Odontology (2024) 112:700–710

https://doi.org/10.1007/s10266-024-00914-4

REVIEW ARTICLE

Tooth whitening: current status and prospects

Kaiyi Li1,2 · Shuang Chen2 · Jingjing Wang3 · Xuan Xiao1,2 · Zhifeng Song1,2 · Shangfeng Liu2,3

Received: 20 September 2023 / Accepted: 7 February 2024 / Published online: 3 April 2024
© The Author(s), under exclusive licence to The Society of The Nippon Dental University 2024

Abstract
As a safe, effective, economical, and convenient technique, tooth whitening is one of the most popular treatments for improv-
ing tooth discoloration. This review summarizes the theoretical and recent research developments in the classification and
mechanisms of tooth discoloration, as well as the principles, agents, effects, and side effects of tooth whitening techniques.
The aim is to provide a basis for the clinical treatment of tooth whitening techniques and to suggest possible new ideas for
further research. The accepted mechanism of whitening is the redox reaction of oxides in the whitening reagent, and the
whitening effect is remarkable. However, side effects such as tooth sensitivity and irritation of gum and other oral soft tissues
can still occur. It is recommended that more monitoring be carried out in the clinic to monitor these side effects, and care
should be taken to protect the soft tissues in the mouth during office whitening procedures. Furthermore, there is a need to
develop new additives or natural whitening products to reduce the occurrence of side effects.

Keywords Tooth whitening · Tooth discoloration · H2O2 · Dental fluorosis

Introduction tooth discoloration, caused by various factors, is a common

problem that affects many individuals. As living standards
Overview of the history and current status of tooth improve, there is a growing demand for effective treatments
whitening. to address this aesthetic flaw. This has led to the emergence
The development and popularity of aesthetic dentistry of tooth bleaching, a treatment that has been popular for over
have become important factors in the field. Recently, 150 years [2]. Bleaching discolored teeth, whether the dis-
patients have been increasingly concerned with achieving coloration is significant or not, has become a highly popular
a visually pleasing smile, and there has been a noticeable solution. It is relatively efficient, cost-effective, and simple,
shift in the perception of beauty in the media [1]. However, while also providing excellent protection for the hard tis-
sues of the teeth.Various methods and ingredients have been
used for tooth whitening. In 1895, Westlake [3] and others
Kaiyi Li, Shuang Chen, Jingjing Wang contributed equally to this reported achieving satisfactory whitening results using a
work. mixture of 30% ­H2O2 and acetaldehyde, along with electron-
warming. Ames et al. [4] mixed 30% ­H2O2 and acetaldehyde
* Zhifeng Song
Shangfeng_liu683@fudan.edu.en in a ratio of 5:1 and successfully removed fluoride plaque
from tooth enamel using this mixture in conjunction with
* Shangfeng Liu
szf9110627@163.com metal apparatus heating, 30 min at a time, for 5–25 ses-
sions. Since the 1930s, the technique of bleaching vital teeth
1
Department of Oral Mucosa, Shanghai Stomatological using ­H2O2, in combination with light, has gradually gained
Hospital, Fudan University, Shanghai 200031, acceptance in dental practices [5]. Klusmier [6] discovered
People’s Republic of China
that the oral anti-inflammatory Glyoxide, which contains
2
Shanghai Key Laboratory of Craniomaxillofacial 10% carbamide peroxide, not only had a suppressive effect
Development and Diseases, Shanghai Stomatological
Hospital, Fudan University, Shanghai 200001,
on gingival inflammation but also improved tooth color
People’s Republic of China when administered to orthodontic patients suffering from
3
School of Materials Science and Engineering, University
gingivitis. Another oral anti-inflammatory drug, Proxigel,
of Shanghai for Science and Technology, Shanghai, containing 10% carbamide peroxide, was introduced as a
People’s Republic of China

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Odontology (2024) 112:700–710 701

highly concentrated and easily adherent tray [7]. As a result, Traditionally, extrinsic tooth discoloration has been clas-
Proxigel became a popular option for tooth whitening. With sified based on its origin and whether it is metallic or non-
the advancement of materials and clinical techniques, mul- metallic [11]. However, this classification is considered too
tiple dental bleaching materials have been used, including simplistic. To explain the mechanism and degree of discolor-
oxalic acid, calcium hypochlorite, hydrogen peroxide (HP), ation, the N (Nathoo) classification has been proposed [12].
carbamide peroxide, and sodium perborate [8]. Currently, N1-type refers to colored substances (chromogen) that bind
the whitening effect primarily occurs through the oxidation to the salivary film on the tooth surface, resulting in staining
reaction of HP [9]. This review provides a summary of the and a tooth color like that of the chromogen. Tannins and
classification and mechanisms of tooth discoloration, com- polyphenols found in tea, wine, and coffee, which contain
mon tooth whitening techniques and bleaching reagents. conjugated double bonds, can interact with the tooth surface
It also discusses the mechanisms, effects, side effects, and through ion exchange, causing staining. N2-type involves
current research advancements in whitening techniques. In color changes that occur when a colored substance binds to
addition, it poses further research questions based on the the saliva film or tooth surface, leading to a darker or dif-
current stage of development in the field of teeth whitening. ferently colored stain than the original color. This category
The review aims to help dentists understand the advantages, also includes the aging brown change or yellow staining in
limitations, and optimal options for teeth whitening. the spaces adjacent to the teeth. N3-type involves colorless
substances or pre-colorants that bond with the teeth through
physical actions before undergoing a chemical reaction to
Tooth discoloration classification produce colored substances or chromophores, resulting in
and principles tooth staining [12]. The treatment of extrinsic discoloration
is relatively simple. After eliminating external causes, the
Extrinsic discoloration and intrinsic discoloration of teeth color of the teeth can generally be restored. Stubborn stain-
and their different causes. ing can be removed through scraping or polishing, but some
Depending on the location and cause of staining, there stains may require bleaching treatment. Intrinsic discolora-
are two types of tooth staining: extrinsic discoloration and tion, unlike extrinsic discoloration, occurs due to the pres-
intrinsic discoloration (as shown in Table 1). Extrinsic ence of chromogenic material within the enamel or dentin.
discoloration is caused by substances such as tea, coffee, Various factors can cause intrinsic staining, including cer-
tobacco, and pharmaceuticals being absorbed into the sur- tain systemic diseases that affect tooth color (e.g., patients
face of the tooth. This attraction is due to long-term electro- with congenital erythropoietic porphyria have purplish-red
static and van der Waals forces, or short-term hydrophobic or brown teeth), enamel or dentin hypoplasia (resulting in
forces, dipole–dipole forces, and hydrogen bonding [10]. brown or black striped teeth), natural thinning of enamel

Table 1  Factors in tooth coloring

Origin of stain Color of stain Mechanism of discoloration Treatment

Extrinsic discoloration Tea, coffee, tobacco and Brown to black Electrostatic and van der Remove exogenous factors
pharmaceuticals Yellow/brown to black Waals forces Scraping or polishing
Dipole–dipole forces and Bleaching
hydrogen bonding
Intrinsic discoloration Tetracycline Classically yellow, brown, Tetracycline and calcium Scraping or polishing
blue, black or grey ions are chelated together Bleaching
to cause staining Aesthetic restoration of teeth
Fluorosis White, yellow, grey or black Pigment penetrates through
the space between hard
tissues
Enamel or dentin hypoplasia Grey black Incomplete mineralization of
enamel or dentin formation
Systemic diseases Congenital erythropoietic Hemoglobin metabolism
porphyria (red/purple disorder
brown)
Pulpal hemorrhage Pink spot Hemoglobin molecules
penetrate the dentin
Aging causes Dark yellow Changes in tooth enamel and
dentin
702 Odontology (2024) 112:700–710

and increased deposits of dentin with age (leading to vary- divided into in-office bleaching treatments and home bleach-
ing degrees of tooth discoloration), bleeding and necrosis ing treatments, depending on where the treatment is carried
of the pulp, excessive calcification of dentin, dehydration of out [20]. In-office bleaching treatments usually involve the
dentin, residual pulp decomposition after root canal treat- use of a strong oxidizing agent, commonly HP at 30% [21].
ment, silver amalgam fillings, and the use of phenolic resin These treatments may also be supplemented with physical
in root canals. Tetracycline and fluorosis are also medical methods like cold-light exposure, laser exposure, or infra-red
factors that can cause tooth discoloration [13]. Dental fluo- exposure, which generate a large amount of active oxygen
rosis is a condition in which the hard tissues of the teeth are radicals in a short period of time [22]. The results of in-
altered, and enamel development is defective, due to exces- office bleaching are immediately visible after the treatment.
sive fluoride intake during tooth development. It is the most Home bleaching, also known as tray or night bleaching, is
common symptom of early-stage chronic fluorosis and can performed using a lower concentration of bleaching agent,
result in abnormal tooth appearance, ranging from slight typically 10–15% carbamide peroxide (CP) [23, 24]. This
white spots to dark brown stains, which affects the patient’s method involves taking upper and lower jaw impressions
aesthetics [14]. The global prevalence of dental fluorosis at the patient’s initial visit to create individual trays. The
has been increasing annually for the past two decades [15]. patient then takes the trays home and applies the bleaching
medication at night before going to bed, wearing the trays
overnight. This process does not disrupt the patient’s daily
Teeth whitening techniques life [24, 25]. Home bleaching techniques have several advan-
tages over in-office bleaching techniques. They are easy to
The history and development of tooth whitening technol- use, can be done by the patient alone at home, require fewer
ogy, the application of internal and external bleaching tech- visits to the dentist, are less expensive, accessible to the
nology, in which external bleaching technology is divided patient, and simple to perform.
into in-office bleaching treatments and home bleaching The development and main types of over-the-counter
treatments. whitening products.
Teeth whitening technology has existed for over Due to the increasing demand of patients for the beauty of
150 years. In fact, the first successful tooth whitening treat- their teeth, there has been an explosion of over-the-counter
ment was performed back in 1877 by Dr. Chapple using whitening products on the market. These over-the-counter
HCL. This external whitening technique is widely accepted teeth whitening techniques and materials can be easily
and does not cause significant damage to the hard tissues of applied at home. The main difference between at-home teeth
the teeth [9]. The primary bleaching reaction for teeth whit- whitening and teeth whitening offered at a dental office (in-
ening involves a chemical redox reaction using hydrogen office) is that at-home teeth whitening requires the patient to
peroxide ­(H2O2) [16]. Another commonly used bleaching purchase the over-the-counter whitener separately and apply
agent is carbamide peroxide ­(CH6N2O3), which ultimately it independently. There are many teeth whitening products
produces ­H2O2 as its main active ingredient [17]. The per- on the market, such as toothpaste, mouthwash, whiten-
oxide molecule is small and easily penetrates the enamel ing strips, whitening floss, toothbrushes, lacquer-coated
surface of the teeth. The strong permeability of the whiten- gels or film activated charcoal. Whitening toothpastes, the
ing drug allows it to reach the deeper layers of the teeth, most common type of over-the-counter tooth whitening
breaking down large pigment molecules into smaller ones. agent, contain abrasives to remove stains, as well as small
These smaller molecules diffuse to the tooth surface and get amounts of HP and urea peroxide [26]. There are also whit-
absorbed, resulting in a whitening effect [18]. Since peroxide ening toothpastes on the market that do not have a fixed
whitening reagents are strong oxidizing agents, direct con- whitening agent or abrasive ingredient, and some contain
tact with the tooth enamel surface is necessary for a certain baking soda, papain, hydroxyapatite, calcium carbonate, and
period to achieve the desired whitening effect. Therefore, sodium fluoride. Two studies have found that cyanobromine
this study focuses on the effect of the tooth enamel surface is a tooth whitening agent. Blue pigment is a pigment that
on peroxide whitening reagents. There are two types of tooth is uniformly deposited and retained on the surface of the
bleaching techniques based on the route of administration: membrane-covered tooth. It is said to change the color from
internal bleaching and external bleaching. Internal bleach- yellow to blue, creating the illusion of whitening teeth [27,
ing, also known as non-vital bleaching or walking bleaching, 28]. Studies have shown that toothpaste whitens teeth “by
involves the application of a bleaching agent through the removing external stains” compared to a placebo [29]. The
pulp chamber. It is typically used for discolored teeth that use of whitening strips is mainly to avoid the use of cus-
have had root canal treatment [19]. External bleaching, on tom trays and allow the public to use them directly. They
the other hand, involves the application of a bleaching agent typically contain 5–14% HP and are used in teeth, with the
directly on the crown surface. This technique can be further active ingredient released within 5–60 min, once or twice a
Odontology (2024) 112:700–710 703

day [30]. Two studies have shown that whitening strips are and hydrophilic structures. The transformed compounds
effective and that increasing exposure time produces bet- are then displaced into light-colored simple compounds,
ter results. Oliveira et al. '’s study determined that strips while the remaining molecules are broken down into safe
with lower HP concentration and longer use time performed and harmless water molecules, which are then discharged
better than strips with higher HP concentration and shorter [26]. This process allows the visible absorption spectrum of
use time [31, 32]. Compared to other over-the-counter tooth the tooth to shift from longer to shorter wavelengths, result-
whiteners, whitening strips are considered effective in most ing in the whitening of colored or less dark compounds.
studies. Whitening mouthwashes typically contain low con- Another whitening agent, ­CH6N2O3 also whitens teeth by
centrations of HP (1.5%) and sodium hexametaphosphate breaking down into urea and HP ­(H2O2). The strong oxidiz-
(4%). Paint gels or varnishes contain HP or carbamide per- ing properties of H ­ 2O2 are then utilized to whiten the teeth
oxide, which can be attached to tooth enamel and applied to [38]. In cold-light whitening, high-intensity blue light with
the tooth surface by an applicator [33, 34]. wavelengths between 480 and 520 nm is used to increase the
release rate of ­H2O2. This allows for concentrated penetra-
tion of the focal ­H2O2 in the short term, without generat-
Mechanisms of teeth whitening ing excessive heat, which could negatively impact the pulp
chamber [39]. This method ensures that the pulp chamber
The redox reaction of HP is currently considered the funda- is not adversely affected. In addition, the gingival and soft
mental principle of tooth whitening. tissues of the oral mucosa are not exposed to the whitening
Traditionally, tooth whitening has been based on the agent during the treatment, making cold-light whitening a
“chromophore theory,” which suggests that HP interacts safe procedure [40]. Previous studies have shown that the
with organic chromophores to lighten the color of teeth [35]. permeability of HP is influenced by various factors, includ-
According to this theory, HP has the ability to penetrate the ing the concentration of HP, duration of application, tem-
enamel and dentin of the tooth, thanks to the high perme- perature during application, size of dentin tubules opening,
ability of these hard tissues [36]. The exact mechanism by and structural changes in the tooth caused by location, acid-
which peroxides whiten teeth is not fully understood and can etching, or restorations [41–45]. The presence or absence of
vary depending on factors such as the type of tooth stain- photo-excitation also affects peroxide permeability, further
ing and environmental conditions like pH, temperature, and emphasizing the importance of these factors in the tooth
light [37]. The redox reaction of HP is currently considered whitening process [46].
the fundamental principle of tooth whitening. When HP
is oxidized, it releases new oxygen and forms superoxide
radicals ­(HO2−). These radicals quickly penetrate the tooth
Common bleaching agents
surface and dentin tubules to break down the pigments that
are attached to the tooth's surface and deeper layers [9]. a) Hydrogen peroxide
The ­HO2− radicals have strong oxidizing properties, which
cause the pigment molecules to degrade from large to small Hydrogen peroxide ­(H2O2) is a colorless liquid with a bitter
molecules. Long chain molecules become short chain mol- taste and is highly soluble in water, resulting in an acidic
­ O2− reacts with
ecules and are dispersed out of the tooth. H solution (Table 2). It was first proposed for dental treatment
the pigmented substances, transforming the organic pig- in 1884 [47]. In dentistry, HP is used at concentrations rang-
ments such as carbon ring structures into non-pigmented ing from 5 to 35% [34]. It acts as a strong oxidizing agent,

Table 2  Type of whitening agent

Common Mechanism Molar mass Advantages Disadvantage
concentra- of whitening
tion

Hydrogen peroxide (­ H2O2) 5–35% Oxidation 34.01 g/mol Low concentrations have signifi- Tooth sensitivity and other side
cant effects effects
Carbamide peroxide ­(CH6N2O3) 10–35% Oxidation 94.07 g/mol Long effective time, high pH Urea may affect the efficiency
value
Sodium perborate ­(NaBO3) NA Oxidation 99.82 g/mol Safety and stability Not yet mature
Needs further validation
Chlorine dioxide ­(ClO2) 0.07% Oxidation 67.45 g/mol Quick to effect Not yet mature
Needs further validation
704 Odontology (2024) 112:700–710

producing reactive oxygen molecules and HP anions. When When it comes into contact with acid and water, it decom-
HP comes into contact with organic matter, a redox reaction poses to form HP, sodium hypoborate, and nascent oxygen,
occurs, leading to the formation of oxygen radicals that are resulting in bleaching [34]. Sodium perborate exists in dif-
chemically active for 0.5–1 h. These neo-oxygen and free ferent forms, such as mono-, tri-, or tetrahydrate ­(NaBO2 •
radicals can penetrate the enamel and dentin, combine with ­H2O2 • ­3H2O), which differ in oxygen content and whiten-
the pigment base in the dentin tubules, and break it down ing efficacy. The release of hydrogen peroxide occurs when
into smaller molecules, resulting in a bleaching effect [48]. water is added [26]. Mixing sodium perborate with water,
In 2020, a meta-analysis on the effect of high concentrations instead of hydrogen peroxide, does not diminish its bleach-
of HP (35%) on tooth bleaching and the occurrence of aller- ing effect [55]. Since 1907, sodium perborate has been used
gic reactions showed a significant objective color change as an oxidizing and whitening agent, particularly in wash-
(95% CI 2.99–0.08; p < 0.0001) before and after treatment, ing powders and detergents [29]. Studies by Rotstein et al.
but no significant difference in subjective color change. In [56] showed that a mixture of sodium perborate and distilled
addition, tooth sensitivity was more likely to occur with water is effective as an intracorneal bleaching agent, and this
increasing concentrations of HP [49]. A review by Kaprice paste is recommended as it reduces the risk of dental tissue
et al. [50] demonstrated that home bleaching using 10% resorption. Sodium perborate is easier to control and safer
hydrogen peroxide is equally effective and is accompanied than high concentrated hydrogen peroxide solutions.
by transient and mild tooth sensitivity. It is worth noting
that some individuals may experience transient symptoms, d) Chlorine dioxide
such as tooth sensitivity, within 48 h of treatment, and some
may experience complications with cervical resorption for Chlorine dioxide ­(CIO2) is an oxidizing agent commonly
a longer period, particularly with the intracorneal bleaching used in water treatment and bleaching (Table 2). In its steady
technique [51]. state, chlorine dioxide is a colorless, odorless, transparent
aqueous solution that is stable, non-flammable, non-volatile,
and non-corrosive, with a molar mass of 67.45 g/mol [57].
b) Carbamide peroxide It has recently been used for tooth whitening techniques in
non-dental applications, and in vitro studies have shown that
Carbamide peroxide (­ CH6N2O3), also known as amide car- 0.07% chlorine dioxide whitens teeth much faster than 35%
bonate, is a white crystalline powder that is easily soluble hydrogen peroxide [58]. However, the technique of using
in water and does not cause obvious irritation (Table 2). It chlorine dioxide for tooth whitening requires further follow-
melts at 75–85 °C and releases reactive oxygen. The con- up records and exploratory analysis of safety.
centrations used for bleaching range from 10 to 35%. A 10%
solution of carbamide peroxide, commonly used as a house-
hold bleach, consists of 3% HP and 7% urea [52]. The urea Whitening change analysis
in carbamide peroxide mainly acts as a stabilizer, prolonging
its shelf life and slowing down the release of HP. It also has a Color effect analysis
caries inhibiting effect. Carbamide peroxide products usually
contain either a Carbopol or glycerin base. The Carbopol There are many methods available to measure the color of
base slows down the release of HP, making it effective over teeth, ranging from visual comparisons using shade guides
a longer period [53]. A review by Suhayla et al. [54] showed to instrumental measurements using spectrophotometers,
that 10% and 15% carbamide peroxide was effective in treat- colorimeters, spectroradiometers, and digital image analy-
ing all types of tooth discoloration in various studies and was sis techniques [8]. The most common clinical method is
a safe and effective method. The side effects of this treat- visual comparison with commercial colorimetric cards.
ment include tooth sensitivity and gingival irritation, but However, this method is subjective and inconsistent, and
they are usually mild to moderate. The decision to proceed can be influenced by various factors leading to errors.
with treatment depends on the degree of symptoms reported Nonetheless, it is an easy and quick method [59]. A spec-
by the patient. However, it is crucial for dental profession- trophotometer is capable of measuring the light energy
als to monitor patients during the bleaching treatment and reflected from an object at specific intervals of 1–25 nm
provide prompt preventive measures in case of side effects. along the visible spectrum. It can then convert the meas-
ured spectral reflectance into color coordinates and vari-
c) Sodium perborate ous tooth shade values [60]. There are various commer-
cial spectrophotometers available for clinical use, each
Sodium perborate is a chemically stable powder at room with different designs, software, and data output. Several
temperature, with a molar mass of 94.07 g/mol (Table 2).
Odontology (2024) 112:700–710 705

studies utilizing digital spectrophotometric systems have Therefore, the choice of light source for activation may
demonstrated significant improvements in tooth bright- yield different whitening effects.
ness and shade following dental bleaching with peroxide
[61, 62]. Kaprice et al. [50] conducted a study using both Changes in the hard tissue structure of the teeth
the Vita Classical shade guide and the Easyshade spec-
trophotometer to assess the effectiveness of home bleach- Dental tissue hardness
ing with 10% hydrogen peroxide. The study found both
subjective and objective improvements in tooth color, Tooth whitening agents may potentially impact the hardness
indicating the efficacy of the bleaching treatment. How- and surface roughness of tooth enamel, thereby altering the
ever, it is important to consider the influence of ambient biomechanical characteristics of teeth [71]. Dental bleach-
light sources when using the spectrophotometer device to ing agents can affect the organic composition of the tooth
ensure accurate measurements in natural light conditions surface and lead directly to changes in the mineralogical
[63]. In addition, some devices require physical contact phase of dental tissue, resulting in changes to the surface
and may cause slight discomfort, as the patient is required morphology of teeth [72]. Rafael et al. [73] discovered that
to keep their head and gingival tissue stable [64]. There all bleaching processes resulted in a decrease in tooth sur-
are also some evaluation indicators for tooth whiteness face hardness after 24 h compared to the control group. Fur-
change, such as CIELAB index or WIO whiteness index. thermore, the higher the peroxide concentration, the greater
CIELAB model is a color model published by the Inter- the decrease in surface hardness. In addition, some studies,
national Commission on Illumination (CIE) in 1976, and analyzed through microhardness measurement, found that
is the most frequently used tool for studying tooth color dental tissue microhardness decreased slightly when bleach-
representation [65]. In the literature, many whiteness indi- ing discolored teeth with a photo-activated oxidant com-
ces have been proposed for various industrial needs, but pared to when the same concentration of oxidant was used
those related only to dental applications are considered alone [74, 75]. Hence, it has been observed that this loss of
here. One of them is the CIE Whiteness Index (WIC), tooth microhardness caused by bleaching agents primarily
which was proposed by the CIE in 1986 for neutral tone occurs due to an oxidative reaction, resulting in tooth dem-
preferences. In addition, it is important to point out that ineralization. However, this change can be reversed using
the color measurement equipment currently used in den- remineralization via saliva [76]. The SEM results suggest
tistry almost exclusively uses the CIEWIC color space for that the cold-light whitening treatment had an impact on the
tooth whiteness measurement (effectiveness of different surface morphology of tooth enamel. In the control group,
bleaching agents) [8]. The WIO whiteness index is opti- the enamel surface displayed normal morphology with only
mized from the CIEWIC and has been developed specifi- superficial surface scratches and no evident pit-like struc-
cally for the evaluation of tooth whiteness. WIO maintains tures. Conversely, the enamel surface of the samples in
the functional form of the CIEWIC index and has proved each whitening group was rough and uneven, characterized
to be adequate for use in teeth whitening research and by porous structures, irregularly shaped pores, and shal-
monitoring [66]. The effectiveness of tooth whitening low disc-shaped pits [8]. In addition, the pH of the bleach-
depends on various factors such as the pH of the whiten- ing reagent plays a crucial role in determining the extent
ing reagent, the ambient temperature, the catalyst used, of impact on enamel hardness. Whitening agents with an
and the choice of light activation source [67]. A review acidic pH significantly reduce the microhardness of dental
study conducted in 2020 showed that low and medium tissue compared to those with a neutral or slightly alkaline
concentrations of hydrogen peroxide for office whitening pH [54]. Studies have demonstrated that the use of 25% HP
were equally effective compared to high concentrations, whitening products with a pH of 3.2 significantly diminishes
with the added benefit of lower risk of tooth sensitivity the microhardness of tooth enamel compared to whitening
[68]. There is still ongoing debate on whether the inclu- products with 38% HP and a pH of 6.7 [77].
sion of photo-activated oxides enhances the effectiveness
of tooth bleaching. However, a recent meta-analysis con- Dental tissue roughness
ducted in 2022 concluded that the use of light-activated
office bleaching gels does not significantly improve color The researchers conducted an analysis and comparison of
change or affect tooth sensitivity, regardless of peroxide changes in enamel surface roughness following various dif-
concentration, without considering changes in the protocol ferent dental bleaching agent treatments. They discovered
[69]. Conversely, the results of a randomized clinical trial that these whitening treatments have the potential to induce
demonstrated that halogen light significantly improved enamel surface roughness [78]. Moraes et al. [79] compared
the level of tooth whitening compared to laser light [70]. the effects of whitening agents containing different concen-
trations of CP on enamel surface roughness. They discovered
706 Odontology (2024) 112:700–710

that the 10% CP group showed no change in roughness, but enamel and dentin, resulting in oxidation reactions in both
the enamel surface showed a significant increase in rough- the chromogenic mass and healthy dental tissue. This leads
ness after 1 week of treatment with 35% CP. However, a to the loss of carbonates and proteins in enamel and dentin
randomized human clinical trial [80] showed no significant through hydrogen peroxide treatment, as well as changes in
difference in enamel roughness after using 38% HP and the representative biological bands of hydroxyapatite and
35% CP. This contradictory result may be attributed to the the destruction of the tooth surface [85]. Another view is
measurement method used in the latter study. Roughness that glycerin, the carrier in whitening products, can cause
was indirectly measured on the surface using a two-stage dehydration of the tooth structure due to its hydrophilic
polysiloxane impression, which was then analyzed using a nature [86]. To reduce the occurrence of tooth sensitivity,
non-contact profilometer. This two-stage non-contact meas- researchers have attempted to add desensitizers to whiten-
urement method increases the risk of errors and may lead to ing products, but these have not significantly reduced the
inconsistent results. Enamel surface roughness is also influ- risk or severity of sensitivity [87]. The main focus now is to
enced by the concentration and pH of the oxides in the whit- minimize the risk of tooth sensitivity using lower concen-
ening agent. Several studies have compared the changes in trations of whitening products, spacing out the whitening
enamel surface roughness following the application of whit- cycles, and reducing the duration of use, while still ensuring
ening products with different pH levels and concentrations. an effective whitening effect. Some ingredients in whiten-
These studies have shown that enamel surface roughness ing products can irritate the gingival tissue or oral mucosa.
increases with decreasing pH and increasing concentration This may be due to the use of unsuitable trays or the use of
[77, 81, 82]. It has also been found that the timing of bleach high concentrations of hydrogen peroxide, which is corro-
application may have a greater impact on changes in enamel sive to soft tissues and may cause chemical burns to the oral
surface roughness than the concentration [83]. In conclusion, mucosa [88]. It is therefore necessary to provide protective
it is recommended to use low-concentration and low acidity measures for the soft tissues inside the mouth and prevent
whitening products in clinical practice to achieve desired the patient from accidentally swallowing the product, which
results while minimizing the alteration of dental tissues and could cause discomfort in the esophagus and stomach. There
avoiding potential side effects. has been speculation that hydrogen peroxide may be a risk
factor for oral cancer, particularly gingival cancer, due to
its potential genotoxicity and carcinogenicity. However, a
Side effects of tooth bleaching review by I.C. Munro et al. [89] suggested that the use of
teeth whitening products does not increase the risk of oral
Side effects of tooth whitening include tooth sensitivity, cancer in heavy drinkers and/or heavy smokers. In addition,
abrasion, gingival irritation, and gingival recession. Pro- dental bleaching agents can affect dental restorative materi-
tective measures have been developed to reduce these side als and dental fillings, and may reduce the adhesion proper-
effects. ties of these materials to the teeth [23]. Bonding operations
It is important to note that hydrogen peroxide not only should not be carried out immediately after teeth have been
interacts with the chromogenic mass when diffusing into bleached, as the bonding strength of both the material and
the dental tissues but also penetrates into the normal tissues the acid-etched enamel may be compromised. To mitigate
and may cause unwanted damage, resulting in sensitivity, these side effects of whitening products, various compounds
wear and tear of the dental tissues, gingival irritation, and have been developed and utilized in these products to pro-
gingival tissue recession [19]. Two-thirds of patients treated vide a whitening effect while avoiding adverse reactions
with home teeth whitening products experience tooth sensi- such as tooth sensitivity. Ingredients such as potassium
tivity. The majority (55%) experience mild sensitivity, while nitrate and amorphous calcium phosphate have been identi-
10% may experience moderate sensitivity and only 4% may fied as capable of reducing hypersensitivity reactions [90].
experience severe sensitivity [84]. Tooth sensitivity is one of Therefore, combining low-concentration bleach with remin-
the most common side effects of the bleaching process and is eralization agents is expected to be a new development in the
generally characterized by sensitivity to hot and cold stimuli. treatment of tooth discoloration. Hydroxyapatite is a natural
It can appear in the early stages of bleaching and typically mineral component present in bones, which makes up 30
disappears in most patients 24–48 h after the termination of to 70 percent of the mass of bones and teeth [91]. Nano-
bleaching [19]. The reported incidence of tooth sensitivity hydroxyapatite (nHA), a highly biocompatible and bioactive
varies considerably in the literature, making it difficult to material, has been incorporated into toothpaste, mouthwash,
accurately assess the degree of allergy due to individual dif- and products for clinical applications to restore the integrity
ferences and the wide range of bleaching agents available. of damaged tooth enamel [92]. Nano-hydroxyapatite, is also
Tooth sensitivity caused by bleaching agents is partly due a bleach adjuvant that helps limit the side effects caused
to the significant interaction of hydrogen peroxide with the by teeth whitening. There are now articles showing the
Odontology (2024) 112:700–710 707

potential beneficial effects of nHA-enriched hydrogen per- bleaching procedure, especially when restorations and
oxide when used in home bleaching treatments [93]. Nano- sensitive teeth are present.
hydroxyapatite can remineralize tooth enamel in two ways: To achieve the desired bleaching effect while minimiz-
(1) by forming a thin and uniform apatite layer on the surface ing side effects, it is recommended to use slightly alkaline
of the demineralized enamel to close its small pores [94, and low-concentration bleaching products and limit the
95]; and (2) by providing calcium and phosphate to maintain exposure time. For patients undergoing home whitening,
the supersaturated state of enamel minerals, and facilitate we suggest a follow-up visit at the 24th or 48th hour to
the deposition of apatite in the enamel layer [96]. Previous assess tooth sensitivity. If the patient experiences moder-
studies have shown that bleach can cause structural changes ate or severe sensitivity that significantly affects their daily
in tooth enamel, such as erosion and depressions. Nano- life, it is advised to pause the treatment and provide an
hydroxyapatite, containing pressure-measuring particles, can anti-allergy treatment.
penetrate these eroded areas, avoid further demineralization, Furthermore, considering the potential for gingival tis-
and promote remineralization as sediments are deposited. sue irritation caused by whitening products, it is advisable
This promotes less mineral loss without interfering with the to perform whitening treatments after aggressive perio-
bleaching effect [97, 98]. Another new biomaterial, casein dontal treatment for patients with pre-existing periodontal
phosphopeptide-amorphous calcium phosphate (CPP-ACP) disease. It is hypothesized that gingival irritation from the
based substances have been developed to reduce side effects whitening products may worsen periodontal disease to a
such as tooth sensitivity and demineralization during and certain extent.
after bleaching. The CPP-ACP complex contains supersatu- Based on the mechanisms, products, effects, and side
rated calcium phosphate, which promotes remineralization effects of teeth whitening, we propose the following poten-
by providing calcium and phosphate to decalcified lesions tial areas for further development:
and increasing the acid tolerance of teeth [99, 100]. Stud-
ies have also shown that CPP-ACP paste can inhibit dentin the mechanism of tooth discoloration is influenced by
demineralization and promote dentin remineralization [101]. the presence of “chromophores”. To further research the
In vitro experiments have shown that the whitening effect effectiveness of tooth whitening technology, it would be
of household urea peroxide gel is not affected when mixed beneficial to quantify the number or quantity of these
with a paste containing CPP-ACP [102]. However, enamel “chromophores” to reduce subjective bias;
caries remineralized with CPP-ACP have a very smooth sur- the possible side effects of whitening products are mainly
face after bleaching, but the bleaching effect is decreased caused by the corrosive and toxic nature of the oxidiz-
[103]. The application of CPP-ACP to the enamel surface ing agents. While there are additives available to prevent
for 5 min after tooth bleaching can effectively restore the lost damage to normal dental tissues, they are not effective
calcium during the bleaching process, but the effect on den- and therefore require extensive in vitro and in vivo test-
tin has not been confirmed [104]. Therefore, the combined ing. In addition, the potential use of nanoarchitecture-
use of bleach and remineralization agents has been found to integrated hydrogel materials to protect teeth and soft tis-
improve the demineralization of tooth enamel, but whether sues has been considered. Hydrogels are one of the most
it affects the whitening effect still needs further in vivo and feasible soft biomaterials and have various applications
in vitro experimental research. in biomedical engineering, such as cancer therapy, wound
healing, cardiac repair, bone regeneration, diabetes treat-
ment, and obesity treatment [105]. In the field of oral
Conclusions and recommendation health, hydrogels are currently being investigated for their
potential in dentin-pulp composite regeneration engineer-
The bleaching of discolored teeth using the redox reaction ing, bone regeneration engineering, cartilage regeneration
of hydrogen peroxide is currently the most popular and rec- engineering, salivary gland regeneration, and head and
ognized method of teeth whitening. Although a variety of neck squamous cell carcinoma [106].
bleaching products have demonstrated outstanding whit-
ening results, their effectiveness is still influenced by sev-
Acknowledgements The work is supported by medical engineering
eral factors including the pH of the bleach, concentration, cross innovation project of University of Shanghai for Science and
bleaching time, and additive composition. Technology, Shanghai.
It is important to note that hydrogen peroxide also
affects the microstructure of healthy dental tissue, poten- Author contributions KL, SC, JW, and SL: conception and design and
manuscript writing; SL and ZS: final approval of manuscript.
tially leading to side effects such as tooth sensitivity and
gingival irritation. Therefore, it is crucial to evaluate the Data availability Data sharing is not applicable to this article as no new
overall condition of the mouth before undergoing the data were created or analyzed in this study.
708 Odontology (2024) 112:700–710

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