Bibliography by zhangyun


Clinical studies:


A study compared the loss of calcium Ca2+ from enamel treated with 38% hydrogen peroxide, 35%
hydrogen peroxide with light, and 10% carbamide peroxide.

Method and materials: Ten extracted premolars were sectioned buccolingually and longitudinally so that
four samples were obtained from each tooth. The samples were randomly assigned into sets 1 to 4 to receive
the following whitening agents:

- Hydrogen peroxide (38%),
- Hydrogen peroxide (35%) with light,
- Carbamide peroxide (10%),
- No agent (reference group).

The samples were treated with an artificial cariogenic solution (pH 4) over 16 days; the solution was
replaced on days 4, 8, 12, and 16. The calcium concentration was determined by a spectrophotometer with
atomic absorption.

Repeated measurements (ANOVA) were carried out on the concentrations on days 4, 8, 12, and 16.

Results: At the end of day 16, the calcium ions released per square millimeter were successively indexed as
         Hydrogen peroxide (38%), 27.52 ± 5.22 µg/mL
         Hydrogen peroxide (35%) with light, 25.15 ± 4.99 µg/mL
         Carbamide peroxide (10%), 19.53 ± 4.03 µg/mL
         No agent (reference group), 18.35 ± 4.00 µg/mL

The differences between the reference group and the 35% hydrogen peroxide group and between the
reference group and the 38% hydrogen peroxide group were statistically significant.

Although the differences in demineralization were noted between the reference group and the 10%
carbamide peroxide group, this difference was not significant.

Conclusions: It is possible to conclude that the 35% hydrogen peroxide used with light and the 38%
hydrogen peroxide may cause appreciably a bigger loss of Ca2+ from the enamel surfaces. (Quintessence
2007 No. 38: 339-347)

Source: Quintessence International April 2007 Volume 38, Issue 4
"Effect of bleaching agents on calcium loss from the enamel surface" (Huseyin Tezel, DDS, PhD / Ozlem
Sogut Ertas, PhD / Ferit Ozata, DDS, PhD / Hande Dalgar, DDS / Ziya Onur Korkut, DDSResearch
Study completed by Richard B. T. Price, DDS, MS, MRCD(C), FDS, RCS (Edin), Mary Sedarous, B.Sc.,
Gregory S. Hiltz, B.Sc.(Hon.), DDS, Dalhousie University, Halifax, 2000,

1. Side effects

Dental whitening products may be in contact with the intra-oral structures (mucous, etc.) during several
hours when they are used daily to bleach the teeth. These products should thus have a relatively neutral pH
(neutral pH = 7) in order to reduce to the minimum the risk of potential damage.

The higher the peroxide concentration, the more acidic is the pH of the product. However, exposing teeth
and oral tissues to low or elevated levels of pH for a long time may cause undesirable reactions.

Thus, at pH levels lower than 5.2, cases of demineralization of the enamel and radicular resorption were

Recent research aimed at studying the effects of pH levels on enamel also seems to establish a link between a
low pH level and a strong concentration of acid and erosion of enamel.

Many dental whitening products attack enamel, causing dissolution of the surface enamel and exposing a
porous surface.

Thus, the untreated enamel appeared smoother than enamel treated with a whitening agent. It has also been
noted that the micro hardness of the surface of the enamel exposed to whitening agents had a tendency to
decrease at the beginning.

The enamel, of epithelial origin, is the most mineral-intense tissue of the body. The apatite crystals (calcium
and phosphates) constitute 96% of its weight. It is not an inert and impenetrable structure. On a microscopic
scale, it has a microporous aspect which offers ways of spreading along the sheath of the prisms which form
its structure.
A pH level of 5.5 is the critical value below which the dissolution of the hydroxyapatite is irreversible. It
results in an escape of calcium and phosphate from the tooth environment. The fluoroapatites start to
dissolve when the pH level reaches 4.6.
Other side effects range from an increase in sensitivity of teeth to live pulp, to temperature, and an irritation
of the gums.

Dental sensitivity is defined as an increased sensitivity in response to a stimulus (mechanical, chemical,
osmotic) applied to an exposed zone of dentine. Such stimuli do not normally cause a response in a healthy
It is a painful syndrome which can lead the patient to neglect hygienic methods. Brushing can indeed
constitute a mechanical stimulus which may be difficult to sustain. This state of affairs can lead to an
aggravation of the surface demineralization of the dentine and to radicular stripping which may support
this syndrome.
The dental whitening procedures available on the market typically are known to produce side effects of
increased sensitivity at the level of teeth and gums.
On average, the pH level of the whitening products on the market varies from 3.67 to 11.13. This range of
values is far from a neutral pH level (7.0).

Our unique active agent has a neutral pH level (7.2) making it perfectly appropriate for use in intra-oral
structures and minimizing the risks of side effects.
2. Exposure time and frequency of use

The exposure time and frequency of use of the product are in question.
For the whitening stage, the majority of manufacturers recommend continuous application of the product
for a period of one to two hours, while certain products must be applied all the night in the same manner (8
hours without interruption).

(§Side effects)

White+™ allows the user to rediscover a bright smile and white, healthy teeth, quickly and without
detrimental effects on enamel, dentine and gums.

3. Trays

The products available in open sale are not available with measuring trays and sometimes come with mouth
rinses or gels which must come in contact with teeth.
However, the pH of these products varies considerably (from 5.09 to 11.13), and they are likely to come in
contact with mouth tissues during the whitening procedure (§ side effects)

Our White +™ kit includes in its process customized trays, thermally formed by your dentist, requiring a
small quantity of product, without the risk of spillages onto the soft tissues.

4. The stability of the pH level

The demineralization of enamel might occur at a pH level lower than 5.2 – 5.8.

Other studies observe radicular resorption when the teeth are exposed to a low pH level. It was noted in
addition that the pH of the whitening agent changes inside the oral cavity during the whitening process.

Thus, the carbamide peroxide breaks up to form hydrogen peroxide and urea. The hydrogen peroxide
breaks up in turn to form oxygen and water, and the urea is transformed into ammonia and carbon dioxide.
The release of ammonia and carbon dioxide results in an increased pH level of the whitening agent in the
oral cavity and, thus, in the creation of a more basic medium, in 15 minutes.

The White+™ product is of neutral pH (7.2) level, patented, and stabilized, with the effects of its
propagation calibrated so that they are diffused gradually and more efficiently, over at least 15 minutes. It
also regulates pH levels; the presence of a metal sequester in our formula makes it possible to avoid the
chain reaction of components at the time of the peroxide decomposition.
Clinical Study: Sources: Research study by JADA FEBRUARY 2004 – Effect of luminous energy on
whitening with peroxide (KAREN LUK, DDS; LAURA TAM, DDS, M. Sc.; MANFRED HUBERT, Ph.D.)

Activation by a source of light at the time of dental whitening is one of the methods used to whiten teeth.
The authors carried out a study to compare the effects of whitening and changes of temperature induced by
various combinations of peroxide based products and sources of light.

The authors worked on 250 human teeth extracted according to a randomized study; groups of 10 teeth
were set up: a gel placebo control, a product with 35% hydrogen peroxide and a product with 10%
carbamide peroxide were placed on the surface of the teeth and were activated, without light for the control
teeth, with a halogen source of light, an infrared source of light, an argon laser and a CO2 laser. The change
of color was evaluated immediately, one day and one week after the treatment, by using a shade applicator
and an electronic colorimeter for analysis of color. The external and internal temperatures of the enamel and
the dentine were measured before and immediately after each 30-second cycle of application of light by
using a thermo coupled thermometer.

The changes of color and temperature were affected to a significant degree by the interaction of the
whitening and various sources of light; the application of sources of light significantly influenced certain
whitening products but caused significant rises in temperature on the external surface of teeth and inside
them. The infrared light and the CO2 laser caused the most significant rises in temperature.

Conclusions: Practitioners using a whitening technique in their offices which calls for a source of additional
light to accelerate the process of bleaching should take into account specifics of the product used as well as
the potential risks of a rise in temperature within the teeth.

Clinical implications: A specific combination of the whitening product and the source of light which
achieves a good change in color and a small rise in temperature must be preferred at the time of the dental
whitening procedure in the office.

Practical case: Dehydration of tooth during a dental whitening session completed in the office

Dehydration of the tooth is a side effect common to all dental whitening techniques. Once the tooth is
dehydrated, it can seem whiter. Once the re-hydration occurs (usually after a few days), the dehydrated
teeth "relapse" towards a darker color. Knowing that the teeth are dehydrated during whitening, one can
wonder about the real effects of quick whitening using the laser in the dentist's chair.

For better understanding of how a source of light can dehydrate teeth, the theory should be explained. In
the whitening procedure with the use of laser radiation, the process allows the light to reach the tooth with a
strong intensity. It is the infrared light and the CO2 laser which cause the largest rises in temperature. Under
the effect of this rise in temperature, the whitening agent on the surface of the tooth evaporates in the air,
which is the path of least resistance. Admittedly, a certain share of the whitening agent will infuse into the
teeth. When the light illuminates the tooth, the deeper parts of the tooth, such as the pulp and dentine
absorb the light without reflecting it. This absorbed light is converted into heat energy. This process
involves heat, which moves from the periphery towards the interior because the tooth cannot eliminate this
internal heat. Thus, the temperature of the fluids in the pulp and dentine increases. This expansion pushes
water out of the tooth through the protein matrix surrounding the stalks of enamel.

The teeth are porous, thus for this same reason, they will allow the penetration of a whitening agent, but
they will also allow for the exit of fluids from the tooth. This dehydration, just as the overheating of the
tooth, is what causes the exacerbated pain which is often reported at the time of the whitening procedures
with the use of light.
The final result of this phenomenon can be that the teeth lose water or are dehydrated and seem whiter for a
limited time, usually around 72 hours. Once they start to recover and absorb the water of saliva, just like a
sponge, they will thereby become darker... This hypothesis would thus explain the numerous "relapses" of
coloring experienced after the fast whitening process in the dentist's chair.

Risks associated with dental whitening

The risks which usually occur during and following each whitening procedure are of two types:

Those which depend on contact of the products with dental and gingival tissues;
Those which are related to the ingestion of the product;

It is the hydrogen peroxide and more precisely the free radicals which pose problems. Its toxicology was re-
examined in detail in 1993 by the European Center for Ecotoxicology and Toxicology of Chemicals

Localized risks

Hypersensitivity of dentine

One of the side effects most frequently observed is the hypersensitivity of dentine characterized by sharp
pains in response to thermal, osmotic (sugar) or tactile stimuli. Generally, such sensitivity disappears when
the treatment is stopped. Desensitizing can be accelerated by application of fluorinated products. Certain
patients give up the treatment as a result of this side effect. Thanks to the unique formula of the White+™
gel, the hypersensitivity of dentine during and after the treatment is reduced and the feeling of discomfort
usually experienced by the patient disappears.

Effect of the whitening products on dental tissue

A reduction of the hardness of enamel and dentine following the use of hydrogen peroxide was observed.
This is related to the decalcifying effect of the preparation used which has a pH level of 3.

There is less sticking of the sealing materials to the teeth following the whitening procedure probably as a
result of the presence of oxygen bubbles in the enamel. The formula of the White+™ gel includes, as a
determining factor, an adequate quantity of calcium to obviate this major disadvantage; the enamel is
protected and regenerated, leaving the teeth of your patient not only white but also healthy.

Effect of the whitening products on soft tissue of the mouth

Several studies have evaluated the effect of whitening gels on gums, tongue, lips, and palate. In these
studies, no serious damage was observed, with the exception for certain transitory damage to gums, most
likely linked to the poor adaptation of trays rather than to the use of carbamide peroxide or hydrogen
peroxide. White+TM is a concept which includes thermally formed trays customized for the patient in order
to prevent any overflow of the product, and by the consistency of the product, so that the patient does not
ingest the gel during the course of the procedure.

Other side effects were listed:

Following the modification of the oral flora, a hypertrophy of the lingual papillae is sometimes observed as
well as secondary infections by Candida Albicans.

 TEST REQUEST ON March 15, 2001

 Reference analysis: 204/0301

 TEST: EUROPEAN STANDARD NF EN 1275 (June 1997): antiseptics and chemical disinfectants – basic
 fungicide activity – testing method and recommendations (Phase 1)

 Dilution – neutralization method

 Partial test for Candida Albicans

Extract of the Report of the Test completed on our active agent
Our formula is based on an active disinfectant and antiseptic agent which meets the standard NF IN 1275. It
is effective against Candida albicans and has an antibacterial and fungicide effect.

General risks

During the first hour of wearing the tray, approximately 50% of the preparation is absorbed by the patient.
Nausea, feelings of oral dryness, exfoliations of the mucous membrane were reported. The mutation
potential of the free radicals released by hydrogen peroxide as well as the enhanced adverse effect of the
recognized carcinogenic agents was reported. For this reason, and also to avoid extrinsic staining, smoking
is contraindicated for the period of use of the whitening products. The unique properties of the active agent
contained in the White+TM gel, because of their calibration, allow the agent to diffuse progressively and
slowly, because of the stability of its formula secured through the chelating agent. The innocuousness of the
product is guaranteed, with its effectiveness increased while risks of side effects are consequently reduced.

Mutation risks

The mutation risk of hydrogen peroxide was raised on the basis of certain in vitro tests. However, on the
basis of in vivo testing, it does not seem to have any mutation risks when used in clinically useful

Oncological risks

Studies on mice
Animal studies completed in Japan by ITO et al. showed the appearance of benign and malignant tumors at
the level of the duodenum in the mice continuously exposed to amounts ranging from 0.1 to 0.4% of H2O2
in their drinking water in periods of up to a hundred weeks. The results of these studies were questioned by
several authors; in particular the researcher is criticized for having used a type of mice producing a very low
dose of catalase at the level of the duodenum, which considerably reinforces the corrosive effect of hydrogen
Studies on rats

ITO et al. gave 169 mg/kg of hydrogen peroxide (which corresponds to human ingestion of more than 10g of
hydrogen peroxide) by gavage for six days per week during a twelve week period. No histopathologic
change was observed. Later on, Ishikawa and Takayama studied the effects on the duodenum of rats of
exposure to H2O2 of 0.3% or 0.6% concentration levels in the water distributed over 26 weeks. They did not
observe any duodenum tumors in this study. On the other hand, Dahl and Becher concluded that the
presence of hydrogen peroxide in dental whitening systems could be hazardous for humans. However, their
studies are difficult to interpret compared to the normal use of carbamide peroxide in dental whitening.
Initially, the method of tube administration maximized the exposure of the gastric mucous membrane by
preventing dilution by saliva or food; secondly, the irritant effects are also quite transitory (corrected within
24 hours). According to Kelleher and Roe, the experiments of Dahl and Becher are not significant with
regard to the night use of whitening systems.

In fact it only confirms the corrosive effect of the strong hydrogen peroxide concentrations on the tissues
with which they come into contact. Other animal studies did not report negative systemic or local effects
following the use of the home whitening techniques supervised by the dentist.

Clinical studies

In order to be able to correlate the animal experiments and the toxicological risks for humans, it would be
beneficial to know with precision the amounts introduced during the treatment. Unfortunately, there are
few clinical trials measuring the quantity of the whitening agent used at the time of each application and
especially the proportion absorbed.

One study showed that less than 50% of the whitening agent was still present after one hour of application.
Haywood V. B., Heymann H. O. estimated that the quantity of carbamide peroxide absorbed was 90 mg per
application. Since then, the formulation of these agents was modified. The current technique of preparation
of the trays has allowed a substantial reduction in the quantity used at the time of each application. The
quantities vary according to the products used and the type of tray. In the whitening systems openly
available for sale, pre-fabricated trays are often provided. They are significantly oversized, which requires
the placement of a great quantity of the whitening product in the tray. Moreover, as a result of their poor
adaptation, they cause a great loss of product during the night. This type of technique is thus not advisable,
but it is often chosen by the patients because of its low cost. Several clinical studies showed the absence of
negative effects of the home whitening system when supervised by dentists.


The technique of whitening of the live teeth by wearing trays containing hydrogen peroxide is an effective
technique. It makes it possible to whiten teeth in the majority of cases, provided this technique is used under
the supervision of the dental surgeon. This technique has been the main one used for many years with, in
the majority of cases, the frequent local side effect of a transitory dentinal hypersensitivity, which is
obviated by the White+TM dental whitening products, thanks to their unique and patented active agent.

To reduce the risks of ingestion, it is necessary to use products of an appropriate concentration and
consistency, not to extend their period of application and to use trays which are properly adapted to the
morphology of the dental arch of the patient. To this the dental whitening process developed by Meodental
responds most perfectly. Its patented formula, its unique active agent, its natural principles which include,
among other things, minerals of the Dead Sea, its application time reduced to the minimum, its studied
texture, make White+TM an unsurpassable reference product in the dental market. In short, it is preferable to
avoid resorting to the systems which are available in open sale and which include standard, unadapted
trays, allowing the spillage of the gel, and consequently its ingestion.
In addition to the implementation of the adapted individual trays, there are other reasons to recommend the
supervision of dental whitening by a practitioner: diagnosis of the cause of discoloration and control over
possible side effects. They will inform the patient of the absence of whitening effect on pre-existing
restorative work and the risk of having to replace them. They will advise patient and will justify his or her
choice, if necessary, of whitening in the dentist’s office, which allows faster results, offering technical
application and permanent control of the dentist throughout the entire duration of the process. Specific
precautions must be taken in the event of extensive restorations or lack of sealing, cervical erosion, cracks in
the enamel or similar problems.

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