitro:
implications in external cervical root resorption. J Endod
24:229–232
49. Joiner A (2006) The bleaching of teeth: a review of the literature.
J Dent 34:412–419
50. Joiner A, Thakker G (2004) In vitro evaluation of a novel 6%
hydrogen peroxide tooth whitening product. J Dent 32:19–25
51. Joiner A, Thakker G, Cooper Y (2004) Evaluation of a 6%
hydrogen peroxide tooth whitening gel on enamel and dentine
microhardness in vitro. J Dent 32:27–34
52. Klein-Szsanto AJP, Slaga TJ (1982) Effects of peroxidases on
rodent skin: epidermal hyperplasia and tumor promotion. J Invest
Dermatol 79:30–34
53. Kruszewski M, Green MHL, Lowe JE, Szumiel I (1994) DNA
strand breakage, cytotoxicity and mutagenicity of hydrogen
peroxide treatment at 4°C and 37°C in L5178 Y sublines. Mutat
Res 308:233–241
54. Leonard RH, Haywood VB, Phillips C (1997) Risk factors for
developing tooth sensitivity and gingival irritation associated with
nightguard vital bleaching. Quintessence Int 28:527–534
55. Leonard RH, Sharma A, Haywood VB (1998) Use of different
concentrations of carbamide peroxide for bleaching teeth: an in
vitro study. Quintessence Int 29:503–507
56. Leonard RH Jr, Smith LR, Garland GE, Caplan DJ (2004)
Desensitizing agent efficacity during whitening in an at-risk
population. J Esthet Restor Dent 16:49–55
57. Li Y (1996) Biological properties of peroxide-containing tooth
whiteners. Food Chem Toxicol 34:887–904
58. Maeda T, Iwanaga T, Fujita T, Takahashi Y, Kobayashi S (1987)
Distribution of nerve fibers immunoreactive to neurofilament
protein in rat molars and periodontium. Cell Tissue Res 249:13–
23
59. Mair L, Joiner A (2004) The measurement of degradation and
wear of three glass ionomers following peroxide bleaching. J Dent
32:41–45
60. Markovic L, Jordan RA, Lakota N, Gaengler P (2007) Micro-
morphology of enamel surface after vital tooth bleaching. J Endod
33:607–610
61. Martin JH, Bishop JG, Guentherman RH, Dorman HL (1968)
Cellular response of gingival to prolonged application of dilute
hydrogen peroxide. J Periodontol 39:208–210
62. McCraken MS, Haywood VB (1996) Demineralization effects of
10 per cent carbamide peroxide. J Dent 24:395–398
63. Mor C, Steinberg D, Dogan H, Rotstein I (1998) Bacterial
adherence to bleached surfaces of composite resin in vitro.
Oral Surg Oral Med Oral Pathol Oral Radiol Endod 86:582–
586
64. Murchison DF, Charlton DG, Moore BK (1992) Carbamide
peroxide bleaching: effects on enamel surface hardness and
bonding. Oper Dent 17:181–185
65. Naik S, Tredwin CJ, Scully C (2005) Hydrogen peroxide tooth-
whitening (bleaching): review of safety in relation to possible
carcinogenesis. Oral Oncol 42:668–674
66. Nutting E, Poe G (1963) A new combination for bleaching teeth. J
South Calif Dent Assoc 128:289–291
67. Oda D, Nguyen MP, Royack GA, Tong DC (2001) H2O2
oxidative damage in cultured oral epithelial cells: the effect of
shortterm. Vitamin C exposure. Anticancer Res 21(4A):2719–
2724
68. Oltu Ü, Gürgan S (2000) Effects of three concentrations of
carbamide peroxide on the structure of enamel. J Oral Rehabil
27:332–340
69. Plotino G, Buono L, Grande NM, Pameijer CH, Somma F (2008)
Nonvital tooth bleaching: a review of the literature and clinical
procedures. J Endod 34:394–407
70. Quirynen M, Bollen CM (1995) The influence of surface
roughness and surface free-energy on supra- and sub-gingival
plaque formation in man. A review of the literature. J Clin
Periodontol 22:1–14
Clin Oral Invest (2010) 14:1–10 9
71. Radosevich CA, Weitzman SA (1989) Hydrogen peroxide induces
squamous metaplasia in a hamster tracheal organ explant culture
model. Carcinogenesis 10:1943–1946
72. Robertello FJ, Dishman MV, Sarrett DC, Epperly AC (1999)
Effect of home bleaching products on mercury release from an
admixed amalgam. Am J Dent 12:227–230
73. Rodrigues JA, Basting RT, Serra MC, Rodrigues AL (2001)
Effects of 10% carbamide peroxide bleaching materials on enamel
microhardness. Am J Dent 14:67–71
74. Rotstein I, Torek Y, Misgav R (1991) Effect of cementum defects
on radicular penetration of 30% H2O2 during intracoronal
bleaching. J Endod 17:230–233
75. Rotstein I, Mor C, Arwaz JR (1997) Changes in surface levels of
mercury, silver, tin, and copper of dental amalgam treated with
carbamide peroxide and hydrogen peroxide in vitro. Oral Surg
Oral Med Oral Pathol Radiol Endod 83:506–509
76. Rotstein I, Dogan H, Avron Y, Shemesh H, Steinberg D (2000)
Mercury release from dental amalgam after treatment with 10%
carbamide peroxide in vitro. Oral Surg Oral Med Oral Pathol Oral
Radiol Endod 89:216–219
77. Ruse ND, Smith DC, Torneck CD, Tiltley KC (1990) Preliminary
surface analysis of etched, bleached, and normal bovine enamel. J
Dent Res 69:1610–1613
78. Schulte JR, Morrissette DB, Gasior EJ, Czajewski MV (1994) The
effects of bleaching application time on dental pulp. J Am Dent
Assoc 125:1330–1335
79. Seale NS, McIntosh JE, Taylor AN (1981) Pulpal reaction to
bleaching of teeth in dogs. J Dent Res 60:948–953
80. Seghi RR, Denry I (1992) Effects of external bleaching on
indentation and abrasion characteristics of human enamel in vitro.
J Dent Res 71:1340–1344
81. Shannon H, Spencer P, Gross K, Tira D (1993) Characterization of
enamel exposed to 10% carbamide peroxide bleaching agents.
Quintessence Int 24:39–44
82. Sinensky MC, Leiser AL, Baqbish H (1995) Oxidative stress
aspects of the cytotoxicity of carbamide peroxide: in vitro studies.
Toxicol Lett 75:101–109
83. Steinberg D, Blank O, Rotstein I (2003) Influence of dental
biofilm on release of mercury from amalgam exposed to
carbamide peroxide. J Biomed Mater Res 15:627–631
84. Timblin CR, Janssen YWM, Mossman T (1995) Transcriptional
activation of the proto-oncogen c-jun by asbestos and H
2
O
2
is
directly related to increased proliferation and transformation of
tracheal epithelial cells. Cancer Res 55:2723–2726
85. Tredwin CJ, Naik S, Lewis NJ, Scully C (2006) Hydrogen
peroxide tooth-whitening (bleaching) products: review of adverse
effects and safety issues. Br Dent J 200:371–376
86. Ulukapî H, Benderli Y, Ulukapi I (2003) Effect of pre- and
postoperative bleaching on marginal leakage of amalgam and
composite restaurations. Quintessence Int 34:505–508
87. Upham BL, Kang KS, Cho HY, Trosko JE (1997) Hydrogen
peroxide inhibits gap junctional intercellular communication in
glutathione sufficient but not in glutathione deficient cells.
Carcinogenesis 18:37–42
88. Watt BE, Proudfoot AT, Vale JA (2004) Hydrogen peroxide
poisoning. Toxicol Rev 23:51–57
89. Weitzman SA, Weitberg AB, Stossel TP, Schwartz J, Shklar G
(1986) Effects of hydrogen peroxide on oral carcinogenesis in
hamsters. J Periodontol 57:685–688
90. White DJ, Kozak KM, Zoladz JR, Duschner HJ, Götz H (2000)
Effects of tooth-whitening gels on enamel and dentin ultrastructure—
a confocal laser scanning microscopy pilot study. Compendium 21:
S29–S34
91. White DJ, Kozak KM, Zoladz JR, Duschner HJ, Götz H (2002)
Peroxide interaction with hard tissues: effects on surface hardness and
surface/subsurface ultrastructural properties. Compendium 23:42–48
92. White DJ, Kozak K, Zoladz JR, Duschner HJ, Götz H (2003)
Effects of Crest® Whitestrips™bleaching on surface morphology
and fracture susceptibility of teeth in vitro. J Clin Dent 14:82–87
93. Zantner C, Beheim-Schwarzbach N, Neumann K, Kielbassa AM
(2007) Surface microhardness of enamel after different home
bleaching procedures. Dent Mater 23:243–250
94. Ziegler-Skylakakis K, Andrae U (1987) Mutagenicity of hydrogen
peroxide in V79 Chinese hamster cells. Mutat Res 192:65–67
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