Kugel PDF

Formattato
A STUDY OF TOOTH WHITENING: SAFETY, EFFICACY AND
MECHANISM OF ACTION
Formattato: Tipo di
carattere: (Predefinito) Arial
Gerard Kugel
Formattato: Inizio sezione:
nuova pagina
Formattato: Superiore: 50,4
pt, In basso: 50,4 pt, Inizio
sezione: nuova pagina, Diversi
per la prima pagina
MECHANISM OF ACTION
Formattato: Centrato
1
MECHANISM OF ACTION
Formattato: Tipo di
Formattato: Portoghese
Dipartimento di Scienze Odontostomatologiche (Brasile)
Università di Siena
Viale Bracci
53100 Siena
Prepared for the graduate committee on June 13, 2004
Gerard Kugel
Boston, MA, USA
Eliminato: 89¶
2
The present thesis is respectfully submitted to Prof Piero Tosi, Rector of the University
of Siena, to Prof Alberto Auteri, Dean of the Faculty of Medicine, University
of Siena, to Prof Egidio Bertelli, vice-Dean of the Faculty of Medicine and Director of the
Department of Dental Science, and to Prof Marco Ferrari, Pro-Rector for
international affairs and President of Dental School, University of Siena.
Graduate Committee:
Formattato: Inglese (U.S.A.)
Promotor Prof. Dr Marco Ferrari
Committee Prof. Dr C.L. Davidson
Prof. Dr F. Tay Formattato: Tipo di
Prof. Dr Toledano
Prof. Dr Balleri Formattato: Tipo di
Formattato: Tipo di
Formattato: Tipo di
This thesis was prepared at Tufts University School of Dental Medicine, Boston MA, carattere: (Predefinito) Arial
USA and at the School of Dentistry University of Siena, Italy. Eliminato: 89¶
3
Contents Formattato: Tipo di
carattere: 14 pt
Formattato: Tipo di
carattere: 13 pt
Chapters
Formattato: Tipo di
carattere: 12 pt
1 Introduction Formattato: Tipo di
carattere: 4 pt
Formattato: Tipo di
2 A Novel Low Dose Tooth-Whitening Delivery System carattere: 12 pt
Formattato: Tipo di
Efficacy and Safety: A Randomized and Controlled Clinical Trial carattere: 11,5 pt
Formattato: Tipo di
carattere: 12 pt
3 Concentration and Dose Response Formattato: Rientro:
Sporgente 36 pt,
Numerazione automatica +
Clinical Trial Evaluating the Peroxide Concentration Response of a Polyethylene Livello:1 + Stile numerazione:
strip Delivery System over 28 Day 1, 2, 3, … + Comincia da:3 +
Allineamento: A sinistra +
Allinea a: 18 pt + Tabulazione
dopo: 36 pt + Rientra di: 36
4 Light activated Tooth Whitening
Formattato: Tipo di
carattere: 11,5 pt
Clinical Evaluation of a 35% Hydrogen Peroxide In-Office Whitening System
Formattato: Tipo di
carattere: 12 pt
5 Chemical Vs Light activated Tooth Whitening Formattato ... [1]
Formattato ... [2]
Clinical Evaluation of Chemical And Light-Activated Tooth Whitening Systems Formattato ... [3]
Formattato ... [4]
6 Tooth whitening and its Effect on Enamel and Dentin Formattato ... [5]
Formattato ... [6]
Daily Use of Whitening Strips on Tetracycline Stained Teeth: Comparative Results
Formattato ... [7]
after Two Months
Formattato ... [8]
Formattato ... [9]
7 Long Term Hydrogen Peroxide Exposure and its Effect on Dentin Formattato ... [10]
Formattato ... [11]
Comparative Study of 6.5% Hydrogen Peroxide Bleaching Strips on Tetracycline
Formattato ... [12]
Stain: Clinical Response after Six Months Daily Use
Formattato ... [13]
Formattato ... [14]
8 Paint on delivery systems Formattato ... [15]
Formattato ... [16]
A clinical Comparison of two Paint on Whitening Systems Formattato ... [17]
Formattato ... [18]
Formattato ... [19]
9 Maintenance of Whitening Formattato ... [20]
Formattato ... [21]
Clinical Study to Evaluate the Maintenance of Whitening after Bleaching Treatment Formattato ... [22]
Formattato ... [23]
Formattato ... [24]
Eliminato: 89¶
4
Formattato: Tipo di
carattere: 8 pt
10 Intrapulpal Temperatures with Light Activated Whitening Formattato: Tipo di
carattere: 12 pt, Grassetto
Effects of a Light Activated Bleaching System on Pulp Chamber Temperature in
Vitro Formattati: Elenchi puntati e
numerati
Formattato: Tipo di
carattere: 12 pt
Formattato: Tipo di
11 Effect of Tooth Whitening on Enamel carattere: 12 pt, Grassetto
Formattato: Tipo di
An exploratory study using SEM to evaluate the enamel surface effects in vivo of a carattere: 12 pt
6% hydrogen peroxide strip bleaching system with that of a 2.5% chlorite tray Formattato: Tipo di
bleaching system carattere: 11,5 pt, Non
Grassetto
Formattato: Rientro: Sinistro:
12 Summary and Conclusions 39,6 pt, Interlinea singola
Formattato: Tipo di
carattere: 11,5 pt
Formattato: Tipo di
carattere: 11,5 pt, Non
Grassetto
Formattato: Tipo di
Formattati: Elenchi puntati e
numerati
Formattato: Tipo di
carattere: (Predefinito) Arial,
11,5 pt, Non Grassetto, Colore
carattere: Automatico, Non
Tutto maiuscole
39,6 pt, Interlinea singola
Formattato: Tipo di
carattere: 11,5 pt, Non
Grassetto
Formattato: Tipo di
carattere: 12 pt
numerati
Formattato: Tipo di
carattere: Grassetto
Formattato: Normale
Eliminato: 89¶
5
Chapter 1 Eliminato: ¶
Formattato: Tipo di
Formattato: Tipo di
carattere: 12 pt
INTRODUCTION
Formattato: Tipo di
Grassetto
The dental profession has succeeded in reducing caries and periodontal diseases and as a Eliminato: ¶
¶
result dental problems have decrease to the point where esthetic improvements are now more ¶
¶
Formattato: Allineato a
attainable 1. One of the fastest growing areas of esthetic dentistry today is the management of sinistra
Eliminato: TOOTH
the discolored and hypoplastic dentition. The demand for an improved appearance and a whiter WHITENING
Formattato: Tutto maiuscole
smile has made tooth whitening a very popular dental procedure. Tooth whitening, sometimes
Eliminato: ¶
referred to as “bleaching”, offers a conservative treatment option for discolored teeth in Formattato: Rientro: Prima
riga: 0 pt
2,3
comparison to resin bonded composites, porcelain veneers or crowns . Candidates for Eliminato:
(Burrell 1997
Formattato: Apice
whitening procedures include patients whose teeth are stained by aging, chromogenic foods, Eliminato: )
Eliminato: (Papathanasiou
endodontic treatment, tetracycline use and smoking or use of other tobacco products. Success 2000, 2001)
of the treatment depends on type, intensity and location of the discoloration and a careful
diagnosis by the practitioner.

Formattato: Tipo di
11 pt
History of Tooth Whitening numerati
Eliminato: Bleaching
Many attempts to find an effective bleaching method have been made through out the history of
Eliminato: :
dentistry. The desire to have whiter teeth dates back at least 2000 years ago. During the first Formattato: Rientro: Prima
riga: 0 pt
century the Romans physicians claimed the use of urine, especially Portuguese, to brush the
(Dale, esthetic dentistry
Eliminato:
4
teeth would whiten the teeth . Barber-surgeons used a solution of nitric acid to lighten the teeth Eliminato:
)
(Dale, esthetic dentistry

Eliminato:
after using a course metal file to abrade the enamel 4, practice until late eighteenth century. )
Eliminato:
Eliminato:
In 1895 it was reported the combination use of pyrozone 25% and electricity to bleach the
(Westlake A, 1895)
Eliminato: .
5
endodontically treated teeth . Later on, in 1916, it was stated the use of hypochloric acid to
(Adams, 1987)
Eliminato: .
treat endemic fluorosis 6. In 1939 it was advocated the use of 30% hydrogen peroxide, ether
Eliminato: 89¶
6
(Younger, 1939
Eliminato:
7
and heat to treat fluorosis staining . In 1966, it was promoted the combination use of Eliminato:
)
hydrochloric acid and hydrogen peroxide to remove “brown stain from mottled teeth” due to a
Mcinnes, 1966
Eliminato:
8
chronic endemic dental fluorosis . The early efforts to whiten teeth relied on the assumption Eliminato: It is interesting to
observe that most of the efforts
of tooth whitening at the time
that the process involved the removal of extrinsic enamel stain. The mechanism of action was were done evolving extrinsic
enamel stains.
poorly understood. Formattato: Tipo di
carattere: Non Grassetto,
Colore carattere: Automatico
Formattato: Colore carattere:
It was only on 1970 that Cohen and Parkins first published a method for bleaching the Automatico
Eliminato:
discolored dentin of young adults with cystic fibrosis who has undergone tetracycline treatment
Eliminato: (Cohen, 1970). T
9
. This publication indicated that the mechanism of tooth whitening using hydrogen peroxide
involves penetration to the dentin. In 1976, Nutting and Poe introduced the walking bleach
technique, which uses 35% hydrogen peroxide and sodium perborate for nonvital teeth
Eliminato:
bleaching10. The breakthrough in tooth whitening was in 1989 when Haywood and Heymann Eliminato: (Nutting, 1976).
11 Eliminato: technique.
published the nightguard vital bleaching technique . This is procedure is still widely used
among the dental community as the take-home bleaching system.

Eliminato: ¶
Eliminato: ¶
Tooth Whitening Systems numerati
Eliminato:
Tooth whitening with various concentrations of peroxide has been demonstrated to be safe and
effective in a variety of regimens, including in-office procedures, dentist-prescribed and

Eliminato: .(
12
supervised home treatments and over the counter system approaches . Most dental practices Eliminato: REFERENCE?
LI?) M
in the United States offer some form of tooth whitening system. Eliminato: and as many as
one out of five patients have
their teeth whitened.
Eliminato:
A) Take- home System Eliminato: :

Eliminato:
The most common regimen is the at-home use for 2 to 4 weeks, based on the color of the teeth Eliminato: (Kugel 2000 and
Haywood).
13,11
at the start of whitening .The use of hydrogen peroxide for removing intrinsic stains from Eliminato: publication
Eliminato: The dentist
vital teeth has been used for many years. Haywood and Heymann published the first article prescribed home-applied
technique most commonly
11 between 10% to 22%
describing night guard vital bleaching in 1989 . A tray is fabricated from a model of the carbamide peroxide.
Eliminato: patients
patient’s teeth using a soft plastic nightguard. This tray is the loaded with carbamide peroxide
Eliminato: 89¶
7
gel and seated over the teeth for approximately 2 hours. The most commonly prescribed
concentrations are 10% to 22% carbamide peroxide.
Eliminato:
The advantage of the take-home systems is the decreased cost when compared to the in office Eliminato: (with minimal in-
office time required to fabricate
trays and educate the patient
bleaching options. The major disadvantages associated with take-home systems are: (a) they on the take-home procedure).
require significant patient compliance with the number of applications usually involving 1-2
hours twice a day or overnight wear, and (b) the entire treatment usually takes at least four
weeks.
Eliminato: ¶
Eliminato: :
B) In-Office System
Eliminato:
The most acceptable applications involve are in-office techniques, dentist prescribed take-home
systems or a combination of both. The in-office bleaching technique generally employs a 15%,
30% or 35% hydrogen peroxide bleaching agent (heated or non-heated).

Formattato: Rientro: Prima
riga: 0 pt
The advantages of the in-office procedure are: (a) it requires minimal patient compliance, and
(b) immediate results are attainable. The disadvantages to this treatment are: (a) chair-time
requirement, and (b) cost to the patient. It is important to note that this procedure usually
requires multiple office visits.

Eliminato: ¶
Eliminato: :
C) Combination Technique
By combining the two techniques (in-office and take-home), there is a reduction in the amount of riga: 0 pt
time and the need for repeated office visits as well as the expense associated with in-office
Eliminato: (Garber 1997).
14
bleaching as a stand-alone technique . The combined technique increases overall success
Eliminato: (Kugel 1997).
and patient satisfaction. This procedure involves the use of a high concentration of hydrogen
peroxide (35%) delivered chair side for one hour followed by a take home regimen of 5days.
Eliminato: (Kugel 1997).
This is often followed by an additional chair side application. 15
Eliminato: 89¶
8
Eliminato: :
D) Whitening Strips
A new method involves using a 5.3% hydrogen peroxide-impregnated polyethylene strip riga: 0 pt
Eliminato: and for offering

(Crest®Whitestrips™) for 30 minutes twice daily. This method is recommended for maintaining treatment…( Kugel, ... [25]
Formattato: Non Apice /
already whitened teeth. It can also be a good option to patients who cannot afford the cost of Pedice
Eliminato: .
other whitening treatment or who do not have the time for multiple dental visits for tray
Formattato ... [26]
13
fabrication . It was published in 2002 the use of the whitening strips for tetracycline stained Eliminato: (Gerlach et al.,
2001).
teeth 13. Formattato ... [27]

Eliminato: (Harris et al.,
2001) … (McMillan et al.,
2001). ... [28]
Development of this flexible, polyethylene whitening strips allows for consistent bleaching using Formattato: Tipo di
11 pt
shorter contact times. Fixing the daily strip regimen at 30 minutes per day, a randomized, Eliminato:
Formattato ... [29]
double blind, a double placebo-controlled clinical study was conducted to evaluate the effects of
Eliminato: ¶
17
increasing the dosing regimen on tooth shade . Also, an in vitro study explored the impact of Eliminato: The main
drawback is that they are
limited to the anterior teeth and
varying concentration of carbamide peroxide ranging from 0.4% to 10% on bleaching efficacy cannot be easily adapted to
the malposed teeth.¶
and the impact of increasing hydrogen peroxide concentration on bleaching strip efficacy and Eliminato: ¶
¶
18 ¶
tolerability under clinical conditions . These studies demonstrated that a modest increase in
Eliminato: :
peroxide concentration on a flexible bleaching strip results in increased whitening effectiveness, Eliminato: Technological
advances in dentistry make it
... [30]
without adversely impacting on overall tolerability. Formattato ... [31]
Formattato ... [32]
Eliminato: , being promoted
... [33]
Eliminato:
E) Light Activated Whitening Systems
Formattato ... [34]
Eliminato: In 2002 one ...
article
[35]
The introduction of light activated devices such as Plasma arc, Light Emitting Diodes (LED),
Formattato ... [36]
,
Argon lasers, metal halide and xenon-halogen lights by dental manufacturers have helped Eliminato: the … ... [37]
Formattato ... [38]
create a public demand for the light enhanced tooth whitening systems. Eliminato:
3
Formattato ... [39]

Eliminato: Reviews of ...
these
[40]
4
Controversial papers were published evaluating the efficacy of light activated bleaching agents Eliminato: …in support…
... [41]
Formattato ... [42]
in 2002. The first article reported positive results19. The other articles concluded the opposite Eliminato: discredited ... [43]
5
20, 21 22 23 Formattato ... [44]

findings . These articles either maintained or questioned the results . The dental
Eliminato: It is apparent...that
[45]
profession still needs more evidence of its effectiveness in order to provide better and more Formattato ... [46]
Eliminato: 89¶
9
Eliminato: The lack of ... [47]
Eliminato: need for more
... [48]
efficient treatment. The high demand for “up to date” dental office by patients and clinicians
Eliminato: even
stimulates manufacturers to inundate the dental profession with advertisements emphasizing Eliminato: more important as
Eliminato: “up to date”...
dental
[49]
that light activated tooth whitening is “the state of the art” and should be part of the Eliminato:
Formattato ... [50]
armamentarium of the office, with not clear evidence of its usefulness.
Formattato ... [51]
Formattato ... [52]
Eliminato: Bleaching is...
the[53]
The use of hydrogen peroxide (H202) for bleaching teeth has been evident with use of heat or Eliminato:
24 Eliminato: In 1970,
not . In order to gain treatment time, clinicians have attempted to accelerate the degradation of
Eliminato: , such as ... [54]
H202 by using heat or light. Cohen and Parkins introduced a technique for bleaching discolored Eliminato:
7
Formattato ... [55]

teeth using hydrogen peroxide and a hand-held heating source 9. Formattato ... [56]
Eliminato:
Formattato ... [57]
Recent in vitro study has shown that the use of intense lights does elevate temperature of the Eliminato: ¶
Eliminato: ¶
bleaching material and as a result caused an increase in intrapulpal temperature. This may Eliminato: Most clinicians
... [58]
25 Formattato ... [59]
have an impact on post bleaching tooth sensitivity and pulpal health . Another research in vitro
Formattato ... [60]
has verified that the use of laser-activated hydrogen peroxide did not produce any perceivable Formattato ... [61]
Formattato ... [62]
colour change 26. Light-activated chair side bleaching systems probably offer the benefit of
Formattato ... [63]
Eliminato: T
being less time-consuming while producing faster results.
Formattato ... [64]
Formattato ... [65]
Formattato ... [66]
The assumption is that clinically tolerable levels of heat will speed the breakdown of H2O2 tooth Eliminato: he introduction of
... [67]
Formattato ... [68]
bleaching chemicals and this accelerated H2O2 breakdown will cause teeth to lighten more
Formattato ... [69]
rapidly per unit time. In a recent study the decomposition of hydrogen peroxide was measured Formattato ... [70]
Eliminato:
by the amount of oxygen released. The data from this study indicated that at temperatures of up Formattato ... [71]
Formattato ... [72]
to 85º C accelerated decomposition of the 35% H2O2 was minimal when compared to the control
Formattato ... [73]
gel 20. Eliminato:
Formattato ... [74]
Formattato ... [75]
Formattato ... [76]
The use of light activated bleaching system to accelerate the bleaching process is still on
Eliminato: Research in...
vitro
[77]
question and more evidence needs to be gathered in order to make a more precise assertion of Formattato ... [78]
Formattato ... [79]
its effectiveness. Formattato ... [80]
Eliminato: 89¶
10
Eliminato: The efficacy of a
bleaching treatment can be
determined through first or
second evaluators or various
technical methods. The use of
F) Toothpaste a shade guide, colorimeter, or
computer digitization to
Many types of toothpaste are available in the market as tooth whitening products, but only a measure color change over
time has been currently
included in clinical trials to
small number of them show stain removal ability and effectiveness. Most of these toothpastes assure efficacy assessment
14, 15
13,
.¶
do not contain bleaching agents in their formulation. The ones that do have very low bleach Formattato: Tipo di
27 11 pt
concentration and contact times relatively too short to be effective . Whitening toothpastes
Formattato: Tipo di
carattere: 12 pt, Non
contain mild abrasives to remove surface stains. The peroxide content in the toothpastes are Grassetto
Formattato: Normale,
Giustificato, Non regolare lo
very low (1% or less), also the exposures of the toothpastes on the tooth is minimal hence any spazio tra testo asiatico e in
alfabeto latino, Non regolare lo
whitening minimal 28. spazio tra testo asiatico e
caratteri numerici
Eliminato: :
Eliminato:
G) Over the Counter Products Eliminato: (Sharif 2000).
Eliminato: ( 1
Easy availability of over the counter whitening products has made whitening of teeth more
Eliminato: less )
popular amongst people of all ages. There are different types of over the counter products like Eliminato: ,
Eliminato: mi
whitening dentifrices, tray based, whitening strips and the recently introduced brush Eliminato: .11
Formattato ... [81]
applications. The latest inclusion to OTC products is a Brush technique. This technique is non-
Eliminato: ¶
tray based paint on application. Gingival irritation can be prevented due to the ease in Eliminato: :
Eliminato:
application. Over the counter bleaching kit requires the consumer to use either a
Eliminato: .10
prefabricated tray or fabricate their own semi-molded tray then fill it with supplied bleaching
Formattato ... [82]
agents. These types are less than ideal because the trays are not custom fitted and the Eliminato: ¶ [83]
...
Formattato ... [84]
formulation is not sophisticated as those dispensed by the dentist 29. Formattati: Elenchi puntati e
numerati ... [85]
Eliminato: a
Eliminato: ECHANISM...
OF[86]
Mechanism of Action
Formattato ... [87]
Many studies have been conducted to evaluate the effectiveness of various bleaching materials Formattato ... [88]
Eliminato: [
27, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 15, 41, 42
and techniques . The brightening effect of the carbamide Eliminato: Mokhlis et al.... [89]
Eliminato: Christensen...
1989,
[90]
peroxide and hydrogen peroxide or of both in a combined technique was reported during the
Eliminato: Cibirka et al. 1999
above investigations. Eliminato: ,

Eliminato: Jones et al. 1999,
Eliminato: Haywood et ...
al.[91]
Eliminato: 89¶
11
The exact mechanism of action is not completely understood. Hydrogen peroxide diffuses
Eliminato: (Bowles et al
through the organic matrix of the enamel and dentin 43, 44, 45. Because the radicals have unpaired 1987, 1986, Fuss et al 1989).
electrons, they are extremely electrophylic and unstable and will attack most other organic
molecules to achieve stability, generating other radicals. These radicals can react with most
unsaturated bonds, resulting in disruption of electron conjugation and a change in the
absorption energy of the organic molecules in tooth enamel. Simpler molecules that reflect less
light are formed, creating a successful whitening action. This process occurs when the oxidizing
agent (hydrogen peroxide) reacts with organic material in the spaces between the inorganic
Eliminato: (Goldstein and
salts in tooth enamel 46. Garber 1995).
Eliminato: ¶
18 pt
Bleaching Penetration Eliminato: ¶
Formattato: Tipo di
Enamel is the most dense tissue of the body a study conducted by Bartelstone in 1951 showed carattere: 12 pt
47
the penetration of I-131 through enamel to dentin which diffused to pulp . Carbamide peroxide riga: 0,05 pt, A sinistra -0,01
ch
breaks down into hydrogen peroxide, carbon dioxide urea and ammonia. Some of the by Formattati: Elenchi puntati e
numerati
43, 48
products penetrate the dentinal tubules reaching the pulp causing reversible pulpitis . Some Formattato: Rientro: Prima
riga: 0 pt
of the pulpal enzymes are sensitive to hydrogen peroxide along with heat. However, in vital Eliminato: (Bartelstone 1951)
Eliminato: . (Gokayo,2000;
bleaching the amount peroxide reaching pulp compared to amount of H2O2 required to cause Bowels, Ugwuneri 1987)
Eliminato: in vital
44
this damage is very low . Gokay et al a higher peroxide diffusion was seen in teeth with Eliminato: (Bowels,Thompso
n 1986)
restorations using a high concentration of carbamide peroxide compared to using a lower
Eliminato: (Gokay 2000)
concentration 48.
Formattato: Tipo di
In vitro data using extracted human teeth have demonstrated that a 10% carbamide peroxide carattere: Non Grassetto,
gel can change the color of dentin over time 49. In this study teeth were sectioned and placed on Formattato: Tipo di
carattere: Non Grassetto,
glass slides. The teeth were sealed at the cut surfaces and bleached for 10 days. Digital photos
were taken from marked areas and lightness values determined.
Eliminato: 89¶
12
Sensitivity is generally mild and transient. Sensitivity occurs earlier in treatment and decreases
as treatment continues. This might occurs due to the close contact of gel to the tooth and
Eliminato: (Michael 2002).
disappearance may be due to sensory accommodation 50.
Eliminato: ¶
Eliminato: discoloration
Tooth Discoloration: External – Internal Staining Formattato: Tipo di
carattere: 12 pt
Tooth discolorations can be superficial changes that affect the enamel surface, or can be Formattato: Rientro: Prima
riga: 0 pt
deeper staining which affects the entire tooth structure. It is essential for the dentist to identify
the type of discoloration in the patient’s tooth, diagnose the cause and define the appropriate
treatment plan. Tooth discoloration in vital teeth can result from aging, tobacco use,
Eliminato: (Haywood 1999).
chromogenic foods, medications and pulpal pathology 51.
Superficial discolorations are usually caused by the staining effects of certain foods, beverages,
or tobacco products. Tea, coffee, red wine, cola and smoking or chewing tobacco usually result
in yellow, brown or black staining with pits, fissures, grooves and enamel defects retaining even
Eliminato: H.
more of the pigmenting effects. Yellow-brown stains are usually external and from accumulation Eliminato: A.
Eliminato: utero
of environmental colorants to an irregularly formed enamel matrix. Conversely, internal staining Eliminato:
Eliminato: Excessive
results from improper calcification and/or hypoplasia. systemic fluoride during
enamel matrix formation and
calcification can result in a
defective matrix and improper
calcification known as endemic
More severe discolorations result from systematically prescribed medication during tooth enamel fluorosis or mottled
enamel (Stewart et al. 1982,
Swift 1988). Fluorosis usually
formation, intake of excessive amount of fluoride during enamel formation and calcification, presents bilaterally with white
chalky spots, yellow or brown
staining
different systemic conditions, dental conditions and/or treatment and aging. In 1956,
Eliminato: .
Schwachman and Schuster first reported tooth discoloration caused by incorporation of Formattato: Tipo di
52 11 pt, Colore carattere:
systemic tetracycline into tooth structure . Tetracycline discoloration occurs with the systemic Automatico
4
Eliminato:
intake of tetracycline during tooth formation (second trimester in uterus to 8 years of age). The
Formattato: Tipo di
discoloration of the permanent dentition depends on the amount and duration of tetracycline use 11 pt, Colore carattere:
Automatico
53
. The portion of the tooth, color and severity of the stains can be determined by the stage of Formattato: Tipo di
11 pt, Colore carattere:
the tooth development at the time of the drug administration. Tetracycline is incorporated into Automatico
Eliminato: 89¶
13
dentin during tooth calcification intra and post partum, probably through chelation with calcium
Formattato: Tipo di
54 carattere: (Predefinito) Arial,
forming tetracycline orthophosphate . It can be deposited in fetal tooth buds when
Automatico
administered in the third trimester of pregnancy or by a child during the development of the
6
Eliminato:
55, 56
tooth (between ages 3 to 4 months and 7 to 8 years) . Colors may vary intensity of gray, Formattato: Tipo di
blue, brown and yellow. The different banding can also be attributed to the variations of the 11 pt, Colore carattere:
Automatico
7
tetracycline derivates Eliminato:
Formattato: Tipo di
Automatico
Tetracycline staining is complex, and may necessitate extensive esthetic intervention. Vital Eliminato: ¶
Eliminato: ¶
bleaching with professional tray or strip systems can yield an evident improvement in
Formattato: Tipo di
appearance within a few weeks. While non-invasive, treatment may need to continue over an 11 pt, Colore carattere:
Automatico
extended period. Some individuals will show favorable response after 3-4 months, after which Formattato: Corpo del testo,
Allineato a sinistra
treatment may be discontinued. Duration may be difficult to predict, given the variable clinical Formattato: Tipo di
manifestations of tetracycline staining. Practitioners and patients should be advised that optimal 11 pt
bleaching of tetracycline staining may necessitate extended daily at-home treatment over a riga: 0 pt
period of 3-6 months. The costs, risks, and benefits of the various treatment options must be Eliminato: management(
57, 58 Formattato: Non Apice /

considered as part of overall patient management . Excessive systemic fluoride during Pedice
Eliminato: Haywood, Kugel
enamel matrix formation and calcification can result in a defective matrix and improper 02) Haywood VB, Leonard
RH, Dickinson GL. Efficacy
59,60 of six months of nightguard
calcification known as endemic enamel fluorosis or mottled enamel . Fluorosis usually vital bleaching of
tetracycline-stained teeth. J
presents bilaterally with white chalky spots, yellow or brown staining Esthet Dent. 1997;9:13-9. ¶
Formattato: Tipo di
Automatico
Systemic conditions can also cause tooth discolorations. Amelogenesis imperfecta may result
Formattato: Tipo di
in hypoplasia or hypocalcification with yellow or brown stains and dentinogenesis imperfecta 11 pt
61
Formattato: Tipo di
with brownish violet, yellowish or gray discolorations . Hypoplasia or hypocalcification can carattere: Grassetto
Eliminato: (Stewart et al.
occur with clefting of the lip and palate or with acquired illnesses such as cerebral palsy, serious 1982, Swift 1988)
Eliminato: (Shafer et al.
46
renal damage and severe allergies . Blue, brownish or green tooth discolorations may be 1974)
caused by destruction of an excessive number of blood-cell erythrocytes in erythroblastosis Garber1995)
Eliminato: (Shafer et al.
fetalis a result of Rh-factor incompatibility between mother and fetus 46, 61. 1974, Goldstein and Garber
1995)
Eliminato: 89¶
14
Eliminato: (Jordan et al.
1984, Faunce 1983, Goldstein
and Garber 1995)
Patients with porphyria, a rare condition that causes an excess production of pigment, may
46, 62, 63 Garber 1995)
result in a red, purplish-brown or brownish tooth discoloration . Dental caries, discolored
Eliminato: Intrinsic Stains:
aging, chromatogenic food and
acrylic or restorations (made of composite, amalgam and/or metal), pins, posts and other drinks, excessive fluoride
intake, medication
materials employed in the dental environment can have an adverse effect on tooth coloration (tetracycline) and others can
be the cause of intrinsic stains.
Tetracycline stains, though,
resulting in a darkened shade of the patient’s dentition. Aging usually brings thinning of the are considered to be the most
difficult types of intrinsic stains
to manage clinically. The
enamel, loss of the translucent enamel layer, and formation of secondary dentin. The devastating effect on tooth
formation of as little as one
gram of tetracycline was
combination of less enamel and more darkened, opaque dentin creates an older-looking darker recognized in the late 1950s
1
and confirmed by a study of

tooth 46. cystic fibrosis patients by
2
Swachman et al . In 1970,
Cohen and Parkins published
a method for bleaching the
discolored dentin of young
adults with cystic fibrosis who
Tooth Whitening Protocol had undergone tetracycline
3
treatment
Tooth whitening, when used with professional supervision, can be safe and effective. A Eliminato: Tetracycline
staining is complex, and may
necessitate extensive esthetic
complete oral examination (with a review of the patient’s medical and dental history) and an intervention. Vital bleaching
with professional tray or strip
systems can yield an evident
updated set of periapical radiographs are necessary before planning any bleaching procedure. improvement in appearance
within a few weeks. While
non-invasive, treatment may
It is very important to determine the severity and cause of the tooth’s discoloration because it need to continue over an... [92]
Formattato ... [93]
will allow the dental clinician to specify which treatment plan options are to be used.
Eliminato: Different variations
of tetracycline and derivates
Discolorations due to medications will need longer and more persistent treatment than stains produce different colors in
... the
[94]
that occurred from aging, smoking or eating habits. Existence of carious lesions, restorations, numerati
Eliminato: .¶
endodontic treatment, pulpal anatomy and any periapical pathology must be determined during
Eliminato: .¶
64 ¶
the clinical and radiographic examination before the onset of the bleaching procedure . Tooth Whitening Protocol
Formattato ... [95]
39
Different pulp size teeth may have different rates of response to bleaching . Existence of
Formattato ... [96]
caries, microcracks in enamel, exposed dentin and open margins in existing restorations must
riga: 0 pt
Eliminato: (Nathanson 1987).
also be taken into consideration before treatment. Restorations that are not properly sealed and
Eliminato:
untreated carious lesions can lead to extensive sensitivity and should be treated before Eliminato: (
Eliminato: Haywood et al.
beginning any bleaching treatment 46. 1994)
Eliminato: treatment
Formattato: Apice
Eliminato: (Goldstein et al.
1995)
Eliminato: 89¶
15
Tooth sensitivity and gingival irritation have always been a concern when tooth whitening is
Eliminato: applied
used. Both in-office and take-home bleaching procedures have been reported to induce
Eliminato: (Nathanson
65 1997).
sensitivity to a significant number of patients . Tooth whitening is generally well tolerated.
Eliminato:
Some patients may experience tooth sensitivity and mild oral mucosa irritation; however, these
symptoms are generally mild and are alleviated at the end of treatment. Tolerability may be
impacted by tray design, poor compliance or product ingestion. Tray thickness may contribute
Eliminato: (Kugel 2000 did
to poor compliance by causing occlusal interferences or jaw pain 13. any other author said this
also?).
Detailed clinical and radiographic examination, fabrication of a custom-fitted, well- adapted
mouth guard, careful selection of the tooth whitening material and proper patient instruction can
significantly decrease the possibility of tooth sensitivity or gingival irritation during the take-home
treatment. The tray fabrication technique should include “scalloping” of the tray material to the
gingival line to reduce the exposure of excess bleaching agent onto the soft tissues.
The thickness of the tray material (0.040” is recommended) is also important to prevent patient
discomfort and other problems associated with the temporo mandibular joint (TMJ). The design
of the tray (with reservoirs or without reservoirs) will be a determinant of the type of tooth
whitening material to be used. Selection of the product to be used should be based on the
concentration of active ingredient, viscosity and other salient features.
Teeth that have composite or amalgam restorations and are being treated with 10% carbamide
peroxide demonstrated increased microleakage in the restorations, according to a study which
evaluated the microleakage of previously restored Class II restoratives after exposure to 10%
carbamide peroxide. Microleakage of previously restored Class II restoratives after exposure to

Formattato: Non Apice /
10% carbamide peroxide 66. Pedice
Eliminato: 89¶
16
Eliminato: (D. Bardwell, C.
The immediate placement of composite resin on bleached teeth has been controversial. Habib, G. Kugel, N. Mehta, C.
Leone Abstract #306, JDR
2000 Special Issue Vol.79.¶
According to a study evaluating the shear bond strength of composite restorations placed on
Eliminato: .
bleached and non bleached teeth, there was no statistically significant difference when the
Eliminato: (Effect of
67 bleaching on Composite Resin
composites were placed at 24 hours, 48 hours, 4 or 6 days . A different study, evaluating the Shear Bond Strength In Vitro.
P. Yu, A. Aboushala, D.
effects of take home bleaching systems on enamel surfaces, suggests that a period of 4 days Bardwell JDR 1999 Vol.78
special issue, abstract #1445)
Eliminato: Effects of the two
must elapse before bonding to a tooth bleached with a peroxide material, while no delay is home bleaching systems on
Enamel surfaces. M. MacKay,
necessary for a non-peroxide based bleaching system 68. R. Perry, E. Swift, M. Varga S
JDR 1997 special issue
abstract #1405. (Check also
two studies I did with Julie
O’Quinn and William Dodge
showing that bond strength is
Most authors and tooth whitener manufacturers recommend the use of reservoirs during impaired immediately after
bleaching. I believe the studies
were published in 1996!).¶
bleaching tray fabrication, in order to increase the effectiveness of the tooth whitening material
Eliminato: (Haywood &
11 Heymann 1989, Goldstein &
. Clinical studies examined the role of reservoirs reveal that the presence or absence Garber 1995, Ultradent
Products 1996, Discus Dental
bleaching solution reservoirs in the bleaching tray did not increase the success of take-home 1996, Dentsply 1996)
Eliminato: reveal that
69
bleaching with 10% carbamide peroxide gel . Tooth whitening products pH differs in a range Eliminato: (
Eliminato: Javaheri & Janis
of 4.0 to 7.5, with more acidic pH in materials with higher peroxide concentration. It is important 2000)
Eliminato: products pH differ
that these materials have a relatively neutral pH, because root resorption, enamel
Eliminato: ( Price et al. 2000)
demineralization and erosion may occur with pH less than 5.2 70

. Dental lasers have been used Eliminato: (Sun 2000)
Eliminato: (Blankenau et al.
1999)
for tooth whitening. Currently the argon laser is the most commonly used laser for power
Eliminato: ¶
bleaching 71. There is not enough evidence to support safety and efficacy of laser bleaching 72. Eliminato: ¶
¶
sinistra
Bleaching Side Effects
Eliminato: ¶
Toxicology Formattato: Tipo di

Eliminato: ¶
FDA has approved hydrogen peroxide and carbamide peroxide to be used for debriding oral
Formattato ... [97]
wounds. Even though bleaching is a longer process than debridment, in vitro toxicological Eliminato: Bleaching
Adverse Effects¶ ... [98]
evaluation of bleaching agents like 10% carbamide peroxide or 4% hydrogen peroxide was Eliminato: :
Eliminato: ¶
lower or comparable to commonly used dental materials like eugenol, dentifrices ,mouth rinses <#>Toxicology:¶
and composites 12. riga: 0 pt
Eliminato: .
Eliminato: (Li 1997)
Eliminato: 89¶
17
Eliminato: (Dahl and Becher
73
Studies have shown that daily exposure of carbamide peroxide should not exceed 10mg/kg . 1995)
Formattato: Tipo di
Li and Matis found that the average amount of bleaching agent used is 502mg per application. carattere: Grassetto
Eliminato: Y.
Even if the patient swallows all the gel, it would not exceed more than 8.37mg /kg 12 . Therefore Eliminato: B
Eliminato: .
the safety factor of the bleaching agent is high.
Eliminato: (Li 1997).
Eliminato: ¶
Oral Side Effects Formattati: Elenchi puntati e

numerati
The mucosal irritation mostly occurs due to ill fitting trays, improper application of bleaching gel Eliminato: side
Eliminato: e
or using it for longer time than prescribed. Schulte J and others showed that the group with the Eliminato: :
74
overnight exposure to the bleaching gel subjects had mucosal irritation . The soft tissue riga: 0 pt
Eliminato:
irritation generally is minimal and is resolved either by adjustment of the bleaching tray, or
Eliminato: (Schulte, 1993)
75 Eliminato: ¶
shortly after cessation of the treatment .
Eliminato: (Haywood VB
1994)
Eliminato: ¶
Tooth Sensitivity Formattati: Elenchi puntati e
numerati
Studies have shown that sensitivity occurs in 55 to 75% of the treatment groups. The placebo Eliminato: :
groups also experienced 20-30% sensitivity. One study reported tooth sensitivity of about 15 % riga: 0 pt
Eliminato: (Haywood VB
wearing only the bleaching tray 76,77. 2001
Eliminato: ; Michael 2002)
The development of tooth sensitivity can be a multifactorial phenomenon. If the whitening tray is Eliminato: (Pohjola R 2002)
Eliminato: (Leonard 1997)
fabricated from a thick material, it can result in an appliance producing minor orthodontic
Eliminato: (
78
movements . Allergies and chemical sensitivity to the composition of the tray or the bleaching Eliminato: Michael 2002)
Eliminato: (
79
gel. And the free radical formation of the whitening gel .It can also result from overzealous Eliminato: Pohjola 2002;
Leonard 1997 )
77
tooth brushing during participation in a clinical trial . Glycerine which is used to carry the active Eliminato: ¶
ingredient can absorb water therefore can have a dehydration effect, hence resulting in sinistra
Eliminato: ¶
sensitivity. 78,79.
Formattato: Tipo di
carattere: 12 pt
Formattato: Tipo di
Summary Eliminato: :
Formattato: Tipo di
In summary, although tooth whitening is one of the most popular dental procedures it is also one carattere: Grassetto
of the least understood. We are still unclear as to its mechanism of action. There is little data of riga: 0 pt
Eliminato: 89¶
18
the effects of both concentration and dose on outcome. The techniques for measuring color
change have been brought into question. The cause(s) of sensitivity are not clear nor are the
issues of long tern exposure to hydrogen peroxide. The issue of rebound in color has not been
well examined and issues related to maintenance of the whitening effect are also poorly
Eliminato:
understood
Most recently there has been a push to find ways to accelerate as well as improve the delivery
of the whitening process. These include the application of a number of different light sources
believed to accelerate the breakdown of peroxide and thus speed up the whitening process.
The research in this area has been controversial with publications having quite different
conclusions as to the efficacy of light activated bleaching. In an effort to improve the delivery
systems both polyethylene strips and paint-on whitening products have been introduced. The
efficacy of the paint-on products has been questioned and little research on these products can
be found
Eliminato: 89¶
19
REFERENCES Eliminato: ¶
¶
¶
1) Burrell KH. ADA supports vital tooth bleaching—but look for the seal. Journal of the ¶
¶
American Dental Association. 128 Suppl:3S-5S, Apr. 1997. ¶
¶
2) Papathanasiou A., Bardwell D, Kugel G : Combining In Office and Take Home Whitening Eliminato: ¶
¶
Systems. Contemporary Esthetics and Restorative Practrice Vol.4:8; 88-91, September ¶
¶
2000. ¶
¶
3) Papathanasiou A., Bardwell D, Kugel G : A Clinical Study Evaluating a New Chairside ¶
¶
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¶
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¶
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¶
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¶
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¶
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¶
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¶
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¶
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¶
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¶
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Eliminato: S
11) Haywood VB, Heymann HO: Nightguard vital bleaching. Quintessence Int 20(3):173-6, Formattato: Tutto maiuscole
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Formattato: Tipo di
13) Kugel G: Nontray Whitening. Compendium, Vol.21, No. 6, June 2000. carattere: Non Grassetto
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the[102]
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Formattato: Tipo di
strip clinical response [abstract #922]. J Dent Res 80:151, 2001 carattere: (Predefinito) Arial,
11 pt, Non Grassetto
18) McMillan DA, Gibb RD, Gerlach RW: Impact of increasing hydrogen peroxide
Formattato: Tipo di
concentration on bleaching strip efficacy and tolerability [Abstract #1102]. J dent Res 80:173, carattere: (Predefinito) Arial,
11 pt
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Eliminato: 89¶
20
Formattato: Tipo di
19) Tavares M. Stultz J. Newman M. Smith V. Kent R. Carpino E. Goodson JM. Light carattere: (Predefinito) Arial
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Association. 134(2):167-75, 2003 Feb + Livello:1 + Stile
numerazione: 1, 2, 3, … +
Comincia da:1 + Allineamento:
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Tedesco (Germania)
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Formattato: Tipo di
24) Goldstein RE. Esthetics in Dentistry-Principles, Comunications, Treatment Methods. 2nd carattere: (Predefinito) Arial,
11 pt
ed; vol 1. Hamilton-London: B.C Becker-Year Book; 1998:245.
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25) Baik JW, Rueggeberg FA, LiewehrFR. Effect of light-enhanced bleaching on in vitro carattere: (Predefinito) Arial,
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27) Sharif N, MacDonald E, Hughes J, Newcombe RG, Addy M: The chemical stain removal automatica + Livello:1 + Stile
properties of “whitening” toothpaste products: studies in vitro. British Dental Journal Comincia da:1 + Allineamento:
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188(11):620-4, 2000. + Tabulazione dopo: 14,4 pt
+ Rientra di: 14,05 pt
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automatica + Livello:1 + Stile
29) Kugel G Over the counter tooth whitening Systems Compendium April 2003; 24;4A 376- numerazione: 1, 2, 3, … +
82 A sinistra + Allinea a: 14,4 pt
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Eliminato: 89¶
21
33) Jones AH, Diaz-Arnold AM, Vargas MA, Cobb DS: Colorimetric assessment of laser and
Eliminato: ¶
home bleaching techniques. J Esth Den 11(2):87-94, 1999. Eliminato: ¶
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Eliminato: ¶
Update 2(4):63-66, 1991.
Formattato: Tipo di
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36) Haywood VB, Heymann HO: Nightguard vital bleaching: how safe is it? Quintessence 11 pt, Non Corsivo, Colore
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Int 22:515-523, 1991. Formattato: Numerazione
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regolare lo spazio tra testo
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carattere: 11 pt, Non Corsivo,
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carattere: 11 pt, Colore
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Formattato: Tipo di
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44) Bowles WH, Thompson LR: Vital bleaching: the effect of heat and hydrogen peroxide on Eliminato: <#>Bardwell D,
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pulpal enzymes. J End 12:108-112, 1986. In vitro evaluation of tooth
color modifications utilizing
... [105]
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carattere: Grassetto
agents. J Endod 15:362-364, 1989.
46) Goldstein RE, Garber DA: Complete dental bleaching. Quintessence books 1995.
Eliminato: hydrogen
47) Bartelstone HJ. Radioiodine Penetration through Intact Enamel with Uptake by peroxide
Eliminato: ¶
Bloodstream and Thyroid Gland. Journal of Dental Research October 1951; 728-733
Formattato: Tedesco
48) Gokay O, Tuncbilek M,Ertan R. Penetration of the pulp chamber by carbamide peroxide (Germania)
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bleaching agents on teeth restored with composite resin. J of Endodontics 2000; 27; 92-94 Szajkis S, Tagger M: Tublar
... [107]
49) McCaslin A.J., Haywood V.B., Potter B.J., Dickinson G.L., Russell C.M. Assessing Formattato ... [108]
Dentin Color Changes From Nightguard Vital Bleaching .JADA. The Journal of the American Formattato: Tipo di
carattere: Non Grassetto
Dental Association, October 1999, vol. 130, no. 10,pp. 1485-1490 Formattato ... [109]
Eliminato: 89¶
22
Formattato: Tedesco
50) Michael G Jorgensen, William B. Carroll. Incidence of tooth sensitivity after home (Germania)
whitening treatment. JADA vol.133 August 2002 ;1076-1082 Formattato: Interlinea 1,5
51) Blankenau R. Goldstein RE. Haywood VB. The current status of vital tooth whitening + Livello:1 + Stile
techniques. Compendium of Continuing Education in Dentistry. 20(8):781-4, 786, 788 Comincia da:1 + Allineamento:
passim; quiz 796, 1999 Aug. + Tabulazione dopo: 14,4 pt
52) Schwachman H, Schuster A: The tetracyclines applied pharmacology. Pediat Clin North
Formattato: Tipo di
Am 3:295, 1956. carattere: (Predefinito) Arial,
11 pt, Tedesco (Germania)
53) Christensen GJ: Bleaching vital tetracycline stained teeth. Quintessence Int.1978 Jun: Formattato: Giustificato,
9(6): 13-9 Livello:1 + Stile numerazione:
1, 2, 3, … + Comincia da:1 +
54) Mello HS. The mechanism of tetracycline staining in primary and permanent teeth. J Allineamento: A sinistra +
Allinea a: 14,4 pt +
Dent Child 1967; 34(6): 478 Tabulazione dopo: 14,4 pt +
Rientra di: 14,05 pt
Formattato: Tipo di
55) Moffitt JM, Cooley RO, Olsen NH, et al. Prediction of tetracycline-induced tooth carattere: (Predefinito) Arial,
11 pt
discoloration. J Am Dent Assoc 1974; 88:547-552
Formattato: Tipo di
56) Mull MM. The tetracycline and the teeth. Dent Abstr 1967; 12:346-350 carattere: (Predefinito) Arial,
11 pt, Non Corsivo
57) Haywood VB, Leonard RH, Dickinson GL. Efficacy of six months of nightguard vital Formattato: Numerazione
bleaching of tetracycline-stained teeth. J Esthet Dent. 9: 13-9, 1997 numerazione: 1, 2, 3, … +
58) Kugel G, Aboushala A, Zhou X, Gerlach RW. Daily use of strips on tetracycline-stained
teeth: comparative results after 2 months. Comp of Cont Edu in Dent. Jan 2002; 23 (1A): 29- + Tabulazione dopo: 14,4 pt
34 Formattato: Interlinea 1,5
59) Stewart RE et al: Pediatric Dentistry. St Louis, CV Mosby Co., p.87, 1982. + Livello:1 + Stile
60) Swift EJ: A method for bleaching discolored vital teeth. Quint Int 19:607, 1988. Comincia da:1 + Allineamento:
61) Shafer WG, Hine MK, Levy BL: A textbook of Oral Pathology, 3rd Ed. Philadelphia, + Tabulazione dopo: 14,4 pt
Saunders, 1974.
Formattato: Interlinea 1,5
62) Jordan RE, Boksman L: Conservative vital bleaching treatment of discolored dentition. righe
Comp Cont Ed Dent 5(10):803-808, 1984. Formattato: Interlinea 1,5

63) Faunce F. Management of discolored teeth. [Review] [30 refs] Dental Clinics of North + Livello:1 + Stile
America.27(4):657-70, Oct. 1983 . Comincia da:1 + Allineamento:
64) Nathanson D, Parra C. Bleaching vital teeth: a review and a clinical study. Compendium + Tabulazione dopo: 14,4 pt
1987; 8:490-8 Formattato: Tipo di
65) Nathanson D: Vital tooth bleaching: sensitivity and pulpal considerations. J Am Dent 11 pt
Assoc., 128(Suppl): 41S-44S, 1997. Formattato: Numerazione
66) Bardwell D, Habib C, Kugel G, Mehta N, Leone L: Microleakage of previously restored numerazione: 1, 2, 3, … +
Class II restoratives after exposure to 10% carbamide peroxide. JDR 2000 Special Issue A sinistra + Allinea a: 14,4 pt
Vol.79, abstract 306. + Rientra di: 14,05 pt
Eliminato: 89¶
23
Formattato: Tipo di
67) P. Yu, A. Aboushala, D. Bardwell. Effect of bleaching on Composite Resin Shear Bond carattere: (Predefinito) Arial,
11 pt
Strength In Vitro. JDR 1999 Vol.78 special issue, abstract #1445
68) MacKay M., Perry R., Swift E., Varga M. S. Effects of the two home bleaching systems
Formattato: Tipo di
on Enamel surfaces. JDR 1997 special issue abstract #1405. carattere: (Predefinito) Arial
69) Javaheri DS, Janis JN: The efficacy of reservoirs in bleaching trays. Operative Dentistry,
2000, 25, 149-151.
70) Price RBT, Sedarous M, Hiltz G: The pH of tooth-whitening products. J Can Den Ass,
Sept. 2000, Vol. 66, No. 8, 421-426.
71) Sun G: The role of lasers in Cosmetic Dentistry Dental Clinics of North America, Vol. 44,
No 4, Oct. 2000, 831-849.
72) Blankenau R, Goldstein R, Haywood V: The current status of vital tooth whitening
techniques. Compendium of Continuing Education in Dentistry, Aug 1999, Vol. 20, No 8, 781-
794.
Formattato: Tipo di
73) DahlJE, Becher R. Acute Toxicity of carbamide peroxide and commercially available carattere: Non Grassetto
tooth bleaching agent in rats; Journal of dental Research 1995; 74: 710-714 Formattato: Interlinea 1,5
74) Schulte J,Morrissette D,Gasior E,Czajewski,M. Clinical Changes on the Gingiva as a + Livello:1 + Stile
result of at-home bleaching. Compendium 1993, VolXIV, no.11; 1362-1371 Comincia da:1 + Allineamento:
75) Haywood VB, Leonard RH, Chauncy NF, Brunson WD. Effectiveness, Side Effects and + Tabulazione dopo: 14,4 pt
Long Term Status of Nightguard Vital Bleaching. JADA, September 1994 ,vol.125pg 1219-
Formattato: Tipo di
1226 carattere: Non Grassetto
76) Haywood VB, Caughman FW,Frazier KB,Myers ML. Tray delivery of potassium nitrate- sinistra, Interlinea 1,5 righe,
fluoride to reduce bleaching sensitivity. Quintessence International ,vol32,no.2,2001;105-108 Livello:1 + Stile numerazione:
1, 2, 3, … + Comincia da:1 +
77) Michael G Jorgensen, William B. Carroll. Incidence of tooth sensitivity after home Allineamento: A sinistra +
Allinea a: 14,4 pt +
whitening treatment. JADA vol.133 August 2002 ;1076-1082 Tabulazione dopo: 14,4 pt +
78) Pohjola R,Browning WD, Hackman ST, Michael ML, Downey MC. Sensitivity and Tooth
Eliminato:
Whitening Agents. Journal of esthetic and Restorative dentistry 2002; vol2, no.2; 85-91, 2002
Eliminato: 2001
79) Leonard RH, Haywood VB, Phillips C. Risk factors for developing tooth sensitivity and Formattato: Tipo di
gingival irritation associated with nightguard vital bleaching. Quintessence International; 1997 11 pt, Tedesco (Germania)
vol. 28 no. 8; 527-534 Formattato: Numerazione
Formattato: Tipo di
11 pt
Eliminato: 89¶
24
Eliminato: ¶
Chapter 2
A Novel Low Dose Tooth-Whitening Delivery System
Efficacy and Safety:

A Randomized and Controlled Clinical Trial
Abstract
A randomized, single-center, double-blind, parallel-group, placebo controlled trial evaluated the
whitening efficacy and safety of 2-week, twice daily use of a 5.3% hydrogen peroxide tooth-
bleaching gel delivered on polyethylene film. Efficacy was based on change in Vita® shade
scores from baseline to the end of treatment. Thirty-three patients in each group completed
treatment. Use of the peroxide-containing gel led to a mean change in baseline Vita® shade
score of –3.70 ± 0.35, compared with a change of –0.87± 0.24 after use of a placebo gel. After
adjustment for baseline scores, the mean difference in shade change between the peroxide
gel–treated group and placebo-treated group was –2.85 ± 0.41 (P < 0.0001). Both treatments
were generally well tolerated. The strips offer ease of use, comfort, and shorter duration of wear
compared with other at-home bleaching systems.
Introduction
Tooth whitening is one of the most widely accepted esthetic procedures today, with treatment
options that include in-office procedures, dentist prescribed home-applied systems, over-the-
counter (OTC) bleaching kits, and a host of whitening dentifrices. Peroxides have been used for
tooth bleaching for more than 100 years, and at-home nightguard vital bleaching, which involves
use of a 10% carbamide peroxide gel in a custom-fitted tray, has met with much success since
its introduction in 1989.1 The safety and efficacy of carbamide peroxide bleaching agents is well
documented, and currently six products have been approved by the American Dental
Association for home whitening.2 Eliminato: 89¶

25
Tooth discoloration in vital teeth can result from chromogenic foods, tobacco products,
medications such as tetracycline and fluoride, pulp pathology, and aging.2 Concentrations of up
to 35% peroxide have been used to resolve discoloration. The most research has been
conducted on 10% carbamide peroxide, which produces substantial lightening of treated teeth
3, 4
after 2 to 6 weeks of treatment, although a period as long as 6 months may be required for
stubborn stains, such as those caused by tetracycline or nicotine.5 After treatment, the whitening
effect may persist for 3 or more years.
Tooth-whitening agents are remarkably well tolerated; the main adverse events are generally
mild and transient tooth sensitivity and gingival irritation.6 Nevertheless, poor compliance and
product ingestion are problems that are encountered with whitening therapy. Many of these are
associated with the delivery trays, even custom-fitted ones, used in most at-home regimens.
Tray insertion and removal can lead to sensitivity and gum irritation, and tray thickness is
believed to contribute to poor compliance and development of occlusal interferences.
One alternative to the rigid delivery tray is a polyethylene strip with a hydrogen peroxide (H2O2)–
containing tooth-whitening gel (Crest® Whitestrips™, a). In this article we report preliminary
results from a randomized, placebo-controlled clinical trial that evaluated the whitening efficacy
and safety of the 2-week, twice-daily use of a peroxide tooth-whitening gel delivered on a
polyethylene film.
Materials and Methods

Formattato: Tipo di
carattere: 12 pt
Study Population
Seventy adults in good general health were selected for the study. To be included, participants
had to have (1) a minimum of 16 natural teeth, including 4 maxillary anterior teeth; and (2) at
least 3 maxillary teeth gradable at Vita®,b shade A2 or darker. Patients with obvious periodontal
Eliminato: 89¶
26
disease (as evidenced by purulent exudate, tooth mobility, or other signs), oral pathoses
requiring prompt treatment, active untreated dental caries, dentinal hypersensitivity, or who had
tetracycline stain, dental fluorosis, or atypical non uniform stain were excluded from the study.
Previous participation in a professional or home-use vital bleaching trial, participation in a
dentifrice-whitening trial in the past year, or having fixed orthodontic appliances on the anterior
teeth were further reasons for exclusion. All participants provided written informed consent and
agreed to delay any elective dentistry (including dental prophylaxis) and to refrain from using
any other than the assigned dentifrices or toothbrushes during the study.
Formattato: Tipo di
carattere: 12 pt
Study Design
The study was a randomized, placebo-controlled, double-blind, parallel-group trial. Subject
eligibility and an average Vita® shade score for each participant were determined at the
screening visit (visit 1). At the baseline visit (visit 2), participants were stratified on the basis of
their screening Vita® shade average score and gender, and randomized to either the placebo or
the active treatment group with a block-randomization protocol. Baseline tooth color and safety
assessments (described below) were performed. These assessments were repeated at the end
of the 2-week treatment period (visit 3).
Formattato: Tipo di
carattere: 12 pt
Treatment
The active treatment product consisted of a polyethylene film with a tooth-whitening gel
containing 5.3% H2O2, supplied as strips for anterior teeth. Polyethylene film with a placebo
tooth-whitening gel served as the control. Except for the presence of peroxide, test products
were identical in composition and packaging. Study participants applied the strips twice daily to
the maxillary anterior teeth for 30 minutes at home and brushed normally twice a day with
Crest®,a toothpaste and provided toothbrushes.
Eliminato: 89¶
27
Efficacy Assessment
Efficacy was assessed as the change in Vita® shade tooth color between baseline and end-of-
treatment visits. Up to six teeth from among the maxillary incisors and cuspids were selected at
baseline on the basis of shade (minimum Vita® shade score of A2) and access for grading. At a
minimum, the four maxillary incisor teeth were graded at baseline for each subject. The Vita®
shade guide has been used successfully in clinical studies to gauge the efficacy of tooth
whitening products.7,8 All assessments were made by a standardized, trained, and calibrated
examiner, and performed in the same operatory throughout the study. All examinations were
performed blinded as to treatment assignment.
Safety Assessment
Extensive safety evaluations were performed to establish the absence of irreversible side
effects associated with the use of the tooth-whitening gel. Assessments were performed at
baseline and at the end of treatment and included the following:

1. Oral soft-tissue (OST) examination—this consisted of a visual examination of the oral numerati
cavity and perioral area, including gingiva (free and attached), hard and soft palate,
oropharynx/uvula, buccal mucosa, tongue, floor of mouth, labial mucosa,
mucobuccal/mucolabial folds, and lips.
2. Oral hard-tissue examination—a visual and tactile examination was performed of the
dentition and restorations.
3. Dentinal hypersensitivity—this parameter was assessed by questioning participants
about tooth hypersensitivity to thermal, air, or other stimuli.
4. Löe and Silness gingival index (GI)—the GI was an assessment of periodontal health
that evaluated the severity of gingivitis on the basis of color, consistency, and bleeding
on probing (BOP). Six gingival areas on each Ramfjord tooth (tooth Nos. 3, 9, 12, 19, 25,
and 28) were scored from 0 to 3, and an average score for each participant was derived
Eliminato: 89¶
28
by dividing the sum of individual scores by the number of evaluable sites. Scoring criteria
were as follows: 0—normal gingiva; 1—mild inflammation (slight color changes and
edema; no BOP); 2—moderate inflammation (redness, edema, and glazing; BOP); 3—
severe inflammation (marked redness, edema, ulceration; tendency toward spontaneous
bleeding); 8—ungradable site; 9—missing tooth.
5. Silness and Löe plaque index (PI)—the PI was an assessment of the plaque deposit at
the gingival area of the tooth. Dental plaque was scored on the facial, lingual, mesial,
and distal surfaces of the Ramfjord teeth at 6 sites per tooth, in both arches (with a
maximum of 36 sites). An average PI score was obtained for each participant, by
dividing the sum of individual scores by the number of gradable sites. Scoring criteria
were as follows: 0—no plaque/debris; 1—film of plaque adherent to free gingival margin
and adjacent tooth area and seen in situ only after probing; 2—gingival area visibly
covered with a thin to moderately thick layer of plaque; 3—abundant soft matter within
the gingival pocket or on the tooth and gingival margin; 8—ungradable site; 9—missing
tooth.
Formattato: Tipo di
carattere: 12 pt
Analysis
Effectiveness was determined by measuring the change in Vita® shade codes from baseline to
end of treatment for each evaluable tooth for the active group (Figures 2A and 2B). Shade
scores were ordered from 1 to 16 according to the brightness grouping recommended by the
manufacturer. Using this ranking, B-1 represented a score of “1,” while C-4 represented a score
of “16.” A decrease in Vita®shade numeric code represented an increase in tooth whiteness. All
adverse events related to OST, hard tissue, and dentinal hypersensitivity were summarized.
Analysis of covariance was used to compare the mean Vita® shade score change from baseline
between the active and placebo groups at the end of the 2-week treatment period. Baseline
Vita® shade score was included as a covariate in the model.
Eliminato: 89¶
29
RESULTS
Demographic and Baseline

Characteristics
The peroxide-treated and placebo groups were comparable with respect to age, sex, and race
distribution (Table 1). Baseline Vita® shade scores were similar for the two treatment groups.
Scores were 8.18 (D-4 to A-3) and 8.28 (D-4 to A-3), and, on average, ranged from A-2 to C-4
and from A-2 to A-4 in the active and placebo groups, respectively. Sixty four percent of teeth
treated in the active group started at scores of C-2 or whiter.
Efficacy
Table 2 summarizes the Vita® shade scores in the 2 treatment groups at the end of the 2- week
treatment period. Data were evaluated for 33 participants in each group. After treatment with the
peroxide-containing gel, the average score declined from 8.18 at baseline to 4.55, which was a
change of –3.7 ± 0.35, representing an average increase in tooth whiteness of approximately 4
Vita® shades. By contrast, the placebo group experienced a Vita® shade score change of only –
0.87 ± 0.24. After adjustment for baseline scores, the mean difference in shade change
between the peroxide gel–treated group and placebo-treated group was –2.85 ± 0.41 (P <
0.0001).
Safety
Abnormal soft-tissue findings were noted at baseline and after completion of treatment. There
were no new notable findings, nor was there any exacerbation of baseline pathology in any soft
tissue for the 66 participants evaluated at the end of treatment. In the placebo group, one
patient had slight cervical inflammation over one tooth. After treatment with peroxide-containing
gel, one patient developed a minor superficial distal cervical lesion on one tooth and a second
patient showed a swollen papilla between two adjacent teeth. The hard-tissue examination and
dentinal hypersensitivity assessment were unremarkable. Both groups experienced a

Eliminato: 89¶
30
significant reduction (P < 0.0001) in gingivitis and plaque scores over the 2-week evaluation
period (Table 3). After adjusting for baseline, there were no significant differences (P > 0.70)
between the treatment groups in either the gingivitis or plaque scores after 2 weeks.
Discussion
This study demonstrates the efficacy and safety of a simple at-home tooth-whitening technique
consisting of 5.3% H2O2 gel applied to disposable polyethylene strips. Twice-daily, 30-minute
applications of the whitening strips for 2 weeks lightened discolored teeth by more than 3 Vita®
shades, compared with a change of less than 1 Vita® shade in teeth treated with placebo gel.
This treatment difference was highly significant after adjusting for baseline. Adverse effects after
treatment were minimal and were observed in less than 10% of subjects in either treatment
group. The main findings in these participants were papillary swelling, minor cervical
inflammation, and a superficial cervical lesion.
Growing public interest in whiter, brighter teeth has increased demand for tooth-whitening
procedures and products. More than 90% of dentists now offer an at-home whitening procedure,
9,10
and 50% to 60% offer an in-office technique. Despite their proven efficacy, these systems
suffer from certain drawbacks. In-office treatments are rarely successful in just a single visit, and
3 to 5 visits are usually needed to achieve reasonable results, making this an expensive
procedure.11 Also, the higher concentrations of H2O2 (30% to 35%) used for in-office bleaching
can cause chemical trauma to gingival tissue and also hold the risk of cervical root resorption.12
Home-whitening systems provide a relatively inexpensive way to lighten discolored teeth but
require patient compliance and discipline. The nightguard system, which requires patients to
wear a custom-fabricated tray all night or for several hours during the day to achieve optimal
results, is cumbersome and requires an average of 2 to 6 weeks of treatment.2 Stubborn stains
may require extended treatment periods of 2 to 6 months. Patient compliance with such lengthy
Eliminato: 89¶
31
regimens is therefore a problem; in a 6-month nightguard vital bleaching study, the rate of
compliance was only 60%.5 To encourage compliance, some offices recall patients on a weekly
basis, which is not an efficient use of office time and also adds to the cost of the procedure.
Many patients may therefore elect to have the procedure completed in the dentist’s office and
will pay the extra cost.13 Thermal tooth sensitivity and gingival irritation, two common adverse
effects that may occur in as many as two thirds of patients undergoing nightguard treatment,
have been ascribed to tray rigidity, multiple changes of the whitening solution in a 24-hour
period, soft-tissue coverage of the guard, and leakage of fluid from the guard.14 Furthermore,
the system may not be favorable for use in certain patient groups. For example, patients with
temporo-mandibular joint disorders can wear trays only during the day, and patients with
bruxism may wear through several trays over the course oftreatment.11
A strong market also exists for OTC products, despite the fact that advertised claims for the
efficacy and safety of these products remain unsubstantiated.11 Additional drawbacks of OTC
systems include lack of professional supervision and poorly adapted bleaching trays, which can
cause occlusal problems, joint and muscle pain, increased salivation, and discomfort during
sleep with extended treatment times.2,11
The treatment described here provides an attractive alternative to current at-home whitening
procedures. The polyethylene film with peroxide gel is supplied as ready-to-use strips and is
easily applied by patients. This ease of use contrasts with the nightguard system, which must be
custom fabricated, precisely fitted, and filled with the bleaching product at each use. In addition,
successful tooth lightening with the film is observed with a much shorter duration of daily wear,
and the thin film is more comfortable and better tolerated by patients. These factors favor
patient acceptance of the procedure and encourage compliance with the whitening regimen.
Eliminato: 89¶
32
Table 1—Demographic Characteristics at Baseline
Peroxide- Tabella formattata

Demographic Containing Gel Placebo Gel Overall
Characteristic (n = 35) (n = 35) (n = 70)
Age (years)
mean range 32.3 (18-66) 33.8 (22-56) 33.0 (18-66)
Sex
Male 15 17 32
Female 20 18 38
Race
Asian 5 2 7
Black 2 2 4
White 27 30 57
Hispanic 1 1 2
S19 Formattato: Tipo di

Table 2—Average Shade Scores by Treatment carattere: (Predefinito) Arial
Tabella formattata
5.3% Peroxide Strip Placebo Strip
End Change End Change

Baseline of Treatment from Baseline Baseline of Treatment from Baseline
(n = 35) (n = 33) (n = 33) (n = 35) (n = 33) (n = 33)
Mean 8.18 4.55 -3.70 8.28 7.49 -0.87
Standard 2.72 2.56 1.99 2.51 3.00 1.35

Deviation
Median 7.00 3.67 -4.00 7.33 6.67 0
Formattato: Tipo di
Eliminato: 89¶
33
Table 3—Gingival (GI) and Plaque Index (PI) Scores at Baseline and 2 weeks
Tabella formattata
Baseline End Of Treatment Change
(2 weeks) (Baseline-
End of
Treatment
)
n Mean SD Range n Mean SD Range Mean
GI
5.3% Peroxide Strip 35 0.75 0.405 (0, 1.6) 33 0.23 0.331 (0, 1) -0.52
Placebo Strip 35 0.65 0.436 (0, 1.5) 33 0.16 0.323 (0, 1) -0.49
PI
5.3% Peroxide Strip 35 0.85 0.437 (0, 1.6) 33 0.24 0.407 (0, 1) -0.61
Placebo Strip 35 0.76 0.450 (0, 1.3) 33 0.18 0.380 (0, 1) -0.59
Formattato: Tipo di
Formattato: Tipo di
Formattato: Tipo di
Eliminato: 89¶
34
REFERENCES Formattato: Tutto maiuscole
1. Haywood VB, Heymann HO: Nightguard vital bleaching. Quintessence Int 20:173-176,
1989.
2. Haywood VB: Current status and recommendations for dentist-prescribed, at-home tooth
whitening. Contemp Esthet 3(suppl 1):2-9, 1999.
3. Haywood VB, Leonard RH, Nelson CF, et al: Effectiveness, side effects, and long-term
status of nightguard vital bleaching. J Am Dent Assoc 125:1219-1226, 1994.
4. Matis BA, Cochran MA, Eckert G, et al: The efficacy and safety of a 10% carbamide
peroxide bleaching gel. Quintessence Int 29:555-563, 1998.
5. Haywood VB, Leonard RH, Dickinson GL: Efficacy of 6 months of nightguard vital
bleaching of tetracycline stained teeth. J Esthet Dent 9:13-19, 1997.
6. Li Y: Biological properties of peroxide-containing tooth whiteners. Food Chem Toxicol
34:887-904, 1996.
7. Croll TP, Sasa IS: Carbamide peroxide bleaching of teeth with dentinogenesis imperfecta
discoloration: report of a case. Quintessence Int 26:683-686, 1995.
8. Small BW: The application of and integration of at-home bleaching into private dental
practice. Compend Contin Educ Dent 19:810-813, 1998.
9. Christensen GJ: Bleaching teeth: practitioner trends. J Am Dent Assoc 128:16S-18S,
1997.
10. Christensen GJ: Bleaching teeth: report of a survey. 1997. J Esthet Dent 10:16-20,
1998.
11. Blankenau R, Goldstein RE, Haywood VB: The current status of vital tooth whitening
techniques. Compend Contin Educ Dent 20:781-794, 1999.
12. Barghi N: Making a clinical decision for vital tooth bleaching: at-home or in-office?
Compend Contin Educ Dent 19:831-838, 1998.
13. Nash RW: In-office bleaching system for quick esthetic change. Compend Contin Educ
Dent 20:986-1000, 1999.
14. Leonard RH: Efficacy, longevity, side effects, and patient perceptions of nightguard vital
bleaching. Compend Contin Educ Dent 19:766-781, 1998.
Formattato: Tipo di
Eliminato: 89¶
35
Chapter 3
Concentration and Dose Response
Clinical Trial Evaluating the Peroxide Concentration Response of a Polyethylene
strip Delivery System over 28 Day

ABSTRACT Formattato: Allineato a
sinistra
OBJECTIVES: The research evaluated the peroxide concentration whitening response Formattato: Tipo di
carattere: Non Corsivo, Tutto
maiuscole
following self-directed use of whitening strips over a 28-day period.
Formattato: Tipo di
carattere: Grassetto, Tutto
maiuscole
MATERIALS AND METHODS: A randomized, double-blind, parallel group clinical study was Formattato: Tipo di
carattere: Non Corsivo, Tutto
maiuscole
conducted. 37 healthy adult volunteers were randomly assigned to one of three groups based
on tooth color at screening – 1.8% hydrogen peroxide strips (HPS), 3.3% HPS or 5.3% HPS.
Subjects applied the assigned maxillary strips twice per day for 30 minutes over 28 days. Tooth
color was evaluated at day 7, 14 & 28 from digital images of the maxillary 6 anterior teeth using
a standard method. Treatments were compared using analysis of covariance (adjusting for
baseline), or analysis of variance at a 0.05 level of significance.
Formattato: Tipo di
RESULTS: Hydrogen peroxide at concentrations ranging from 1.8-5.3% resulted in significant carattere: Non Corsivo, Tutto
maiuscole
(p < 0.05) color improvement versus baseline as early as Day 7. There was a clear Formattato: Tipo di
carattere: Grassetto, Tutto
maiuscole
concentration-response for all color parameters (Δb*, ΔL* and ΔE*) at all timepoints, favoring the
Formattato: Tipo di
carattere: Grassetto, Corsivo
higher concentrations. While the concentration-whitening relationship approached a linear
Formattato: Tipo di
carattere: Arial, 11 pt,
response at Day 7, continued treatment resulted in incremental color improvement. All three Grassetto, Non Corsivo, Colore
carattere: Automatico, Inglese
(U.S.A.), Tutto maiuscole
peroxide concentrations were well tolerated, and no subjects discontinued early due to a
Formattato: Tipo di
carattere: Arial, 11 pt, Inglese
treatment-related adverse event. (U.S.A.)
Formattato: Tipo di
carattere: Arial, 11 pt, Non
Grassetto, Inglese (U.S.A.)
CLINICAL SIGNIFICANCE: Digital image analysis demonstrated a concentration gradient for Formattato: Tipo di
Grassetto
whitening response following use of a low peroxide dose strip whitening system.
Eliminato: 89¶
36
Formattato: Tipo di
INTRODUCTION Tutto maiuscole
Formattato: Corpo del testo
Discoloration of the natural dentition may occur as a result of exposure to various chemicals or 2
Formattato: Tipo di
medicines, disease processes, and other factors.1 Much of this staining is intrinsic in nature, and carattere: Arial, 11 pt, Non
Grassetto
a likely product of the aging process that can be readily measured as increased yellowness and Formattato: Tipo di
decreased brightness in tooth color.2 Treatment typically involves peroxide-based vital Grassetto
Formattato: Tipo di
bleaching, sometimes in combination with other esthetic dental procedures. In practice, carattere: Arial, 11 pt, Non
Grassetto
Formattato: Tipo di
peroxide-containing gels may be applied using a tray, strip or other barrier system, at-home carattere: Arial
Formattato: Tipo di
over time, or in-office with gingival isolation, to assure necessary contact time for peroxide carattere: Arial, 11 pt, Non
Grassetto
diffusion through enamel to the underlying stain. Formattato: Tipo di
Grassetto
Formattato: Tipo di
Practiced widely since the late 1980s, vital bleaching is recognized as safe and effective. There carattere: Arial, 11 pt, Non
Grassetto
are several contemporary reviews that support tooth whitening using peroxide-containing gels in
Formattato: Tipo di
combination with barrier systems.3-5 Some cases with extensive staining, from tetracycline or carattere: Arial, 11 pt, Non
Grassetto
other agents, have been treated daily with peroxide for several weeks or months without Formattato: Tipo di
Grassetto
significant adverse response.6,7 Post-treatment follow-up, which has now exceeded a decade in
Formattato: Tipo di
8,9
some instances, provides further evidence of safety with vital bleaching. Grassetto
Formattato: Tipo di
Grassetto
Peroxide concentration and contact time with tooth surfaces are recognized as playing a Formattato: Tipo di
Grassetto
prominent role in the clinical response seen with vital bleaching.10 Since the 1980s, use of
higher peroxide concentration gels has become more commonplace, in turn, lowering Formattato ... [112]
recommended treatment times from several weeks to only a few days. At the extreme, very Formattato ... [114]
high concentrations of hydrogen peroxide in the range of 35-38% provide a basis for tooth
whitening as an in-office procedure.11,12 Research on peroxide degradation in vivo, and in vitro Formattato ... [117]
shade measurements on extracted teeth further support a relationship between peroxide Formattato ... [119]
13,14 Formattato ... [120]

concentration and whitening.
Eliminato: 89¶
37
Although widely-accepted and plausible, there are surprisingly few peroxide concentration
ranging studies in the clinical trials literature. Such evidence is largely confined to the tray-
based, professional bleaching systems at hydrogen peroxide-equivalent concentrations of 3-

Formattato: Tipo di
7%.7,15 carattere: Arial, 11 pt, Non
Apice / Pedice
Concentration ranging studies provide important evidence, not only of product response, but Formattato: Tipo di
carattere: Arial, 11 pt
also of measurement validity in clinical trials applications. New clinical research was conducted Formattato: Tipo di
to evaluate the effects of peroxide concentration on clinical response using one of the new self-
directed strip-based bleaching systems. Digital image analysis was used to extend the dose
Formattato: Tipo di
ranging evidence from older tray-based research to the newer strip delivery system.15 carattere: Arial, 11 pt
Formattato: Tipo di
Formattato: Tipo di
carattere: 12 pt, Grassetto,
MATERIALS AND METHODS Colore carattere: Nero, Tutto
maiuscole
A randomized, double-blind, parallel group clinical trial was conducted to evaluate the impact of Formattato: Colore carattere:
Nero, Tutto maiuscole
peroxide concentration and treatment duration on whitening effectiveness. The research was Formattato: Normale
conducted within a private dental practice located in western Tuscany, Italy. Following informed
consent, 37 healthy adult volunteers underwent vital bleaching of the maxillary anterior teeth
using a flexible polyethylene strip coated on one side with an experimental, hydrogen peroxide
bleaching gel. After balancing for baseline tooth color, subjects were randomly assigned to one
of three experimental groups: 1.8% hydrogen peroxide strips, 3.3% hydrogen peroxide strips or
5.3% hydrogen peroxide strips (The Procter & Gamble Company, Cincinnati, OH USA).
Maxillary strips carried 0.200 mg of hydrogen peroxide gel distributed uniformly across the 9.9
cm2 strip surface. In this double-blind study, treatment groups differed only in peroxide
concentration, and otherwise, were identical in appearance, aesthetics, packaging, and labeling.
Usage was twice daily for 30 minutes over a 28-day period, at-home and unsupervised. Study
participants returned for efficacy and safety evaluations at day 7, day 14, and day 28.
Efficacy and safety assessments were conducted at baseline and subsequent visits blind as to
treatment assignment. Efficacy was assessed as change in tooth color as measured from Eliminato: 89¶
38
standard digital images of the maxillary anterior teeth. This objective and instrumental color
measurement method had previously been used to demonstrate a peroxide concentration
response for tray-based professional bleaching systems.15 Using this method, subjects were
first positioned in a chin rest, retractors were inserted, and standard bilateral illumination of the
arch was obtained from two 150-watt lights and linear polarizers. Images were then captured
using a photographic system using a HC1000 CCD high resolution digital camera manufactured
by Fuji a Fujinon A8x12BMD, 1:2.8/12-96mm zoom lens, and a personal computer. Color
measurements were calibrated to known standards daily prior to use and hourly thereafter to
assure proper operation. Safety was assessed by interview and clinical examination at each
visit. The interview focused on tooth sensitivity or oral irritation during treatment, since these
have been recognized as the most common adverse events associated with vital bleaching.16
The clinical examination, using a standard dental light, dental mirror, and gauze, evaluated the
oral and perioral regions, including the gingiva (free and attached), hard and soft palate,
oropharynx/uvula, buccal mucosa, tongue, floor of the mouth, labial mucosa,
mucobuccal/mucolabial folds, and lips to assess any changes in oral status with treatment.
For analysis, red-green-blue values for the 6 maxillary teeth were derived with reference to
calibration standards, and then, these average values were transformed to yield CIELAB tooth
color values for b* (yellow – blue), L* (lightness), and a* (red – green).17 Change values were
calculated for any given post-baseline visit as: Δb* = b*visit - b*baseline, ΔL* = L*visit - L*baseline, Δa* =
a*visit - a*baseline. In addition, a composite parameter, ΔE*, was derived from the square root of
the sum of the squares of the individual L*a*b* changes. Reduction in yellowness (Δb*) was
selected a priori as the primary endpoint, because this parameter has been previously shown to
correlate with subjective perception of whitening following vital bleaching.18
A paired difference t-test was used to evaluate absolute color improvement (change from
baseline). Between-group efficacy comparisons were made at each time point using analysis of
Eliminato: 89¶
39
covariance with the baseline value as the covariate. A separate model was fit for Δb* and ΔL*.
Treatment comparisons for ΔE* used analysis of variance methods. All testing was two-sided at
a 5% significance level without adjusting for multiple comparisons. Tolerability outcomes were
tabulated by treatment.

RESULTS
Of the 37 subjects randomized, one had a baseline image that was not evaluable, one had
extensive facial anterior restorations, and one had heavy, atypical extrinsic stain. Of the 34
remaining subjects, 32, 29 and 28 were present and evaluable at Days 7, 14 and 28,
respectively. This sample ranged in age from 21-66 years, with mean (SD) age of 37.2 (11.4).
Males (53%) and females (47%) were similarly represented in the population. Study subjects
exhibited considerable diversity with respect to tooth color. At baseline, b* (yellowness) ranged
from 16.2 to 22.7, L* (brightness) ranged from 66.3 to 77.2, and a* (redness) ranged from 5.9 to
9.1. Treatment groups were balanced (p > 0.18) with respect to age, gender, and tooth color at
baseline.
All three treatments resulted in significant whitening, with color improvement evident as early as
Day 7. For the primary response parameter, the Day 7 mean (SD) Δb* values were –0.44
(0.558), –0.86 (0.509), and –1.41 (0.690) in the 1.8%, 3.3% and 5.3% hydrogen peroxide strip
groups, respectively, with each group differing significantly from baseline (p < 0.05) at this initial
timepoint. Outcomes were generally similar for ΔL*, as well as the composite parameter ΔE*,
with each differing significantly (p < 0.05) from baseline at Day 7. Continued use past Day 7
resulted in incremental color improvement. This was evident for the individual parameters Δb*
and ΔL*, as well as the composite parameter, ΔE*.
Between-group comparisons generally favored the higher concentration groups (Table 1-3). At
Day 7, the 5.3% strips exhibited significant (p < 0.05) reduction in yellowness versus the other
Eliminato: 89¶
40
two groups, while at Day 14, both the 5.3% and 3.3% groups differed significantly (p < 0.03)
from the lowest concentration 1.8% strips. These outcomes generally held (directionally or
significantly) for ΔL*, and for the composite parameter ΔE*. At Day 7, mean (SE) ΔE* was 1.01
(0.204), 1.66 (0.204) and 2.30 (0.214) for the 1.8%, 3.3% and 5.3% groups, respectively. All
three treatments differed significantly (p < 0.05), with increasing concentration contributing to
greater composite color change. Results were similar over time, though by Day 28, the
composite ΔE* for the intermediate concentration approached that seen with the higher
concentration. Mean (SE) ΔE* was 3.23 (0.272) and 3.26 (0.246) for the 3.3% and 5.3%,
respectively, with these higher concentration strips not differing significantly (p = 0.944).
Figure 1 illustrates the concentration response for the primary whitening parameter Δb* over
time. (Because yellowness is removed during bleaching, negative change in b* is
representative of color improvement. The graph illustrates –Δb* in order to be consistent with
ΔL*, where positive change represents improvement.) The linear concentration response is
most evident at Day 7 across the concentration ranges tested in this research. Similar results
are evident for ΔL*, and the mathematical composite parameter ΔE* (Figures 2-3). Overall,
twice-daily use of 5.3% strips for 14 days yielded generally similar whitening (Δb*, ΔL and ΔE*)
to the 3.3% strips used for 28 days.
Transient oral irritation represented the most common side effect associated with treatment.
Oral irritation was reported only in the lower concentration group (25% of subjects), and the
higher concentration group (36% of subjects). One subject (in the 5.3% hydrogen peroxide
group) had an aphthous ulcer during treatment. Other safety findings were generally
unremarkable. Most (75%) oral soft tissue findings were judged “mild” in severity, with only two
events (in the higher concentration group) scored as moderate. All peroxide concentrations
were well tolerated overall, and none of the study participants discontinued strip use due to a
product-related adverse event.

Eliminato: 89¶
41
Formattato: Tipo di
DISCUSSION 12 pt
Formattato: Tipo di
This double-blind clinical trial evaluated the effect of peroxide concentration on whitening carattere: (Predefinito) Arial,
Tutto maiuscole
response following repeated daily use of a self-directed bleaching system. In this research, Formattato: Corpo del testo
2
hydrogen peroxide at concentrations ranging from 1.8-5.3% resulted in significant color Formattato: Tipo di
Grassetto, Colore carattere:
improvement compared to baseline. This was evident for all individual L*a*b* color parameters Automatico
measured in the study, as well as the mathematical composite parameter ΔE*, beginning as
early as Day 7.
Formattato: Tipo di
carattere: Arial
Formattato: Tipo di
Extended treatment duration past Day 7 contributed to greater observed whitening response for carattere: Arial, 11 pt, Non
Automatico
each of the strip concentrations. This was evident for all parameters (Δb*, ΔL* and ΔE*)
measured in this study. Such results are consistent with previous research which demonstrated
a favorable impact of treatment duration on tooth color in head-to-head testing comparing a

Formattato: Tipo di
popular tray and strip-based system.19 Use of hydrogen peroxide under barrier conditions at carattere: Arial, 11 pt, Non
Grassetto
lower concentrations (~2%) is likely to require a much greater treatment duration. In this Formattato: Tipo di
research, the observed whitening response at Day 7 with the 5.3% strips (Δb*, ΔL* and ΔE*) Automatico
exceeded that achieved with the 1.8% strips at Day 28. Clinical implications with respect to
compliance and other factors may suggest use of higher concentrations where possible.
Formattato: Tipo di
carattere: Arial
Formattato: Tipo di
The research provides clear evidence of a peroxide concentration whitening response. carattere: Arial, 11 pt, Non
Automatico
Whitening efficacy was greatest for the highest concentration group (5.3% hydrogen peroxide),
while the intermediate concentration group had an intermediate response. Not surprisingly, this
effect most approached linearity at the earliest time point (Day 7). At that time, adjusted mean
Δb* for was –1.43, –0.84, and –0.44 in the higher, intermediate and lower concentration groups,
respectively. Relative to the lowest concentration strip, this represented a 225% improvement
in whitening for the 5.3% strip (a 194% increase in concentration), and a 91% improvement in
whitening for the 3.3% strip (a 83% increase in concentration). As such, peroxide concentration
Eliminato: 89¶
42
alone likely contributed the measured differences in response at that time point, results that are
completely consistent with the physical chemical bleaching process.

Formattato: Tipo di
carattere: Arial
Formattato: Tipo di
With extended treatment, the concentration response curve flattened out especially at the two carattere: Arial, 11 pt, Non
Automatico
higher peroxide concentrations. At Day 28, the adjusted mean Δb* was 20% higher in the 5.3%
group compared to the 3.3% group (a 61% difference in concentration). While sample sizes
were small, there were no statistically significant differences in Δb*, ΔL* or ΔE* between the
higher and intermediate concentrations at Day 28. This flattening with extended treatment may
be expected in dose ranging, especially where the response substrate (intrinsic stain) is non-
renewal or slowly renewable, as it is with vital bleaching.

Formattato: Tipo di
carattere: Arial
Formattato: Tipo di
Despite the concentration differences (there was nearly a three-fold difference between the carattere: Arial, 11 pt, Non
Automatico
lowest and highest concentration tested in this research), all three strips tested in this research
carried a low total amount of peroxide. The total amount of hydrogen peroxide on each pre-
dispensed strip ranged only from 3.6-10.6 mg. Relative to some tray-based systems, which
may deliver up to 2 grams of bleaching gel, total peroxide delivered with any of these strips was
remarkably low. This likely contributed to the low overall adverse event rate seen in this trial.
All three treatments were well tolerated, with no subjects reducing or discontinuing treatment
due to bleaching-related adverse events.

Formattato: Tipo di
carattere: Arial
Formattato: Tipo di
This new clinical research provides evidence of a concentration gradient for whitening response carattere: Arial, 11 pt, Non
Automatico
following use of a low peroxide dose strip whitening system. As such, this may represent a first
example of concentration ranging for one of the self-directed bleaching systems. More
importantly, the research also provides evidence of the sensitivity and robustness of the
measurement method – in this instance – digital imaging. While previous concentration ranging
research was conducted in the US on tray-based systems, this work was done in Italy, in a
private dental practice using strips for peroxide delivery.15 The authors are unaware of any other
Eliminato: 89¶
43
method (whether subjective shade assessment or objective colorimetry) that has demonstrated
Formattato: Tipo di
carattere: Arial
similar measurement sensitivity under such diverse clinical research conditions.
Formattato: Tipo di
Concentration ranging trials, like this one, represent one of the most complex and difficult carattere: Arial, 11 pt
studies types in the clinical research arena. Research of this nature may be particularly Interlinea doppia
exemplary of the measurement sensitivity (or lack thereof) of the clinical method used in the
study. By design, the goal of this research was to distinguish both the effect of increased
peroxide concentration (three treatment groups) and increased treatment duration (three post-
treatment timepoints) within the constraints and variability seen with unsupervised human
testing. Moreover, the research involved a degree of blinding, both with respect to the test
products (identical appearing peroxide-containing strips), and clinical methods (instrumental
color measurement from digital images) greater than that seen in most vital bleaching clinical
trials. Despite these complexities, the research adequately differentiated multiple
concentrations from low to high over time. With Δb* as an endpoint, the study demonstrated a
nearly linear concentration response relationship, with measured efficacy differences at Day 7
that reasonably modeled the real concentration differences between groups. As such, the
research provides important evidence of the validity of this method and endpoint for practice-
relevant evaluation of vital bleaching technologies.
Eliminato: 89¶
44
Tables and Figures
Table 1 Adjusted Mean Δb* and ANCOVA Treatment Comparisons
Table 2 Adjusted Mean ΔL* and ANCOVA Treatment Comparisons
Table 3 Mean ΔE* and ANOVA Treatment Comparisons
Figure 1 Peroxide Concentration on Strip and Adjusted Mean –Δb* at 7, 14 & 28 Days
Figure 2 Peroxide Concentration on Strip and Adjusted Mean ΔL* at 7, 14 & 28 Days
Figure 3 Peroxide Concentration on Strip and Adjusted Mean ΔE*at 7, 14 & 28 Days
Eliminato: 89¶
45
Formattato
Table 1
Adjusted Mean Δb* and ANCOVA Treatment Comparisons
Evaluable Subjects (N=34)
Adjusted Mean Two-Sided p-Value
Visit/Group Change From
Baseline (SE)a 3.3% H2O2 5.3% H2O2
Day 7
1.8% H2O2 -0.44 (0.181) 0.122 0.001
3.3% H2O2 -0.84 (0.182) 0.041
5.3% H2O2 -1.43 (0.195)
Day 14
1.8% H2O2 -1.02 (0.203) 0.026 0.006
3.3% H2O2 -1.77 (0.245) 0.525
5.3% H2O2 -1.99 (0.240)
Day 28
1.8% H2O2 -1.23 (0.284) 0.094 0.010
3.3% H2O2 -1.91 (0.272) 0.308
5.3% H2O2 -2.30 (0.251)
a
Means adjusted for baseline b*
Eliminato: 89¶
46
Table 2
Adjusted Mean ΔL* and ANCOVA Treatment Comparisons
Adjusted Mean Two-Sided p-Value
Visit/Group Change From
Baseline (SE)a 3.3% H2O2 5.3% H2O2
Day 7
1.8% H2O2 0.74 (0.281) 0.423 0.175
3.3% H2O2 1.07 (0.287) 0.580
5.3% H2O2 1.31 (0.297)
Day 14
1.8% H2O2 1.20 (0.203) 0.717 0.051
3.3% H2O2 1.32 (0.249) 0.140
5.3% H2O2 1.86 (0.240)
Day 28
1.8% H2O2 1.28 (0.318) 0.100 0.051
3.3% H2O2 2.03 (0.302) 0.776
5.3% H2O2 2.15 (0.275)
a
Means adjusted for baseline L*
Eliminato: 89¶
47
Table 3
Mean ΔE* and ANOVA Treatment Comparisons
Mean Change Two-Sided p-Value
Visit/Group From
Baseline (SE) 3.3% H2O2 5.3% H2O2
Day 7
1.8% H2O2 1.01 (0.204) 0.031 <0.001
3.3% H2O2 1.66 (0.204) 0.041
5.3% H2O2 2.30 (0.214)
Day 14
1.8% H2O2 1.83 (0.182) 0.061 0.001
3.3% H2O2 2.39 (0.223) 0.158
5.3% H2O2 2.84 (0.211)
Day 28
1.8% H2O2 2.00 (0.289) 0.005 0.003
3.3% H2O2 3.23 (0.272) 0.944
5.3% H2O2 3.26 (0.246)
Formattato: Tipo di
Interlinea singola
Eliminato: 89¶
48
Formattato: Tipo di
Figure 1 carattere: Arial, Italiano (Italia)
Eliminato: 89¶
49
Figure 2
Eliminato: 89¶
50
Figure 3
Eliminato: 89¶
51
REFERENCES
1. Watts A, Addy M. Tooth discolouration and staining: a review of the literature. Br Dent J
2001;190:309-16.
2. Odioso LL, Gibb RD, Gerlach RW. Impact of demographic, behavioral and utilization Formattato: Inglese (U.S.A.)
parameters on tooth color and personal satisfaction. Compend Contin Educ Dent 2000;21:S35-
41.
3. Niederman R, Tantraphol MC, Slinin P, Hayes C, Conway S. Effectiveness of dentist-
prescribed, home-applied tooth whitening. A meta analysis. J Contemp Dent Pract 2000;15:20-
36.
4. Haywood VB. Current status of nightguard vital bleaching. Compend Contin Educ Dent
2000;28:S10-7.
5. Gerlach RW, Zhou X. Vital bleaching with whitening strips: Summary of clinical research on
effectiveness and tolerability. J Contemp Dent Pract 2001;2:1-16.
6. Kugel G, Aboushala A, Zhou X, Gerlach RW. Daily use of whitening strips on tetracycline- Formattato: Inglese (U.S.A.)
stained teeth: comparative results after 2 months. Compend Contin Educ Dent 2002;23:29-34.
7. Matis BA, Wang Y, Jiang T, Eckert GJ. Extended at-home bleaching of tetracycline-stained Formattato: Inglese (U.S.A.)
teeth with different concentrations of carbamide peroxide. Quintessence Int 2002;33:645-55.
8. Ritter AV, Leonard RH Jr, St Georges AJ, Caplan DJ, Haywood VB. Safety and stability of
nightguard vital bleaching: 9 to 12 years post-treatment. J Esthet Restor Dent 2002;14:275-85.
9. Leonard RH Jr, Van Haywood B, Caplan DJ, Tart ND. Nightguard vital bleaching of
tetracycline-stained teeth: 90 months post treatment. J Esthet Restor Dent. 2003;15:142-52.
10. Matis BA. Tray whitening: what the evidence shows. Compend Contin Educ Dent
2003;24:354-62.
11. Gallagher A, Maggio B, Bowman J, Borden L, Mason S, Felix H. Clinical study to compare
two in-office (chairside) whitening systems. J Clin Dent 2002;13:219-24.
12. Papathanasiou A, Kastali S, Perry RD, Kugel G. Clinical evaluation of a 35% hydrogen
peroxide in-office whitening system. Compend Contin Educ Dent 2002;23:335-44.
13. Matis BA, Yousef M, Cochran MA, Eckert GJ. Degradation of bleaching gels in vivo as a Formattato: Inglese (U.S.A.)
function of tray design and carbamide peroxide concentration. Oper Dent 2002;27:12-8.
14. Leonard RH, Sharma A, Haywood VB. Use of different concentrations of carbamide
peroxide for bleaching teeth: an in vitro study. Quintessence Int 1998;29:503-7.
15. Gerlach RW, Gibb RD, Sagel PA: A randomized clinical trial comparing a novel 5.3%
hydrogen peroxide bleaching strip to 10%, 15% and 20% carbamide peroxide tray-based
bleaching systems. Compend Contin Educ Dent 2000;21:S22-28.
16. Leonard RH, Haywood VB, Phillips C. Risk factors for developing tooth sensitivity and
gingival irritation associated with nightguard vital bleaching. Quintessence Int 1997;28:527-34.
17. Commission Internationale de L’Eclairage: Recommendations on uniform color spaces.
Color difference equations. Psychometric color terms. Suppl 2 to CIE pub 15 (E-13.1)1971/(TC-
1.3), Paris, France: Bureau Central de la CIE, 1978.
18. Gerlach RW, Barker ML, Sagel PA. Objective and subjective whitening response of two
self-directed bleaching systems. Am J Dent 2002;15:7-12A.
19. Karpinia KA, Magnusson I, Sagel PA, Zhou X, Gerlach RW. Vital bleaching with two at-
home professional systems. Am J Dent 2002;15:13-18A.
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52
Chapter 4
Light activated Tooth Whitening
Clinical Evaluation of a 35% Hydrogen Peroxide In-Office Whitening System

ABSTRACT
Formattato: Tipo di
This study evaluated the effectiveness of light-curing (heat conversion) vs no light-curing (no carattere: 11 pt
heat conversion) of a 35% hydrogen peroxide in-office tooth whitening system. Twenty patients
with sound medical history (without tooth sensitivity) participated in this randomized, parallel
clinical evaluation. Only six maxillary anterior teeth with discoloration and a tooth shade of A3 or
darker were selected. Patients received a complete prophylaxis and were evaluated for initial
(baseline) shade by three independent evaluators, precalibrated at 85% rater reliability in
determining shades before the experiment began. Participants received a 20-minute chairside
whitening treatment with a 35% hydrogen peroxide agent using a reflective resin barrier for
gingival isolation. During the whitening treatment, the 35% hydrogen peroxide agent was light
activated with a halogen curing light on teeth Nos. 6 through 8 (Group I), but was not light-
activated on teeth Nos. 9 through 11 (Group II). All patients returned 24 hours after the
whitening application for shade evaluation. Although there were isolated instances (7 out of 20
patients) of greater degrees of lightening in the light-curing group, there was no statistically
significant difference using the Mann-Whitney U test (P > .05). This study indicates that light-
curing is optional with this 35% tooth whitening system.
Eliminato: 89¶
53
Learning Objectives
After reading this article, the reader should be able to:

Formattato: Tipo di
carattere: 11 pt
describe an in-office whitening technique using 35% hydrogen peroxide.
discuss tooth color modifications produced using a 35% hydrogen peroxide.
recognize the effectiveness of tooth color modifications produced with 35% hydrogen
peroxide in-office technique.
Tooth whitening has become one of the most popular esthetic dental procedures. The
management of the discolored dentition is not new to the dental profession—it was first reported
1
in 1877. Whitening offers a conservative, simplified, and economical approach to changing the
color of one’s teeth. Candidates for whitening include patients whose teeth have been stained
over time by aging, chromogenic foods, endodontic treatment, tetracycline use, and smoking or
2
the use of other tobacco products.
Acceptable whitening techniques include the in-office procedure, the dentist-prescribed home-
applied technique, or a combination of the two. Recently, whitening strips have been introduced
3
as an alternative whitening method. In the 1970s, vital tooth whitening was being performed
with in-office treatments using different concentrations of liquid hydrogen peroxide solutions and
4
(sometimes) a heat lamp. In 1989, the first article on nightguard vital bleaching using
carbamide peroxide was published by Haywood and Heymann after evaluation at the University
5
of North Carolina. Currently, the in-office whitening technique uses a 15% to 35% hydrogen
peroxide whitening agent (heated or nonheated); the dentist-prescribed home-applied technique
most commonly uses a 10% to 15% carbamide peroxide gel.
The advantage of the in-office procedure is that it does not require patient compliance and
results may be seen immediately. The disadvantage is the chair time, cost to the patient, and
the possibility of multiple visits. A light-activated chairside whitening system has the potential
advantages of taking less time and providing quicker results.

Eliminato: 89¶
54
The purpose of this study was to evaluate:
Formattato: Tipo di
carattere: 11 pt
1. The effectiveness of a 35% hydrogen peroxide in-office system
® ®,a ®,a
(Opalescence Xtra and OpalDam ) in tooth color modifications.
2. The effect of light when compared to no-light activation (light-to-heat
activator and light-to-nonheated activator).
3. The incidence of soft tissue irritation related to the active whitening
chemical, hydrogen peroxide.
4. Patient responses to the whitening treatment.

METHODS AND MATERIALS Formattato: Tabulazioni: 0
pt, Allineato a sinistra
Before participating in this blinded, parallel tooth whitening study, all patients were Formattato: Normale,
Interlinea doppia, Tabulazioni:
0 pt, Allineato a sinistra + 54
asked to sign an informed consent form. Both the form and the research protocol were reviewed pt, Allineato a sinistra
and approved by the Human Investigational Review Committee at Tufts University. A total of 20
patients (with no medically compromised history or tooth sensitivity) were recruited from the
Tufts University dental clinic to participate in this randomized, parallel clinical evaluation. The
criteria used to recruit participants for this investigation included:

Formattato: Tipo di
carattere: 11 pt
No active caries.
Formattato: Tipo di
18 years of age or older. carattere: 11 pt
Formattato: Tipo di
Maxillary and mandibular teeth with the same color. carattere: 11 pt
The exclusion criteria were: riga: 36 pt
Intrinsic dental staining (ie, tetracycline or fluorosis).
Nonvital teeth.
Patients that had previous tooth whitening procedures.
Extended composite restorations at the teeth that would be included in
this study.
Eliminato: 89¶
55
Formattato: Tipo di
Only 6 maxillary anterior teeth with minor uniform staining or discoloration with a shade no carattere: 11 pt
lighter than A3 were selected. The six mandibular anterior and contralateral maxillary, non–light-
cured teeth were used as the control group.

At the initial appointment, all necessary consent forms were signed before any treatment was Interlinea doppia
rendered. Then, a thorough clinical and medical evaluation was taken for each patient. All
patients received a complete oral prophylaxis (cleaning and polishing) 2 weeks before beginning
the whitening process. At the next appointment, all of the subjects underwent a baseline
periodontal evaluation, which included color, size, shape, and consistency of the involved
gingival tissue. Each patient was evaluated for initial (baseline) shade by three independent
evaluators. The evaluators consisted of the subject, the dentist treating the subject, and a
second dentist. All evaluators were calibrated at 85% rater reliability in determining shades
Formattato: Tipo di
carattere: 12 pt
before the onset of this project. A consensus method (two of the three evaluators) was used
to record the shades of the 6 test anterior maxillary teeth and 6 lower anterior teeth as
Formattato: Tipo di
carattere: 12 pt, Tedesco
the control group. Shades were assessed using the Standard Vita Shade Guideb. All (Germania), Non Alzato/
Abbassato
shade measurements were recorded at baseline and an initial photograph was taken of the Formattato: Tipo di
carattere: 12 pt
maxillary and mandibular teeth. Formattato: Tipo di
carattere: 12 pt, Non Alzato/
At this appointment, the 20 participants received a 20-minute chairside whitening treatment with Abbassato
Formattato: Tipo di
a 35% hydrogen peroxide whitening agent (Opalescence Xtra), using OpalDam for gingival carattere: 12 pt
isolation. Before the hydrogen peroxide application, all teeth were cleaned using pumice and a
slow-speed rotary brush/prophy cup. Teeth Nos. 6 through 11 were whitened using the 35%
hydrogen peroxide whitening agent, but only teeth Nos. 6 through 8 were light activated with a
curing light. A questionnaire was provided to the patients for recording any comments. All
Formattato: Tipo di
carattere: 12 pt
participants were able to contact any of the principle investigators if any side effects such
as tooth sensitivity, gum tissue irritation, or bad taste were experienced.
All patients were required to return 24 hours after the day of the second appointment for
a recall appointment. A final periodontal evaluation was taken for all patients, which
consisted of visual gingival recordings using standardized Löe and Silness Gingival Index: Eliminato: 89¶
56
Formattato: Tipo di
0 = No inflammation carattere: 11 pt
1 = Slight inflammation
2 = Moderate inflammation
3 = Severe inflammation
In addition, recordings of loss of sensation, change in gingival texture, spontaneous bleeding, Interlinea doppia
and the sloughing of gingival tissue were noted. A final shade was then selected and a final
intraoral photograph was taken at the 24-hour recall appointment.

Formattato: Tipo di
Data (degree of color change from baseline) were analyzed using statistical tests to determine carattere: 11 pt
the significance of the light activation when using the 35% hydrogen peroxide tooth whitening
agent.

RESULTS
Formattato: Tipo di
The 35% hydrogen peroxide in-office tooth whitening system was effective in lightening teeth. carattere: 11 pt
However, the purpose of this study was to evaluate the effectiveness of light-curing vs no light-
curing of this whitening system. Although there were isolated instances (7 out of 20 patients) of
greater degrees of lightening in the light-curing group (median for Group I was 7.21 and Group
II was 6.78) (Table 1), there was no statistical significant difference using the Mann-Whitney U
test (P > .05). Both whitening protocols were effective in the lightening of teeth with no adverse
effects. All shade evaluations using the Vita Shade Guide were recorded with the guide
arranged in value order, where they are assigned a number from 1 through 16. This order is
shown at the bottom of Table 1.
Patients were given questionnaires to record tooth sensitivity, gingival irritation, bad taste, and
noticeable shade change. One patient experienced slight tooth sensitivity (only at one tooth) at
the end of the whitening procedure, which subsided before the 24-hour recall visit. No bad taste
and no gingival irritation were reported and OpalDam appeared to be effective in isolating the
Formattato: Tipo di
tissues against any caustic behavior. All participants in the study expressed satisfaction with the carattere: 11 pt
whitening process and the results (Table 2). Eliminato: 89¶

57
DISCUSSION
Traditionally, in-office whitening products have been used to give a patient a head start in the
whitening process, to touch-up postwhitening cases if they should regress in shade, and to
6
function solely as a whitening product. Opalescence Xtra is a commonly used 35%
hydrogen peroxide tooth whitening agent for in-office treatment. After gingival isolation with
OpalDam , the whitening material was applied to each facial enamel surface on the six
maxillary anterior teeth, but was light-cured only on teeth Nos. 6 through 8. This light-activated
material is contained in a carotene base to absorb light, providing an increased whitening
7
effect. The results of this study revealed that the use of the halogen light improved the
effectiveness of the whitening material in some cases. However, in those cases, the difference
between light-cured vs non–light-cured teeth was 1 to 3 shades, which was not noticeable to the
®
patients. Shade evaluation determined Vita shade B1 for teeth Nos. 6 through 8 (light-cured)
and A1 for teeth Nos. 9 through 11 (non–light-cured).

Formattato: Tipo di
As stated earlier, the purpose of this study was to determine if the use of a light in the in-office carattere: 11 pt
Formattato: Corpo del testo
whitening process would increase the effect of whitening on the teeth. Of the 20 patients in this 3, Tabulazioni: 36 pt, Allineato
a sinistra
study, 7 patients experienced an increase in lightening of the split arch protocol. The increase
was an average lightened increase of 1.714 shades as compared to the non–light-cured side.
This was not a significant clinical change. Any shade difference as noted by the light-activated
side was most likely a result of dehydration resulting from heat generated by the halogen curing
light. Statistically, there was no significant difference between the light-activated side when
compared to non–light-activated side.

Formattato: Tipo di
The results contradict other studies, which have indicated that light activation causes an carattere: 11 pt
8,9
increased whitening effect as used with hydrogen peroxide whitening agents. Based on the
Clinical Research Associates’ report, the use of a curing light in addition to the manufacturer-
Formattato: Tipo di
carattere: 11 pt
recommended exposure times, does not produce sufficient heat generation was to significantly
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58
Formattato: Tipo di
10 carattere: 11 pt
increase the breakdown of H2O2. It is this activation of H2O2 that results in the increased
Formattato: Tipo di
whitening effect. A transient whitening effect may be the result of dehydration. To potentiate the carattere: 11 pt
effect of H2O2, high temperatures must be reached, which could potentially cause damage to
the tooth. This report also states that Opalescence Xtra experiences a relatively low rate
10
increase in H2O2 even when temperatures are raised as high as 100° C. This would also
support our findings that the addition of light does not increase the effect of the whitening
Formattato: Tipo di
process. carattere: 11 pt

CONCLUSION
Formattato: Tipo di
This study evaluated the effectiveness of light-curing vs no light-curing of a 35% hydrogen carattere: 11 pt
peroxide in-office tooth whitening system. Tweny patients with sound medical history (without
tooth sensitivity) participated in this randomized, parallel clinical evaluation. The outcome of this
study leads to the conclusion that the use of a halogen curing light to increase the activation of
35% hydrogen peroxide is of no benefit to the dentist or the patient.
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59
Table 1 Formattato: Tipo di
carattere: Arial
Tooth Color Modifications as Ascertained by The Consensus Method
Subject Initial Final (Light Cured) Final (No
Light Cured)
1 A3 B1 (8) A1 (7)
2 A3 A1 (7) A2 (4)
3 A3.5 A2 (7) A2 (7)
4 A3 A1 (7) A1 (7)
5 A3 A1 (7) D2 (5)
6 D3 B1 (9) A1 (8)
7 A3 A1 (7) A1 (7)
8 D3 A1 (8) A1 (8)
9 C3 C1 (8) C1 (8)
10 A3 A2 (4) A2 (4)
11 A3 A1 (7) A1 (7)
12 A3 A2 (4) A2 (4)
13 A3 D2 (5) D2 (5)
14 D3 A1 (8) A2 (5)
15 A3 D2 (5) D2 (5)
16 A3 A1 (7) A1 (7)
17 D3 A1 (8) A1 (8)
18 A3 B1 (8) A1 (7)
19 A3 D2 (5) A2 (4)
20 A3 B1 (8) B1 (8)
Totals: Group I:137, Group II:125. Median Group I: 7.21 Median Group II: 6.78
The numbers in parentheses show how many shade changes were accomplished with the use
® ®
of Opalescence Xtra during the study, from the initial to the final appointment.
®
Vita Shade Guide arranged in value order:
B1 A1 B2 D2 A2 C1 C2 D4 A3 D3 B3 A3.5 B4 C3 A4 C4
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16
Table 2—Tooth Sensitivity, Gingival Irritation, Bad Taste, and Noticeable
Shade Change Evaluation by Each Subject in the Exit Questionnaire
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60
Subject Tooth Sensitivity Gingival Irritation Bad Taste Noticeable
Shade Change
1 No No No Yes
2 No No No Yes
3 No No No Yes
4 No No No Yes
5 No No No Yes
6 No No No Yes
7 No No No Yes
8 No No No Yes
9 No No No Yes
10 No No No Yes
11 Yes No No Yes
12 No No No Yes
13 No No No Yes
14 No No No Yes
15 No No No Yes
16 No No No Yes
17 No No No Yes
18 No No No Yes
19 No No No Yes
20 No No No Yes
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61
PRODUCT REFERENCES
a
Ultradent Products, Inc., South Jordan, UT 84095; (800) 552-5512
b
Vita Zahnfabrik, Germany, distributed in US by Vident, Brea, CA 92621; (800) 828-3839).
REFERENCES
1. Fasanaro TS: Bleaching teeth: history, chemicals and methods used for common tooth
discoloration. J Esthet Dent 4: 71-78, 1992.
2. Kugel G: Nontray whitening. Compend Contin Educ Dent 21(6):524-528, 2000.
3. Kugel G, Kastali S: Tooth whitening eficacy and safety: randomized and control clinical trial.
Compend Contin Educ Dent 21(Suppl 28): 2000.
4. Nathanson D: Vital bleaching sensitivity and pulpal considerations. J Am Dent Assoc
128(Suppl):41S-44S, 1997.
5. Haywood VB, Heymann HO: Nightguard vital bleaching. Quintessence Int 20(3):173-176,
1989.
6. Kugel G, Perry RD, Hoang E, et al: Effective tooth bleaching in 5 days: using a combined in-
office and at-home bleaching system. Compend Contin Educ Dent 18(4):378-383, 1997.
7. Gultz J, Kaim J, Scherer W, et al: Two in-office bleaching systems: a scanning electron
microscope study. Compend Contin Educ Dent 20(10):965-970, 1999.
8. Li Y, Cartwright S, Lezama M, et al: Effect of light application on an in-office bleaching gel
[abstract]. J Dent Research 80(147), 2001. Abstract 895.
9. Tavares M, Goodson JM, Stutz J, et al: A randomized single blind clinical trial of tooth
whitening with peroxide and light [abstract]. J Dent Research 80(182):2001. Abstract 1171.
10. CRA Newsletter August, 2000.
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62
CHAPTER 5
CHEMICAL VS LIGHT ACTIVATED TOOTH WHITENING
Clinical Evaluation of Chemical and Light-Activated Tooth Whitening Systems
ABSTRACT
Formattato: Tipo di
BACKGROUND carattere: 11 pt, Tutto
maiuscole
Tooth whitening has become one of the most popular of dental treatments. There are many Formattato: Tipo di
carattere: 11 pt
options available. The paper attempts to compare the efficacy of two in-office whitening Formattato: Tipo di
carattere: 11 pt
systems.
Formattato: Tipo di
METHODS carattere: 11 pt, Tutto
maiuscole
In this split-arch, randomized, parallel, blinded clinical evaluation six maxillary anterior teeth Formattato: Tipo di
maiuscole
(N=60) A-2 or darker were selected using the value order Vita Shade Guide. Patients received
Formattato: Tipo di
carattere: 11 pt
one-hour light-activated chairside treatment using 15% H2O2 teeth 6-8 (Group I), teeth 9-11
Formattato: Tipo di
carattere: 11 pt
received a 38% H2O2 system for 1 hr without a light (Group II). Before and after treatment Formattato: Tipo di
carattere: 11 pt
images were taken. L*, a* and b* and Vita shades were measured. Patients returned after 2 Formattato: Tipo di
carattere: 11 pt
weeks for final shade evaluation. Formattato: Tipo di
carattere: 11 pt
Formattato: Tipo di
carattere: 11 pt
RESULTS Formattato: Tipo di
carattere: 11 pt
Both in-office tooth whitening systems were effective. Group I averaged 5.9 ± 2.5 and Group II Formattato: Tipo di
carattere: 11 pt
3.97 ± 2.33 shade changes immediately after treatment. At the 2-week recall, Group I scored an Formattato: Tipo di
carattere: 11 pt
average of 4.6 ± 2.14 and Group II 4.6 7± 2.3 shade changes, compared to the pre-bleaching Formattato: Tipo di
shades. A paired sample t-test revealed statistically significant difference (p<0.0001) between maiuscole
Formattato: Tipo di
Groups I and II immediately after bleaching, with Group I performing better. At the 2-week recall, carattere: 11 pt
Formattato: Tipo di
however, only Group I showed a significant rebound (p=0.0002). At the completion of the study, carattere: 11 pt
there was no significant difference between Groups I and II (p=0.7826). Eliminato: 89¶
63
Formattato: Tipo di
CONCLUSION carattere: 11 pt, Tutto
maiuscole
This study indicated that both chairside tooth whitening systems are effective and that no Formattato: Tipo di
carattere: 11 pt
statistically significant differences were observed over the 2-week period of observation. Formattato: Tipo di
carattere: 11 pt
Formattato: Tipo di
CLINICAL IMPLICATIONS Both systems were effective in whitening teeth. The use of light did carattere: 11 pt, Tutto
maiuscole
not demonstrate an increase in the effectiveness of Britesmile after a two-week recall. Formattato: Tipo di
carattere: 11 pt
Formattato: Tipo di
INTRODUCTION carattere: Arial
Technological advances in dentistry make it possible for the practitioner to deliver the highest
level of care in an efficient and often economical way. With the introduction of light activated
devices such as Plasma arc, Light Emitting Diodes (LED), Argon lasers, metal halide and
xenon-halogen lights, being promoted as “the future of dentistry,” dental manufacturers have
helped create a public awareness and demand for the so-called: “ Light enhanced tooth
whitening systems”.
Formattato: Tipo di
In 2002 one article and more recently two papers were published evaluating the efficacy of light carattere: 11 pt
activated bleaching agents. One study reported positive results1, whereas the other articles
concluded the opposite 2,3. Reviews of these articles were either in support 4 or discredited the
findings5. It is apparent that the dental profession needs more evidence in order to provide for
better and more efficient treatment. The lack of knowledge is to the detriment of the dentist and
patient alike. The need for more knowledge becomes even more important as manufacturers
inundate the dental profession with advertisements emphasizing that light activated tooth
whitening is “the state of the art” and should be part of the armamentarium of the “up to date”
dental office.
Bleaching is the most conservative treatment for discolored teeth when compared to resin
bonded composites, porcelain veneers or crowns. It offers a simple and economical approach to
changing the color of teeth. Success of the treatment depends on a careful diagnosis by the
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64
practitioner. Candidates for whitening procedures include patients whose teeth are stained by
aging, chromogenic foods, endodontic treatment, tetracycline use and smoking or use of other
tobacco products.
Acceptable tooth whitening techniques include the in-office technique, dentist-prescribed home-
applied technique, or a combination of the two. The use of hydrogen peroxide (H202) for
bleaching teeth dates back to 1995 6. To reduce treatment time, clinicians attempted to
accelerate the degradation of H202 by heat or light. In 1970, Cohen and Parkins introduced a
technique for bleaching discolored teeth, such as tetracycline stained-teeth, using hydrogen
peroxide and a hand-held heating source 7.
Most clinicians know that hydrogen peroxide is a bleaching agent that can attain a desired
whitening effect. Bleaching can also be accomplished with Carbamide Peroxide, a lower
concentration of hydrogen peroxide and urea, which breaks down to 3.6% hydrogen peroxide
8,9
.The degree of whitening correlates directly with the amount of contact time and concentration
of the active ingredient, the pH and viscosity 9. The side effects are usually diminished when
lower concentrations are used.
The in-office bleaching treatment using hydrogen peroxide and an accelerating source (heat or
Formattato: Tipo di
light) were predominant until 1989 when Haywood published the first article on nightguard vital carattere: 11 pt
bleaching using carbamide peroxide 10. Currently, the in-office bleaching technique employs a
15 - 40% hydrogen peroxide bleaching agent (heat activated or not), while the dentist
prescribed home-applied technique most commonly uses a 10 - 15% carbamide peroxide gel.
The advantages of an in-office procedure are twofold. It does not require patient compliance
and immediate results can be accomplished. The disadvantages are the chair side time
involved and the cost to the patient, as the procedure usually requires multiple visits. Light-
activated chair side bleaching systems potentially offer the benefit of being less time-consuming
while producing faster results.

Formattato: Tipo di
The introduction of very high intensity Plasma Arc lights and Argon Lasers meets the need of an carattere: 11 pt
ever increasing demand for whiter teeth. Research in vitro has demonstrated that the use of
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65
laser-activated hydrogen peroxide did not produce any perceivable color change 11. Another
recent in vitro study, and one which should be of concern to the practitioner, has shown that the
use of these intense lights does elevate temperature of the bleaching material and as a result
caused an increase in intrapulpal temperature. This may have an impact on post bleaching
tooth sensitivity and pulpal health 12.

Formattato: Tipo di
The efficacy of a bleaching treatment can be determined through first or second evaluators or carattere: 11 pt
various technical methods. The use of a shade guide, colorimeter, or computer digitization to
measure color change over time has been currently included in clinical trials to assure efficacy
Formattato: Tipo di
assessment 13, 14, 15. carattere: 11 pt
The purpose of this study was to compare the efficacy of color changes of two in-office tooth
a
whitening systems, Brite Smile, a 15% Hydrogen peroxide system and Opalescence Xtra
Boost, a 38% Hydrogen Peroxide system b. In addition, feed back from the participants allowed
for an evaluation of their satisfaction with the results of the treatment and the occurrence of
sensitivity during and after the bleaching treatment.
Formattato: Tipo di
carattere: Arial
MATERIALS AND METHODS
Formattato: Tipo di
Ten patients with no medical contraindications to treatment and an absence of tooth sensitivity carattere: 11 pt
were asked to participate in this split-arch, randomized, parallel, blinded clinical evaluation. Only
six to eight upper anterior teeth with minor uniform intrinsic staining or discoloration with a
shade no lighter than A-3 were selected. The six lower anterior teeth and contra lateral upper
incisors were used as control groups.
All patients had received a prophylaxis (cleaning and polishing) less than 3 months before
starting the experiment. Each patient was evaluated for initial (baseline) shade by two
evaluators. The evaluators consisted of the dentist treating the subject and a second dentist.
Both evaluators were calibrated at 85% rater reliability in determining shades before the onset
of this project. Calibration was conducted pre and post study to ensure inter and intra rater
reliability.
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66
At the initial appointment shades were assessed using a Standard Vita Shade Guide c. All
shade measurements were recorded at baseline and an initial photograph was taken of the
upper and lower teeth.
At the same appointment the patient received a one-hour chair side bleaching treatment for
teeth 5-8 using Brite Smile according to manufacturer’s recommendations; 3 applications of 20
minutes each in one visit. Opal Dam b was used for gingival isolation. Teeth 9-12 were isolated
from the Brite Smile material and light source during treatment by means of a custom made poly
vinylsiloxane (PVS) block. Teeth were also kept moist using wet gauze under the PVS block.
Upon completion, teeth 5-8 were isolated as descrived above and teeth # 9-12 were treated with
Opalescence Xtra Boost without the use of a curing light (3 applications of 20 minutes each in
one visit), following the manufacturer’s recommendations. Three measurements were recorded
from each side before and immediately after treatment. In addition 35mm transparencies, as
well as digital photos were taken before and after treatment.
All patients were scheduled to return 2 weeks after the day of the tooth whitening treatment for
a recall appointment. Once more post bleaching records by means of transparencies and digital
photography were taken. In addition a determination of the final shade was made. As a service
to the patient the mandibular teeth were whitened after final recording at the end of the study
using Opalescence 10% carbamide peroxide take-home system. b
A. Efficacy Assessment
Formattato: Tipo di
The efficacy of the whitening system was evaluated with the use of a Digital Imaging Camera d, carattere: 11 pt
a 35 mm camera e and Standard Vita Shade Guidec15,16.
The Olympus C2500L high resolution digital camera is utilized for sampling. To ensure proper
color analysis an extended procedure of sampling nine locations on the central incisor, lateral
incisors of the maxillary and mandibular arches was completed. This data is then averaged to
find a mean color and standard deviation of color on each tooth. A Gaussian blur filter was
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67
applied during post processing which does an averaging of color over the digitally sampled
photo. All digital images were then analyzed to yield L*, a* and b* data 15.
All individuals are located in the same position in a single operatory with the camera positioned
9 inches and perpendicular from the tooth surface of the left central incisor. Patients are
presented edge to edge with retractors and asked to touch the tip of their tongue to their soft
palate. This allows light to readily pass through the tooth surface and reduce reflectance from
Formattato: Tipo di
their tongue. A polarized filter is used on the camera to reduce the gloss that occurs from the carattere: 11 pt
flash further ensuring the reduction of hot spots and increase consistent color accuracy. The
camera flash is used to ensure the consistency of light source due to its great influence on value
data. The camera is plugged in to a 120-volt source to ensure no fluctuation of flash intensity
between subjects and maintain stability of the light source.
A Standard Vita Shade Guide, arranged in order of value, was used for subjective evaluation of
the shades. Furthermore, 35mm transparencies were taken as part of the shade evaluation
protocol.
Each participant was asked to brush with water and an extra-soft toothbrush, according to Brite
Smile recommendations, to remove any debris that could interfere with shade evaluation and
photography. To standardize the photography, cheek retractors were used to retract the cheeks
and lips and the patient was instructed to line-up the lower incisal edges with the upper front
teeth. Additional photos were taken positioning the baseline shade tab next to the teeth to be
evaluated. All digital photos and analysis were performed by a blinded evaluator.
Formattato: Tipo di
B. Safety Assessment carattere: 11 pt
Formattato: Tipo di
This clinical study assessed the efficacy and patient tolerance of two different in-office tooth carattere: 11 pt
whitening systems after a single visit one-hour application. Clinical safety data information
indicated that the use of these systems, when used according to the protocol specified in this
clinical trial, did not present any undue risks to the participants.
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68
This was a randomized, blinded, parallel group study with 10 healthy participants, which
approved by the Institutional Review Board of the University where the study was conducted.
Subjects that met inclusion criteria were asked to report whether they had any teeth that were
sensitive. During the initial visit an informed consent form and an explanation of the eligibility
criteria were presented. The health of the oral soft tissues was examined and recorded and a
shade determination made. Photography as described previously was also done at this visit.
Both whitening systems were used for each patient. The Brite Smile System for teeth #5-8 and
Opalescence Xtra Boost for teeth # 9-12. The application lasted for 60 minutes, according to the
protocol and instructions provided by the manufacturers. An evaluation of the oral soft tissues,
tooth sensitivity and change in shade was completed after the tooth whitening treatment and
two weeks after application. The mandibular teeth were whitened after the end of the study
using Opalescence, a 10% carbamide peroxide tray-delivered home bleaching system.
Safety and comfort was determined by an absence of irreversible effects associated with the
use of the systems and included assessment of oral soft tissues and the degree of tooth
hypersensitivity. Oral soft tissue examination was conducted visually utilizing a standard dental
light, dental mirror and gauze. Abnormal soft tissue findings were noted after the tooth whitening
treatment had been completed.

Formattato: Tipo di
The Brite Smile System consists of a 15% hydrogen peroxide gel, Opalescence Xtra Boost of carattere: 11 pt
38% hydrogen peroxide gel and Opalescence is 10% carbamide peroxide. All three whitening
systems have undergone previous clinical safety testing 17,18. Two types of adverse reactions
have been reported, i.e. oral soft tissue irritation and tooth sensitivity 17,18. The occurrence of
these reactions were carefully evaluated and recorded following completion of the bleaching
treatment.
RESULTS
Formattato: Justified para,
Rientro: Prima riga: 0 pt,
During the in-office treatment, soft tissue irritation was usually avoided with the appropriate Spazioprima 6 pt, Tabulazioni:
468 pt, Allineato a sinistra
placement of a gingival isolation gel recommended and included in each in-office tooth
Eliminato: 89¶
69
whitening system. Soft tissue irritation was typically of mild severity and was usually observed at
the gingival margin. The irritation resolved while the subject were still undergoing tooth
whitening treatment or within 1-3 days after discontinuation of use. Baseline values were
Formattato: Tipo di
confirmed using the lower teeth as a control group. Tooth sensitivity was experienced and carattere: (Predefinito) Arial
Formattato: Tipo di
recorded and was of mild severity, which resolved usually within 1-2 days after discontinuation carattere: 11 pt
of the product.
Rientro: Prima riga: 0 pt,
Interlinea singola
A. Shade Guide Evaluation
Formattato: Non Tutto
maiuscole
Both in-office whitening systems were effective in making teeth lighter. The Vita Shade Guide
scores from the lightest to the darkest shade in numeric code order (Table I). The recorded
shades utilizing the Vita Shade Guide showed that Brite Smile averaged 5.9 ± 2.5 and
Opalescence Xtra Boost averaged 3.97 ± 2.33 shade changes immediately after the whitening
procedure. At the 2 week recall, Brite Smile’s effect was reduced to an average of 4.6 ± 2.14
while Opalescence Xtra Boost increased to 4.67 ± 2.3 shade changes (Table II and Table III).
Patients were given a questionnaire to record tooth sensitivity, gingival irritation, bad taste and
noticeable shade changes. Six patients experienced tooth sensitivity in which four patients
reported sensitivity in both sides; one patient reported sensitivity on the Britesmile side and the
other patient reported sensitivity on the Opalescence Xtra Boost side. One patient reported
gingival irritation at the end of the whitening procedure, observed in both sides, which subsided
in less than 24 hour. No bad taste was reported and all participants in the study expressed
satisfaction with the whitening process and the results.
Formattato: Tipo di
B. Digital Photography Evaluation carattere: Arial, Non
Maiuscoletto
The digital photography revealed the following results (Table IV): Whitening benefit
is defined as tooth color change from baseline assessed by the digital imaging
measurements b* (yellow – blue), L* (light – dark), and a* (red – green). For a given
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70
post-baseline visit: Δb* = b*visit - b*baseline, ΔL* = L*visit - L* baseline, Δa* = a* visit
- a* baseline.
Preoperative vs. Immediate Post Bleaching
There was a significant difference in b∗ (p=0.01) for the BriteSmile compared to
Opalescence Xtra Boost immediately post bleaching, while Opalescence Xtra Boost had a
significant decrease in the a∗ score (p=0.01) post bleaching compared to BriteSmile. The
other values showed no significant differences between the two products. The data
indicates that BriteSmile had a greater whitening effect when evaluated immediately post
bleaching based on L* and b* which are directly linked to bleached dentition (citation). Both
products show statistical difference (P=.01) before and after treatment for L* and b*.
Immediate Postoperative vs. 2 Weeks Post Bleaching
BriteSmile demonstrated a significant rebound by a positive b∗ value (p<0.001). This signifies
that the BriteSmile subjects had an increase in yellow coloration. This may be attributed to
dehydration of the tooth from the application of the light or it may be a normal response of
rebound. The Opalescence Xtra Boost may not have displayed this rebound due to the
prolonged activity of the bleaching material after the sample readings were taken immediately
post bleaching. The a* values showed no statistical change in either group. The L* displayed no
significant change for the Britesmile yet the Ultra Boost showed the mean L* increase in value
by 1.7 units.
Preoperative vs. 2 Weeks Post Bleaching (Overall)
The data indicates that both BriteSmile and Opalescence Xtra Boost whitened teeth to
statistically significant level (P=.01) for L* 3.6 (BriteSmile), 3.8 (Xtra Boost) and b* -6.0
(BriteSmile), -5.0 (Xtra Boost) equivalent to between 3 and 6 shades as determined on a Vita
shade guide (cite). The two whitening systems were not statistically significantly different from
pre-bleaching to two weeks post bleaching. All patients reported to be satisfied with the results Eliminato: 89¶
71
at the end of the treatment. Sensitivity appeared not to be an issue and none of the patients
expressed concern or complained about this side effect.
DISCUSSION
Formattato: Tipo di
The question as to whether to use light activation during chair side bleaching or not and the carattere: 11 pt
purported benefits are still an issue of debate. The use of two blinded and calibrated evaluators
in this study set it apart it from other publications evaluating this technology 1. In this study, the
direct in-office whitening system using a gas plasma light for three twenty minute applications in
conjunction with 15%hydrogen peroxide gel, was compared to a chemically activated system
using 38% hydrogen peroxide. Either heat or a chemical reaction can cause the peroxide to
break down into oxygen radicals and water more quickly. The more oxygen is liberated, the
more oxydation can take place. In the absence of heat, lowering the pH is one such mechanism,
by which, when Opal Xtra Boost is chemically activated, oxygen and water are liberated.
The clinical observation using a value ordered Vita Shade Guide was confirmed using digital
15
analysis of L*, a*, b* color values . In addition the digital camera was calibrated for each
image. Unlike other studies, the teeth of the one side were kept moist during bleaching, thus
minimizing the effect of dehydration that can occur while the other lateral side was being
bleached. This might explain why our data does not show the dramatic results reported in
another paper 1.
The use of light activation using the Britesmile in-office bleaching system resulted in increased
whitening compared to Opalescence Xtra Boost, which does not require light activation. This is
believed to be the result of dehydration of the tooth caused by the generation of heat from the
curing light 2. This increase, however, was of temporary nature, as after 2 weeks no differences
were recorded between the two systems. The initial improvement in tooth whitening observed
with the Britesmile system is therefore most probably the result of dehydration. The Britesmile
system incorporates the use of “hydrogel” and it has been suggested that this hydrogel (the
company does not volunteer the composition), prevents the teeth from dehydrating. Prevention Eliminato: 89¶
72
of dehydration of any light activated in office bleaching procedure is virtually impossible,
however.
Opalescence Xtra Boost did not demonstrate significant rebound and actually showed a slight
improvement after 2 weeks. This is possibly due to the fact that there was less dehydration
since no light and /or heat are required to activate the system. Furthermore, it is also possible
that a prolonged exposure and activity after the gel took place after it was rinsed off. It is
believed that continued oxydation can take place over time with the chemically activated
system, as activated hydrogen peroxide in water is able to penetrate deeper and/or reside in the
tooth longer, since it is not driven out by evaporation due the application of heat.
It is reasonable to conclude that with the increase in temperature, dehydration did occur, which
was subsequently followed by rehydration. Therefore in spite of the initial perception that an
increase in whitening took place, the 2-week post-operative evaluation did not demonstrate a
difference, which was confirmed by an absence of a statically significant difference between the
two materials.
We realize that this study represents a small sample size. This was due in part to the difficulty in
obtaining a Bristesmile unit. More independent research evaluating a larger sample size is
recommended. Factors such as cost of the light, operatory space, and maintenance should be
entered in the equation when purchasing a light. Advantages and disadvantages of light
activated whitening systems should be carefully considered.
CONCLUSIONS
numerati
1. BriteSmile and Opalescence Xtra Boost whitened teeth between 3 and 6 shades and
were not statistically significantly different from pre-bleaching to two weeks post
bleaching,
Formattato: Tipo di
carattere: 11 pt
2. BriteSmile had a greater whitening effect when evaluated immediately post bleaching,
but demonstrated a significant rebound of the b∗ score (p<0.001). This may be attributed
Eliminato: 89¶
73
to dehydration of the tooth from the application of the light (heat) or it may be a normal
response of rebound,
3. Opalescence Xtra Boost did not display this rebound effect, probably due to a more
prolonged activity of the bleaching material after the sample readings were taken
immediately post bleaching,
4. All patients reported to be satisfied with the results at the end of the treatment;
5. Sensitivity appeared not to be an issue and none of the patients expressed concern or
complained about this side effect.

a
BriteSmileTM,Inc., Walnut Creek, CA 94598;(925) 941-6260
b
Ultradent Products Inc., South Jordan, UT USA
c
VITA Zahnfabrik, Bad Säckingen, Germany
d
Olympus Camedia C2500L-SLR, Olympus America Inc., Melville, NY USA
e
Dental Eye III, Yashica-kyocera, Somerset, New Jersey USA
Tables:
Table I: Vita Shade Guide c scores from the lightest to the darkest shade in
numeric code order.
Table II: Mean Shade Change from Baseline
Table III: Mean Shade Change from Baseline
Table IV: Results showed from digital photography analysis
Formattato: Tipo di
TABLE I carattere: 12 pt
Lightest Darkest
Tabella formattata
B1 A1 B2 D2 A2 C1 C2 D4 A3 D3 B3 A3.5 B4 C3 A4 C4
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16
Corresponding Numeric Code Formattato: Centrato
Eliminato: 89¶
74
TABLE II
Opal. Xtra Opal. Xt.

Initial Brite Smile Brite Smile
Boost Boost
Patient Teeth Shade (# 6-8) (# 6-8)
(#9-11) (#9-11)
(# 6-11) Postoper. 2 w. recall
Postoper. 2 w. rec.
1 central C1 A1 (4) A1 (4) A1 (4) A1 (4)
lateral A2 B1 (4) A1 (3) A1 (3) A1 (3)
canine B3 A1 (9) A3 (2) A2 (6) A2 (6)
2 central B4 A2 (8) A2 (8) C2 (6) C2 (6)
lateral B4 A1 (11) D2 (9) C1 (7) C1 (7)
canine A4 A3 (6) A3 (6) A3 (6) A3 (6)
3 central A3 B1 (8) B2 (6) A1 (7) A1 (7)
lateral B1 (11) A2 (7) A2 (7) A2 (7)
A3.5
canine A2 (7) A3 (3) A2 (7) A2 (7)
A3.5
4 central A2 A1 (3) A1 (3) A1 (3) A1 (3)
lateral A2 A1 (3) A1 (3) A1 (3) A1 (3)
canine A2 (7) A2 (7) A2 (7) A2 (7)
A3.5
5 central A2 B1 (4) B1 (4) D2 (1) D2 (1)
lateral A2 A1 (3) A1 (3) D2 (1) D2 (1)
canine A3 A1 (7) D2 (5) D2 (5) D2 (5)
6 central D3 A1 (8) B2 (7) A1 (8) A1 (8)
lateral A1 (10) A2 (7) A2 (7) A2 (7)
A3.5
canine A4 A3 (6) A3.5 (3) A3 (6) A2 (10)
7 central A2 A1 (3) B2 (2) A1 (3) B2 (2)
lateral A2 A1 (3) A1 (3) A1 (3) A1 (3)
canine B3 A2 (6) A3 (2) A2 (6) A3 (2)
8 central A2 A1 (3) A2 (0) A1 (3) B2 (2)
lateral A2 A1 (3) A2 (0) A1 (3) A1 (3)
canine A3 B2 (6) A3 (0) A3 (0) A2 (4)
9 central D3 A1 (8) A2 (5) A2 (5) A2 (5)
lateral A3 D2 (5) A2 (4) A2 (4) A2 (4)
canine A3.5 A2 (7) A3 (3) A3 (3) A3 (3)
10 central A2 A1 (3) A1 (3) A1 (3) A1 (3)
lateral A2 B1 (4) B1 (4) B1 (4) B1 (4)
canine A2 (7) A3 (3) A2 (7) A2 (7)
A3.5
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75
TABLE III Formattato: Tipo di
carattere: 12 pt
Mean Shade Change from Baseline Formattato: Tipo di

Formattato: Tipo di
carattere: Arial
12
10
-2
Brite Smile - Brite Smile - 2 Opal Boost - Opal Boost - 2
After bleaching week recall After bleaching week recall
n Mean SD SE 95% CI of Mean Median IQR 95% CI of Median Tabella formattata

Brite Smile -
After bleaching 30 5.900 2.524 0.461 4.958 to 6.842 6.000 4.000 4.000 to 7.000
Brite Smile -
2 week recall 30 4.600 2.143 0.391 3.800 to 5.400 4.500 3.250 3.000 to 6.000
Opal Boost -
After bleaching 30 3.967 2.327 0.425 3.098 to 4.835 3.000 2.250 3.000 to 5.000
Opal Boost -
2 week recall 30 4.667 2.294 0.419 3.810 to 5.523 4.000 4.000 3.000 to 6.000
Formattato: Tipo di
carattere: Arial
TABLE IV
Formattato: Tipo di
Pre Post 2 Week Formattato: Tipo di
Brite Smile Ultradent Boost Brite Smile Ultradent Boost carattere: Arial
L* a* b* L* a* b* L* a* b* L* a* b* L* a* b*
Mean 70.4 -2.8 7.3 73.6 -2.6 0.2 72.5 -1.9 3.2 74.0 -2.4 1.6 74.2 -1.9 2.0
St.Dev. 7.4 1.9 4.4 6.0 0.7 2.3 6.1 1.2 3.0 5.4 0.9 1.8 5.3 1.3 2.4
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76
1. Tavares M. Stultz J. Newman M. Smith V. Kent R. Carpino E. Goodson JM. Light augments
tooth whitening with peroxide.[comment]. Journal of the American Dental Association.
134(2):167-75, 2003 Feb
2. Hein DK. Ploeger BJ. Hartup JK. Wagstaff RS. Palmer TM. Hansen LD. In-office vital tooth
bleaching--what do lights add?. Compendium of Continuing Education in Dentistry. 24(4A):340-
52, 2003 Apr.
3. Papathanasiou A, Kastali S, Perry RD, Kugel G. Clinical evaluation of a 35% hydrogen
peroxide in-office whitening system. Compend Contin Educ Dent. 2002 Apr; 23(4): 335-8, 340,
343-4 passim; quiz 348
4. Jones AH, Diaz-Arnold AM, Vargas MA, Cobb DS.Colorimetric assessment of laser and
home bleaching techniques. J Esthet Dent. 1999; 11(2): 87-94
5. Anonymous. Laser-assisted bleaching: an update. ADA Council on Scientific
Affairs.[comment]. Journal of the American Dental Association. 129(10):1484-7, 1998 Oct
nd
6. Goldstein RE. Esthetics in Dentistry-Principles, Comunications, Treatment Methods. 2 ed;vol 1. Hamilton-London: B.C Becker-
Year Book; 1998:245.
7. Cohen S, Parkins FM. Bleaching tetracycline-stained vital teeth. Oral Surg 1970 Mar; 29:465-
71
8. Goldstein RE, Garber DA. Complete dental bleaching. Chicago: Quintessence, 1995
9. Clinical Research Associates. Tooth Bleaching, state-of-art ’97. CRA Newsletter. April, 1997
10. Haywood VB, Heymann HO. Nightguard vital bleaching. Quintessence Int 1989;20:
173-6.
11. Jones AH. Diaz-Arnold AM. Vargas MA. Cobb DS. Colorimetric assessment of laser and
home bleaching techniques. Journal of Esthetic Dentistry. 11(2):87-94, 1999
12. Baik JW, Rueggeberg FA, LiewehrFR. Effect of light-enhanced bleaching on in vitro surface Formattato: Inglese (U.S.A.)
and intrapulpal temperature rise. J Esthet Restor Dent. 2001; 13(6): 370-8
13. Haywood VB. Historical development of whiteners: clinical safety and efficacy. Dent
Update. 1997;24:98-104.
14. Gegauff AG, Rosenstiel SF, Langhout KJ, Johnston WM.Evaluating tooth color
change from carbamide peroxide gel. J Am Dent Assoc. 1993;124:65-72
15. Kugel G, Aboushala A, Sharma S, Ferreira S, Anderson C. Maintenance of
Whitening with Sonicare Advance Toothbrush after bleaching treatment. Compend
Contin Educ Dent. 2004 Feb; 25(2): 17-24; quiz 25
16. Anderson C, Kugel G. Rebound evaluation of tetracycline stained subjects treated
with a 6.5% hydrogen peroxide gel; quantitative assessment by standard digital
photography[abstract]. J Dent Res. 2002;81(special issue):A-429.Abstract 3488.
17. Deliperi S, Bardwell D, Papathanasiou A, Kim M-J. Effectiveness of a Combined In-office
and Take-home Bleaching System. AADR Abstract. March 2003
18. Papathanasiou A, Deliperi S, Bardwell D, Wegley C. In vitro Evaluation of a Combined
In-office and Take-home Bleaching System. AADR Abstract. March 2003.
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Formattato: Tipo di
Chapter 6 carattere: Arial
Tooth whitening and its Effect on Dentin
Formattato: Centrato, Destro

Daily Use of Whitening Strips on Tetracycline Stained Teeth: 80,3 pt
Comparative Results After Two Months
Formattato: Tipo di
carattere: Arial, Tutto
ABSTRACT maiuscole
Formattato: Tipo di
This clinical article reviews the efficacy of a new 6.5% hydrogen peroxide tooth-whitening gel carattere: Arial
strip for bleaching teeth that have been intrinsically stained from tetracycline. Given the severity
of the staining in the cases presented during a recently conducted clinical trial, the resulting
efficacy is dramatic. Additionally, the continuous use of these strips for 30 minutes per day,
twice daily for 4 months with no adverse effects—unlike many previously prescribed whitening
alternatives—is also noteworthy.
Formattato: Tipo di
INTRODUCTION maiuscole
Formattato: Tipo di
In cases requiring esthetic enhancement of discolored dentition, those involving tetracycline carattere: Arial
Formattato: Tabulazioni:
stains are among the most challenging. These intrinsic stains, which cannot be removed with 432 pt, Allineato a sinistra +
450 pt, Allineato a sinistra +
polishing or abrasive mechanisms, may result from the administration of tetracycline during 468 pt, Allineato a sinistra
childhood for the treatment of disease. The color and severity of stains vary and are influenced
by the duration of tetracycline use, and the stage of tooth development at the time the
Formattato: Tipo di
medication was prescribed. While some patients may select veneers or full-coverage crown carattere: Arial
Formattato: Tipo di
restorations as the method with which to brighten their smile, still others may desire a more carattere: Arial
conservative approach. To that end, tooth whitening offers a conservative, simplified, and
economical alternative for changing tooth color.
Eliminato: 89¶
78
When clinicians are faced with the prospect of whitening a patient’s intrinsically stained teeth,
considerations for treatment include shade and location of discoloration,1 as well as which
formulation of whitening solutions to use. Whether whitening should take place in the office or at
home under the dentist’s supervision, along with the longevity of the whitening protocol, must
also be decided. It has been suggested that when discoloration appears at the neck of the tooth,
the whitening results may be poorest; when the stain is dark gray or blue, the prognosis is
similarly unimpressive. When whitening tetracycline-stained teeth, patients may need to commit
to a course of treatment lasting several weeks or months.2-4
Treatment commonly involves the use of at-home vital bleaching kits, which were first
introduced in 1989.5 According to some reports, tetracycline-stained teeth have been shown to
demonstrate a favorable prognosis dependent upon the treatment considerations, even though
they are the most resistant to bleaching.6 Specifically, one report showed that 97% of patients
with tetracycline stains experienced successful tooth lightening when a carbamide peroxide
whitening solution was used in a nightguard.1
A recently introduced 6.5% hydrogen peroxide whitening delivery system (Crest® Professional
Whitestrips)a shows promise for use in whitening tetracycline-stained dentition when used at
home for two months and under a dentist’s supervision. The hydrogen peroxide-impregnated
polyethylene strips represent a treatment alternative for patients who cannot afford the cost of
other whitening treatments and/or do not have time for multiple dental visits.7 This article
presents the recent research findings of a clinical trial designed to evaluate the efficacy of two
at-home vital bleaching systems on tetracycline-stained teeth.
Formattato: Tipo di
METHODS maiuscole
Formattato: Tipo di
A randomized clinical trial compared the efficacy of two at-home vital bleaching systems on carattere: Arial
tetracycline-stained teeth. Daily bleaching was conducted over two months. Eligibility was
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79
limited to healthy adult volunteers who had 16 or more natural teeth, including at least 3
gradable maxillary incisors with significant tetracycline staining. Individuals demonstrating tooth
sensitivity or an immediate need for dental treatment were excluded from participation in this
trial.
The study protocol, informed consent, and advertising were reviewed and approved by the
Institutional Review Board. Written and verbal informed consent was received prior to study
initiation. After informed consent and baseline measurements, subjects were randomized 3:1 to
a strip-based, hydrogen peroxide tooth-whitening system (Crest® Professional Whitestrips) or a
marketed tray-based, carbamide peroxide whitening system control (Opalescence® 10%)b.
Subjects in both groups were supplied with a standard dentifrice (Crest® Cavity Protection
Regular Paste)a, and soft toothbrush (Crest® Complete)a, for use throughout the study. All test
products were overpackaged in 1-month product kits, and all labeling was identical except for a
unique subject identification number.
Formattato: Tipo di
carattere: Arial, Non Grassetto
The 40 randomized subjects included 30 assigned to the strip group and 10 assigned to
the tray group. The study population ranged from 22 to 70 years of age. Approximately
half of the sample presented with moderate to severe tetracycline staining (levels II
Formattato: Tipo di
carattere: Arial, Non Grassetto
through IV), one third of who had the more severe banding that is occasionally reported
following childhood antibiotic use. While tobacco use was uncommon (15% of the
sample), 95% of the study participants consumed coffee, tea, or cola beverages daily.
Treatment groups were generally well balanced with respect to demographic and
behavioral parameters and tetracycline stain levels.

Formattato: Tipo di
carattere: Arial
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80
The first product application was supervised for instructional purposes, but all other treatment
was unsupervised. Only the maxillary arch was treated. Participants in the strip group were
instructed to wear a whitening strip for 30 minutes twice daily. Individuals in the tray group had a
custom soft, full-arch bleaching tray fabricated with gingival scalloping and gel reservoirs using
materials supplied by the manufacturer. Subjects in that group were instructed to place one half
to three quarters of the contents of a bleaching syringe into the custom tray and wear the device
for two hours daily.
Clinical response was evaluated at entry and again each month after treatment. First, the level
of tetracycline staining on the maxillary anterior teeth was assessed using a modified standard
3-point index.8 This modification recognized the possibility of successfully bleaching teeth with
relatively severe tetracycline stain (Table 1). These baseline values, along with age, were used
for balance and assignment during treatment randomization. Efficacy was assessed using a
standard 16-step value-oriented tooth shade guidec used in dentistry to match artificial crowns
to the natural dentition. Shade assessments were performed in a neutral-colored dental
operatory under color-balanced lighting conditions by a trained and calibrated examiner.
Tolerability was assessed by intraoral examination and subject report at each study visit (Table
1).
Formattato: Tipo di
Individual shade scores were determined by ordering the 16 shades arranged from dark to light carattere: Arial, 11 pt, Non
Grassetto
according to the rank ordering suggested by the manufacturer. To account for unusually dark
colors (often seen with tetracycline stain) or white colors (often seen postbleaching), this 16-
step guide was supplemented by 2 additional values (C4+ and B1-) representing shades darker
than C4 or lighter than B1. Effectiveness was determined by calculating the change in shade
scores from baseline at each posttreatment visit. Using this method, a decrease in numeric
shade score represented an increase in tooth whiteness. Treatment groups were compared
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81
using analysis of covariance with the baseline shade as the covariant. Comparisons to baseline
were 1-sided, while between-group comparisons were 2-sided using a 5% significance level.
Formattato: Tipo di
carattere: Arial
Formattato: Tipo di
carattere: Arial, Grassetto,
RESULTS Colore carattere: Automatico,
Tutto maiuscole
Both treatments were effective overall in improving the shade of tetracycline-stained teeth Formattato: Tipo di
(Table 2). Relative to baseline, the 2 groups averaged approximately 4 to 6.5 units of shade Grassetto
improvement after 2 months of treatment. Observed changes were greater on average after 2
months as compared to 1 month. Response was faster in the strip group. During the first
month’s treatment, individuals in the strip group averaged greater than a 4-unit reduction in
tooth shade, which represented a highly statistically significant (P < .0001) improvement vs
baseline. In contrast, subjects in the tray group averaged less than a 1-shade reduction during
the first month, not differing statistically from baseline (P > .10). Adjusting for baseline, the strip
group averaged 2.6 to 3.2 units more shade reduction compared with the tray group control.
With respect to between-group comparisons, the strip group experienced statistically

Formattato: Tipo di
significantly superior reductions (P < .01) in shade compared with the tray group at both the 1- carattere: Arial, 11 pt
and 2-month time points (Table 3).

Formattato: Tipo di
carattere: Arial
Formattato: Tipo di
Both treatments were generally well tolerated. Mild and transient tooth sensitivity and oral carattere: Arial, 11 pt, Non
Grassetto
irritation were the most common adverse events associated with daily bleaching (Table 4). All
such events were typically reported early in the treatment regimen, and there were no clinical
manifestations present at the Month 1 or Month 2 clinical examinations. Six subjects
discontinued treatment during the first 2 months (3 in each treatment group). Of these, 2
individuals in the tray group reported the regimen was inconvenient and withdrew after the
Month 1 visit. No one withdrew early or reported modifying their treatment regimen because of
an adverse event.
Formattato: Tipo di
carattere: Arial
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82
Formattato: Tipo di
DISCUSSION Colore carattere: Automatico,
Tutto maiuscole
This study was designed to evaluate clinical response following longer-term, daily use of 6.5% Formattato: Tipo di
hydrogen peroxide whitening strips. The researchers elected to test extended treatment in Grassetto
individuals with tetracycline staining, because this clinical condition is reported to require
extended treatment of several weeks or months in order to achieve meaningful whitening.9 A
marketed 10% carbamide peroxide, tray-based system was selected as the control group,
because this agent has been previously used and reported to be effective in longer-term studies
of tetracycline staining.10,11
Formattato: Tipo di
carattere: Arial
Formattato: Tipo di
Both the strip and tray-bleaching systems were effective, with both groups differing significantly carattere: Arial, 11 pt, Non
Grassetto
from baseline at the end of the 2-month monitoring period. Color response in the strip group
Formattato: Tipo di
was superior to the tray group, as evidenced by the significant (P < .01) between-group carattere: Arial, 11 pt, Non
Grassetto, Non Corsivo
treatment differences at both Months 1 and 2, favoring the “trayless” whitening strip system. Formattato: Tipo di
Grassetto
Onset of these clinical benefits was more rapid in the strip group. After 1 month of treatment, the
Formattato: Tipo di
strip group averaged more than a 4-shade improvement compared to less than 1 shade in the carattere: Arial
Formattato: Tipo di
tray group, with only the strip group experiencing statistically significant improvements in tooth carattere: Arial, 11 pt, Non
Grassetto
color after 1 month. After 2 months, the strip group averaged a 67% greater shade improvement Formattato: Tipo di
Grassetto
overall compared to the tray control group. While overnight tray use may improve clinical
Formattato: Tipo di
response in that group, such daily treatment conducted during the long term could also affect Grassetto
subject compliance.
Treatment response in some individuals was impressive (Figures 1 and 2). However, this study
confirms early observations of the need for extended contact time in many tetracycline-stained
patients. After 2 months of daily treatment, involving approximately 60 hours of strip use or 120
Formattato: Tipo di
hours of tray use, no subjects had yet reached the predetermined bleaching cutoff (B1-). In carattere: Arial
Formattato: Tipo di
these subjects, additional time may be necessary to affect maximum color change. Previous carattere: Arial, 11 pt, Non
Grassetto
reports suggest a minimum of 2 months of treatment, hence the time point elected in this
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83
Formattato: Tipo di
study.12 The researchers expect to continue treatment and observation of this study population carattere: Arial, 11 pt, Non
Grassetto, Non Apice / Pedice
for up to 6 months to further assess the effectiveness and tolerability of these agents with even Formattato: Tipo di
Grassetto
longer-term exposure.
Twice-daily use of the 6.5% hydrogen peroxide whitening strips was well tolerated over the 2-
month treatment period. The side effects in this study—transient tooth sensitivity and gingival
Formattato: Tipo di
irritation—were generally similar in nature and severity to the primary events reported in other carattere: Arial
Formattato: Tipo di
longitudinal trials using the at-home tray-bleaching systems.9 In the current study, where the carattere: Arial, 11 pt, Non
Grassetto
whitening strips were used for a total of 60 contact hours over a 2-month period, no subject in Formattato: Tipo di
the strip group discontinued treatment due to an adverse event. This extended exposure
Formattato: Tipo di
associated with long-term, daily treatment of tetracycline stain corroborates and extends the Grassetto
Formattato: Tipo di
safety of strip-based tooth whitening as reported in earlier, shorter-duration clinical trials.13-20 carattere: Arial, 11 pt, Non
Formattato: Tipo di
Grassetto
CONCLUSION Formattato: Tipo di
carattere: Arial
The use of whitening strips has been proposed as a viable option for longer-term whitening Formattato: Tipo di
because of favorable compliance, lower systemic exposure, and other factors associated with Colore carattere: Automatico,
Tutto maiuscole
this easy-to-use bleaching system.14 New clinical research involving extended treatment of Formattato: Tipo di
Grassetto
tetracycline stain over 2 months confirms this proposition. In the current study, daily treatment
for 1 month with a 6.5% hydrogen peroxide whitening strip provided similar efficacy as 2 months
Formattato: Tipo di
of treatment with a 10% carbamide peroxide tray system. carattere: Arial, 11 pt
Formattato: Tipo di
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84
Formattato: Tipo di
Tables Sottolineato
Formattato: Tipo di
Table 1—Tetracycline Stain Classification carattere: Arial
Table 2—Baseline Demographic and Behavioral Information
Table 3—Tooth Shade by Treatment and Time
Table 4—Tooth Sensitivity and Oral Irritation
Formattato: Tipo di
Table 1—Tetracycline Stain Classification* carattere: Arial
Score Clinical Presentation

0 No tetracycline staining evident
I Uniform light yellow, brown, or grey stain confined to incisal three-quarters of
the crown
II Deep yellow, brown, or grey stain, without banding
III Dark grey or blue stain with marked banding
IV More severe or extreme staining
*Modified from Boksman and Jordan, 1983.
Formattato: Tipo di
carattere: Arial
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85
Table 2—Baseline Demographic, Behavioral and Tooth Shade Information
Demographic Strip Tray Overall Two-Sided

Characteristic/Statistic (n =30) (n =10) (n =40)
P-value
Age (Years)
Mean (SD) 37.7 (9.46) 38.9 (14.72) 38 (10.81) .7591
Minimum - Maximum 22 - 58 25 - 70 22 - 70
Sex
Female 19 (63.3%) 3 (30%) 22 (55%) .1401
Male 11 (36.7%) 7 (70%) 18 (45%)
Race
Asian (Oriental) 6 (20%) 4 (40%) 10 (25%) .2323
Caucasian 24 (80%) 6 (60%) 30 (75%)
Tobacco Use
No 25 (83.3%) 9 (90%) 34 (85%) 1.0000
Yes 5 (16.7%) 1 (10%) 6 (15%)
Daily Coffee/Tea/Cola Consumption
No 2 (6.7%) 0 (0.0%) 2 (5%) 1.0000
Yes 28 (93.3%) 10 (100%) 38 (95%)
Tetracycline Stain Levels
I 15 (50%) 4 (40%) 19 (47.5%) .3176
II 7 (23.3%) 1 (10%) 8 (20%)
III 8 (26.7%) 4 (40%) 12 (30%)
IV 0 (0.0%) 1 (10%) 1 (2.5%)
Tooth Shade
Mean 11.1 13.5 11.7 .0823
Minimum-Maximum 6-17 7-17 6-17
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86
Formattato: Tipo di
Table 3—Tooth Shade by Treatmemt and Time carattere: Arial
Comparison to Baseline Between-Group

Comparisons
N Mean Change P-Value Mean P-Value
(S.E.) Treatment
Difference
(S.E.)
Month 1
Strip 26 -4.05 (0.397) <. 0001 -3.15 (0.852) .0005
Tray 9 -0.9 (0.696) 0.1014
Month 2
Strip 26 -6.6 (0.418) <. 0001 -2.63 (0.993) .0097
Tray 7 -3.96 (0.835) <. 0001
Table 4—Tooth Sensitivity and Oral Irritation

Formattato: Tipo di
Strip Tray Overall carattere: Arial, Portoghese
(Brasile)
(n=30)(n=10)(n=40)
No. % No. % No. %

Formattato: Tipo di
Subj. Subj. Subj. Subj. Subj. Subj. carattere: Arial
Reported
Gingival Irritation 10 33.3 1 10 11 27.5
Tooth Sensitivity 13 43.3 4 40 17 42.5
Observed
Gingival Irritation 0 0 0 0 0 0
Formattato: Tipo di
carattere: Arial
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87
Formattato: Tipo di
PRODUCT REFERENCES maiuscole
a Formattato: Tipo di
The Procter & Gamble Co, Cinncinati, OH 45202; 800-492-7378 carattere: Arial
b
Ultradent Products, Inc, South Jordan, UT 84095; 800-552-5512
c
Vita Zahnfabrik, Germany; distributed in the US by Vident™, Brea, CA 92621; 800-828-3839
Formattato: Tipo di
carattere: Arial
REFERENCES Formattato: Tipo di

maiuscole
1. Haywood VB, Leonard RH, Nelson CF, et al: Effectiveness, side effects and long-term status
Formattato: Tipo di
of nightguard vital bleaching. J Am Dent Assoc 125(9):1219-1226, 1994. carattere: Arial
2. Haywood VB, Leonard RH, Dickinson GL: Efficacy of six months of nightguard vital
bleaching of tetracycline-stained teeth. J Esthet Dent 9(1):13-19, 1997.
3. Haywood VB: Extended bleaching of tetracycline-stained teeth. Contemporary Esthetics and
Restorative Practice 1(1):14-21, 1997.
4. Haywood VB: Bleaching tetracycline-stained teeth. Esthet Dent Update 7(1):25-26, 1996.
5. Haywood VB, Heymann HO: Nightguard vital bleaching. Quintessence Int 20(3):173-176,
1989.
6. Haywood VB, Leonard RH, Nelson CF: Efficacy of 6-months nightguard vital bleaching of
tetracycline-stained teeth. J Dent Res 73 1994.
7. Kugel G: Nontray whitening. Compend Contin Educ Dent 21(6):524-528, 2000.
8. Boksman L, Jordan RE: Conservative treatment of the stained dentition: vital bleaching. Aust
Dent J 28(2):67-72, 1983.
9. Leonard RH: Nightguard vital bleaching: Dark stains and long-term results. Compend Contin
Educ Dent 21(suppl 28):S18-S27, 2000.
10. Leonard RH, Haywood VB, Eagle JC, et al: Nightguard vital bleaching of tetracycline-
stained teeth: 54 months post treatment. J Esthet Dent 11(5):265-77, 1999.
11. Matis BA, Wang Y, Jiang T, et al: Six-month evaluation of bleaching agents in patients with
tetracycline staining (abs). J Dent Res 80:182, 2001.
12. Haywood VB: Current status of nightguard vital bleaching. Compend Contin Educ Dent
21(suppl 28):S10-S17, 2000.
13. Gerlach RW: Shifting paradigms in whitening: introduction of a novel system for vital tooth
bleaching. Compend Contin Educ Dent 21(suppl 29):S4-S9, 2000.
14. Kugel G, Kastali S: Tooth whitening efficacy and safety: a randomized and controlled
clinical trial. Compend Contin Educ Dent 21(suppl 29):S16-S21, 2000.
15. Gerlach RW, Jeffers MJ, Pernik PS, et al: Impact of prior tooth brushing on whitening strip
clinical response (abs). J Dent Res 80:151, 2001.
16. Gerlach RW, Campolongo KL, Hoke PD, et al: Use of peroxide-containing polyethylene
strips: effect of dosing duration on initial and sustained shade change (abs). J Dent Res 80:150,
2001.
17. Gerlach RW, Gibb RD, Sagel PA: A randomized clinical trial comparing a novel 5.3%
hydrogen peroxide whitening strip to 10%, 15% and 20% carbamide peroxide tray-based
bleaching systems. Compend Contin Educ Dent 21(suppl 29):S22-S28, 2000.
18. McMillan DA, Gibb RD, Gerlach RW: Impact of increasing hydrogen peroxide concentration
on bleaching strip efficacy and tolerability (abs). J Dent Res 80:173, 2001.
19. Swift EJ, Heymann HO, Ritter AV, et al: Clinical evaluation of a novel “trayless”
tooth whitening system. J Dent Res 80:151, 2001
Eliminato: 89¶
88
Chapter 7
Long Term Hydrogen Peroxide Exposure and its Effect on Dentin
Comparative Study of 6.5% Hydrogen Peroxide Bleaching Strips On Tetracycline

Stain: Clinical Response After Six Months Daily Use

ABSTRACT
Formattato: Tipo di
BACKGROUND A variety of indications exist for bleaching single or multiple teeth, including carattere: Grassetto, Non
Corsivo, Tutto maiuscole
tetracycline staining. The primary objective of this study was to evaluate clinical response
following extended daily use of a trayless 6.5% hydrogen peroxide tooth bleaching gel (Crest®
Professional Whitestrips, The Proctor & Gamble, Cincinnati, OH USA) on tetracycline stain. In
this research, 10% carbamide peroxide in an at-home daytime tray delivery system
(Opalescence® 10%, Ultradent Products, Inc., South Jordan, UT, USA) was used for
comparison purposesas an experimental control.

Formattato: Tipo di
MATERIALS AND METHODS In this single-blind clinical trial, subjects were randomly carattere: 11 pt, Non Corsivo,
Tutto maiuscole
assigned to a Strip group (30 subjects) or a Tray group (10 subjects) following screening for
tetracycline staining. Subjects used their respective products for approximately 6 months, with
clinical safety and efficacy measurements taken at the end of each month. The strip product
was used for 30 minutes, twice daily (maxillary arch only). The tray product was used for 2
hours daily (maxillary arch only). Treatment efficacy was determined by the tooth color change
from baseline using an expanded Vita Shade guide.

Formattato: Tipo di
RESULTS The Strip group averaged greater shade reduction compared to the day wear Tray carattere: 11 pt, Non Corsivo,
Tutto maiuscole
group at the Months 1, 2, and 3 visits, respectively. After Month 3, there were no significant
between-group differences in shade. Of the subjects in the Strip group, 65 % reached B1 tooth
color by Month 6, while 43% of subjects in Tray group obtained this result after 6 months. Both
treatments were generally well tolerated. Mild and transient tooth sensitivity (40-47%) and oral
irritation (30-47%) were the most common adverse events associated with daily bleaching, yet
Eliminato: 89¶
89
neither affected study participation. Conclusions: Both the 6.5% H2O2 experimental bleaching
strip (Crest Professional Whitestrips) and daywear marketed tray-based carbamide peroxide
system (Opalescence 10%) provided significant tooth whitening in subjects with tetracycline
stain. The Strip group obtained the results in a shorter pproximately half the time compared to
the day wear Tray group.

CLINICAL SIGNIFICANCE
When used daily for 6 months, a 6.5% H2O2 bleaching strip and the 10% carbamide peroxide
tray system can be effective in whitening tetracycline stain. Both the professional strip and tray
systems were well tolerated throughout the 6-month usage period. This extended use provides
additional evidence of clinical safety associated with use of these products for vital bleaching.
Formattato: Tipo di
Formattato: Titolo 1,
Interlinea doppia
INTRODCUTION
Aging, chromatogenic food and drinks, excessive fluoride intake, medication (tetracycline) and Formattato: Tipo di
maiuscole
others can be the cause of intrinsic stains. Tetracycline stains, though, are considered to be the
Formattato: Tipo di
most difficult types of intrinsic stains to manage clinically. The devastating effect on tooth Grassetto, Colore carattere:
Nero
formation of as little as one gram of tetracycline was recognized in the late 1950s1 and
confirmed by a study of cystic fibrosis patients by Swachman et al 2. In 1970, Cohen and
Parkins published a method for bleaching the discolored dentin of young adults with cystic
fibrosis who had undergone tetracycline treatment 3.

Different variations of tetracycline and derivates produce different colors in the tooth. When the Giustificato
Formattato: Tipo di
teeth are exposed to the sunlight, they become darker, with a distinct gray/blue tinge. It is carattere: Arial
Formattato: Tipo di
suggested that the reason that the front incisor teeth darken while the molars remain yellow carattere: Arial, 11 pt, Non
Nero
longer is the different exposure to light 3. The discoloration of the permanent dentition depends
on the amount and duration of tetracycline use4. The portion of the tooth, color and severity of
the stains can be determined by the stage of the tooth development at the time of the drug
administration. Tetracycline is incorporated into dentin during tooth calcification intra and post
Eliminato: 89¶
90
partum, probably through chelation with calcium forming tetracycline orthophosphate 5. It can
be deposited in fetal tooth buds when administered in the third trimester of pregnancy or by a
child during the development of the tooth (between ages 3 to 4 months and 7 to 8 years) 6, 7.
Formattato: Tipo di
Colors may vary intensity of gray, blue, brown and yellow. The different banding can also be carattere: Arial
Formattato: Tipo di
attributed to the variations of the tetracycline derivates. carattere: Arial, 11 pt, Non
Nero
Clinicians are aware of the results from the use of tetracycline in pregnancy and young children.
Even though physicians and dentists should seek other sources of treatment, tetracycline is still
the drug of choice for treatment of Rocky Mountain spotted fever and it is also the most
prescribed medication for acne.
Tetracycline stained teeth may respond to bleaching treatments but in a different rate from the
other types of stains 8,9. Treatment is usually achieved by at-home vital bleaching kits, which
were first introduced in 1989 10. The most common regimen in the literature involves overnight
application of the bleaching tray for periods of several months8. Even with this extended
treatment, clinical outcomes may be mixed.

Formattato: Tipo di
Recently, a strip-based system was developed to deliver peroxide topically without
11,12
fabrication of a custom tray . This trayless approach may be particularly relevant
where professionally-directed long term use is indicated, and where compliance with
trays may be problematic12. This new research was conducted to extend strip treatment
over a much longer duration than heretofore in order to evaluate clinical safety and
effectiveness of vital bleaching in patient’s longer treatment.
MATERIALS AND METHODS Formattato: Tutto maiuscole
Clinical research was conducted to evaluate clinical safety and effectiveness of a hydrogen
peroxide-based tooth whitening system under conditions of extended (long term) daily use. The
research was a randomized, examiner-blind, parallel group clinical trial comparing two peroxide
systems that differed with respect to delivery, and peroxide source. The experimental group
Eliminato: 89¶
91
was 6.5% hydrogen peroxide whitening strips (Crest® Professional Whitestrips, The Procter &
Gamble Co., Cincinnati, OH USA). The comparison group positive control was a 10%
carbamide peroxide gel (Opalescence® 10%, Ultradent Products, Inc., South Jordan, UT, USA)
delivered in a custom bleaching tray. This system, which carries the American Dental
Association “Seal of Acceptance”13 for tooth whitening products, has been shown to be safe and
effective in numerous clinical trials14,15,16,17.
Bleaching was conducted each day over a 6 month period. The target population was
individuals with tetracycline staining, because these case types are widely recognized to require
18
several months of treatment . Eligibility was limited to healthy adult volunteers who had a
minimum of 16 natural teeth, including all 4 maxillary central and lateral incisors, and at least 3
gradable maxillary incisors having clinical evidence of tetracycline-related staining. Individuals
with untreated periodontal disease or dental caries, or dentinal hypersensitivity were excluded
from participation.
The study protocol, informed consent, and advertising were reviewed and approved by Tufts
University Institutional Review Board. Written and verbal informed consent was received
prior to initiating the study. Because the tray system had been used for an extended period,
and shown to be safe, this research was specifically designed to thoroughly evaluate the
clinical safety and effectiveness of the strip system under extended usage conditions.
Because of the difficulty in identifying patients who would participate in long term research,
and to assure an adequate sample size in the strip group, subjects were randomized 3:1 to
the whitening strips or tray control group.
A dental impression was taken of the maxillary arch of those subjects assigned to the tray
group to make custom bleaching trays. Subjects in that group received a custom, soft, full-
arch bleaching tray fabricated with gingival scalloping and gel reservoirs using materials Eliminato: 89¶
92
supplied by the manufacturer (Ultradent Products, Inc. South Jordan, UT USA). Each strip
kit contained one carton of 56 upper strips in pouches. Each tray kit contained 24 unit-dose
syringes and 1 pocket tray case for the custom maxillary bleaching tray. In addition to the
test products (and custom tray where appropriate), all subjects were supplied with an
anticavity dentifrice (Crest® Cavity Protection, The Procter & Gamble Co., Cincinnati, OH
USA), and 2 soft toothbrushes (Crest® Complete, The Procter & Gamble Co., Cincinnati, OH
USA). All study-related products and materials were dispensed every four weeks in non-
identifiable kits with. For blinding purposes, kit labeling was identical, except for a unique
subject identification numbers.
Only the maxillary arch was treated. Strip use was 30 minutes twice daily. Subjects in the
tray group were instructed to place half to three quarters of the contents of a bleaching
syringe into the custom tray and wear the device for 2 hours daily. Because both groups
were assigned to a peroxide-containing product, and because only the maxillary arch was
treated, all subjects were offered a marketed, peroxide-based tooth whitening system for
“compassionate use” on the mandibular arch after study completion.
Clinical response was evaluated at baseline and again every 4 weeks after treatment. The
level of tetracycline stain on the maxillary anterior teeth was assessed using a modified
standard index (Jordan and Boksman Tetracycline Stain Classification) that recognized the
19,9
possibility of successfully bleaching teeth with relatively severe tetracycline stain .
Tetracycline stain (I or II versus III or IV) and age were used for balancing during treatment
randomization.
Efficacy was assessed using a standard 16-steptab value-oriented tooth shade guide (Vita
Lumin, Vita Zahhnfabrik, Bad Sackingen, Germany). Shade examinations were performed
Eliminato: 89¶
93
under color-balanced lighting conditions by a trained and calibrated examiner. Safety was
assessed at baseline and each subsequent visit. Subjects were interviewed at each visit to
ascertain the occurrence of any tooth hypersensitivity and/or oral irritation anytime during
treatment. All adverse events were collected irrespective of causality. For subjects with
findings, severity and duration were assessed, along with any interventions (rescue
medications, treatment alteration, and the like) in accordance with pharmaceutical research
standards.
Where banding was present, shade measurements were based on the predominant shade
scored ofn the tooth outside of the banded zone. All shades were collected by an examiner
who was blind to treatment assignment. Individual shade scores were determined by
ranking the 16 shade tabs, arranged from light to dark, according to the rank order
suggested by the manufacturer. This value-ordered ranking assigned “B1” as the first
(lowest) step, and “C4” as the last (highest) step of the 16 possible outcomes. To account
for exceedingly light or dark tooth colors, shade scores were expanded to include two
additional categories representing colors lighter or darker than those available using this
value-oriented system: shade “B1–“ (whiter than “B1”) with a numerical code “0”, and shade
“C4+” (darker than “C4”) with numerical code “17”.
Effectiveness was determined by calculating the change in shade scores from baseline at
each post-treatment visit. Using the expanded 18-tabstep rank order, a decrease in numeric
shade score represented an increase in tooth whiteness. Anticipating the effectiveness of
long term peroxide treatment, any subject who reached the lowest numerical shade (B1 or
lower) before end-of-treatment was withdrawn from active treatment by the investigator. For
those subjects who were withdrawn from treatment (< or = B1 before Month 6), the “last
observation carried forward” method was used to compute shade improvement at
Eliminato: 89¶
94
subsequent visits. Tobit censored regression models were used to adjust for possible bias
attributable to effectiveness-related early withdrawals20,21. Treatment groups were
compared using analysis of covariance with the baseline shade as the covariant.
Comparisons to baseline were 1-sided, while between-group comparisons were 2-sided
using a 5% significance level.

RESULTS
Age at baseline ranged from 22 years to 70 years, with mean (SD) age of 38 (10.8) years (Table
1). Females accounted for 55% of the population. 25% of subjects reported Southeast Asian
origin. There was considerable variation in tetracycline staining, with 52% of subjects
presenting with moderate-to-severe tetracycline staining (levels II-IV). Only one subject in the
tray group exhibited the most severe staining/banding (level IV) at baseline. Shade scores
ranged from 6 (corresponding to the “C1” tab) to 17 (“C4+”). While tobacco use was uncommon
(15% of the sample), 95% of study participants consumed coffee, tea, or cola beverages daily.
Treatment groups were balanced (p > 0.14) with respect to demographics, behavioral
parameters and tetracycline stain levels.

Formattato: Tipo di
carattere: Arial
Formattato: Tipo di
Both treatments were effective overall in improving the shade of tetracycline-stained teeth, as carattere: Arial, 11 pt, Non
Grassetto
evidenced by the significant (p < 0.05) improvement in shade after 1-2 months depending on
treatment. After 1-month treatment, the strip group averaged more than a 4-shade
improvement compared to a less than 1 shade in the tray group. The strip group exhibited a
statistically significant (p<0.0001) improvement in tooth shade after 1 month (Table 2). Both
groups experienced incremental shade improvement with continued use after Month 1. This
incremental benefit was more apparent in the tray group, such that, by Month 4, there were no
significant (p > 0.48) differences between groups with respect to mean shade improvement from
baseline. After 6-months daily use, the groups averaged a 10-11 shade improvement from
baseline. Eliminato: 89¶

95
Formattato: Tipo di
carattere: Arial
Formattato: Tipo di
During the first 2 months of continuous daily treatment, no subjects in either treatment group carattere: Arial, 11 pt, Non
Grassetto
reached or exceeded the minimum shade level. By Month 3, only 2 subjects (both in the strip
group reached) reached “B1” or lighter and were withdrawn from treatment. After 6 months
daily treatment, 40% of study subjects still had not reached or exceeded this minimal shade cut-
off. Use of Tobit (censored regression) models, which adjusted for the biases in the treatment
difference at Month 3, 4, 5 and 6 visits, yielded treatment differences ranging from 1.3 to 0.6
shades favoring of the strip group (Table 3). Groups differed significantly (p = 0.04) with respect
to this “carry-forward” response only at the Month 3 time point.

Formattato: Tipo di
carattere: Arial
Formattato: Tipo di
Mild and transient tooth sensitivity and oral irritation were the most common adverse events carattere: Arial, 11 pt, Non
Grassetto
associated with treatment (Table 4). Findings were symptomatic in nature, as there were no
product-related clinical manifestations present at any of the monthly clinical examinations.
Occurrence of tooth sensitivity and oral irritation, which ranged from 30-47%, was somewhat
higher in the strip group compared to the tray group. Onset was generally during the first month
of treatment, and transitory, resolving fully concurrent with treatment.
Six subjects discontinued treatment during the first 2 months (3 in each treatment group). Two
individuals (both in the tray group) found the daily treatment regimen to be inconvenient and
withdrew after the Month 1 visit. The other 4 were “lost-to-follow-up”. There were no systemic
or non-oral adverse events (nausea or others) relating to product usage anytime during the 6-
month treatment period. No subjects reported using any “rescue medication” such as
analgesics because of treatment-related sensitivity. There were no reports of early withdrawal
due to a product-related adverse event, and none of the study subjects reported modifying
usage because of treatment-related irritation or sensitivity.

Formattato: Tipo di
carattere: Arial
Eliminato: 89¶
96
DISCUSSION
Formattato: Tipo di
This study evaluated clinical response following longer-term, daily use of hydrogen peroxide- carattere: Arial, 11 pt, Non
Grassetto
containing whitening strips relative to thea carbamide peroxide day wear tray-based
group.control. The target population consisted of individuals with tetracycline staining, because
clinical research repeatedly has demonstrated the need for extended treatment over several
220
months to achieve meaningful whitening with these cases . A marketed 10% carbamide
peroxide, tray-based system was selected for as the comparisoncontrol group, because this
agent has been previously reported to be safe and effective on tetracycline stain when used
overnight over a 6 month period.(1144) .. Subjects used their assigned treatment regimen
throughout the 6-month test period unless they reached an average Vita Shade score of “B1” or
lighter prior to last evaluation. Those attaining this degree of whiteness were withdrawn from
additional bleaching but were followed through the remainder of the trial for efficacy and safety
outcomes.
In this research, both the strip and tray bleaching systems were effective, yielding a highly
significant (p < 0.001) and similar 10-11 mean shade improvement from baseline after 6 months
use. That both systems were comparable with respect to end-of-treatment efficacy may be
expected given certain overt similarities between treatments. The 6.5% hydrogen peroxide strip
system was used twice daily for 30 minutes, a 1-hour total daily contact time. The 10%
carbamide peroxide tray system (equivalent to ~3.5% hydrogen peroxide) was used once daily
for 2-hours.
In this study, onset of shade improvement was earlier, and the magnitude of the change was
greater with strips compared to trays. Through Month 3, the strip group exhibited a statistically
significant (p < 0.05) 1.3 to 3.2 shade improvement relative to the tray control. What
accounteds for the significant between-group differences in shade improvement seen early in
treatment? One likely explanation is that tTwice a day use of a strip for 30 minutes applied a
Eliminato: 89¶
97
higher concentration of peroxide more frequently , which allows for episodic treatment, could
represent an easier regimen for some individuals when compared to 2-hours of continuous tray
use of the lower concentration carbamide peroxide gel. Other factors could have contributed to
these findings, including the small sample size in the tray group, differences in the tetracycline
staining at baseline, and/or compliance (strips versus the day wear regimen used for the trays).
The portability and flexibility of strips may aid in treatment compliance, especially early in the
treatment regimen. However, shade guides represent an imperfect measure of efficacy,
especially for complex clinical presentations like those seen with tetracycline staining. As such,
the comparative effectiveness of outcomes must be evaluated with caution because causality
cannot be assessed from multi-factorial research like this clinical trial.
This study provides new evidence of an expanded safety in-use with strip-based tooth
whitening. Both bleaching systems in this trial were well tolerated with daily use over a 6-month
treatment period. No subjects in either group discontinued treatment early due to product-
related adverse events. For the tray system, these findings corroborate other reports of safe
231,242
continuous daytime use of 10% carbamide peroxide on tetracycline stain . The research
provides additional assurance of the clinical safety of this 10% carbamide peroxide tray system
with conventional use over a few weeks, and longer term use for treatment of tetracycline
staining. For the strip system, the findings provide first evidence of in-use clinical safety with
extended treatment. The research, which expands on an earlier report establishing clinical
safety at concentrations up to 6.5% hydrogen peroxide on strips for periods of up to 2 months
daily use, extends treatment duration through 6-months 9. Twice-daily use of the 6.5% hydrogen
peroxide whitening strips was well tolerated over that period, with the principal side effects being
—ttransient tooth sensitivity and gingival irritation. These events were observed to occur more
frequently in the strip group. Differences in occurrence rates between groups could be
attributable to the higher peroxide concentration in the strip versus the day wear tray group, or
other factors, including random chance. —being similar in nature and severity to the carbamide
Eliminato: 89¶
98
peroxide, tray-based control group. Compared to the earlier 2-month findings, extended use
resulted in only a few additional reports of sensitivity/irritation, with no increasing severity or
persistence. Longer-term use through Month 6 showed no evidence of any cumulative toxicity.
While the sample size is small, (n=7) this research also suggests that a 10% carbamide
peroxide tray based system can result a meaningful reduction in tetracycline stain with day-time
use. Previous research showed the effectiveness of 10% carbamide peroxide used overnight in
a tray based system 8. This new research suggests day-time use may be a viable option where
indicated due to compliance, patient preference or other factors.
Long term clinical trials of this duration may be particularly relevant in establishing clinical safety
associated with routine treatment, as a research model that evaluates extreme (intentional or
unintentional) use. Such research may only be appropriate with populations such as this one,
where long-term treatment is common and/or necessary to achieve a desired endpoint, where
ethical and experimental controls are adequate to interpret outcomes, and where rigorous and
sufficient exit criteria are established to assure in-use safety. Under these conditions, longer
duration trials represent a “torture test” of sorts, offering additional insight on short-term clinical
safety. This extended duration research, wherein whitening strips were professionally-
dispensed following clinical examination, and used for 180 contact hours over a 6-month period
to treat tetracycline stain, corroborates and extends the safety of strip-based tooth whitening as
reported in earlier, shorter duration clinical trials 9,253-27,24.
Tetracycline staining is complex, and may necessitate extensive esthetic intervention. Vital
appearance within a few weeks. While this non-invasive, treatment may need to continue over
an extended period. Some individuals will show favorable response after 3-4 months, after
which treatment may be discontinued. Duration may be difficult to predict, given the variable
Eliminato: 89¶
99
clinical manifestations of tetracycline staining. Practitioners and patients should be advised that
optimal bleaching of tetracycline staining may necessitate extended daily at-home treatment
over a period of 3-6 months. The costs, risks, and benefits of the various treatment options
must be considered as part of overall patient management.

CONCLUSION
Both the 6.5% hydrogen peroxide bleaching strip (Crest Professional Whitestrips) and the
daytime tray-based carbamide peroxide tray systems (Opalescence 10%) provided significant
tooth whitening of tetracycline stain. While shade improvement generally occurred earlier with
the strips compared to the trays, by Month 4, groups did not differ significantly in this whitening
end point. Both groups demonstrated similar results after 6 months. Daily use of strips or
daytime tray bleaching for an extended 6-month period (approximately 180 contact hours) was
generally well-tolerated, with no subjects discontinuing treatment early due to an adverse event,
and with the principal adverse events—mild tooth sensitivity or and oral irritation—being similar
to that seen with the at-home carbamide peroxide tray system.

Formattato: Tipo di
9 pt
Eliminato: 89¶
100
Tables and Figures
Formattato: Tipo di
Table 1. BASELINE DEMOGRAPHIC CHARACTERISTICS AND TETRACYCLINE STAINING carattere: (Predefinito) Arial,
11 pt, Non Grassetto
Table 2. Treatment Comparisons, Mean Shade Change at Months 1-3
Figure 1. Mean Shade Change by Group
Figure 2. Percent of Subjects Who Reached Minimum (“B1”) Shade by Group
Table 3. Treatment Comparisons, Percent of Subjects Who Reached Minimum Shade at
Months 3-6
Table 4. Occurrence of Oral Irritation and Tooth Sensitivity
TABLE 1
BASELINE DEMOGRAPHIC CHARACTERISTICS AND TETRACYCLINE STAINING
CHARACTERISTIC STRIP GROUP TRAY GROUP OVERALL TWO-SIDED

STATISTIC (n =30) (n =10) (n =40) p-VALUE
AGE (YEARS)
Mean (SD) 37.7 (9.46) 38.9 (14.72) 38.0 (10.81) 0.7591
Minimum -
22 - 58 25 - 70 22 - 70
Maximum
Sex
Female 19 (63.3%) 3 (30%) 22 (55%) 0.1401 e
Male 11 (36.7%) 7 (70%) 18 (45%)
TETRACYLINE STAIN LEVEL
I 15 (50%) 4 (40%) 19 (47.5%) 0.3176 e
II 7 (23.3%) 1 (10%) 8 (20%)
III 8 (26.7%) 4 (40%) 12 (30%)
IV 0 (0.0%) 1 (10%) 1 (2.5%)
Eliminato: 89¶
101
Table 2
Treatment Comparisons
Shade Change from Baseline at Months 1-3
CHANGE FROM BASELINE

ADJ. MEAN ADJUSTED 95% ADJUSTED
N (S.E.) MEAN CHANGE C. I. MEAN P-
(P-VALUE ) TREATMENT VALUE
DIFFERENCE
(S.E.)
Month 1
Strip -4.05 (-4.83,- -3.15
26 8.13(0.397) <0.001
Group (<0.001) 3.27) (0.852)
Tray 11.28(0.696) -0.9 (0.101) (-2.27,0.46)
9
Group
Month 2
Strip -6.61 (-7.43,- -2.64
26 5.49(0.417) 0.010
Group (<0.001) 5.79) (0.991)
Tray -3.98 (-5.61,-
7 8.13(0.833)
Group (<0.001) 2.34)
Month 3
Strip -8.59 (-9.11,- -1.26
26 3.52 (0.267) 0.048
Group (<0.001) 8.07) (0.634)
Tray -7.33 (-8.38,-
7 4.77 (0.533)
Group (<0.001) 6.29)
Month 4
Strip -9.84 (-10.45,- -0.41
24 2.37 (0.309) 0.5484
Group (<.0001) 9.24) (0.713)
Tray -9.43 (-10.59,-
7 2.78 (0.592)
Group (<.0001) 8.27)
Month 5
Strip -10.35 (-10.86,- -0.31
23 2.04 (0.262) 0.5876
Group (<.0001) 9.83) (0.593)
Tray -10.04
7 2.35 (0.49) (-11,-9.08)
Group (<.0001)
Month 6
Strip 1.71 -10.67 (-11.23,- -0.18
23 0.7764
Group (0.285) (<.0001) 10.12) (0.645)
Tray 1.89 -10.5 (-11.54,-
7 (0.532) (<.0001) 9.45)
Group
Eliminato: 89¶
102
Table 3
Treatment Comparisons
Percent of Subjects Who Reached Minimum Shade at Months 3-6
Formattato: Tipo di
Subjects who Reached B1/B1- Treatment Difference carattere: (Predefinito) Arial
N # (%) SUBJECTS P-VALUE ADJUSTED P-VALUE

MEAN
TREATMENT
DIFFERENCE
(S.E.)
Month 3
Strip Group 26 2 (7.7%) 1.00 -1.26 (0.61) 0.039
Tray Group 7 0 (0%)
Month 4
Strip Group 24 11 (45.8%) 0.202 -0.63 (0.96) 0.511
Tray Group 7 1 (14.3%)
Month 5
Strip Group 23 12 (52.2%) 0.103 -0.60 (0.85) 0.481
Tray Group 7 1 (14.3%)
Month 6
Strip Group 23 15 (65.2%) 0.394 -0.55 (1.25) 0.657
Tray Group 7 3 (42.9)
Eliminato: 89¶
103
Formattato: Tipo di
Table 4 Grassetto, Non Corsivo
OCCURRENCE OF ORAL IRRITATION AND TOOTH SENSITIVITY Formattato: Tipo di
STRIP GROUP TRAY GROUP OVERALL

(n =30)a (n =10)a (n =40)a
AE SOURCE/AE CLASSIFICATION No. % No. % No. %
Subj. Subj. Subj. Subj. Subj. Subj.
Reported
Oral Discomfort 13 43.3 3 30 16 40.0
Tooth Sensitivity 14 46.7 4 40 18 45.0
Observed
Oral Irritation 0 0 0 0 0 0
Figure 1
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Figure 2
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105
REFERENCES Formattato: Tipo di
Tutto maiuscole
1. Arens D. The role of bleaching in esthetics. Dent Clin North Am 1989; 33:319-36
Formattato: Tipo di
2. Swachman H, Fekete E, Kulezychi L, Foley T. The effect of long-term antibiotic therapy in carattere: (Predefinito) Arial
patients with cystic fibrosis of the pancreas. Antibiot Annu 1958; 9:622-9
3. Cohen S, Parkins FM. Bleaching tetracycline-stained vital teeth. Oral Surg 1970; 29:465
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13-9
5. Mello HS. The mechanism of tetracycline staining in primary and permanent teeth. J Dent
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6. Moffitt JM, Cooley RO, Olsen NH, et al. Prediction of tetracycline-induced tooth
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7. Mull MM. The tetracycline and the teeth. Dent Abstr 1967; 12:346-350
8. Haywood VB, Leonard RH. Six-and 12-month color stability after 6 months bleaching
tetracycline teeth [abstract 2891]. J Dent Res 1996; 75(special issue): 379
9. Kugel G, Aboushala A, Zhou X, Gerlach RW. Daily use of strips on tetracycline-stained Formattato: Inglese (U.S.A.)
teeth: comparative results after 2 months. Comp of Cont Edu in Dent. Jan 2002; 23 (1A): 29-
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10. Haywood VB, Heymann HO:Nightguard vital bleaching . Quintessence Int 20(3):173-
176,1989.
Kugel G. Nontray whitening. Compend Contin Educ Dent 2000;6:524-528. Formattato: Tipo di
11. Gerlach RW. Whitening paradigms 1 year later: Introduction of a novel
professional tooth-bleaching system. Compend Contin Educ Dent 2002;23:4-8.
12. Siew C. American Dental Association. ADA Guidelines for the acceptance of
tooth-whitening products. Compend Contin Educ Dent. Supplem (28): S44-7, 2000
Jun.
13. Haywood VB, Leonard RH, Dickinson GL. Efficacy of six months of nightguard vital
bleaching of tetracycline-stained teeth. J Esthet Dent. 1997;9:13-9.
14. Matis BA, Cochran MA, Eckert G, Carlson TJ. The efficacy and safety of a 10%
carbamide peroxide bleaching gel. Quintessence Int. 1998;29:555-63.
15. Gerlach RW, Gibb RD, Sagel PA. A randomized clinical trial comparing a novel 5.3% Formattato: Inglese (U.S.A.)
hydrogen peroxide bleaching strip to 10%, 15% and 20% carbamide peroxide tray-based
bleaching systems. Compend Contin Educ Dent 2000;21:S22-S28.
16. Matis BA. Tray whitening: What the evidence shows. Compend Contin Educ Dent
2003;24:354-362.
17. Haywood VB. Frequently asked questions about bleaching. Compend Contin Educ Dent
2003;24:324-338.
18. Boksman L, Jordan RE. Conservative treatment of the stained dentition: vital bleaching.
Aust Dent J 1983;28:67-72.
19. Tobin, J. Estimation of Relationships for Limited Dependent Variables. Econometrica, Formattato: Inglese (U.S.A.)
1958;26, 24 -36. Formattato: Inglese (U.S.A.)
20. Green, W.H. Econometric Analysis, 2nd Edition, New York: Cambridge University Press, Formattato: Inglese (U.S.A.)
1993.
21. Leonard RH. Long-term treatment results with nightguard vital bleaching. Compend
Contin Educ Dent. 2003;24:364-74.
22. Leonard RH Jr, Haywood VB, Caplan DJ, Tart ND. Nightguard vital bleaching of
tetracycline-stained teeth: 90 months post treatment. J Esthet Restor Dent. 2003;15:142-52
23. Matis BA, Wang Y, Jiang T, Eckert GJ. Extended at-home bleaching of tetracycline-
stained teeth with different concentrations of carbamide peroxide. Quintessence Int.
2002;33:645-55. Formattato: Inglese (U.S.A.)
24. Gerlach RW. Zhou X. Comparative clinical efficacy of two professional bleaching
systems. Compend Contin Educ Dent 2002;23:35-41.
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25. Karpinia KA, Magnusson I, Sagel PA, Zhou X, Gerlach RW. Vital bleaching with two at-
home professional systems. Am J Dent 2002;15:13-18A. Formattato: Tedesco
1. Li Y, Lee SS, Cartwright SL, Wilson AC. Comparison of clinical efficacy and safety of (Germania)
three professional at-home tooth whitening systems. Compend Contin Educ Dent Formattati: Elenchi puntati e
numerati
2003;24(5):357-64.
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carattere: Arial
Eliminato: 89¶
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Chapter 8
Paint on delivery systems

Formattato: Tipo di
carattere: Arial
A Clinical Comparison of Two Paint on Whitening Systems
Formattato: Tipo di
carattere: Arial
Formattato: Tipo di
carattere: Arial
INTRODUCTION Formattato: Tipo di
Non Corsivo
The use of peroxide to whiten teeth dates back over 100 years. The advent of patient-applied Formattato: Tipo di
11 pt
kits, bleaching has become both common and popular, and use of peroxide is now generally
recognized as a safe and effective method for tooth whitening1-3. There are a variety of
indications for bleaching single or multiple teeth, including staining from chromagenic foods or
other sources, dental fluorosis, tetracycline staining and devital discolored teeth4-7. Delivery is
via in-office, at-home regimens, such as polyethylene strips and paint-on, or combination
regimens with or without professional supervision8-9.
Easy availability of over the counter whitening products has made whitening of teeth more
Formattato: Tipo di
popular amongst people of all ages. There are different types of over the counter products like carattere: (Predefinito) Arial
Formattato: Tipo di
whitening dentifrices, tray based, whitening strips and the recently introduced brush carattere: (Predefinito) Arial,
11 pt
applications.
Over the counter bleaching kit requires the consumer to use either a prefabricated tray or
fabricate their own semi-molded tray then fill it with supplied bleaching agents. These types are
less than ideal because the trays are not custom fitted and the formulation is not sophisticated
as those dispensed by the dentist.10
Whitening toothpastes contain mild abrasives to remove surface stains. The peroxide content in
the toothpastes are very low ( 1% or less ), also the exposures of the toothpastes on the tooth is
minimal hence any whitening minimal.11

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108
Formattato: Tipo di
Formattato: Tipo di
Whitening Strips is an alternative to rigid tray system for vital tooth whitening. The strip carattere: (Predefinito) Arial,
11 pt
technology uses same peroxide chemistry used in tray systems. The main drawback is that they
are limited to the anterior teeth and cannot be easily adapted to the malposed teeth.
The latest inclusion to OTC products is a Brush technique. This technique is non-tray based
Formattato: Tipo di
paint on application. These products include a 19% sodium percarbonate film (5.3% hydrogen carattere: Arial, 11 pt
Formattato: Tipo di
peroxide) along with an 18% carbamide peroxide paint-on gel. The advantages to the paint- on carattere: Arial, 11 pt
Formattato: Tipo di
products is ease of use as well as the elimination of the need for a tray. These systems also carattere: (Predefinito) Arial,
11 pt
limit gingival exposure. There is little data on efficacy of these products. Formattato: Tipo di
Formattato: Tipo di
11 pt
Formattato: Tipo di
Study Objectives 11 pt
Formattato: Tipo di
The objective of this trial was to compare the safety and whitening efficacy of an experimental carattere: Arial
Formattato: Tipo di
liquid strip (four weeks of use) to Colgate Simply White (three weeks of use). carattere: Arial, 11 pt
Formattato: Tipo di
Formattato: Tipo di
carattere: Arial
Study Design
Formattato: Tipo di
This was a randomized, controlled, double-blind, parallel, single-center study. Fifty (50) carattere: Arial, 11 pt
generally healthy subjects who desired to have their teeth whitened were enrolled in the study.
Subjects who qualified for the study based on the results of their Baseline visit were randomly
assigned to one of two treatment groups. The first product use was supervised at the Product
Distribution visit. All product use followed the labeled use instructions. Digital imaging and oral
Formattato: Tipo di
tissue examinations were conducted at Baseline, Week 2, Week 3, and Week 4. Subjects carattere: Arial
Formattato: Tipo di
assigned to Simply White discontinued product use after the Week 3 visit and returned one carattere: Arial, 11 pt
week later for digital imaging and oral tissue examinations. Subjects assigned to the
experimental product continued product use for all four weeks of the study. During the entire
Eliminato: 89¶
109
Formattato: Tipo di
study period (treatment and post-treatment), subjects brushed with Crest® Cavity Protection Apice / Pedice
Formattato: Tipo di
dentifrice and an extra-soft toothbrush. carattere: Arial, 11 pt
Formattato: Tipo di
. carattere: Arial
Selection of Study Population sinistra
Formattato: Tipo di
Fifty (50) generally healthy adults with a Vita Shade score of B2 or darker who met all study carattere: Arial, 11 pt
entrance criteria were enrolled. Subjects who withdrew from the study were not replaced.
Formattato: Tipo di
INCLUSION CRITERIA carattere: Arial, 11 pt
Formattato: Tipo di
To be included in this study, each subject must have: carattere: Arial, 11 pt

a. presented with a Vita Shade score of B2 or darker on Teeth 8 and 9; numerati
Formattato: Tipo di
b. provided written informed consent prior to their participation and be given a copy of the numerati
signed consent form;

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c. been at least 18 years of age at the time of enrollment; numerati
Formattato: Tipo di
d. agreed not to participate in any other oral/dental product clinical studies during the course of numerati
this study;
Formattato: Tipo di
e. agreed to return for the scheduled visits and follow the study procedures; and numerati
Formattato: Tipo di
carattere: Arial

f. agreed to refrain from the use of any non-study dentifrices and tooth whitening products for numerati
the study duration.
Formattato: Tipo di
EXCLUSION CRITERIA carattere: Arial, 11 pt
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The subjects were excluded from this study if they: carattere: Arial, 11 pt
Eliminato: 89¶
110
a. had dental crowns or clinically meaningful malocclusion involving the maxillary or 0 pt, Numerazione automatica
+ Livello:1 + Stile
numerazione: a, b, c, … +
mandibular anterior dentition (also confirmed by Investigator at Baseline visit); Comincia da:1 + Allineamento:
A sinistra + Allinea a: 18 pt +
Tabulazione dopo: 36 pt +
Rientra di: 36 pt, Tabulazioni:
Non a 36 pt
b. reported having teeth previously bleached by a professional treatment, over-the-counter Formattato: Tipo di
carattere: Arial
bleaching kit, or clinical trial test product; Formattato: Rientro: Sinistro:
0 pt, Numerazione automatica
+ Livello:1 + Stile
c. presented with any pre-existing oral or medical condition that the examiner or Investigator A sinistra + Allinea a: 18 pt +
determined may have placed the subject at increased health risk from study participation; Non a 36 pt
Formattato: Tipo di
carattere: Arial
d. had any dental care planned during the duration of the study that may have: 0 pt, Numerazione automatica
+ Livello:1 + Stile
• impacted the general health of the subject, A sinistra + Allinea a: 18 pt +
• impacted the ability of the subject to bleach teeth according to the protocol, Non a 36 pt
Formattato: Tipo di
carattere: Arial
• required a dental prophylaxis, or
• involved the anterior dentition; numerati
Formattato: Tipo di
carattere: Arial
e. were undergoing current treatment for gingivitis, periodontitis, or caries; numerati
Formattato: Tipo di
carattere: Arial
f. were currently using a chlorhexidine mouth rinse or Listerine® mouth rinse; numerati
Formattato: Tipo di
carattere: Arial

g. had teeth with clinically meaningful intrinsic staining due to tetracycline, fluorosis or numerati
hypocalcification;
Formattato: Tipo di
carattere: Arial

h. had self-reported dentinal sensitivity, or numerati
Formattato: Tipo di
carattere: Arial
Eliminato: 89¶
111
i. had teeth that could not be imaged. numerati
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CONTINUANCE CRITERIA carattere: Arial, 11 pt
Formattato: Tipo di
Subjects may have been discontinued from the study or been excluded from the efficacy carattere: Arial, 11 pt
analysis if they:

a. used a chlorhexidine mouth rinse and/or Listerine® mouth rinse; + Livello:1 + Stile
b. received a dental prophylaxis; or Rientra di: 72 pt, Tabulazioni:
Non a 72 pt
+ Livello:1 + Stile
c. used any tooth whitening products other than assigned study products. numerazione: a, b, c, … +
Removal of Subjects from the Study Non a 72 pt
Formattato: Tipo di
carattere: Arial
Subjects were encouraged to complete the full course of the study; however subjects may have Formattato: Rientro: Sinistro:
+ Livello:1 + Stile
withdrawn from the study at any time or for any reason. The reason for withdrawal was numerazione: a, b, c, … +
documented on the appropriate case report form (CRF). The Investigator may have removed A sinistra + Allinea a: 54 pt +
subjects from the study for medical reasons and where, in his judgment, there was significant Non a 72 pt
Formattato: Tipo di
lack of compliance at any time. carattere: Arial
sinistra
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carattere: Arial
Formattato: Normale
Formattato: Tipo di
Formattato: Tipo di
carattere: Arial
sinistra, Destro 16,55 pt,
Interlinea singola
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carattere: Arial
Study Procedures
Formattato: Normale
Eliminato: 89¶
112
Formattato: Tipo di
There were 5 study visits. A table detailing the procedures performed at each visit is provided in carattere: Arial, 11 pt
Formattato: Tipo di
Table 1. carattere: Arial, 11 pt,
Grassetto
Formattato: Tipo di
SCHEDULE OF EVENTS carattere: Arial
Formattato: Tipo di
Study No. 2002147
Table 1
Schedule of Events
Pre-
Treatment Treatment
Visit 2
Visit 1 Product Visit 3 Visit 4 Visit 5
Procedures Baseline Distribution Week 2 Week 3 Week 4
Informed Consent X
Inclusion/Exclusion Criteria X
Demographics X
Balance & Assignment X
Supervised Product X
Application
Product Distribution X
Product Return X
Oral Status Interview X X X X
Oral Hard & Soft Tissue X X X X
Examination
Continuance Criteria X X X X
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113
Study No. 2002147
Table 1
Schedule of Events
Pre-
Treatment Treatment
Visit 2
Visit 1 Product Visit 3 Visit 4 Visit 5
Procedures Baseline Distribution Week 2 Week 3 Week 4
Digital Imaging X X X X
Adverse Events X X X
Subject Accountability X
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carattere: Arial
BASELINE VISIT
Formattato: Tipo di
Written informed consent was obtained from each subject following review of the study design carattere: Arial, 11 pt
and test regimen. Demographic information and inclusion/exclusion criteria were obtained and
documented on the appropriate CRF. Each subject was given an oral status interview prior to
receiving an oral soft tissue (OST) examination that included a self-reported tooth sensitivity
assessment. Digital images of the facial anterior dentition were collected.
Formattato: Tipo di
carattere: Arial
PRODUCT DISTRIBUTION/BALANCE & ASSIGNMENT VISIT
Formattato: Tipo di
The b* and L* digital imaging scores obtained at the Baseline visit, along with age, were arrayed carattere: Arial, 11 pt
to balance and assign subjects to treatment groups. Test product (kit boxes plus Crest) was
distributed and written instructions were reviewed. Subjects completed their first product use
under supervision.
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Eliminato: 89¶
114
Formattato: Tipo di
WEEK 2 VISIT carattere: Arial, 11 pt
Formattato: Tipo di
Approximately 2 weeks after beginning test product use, subjects returned to the clinical site. carattere: Arial, 11 pt
Continuance criteria were assessed. An oral status interview and an oral exam were
conducted. Self-reported, clinical OST and tooth sensitivity abnormal findings not present at
Baseline were documented on the AE CRF. Digital images of the facial anterior dentition were
collected.
Formattato: Tipo di
carattere: Arial
Formattato: Tipo di
Formattato: Tipo di
Approximately 3 weeks after beginning test product use, subjects returned to the clinical site. carattere: 11 pt
Formattato: Tipo di
Continuance criteria were assessed. An oral status interview and an oral tissue exam were carattere: Arial, 11 pt
Formattato: Tipo di
conducted. Self-reported, clinical OST and tooth sensitivity abnormal findings not present at carattere: Arial, 11 pt
collected. Subjects assigned to Simply White discontinued product use at this time (per
labeling), but continued to brush with the provided toothbrush and dentifrice.
Formattato: Tipo di
Formattato: Tipo di
Formattato: Tipo di
Continuance criteria were assessed. An oral status interview and an OST exam were carattere: Arial, 11 pt
Formattato: Tipo di
conducted. Self-reported, clinical OST, and tooth sensitivity abnormal findings not present at carattere: Arial, 11 pt
collected. All test product was returned. Subjects were exited from the study
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carattere: Arial
EFFICACY ASSESSMENTS
DIGITAL IMAGING CAMERA

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The photographic system consisted of a HC2500 CCD high resolution digital camera carattere: Arial, 11 pt
manufactured by Fuji. It was equipped with a Fujinon A8x12BMD, 1:2.8/12-96mm zoom lens
Formattato: Tipo di
and a linear polarizer to permit cross-polarized light. Two 150-watt lights located on each side carattere: Arial, 11 pt
of a CCD camera provided the lighting. The unit was connected to a personal computer which
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recorded and analyzed the images. Prior to daily use, the system was calibrated to assure
proper operation. Additionally, a color standard was centered and imaged every hour, then was
removed prior to imaging subjects. Maxillary anterior facial surfaces were measured for tooth
color using the digital image technology. One color value (L* a* b*) was generated from the
complete surface of the measured teeth.

Formattato: Tipo di
carattere: Arial
Formattato: Tipo di
For each examination period, lighting in the exam room was background or ambient. Each carattere: Arial, 11 pt
Formattato: Tipo di
subject was asked to brush with water and an extra-soft toothbrush to dislodge any debris that carattere: (Predefinito) Arial,
11 pt
may have interfered with photography. The subject sat on a stool in front of a chin rest used to Formattato: Tipo di
hold the head still. The subject placed his/her chin on the chin rest, then positioned two plastic
retractors into the mouth to retract his/her lips and cheeks.

Formattato: Tipo di
carattere: Arial
Formattato: Tipo di
It was also acceptable for the subject to position the retractors, then place their chin on the chin carattere: Arial, 11 pt
rest. The subject was instructed to use the retractors to retract his/her lips and cheeks (toward
their ears) as far as possible. The incisal edges of the front teeth were placed together and
centered in the camera. The chin rest may have been adjusted to bring the teeth into the plane
of focus and ensured the image was centered. Prior to exposure, the subject was instructed to
draw air through their teeth and to position their tongue away from the teeth so that the tongue
was not visible. By proper positioning of the camera, frontal images of each subject were taken
at each visit.
Formattato: Tipo di
Formattato: Tipo di
carattere: Arial
SAFETY ASSESSMENTS
Formattato: Tipo di
In this study, an AE was defined as any negative oral cavity health effect, either reported by the carattere: Arial, 11 pt
subject or noted by the Investigator. Serious adverse events (SAEs), which occurred during the
course of the study and were reported to or observed by the study Investigator/examiner, were
documented on the appropriate CRF. All SAEs were to be followed until resolution or until
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116
discharge from follow-up was warranted based on consultation between the Sponsor and the
Investigator.
Serious AEs were defined as one or more of the following: a) death, b) life-threatening, c)
required in-patient hospitalization, and d) resulted in persistent or significant disability. When
the Investigator was notified of an SAE, the Investigator must have promptly (within 24 hours)
notified Procter & Gamble (P&G, the CRA or the Medical Monitor) of the SAE, regardless of
causality. Within 5 working days, a written report describing the circumstances of the event
must have been submitted to P&G.

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carattere: Arial
Formattato: Tipo di
ORAL SOFT TISSUE (OST) EXAMINATION
Formattato: Tipo di
Assessment of the OST was conducted via a visual examination of the oral cavity and perioral carattere: Arial, 11 pt
area utilizing a standard dental light, dental mirror, and gauze. The structures examined
included the gingiva (free and attached), hard and soft palate, oropharynx/uvula, buccal
mucosa, tongue, floor of the mouth, labial mucosa, mucobuccal/mucolabial folds, lips, and
perioral area. All abnormal OST findings noted after test product assignment which were not
documented at Baseline, or were present at Baseline but had worsened during test product
usage, were recorded as AEs on the AE CRF.

Formattato: Tipo di
Formattato: Tipo di
carattere: Arial
TREATMENTS
Formattato: Tipo di
Method of Assigning Subjects to Treatment Groups Formattato: Tipo di
After the Baseline visit, digital images were processed and subjects were randomly assigned in maiuscole
approximately equal numbers to one of the two treatment groups. The randomization balanced sinistra
Formattato: Tipo di
for Baseline b* and L* scores, as well as age. Subjects who resided in the same household carattere: Arial, 11 pt
were assigned to identical marketed products. A statistician that was not a member of the
project team carried out the assignment procedure.

Formattato: Tipo di
Eliminato: 89¶
117
Formattato: Tipo di
carattere: Arial
TREATMENTS ADMINISTERED
Formattato: Tipo di
carattere: Arial, Non
Experimental Whitening Product Maiuscoletto
Formattato: Non
Maiuscoletto
Formattato: Tipo di
Subjects were instructed to follow their customary brushing regimen for the study duration using carattere: Arial
Formattato: Tipo di
the Crest Cavity Protection dentifrice and toothbrush provided. Prior to using the test product, carattere: Arial, 11 pt
subjects were instructed to brush and dry their teeth. Subjects applied the liquid strip to the
facial surfaces of the maxillary anterior teeth once daily just prior to bedtime. Subjects were
instructed not to eat, drink, or smoke for 90 minutes following treatment application. The test
product was removed each morning by thoroughly brushing the teeth. Subjects were supplied
with written instructions and shown pictures on how to apply the product. The first product use
was completed under supervision at the Product Distribution visit. All other uses were
unsupervised at-home.
Formattato: Tipo di
carattere: Arial
Formattato: Tipo di
Colgate Simply White Maiuscoletto
Formattato: Tipo di
Subjects followed the manufacturer directions for product use, and followed their customary carattere: Arial, 11 pt
brushing regimen for the study duration using Crest Cavity Protection dentifrice and the
toothbrush provided. Prior to using the test product, subjects were instructed to brush and dry
their teeth. Subjects applied the whitening product to the facial surfaces of the maxillary anterior
teeth twice per day. Subjects were instructed not to eat or drink for 30 minutes following
treatment application. Subjects were supplied with the marketed instructions for use and shown
pictures on how to apply the product. The first product use is completed under supervision at
the Product Distribution visit. All other uses are unsupervised at-home.
Formattato: Tipo di
Formattato: Tipo di
carattere: Arial
IDENTITY OF INVESTIGATIONAL PRODUCTS
numerati
• Experimental tooth whitener (19.0% sodium percarbonate, equivalent to 5.3% hydrogen
peroxide), manufactured by The Procter & Gamble Company. Packaged in individual
sachets / stick packs. Eliminato: 89¶

118
Formattato: Tipo di
carattere: Arial
• Colgate Simply White (commercial product)
Formattato: Tipo di
Experimental Whitening Product Maiuscoletto
Formattato: Tipo di
Each kit contained a four-week supply of single unit doses (sachets), 20 micro brushes for carattere: Arial, 11 pt
product application, one tube of toothpaste (Cavity Protection Crest, The Procter & Gamble Co.,
Cincinnati, OH, USA) one extra-soft toothbrush (Crest Complete, The Procter & Gamble Co.,
Cincinnati, OH, USA), and one instruction sheet. The sachets were labeled with study number,
product number, applicable caution and warning statements, usage directions and other
information as dictated by internal regulatory requirements and clinical standard operating
procedures (SOPs).
Formattato: Tipo di
carattere: Arial
Formattato: Tipo di
Colgate Simply White Maiuscoletto
Formattato: Tipo di
Product was supplied in subject kit boxes. Each kit contained one 0.34 oz polypropylene bottle carattere: Arial, 11 pt
with applicator, one tube of toothpaste (Cavity Protection Crest, The Procter & Gamble Co.,
Cincinnati, OH, USA) one extra-soft toothbrush (Crest Complete, The Procter & Gamble Co.,
Cincinnati, OH, USA), and one instruction sheet. The kits were labeled with study number,
product number, applicable caution and warning statements, labeled usage directions and other
information as required by internal regulatory and clinical SOPs.

Formattato: Tipo di
carattere: Arial
Formattato: Tipo di
Supplemental product was provided to the Investigator if additional product was needed, and carattere: Arial, 11 pt
was dispensed only after consulting with the Sponsor for correct treatment group identification.
The shipping containers were labeled with the "ship to" clinical site address and a "content
statement" listing study number and subject numbers contained within.
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Formattato: Tipo di
carattere: Arial
BLINDING
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This was a double-blind study. Product use was conducted in an area where the examiner was carattere: Arial, 11 pt
not present. Subjects were instructed not to discuss product appearance or physical qualities
with the examiner.

Formattato: Tipo di
carattere: Arial
TREATMENT COMPLIANCE
Formattato: Tipo di
Subjects received verbal and written instructions on dentifrice usage. Subjects used their carattere: Arial, 11 pt
product for the first time on site under supervision as part of the instructions. Subjects were
queried regarding compliance at each visit.

Formattato: Tipo di
Formattato: Tipo di
carattere: Arial
STATISTICAL ANALYSIS PLANS
Formattato: Tipo di
The primary assessment compared the treatment groups for yellowness reduction (Δb*) at the
end-of-treatment visit. The secondary assessment compared the treatment groups for
yellowness reduction (Δb*) at the Week 2 visit. The tertiary assessment compared the
treatment groups for yellowness reduction (Δb*) at the end-of-study visit. The mean whitening
benefit for each treatment group was assessed at the post-baseline visits. The safety profile of
each treatment group was characterized.

Formattato: Tipo di
carattere: Arial, Non Corsivo
Operational Trial Hypotheses

Formattato: Tipo di
Tooth color was assessed by the digital imaging measurements b* (yellow – blue), L* carattere: Arial, 11 pt
(lightness), and a* (red – green). For a given post-baseline visit: Δb* = b*visit - b*baseline, ΔL* =
L*visit - L*baseline, Δa* = a*visit - a*baseline, and ΔE* = (ΔL*2 + Δa*2 + Δb*2) ½. In the case of tooth
color, whitening benefit resulted primarily from negative Δb* (yellowness reduction).
Formattato: Tipo di
carattere: Arial
Additionally, positive ΔL* (increasing lightness) and negative Δa* (redness reduction) may have
Formattato: Tipo di
been observed. Changes in Δb*, ΔL*, and Δa* resulted in increased ΔE* (overall color change).
Formattato: Tipo di
carattere: Arial
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Formattato: Tipo di
An additional color quantity was computed from the L*a*b* color values for each subject and carattere: Arial, 11 pt
visit: W* = (b*visit2 + a*visit2 + (L*visit - 100)2) ½ which represented the distance to pure white for a
given visit. One may have defined ΔW* = (b*visit2 + a*visit2 + (L*visit - 100)2) ½ – (b*baseline2 +
a*baseline2 + (L*baseline - 100)2) ½ as the distance to pure white at a given visit minus the distance to
pure white at Baseline. In the equations above, pure whiteness was achieved when b* = 0, a* =
0, and L* = 100.
Formattato: Tipo di
Primary Hypotheses Maiuscoletto
Formattato: Tipo di
The following hypothesis was tested at the end-of-treatment visit. carattere: Arial, 11 pt
Null: The mean level of Δb* in the experimental group is equal to the mean level of Δb*
in the Simply White group.
Alternative: The mean level of Δb* in the experimental is not equal to the mean level of Δb* in
the Simply White group.

Formattato: Tipo di
carattere: Arial
Formattato: Tipo di
Secondary Hypotheses Maiuscoletto
Formattato: Tipo di
The following hypothesis was tested at the Week 2 visit. carattere: Arial, 11 pt
Formattato: Tipo di
carattere: Arial
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Formattato: Tipo di
Tertiary Hypotheses Maiuscoletto
Formattato: Tipo di
The following hypothesis was tested at the end-of-study visit. carattere: Arial, 11 pt
The following hypothesis was tested for each treatment group and post-baseline visit.
Null: The mean level of Δb* is equal to zero.
Alternative: The mean level of Δb* is not equal to zero.
The hypotheses above were investigated for other color parameters as well.
Formattato: Tipo di
carattere: Arial
Formattato: Tipo di
Efficacy Analysis Plans

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Summary statistics (e.g., means, standard deviations, frequencies, etc.) of the demographic carattere: Arial, 11 pt
characteristics, b*, L*, a*, W*, and ΔE* were calculated for each treatment group and visit. The
treatment groups were compared using analysis of covariance (ANCOVA) methods. The
response was color change from Baseline and the covariate was the color at Baseline. Age
Formattato: Tipo di
was used as a covariate. Treatment comparisons were tested at the 0.05 level of significance. carattere: Arial
Formattato: Tipo di
Whitening benefit at each post-baseline visit was investigated using the mean color change carattere: Arial, 11 pt
from Baseline within each treatment group and then performing one-sample t-tests.
Comparisons to Baseline were tested using a two-sided 0.05 level of significance.
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Safety Analysis Plans
Formattato: Tipo di
The safety data were summarized with respect to tooth sensitivity and oral irritation. Following carattere: Arial, 11 pt
the end-of-study visit, all AEs, including OST-related AEs and dentinal hypersensitivity AEs
were summarized overall and by treatment group. The safety data were also summarized
through the Week 2 visit.

Formattato: Tipo di
Formattato: Tipo di
carattere: Arial
POWER AND SAMPLE SIZE CONSIDERATIONS
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At least 23 subjects per treatment group completing the study ensured at least 80% power to carattere: Arial, 11 pt
detect a difference of 0.7 b* units between the treatment groups with a common standard
deviation of 0.7, in two-sided testing at a 0.05 significance level. A target of up to 25 subjects
was recruited per group (total of up to 50).

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carattere: Arial
CHANGES TO THE ANALYSIS PLANS

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All planned analyses were performed. In addition, efficacy comparisons were made between carattere: Arial, 11 pt
Week 2 for the Experimental Film group and Week 3 for the Colgate Simply White group. Also,
the treatment groups were compared at the Week 3 visit as well. Safety data was also
summarized through the Week 2 visit of the study.
Formattato: Tipo di
carattere: Arial, Nessuna
RESULTS sottolineatura, Tutto maiuscole
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DISPOSITION OF SUBJECTS carattere: Arial
Formattato: Tipo di
Fifty-one subjects were screened, however, Subject 3021 was dropped from the study at carattere: Arial
Interlinea singola
Baseline due to investigator recommendation. Fifty subjects were randomized to treatment, and
Formattato: Tipo di
47 subjects received product. Three subjects failed to present for product distribution visit:
Subject 3007 voluntarily withdrew from the study, Subjects 3013 and 3041 were lost to follow-
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up. Thirty-nine subjects completed the study. Eight subjects 3024, 3025, 3027, 3032, 3033,
3045, 3057, 3016 were lost to follow-up (Table 3).

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carattere: Arial
DATA SETS ANALYZED

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Demographic, digital imaging and adverse event data were all analyzed for this study. Three carattere: Arial, 11 pt
Formattato: Tipo di
subjects failed to present for the product distribution visit: Subject 3007 voluntarily withdrew carattere: Arial, 11 pt
from the study, Subjects 3013 and 3041 were lost to follow-up. In the Colgate Simply White
group, one subject (3045) was lost follow-up starting at the Week 2 visit and six subjects (3024,
3025, 3027, 3032, 3033, and 3057) were lost to follow-up at the Week 4 visit, two subjects
(3002 and 3015) each missed one visit. In the Experimental Film group, one subject (3016) was
lost follow-up starting at the Week 2 visit, two subjects (3008 and 3022) each missed one visit
(Table 3).
Formattato: Tipo di
carattere: Arial
DEMOGRAPHIC AND BASELINE CHARACTERISTICS

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Subjects ranged in age from 21 to 70 years with an average of 35 years. Sixty-four percent of carattere: Arial, 11 pt
the subjects were female. Twenty-eight subjects (59.6%) were Caucasian, 12 subjects (25.5%)
were Black, 3 subjects (6.4%) were Asian, 2 subjects (4.3%) were Asian and 2 subjects (4.3%)
were Multi-racial. Cigarette and cigar smokers accounted for 10.6% of the subjects. Coffee,
tea, and dark cola drinkers accounted for 89.4% of the subjects with a median of 2 drinks per
day. Treatment groups were relatively balanced in demographic characteristics and behavioral
parameters (Table 4-5).

Formattato: Tipo di
carattere: Arial
sinistra
Efficacy Results
PRIMARY EFFICACY
The end-of-treatment comparison compared the Experimental Film group at Week 4 relative to
the Colgate Simply White group at Week 3. At the end-of-treatment visit, the Experimental Film
group provided more than 7.9 times greater reduction in yellowness (Δb*) when compared to the Eliminato: 89¶
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Colgate Simply White group with estimated means and standard errors of –0.782 ± 0.137 and –
0.098 ± 0.131, respectively. The treatment comparison for Δb* was statistically significant (p-
value = 0.0009 from Table 16).
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carattere: Arial
SECONDARY EFFICACY
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At Week 2 visit, the Experimental Film group provided more than 3.0 times greater reduction in carattere: Arial, 11 pt
yellowness (Δb*) when compared to the Colgate Simply White group with estimated means and
standard errors of –0.691 ± 0.124 and –0.230 ± 0.116, respectively. The treatment comparison
for Δb* was statistically significant (p-value = 0.0109 from Table 11).
Formattato: Tipo di
Formattato: Tipo di
carattere: Arial
TERTIARY EFFICACY
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At the end-of-study visit (Week 4), the Experimental Film group provided more than 4.4 times carattere: Arial, 11 pt
greater reduction in yellowness (Δb*) when compared to the Colgate Simply White group with
estimated means and standard errors of –0.788 ± 0.140 and –0.177 ± 0.152, respectively. The
treatment comparison for Δb* was statistically significant (p-value = 0.006 from Table 11).
Formattato: Tipo di
carattere: Arial
Formattato: Tipo di
For the whitening benefit measured by mean change in b* (yellowness) from Baseline, the carattere: Arial, 11 pt
Experimental Film group was effective at each post-baseline visit (p-values ≤ 0.0003 from Table
6), while the Colgate Simply White group was only statistically significant at the Week 2 visit (p-

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Formattato: Tipo di
carattere: Arial
ADDITIONAL EFFICACY
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Summary statistics were calculated for b*, L*, a*, ΔW* and ΔE* (Tables 6-10). The treatment
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groups were well balanced on b* (yellowness), L* (lightness), and a* (redness) at Baseline.
Figure 1 displays the adjusted means of Δb* for each treatment group at each visit. Figure 2
displays the adjusted means of ΔL* for each treatment group at each visit.
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Formattato: Tipo di
carattere: Arial

END-OF-TREATMENT
(Experimental Film at Week 4 versus Colgate Simply White at Week 3)

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At the end-of-treatment visit, the Experimental Film group provided more than 7.3 times greater carattere: Arial, 11 pt
improvement in lightness (ΔL*) when compared to the Colgate Simply White group with
estimated means and standard errors of 1.061± 0.124 and 0.145 ± 0.118, respectively. The
treatment comparison for ΔL* was statistically significant (p-value < 0.0001 from Table 16). The
Experimental Film group provided more than 39 times greater improvement in redness (Δa*)
when compared to the Colgate Simply White group with estimated means and standard errors
of –0.394 ± 0.073 and –0.010 ± 0.070, respectively. The treatment comparison for Δa* was
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statistically significant (p-value = 0.0005 from Table 16). The Experimental Film group provided carattere: Arial
Formattato: Tipo di
more than 8 times greater improvement in composite whiteness (ΔW*) when compared to the carattere: Arial, 11 pt
Colgate Simply White group with estimated means and standard errors of –1.377 ± 0.149 and
–0.172 ± 0.142, respectively. The treatment comparison for ΔW* was statistically significant (p-
value < 0.0001 from Table 16). The Experimental Film group provided more than 2.3 times
greater overall color change (ΔE*) when compared to the Colgate Simply White group with
estimated means and standard errors of 1.526 ± 0.137 and 0.670 ± 0.131, respectively. The
treatment comparison for ΔE* was statistically significant (p-value < 0.0001 from Table 16).
Formattato: Tipo di
carattere: Arial
Formattato: Tipo di
ADDITIONAL TREATMENT COMPARISONS maiuscole
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(Experimental Film at Week 2 versus Colgate Simply White at Week 3) carattere: Arial
Formattato: Tipo di
The Experimental Film group at Week 2 provided more than 6.3 times greater reduction in carattere: Arial, 11 pt
yellowness (Δb*) when compared to the Colgate Simply White group at Week 3 with estimated
means and standard errors of –0.691 ± 0.122 and –0.108 ± 0.114, respectively. The treatment
comparison for Δb* was statistically significant (p-value = 0.0014 from Table 17). The
Experimental Film group at Week 2 provided more than 4.5 times greater improvement in
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lightness (ΔL*) when compared to the Colgate Simply White group at Week 3 with estimated
means and standard errors of 0.690 ± 0.114 and 0.152 ± 0.106, respectively. The treatment
comparison for ΔL* was statistically significant (p-value = 0.0015 from Table 17). The
Experimental Film group at Week 2 provided more than 29.9 times greater improvement in
redness (Δa*) when compared to the Colgate Simply White group at Week 3 with estimated
means and standard errors of –0.419 ± 0.067 and –0.014 ± 0.062, respectively. The treatment
comparison for Δa* was statistically significant (p-value < 0.0001 from Table 17). The
Experimental Film group provided more than 5.5 times greater improvement in composite
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carattere: Arial
whiteness (ΔW*) when compared to the Colgate Simply White group with estimated means and
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standard errors of –1.028 ± 0.138 and –0.185 ± 0.129, respectively. The treatment comparison
for ΔW* was statistically significant (p-value < 0.0001 from Table 17). The Experimental Film
group provided more than 1.7 times greater overall color change (ΔE*) when compared to the
Colgate Simply White group with estimated means and standard errors of 1.183 ± 0.114 and
0.683 ± 0.106, respectively. The treatment comparison for ΔE* was statistically significant (p-

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carattere: Arial
Formattato: Tipo di
Week 2 Comparisons carattere: 11 pt
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At the Week 2 visit, only Experimental Film group was effective in whitening teeth as measured carattere: Arial, 11 pt
by mean change in L* (lightness) from Baseline (p-value < 0.0001 from Table 7). The
Experimental Film group provided more than 13 times greater improvement in lightness (ΔL*)
of 0.693 ± 0.132 and 0.053 ± 0.123, respectively. The treatment comparison for ΔL* was
statistically significant (p-value = 0.0012 from Table 12). Both treatments were effective in
whitening teeth as measured by mean change in a* (redness) from Baseline: the Experimental
Film group had a p-value < 0.0001 and the Colgate Simply White group had a p-value equal to
0.0163 (Table 8). The Experimental Film group provided more than 3.4 times greater
improvement in redness (Δa*) when compared to the Colgate Simply White group with Eliminato: 89¶
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treatment comparison for Δa* was statistically significant (p-value = 0.0010 from Table 13).
Only the Experimental Film group was effective in whitening teeth as measured by mean
change in W* (composite whiteness) from Baseline with p-value < 0.0001 (Table 9). The
Experimental Film provided more than 5.3 times greater improvement in composite whiteness
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carattere: Arial
(ΔW*) when compared to the Colgate Simply White group with estimated means and standard
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errors of –1.034 ± 0.148 and –0.193 ± 0.138, respectively. The treatment comparison for ΔW*
was statistically significant (p-value = 0.0002 from Table 14). Both treatments were effective at
increasing overall color change (ΔE*) with p-values < 0.0001 (Table 10). The Experimental Film
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carattere: Arial
Formattato: Tipo di
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carattere: Arial
Formattato: Tipo di
Week 3 Comparisons carattere: 11 pt
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At the Week 3 visit, the Experimental Film group provided more than 6.3 times greater reduction carattere: Arial, 11 pt
in yellowness (Δb*) when compared to the Colgate Simply White group with estimated means
and standard errors of –0.705 ± 0.129 and –0.111 ± 0.123, respectively. The treatment
comparison for Δb* was statistically significant (p-value = 0.0021 from Table 11). Only the
Experimental Film group was effective in whitening teeth as measured by mean change in L*
(lightness) from Baseline (p-value < 0.0001 from Table 7). The Experimental Film group
provided more than 7 times greater improvement in lightness (ΔL*) when compared to the
Colgate Simply White group with estimated means and standard errors of 1.071± 0.137 and
0.149 ± 0.131, respectively. The treatment comparison for ΔL* was statistically significant (p-
value < 0.0001 from Table 12). Only the Experimental Film group effective in whitening teeth
as measured by mean change in a* (redness) from Baseline (p-value = 0.0025 from Table 8).
The Experimental Film provided more than 15.7 times greater improvement in redness (Δa*) Eliminato: 89¶
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of –0.268 ± 0.069 and –0.017 ± 0.066, respectively. The treatment comparison for Δa* was
statistically significant (p-value = 0.0126 from Table 13). Only the Experimental Film group was
effective in whitening teeth as measured by mean change in W* (composite whiteness) from
Baseline with p-value < 0.0001 (Table 9). The Experimental Film group provided more than 6.9
times greater improvement in composite whiteness (ΔW*) when compared to the Colgate
Simply White group with estimated means and standard errors of –1.313 ± 0.159 and –0.188 ±
0.152, respectively. The treatment comparison for ΔW* was statistically significant (p-value <
0.0001 from Table 14). Both treatments were effective at increasing overall color change (ΔE*)
with p-values < 0.0001 (Table 10). The Experimental Film provided more than 1.9 times greater
overall color change (ΔE*) when compared to the Colgate Simply White group with estimated
means and standard errors of 1.464 ± 0.136 and 0.692 ± 0.129, respectively. The treatment
comparison for ΔE* was statistically significant (p-value = 0.0002 from Table 15).
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End-of-Study (Week 4) Comparisons carattere: 11 pt
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At the Week 4 visit, only the Experimental Film group was effective in whitening teeth as carattere: Arial, 11 pt
measured by mean change in L* (lightness) from Baseline (p-value < 0.0001 from Table 7).
The Experimental Film group provided more than 4 times greater improvement in lightness (ΔL*)
of 1.065± 0.135 and 0.263 ± 0.146, respectively. The treatment comparison for ΔL* was
statistically significant (p-value = 0.0003 from Table 12). Only the Experimental Film group
effective in whitening teeth as measured by mean change in a* (redness) from Baseline (p-
value = 0.0003 from Table 8). The Experimental Film group provided more than 3.8 times
greater improvement in redness (Δa*) when compared to the Colgate Simply White group with
treatment comparison for Δa* was statistically significant (p-value = 0.0099 from Table 13).
Both treatments were effective in whitening teeth as measured by mean change in W* Eliminato: 89¶
129
(composite whiteness) from Baseline with p-values ≤ 0.0029 (Table 9). The Experimental Film
group provided more than 4.2 times greater improvement in composite whiteness (ΔW*) when
compared to the Colgate Simply White group with estimated means and standard errors of
–1.385 ± 0.146 and –0.325 ± 0.158, respectively. The treatment comparison for ΔW* was
statistically significant (p-value < 0.0001 from Table 14). Both treatments were effective at
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carattere: Arial, Colore
SAFETY RESULTS carattere: Automatico, Tutto
maiuscole
For Adverse Events Through Week 4 (End-of-Study) Formattato: Allineato a
sinistra
Only the Experimental Film group had reported or observed tooth sensitivity and oral irritation. Formattato: Tipo di
carattere: 11 pt
Eight subjects (36.4%) reported oral irritation and four subjects (18.2%) reported tooth Formattato: Tipo di
sensitivity. Two subjects (9.1%) had both tooth sensitivity and oral irritation (Table 18.1).
Overall, there were a total of 14 adverse events involving 11 different study subjects: Ten
subjects in the Experimental Film group and one subject in the Colgate Simply White group
(Table 19.1). By type, the most frequently reported AEs were gingivitis and hyperesthesia
which accounted for 50% and 36%, respectively, of all events (Table 18).
One hundred percent of all events were “mild” in severity. No subjects discontinued treatment
early “for cause” – that is – due to a treatment-related adverse events (Table 3).
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For Adverse Events Beginning On or Before Week 2 carattere: 11 pt
Formattato: Tipo di
Only the Experimental Film group had reported or observed tooth sensitivity and oral irritation. carattere: Arial, 11 pt
Two subjects (9.1%) reported oral irritation and two subjects reported tooth sensitivity. No
subjects reported both tooth sensitivity and oral irritation (Table 18.2). Overall, there were a
total of 5 adverse events involving 5 different study subjects who were all in the Experimental
Film group. One hundred percent of all events were “mild” in severity (Table 19.2).
Formattato: Tipo di
Formattato: Tipo di
carattere: Arial, Nessuna
CONCLUSIONS sottolineatura, Tutto maiuscole
Formattato: Tipo di
carattere: Arial
Formattato: Tipo di
• The Experimental Film provided significant whitening improvement from Baseline as carattere: Arial, 11 pt
measured by all color parameters at all post-baseline visits. numerati
• In general, the Colgate Simply White did not differ statistically from Baseline with the
exception of Δb* at the Week 2 visit.
• The Experimental Film provided significant whitening improvement relative to Colgate
Simply White for all comparisons of interest and all color parameters. Whitening benefit
for the Experimental Film group improved slightly after 2 weeks of treatment, in contrast,
whitening benefit for the Colgate Simply White relapsed by Week 3 and rebounded for
subjects completing the study at 1 week post-treatment (Week 4).
• Both products were generally well tolerated overall.
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11 pt
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Formattato: Tipo di
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Tables and Figures Formattato: Tipo di
carattere: Arial
Formattato: Tipo di
TABLE 1
SUBJECT DISPOSITION
a,b
NUMBER OF SUBJECTS ENROLLED AT EACH VISIT
VISIT COLGATE SIMPLY WHITE EXPERIMENTAL FILM OVERALL
Baseline 25 25 50
Week 2 25 22 47
Week 3 25 22 47
Week 4 25 22 47
a
See Appendices 2.1 for data listing and evaluability memo for details.
b
Randomization to treatment occurred after the Baseline visit and prior to product distribution.
c
Fifty-one subjects were screened, however, Subject 3021 was dropped from the study at Baseline
due to investigator recommendation. Fifty subjects were enrolled and randomized to treatment,
and 47 subjects received product.
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TABLE 2
a
SUMMARY OF EVALUABLE SUBJECT POPULATION
EVALUABLE NON-EVALUABLE
VISIT/ NO. NO. % NO. %
TREATMENT GROUP SUBJ. SUBJ. SUBJ.b SUBJ. SUBJ.b
BASELINE Formattato: Tipo di
Colgate Simply White 25 25 100.0 0 0.0 Formattato: Tipo di
carattere: Arial
Experimental Film 22 22 100.0 0 0.0
Formattato: Tipo di
carattere: Arial
Overall 47 47 100.0 0 0.0
Formattato: Tipo di
WEEK 2 carattere: Arial
Formattato: Tipo di
Colgate Simply White 25 23 92.0 2 8.0 carattere: (Predefinito) Arial
Experimental Film 22 20 90.9 2 9.1 Formattato: Tipo di
carattere: Arial
Overall 47 43 91.5 4 8.5 Formattato: Tipo di
carattere: Arial
WEEK 3
Formattato: Tipo di
Colgate Simply White 25 23 92.0 2 8.0 carattere: Arial
Formattato: Tipo di
Experimental Film 22 21 95.5 1 4.5 carattere: (Predefinito) Arial
Overall 47 44 93.6 3 6.4 Formattato: Tipo di

carattere: Arial
WEEK 4 Formattato: Tipo di
carattere: Arial
Colgate Simply White 25 18 72.0 7 28.0
Formattato: Tipo di
Experimental Film 22 21 95.5 1 4.5 carattere: (Predefinito) Arial
Formattato: Tipo di
Overall 47 39 83.0 8 17.0 carattere: Arial
See Appendices 3.1 and 4.1 for the statistical analysis program and output, respectively.
b
Percent of subjects evaluable or non-evaluable out of the number of subjects treated. Formattato: Tipo di
Formattato: Tipo di
carattere: Arial
Formattato: Tipo di
carattere: Arial
Formattato: Tipo di
carattere: Arial
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TABLE 3
LISTING OF SUBJECTS EXCLUDED FROM EVALUABLE POPULATIONa,b
TREATMENT/ NON-EVALUABLE
c REASON(S)
SUBJECT NO. VISIT(S)
COLGATE SIMPLY WHITE
3002 Week 3 Missed Visit
3024 Week 4 Lost to Follow-up
3045 Week 2+ Lost to Follow-up
EXPERIMENTAL FILM
3016 Week 2+ Lost to Follow-up
a
See Appendix 2.1 for the data listing and evaluability memo for details.
b
Three subjects failed to present for product distribution visit: Subject 3007 voluntarily withdrew
from the study, Subjects 3013 and 3041 were lost to follow-up.
c
“+” indicates that the subject was excluded from the evaluable population at the indicated visit
and all subsequent visits.
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Formattato: Tipo di
TABLE 4 carattere: (Predefinito) Arial
BASELINE DEMOGRAPHIC CHARACTERISTICSa,b

ALL SUBJECTS TREATED
COLGATE EXPERIMENTAL
BASELINE SIMPLY WHITE FILM OVERALL TWO-
c c c
CHARACTERISTIC/ (n = 25) (n = 22) (n = 47) SIDED
STATISTIC p-VALUE
AGE (YEARS)
Mean (SD) 36.9 (13.02) 32.6 (11.72) 34.9 (12.48) 0.2446 f Formattato: Tipo di
carattere: Arial
Minimum-Maximum 21 - 65 22 - 70 21 - 70
Formattato: Tipo di
SEX carattere: Arial
Female d 15 (60.0%) 15 (68.2%) 30 (63.8%) 0.7617 g Formattato: Tipo di
Male d 10 (40.0%) 7 (31.8%) 17 (36.2%) carattere: (Predefinito) Arial
RACE Formattato: Tipo di
carattere: Arial
Asian d 1 (4.0%) 2 (9.1%) 3 (6.4%) 0.9463 g
Formattato: Tipo di
Black d 7 (28.0%) 5 (22.7%) 12 (25.5%) carattere: Arial
Caucasian d 15 (60.0%) 13 (59.1%) 28 (59.6%) Formattato: Tipo di
Hispanic d 1 (4.0%) 1 (4.5%) 2 (4.3%) carattere: (Predefinito) Arial
Multi - racial d 1 (4.0%) 1 (4.5%) 2 (4.3%) Formattato: Tipo di
carattere: Arial
SMOKER
Formattato: Tipo di
No d 22 (88.0%) 20 (90.9%) 42 (89.4%) 1.0000 g carattere: Arial
Yes d 3 (12.0%) 2 (9.1%) 5 (10.6%) Formattato: Tipo di
COFFEE/TEA/COLA carattere: (Predefinito) Arial
e
DRINKER Formattato: Tipo di
carattere: Arial
No d 2 (8.0%) 3 (13.6%) 5 (10.6%) 0.6536 g
Formattato: Tipo di
Yes d 23 (92.0%) 19 (86.4%) 42 (89.4%) carattere: Arial
NUMBER OF DRINKS PER Formattato: Tipo di
DAY carattere: Arial
Median 2.0 2.0 2.0 0.7502 h Formattato: Tipo di
Minimum-Maximum 0-8 0 - 14 0 - 14
See Appendices 2.1, 3.2, and 4.2 for the data listing, statistical analysis program, and output, respectively. carattere: Arial
b
Demographics were collected at the baseline visit. Formattato: Tipo di
c carattere: Arial
n = number of treated subjects in each treatment group and overall.
d Formattato: Tipo di
Number and percent of subjects in each category. carattere: Arial
e
A drink consists of a cup for coffee or tea or a 12 ounce can of dark cola. Formattato: Tipo di
f carattere: (Predefinito) Arial
Two-sided p-value for the treatment comparison from a two-sample t-test.
g Formattato: Tipo di
Two-sided p-value for the treatment comparison from Fisher's Exact test. carattere: Arial
h
Two-sided p-value for the treatment comparison from an exact Wilcoxon rank-sum test. Formattato: Tipo di
Formattato: Tipo di
carattere: Arial
Formattato: Tipo di
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Formattato: Tipo di
Tabella formattata
TABLE 5
a
DESCRIPTIVE SUMMARY
BASELINE COLOR VALUES

Formattato: Tipo di
COLOR VALUE /
N MINIMUM MEDIAN MAXIMUM MEAN (SD) P-VALUEb carattere: Arial
TREATMENT Formattato: Tipo di
b* carattere: (Predefinito) Arial
Formattato: Tipo di
17.89 carattere: Arial
Colgate Simply White 25 13.79 17.57 21.58 0.6825
(2.059) Formattato: Tipo di
17.67 carattere: (Predefinito) Arial
Experimental Film 22 15.27 17.63 20.64
carattere: Arial
L*
Formattato: Tipo di
Colgate Simply White 25 66.94 73.68 77.43 0.5026
carattere: Arial
73.67
Experimental Film 22 68.10 73.91 78.73 Formattato: Tipo di
(2.382) carattere: (Predefinito) Arial
a* Formattato: Tipo di
Colgate Simply carattere: Arial
25 5.30 6.70 9.57 6.78 (0.919) 0.3052
White Formattato: Tipo di
carattere: Arial
Experimental Film 22 4.88 6.61 7.79 6.52 (0.814) Formattato: Tipo di
W* carattere: (Predefinito) Arial
Colgate Simply 33.01 Formattato: Tipo di

25 27.58 32.18 40.25 0.5017 carattere: Arial
White (3.417)
Formattato: Tipo di
Experimental Film 22 26.95 32.67 37.60
a carattere: Arial
See Appendices 2.1, 3.3, and 4.3 for the data listing, statistical analysis program, and output, respectively.
b Formattato: Tipo di
Two-sided p-value for the treatment comparison from a two-sample t-test. carattere: (Predefinito) Arial
Formattato: Tipo di
carattere: Arial
Formattato: Tipo di
Formattato: Tipo di
carattere: Arial
Formattato: Tipo di
Formattato: Tipo di
carattere: Arial
Formattato: Tipo di
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136
Formattato: Tipo di
TABLE 6
a
DESCRIPTIVE SUMMARY
b*
EVALUABLE SUBJECTS

P-
COLOR VALUE / MEAN MINI MEDIA MAXI MEAN VALU Formattato: Tipo di
b carattere: Arial
TREATMENT N (SD) MUM N MUM (SD) E
Formattato: Tipo di
23 17.69 - -0.370 0.67 -0.257 0.030 Formattato: Tipo di

Colgate carattere: (Predefinito) Arial
(2.097) 1.21 2 (0.532) 5
Simply White Formattato: Tipo di
4 carattere: Arial
20 17.14 - -0.529 0.11 -0.660 <
Experimental Formattato: Tipo di
(1.484) 1.93 7 (0.592) 0.000 carattere: (Predefinito) Arial
Film
5 1 Formattato: Tipo di
carattere: Arial
WEEK 3
Formattato: Tipo di
23 17.84 - -0.270 0.86 -0.135 0.221 carattere: Arial
Colgate
(2.094) 1.15 0 (0.516) 1 Formattato: Tipo di
Simply White
3 carattere: (Predefinito) Arial
21 16.95 - -0.636 0.77 -0.677 0.000 Formattato: Tipo di

Experimental carattere: Arial
(1.466) 2.17 5 (0.682) 2
Film Formattato: Tipo di
4 carattere: (Predefinito) Arial
carattere: Arial
18 17.93 - -0.260 0.68 -0.232 0.111
Colgate Formattato: Tipo di
(2.006) 1.30 5 (0.587) 5
Simply White carattere: Arial
3
Formattato: Tipo di
21 17.03 - -0.771 0.72 -0.741 0.000 carattere: (Predefinito) Arial
Experimental
(1.422) 2.07 7 (0.765) 3 Formattato: Tipo di
Film
4 carattere: Arial
See Appendices 2.1, 3.4, and 4.4 for the data listing, statistical analysis program, and output,
respectively.
Two-sided p-value for the mean color change from screening using the one-sample t-test.
Formattato: Tipo di
Formattato: Normale
Formattato: Posizione:
Orizzontale: 288 pt, Rispetto
a: Pg, Verticale: 2,15 pt,
Rispetto a: Paragrafo
137
Tabella formattata
TABLE 7
DESCRIPTIVE SUMMARYa
L*
EVALUABLE SUBJECTS
Formattato: Tipo di
carattere: Arial
Formattato: Tipo di
carattere: Arial
COLOR VALUE / MEAN MINIMU MAXIMU MEAN P-
TREATMENT N (SD) M MEDIAN M (SD) VALUE
Colgate Simply 23 73.14 -1.242 0.058 0.864 0.046 0.7189
Formattato: Tipo di
White (3.142) (0.600) carattere: Arial
Experimental 20 74.19 -0.126 0.869 1.554 0.702 < Formattato: Tipo di
Film (2.124) (0.534) 0.0001 carattere: (Predefinito) Arial

carattere: Arial
Colgate Simply 23 73.15 -0.886 0.137 1.071 0.141 0.1477 Formattato: Tipo di
White (3.145) (0.452) carattere: (Predefinito) Arial
Experimental 21 74.65 -0.172 1.149 3.019 1.079 < Formattato: Tipo di

carattere: Arial
Film (2.430) (0.745) 0.0001
Formattato: Tipo di
WEEK 4 carattere: (Predefinito) Arial
Colgate Simply 18 73.74 -1.291 0.420 1.081 0.264 0.0575 Formattato: Tipo di
Formattato: Tipo di
Experimental 21 74.49 0.160 0.903 2.463 1.064 < carattere: (Predefinito) Arial
Film (2.111) (0.638) 0.0001
Formattato: Tipo di
a
b
Two-sided p-value for the mean color change from screening using the one-sample t-test. Formattato: Tipo di
Formattato: Tipo di
carattere: Arial
Formattato: Tipo di
Formattato: Tipo di
138
Formattato: Tipo di
TABLE 8
Tabella formattata
DESCRIPTIVE SUMMARYa
a*
EVALUABLE SUBJECTS

COLOR VALUE / MINIMU MAXIMU P-
b
TREATMENT N MEAN (SD) M MEDIAN M MEAN (SD) VALUE

carattere: Arial
Colgate Simply 23 6.71 -0.943 -0.084 0.356 -0.151 0.0163 Formattato: Tipo di
Experimental 20 6.15 -0.871 -0.472 0.125 -0.398 < Formattato: Tipo di

Film (0.786) (0.310) 0.0001
Formattato: Tipo di
carattere: Arial
White (0.913) (0.293)
Formattato: Tipo di
Experimental 21 6.25 -0.666 -0.315 0.533 -0.252 0.0025 carattere: (Predefinito) Arial
Film (0.790) (0.333) Formattato: Tipo di
Formattato: Tipo di
Colgate Simply 18 6.80 -1.026 -0.094 0.287 -0.136 0.0836 carattere: (Predefinito) Arial
White (0.926) (0.314)
Formattato: Tipo di
Experimental 21 6.18 -1.132 -0.428 0.290 -0.370 0.0003 carattere: Arial
Film (0.790) (0.382) Formattato: Tipo di
a carattere: (Predefinito) Arial
Two-sided p-value for the mean color change from screening using the one-sample t-test. carattere: Arial
Formattato: Tipo di
Formattato: Tipo di
carattere: Arial
Formattato: Tipo di
Formattato: Tipo di
carattere: Arial
Formattato: Tipo di
Formattato: Tipo di
139
Tabella formattata
TABLE 9
a
DESCRIPTIVE SUMMARY
W*
EVALUABLE SUBJECTS

COLOR VALUE / MINIMU MAXIMU P-
b
TREATMENT N MEAN (SD) M MEDIAN M MEAN (SD) VALUE Formattato: Tipo di
carattere: Arial
WEEK 2
Formattato: Tipo di
Colgate Simply 23 32.88 -1.234 -0.270 0.927 -0.212 0.0992 carattere: Arial
White (3.638) (0.591) Formattato: Tipo di
20 31.64 -2.280 -0.833 -0.128 -1.012 <
Experimental Film Formattato: Tipo di
(2.060) (0.694) 0.0001 carattere: (Predefinito) Arial
carattere: Arial
Colgate Simply 23 32.98 -1.145 -0.227 0.744 -0.199 0.0724
White (3.637) (0.505) Formattato: Tipo di
21 31.18 -3.530 -1.232 -0.026 -1.302 <
Experimental Film Formattato: Tipo di
(2.447) (0.879) 0.0001 carattere: Arial

21 31.33 -2.704 -1.221 -0.090 -1.348 < Formattato: Tipo di
Experimental Film carattere: (Predefinito) Arial
(2.077) (0.825) 0.0001
b
Two-sided p-value for the mean color change from screening using the one-sample t-test. Formattato: Tipo di
Formattato: Tipo di
carattere: Arial
Formattato: Tipo di
Formattato: Tipo di
carattere: Arial
Formattato: Tipo di
Formattato: Tipo di
140
Tabella formattata
TABLE 10
a
DESCRIPTIVE SUMMARY
ΔE*
EVALUABLE SUBJECTS

COLOR VALUE /
b
TREATMENT N MINIMUM MEDIAN MAXIMUM MEAN (SD) P-VALUE

carattere: Arial
23 0.107 0.759 1.706 0.796 < 0.0001
Colgate Simply White Formattato: Tipo di
(0.392) carattere: Arial
20 0.238 1.099 2.371 1.172 < 0.0001 Formattato: Tipo di
Experimental Film carattere: (Predefinito) Arial
(0.656)
Formattato: Tipo di
Colgate Simply White carattere: (Predefinito) Arial
(0.309)
Formattato: Tipo di
21 0.342 1.353 3.534 1.463 < 0.0001
Experimental Film carattere: Arial
(0.809)
Formattato: Tipo di

Colgate Simply White carattere: Arial
(0.415)
Formattato: Tipo di
21 0.271 1.272 2.815 1.501 < 0.0001 carattere: (Predefinito) Arial
Experimental Film
a carattere: Arial
Two-sided p-value for the mean color change from screening using the one-sample t-test.
Formattato: Tipo di
carattere: Arial
Formattato: Tipo di
Formattato: Tipo di
141
Formattato: Tipo di
TABLE 11
TREATMENT COMPARISONS
a
ANALYSIS OF COVARIANCE
MEAN b* ADJUSTED FOR BASELINE AND AGE
EVALUABLE SUBJECTS
TREATMENT COMPARISON
ADJUSTED MEAN TREATMENT
VISIT/ BASELINE CHANGE FROM DIFFERENCE
b
TREATMENT GROUP N MEAN (SE) BASELINE (SE) (SE) p-VALUEc
Colgate Simply White 23 17.948 (0.446) -0.230 (0.116) 0.462 (0.173) 0.0109 Formattato: Tipo di
carattere: Arial
Experimental Film 20 17.805 (0.356) -0.691 (0.124)
Formattato: Tipo di
Formattato: Tipo di
Colgate Simply White 23 17.974 (0.443) -0.111 (0.123) 0.594 (0.180) 0.0021 carattere: Arial
Formattato: Tipo di
Experimental Film 21 17.629 (0.355) -0.705 (0.129) carattere: Arial

carattere: Arial
carattere: Arial
Experimental Film 21 17.775 (0.340) -0.788 (0.140) Formattato: Tipo di
a carattere: Arial
Means adjusted for baseline b* value and age. carattere: (Predefinito) Arial
c
Two-sided p-value for the treatment comparison of the difference in mean change of Δb*. Formattato: Tipo di
carattere: Arial
Formattato: Tipo di
Formattato: Tipo di
Formattato: Tipo di
142
Formattato: Tipo di
TABLE 12
a
MEAN L* ADJUSTED FOR BASELINE AND AGE
EVALUABLE SUBJECTS
b
TREATMENT GROUP N MEAN (SE) BASELINE (SE) (SE) p-VALUEc
Colgate Simply White 23 73.092 (0.638) 0.053 (0.123) -0.640 (0.183) 0.0012 Formattato: Tipo di
carattere: Arial
Experimental Film 20 73.490 (0.489) 0.693 (0.132)
Formattato: Tipo di
Formattato: Tipo di
Colgate Simply White 23 73.004 (0.627) 0.149 (0.131) -0.922 (0.192) < 0.0001 carattere: Arial
Formattato: Tipo di
Experimental Film 21 73.566 (0.522) 1.071 (0.137) carattere: Arial

carattere: Arial
carattere: Arial
Experimental Film 21 73.428 (0.469) 1.065 (0.135) Formattato: Tipo di
a carattere: Arial
Means adjusted for baseline L* value and age. carattere: (Predefinito) Arial
c
Two-sided p-value for the treatment comparison of the difference in mean change of ΔL*. Formattato: Tipo di
carattere: Arial
Formattato: Tipo di
Formattato: Tipo di
Formattato: Tipo di
143
TABLE 13
a
MEAN a* ADJUSTED FOR BASELINE AND AGE
EVALUABLE SUBJECTS
b c
TREATMENT GROUP N MEAN (SE) BASELINE (SE) (SE) p-VALUE
carattere: Arial
Formattato: Tipo di
Formattato: Tipo di
Formattato: Tipo di

carattere: Arial
carattere: Arial
a carattere: Arial
Means adjusted for baseline a* value and age. carattere: (Predefinito) Arial
c
Two-sided p-value for the treatment comparison of the difference in mean change of Δa*. Formattato: Tipo di
carattere: Arial
Formattato: Tipo di
Formattato: Tipo di
Formattato: Tipo di
144
TABLE 14
a
MEAN W* ADJUSTED FOR BASELINE AND AGE
EVALUABLE SUBJECTS
b c
TREATMENT GROUP N MEAN (SE) BASELINE (SE) (SE) p-VALUE
carattere: Arial
Formattato: Tipo di
Formattato: Tipo di
Colgate Simply White 23 33.178 (0.730) -0.188 (0.152) 1.125 (0.222) < 0.0001 carattere: Arial
Formattato: Tipo di

carattere: Arial
Colgate Simply White 18 32.910 (0.842) -0.325 (0.158) 1.060 (0.217) < 0.0001 Formattato: Tipo di
carattere: Arial
a carattere: Arial
Means adjusted for baseline W* value and age. carattere: (Predefinito) Arial
c
Two-sided p-value for the treatment comparison of the difference in mean change of ΔW*. Formattato: Tipo di
carattere: Arial
Formattato: Tipo di
Formattato: Tipo di
Formattato: Tipo di
145
TABLE 15
a
MEAN ΔE* ADJUSTED FOR BASELINE AND AGE
EVALUABLE SUBJECTS
MEAN CHANGE
VISIT/ FROM BASELINE TREATMENT
TREATMENT GROUP N (SE) DIFFERENCE (SE) p-VALUEb
Colgate Simply White 23 0.773 (0.112) -0.426 (0.168) 0.0154 Formattato: Tipo di
carattere: Arial
Experimental Film 20 1.199 (0.120)
Formattato: Tipo di
carattere: Arial
WEEK 3
Formattato: Tipo di
Colgate Simply White 23 0.692 (0.129) -0.772 (0.190) 0.0002 carattere: Arial
Formattato: Tipo di
Experimental Film 21 1.464 (0.136) carattere: Arial

carattere: Arial
Colgate Simply White 18 0.788 (0.160) -0.746 (0.222) 0.0020 Formattato: Tipo di
carattere: Arial
Experimental Film 21 1.534 (0.147) Formattato: Tipo di
a carattere: Arial
See Appendices 2.1, 3.5, and 4.5 for the data listing, statistical analysis program, and output,
respectively. Formattato: Tipo di
b carattere: (Predefinito) Arial
Means adjusted for baseline b*, L*, and a* values as well as age.
Formattato: Tipo di
c Two-sided p-value for the treatment comparison of the difference in mean change of ΔE * . carattere: Arial
Formattato: Tipo di
Formattato: Tipo di
Formattato: Tipo di
146
Formattato: Distanza piè di
pagina dal bordo: 57,6 pt
Formattato: Tipo di
TABLE 16 carattere: (Predefinito) Arial
END-OF-TREATMENT COMPARISONS – ANALYSIS OF COVARIANCE a
EXPERIMENTAL FILM AT WEEK 4 VS COLGATE SIMPLY WHITE AT WEEK 3 Formattato: Tipo di
ADJUSTED FOR BASELINE AND AGE
Formattato: Tipo di
EVALUABLE SUBJECTS carattere: Arial
TREATMENT COMPARISON Formattato: Tipo di
carattere: Arial
CHANGE FROM DIFFERENCE Formattato: Tipo di
VISIT/ BASELINE carattere: (Predefinito) Arial
TREATMENT GROUP N MEAN (SE) BASELINE (SE)b (SE) p-VALUEc
Formattato: Tipo di
Δb* carattere: Arial
Formattato: Tipo di

ΔL* Formattato: Tipo di
carattere: Arial
Colgate Simply White 23 73.004 (0.627) 0.145 (0.118) -0.916 (0.173) < 0.0001 Formattato: Tipo di
Experimental Film 21 73.428 (0.469) 1.061 (0.124)
Formattato: Tipo di
Δa* carattere: Arial
Colgate Simply White 23 6.847 (0.192) -0.010 (0.070) 0.384 (0.102) 0.0005
Experimental Film 21 6.553 (0.179) -0.394 (0.073) Formattato ... [127]
Formattato
ΔW* ... [128]
Colgate Simply White 23 33.178 (0.730) -0.172 (0.142) 1.205 (0.208) < 0.0001 Formattato ... [130]
ΔE*
Colgate Simply White 23 0.670 (0.131) -0.855 (0.193) < 0.0001 Formattato ... [134]
Experimental Film 21 1.526 (0.137) Formattato ... [135]
a Formattato ... [136]
b Formattato ... [137]
Means adjusted for baseline color and age.
c Formattato ... [138]
Two-sided p-value for the treatment comparison of the difference in mean color change from baseline.
147
Formattato: Tipo di
TABLE 17 Formattato: Tipo di

ADDITIONAL TREATMENT COMPARISONS – ANALYSIS OF COVARIANCE a
Formattato: Tipo di
EXPERIMENTAL FILM AT WEEK 2 VS COLGATE SIMPLY WHITE AT WEEK 3 carattere: Arial
ADJUSTED FOR BASELINE AND AGE Formattato: Tipo di
EVALUABLE SUBJECTS carattere: Arial
TREATMENT COMPARISON Formattato: Tipo di

ADJUSTED MEAN TREATMENT Formattato: Tipo di
VISIT/ BASELINE CHANGE FROM DIFFERENCE carattere: Arial
TREATMENT GROUP N MEAN (SE) BASELINE (SE)b (SE) p-VALUEc Formattato: Tipo di
carattere: Arial
Δb*
Formattato: Tipo di
Colgate Simply White 23 17.974 (0.443) -0.108 (0.114) 0.583 (0.170) 0.0014 carattere: (Predefinito) Arial
Formattato: Tipo di
ΔL* Formattato: Tipo di

carattere: Arial
Experimental Film 20 73.490 (0.489) 0.690 (0.114) Formattato: Tipo di
carattere: Arial
Δa*
Formattato: Tipo di
Colgate Simply White 23 6.847 (0.192) -0.014 (0.062) 0.405 (0.093) < 0.0001 carattere: (Predefinito) Arial
Formattato: Tipo di
Formattato
ΔW* ... [147]
Colgate Simply White 23 33.178 (0.730) -0.185 (0.129) 0.843 (0.192) < 0.0001 Formattato ... [149]
ΔE*
Colgate Simply White 23 0.683 (0.106) -0.501 (0.159) 0.0032 Formattato ... [153]
Experimental Film 20 1.183 (0.114) Formattato ... [154]
a Formattato ... [155]
b Formattato ... [156]
Means adjusted for baseline color and age.
c Formattato ... [157]
Two-sided p-value for the treatment comparison of the difference in mean color change from baseline.
148
Formattato: Superiore: 108
pt, In basso: 108 pt,
Larghezza 612 pt, Altezza: 792
pt, Distanza piè di pagina dal
bordo: 57,6 pt
TABLE 18.1
POSSIBLE OR PROBABLE TREATMENT RELATED (BY WEEK 4) Formattato: Tipo di
ORAL IRRITATION OR TOOTH SENSITIVITY
Tabella formattata
COLGATE SIMPLY EXPERIMENTAL OVERALL

WHITE FILM (n = 47)b
b b
(n = 25) (n = 22)
AE SOURCE/AE NO. SUBJ. (% NO. SUBJ. (% NO. SUBJ. (%
CLASSIFICATION SUBJ.)c SUBJ.)c SUBJ.)c
SELF REPORTED
Formattato: Tipo di
Oral Irritation 0 (0) 8 (36.4) 8 (17.0) carattere: Arial
Tooth Sensitivity 0 (0) 4 (18.2) 4 (8.5) Formattato: Tipo di

carattere: Arial
Oral Irritation and Formattato: Tipo di
0 (0) 2 (9.1) 2 (4.3)
Tooth Sensitivity carattere: Arial
Oral Irritation or Tooth Formattato: Tipo di

0 (0) 10 (45.5) 10 (21.3) carattere: Arial
Sensitivity
OBSERVED Formattato: Tipo di
carattere: Arial
Oral Irritation 0 (0) 1 (4.5) 1 (2.1) Formattato: Tipo di
carattere: Arial
EITHER OBSERVED OR
Formattato: Tipo di
SELF REPORTED carattere: Arial
Oral irritation 0 (0) 8 (36.4) 8 (17.0) Formattato: Tipo di

carattere: Arial
Tooth Sensitivity 0 (0) 4 (18.2) 4 (8.5) Formattato: Tipo di
carattere: Arial
Oral irritation and
0 (0) 2 (9.1) 2 (4.3) Formattato: Tipo di
Tooth Sensitivity carattere: Arial
Oral irritation or Tooth Formattato: Tipo di
0 (0) 10 (45.5) 10 (21.3)
Sensitivity carattere: Arial
a Tabella formattata
See Appendices 2.1, 3.8, and 4.8 for the data listing, statistical analysis program, and
output, respectively.
b
Number of subjects randomized in each group and overall.
c Formattato: Posizione:
Number (Percent) of randomized subjects with the indicated AE (out of the number reported Orizzontale: 288 pt, Rispetto
in each group). a: Pg, Verticale: 2,15 pt,
149
Tabella formattata
Formattato: Tipo di
TABLE 18.2 carattere: Arial
POSSIBLE OR PROBABLE TREATMENT RELATED (BY WEEK 2) Formattato: Tipo di

a carattere: Arial
ORAL IRRITATION OR TOOTH SENSITIVITY
Formattato: Tipo di
ALL SUBJECTS TREATED carattere: (Predefinito) Arial
Formattato: Tipo di
COLGATE SIMPLY EXPERIMENTAL OVERALL carattere: (Predefinito) Arial
b
WHITE FILM (n = 47) Formattato: Tipo di
(n = 25)b (n = 22)b carattere: Arial
Formattato: Tipo di
AE SOURCE/AE CLASSIFICATION NO. SUBJ. (% SUBJ.)c NO. SUBJ. (% NO. SUBJ. (% carattere: (Predefinito) Arial
c c
SUBJ.) SUBJ.) Formattato: Tipo di
carattere: Arial
SELF REPORTED
Formattato: Tipo di
Oral Irritation 0 (0) 2 (9.1) 2 (4.3) carattere: (Predefinito) Arial
Formattato: Tipo di
Tooth Sensitivity 0 (0) 2 (9.1) 2 (4.3) carattere: Arial
Oral Irritation and Tooth Formattato: Tipo di
0 (0) 0 (0) 0 (0) carattere: Arial
Sensitivity
Formattato: Tipo di
Oral Irritation or Tooth carattere: (Predefinito) Arial
0 (0) 4 (18.2) 4 (8.5)
Sensitivity Formattato: Tipo di
OBSERVED carattere: (Predefinito) Arial
Formattato: Tipo di
Oral Irritation 0 (0) 1 (4.5) 1 (2.1) carattere: Arial
EITHER OBSERVED OR SELF Formattato: Tipo di

carattere: Arial
REPORTED
Formattato: Tipo di
Oral irritation 0 (0) 2 (9.1) 2 (4.3) carattere: (Predefinito) Arial
Formattato: Tipo di
Tooth Sensitivity 0 (0) 2 (9.1) 2 (4.3) carattere: Arial
Oral irritation and Tooth Formattato: Tipo di
0 (0) 0 (0) 0 (0) carattere: (Predefinito) Arial
Sensitivity
Formattato: Tipo di
Oral irritation or Tooth
0 (0) 4 (18.2) 4 (8.5) carattere: (Predefinito) Arial
Sensitivity
Formattato: Tipo di
a carattere: Arial
Number of subjects randomized in each group and overall.
c
Number (Percent) of randomized subjects with the indicated AE (out of the number reported in each group). Formattato ... [166]
150
Tabella formattata
TABLE 19.1
a
SUMMARY OF ADVERSE EVENTS (BY WEEK 4)
COLGATE SIMPLY EXPERIMENTAL FILM OVERALL
WHITE (n = 22)b (n = 47)b
b
(n = 25)
NO. NO. AES NO. NO. AES NO. SUBJ. NO. AES
d
SUBJ. (% SUBJ. (% (% (% AES)
(% AES)d (% AES)d SUBJ.) c
c c
SUBJ.) SUBJ.)
Formattato: Tipo di
Serious AEs 0(0) 0(0) 0(0) 0(0) 0(0) 0(0) carattere: Arial
Mild AEs 1(4) 1(100) 10(45) 13(100) 11(23) 14(100) Formattato: Tipo di
carattere: Arial
Moderate AEs 0(0) 0(0) 0(0) 0(0) 0(0) 0(0) Formattato: Tipo di
carattere: Arial
Severe AEs 0(0) 0(0) 0(0) 0(0) 0(0) 0(0) Formattato: Tipo di
carattere: Arial
Not Related 0(0) 0(0) 0(0) 0(0) 0(0) 0(0)
Formattato: Tipo di
Doubtful Related 1(4) 1(100) 1(5) 1(8) 2(4) 2(14) carattere: Arial
Formattato: Tipo di
Possibly Related 0(0) 0(0) 7(32) 8(62) 7(15) 8(57) carattere: Arial
Probably Related 0(0) 0(0) 4(18) 4(31) 4(9) 4(29) Formattato: Tipo di
carattere: Arial
Total 1(4) 1(100) 10(45) 13(100) 11(23) 14(100) Formattato: Tipo di
carattere: Arial
Mean number of AEs per
0.04 0.59 0.3 Formattato: Tipo di
subject (all subjects) carattere: Arial
Mean number of AEs per Formattato: Tipo di
subject (only subjects with 1 1.3 1.27 carattere: Arial
AEs) Formattato: Tipo di
a carattere: Arial
b
n = number of subjects within the specified treatment group or overall.
c
Number (Percent) of subjects with the indicated AE category (out of the number of subjects in each group).
d
Number (Percent) of AEs reported within the category (out of the total number of AEs reported in each group).
151
Tabella formattata
Formattato: Tipo di
TABLE 19.2 carattere: Arial
a
SUMMARY OF ADVERSE EVENTS (BY WEEK 2) Formattato: Tipo di
ALL SUBJECTS TREATED carattere: Arial
Formattato: Tipo di
COLGATE SIMPLY EXPERIMENTAL FILM OVERALL carattere: (Predefinito) Arial
WHITE (n = 22)b (n = 47)b Formattato: Tipo di
b
(n = 25) carattere: Arial
NO. SUBJ. NO. AES NO. NO. AES NO. SUBJ. NO. AEFormattato:
S Tipo di
carattere:
d (Predefinito) Arial
(% (% SUBJ. (% (% (% AES)
Formattato: Tipo di
SUBJ.)c AES)d (% AES)d SUBJ.)c carattere: Arial
c
SUBJ.)
Formattato: Tipo di
Serious AEs 0(0) 0(0) 0(0) 0(0) 0(0) 0(0) carattere: (Predefinito) Arial
Formattato: Tipo di
Mild AEs 0(0) 0(0) 5(23) 5(100) 5(11) 5(100)carattere: Arial
Moderate AEs 0(0) 0(0) 0(0) 0(0) 0(0) 0(0) Formattato: Tipo di
Severe AEs 0(0) 0(0) 0(0) 0(0) 0(0) 0(0) Formattato: Tipo di
carattere: Arial
Not Related 0(0) 0(0) 0(0) 0(0) 0(0) 0(0) Formattato: Tipo di
Doubtful Related 0(0) 0(0) 1(5) 1(20) 1(2) 1(20)
Formattato: Tipo di
Possibly Related 0(0) 0(0) 0(0) 0(0) 0(0) 0(0) carattere: Arial
Formattato: Tipo di
Probably Related 0(0) 0(0) 4(18) 4(80) 4(9) 4(80) carattere: (Predefinito) Arial
Total 0(0) 0(0) 5(23) 5(100) 5(11) 5(100)Formattato: Tipo di
carattere: Arial
0 0.23 0.11
subject (all subjects) carattere: (Predefinito) Arial
carattere: Arial
subject (only subjects with 0 1 1
AEs) Formattato: Tipo di
n = number of subjects within the specified treatment group or overall. carattere: (Predefinito) Arial
c
Number (Percent) of subjects with the indicated AE category (out of the number of subjects in each group). Formattato: Tipo di
d carattere: Arial
Formattato: Tipo di
152
TABLE 20
ADVERSE EVENTS IN DECREASING ORDER OF INCIDENCE
a
BY COSTART PREFERRED TERM AND TREATMENT GROUP
b b
WHITE (n = 22) (n = 47)
b
COSTART (n = 25)
PREFERRED TERM NO. SUBJ. NO. AES NO. SUBJ. NO. AES NO. SUBJ. NO. AES
(% SUBJ.)c (% AES)d (% SUBJ.)c (% AES)d (% SUBJ.)c (% AES)d
Formattato: Tipo di
GINGIVITIS 1(4) 1(100) 6(27) 6(46) 7(15) 7(50) carattere: Arial
HYPERESTHESIA 0(0) 0(0) 5(23) 5(38) 5(11) 5(36) Formattato: Tipo di

carattere: Arial
CHEILITIS 0(0) 0(0) 1(5) 1(8) 1(2) 1(7) Formattato: Tipo di
carattere: Arial
STOMATITIS 0(0) 0(0) 1(5) 1(8) 1(2) 1(7)
Formattato: Tipo di
carattere: Arial
Formattato: Tipo di
TOTAL 1(4) 1(100) 10(45) 13(100) 11(23) 14(100) carattere: Arial
a
See Appendices 2.1, 3.12, and 4.12 for the data listing, statistical analysis program, and output, respectively. Formattato: Tipo di
b carattere: Arial
c
d
153
TABLE 21
MILD ADVERSE EVENTS
a
b b
WHITE (n = 22) (n = 47)
b
COSTART (n = 25)
(% SUBJ.)c (% AES)d (% SUBJ.)c (% AES)d (% (% AES)d
c
SUBJ.)
Formattato: Tipo di

carattere: Arial
carattere: Arial
STOMATITIS 0(0) 0(0) 1(5) 1(8) 1(2) 1(7)
Formattato: Tipo di
carattere: Arial
Formattato: Tipo di
a
b carattere: Arial
n = number of subjects within the specified treatment group or overall .
c
d
154
TABLE 22
NOT OR DOUBTFUL TREATMENT RELATED ADVERSE EVENTS
a
ALL EVALUABLE SUBJECTS
b b
WHITE (n = 22) (n = 47)
COSTART (n = 25)b
c d c d c d
(% SUBJ.) (% AES) (% SUBJ.) (% AES) (% SUBJ.) (% AES)
Formattato: Tipo di

carattere: Arial
Formattato: Tipo di
carattere: Arial
TOTAL 1(4) 1(100) 1(5) 1(8) 2(4) 2(14)
b
c
d
Formattato: Tipo di
Formattato: Normale
155
TABLE 23
POSSIBLE OR PROBABLE TREATMENT RELATED ADVERSE EVENTS
a
b b
WHITE (n = 22) (n = 47)
b
COSTART (n = 25)
(% SUBJ.)c (% AES)d (% SUBJ.)c (% AES)d (% SUBJ.)c (% AES)d
Formattato: Tipo di

carattere: Arial
carattere: Arial
STOMATITIS 0(0) 0(0) 1(5) 1(8) 1(2) 1(7)
Formattato: Tipo di
carattere: Arial
Formattato: Tipo di
a
b carattere: Arial
c
d
156
Figure 1: Adjusted Mean Yellowness Improvement (–Δb*)
0.8
0.6
0.4
0.2
0
Week 2 Week 3 Week 4
C olgate Sim ply White Experim ental Film
Figure 2: Adjusted Mean Lightness Improvement (ΔL*)
1.2
0.8
0.6
0.4
0.2
0
Week 2 Week 3 Week 4
C olgate Sim ply White Experim ental Film
Eliminato: 214¶
156
1. HaywoodVB, Heymann HO. Nightguard vital bleaching. Quintessence Int.

1989; 20:173-6
2. Goldstein RE.In-office bleaching: where we came from, where we are today. Jam Dent
Assoc1997;128:11S-15S
3. BurrellKH.ADA supports vital tooth bleaching –but look for the seal. J Am Dent
Assoc1997 128:3S-5S.
4. CrollTP, SasaIS.Carbemide peroxide of teeth with dentiogenisis imperfecta
discoloration: report of a case. Quintessence Int. 1995; 26:683-6
5. Haywood VB. Night guard bleaching to lighten a restored, nonvital discolored tooth.
Compend Continuing Education Dent 1998;19:810-3
6. Frazier KB. Nightguard bleaching to lighten a restored, nonvital discolored tooth.
Compend Contin Educ Dent 1998; 19:810-3
7. Small BW. The application and integration of at-home bleaching into private dental
practice. Compend Contin Educ Dent 1998;19:799-806
8. HaywoodVB, Robinson FG.Vital tooth bleaching with nightgaurd vital bleaching.
Curr.Opin CosmeticDent1997;4:45-52
9. KugelG,PerryRD, Hoang E,Scherer W.Effective tooth bleaching in 5days: using a
combined in office and at home bleaching system . Comp contin Educ Dent
1997 ;18:378-83
10. Kugel G Over the counter tooth whitening Systems Compendium April 2003; 24;4A
376-82
11. Donly KJ, DonlyAS, BaharlooL, et al. Tooth whitening in children, Compend Contin
Edu Dent. 2002; 3:22-27.
Eliminato: 214¶
157
Chapter 9
Maintenance of Whitening
Clinical Study to Evaluate the Maintenance of Whitening after Bleaching Treatment
Abstract
Formattato: Interlinea doppia
A randomized, parallel, examiner-blind clinical study was conducted to examine the ability of 2
toothbrushes to maintain teeth whitening after at-home bleaching. Forty subjects used a 15%
carbamide peroxide tray bleaching system at home for 2 weeks per the manufacturer’s instructions
and then were randomly assigned to use either the Sonicare® Advance power toothbrush or a
manual toothbrush as part of their home oral hygiene routine for 6 months. The color of the labial
surfaces of the subjects’ maxillary anterior dentition was assessed before bleaching and
immediately, 2 months, 3 months, and 6 months after bleaching. Color was assessed by
comparison with Vita® Classical shade tabs and by digital image analysis in the CIE L*a*b* color
space. Both groups demonstrated a rebound effect at the 2-month visit and beyond, with mean Vita
shade scores significantly higher than immediately after bleaching. At the 6-month evaluation, there
was a significant difference in the amount of rebound in each group. Specifically, the rebound of the
Sonicare brush group was on average 1.12 Vita shades less than that of the manual brush group.
The 6-month difference was confirmed through digital image analysis, with the Sonicare brush
group 4.8 L* units lighter, corresponding to 2 Vita shades, and 2.1 b* units less yellow than the
manual brush group. This clinical trial demonstrates that the Sonicare Advance toothbrush better
maintains whitening after bleaching treatment than a manual toothbrush.
Eliminato: 214¶
158
Learning Objectives
Formattato: Normale
After reading this article, the reader should be able to: Formattato: Interlinea doppia
Formattato: Puntato +
• Understand maintenance of whitening after bleaching using an electric toothbrush. Livello:1 + Allinea a: 18 pt +
Rientra di: 36 pt
• To demonstrate that significant rebound can occur post bleaching.
• To demonstrate the use of digital photography in determining L* a* b* values

The use of peroxide to whiten teeth has a lengthy history dating to the early 20th century. With the
advent of patient-applied kits, bleaching has become both common and popular, and use of
peroxide is now generally recognized as a safe and effective method for tooth whitening.1-3 There
are a variety of indications for bleaching single or multiple teeth, including staining from
chromogenic foods, dental fluorosis, tetracycline staining, and devital discolored teeth.4-7 Up to 90%
of U.S. dental practices offer vital tooth bleaching, and in some dental practices, up to one-fifth of
patients undergo bleaching.8-9
Concentrations of up to 35% peroxide are used alone or in combination with various agents for
tooth bleaching. Delivery is via in-office, at-home, or combination regimens, with or without
professional supervision.10,11 Of these, bleaching is most commonly accomplished at home over a
period of a few weeks.12 Treatment duration may vary based on the degree of staining because
whitening is reported to be a product of peroxide concentration and contact time.13 For some
difficult stains like tetracycline, daily bleaching for up to 6 months may be indicated.14

Treatment is generally effective, with 90% or more of clinical trial subjects experiencing initial
whitening.15,16 The efficacy of a bleaching treatment may be established through first or second
person observation or various technical methods. Clinical trials most commonly include the use of a
shade guide, colorimeter, or computer digitization to measure color change over time.17,18 In these
studies, efficacy is commonly monitored for 6 months.13,16 While there may be some shade
deterioration over time, most patients experience a whitening effect that may persist, to at least
Eliminato: 214¶
159
some degree, 3 years or more after initial treatment.13,15 In addition to the cosmetic benefits,
bleaching is believed to contribute to various intangibles, including heightened patient involvement
and increased interest in dentistry and oral health.7,8
Some patients who have undergone bleaching are concerned with the stability of their newly
bleached teeth. Practitioners often have no real answer for the patient concerning the stability of
bleached dentition. Rebound, the re-coloring of bleached teeth, is assumed to be a multifactor
process. The factors may include the structure and composition of an individual’s dentin and
enamel, the types of food and drink he or she consumes, and the oral hygiene routine. In the
current study, we examined the impact of the oral hygiene routine. Specifically, we assessed the
ability of the Sonicare® Advance powered toothbrusha to prevent rebound compared with a
standard manual toothbrush.

The Sonicare Advance toothbrush operates with high-frequency bristle movement (260 Hz; 31,000
brush strokes per minute). In addition to cleaning by direct bristle contact, the Sonicare Advance
generates significant fluid activity, which has been hypothesized as the reason for the brush’s ability
to clean beyond the reach of the bristles as demonstrated in several laboratory studies.19-22 The
Sonicare Advance also has been shown to remove stains in clinical and laboratory studies,
removing more stain in vivo than a manual toothbrush.23, 24 A study of the brush’s ability to inhibit
rebound after bleaching, a natural extension of this earlier work, was the focus of the current study.
sinistra, Interlinea doppia, Non
Methods and Materials mantenere con successivo
Population Selection
Potential subjects were screened and enrolled in this clinical trial at Tufts University, Boston,
Massachusetts, after meeting the inclusion/exclusion criteria. At screening, written informed
consent was obtained from each subject after review of the study design and test regimen. Using
the Vita® Classical shade guideb, Vita shade scores were recorded for each subject on labial Formattato: Centrato
Eliminato: 214¶
160
surfaces of the maxillary anterior teeth. Subjects with individual tooth scores of A2 or darker were
eligible for enrollment. Dentinal sensitivity, use of tobacco products, the presence of tetracycline
stain, dental fluorosis, atypical nonuniform stain, fixed orthodontic appliances, and large intake of
stain-inducing beverages were all reasons for exclusion. Subjects who qualified and agreed to
participate were enrolled in the study. At the postbleaching evaluation, subjects exhibiting a
decrease of at least 2 Vita shades were allowed to continue in the study; all subjects met this
requirement.

STUDY DESIGN
This was an examiner blind, parallel-group, 6-month study with clinical evaluations both before
(prebleaching baseline) and after (postbleaching baseline) a two-week bleaching treatment and at
one, 2, 3, and 6 months after the end of bleaching. At each visit, oral soft and hard tissues were
examined, subjects were questioned about presence or absence of tooth hypersensitivity to
thermal, air, or other such stimuli, and a Vita shade assessment of the labial surfaces of the anterior
maxillary teeth was recorded. A subset of 14 subjects, 7 per treatment group, was randomly
selected for digital image analysis. For subjects in this subset, digital images of the maxillary
anterior teeth also were captured at each visit.
At the screening appointment, impressions of the maxillary teeth were taken and used to fabricate
the bleaching trays. The trays were distributed at the first study visit, baseline prebleaching, along
with a standard home bleaching system of 15% carbamide peroxide (Opalescencec). All subjects
were given a standard manual toothbrush (Crest® Extra Softd) and sodium fluoride dentifrice (Crest
Cavity Protectiond) for use during the bleaching period. Subjects received oral and written
instructions on the bleaching system’s recommended use and the Bass brushing technique.25
Subjects were asked to use the bleaching trays twice per day for 60 minutes at each use and to
brush with the manual toothbrush twice per day for 2 minutes at each brushing. At the
postbleaching baseline appointment 2 weeks later, bleaching trays were collected and study
Eliminato: 214¶
161
toothbrushes were distributed according to a stratified randomization designed to foster similar
shade distributions at prebleaching baseline (low / medium / high Vita shade score means) in each
brush group. Subjects exhibiting a mean Vita shade score improvement of at least 2.0 were
permitted to continue in the study. Subjects in one group were asked to continue using the manual
toothbrush as previously instructed. Subjects in the other group were given a Sonicare Advance
toothbrush, instructed in its use according to the manufacturer’s instructions, and asked to use the
toothbrush with the same study dentifrice twice daily for 2 minutes at each brushing.

EFFICACY ASSESSMENTS Formattato: Interlinea doppia
Vita Shade Guide Assessment Assessments of tooth color with the Vita Classical shade guide
included the maxillary incisors. The Vita shade guide is a standard scale of multiple tooth-shaped
tabs, each having a different color. Commonly used in dentistry to match artificial crowns to the
natural dentition, the Vita shade guide has been successfully applied in clinical studies to assess
the efficacy of tooth whitening products.4,7-9
All examinations were performed under color balanced lighting conditions using diffused lighting,
with color temperature approximately 5500 K. To reduce variation, all examinations were performed
in the same operatory—and thus under the same lighting conditions—whenever possible. The
operatory colors were neutral, and both the evaluator and subject were instructed to avoid wearing
bright clothing. A blue bib was draped over all subjects, and they were instructed to remove jewelry,
eyeglasses, lipstick, and anything else that could interfere with shade selection. Without drying the
teeth, the evaluators judged tooth color by selecting the closest shade tab on the guide. Between
individual observations, the evaluators looked at a light blue card for a few seconds. Assessment of
brushing treatment efficacy was performed by a rank ordering of shade tabs arranged from dark to
light according to the rank ordering suggested by the manufacturer (Table 1).
To ensure maximum integrity of the data, only 2 evaluators performed Vita shade assessments in
the study. Before the screening visit, the clinical evaluators examined a subset of subjects for tooth Eliminato: 214¶
162
color using the Vita shade guide to establish intra-evaluator repeatability. Intra-examiner kappa
statistics at 3 months were 1.00 (95% confidence interval (CI): 0.73, 1.00) and 0.88 (95% CI: 0.62,
1.00) for the examiners, and the inter-examiner kappa for the 2 examiners was 0.88.

DIGITAL IMAGING
Formattato: Interlinea
Using existing technologies of digital photography and photographic analysis software used in the doppia, Non regolare lo spazio
tra testo asiatico e in alfabeto
latino
printing industry, it is possible to assess the color of teeth that currently cannot be matched by
existing shade guides, making it possible to assess differences as small as one-eighth of a Vita
shade.26 In recent years the CIE L*a*b* color space has been accepted as the benchmark for
assessing color.27 This space covers the entire range of color seen by the human eye. The L*a*b*
color model consists of a luminance component, L* (black to white), and 2 chromatic components,
a* (green to red) and b* (blue to yellow). Figure 1 presents the CIE L*a*b* scale as a 3-dimensional
visualization. The subjects’ baseline post bleaching and 6-month rebound images were
photographed using the same standard digital camera under lighting conditions identical to those
used during the Vita shade assessments. Subjects were positioned with the central incisal edge 9
inches from the lens of the camera, which was mounted on an axis perpendicular to the facial
surface of the central incisors. Patients were presented edge-to-edge with retractors and were
asked to touch the tip of their tongue to their soft palate. This allowed light to readily pass through
the tooth surface and reduce reflectance from the tongue. The camera’s flash unit was used to
ensure the consistency of light source and an ultraviolet filter was used on the camera to reduce
glossing, which may occur with flash usage, thereby reducing the likelihood of hot spots and
increasing the consistency of color accuracy between images. The camera was plugged into a 120-
volt power source to ensure a constant flash intensity between images. Vita Classical and 3D
Master shade guides were photographed as well, providing controls to ensure maintenance of
Eliminato: 214¶
163
photographic settings and quality and to establish a guideline for comparison between the L*a*b*
and Vita shade guide subject data collected.

Adobe Photoshop softwaree was used to generate the L*a*b* scores. To ensure accuracy, 9
locations were sampled on each of the central incisors, lateral incisors and canines of the maxillary
arch, and L*a*b* scores were generated at these points. These data were then averaged to find a
mean color and standard deviation of color on each tooth. A Gaussian blur filter set at 13 units,
which averages color over an entire photo, was then applied to the original digital image. Using this
filtering technique, 4 sampling locations were identified as optimal—the incisal-middle third and the
middle-middle third of the maxillary left central and lateral incisors—because they provided the
same information obtained from sampling the 9 locations without a filter. This allowed for faster
sampling and decreased variability in the data by moderating the color extremes.
Efficacy of the brushing treatment was made by comparison of L*a*b* scores derived from images
captured at the first post bleaching clinical visit (post bleaching baseline) and 3 and 6 months
thereafter. L* and b* are the 2 components of L*a*b* scores most recognized as being influenced
by bleaching treatment, with an increase in L* indicating lightening and a decrease in b* indicating
decreasing yellow and thus decreasing stain.

STATISTICAL ANALYSIS
The primary analysis used linear mixed effect models appropriate for a repeated measures design.
This type of analysis supports the use of incomplete cases and allows for the testing of overall
differences between brushes, overall change over time, and differences in brushes over time. The
primary Vita shade analysis focused on comparing mean Vita shade scores between treatment
groups over time. Secondary Vita shade analysis included comparisons between mean Vita shade
scores of individual teeth over time. The luminance component of the L*a*b* scores generated from
the digital images collected on the subset of 14 subjects was analyzed with 2-sample Student t-
Eliminato: 214¶
164
tests, comparing differences in L* and b* (post bleaching baseline to 6 months post bleaching)
between groups.
sinistra, Interlinea doppia
RESULTS Formattato: Interlinea doppia
A total of 43 subjects 18 years of age or older and in good health were enrolled in the study. At the doppia, Non regolare lo spazio
latino
pre-bleaching baseline examination, the groups were comparable in terms of Vita shade scores and
age (Tables 2 and 3). Three subjects did not return after the bleaching treatment and were dropped
from the study, making the total sample size 40. The study sample was composed of 23 women
and 17 men. Thirty-one subjects, 18 from the Sonicare group and 13 from the manual toothbrush
group, returned for all clinical evaluations over the course of the 6-month study. Twelve subjects, 3
from the Sonicare group and 9 from the manual toothbrush group, missed at least 1 visit over the
course of the 6-month study. The mean Vita shade scores over time overall and by individual tooth
are presented in FiFigure 2 and Figure 3, respectively.

After completion of the bleaching treatment, the average shade score in the manual toothbrush
group was approximately 1.3 Vita shades lower than that of the Sonicare group. Clearly the 2
groups responded differently to the bleaching treatment, though both were using the same
dentifrice and manual toothbrush during the bleaching process. To assess the statistical
significance of the observed difference, a 2-sample Student t-test was used to test the null
hypothesis of no difference in mean Vita score between groups after bleaching. Because the result
was not statistically significant (P = .06), the null hypothesis of no difference in mean post bleaching
shade scores between brush groups was accepted.
Results of the linear mixed effects model using the complete case data indicate a statistically
significant effect per visit. With the exception of the 1-month evaluation, all visits were found to have
significantly different mean Vita scores (1 month P = .14; 2 months P < .001; 3 months P = .013; 6
Eliminato: 214¶
165
months P < .001), relative to the first post bleaching exam. That is, for both brush groups at the 2-
month visit and beyond, mean Vita shade scores were significantly higher (darker) than
immediately after bleaching. This indicates a rebound effect after 2 months. No statistically
significant effect between groups, or brush type, was found (P = .07). This is not surprising because
the groups were designed to have similar shade levels and this tests the combined group averages
across all visits.
To determine if rebound was affected over time by brush type, the interaction of brush type and visit
was tested. A statistically significant difference was found at the 6-month evaluation (P = .04),
indicating that the brush groups rebounded differently after 6 months of brushing. On average, the
manual brush group rebound was 1.12 Vita shades greater than that of the Sonicare brush group.
The 2-sample Student t-test assessing the mean change in luminance L* between brush groups
(post bleaching baseline to 6 months post bleaching) returned a statistically significant result (P <
.001), indicating teeth darkened with the use of the manual toothbrush compared with the use of the
Sonicare toothbrush. The difference was estimated at –4.8 (95% CI: –6.5, –3.1); that is, after 6
months of toothbrush use, the manual toothbrush group mean was 4.8 L* units darker than the
Sonicare toothbrush group mean. This difference in luminance was equivalent to 2 Vita Classical
shades. The mean change in the blue-yellow axis b* also was assessed with a 2-sample Student t-
test (post bleaching baseline to 6 months post bleaching). Again, the Sonicare toothbrush group
showed a statistically significant difference from the manual toothbrush group (P < .001), indicating
less of the yellow component for the Sonicare toothbrush group. The difference between groups
was estimated at 2.1 b* units (95% CI: 0.9 to 3.2). (Table 4)
Three subjects showed signs of gingival sensitivity associated with the bleaching treatment; all
subsequently resolved with the completion of the bleaching treatment. Both brushes had excellent
safety records with no adverse events or abnormal intraoral exams reported after bleaching. Eliminato: 214¶
166
Photographs representing the type of changes observed in each group are presented in Figure 4 doppia, Non regolare lo spazio
latino
and Figure 5.

DISCUSSION
The analyses of the digital images and the Vita shade data both show the Sonicare toothbrush to
be superior to a manual toothbrush at maintaining whitening 6 months after bleaching. While this is
the first study examining the effect of Sonicare on maintaining whitening, there are other data on
the effect of a manual toothbrush. Matis and colleagues,28 for example, report an increase of 5.2 L*
units and 2.9 shade guide units only 6 weeks after a 2-week bleaching regimen using 15%
carbamide peroxide. Our results show a more modest but still measurable rebound effect for
manual brushing.
The estimated 6-month Vita shade difference between groups was larger in the digital analysis (2 doppia, Non regolare lo spazio
latino
Vita shades) than in the Vita shade analysis (1.12 Vita shades). This difference in estimates may be
the result of the varying precision and accuracy of the 2 efficacy measures. We additionally note
that the ordering of the Vita Classical shade guide does not follow the order suggested by digital
image analysis of the shade tabs. In particular, ranking the tabs by decreasing luminance L*, that is
the pure value axis of the L*a*b* color sphere, suggests not only that the color tabs are incorrectly
ordered but also that the color change between tabs is nonlinear (Figure 6). Similar observations
have been reported by O’Brien and colleagues29 and Paravina and colleagues.30 These factors also
may contribute to the difference in estimates between the 2 efficacy measures.

The choice of randomization based on pre-bleaching mean Vita scores was made after considering
the alternative of basing the randomization on the post bleaching mean Vita scores. The use of the
former generated treatment groups with similar color shade distribution before bleaching. It was
Eliminato: 214¶
167
believed that the method would produce groups with similar rebound patterns because the 2 groups
were comparable before bleaching. The latter method would have produced comparable groupings
after bleaching, but would have ignored the initial, pre-bleaching color distributions. This could have
lead to groups with different rebound responses if their initial shade colors were very different.

CONCLUSIONS
The demand for tooth bleaching products and their use by professionals and patients is increasing
every day. Treatment options include in-office bleaching, take-home bleaching, or a combination of
the 2, with or without professional supervision. The take-home system is the most convenient for
patients and professionals alike and proves to be very effective over a period of a few weeks.
Studies have shown that there is some shade rebound over time. The clinician should keep in mind
that the patient’s eating and drinking habits are likely to affect rebound as extrinsic staining can be
caused by the use of coffee, tea, tobacco, red wine, and red grapes. The patients’ main concern
after a successful bleaching treatment remains maintaining the bleached color over a period of
time. In the current study the Sonicare Advance toothbrush was proven more effective than a
manual toothbrush in maintaining the color of bleached teeth for 6 months. This finding, added to
the established record of safety, superior plaque removal, and gingivitis reduction31-33 and extrinsic
stain removal for this device, make Sonicare an excellent choice for patients interested in overall
oral health and specifically tooth whitening maintenance.
Eliminato: 214¶
168
Table 2—Ranking and Scoring of Vita Classical Shades
Shade Score sinistra, Interlinea doppia, Non
mantenere con successivo
B1– 1 Lightest Formattato: Allineato a

B1 2
A1 3
B2 4
D2 5
A2 6
C1 7
C2 8
D4 9
A3 10
D3 11
B3 12
A3.5 13
B4 14
C3 15
A4 16
C4 17 Darkest
Eliminato: 214¶
169
Table 3—Number of Subjects per Group by Visit
Manual Sonicare
Screening 22 21
Baseline prebleaching 22 21
Baseline postbleaching 19 21
1 Month 18 19
2 Months 17 19
3 Months 14 18
6 Months 13 18
Eliminato: 214¶
170
Table 4—Study Demographics (Age)
Statistic Manual Sonicare sinistra, Interlinea doppia, Non
mantenere con successivo
Minimum 20 21 Formattato: Allineato a

1st quartile 26 27
Mean 34.0 36.7
Median 29 32
3rd quartile 44 46
Maximum 51 66
N 22 21
Missing 1 0
Standard deviation 10.6 13.3
Table 5—L*a*b* Mean Differences (postbleaching baseline to 6 months)

Difference in Mean (SD)
L* a* b*
Manual Sonicare Manual Sonicare Manual Sonicare
–3.3 (3.5) 1.5 (2.9) 0.9 (1.5) 0.3 (1.4) 2.3 (2.6) 0.2 (1.6)
Eliminato: 214¶
171
Figures
+L*
–a*
–b*
CIE L*a*b*
Color Space
+b*
+a*
–L*
Figure 1—CIE L*a*b* Color Space
Eliminato: 214¶
172
Mean Vita Scores
All Teeth
Manual
8
Sonicare
7
Mean (All Teeth) Vita Score
Fi
5
4
3
0 5 10 15 20 25
# Weeks Post-Bleaching
Figure 2—Overall mean Vita scores over time.
Eliminato: 214¶
173
Mean Vita Scores Mean Vita Scores
Tooth 7 Tooth 8
8
8
Mean (Tooth 7) Vita Score

Manual Manual
Sonicare Sonicare
7
7
6
6
5
5
4
4
3
3
0 5 10 15 20 25 0 5 10 15 20 25
# Weeks Post-Bleaching # Weeks Post-Bleaching
Mean Vita Scores Mean Vita Scores

Tooth 9 Tooth 10
8
8
Manual Manual
Sonicare Sonicare
7
7
6
6
5
5
4
4
3
0 5 10 15 20 25 0 5 10 15 20 25
# Weeks Post-Bleaching # Weeks Post-Bleaching
Figure 3—Mean Vita scores by tooth over time.
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174
Formattato: Tipo di
11 pt
(a)
Formattato: Tipo di
11 pt
(b)
Formattato: Tipo di
11 pt
(c)
Figure 4—Images of a representative subject from the manual toothbrush group (a) at
screening, (b) at post bleaching baseline, (c) at 6 months after the end of bleaching.
Eliminato: 214¶
175
Formattato: Tipo di
11 pt
(a)
Formattato: Tipo di
11 pt
(b)
Formattato: Tipo di
11 pt
(c)
Figure 5—Images of a representative subject from the Sonicare toothbrush group (a) at
screening, (b) at post bleaching baseline, (c) at 6 months after the end of bleaching.
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176
80
70
Luminance L*
60
50
40
B1
A1
B2
A2
A3
B3
B4
A4
2
1
2
4
.5
4
D
C
C
D
C
A3
Vita Classical shades in manufacturer's order
Figure 6—Luminance component of CIE L*a*b* color (middle-middle third of tab) vs

manufacturer’s order for Vita Classical shade tabs.
Acknowledgments
This work was supported by Philips Oral Healthcare, Inc.
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PRODUCT REFERENCES Formattato: Tutto maiuscole
Formattato: Tipo di
1
Philips Oral Healthcare, Inc, Snoqualmie, WA 98065; (800) 676-SONIC carattere: (Predefinito) Arial
b
Vita Zahnfabrik, Bad Säckingen, Germany; distributed in the USA by Vident, Brea, CA 92621;
(800) 828-3839
c
Ultradent Products, Inc, South Jordan, UT 84095; (800) 496-8337
d
The Procter & Gamble Company, Cincinnati, OH 45202; (800) 492-7378
e
Adobe Systems, Inc, San Jose, CA 95110; (800) 833-6687
1. Haywood VB, Heymann HO. Nightguard vital bleaching. Quintessence Int. 1989;20:173-176.
2. Goldstein RE. In-office bleaching: where we came from, where we are today. J Am Dent Assoc.
1997;128(suppl):11S-15S.
3. Burrell KH. ADA supports vital tooth bleaching—but look for the seal. J Am Dent Assoc.
1997;128(suppl):3S-5S.
4. Croll TP, Sasa IS. Carbamide peroxide bleaching of teeth with dentinogenesis imperfecta
discoloration: report of a case. Quintessence Int. 1995;26:683-686.
5. Haywood VB. Current status of nightguard vital bleaching. Compend Cont Educ Dent.
2000;21(suppl 28):S10-S17.
6. Frazier KB. Nightguard bleaching to lighten a restored, nonvital discolored tooth [published
erratum appears in Compend Contin Educ Dent. 1998;19:864]. Compend Contin Educ Dent.
1998;19:810-813.
7. Small BW. The application and integration of at-home bleaching into private dental practice.
Compend Contin Educ Dent. 1998;19:799-808.
8. Christensen GJ. Bleaching teeth: practitioner trends. J Am Dent Assoc. 1997;128(suppl):16S-
18S.
9. Christensen GJ. Bleaching teeth: report of a survey, 1997. J Esthet Dent. 199810:16-20.
10. Haywood VB, Robinson FG. Vital tooth bleaching with Nightguard vital bleaching. Curr Opin
Cosmet Dent. 1997;4:45-52.
11. Kugel G, Perry RD, Hoang E, Scherer W. Effective tooth bleaching in 5 days: using a combined
in-office and at-home bleaching system. Compend Contin Educ Dent. 1997;18:378-383.
12. Li Y. Toxicological considerations of tooth bleaching using peroxide-containing agents. J Am
Dent Assoc. 1997;128(suppl):31S-36S.
13. Leonard RH Jr. Efficacy, longevity, side effects, and patient perceptions of nightguard vital
bleaching. Compend Contin Educ Dent. 1998;19:766-774.
14. Haywood VB, Leonard RH, Dickinson GL. Efficacy of six months of nightguard vital bleaching
of tetracycline-stained teeth. J Esthet Dent. 1997;9: 13-19.
15. Haywood VB, Leonard RH, Nelson CF, Brunson WD. Effectiveness, side effects and long-term
status of nightguard vital bleaching. J Am Dent Assoc. 1994;125:1219-1226.
16. Matis BA, Cochran MA, Eckert G, Carlson TJ. The efficacy and safety of a 10% carbamide
peroxide bleaching gel. Quintessence Int. 1998;29:555-563.
17. Haywood VB. Historical development of whiteners: clinical safety and efficacy. Dent Update.
1997;24:98-104.
18. Gegauff AG, Rosenstiel SF, Langhout KJ, Johnston WM. Evaluating tooth color change from
carbamide peroxide gel. J Am Dent Assoc. 1993;124:65-72.
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19. Stanford CM, Srikantha R, Wu CD. Efficacy of the Sonicare® toothbrush fluid dynamic action on
removal of human supragingival plaque. J Clin Dent. 1997;8(1 Spec No):10-14.
20. Stanford CM, Srikantha R, Kirchner HL, Wu CD. Removal of supragingival plaque in an
intraoral model by use of the Sonicare® toothbrush. J Int Acad Periodontol. 2000;2:115-119.
21. Wu-Yuan CD, Anderson RD, McInnes C. Ability of the Sonicare® electronic toothbrush to
generate dynamic fluid activity that removes bacteria. J Clin Dent. 1994;5:89-93.
22. Hope CK, Petrie A, Wilson M. In vitro assessment of the plaque-removing ability of
hydrodynamic shear forces produced beyond the bristles by two electric toothbrushes. J
Periodontol. In press.
23. McInnes C, Johnson B, Emling RC, Yankell SL. Clinical and computer-assisted evaluations of
the stain removal ability of the Sonicare® electronic toothbrush. J Clin Dent. 1994;5:13-18.
24. Zammitti S, Habib C, Kugel G. Use of environmental scanning electron microscopy to evaluate
dental stain removal. J Clin Dent. 1997;8(1 Spec No):20-25.
25. Bass CC. An effective method of personal oral hygiene; part II. J La State Med Soc.
1954;106:100-112.
26. Anderson C, Kugel G. Rebound evaluation of tetracycline stained subjects treated with a 6.5%
hydrogen peroxide gel; quantitative assessment by standard digital photography [abstract]. J Dent
Res. 2002;81(spec iss):A-429. Abstract 3488.
27. Commission Internationale de l’Eclairage. Colorimetry Official Recommendation of the
International Commission on Illumination. Paris: Bureau Central de la CIE; 1971.CIE Publication 15
(E-13.1).
28. Matis BA, Mousa HN, Cochran MA, Eckert GJ. Clinical evaluation of bleaching agents of Formattato: Portoghese
different concentrations. Quintessence Int. 2000;31:303-310. (Brasile)
29. O'Brien WJ, Groh CL, Boenke KM. A new, small-color-difference equation for dental shades. J Formattato: Inglese (U.S.A.)
Dent Res. 1990;69:1762-1764.
30. Paravina RD, Powers JM, Fay RM. Dental color standards: shade tab arrangement. J Esthet
Restor Dent. 2001;13:254-263.
31. Tritten CB, Armitage GC. Comparison of a sonic and a manual toothbrush for efficacy in
supragingival plaque removal and reduction of gingivitis. J Clin Periodontol. 1996;23:641-648.
32. Johnson BD, McInnes C. Clinical evaluation of the efficacy and safety of a new sonic
toothbrush. J Periodontol. 1994;65:692-697.
33. O’Beirne G, Johnson RH, Persson GR, Spektor MD. Efficacy of a sonic toothbrush on Formattato: Inglese (U.S.A.)
inflammation and probing depth in adult periodontitis. J Periodontol. 1996;67:900-908.
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Chapter 10
Formattato: Tipo di
Intrapulpal Temperatures with Light Activated Whitening carattere: 14 pt
Effects of a Light Activated Bleaching System on Pulp Chamber Formattato: Tipo di

Temperature in Vitro
ABSTRACT Formattato: Tipo di

carattere: 12 pt
Several new techniques and materials for in-office bleaching have been introduced recently. The
aim of this in vitro study was to measure the temperature increase in pulp chamber produced by
Zoom light and to investigate the influence of this light in conjunction with the application of
bleaching gel on temperature rise. Ten extracted caries-free, unrestored human maxillary anterior
teeth were used for the study. Each tooth was exposed three times in both groups (n=30 per
group). The root of each tooth was cut about approximately 2-3mm apically to the CEJ and the
apical orifice of the root canal was enlarged. The remaining pulp tissue was removed and the empty
pulp chamber was filled with a heat sink compound which replaced the pulp tissue as a heat
conducting medium. A thin K-type thermocouple was inserted to the pulp chamber through the cut
root area. The root surfaces of the tooth were partially submerged in a water bath during the testing
procedure at 37.5oC . In the first group, whitening gel, 25% hydrogen peroxide was applied to the
buccal surfaces of teeth, approximately 1-2mm thick. Then the light was positioned at ~2.50 inches.
The material was applied according to manfacturers instrutions. In the second group, the same
teeth were exposed with the Zoom light without application of bleaching gel. The temperature at
the pulp before treatment (baseline) and temperature increase during exposing the light were
measured for both treatment modalities. There was a 5 minutes interval between the end of one
measurement and begining of the next. The mean temperature rise for group I (light and bleaching
gel) was 1.11oC(0.18 ). The mean temperature use for group II (light alone) was 1.01 oC (0.12 ).
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180
There was a statistically significant difference between two groups (p= 0.003). Application of Zoom
light in conjuction with the application of bleaching gel produced greater temperature rise than did
the light alone. The maximum temperature rise was seen in the first 5 minutes of the treatment for
both groups then the temperature decreased. Although a difference was noticed between the
group receiving light and gel (group I) versus the group receiving light (group II), neither group
showed significant increase in the intrapulpal temperature of teeth when used for the recommended
exposure time.
INTRODUCTION
Tooth Whitening has become one of dentistry’s most popular esthetic procedures as it is a
conservative treatment for discolored teeth 1. Power bleaching is an in-office whitening technique
developed to bleach teeth in a single visit. It’s done by the combination of a whitening agent, such
2, 3
as, peroxide, and an auxiliary, such as light . Currently, the in-office whitening technique uses a
15% to 35% hydrogen peroxide whitening agent (heated or non-heated); the dentist-prescribed
home-applied technique most commonly uses a 10% to 15% carbamide peroxide gel. The
advantage of the in-office procedure is that it does not require patient compliance and results may
be seen immediately. The disadvantage is the chair time, cost to the patient, and the possibility of
multiple visits. A light-activated chairside whitening system has the potential advantages of taking
less time and providing quicker results.
Recently, several new techniques and materials for in-office bleaching have been introduced. The
Zoom Chairside teeth whitening system is one of the power bleaching systems that consists of a
mercury Halide lamp filtered to emit light in the 350-400nm range.
Tooth sensitivity is the most common side effect of whitening4 .Concerns have been raised with the
use of in-office whitening system energy sources like lasers, plasma arc lights and infrared lamps.
It’s believed that these systems activate peroxide formulations and may induce a temperature rise
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that could cause sensitivity. Additionally, it has been reported that the light by itself might have a
bleaching effect 2.
Lately, one study article reported the efficacy of the light whitening system whereas another study
publication accomplished the opposite1, 2. In a recent investigation done in our lab employing a
mercury halide light activated bleaching system significant sensitivity was reported. In this study 30
patients received treatment with the light & 25% hydrogen peroxide gel, gel alone or light alone.
The gel and light group reported a 90 % severe to moderate tooth sensitivity rate. This was
significantly higher than the other groups. (submitted to IADR, 2004).Therefore the aim of this in
vitro study was to measure the temperature increase in pulp chamber produced by Zoom light and
to investigate the influence of this light in conjunction with the application of bleaching gel on the
temperature rise.
EXPERIMENTAL DESIGN
Ten extracted caries-free, unrestored human maxillary anterior teeth were used for the study.
Teeth were randomized and used for three separate temperature recordings for a total of thirty
readings per group. Two groups were designed Group 1 was treated with bleaching gel and ZOOM
light was applied for three cycles of 20 minutes .Group 2 was treated only with ZOOM light for three
cycles of 20 minutes. Every 5 minutes temperatures were measured for each group using K-type
thermocouple. The mean temperature and p-value for group 1 and group 2 were calculated.
MATERIALS AND METHODS
Ten extracted caries-free, unrestored human maxillary anterior teeth were used for the study. After
the teeth were polished with pure pumice to remove any surface debris or contaminants, they were
stored in distilled water until used. The root of each tooth was cut about 2-3mm apically to the CEJ
and the apical orifice of the root canal was enlarged. The remaining pulp tissue was removed and Formattato: Centrato
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182
the empty pulp chamber was filled with heat sink compound (American Oil and Supply Co., Newark,
NJ, USA) which replaced the pulp tissue as a heat conducting medium. A thin K-type thermocouple
was inserted to the pulp chamber through the cut root area.
The root surfaces of the tooth were partially submerged in a water bath during the testing
procedure. This method effectively stabilized the internal baseline temperature at 37.5°C This also
minimized the effects of ambient temperature changes and provided a consistent initial temperature
for each data set. In the first group, whitening gel, 25% hydrogen peroxide was applied to the
buccal surfaces of teeth, approximately 1-2mm thick. Then the light was positioned according to the
manufacturer’s instructions using the integral bite appliance guide to set the distance between the
teeth and the light source approximately 2.50 inches. The teeth were exposed with the Zoom light
for 20 minutes. After each 20minute session the whitening gel was rinsed off, and reapplied. In the
second group, the same teeth were exposed with the Zoom light without application of bleaching
gel. The temperature at the pulp before treatment (baseline) and temperature increase during
exposing the light were used for both treatment modalities. There was a 5 minute interval between
the end of one measurement and the beginning of the next.
RESULTS
The mean temperature rise was 1.11ºC(0.18) in the first group where the light was used with
bleaching gel and 1.01ºC(0.12) in the second group at 5 minutes (graph 1). According to ANOVA
test, there was a statistically significant difference between two groups (p= 0.003). Application of
Zoom light in conjuction with the application of bleaching gel produced greater temperature rise
than did light alone at the 5 minute exposure time. The maximum temperature rise was seen in the
first 5 minutes of the treatment for both groups. Temperature slowly decreased for the 10, 15 and
20 minute recordings (table1).
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183
During the 20 minute exposure time temperatures slowly decreased to 0.43ºC for the light and
0.53ºC for the gel and light system. None of the samples returned to the baseline level during the
20 minute application (table 1).
DISCUSSION
Tooth whitening lights lights may emit heat. The effects of heat on the pulp tissue has been well-
documented. Due to its low compliance nature, lights may cause a temperature increase within the
pulp chamber that may harm the pulp and/or cause tooth sensitivity 5. Zach and Cohen found that a
temperature rise of 5,5 C in a healthy pulp resulted in necrosis in 15% of the Macaca rhesus
monkey teeth 6. However in our study the maximum temperature rise was 1,01. Therefore the zoom
light was found to cause only a slight increase in the temperature. However temperature was
increaed when the light was used in conjunction with the 25% hydroge peroxide bleaching agent.
Since these results were obtained in vitro, long-term clinical trials are needed to fully understand
the reasons of hyersensitivity and performance of this new whitening sytem.
SUMMARY
This study concluded the mean temperature rise was 1.11°C for the gel & light when samples are
4
maintained at body temperature ( table 1). Recently an article published by Hein showed that in
vivo gel temperature change, Zoom! Light bleach gel reached 5°C on the tooth surface during its 20
minute exposure time. The Zoom! Light was designed specifically for tooth bleaching. The results
achieved by this study indicate that although previous reports showed significant temperature rise
on the tooth surface our results demonstrate that the intrapulpal temperature increases only slightly
during the exposure time. Therefore the Zoom light was found to cause only a slight increase in
intrapulpal temperature. The use of the light and gel demonstrated a significantly higher
temperature increase than the light alone. However, this increase is still lower than the necessary to
cause pulpal damage (5.5 °C). The sensitivity noted during light activated bleaching is most
Eliminato: 214¶
184
probably increase dehydration on the surface of the tooth. This may relate to 5°C surface
temperature change previously reported on the enamel surface.
Since these results were obtained in vitro, long-term clinical trials are needed to fully understand
the reasons of hypersensitivity and performance of these new whitening systems. The effects of
light activated bleaching systems on temperature rise in the pulp are not clinically significant.
Hanning and Bott have shown that temperatures exceeding 42.5 °C can result in irreversible
damage to pulp tissue 7. The distance between the light and tooth could affect the temperature rise
in the pulp chamber. It is interesting to comment that normally hot liquids are consumed with short
term temperatures at 60 °C to 70° C. It’s believed that the pulp only increases a few degrees due to
the thermal insulting properties of the dental hard tissue, when using a regular halogen curing light
7
.Our study would indicate no long term pulpal damage from this light activated bleaching system.
Graph 1:
Zoom Light
Zoom Light + Bleaching Gel
1.2
1
Mean Temperature Rise
0.8
0.6
0.4
0.2
0
0 5 10 15 20
Time of Exposure Formattato: Centrato

Eliminato: 214¶
185
Table 1:
Mean Temperature Rise

Time in Minutes
Zoom Light Zoom Light + Bleaching Gel
Baseline 0 OC(37.5ºC) 0 OC(37.5ºC)

5 1.01OC 1.11 OC
10 0.82 OC 0.98 OC
15 0.60 OC 0.77 OC
20 0.43 OC 0.53 OC
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186
REFERENCES:
1. Papathanasiou A, Bardwell D, Kugel G. A clinical study evaluating a new chairside and take- 0 pt, Numerazione automatica
+ Livello:1 + Stile
home whitening system. Compendium 2001; 22: 289-297. Comincia da:1 + Allineamento:
2. Tavares M, Stultz J, Newman M, Smith V, Kent R, Carpino E, Goodson JM. Light augments Rientra di: 36 pt, Tabulazioni:
18 pt, Tabulazione elenco +
tooth whitening with peroxide. JADA 2003; 134: 167-175. Non a 36 pt
3. Nathanson D. Vital tooth bleaching: sensitivity and pulpal considerations. JADA 1997; 128:
suppl: 41S-44S.
4. Hein DK. Ploeger BJ. Hartup JK. Wagstaff RS. Palmer TM. Hansen LD. In-office vital tooth
bleaching--what do lights add?. Compend of Contin Educ Dent. 2003 Apr; 24(4A):340-52.
5. Blankenau R, Goldstein R, Haywood VB. The current status of vital tooth whitening techniques.
Compendium 1999; 20: 781-794.
6. Zach L, Cohen G. Pulp response to externally applied heat. Oral Surg Oral Med Oral Pathol
1965; 19: 515-530.
7. Hannig M, Bott B. In-vitro pulp chamber temperature rise during composite resin polymerization
with various light-curing sources. Dent Mater. 1999 Jul;15(4):275-81
Formattato: Tipo di
carattere: Arial, Turco
Formattato: Tipo di
carattere: Arial
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187
Chapter 11
Formattato: Tipo di
Effect of Tooth Whitening on Enamel carattere: 14 pt
An exploratory study using SEM to evaluate the enamel surface effects in Formattato: Tipo di
vivo of a 6% hydrogen peroxide strip bleaching system with that of a 2.5%
chlorite tray bleaching system
Formattato: Tipo di
carattere: Arial
INTRODUCTION sinistra
Tooth whitening has become both common and popular, and use of peroxide is now generally
1-3
recognized as a safe and effective method for tooth whitening . There are a variety of indications
for bleaching single or multiple teeth, including staining from chromagenic foods or other sources,
4-6
dental fluorosis, tetracycline staining and devital discolored teeth . Concentrations of up to 35%
peroxide are used alone or in combination with various agents for tooth bleaching. Delivery is via
7, 8
in-office, at-home regimens or combination regimens with or without professional supervision .
Of these, bleaching is most commonly accomplished at-home over a period of a few weeks 9.
Treatment duration may vary based on the degree of staining, since whitening is reported to be a
10
product of peroxide concentration and contact time . For some difficult stains like tetracycline,
daily bleaching for periods of up to 6 months may be indicated 11.
Efficacy may be established through first or second person observation or various technical
methods. Clinical trials most commonly include use of a shade guide, colorimeter, or computer
digitization to measure color change over time. Of these, methods that assess three-direction
(dimension) color space are reported to be more objective and linear, and as such, may be
preferred for clinical trials research 12,13.
A comprehensive literature review found tooth bleaching agents to be remarkably well-tolerated.
The principal adverse events — tooth sensitivity to temperature changes and local oral mucosal
irritation — were generally mild and transient. Patients with pre-existing sensitivity may be at Formattato: Centrato
Eliminato: 214¶
188
highest risk for after-bleaching sensitivity. Several factors are reported to contribute to hard and
soft tissue events, including tray design, formulation, and others 10.
Tolerability may be impacted by poor compliance, overuse, unnecessary product ingestion, and
others 5,. Many of these factors may be associated with the delivery trays (either custom or stock)
which are commonly used in most at-home regimens. Rapid innovation, especially with the advent
of new in-office options for immediate care and the emerging popularity of the direct-to-consumer
systems, challenges many of the basic tray-based precepts of the previous decade. One of the
most prominent of these is the whitening strip (Crest®, Blend-a-Med® or AZ® Whitestrips™), a
novel system that uses a flexible polyethylene strip to deliver a hydrogen peroxide bleaching gel to
the anterior dentition. These whitening strips are reported to offer specific advantages vs the more
conventional custom tray-based systems, with respect to total peroxide dose, contact time, and
ease of use. Evidence of safe and effective use has been established in clinical and pre-clinical
studies comparing whitening strips to various negative and positive controls. The application of
such bleaching agents to whiten vital-teeth is less well-characterized with little research published
in the scientific literature.
There have been a number of studies evaluating the effect of bleaching on the hardness and
morphology of enamel. The results from these studies have varied. One study concluded that the
14
use of bleaching agents resulted in a significant reduction in Calcium/Phosphate ratio in enamel
and they concluded that bleaching materials may adversely affect the dental hard tissue. Other
authors state that surface hardness and tooth morphology are not deleteriously affected by
, 16
Eliminato:
15
bleaching .
Eliminato: ¶
This clinical trial evaluated the safety of a recently introduced 2.5% sodium chlorite tray-based Formattato: Tipo di
carattere: Arial
whitening system, Odol-med 3 Beauty Kurr, versus a currently marketed 6% hydrogen peroxide
Eliminato: 214¶
189
Formattato: Tipo di
strip system. Sodium chlorite is the only chlorite salt produced commercially in significant quantities. carattere: Arial
It is used mainly for the generation of chlorine dioxide in situ for bleaching textiles, in pulp and
paper processing, and for disinfection. Scanning Electron Micrographs from replicas were used to
observe surface effects/ morphological changes in teeth enamel after treatment with bleaching
agents. The observations included any changes in the porosity, precipitations, erosive process,
destruction and depression areas, with the formation of craters and exposure of enamel rods.
Formattato: Tipo di
Formattato: Tipo di
OBJECTIVE carattere: Arial
The aim of this exploratory study was to assess any surface morphological changes in tooth
enamel after treating with a currently marketed hydrogen peroxide strip bleaching system and a
currently marketed sodium chlorite tray-based system using an SEM Investigation.
Formattato: Tipo di
MATERIAL AND METHODS carattere: Arial
Formattato: Giustificato
This was a parallel, examiner-blind, single-center study. Approximately 10 generally healthy
subjects (5 per treatment group) were randomly selected from a pool of subjects undergoing a 3
week regimen of vital tooth bleaching with either a 6% whitening strip (Group I) or 2.5% sodium
chlorite tray system (Group II). The Test Products were:

• AZ Whitestrips (Polyethylene strips containing 6% Hydrogen Peroxide gel). numerati
Manufactured by The Procter & Gamble Company.
• Odol-med 3 Beauty Kur (Tooth Whitening System including the Activator containing 2.5%
Sodium Chlorite). Manufactured by Glaxo Smithkline.

Formattato: Tipo di
Subjects assigned to Crest Whitestrips treated their anterior maxillary tooth surfaces for a period of carattere: Arial
three weeks. The product was used twice a day for 30 minutes each. Subjects assigned to Odol-
med 3 also treated their maxillary surfaces for three-week duration, as per the manufacturer’s
Eliminato: was supervised
instructions. This product was used twice a day for 10 minutes. The first product use was
Eliminato: 214¶
190
Formattato: Tipo di
supervised at the Product Distribution visit. All other uses were completed at home and were carattere: Arial
unsupervised.
Formattato: Tipo di
Subjects on the Group I brushed twice daily with AZ Protezione Caries toothpaste (currently Formattato: Tipo di
carattere: Arial
marketed cavity protection toothpaste). It contains 0.32% Sodium Fluoride (Procter & Gamble Eliminato: I brushed
Formattato: Tipo di
Company). Subjects on the Group II had whitening toothpaste provided to them with their test carattere: Arial
Formattato: Tipo di
product. All subjects were assigned an Oral B40 Soft Bristle toothbrush (Braun Oral B Company). carattere: Arial
Formattato: Tipo di
carattere: 8 pt
Inclusion Criteria Formattato: Tipo di

carattere: Arial
The subjects were included if they:

1. provided written informed consent prior to their participation and be given a copy of the signed numerati
consent form,
2. were at least 18 years of age at the time of enrolment,
3. had a minimum of 16 natural teeth, specifically all 4 maxillary anterior central and lateral
incisors.
4. agreed to return for the scheduled visits and follow the study procedures,
5. agreed not to participate in any other oral /dental product clinical studies during the course of
this study,
6. agreed to refrain from the use of any non-study dentifrices and tooth whitening products for the
study duration and
7. had teeth sufficiently free of caries

Formattato: Tipo di
carattere: 8 pt
Exclusion Criteria Formattato: Tipo di

carattere: Arial
The subjects were excluded from the 2003088 study if they:

numerati
1. had restorations or dental crowns, generalized gingival recession or clinically meaningful
Eliminato: generalised
malocclusion involving the maxillary or mandibular anterior dentition, Formattato: Tipo di

carattere: Arial
Eliminato: 214¶
191
2. presented with any pre-existing oral or medical condition that the examiner or investigator
determines may place the subject at increased health risk from study participation,
3. had any dental care planned during the duration of the study that may:
• impact the general health of the subject
• impact the ability of the subject to bleach teeth according to the protocol
• require a dental prophylaxis
• involve the anterior dentition
4. were undergoing current treatment for gingivitis, periodontitis, or caries,
5. reported having teeth previously bleached by a professional treatment, over-the-counter
bleaching kit, or clinical trial test product,
6. were currently using a chlorhexidine mouth rinse or Listerine mouth rinse,
7. had teeth with clinically meaningful intrinsic staining due to tetracycline, fluorosis or
hypocalcification,
8. had self-reported dentinal sensitivity, or
9. had teeth that cannot be imaged.
Formattato: Sottolineato
Continuance Criteria Eliminato:
Subjects were discontinued for the following reasons: sinistra
Formattato: Tipo di
1. use of dentifrices or mouthrinses or tooth whitening products other than those assigned; carattere: Arial
2. elective dentistry prior to study completion, including dental prophylaxis; numerati
3. Inability or unwillingness to comply with study procedures including test product regimen.
The same continuance criteria were governing the subject’s eligibility to continue participation in
this study.
An SEM Investigation was done on Baseline, Day 14 and Day 21. Subjects discontinued product
use at the Day 21 visit. During the entire study period subjects brush with their assigned toothbrush
Eliminato: 214¶
192
and toothpaste. An impression of the dentition and SEM investigation was conducted and used as
the post treatment assessment. A rubber impression of both the maxillary and the mandibular
anterior teeth was taken for each of the selected subject. These were done both at the baseline
(pre-treatment) and after completing the product usage (post treatment).
The impressions were poured with epoxy resin material. The buccal surfaces of the two upper
central incisors were evaluated. The buccal surfaces of central incisors were gold sputtered and
Eliminato: labelled
then mounted in metallic stubs. All the study material was labeled with the subject number, tooth Formattato: Tipo di
carattere: Arial
number and the evaluation day.
Observations under the SEM were made on changes in porosity, precipitations, erosive process,
destruction and depression areas, with the formation of craters and exposure of enamel rods.
Photographs of the scans were taken. Two different evaluators who were blinded to the test product
did the observations and scoring. The scoring was done independent of one another.
The scoring was done at constant magnifications (x500, x2000 and x5000). Four readings were
made on each tooth, dividing the surface into four quadrants (figure 1). The reading was performed
in the centre of each quadrant. All the scores were collected and evaluated according with the
scores (figure 2) and the location. The SEM scores were done by two independent graders using a
scoring system of 0-4.
Due to small sample size, non-parametric methods were used to explore the data (figures 3-6). In
addition to the visual observation models were poured in epoxy die and 3D laser profilometry was
done on all samples. Delta Ra data was obtained and statistical differences from baseline were
determined.
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RESULTS
Scores from the visual evaluation of the SEM data indicated that there was little evidence of any
increased surface roughness in either group following treatment (Table 1). This is based on the
visual evaluation of two independent calibrated evaluators. Evaluations were based on a
comparison between baseline (no treatment) and after 21 days of exposure. It should be noted that
all evaluations indicated that the roughness noted was superficial with no deep roughness
observed.
The profilometry data (table 2) shows a good biological diversity with both products producing a
similar but insignificant change in surface roughness. Differences between groups showed no
statistical significance using a nonparametric analysis, the Wilson rank sum test. This produces a
P-value =0.69 which indicates that neither treatment had any adverse effects on the surface
morphology the teeth examined. These results confirm the data presented in table 1.
Formattato: Tipo di
DISCUSSION carattere: Arial
Eliminato: ¶
This study represents the first paper to evaluate enamel following tooth whitening using both visual
Eliminato: o
analysis and laser profilometry. There have been other studies to evaluate the hard tissue effects of Formattato: Tipo di
carattere: Arial
14,
tooth whitening. These have employed microhardness and SEM analysis of the enamel surfaces Eliminato:
20
15 Formattato: Tipo di
. In this study the use of a visual scoring system for changes on enamel morphology indicated that carattere: Arial
21
Eliminato:
there were no significant changes from the baseline in either the 6% Hydrogen Peroxide gel group
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carattere: Arial
or the 2.5% Sodium Chlorite group. It is important to note that in all evaluations the roughness
observed was superficial in nature and that all teeth varied slightly at baseline. This is expected
given the variability of enamel clinically and these observations are only relevant when compared
within the sample.
In order to confirm our SEM visual evaluation Laser profilometry was done for both groups.
Measurements were compared using baseline (before treatment) and following 21 days of Formattato: Centrato
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194
Eliminato: analysed
exposure. Samples were analyzed for differences from baseline for both the 6% hydrogen peroxide Formattato: Tipo di
carattere: Arial
and the 2.5% Sodium Chlorite groups. There is no statistical difference between the baseline and
21 day samples. This is true for both tooth whitening systems. In both groups the 21 day dosing
Eliminato: ¶
has no effect on surface roughness of the exposed teeth. In conclusion this study indicates that 21 Formattato: Tipo di
carattere: Arial
day exposure to two different tooth whitening systems had no observable or measurable adverse Eliminato: n
effects on enamel.
Formattato: Tipo di
Tables and figures: Formattato: Tipo di
carattere: Arial
Figure 1 Four readings were made on each tooth, dividing the surface into four quadrants
Figure 2: Scoring scales for SEM evaluation
Figure 3: Samples of SEM 2,000X with roughness score 0
Table 1: Average scores per group by quadrant
Table 2: Laser profilometry Ra analysis
Figure 1:
A B
C D
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carattere: Arial
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195
Figure 2:
SEM Scores
Score 0 no visible surface roughness
Score 1 5-25% of the surface displays roughness
Figure 3: Formattato: Tipo di

carattere: Arial
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carattere: Arial
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196
Figure 4:
Figure 5: Formattato: Tipo di

carattere: Arial
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197
Figure 6:
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Table 1: carattere: Arial
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Quadrant A Formattato: Tipo di

carattere: Arial
Average per Group
500X 2000X
Baseline 14-Day 21-Day Baseline 14-Day 21-Day
GROUP I
0 0.4 0.2 1.4 1.6 0.8
GROUP II 0 0 0.2 1.6 1.6 0.4
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carattere: Arial
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198
Quadrant B
Average per Group
500X 2000X
GROUP I Formattato: Tipo di

0.2 0.4 0 1.6 1.8 1 carattere: Arial, 11 pt
GROUP II 0.2 0.2 0 1.6 1.6 0.6 Formattato: Tipo di

Quadrant C
Average per Group
500X 2000X

0.4 0.4 0 2 1.8 0.6 carattere: Arial, 11 pt
GROUP II 0.4 0.6 0 2 1.4 0.6 Formattato: Tipo di

Eliminato: ¶
Formattato: Tipo di
Quadrant D carattere: Arial
Average per Group
500X 2000X

0.8 0.4 0 2.2 1.6 0.6 carattere: Arial, 11 pt
GROUP II 0.6 0.2 0 1.2 1.6 0.6 Formattato: Tipo di

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Table 2: Eliminato: ¶
Specimen Treatment Baseline 21 day Delta Ra Formattato: Tipo di

5 Group I 0.5192 0.7154 0.1962 carattere: Arial, Grassetto
12 Group I 0.2458 0.3715 0.1257

20 Group I 0.1815 0.2208 0.0393
24 Group I 0.2189 0.2034 -0.0155
32 Group I 0.3545 0.2613 -0.0932
Mean Value 0.30398 0.35448 0.0505 Formattato: Tipo di
carattere: Arial, Grassetto
Formattato: Tipo di
carattere: Arial
Specimen Treatment Baseline 21 day Delta Ra
1 Group II 0.1305 0.1976 0.0671 Formattato: Tipo di
3 Group II 0.2588 0.2505 -0.0083
4 Group II 0.2792 0.2748 -0.0044
25 Group II 0.3158 0.3244 0.0086
27 Group II 0.3365 0.3 -0.0365
Mean Value 0.26416 0.26946 0.0053 Formattato: Tipo di
Formattato: Tipo di
carattere: Arial
REFERENCE
1. Haywood VB, Heymann HO. Nightguard vital bleaching. Quintessence Int 1989;20: 173-6. 0 pt, Numerazione automatica
+ Livello:1 + Stile
2. Goldstein RE. In-office bleaching: where we came from, where we are today. J Am Dent Assoc numerazione: 1, 2, 3, … +
1997; 128: 11S – 15S A sinistra + Allinea a: 18 pt +
3. Burrell KH. ADA supports vital tooth bleaching – but look for the seal. J Am Dent Assoc 1997 Rientra di: 36 pt, Tabulazioni:
18 pt, Tabulazione elenco +
128:3S-5S. Non a 36 pt
4. Croll TP, Sasa IS. Carbamide peroxide bleaching of teeth with dentinogenisis imperfecta
discoloration: report of a case. Quintessence Int 1995; 26:683-6
5. Frazier KB. Nightguard bleaching to lighten a restored, nonvital discolored tooth. Compend
Contin Educ Dent 1998; 19:810-3
6. Small BW. The application and integration of at-home bleaching into private dental practice.
Compend Contin Educ Dent 1998;19:799-806 Formattato: Centrato
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200
7. Kugel G, Perry RD, Hoang E, Scherer W. Effective tooth bleaching in 5 days: using a combined
in-office and at-home bleaching system. Comp Contin Educ Dent 1997; 18:378-83.
8. Li Y. Toxicological considerations of tooth bleaching using peroxide-containing agents. J Am
Dent Assoc 1997; 128:31S-36S
9. Leonard RH. Efficacy, longevity, side effects, and patient perceptions of nightguard vital
bleaching. Compend Contin Educ Dent 1998; 19: 177-780
10. Haywood VB, Leonard RH, Dickinson GL. Efficacy of six months of nightguard vital bleaching
of tetracycline-stained teeth. J Esthet Dent 1997;9: 13-9
11. Haywood VB, Leonrd RH, Nelson CF, Brunson WD. Effectiveness, side effects, and long-term
status of nightguard vital bleaching. J Am Dent Assoc 1994; 125 1219-26
Formattato: Tipo di
12. Gegauff AG, Rosenstiel SF, Langout KJ, Johnston WM. Evaluation of tooth color change from carattere: Arial, Tedesco
(Germania)
carbamide peroxide gel. J Am Dent Assoc 1993;124:65-72.
Formattato: Tipo di
13. Rotstein I. Dankner E. Goldman A. Heling I. Stabholz A. Zalkind M. Histochemical analysis of carattere: Arial
dental hard tissues following bleaching. Journal of Endodontics. 22(1):23-5, 1996 Jan.
14. White DJ. Kozak KM. Zoladz JR. Duschner HJ. Gotz H. Effects of Crest Whitestrips bleaching
on surface morphology and fracture susceptibility of teeth in vitro. Journal of Clinical Dentistry.
14(4):82-7, 2003.
Formattato: Tipo di
15. Spalding M. Taveira LA. de Assis GF. Scanning electron microscopy study of dental enamel carattere: Arial, Portoghese
(Brasile)
surface exposed to 35% hydrogen peroxide: alone, with saliva, and with 10% carbamide
Formattato: Tipo di
peroxide. Journal of Esthetic & Restorative Dentistry: Official Publication of the American carattere: Arial
Academy of Esthetic Dentistry. 15(3):154-64; discussion 165, 2003.
Summary and Discussion
In Chapter 1, as an introduction to the main topic of this study, a major aspect of modern dentistry
was presented. The area of tooth whitening, although one of the fastest growing and affecting
millions of patients, it relies on a weak base of scientific evidence. The actual mechanism of action
of hydrogen peroxide on enamel and dentin is presumed to be an oxidation process that affects
both enamel and dentin. The assumption is that because the radicals have unpaired electrons, they
are extremely electrophylic and unstable and will attack most other organic molecules to achieve
stability, generating other radicals. These radicals can react with most unsaturated bonds, resulting
in disruption of electron conjugation and a change in the absorption energy of the organic Eliminato: 214¶
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molecules in tooth enamel. Simpler molecules that reflect less light are formed, creating a
successful whitening action. This process occurs when the oxidizing agent (hydrogen peroxide)
reacts with organic material in the spaces between the inorganic salts in tooth enamel. This
assumption is difficult to prove. Our data supports the idea that there must be significant
penetration of the peroxide into dentin and that once it reaches the dentin it is in a form that is able
to oxidize the organic material causing a lightening effect. The early work on tetracycline staining
supports the idea that there is a penetration of the free radical. These studies relied on small
sample sizes and incorporated high dose delivery systems. The causes of both intrinsic and
extrinsic staining were reviewed following the section on penetration of hydrogen peroxide. This
was done to support the belief that these intrinsic stains require significant penetration in order for
these to be lightened.
It is interesting that so little is known about the concentration and dose response during the
whitening process. The assumption has been that the higher the concentration the better the effect.
It has also been assumed that a dose of 30-50 mg was required to whiten teeth. We examine in this
thesis the use of a novel low dose delivery system using 9-11 mg of carbamide peroxide on a
polyethylene strip.
A review of the evolution of tooth whitening demonstrates the field is not new. The review of the
literature also shows that there a number of systems available for tooth whitening. The most
common bring the night guard vital bleaching method. Other systems have been more recently
introduced such as the polyethylene strip and paint-on products. The area of light activated
bleaching as indicated in the introduction remains one of the most controversial areas in this field.
This is due to the poor quality of many of these studies the results have been questioned. The
mechanism of action of these light (and heat) activated systems is addressed along with the
evidence that the assumed increased breakdown of the hydrogen peroxide and thus increased
efficacy would require temperatures the would be detrimental to vital teeth. Eliminato: 214¶
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Finally; the issue of adverse events and possible side effects were reviewed. The toxicological side
effects seem to be minimal however tooth sensitivity can be quite significant. Studies have shown
that sensitivity occurs in 55 to 75% of the treatment groups. The placebo groups also experienced
20-30% sensitivity. The causes of tooth sensitivity are poorly understood. It is most often seen as
the result of tooth dehydration.
In Chapter 2 a randomized, single-center, double-blind, parallel-group, placebo controlled trial
evaluating the whitening efficacy and safety of 2-week, twice daily use of a 5.3% hydrogen
peroxide tooth-bleaching gel delivered on polyethylene film. This system employed a low dose
delivery of 9-11 mg of carbamide peroxide gel. Efficacy was based on change in Vita® shade
scores from baseline to the end of treatment. Baseline Vita® shade scores were similar for the two
treatment groups. Scores were 8.18 (D-4 to A-3) and 8.28 (D-4 to A-3), and, on average, ranged
from A-2 to C-4 and from A-2 to A-4 in the active and placebo groups, respectively. Sixty-four
percent of teeth treated in the active group started at scores of C-2 or whiter. Thirty-three patients in
each group completed treatment. Use of the peroxide-containing gel led to a mean change in
baseline Vita® shade score of –3.70 ± 0.35, compared with a change of –0.87± 0.24 after use of a
placebo gel. After adjustment for baseline scores, the mean difference in shade change between
the peroxide gel–treated group and placebo-treated group was –2.85 ± 0.41 (P < 0.0001). Both
treatments were generally well tolerated. Adverse effects after treatment were minimal and were
observed in less than 10% of subjects in either treatment group. The main findings in these
participants were papillary swelling, minor cervical inflammation, and a superficial cervical lesion.
This was the first study to examine the use of such a thin film of hydrogen peroxide gel in tooth
whitening. Prior to the research dentist would us a night guard fabricated to a stone model of the
patient and contoured at the margins Spacer was routinely used on the facings of the teeth to
insure that a high dose of material could be delivered to the teeth with the assumption that this was
necessary to have a significant amount of material in contact with the teeth for tooth whitening to Eliminato: 214¶
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occur. This study was the first to demonstrate that a low dose (9-11 mgs) but higher concentration
5.3 % hydrogen peroxide applied for 30 minutes twice daily resulted in significant lightening when
compared to placebo control. This study was controversial since this delivery system was easy to
apply, effective, minimal adverse events and did not require the fabrication of a tray and therefore
had the potential to be used as over-the-counter product.
In Chapter 3 the question of concentration response using a low dose (4-11 mg) delivery system
was addressed employing digital image analysis of treatment groups in order to analyze the
CIELAB tooth color values for b* (yellow – blue), L* (lightness), and a* (red – green).17 Change
values were calculated for any given post-baseline visit. The objective of this study was to
evaluate the peroxide concentration whitening response following self-directed use of whitening
strips over a 28-day period.
A randomized, double-blind, parallel group clinical study was conducted. Thirty-seven healthy adult
volunteers were randomly assigned to one of three groups based on tooth color at screening –
1.8% hydrogen peroxide strips (HPS), 3.3% HPS or 5.3% HPS. Subjects applied the assigned
maxillary strips twice per day for 30 minutes over 28 days. Tooth color was evaluated at day 7, 14 &
28 from digital images of the maxillary 6 anterior teeth using a standard method. Treatments were
compared using analysis of covariance (adjusting for baseline), or analysis of variance at a 0.05
level of significance.
The results of this study demonstrated hydrogen peroxide at concentrations ranging from 1.8-
5.3% resulted in significant (p < 0.05) color improvement versus baseline as early as Day 7. There
was a clear concentration-response for all color parameters (Δb*, ΔL* and ΔE*) at all time points,
favoring the higher concentrations. While the concentration-whitening relationship approached a
linear response at Day 7, continued treatment resulted in incremental color improvement. All three Formattato: Centrato
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peroxide concentrations were well tolerated, and no subjects discontinued early due to a treatment-
related adverse event.
The research provides clear evidence of a peroxide concentration whitening response. Whitening
efficacy was greatest for the highest concentration group (5.3% hydrogen peroxide), while the
intermediate concentration group had an intermediate response. Not surprisingly, this effect most
approached linearity at the earliest time point (Day 7). At that time, adjusted mean Δb* for was –
1.43, –0.84, and –0.44 in the higher, intermediate and lower concentration groups, respectively.
Relative to the lowest concentration strip, this represented a 225% improvement in whitening for the
5.3% strip (a 194% increase in concentration), and a 91% improvement in whitening for the 3.3%
strip (a 83% increase in concentration).
Despite the concentration differences (there was nearly a three-fold difference between the lowest
and highest concentration tested in this research), all three strips tested in this research carried a
low total amount of peroxide. The total amount of hydrogen peroxide on each pre-dispensed strip
ranged only from 3.6-10.6 mg. Relative to some tray-based systems, which may deliver up to 2
grams of bleaching gel, total peroxide delivered with any of these strips was remarkably low. This
likely contributed to the low overall adverse event rate seen in this trial.
This new clinical research provides evidence of a concentration gradient for whitening response
following use of a low peroxide dose strip whitening system. As such, this may represent a first
example of concentration ranging for one of the self-directed bleaching systems. More importantly,
the research also provides evidence of the sensitivity and robustness of the measurement method
– in this instance – digital imaging.
The study in Chapter 3 compliments the earlier work done in Chapter 2. In Chapter 2 we discussed
the introduction of a low dose novel delivery system and we demonstrate its effectiveness vs contro
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using a value-ordered shade guide. In Chapter 3 we determine that there is a concentration
response when measured digitally using this low dose system.
This research adequately differentiated multiple concentrations from low to high over time. With
Δb* as an endpoint, the study demonstrated a nearly linear concentration response relationship,
with measured efficacy differences at Day 7 that reasonably modeled the real concentration
differences between groups. As such, the research provides important evidence of the validity of
this method and endpoint for practice-relevant evaluation of vital bleaching technologies.
In Chapter 4 we evaluated the effectiveness of light-curing (heat conversion) vs. no light-
curing (no heat conversion) of a 35% hydrogen peroxide in-office tooth whitening system.
Heat conversion is used as a means of speeding up the breakdown and thus increasing the
efficacy of the hydrogen peroxide oxidation process. This was one of the first controlled
studies to evaluate light activated bleaching.
Twenty patients with sound medical history (without tooth sensitivity) participated in this
randomized, parallel clinical evaluation. Only six maxillary anterior teeth with discoloration and a
tooth shade of A3 or darker were selected. Patients received a complete prophylaxis and were
evaluated for initial (baseline) shade by three independent evaluators, precalibrated at 85% rater
reliability in determining shades before the experiment began. Participants received a 20-minute
chairside whitening treatment with a 35% hydrogen peroxide agent using a reflective resin barrier
for gingival isolation. During the whitening treatment, the 35% hydrogen peroxide agent was light
activated with a halogen curing light on teeth Nos. 6 through 8 (Group I), but was not light-activated
on teeth Nos. 9 through 11 (Group II). All patients returned 24 hours after the whitening application
for shade evaluation. Although there were isolated instances (7 out of 20 patients) of greater
degrees of lightening in the light-curing group, there was no statistically significant difference using Formattato: Centrato
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the Mann-Whitney U test (P > .05). This study indicates that light-curing is optional with this 35%
tooth whitening system.
Of the 20 patients in this study, 7 patients experienced an increase in lightening of the split arch
protocol with an average lightened increase of 1.714 shades as compared to the non–light-cured
side. This was not a significant clinical change. Any shade difference as noted by the light-activated
side was most likely a result of dehydration resulting from heat generated by the halogen curing
light. Statistically, there was no significant difference between the light-activated side when
compared to non–light-activated side.
The results contradict other studies, which have indicated that light activation causes an
increased whitening effect as used with hydrogen peroxide whitening agents
The study in Chapter 5 is complimentary to that in Chapter 4. The purpose of this study
was to compare the efficacy of color changes of two in-office tooth whitening systems, a
15% Hydrogen peroxide light activated system and a 38% non-light activated hydrogen
peroxide system.
In this split-arch, randomized, parallel, blinded clinical evaluation six maxillary anterior teeth
(N=60) A-2 or darker were selected using the value order Vita Shade Guide. Patients
received one-hour light-activated chair side treatment using 15% H2O2 teeth 6-8 (Group I),
teeth 9-11 received a 38% H2O2 system for 1 hr without a light (Group II). Before and after
treatment images were taken. L*, a* and b* and Vita shades were measured. The Olympus
C2500L high resolution digital camera is utilized for sampling. To ensure proper color
analysis an extended procedure of sampling nine locations on the central incisor, lateral
incisors of the maxillary and mandibular arches was completed. This data is then averaged Formattato: Centrato
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to find a mean color and standard deviation of color on each tooth. A Gaussian blur filter
was applied during post processing which does an averaging of color over the digitally
sampled photo. All digital images were then analyzed to yield L*, a* and b* data Patients
returned after 2 weeks for final shade evaluation.
The L*, a* and b* data indicates that both BriteSmile and Opalescence Xtra Boost whitened teeth to
statistically significant level (P=.01) for L* 3.6 (BriteSmile), 3.8 (Xtra Boost) and b* -6.0 (BriteSmile),
-5.0 (Xtra Boost) equivalent to between 3 and 6 shades as determined on a Vita shade guide. The
two whitening systems were not statistically significantly different from pre-bleaching to two weeks
post-bleaching. The Vita Shade Guide results showed that both in-office tooth whitening systems
were effective. Group I averaged 5.9 ± 2.5 and Group II 3.97 ± 2.33 shade changes immediately
after treatment. At the 2-week recall, Group I scored an average of 4.6 ± 2.14 and Group II 4.6 7±
2.3 shade changes, compared to the pre-bleaching shades. A paired sample t-test revealed
statistically significant difference (p<0.0001) between Groups I and II immediately after bleaching,
with Group I performing better. At the 2-week recall, however, only Group I showed a significant
rebound (p=0.0002). At the completion of the study, there was no significant difference between
Groups I and II (p=0.7826).
The clinical observation using a value ordered Vita Shade Guide was confirmed using digital
15
analysis of L*, a*, b* color values . In addition the digital camera was calibrated for each image.
Unlike other studies, the teeth of the one side were kept moist during bleaching, thus minimizing the
effect of dehydration that can occur while the other lateral side was being bleached. This might
explain why our data does not show the dramatic results reported in another paper. It is reasonable
to conclude that with the increase in temperature, dehydration did occur, which was subsequently
followed by rehydration. Therefore, in spite of the initial perception that an increase in whitening
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took place, the 2-week post-operative evaluation did not demonstrate a difference, which was
confirmed by an absence of a statistically significant difference between the two materials.
This data is particularly relevant since the use of light activated bleaching has been gaining in
popularity in the US. This is partially due to the fact that there are few well controlled, independent
studies in the field. In a study that we just completed at our University but the (data yet
unpublished) we used a metal halide (Zoom) light N=30 patients and we once again found no value
to use of a light in bleaching.
In Chapter 6 we address the issue of hydrogen peroxide penetration as well as mechanism of
action by examining the efficacy of a low dose delivery system on bleaching tetracycline-stained
teeth. We incorporate a patient population with documented intrinsic staining so that we could
evaluate the ability of the low dose gel to penetrate to the dentin. This clinical article reviews the
efficacy of a new 6.5% hydrogen peroxide tooth-whitening gel strip for bleaching teeth that have
been intrinsically stained from tetracycline. Given the severity of the staining in the cases presented
during this conducted clinical trial, the resulting efficacy is dramatic.
A randomized clinical trial compared the efficacy of two at-home vital bleaching systems on
tetracycline-stained teeth. Daily bleaching was conducted over two months. Eligibility was limited to
healthy adult volunteers who had 16 or more natural teeth, including at least 3 gradable maxillary
incisors with significant tetracycline staining. Individuals demonstrating tooth sensitivity or an
immediate need for dental treatment were excluded from participation in this trial.
The 40 randomized subjects included 30 assigned to the strip group and 10 assigned to the tray
group. The study population ranged from 22 to 70 years of age. Approximately half of the sample
presented with moderate to severe tetracycline staining (levels II through IV), one third of whom
had the more severe banding that is occasionally reported following childhood antibiotic use. While
tobacco use was uncommon (15% of the sample), 95% of the study participants consumed coffee, Eliminato: 214¶
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tea, or cola beverages daily. Treatment groups were generally well balanced with respect to
demographic and behavioral parameters and tetracycline stain levels. Efficacy was assessed using
a standard 16-step value-oriented tooth shade guidec used in dentistry to match artificial crowns to
the natural dentition. Shade assessments were performed in a neutral-colored dental operatory
under color-balanced lighting conditions by a trained and calibrated examiner. Tolerability was
assessed by intraoral examination and subject report at each study visit.
Individual shade scores were determined by ordering the 16 shades arranged from dark to light
according to the rank ordering suggested by the manufacturer. To account for unusually dark colors
(often seen with tetracycline stain) or white colors (often seen post-bleaching), this 16-step guide
was supplemented by 2 additional values (C4+ and B1-) representing shades darker than C4 or
lighter than B1. Effectiveness was determined by calculating the change in shade scores from
baseline at each post-treatment visit. Using this method, a decrease in numeric shade score
represented an increase in tooth whiteness. Treatment groups were compared using analysis of
covariance with the baseline shade as the covariant. Comparisons to baseline were 1-sided, while
between-group comparisons were 2-sided using a 5% significance level.
Both treatments were effective overall in improving the shade of tetracycline-stained teeth. Relative
to baseline, the 2 groups averaged approximately 4 to 6.5 units of shade improvement after 2
months of treatment. Observed changes were greater on average after 2 months as compared to 1
month. Response was faster in the strip group. During the first month’s treatment, individuals in the
strip group averaged greater than a 4-unit reduction in tooth shade, which represented a highly
statistically significant (P < .0001) improvement vs. baseline. In contrast, subjects in the tray group
averaged less than a 1-shade reduction during the first month, not differing statistically from
baseline (P > .10). Adjusting for baseline, the strip group averaged 2.6 to 3.2 units more shade
reduction compared with the tray group control. With respect to between-group comparisons, the
strip group experienced statistically significantly superior reductions (P < .01) in shade compared
with the tray group at both the 1- and 2-month time points. Eliminato: 214¶
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This study confirms early observations of the need for extended contact time in many tetracycline-
stained patients. After 2 months of daily treatment, involving approximately 60 hours of strip use or
120 hours of tray use, no subjects had yet reached the predetermined bleaching cutoff (B1-). In
these subjects, additional time may be necessary to affect maximum color change. Previous reports
suggest a minimum of 2 months of treatment, hence the time point elected in this study.
This data demonstrates the difficulty, regardless of the delivery system, in bleaching tetracycline-
stained teeth. This confirms that the peroxide does penetrate to the dentin and that the oxidation
process affects the color of the stained dentin. It also confirms that this is a slow process and
requires extended exposure.
Chapter 7 is the continuation of the 2 month study described in Chapter 6. Chapter 6 was the
published data from the first 2 month of this 6 month study. A variety of indications exist for
bleaching single or multiple teeth, including tetracycline staining. The primary objective of this study
was to evaluate clinical response following extended daily use of a trayless 6.5% hydrogen
peroxide tooth bleaching gel on tetracycline stain. In this research, 10% carbamide peroxide in an
at-home daytime tray delivery system was used for comparison purposes.
As in Chapter 6 this is a single-blind clinical trial, subjects were randomly assigned to a Strip group
(30 subjects) or a Tray group (10 subjects) following screening for tetracycline staining. Subjects
used their respective products for approximately 6 months, with clinical safety and efficacy
measurements taken at the end of each month.
The strip product was used for 30 minutes, twice daily (maxillary arch only). The tray product was
used for 2 hours daily (maxillary arch only). Treatment efficacy was determined by the tooth color
change from baseline using an expanded Vita Shade guide. The Strip group averaged greater
shade reduction compared to the day wear Tray group at the Months 1, 2, and 3 visits, respectively.
After Month 3, there were no significant between-group differences in shade. Of the subjects in the
Strip group, 65% reached B1 tooth color by Month 6, while 43% of subjects in Tray group obtained
this result after 6 months. Both treatments were generally well tolerated. Mild and transient tooth Eliminato: 214¶
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sensitivity (40-47%) and oral irritation (30-47%) were the most common adverse events associated
with daily bleaching, yet neither affected study participation. Both the 6.5% H2O2 experimental
bleaching strip and daywear marketed tray-based carbamide peroxide system provided significant
tooth whitening in subjects with tetracycline stain. The Strip group obtained the results in a shorter
time compared to the daywear tray group.
In this study, onset of shade improvement was earlier, and the magnitude of the change was
greater with strips compared to trays. Through Month 3, the strip group exhibited a statistically
significant (p < 0.05) 1.3 to 3.2 shade improvement relative to the tray control. What accounted for
the significant between-group differences in shade improvement seen early in treatment? One
likely explanation is that twice a day use of a strip for 30 minutes applied a higher concentration of
peroxide more frequently compared to 2-hours of continuous tray use of the lower concentration
carbamide peroxide gel. Other factors could have contributed to these findings, including the small
sample size in the tray group, differences in the tetracycline staining at baseline, and/or compliance
(strips versus the day wear regimen used for the trays). However, shade guides represent an
imperfect measure of efficacy, especially for complex clinical presentations like those seen with
tetracycline staining. As such, the comparative effectiveness of outcomes must be evaluated with
caution because causality cannot be assessed from multi-factorial research like this clinical trial.
This study provides new evidence of an expanded safety in-use with strip-based tooth whitening.
Both bleaching systems in this trial were well tolerated with daily use over a 6-month treatment
period. No subjects in either group discontinued treatment early due to product-related adverse
events. For the tray system, these findings corroborate other reports of safe continuous daytime
23,24
use of 10% carbamide peroxide on tetracycline stain . The research provides additional
assurance of the clinical safety of this 10% carbamide peroxide tray system with conventional use
over a few weeks, and longer term use for treatment of tetracycline staining. For the strip system,
the findings provide first evidence of in-use clinical safety with extended treatment. Long term
clinical trials of this duration may be particularly relevant in establishing clinical safety associated Eliminato: 214¶
212
with routine treatment, as a research model that evaluates extreme (intentional or unintentional)
use. Such research may only be appropriate with populations such as this one, where long-term
treatment is common and/or necessary to achieve a desired endpoint, where ethical and
experimental controls are adequate to interpret outcomes, and where rigorous and sufficient exit
criteria are established to assure in-use safety. Under these conditions, longer duration trials
represent a “torture test” of sorts, offering additional insight on short-term clinical safety.
bleaching with professional tray or strip systems can yield an evident improvement in appearance
within a few weeks. This non-invasive treatment may need to continue over an extended period.
Some individuals will show favorable response after 3-4 months, after which treatment may be
discontinued. Duration may be difficult to predict, given the variable clinical manifestations of
tetracycline staining. This study confirms that hydrogen peroxide will penetrate enamel and oxidize
dentin. Even with long term exposure to these various whitening regimens no adverse results were
noted.
In Chapter 8 we explore a new delivery system for tooth whitening. This is one of the first studies to
do a direct comparison of two paint-on delivery systems. The latest inclusion to OTC products is a
Brush technique. This technique is non-tray based paint on application. These products include a
19% sodium percarbonate film (5.3% hydrogen peroxide) along with an 18% carbamide peroxide
paint-on gel. The advantages to the paint- on products are ease of use as well as the elimination of
the need for a tray. These systems also limit gingival exposure. There is little data on efficacy of
these products. The objective of this trial was to compare the safety and whitening efficacy of an
experimental liquid strip (four weeks of use) to Colgate Simply White (three weeks of use).
This was a randomized, controlled, double-blind, parallel, single-center study. Fifty (50) generally
healthy subjects who desired to have their teeth whitened were enrolled in the study. Subjects who
qualified for the study based on the results of their Baseline visit were randomly assigned to one of
Eliminato: 214¶
213
two treatment groups. Data was obtained using a HC2500 CCD high resolution digital camera
manufactured by Fuji. It was equipped with a Fujinon A8x12BMD, 1:2.8/12-96mm zoom lens and a
linear polarizer to permit cross-polarized light. Two 150-watt lights located on each side of a CCD
camera provided the lighting. The unit was connected to a personal computer which recorded and
analyzed the images. Prior to daily use, the system was calibrated to assure proper operation.
Additionally, a color standard was centered and imaged every hour, and then was removed prior to
imaging subjects. Maxillary anterior facial surfaces were measured for tooth color using the digital
image technology. One color value (L* a* b*) was generated from the complete surface of the
measured teeth.
At the Week 4 visit, only the Experimental Film group was effective in whitening teeth as measured
by mean change in L* (lightness) from Baseline (p-value < 0.0001 from Table 7). The Experimental
Film group provided more than 4 times greater improvement in lightness (ΔL*) when compared to
the Colgate Simply White group with estimated means and standard errors of 1.065± 0.135 and
0.263 ± 0.146, respectively. The treatment comparison for ΔL* was statistically significant (p-value
= 0.0003 from Table 12). Only the Experimental Film group effective in whitening teeth as
measured by mean change in a* (redness) from Baseline (p-value = 0.0003 from Table 8). The
Experimental Film group provided more than 3.8 times greater improvement in redness (Δa*) when
compared to the Colgate Simply White group with estimated means and standard errors of –0.397
± 0.072 and –0.104 ± 0.078, respectively. The treatment comparison for Δa* was statistically
significant (p-value = 0.0099 from Table 13). Both treatments were effective in whitening teeth as
measured by mean change in W* (composite whiteness) from Baseline with p-values ≤ 0.0029
(Table 9). The Experimental Film group provided more than 4.2 times greater improvement in
composite whiteness (ΔW*) when compared to the Colgate Simply White group with estimated
means and standard errors of
–1.385 ± 0.146 and –0.325 ± 0.158, respectively. The treatment comparison for ΔW* was Formattato: Centrato
Eliminato: 214¶
214
statistically significant (p-value < 0.0001 from Table 14). Both treatments were effective at
Colgate Simply White group with estimated means and standard errors of 1.534 ± 0.147 and 0.788
± 0.160, respectively. The treatment comparison for ΔE* was statistically significant (p-value =
0.0020 from Table 15). This study indicated that the 19% sodium percarbonate film (5.3%
hydrogen peroxide) paint-on whitening product was affective in whitening teeth, however neither
system tested was as affective as the tray or strip systems previously tested.
In Chapter 9 we explore the rebound that occurs post bleaching as well as methods to limit its
affect. A randomized, parallel, examiner-blind clinical study was conducted to examine the ability of
2 toothbrushes to maintain teeth whitening after at-home bleaching. Forty subjects used a 15%
carbamide peroxide tray bleaching system at home for 2 weeks per the manufacturer’s instructions
and then were randomly assigned to use either the Sonicare® Advance power toothbrush or a
manual toothbrush as part of their home oral hygiene routine for 6 months. The color of the labial
surfaces of the subjects’ maxillary anterior dentition was assessed before bleaching and
immediately, 2 months, 3 months, and 6 months after bleaching. Color was assessed by
comparison with Vita® Classical shade tabs and by digital image analysis in the CIE L*a*b* color
space. Both groups demonstrated a rebound effect at the 2-month visit and beyond, with mean Vita
shade scores significantly higher than immediately after bleaching. At the 6-month evaluation, there
was a significant difference in the amount of rebound in each group. Specifically, the rebound of the
Sonicare brush group was on average 1.12 Vita shades less than that of the manual brush group.
The 6-month difference was confirmed through digital image analysis, with the Sonicare brush
group 4.8 L* units lighter, corresponding to 2 Vita shades, and 2.1 b* units less yellow than the
manual brush group. This clinical trial demonstrates that the Sonicare Advance toothbrush better
maintains whitening after bleaching treatment than a manual toothbrush.

Eliminato: 214¶
215
The analyses of the digital images and the Vita shade data both show the Sonicare toothbrush to
be superior to a manual toothbrush at maintaining whitening 6 months after bleaching. While this is
the first study examining the effect of Sonicare on maintaining whitening, there are other data on
the effect of a manual toothbrush. Matis and colleagues, for example, report an increase of 5.2 L*
units and 2.9 shade guide units only 6 weeks after a 2-week bleaching regimen using 15%
carbamide peroxide. Our results show a more modest but still measurable rebound effect for
manual brushing. The estimated 6-month Vita shade difference between groups was larger in the
digital analysis (2 Vita shades) than in the Vita shade analysis (1.12 Vita shades). This difference in
estimates may be the result of the varying precision and accuracy of the 2 efficacy measures. We
additionally note that the ordering of the Vita Classical shade guide does not follow the order
suggested by digital image analysis of the shade tabs. In particular, ranking the tabs by decreasing
luminance L*, that is the pure value axis of the L*a*b* color sphere, suggests not only that the color
tabs are incorrectly ordered but also that the color change between tabs is nonlinear. Similar
observations have been reported by O’Brien and colleagues and Paravina and colleagues. These
factors also may contribute to the difference in estimates between the 2 efficacy measures.
This study is important in a number of ways. It confirms that post bleaching rebound occurs as soon
as 1 month after bleaching and this rebound continues at a slower rate up to 6 month. Secondly this
data questions the degree of rebound reported in other studies. Finally this study brings in question
the adequacy of the value ordered shade guide in its present form for bleaching studies.
Formattato: Tipo di
In Chapter 10 an in vitro study was performed to measure the temperature increase in pulp carattere: Non Grassetto
Formattato: Tipo di
chamber produced by Zoom light (mercury halide) and to investigate the influence of this light in carattere: Grassetto
Formattato: Tipo di
conjunction with the application of bleaching gel on the intrapulpal temperature. The Zoom! Light carattere: (Predefinito) Arial
was designed specifically for tooth bleaching. The results achieved by this study indicate that
although previous reports showed significant temperature rise on the tooth surface our results
demonstrate that the intrapulpal temperature increases only slightly during the exposure time.
Therefore the Zoom light was found to cause only a slight increase in intrapulpal temperature. The Eliminato: 214¶
216
use of the light and gel demonstrated a significantly higher temperature increase than the light
alone. However, this increase is still lower than the necessary to cause pulpal damage (5.5 °C).
The sensitivity noted during light activated bleaching is most probably increase dehydration on the
surface of the tooth. This may relate to 5°C surface temperature change previously reported on the
enamel surface.
Finally this study supports the clinical observation that light activated bleaching does not result in
long term pulp damage and it suggests that the sensitivity noted during light activated tooth
whitening may be the result of dehydration and not pulpal irritation.
Formattato: Tipo di
In Chapter 11 an exploratory study was done to assess any surface morphological changes in carattere: Grassetto
Formattato: Tipo di
tooth enamel after treating with a currently marketed hydrogen peroxide strip bleaching system and carattere: Non Grassetto
Formattato: Tipo di
a currently marketed sodium chlorite tray-based system using an SEM Investigation. This study carattere: Arial
represents the first paper to evaluate enamel following tooth whitening using both visual analysis
and laser profolometry. In this study the use of a visual scoring system for changes on enamel
morphology indicated that there were no significant changes from the baseline in either the 6%
Hydrogen Peroxide gel group or the 2.5% Sodium Chlorite group. It was also noted that in all
evaluations the roughness observed was superficial in nature and that all teeth varied slightly at
baseline.
The laser profilometry data indicated that there is no statistical difference between the baseline and
21 day samples. This is true for both tooth whitening systems. In both groups the 21 day dosing
has no effect on surface roughness of the exposed teeth.
Using two different measurement techniques the results from both tests have the same conclusion
that 21 day exposure to two different tooth whitening systems had no observable or measurable
adverse effects on enamel.
Formattato: Tipo di
carattere: 12 pt
Conclusions and Recommendations Formattato: Centrato

Eliminato: 214¶
217
The following conclusions and recommendations may be drawn from our studies on tooth
whitening:
1. The use of a low dose delivery system is adequate to get significant whitening. numerati
2. The use of a polyethylene strip containing 5.3% hydrogen peroxide 30 minutes twice per
day results in significant whitening.
3. This research provides clear evidence of a peroxide concentration whitening response.
Whitening efficacy was greatest for the highest concentration group while the intermediate
concentration group had an intermediate response. This effect most approached linearity at
the earliest time point (Day 7).
4. This clinical research provides evidence of a concentration gradient for whitening response
following use of a low peroxide dose whitening system. As such, this may represent a first
example of concentration ranging for one of the self-directed bleaching systems. There is a
measurable concentration affect during bleaching.
5. The use of a light and/or heat to speed up the oxidation process in tooth whitening is of no
benefit. This was tested using the Halogen. Gas Plasma and Metal Halide light sources.
Dehydration appears to cause the initial improvement that is noted immediately post
bleaching.
6. The use of a mercury halide light for tooth whitening does not result in pulpal temperatures
that would cause irreversible pulp damage but might be able to result in dehydration of
exposed teeth.
7. Our data demonstrates the difficulty, regardless of the delivery system, in bleaching
tetracycline stained teeth. This confirms that the peroxide does penetrate to the dentin and
that the oxidation process affects the color of the stained dentin. It also confirms that this is
a slow process and requires extended exposure.
8. Long term exposure (6 month continuous use) to either 10% carbamide peroxide in a tray
system or 6.5% hydrogen peroxide strip resulted in no serious adverse events. This study
Eliminato: 214¶
218
represents the largest sample size for this type of study and the first to use the strip delivery
system.
9. Paint-on whitening systems vary in effectiveness and none of those tested equal the
efficacy found with the tray or strip systems.
10. Post bleaching rebound occurs as soon as 1 month after bleaching and this rebound
continues at a slower rate up to 6 month.
11. The adequacy of the value ordered shade guide in its present form for bleaching studies is
inadequate. This ordering on the shades is incorrect when checked using digital L*a*b*
analysis. The ADA needs to re-evaluate its requirement for this method of evaluation in
order to obtain ADA approval for tooth whitening systems.

Formattato: Tipo di
12. Tooth whitening systems tested had no observable or measurable adverse effects on carattere: Arial
enamel.
Acknowledgements
I wish to express my sincere gratitude to all who contributed to this work.
Prof. Dr Marco Ferrari who has supported me in many ways both as a friend and fellow researcher.
He has encouraged me to complete this thesis and pushed me to become a better scientist, as he
pushes himself. He has always been there when I have needed advise and I value him dearly.
Prof. Dr C.L. Davidson who has inspired me as a researcher and who I am always trying to emulate
in both my research and in my life.
Dr. Robert Gerlach, my good friend and fellow researcher. We have spent many hours discussing
our projects and he is a constant source of advice and friendship.
Dr’s Ferreria and Sharma who are wonderful young investigators always willing to help and always
wanting to learn. Formattato: Centrato

Eliminato: 214¶
219
Isabella Desir, my staff assistant, who is willing to put in long hours and always with a smile.
To my family that has always been there when I need them and support me in every way. To my
wife, Karen, who has been with me through it all and is a constant source of inspiration to me. My
children, Kurt and Chrissy; they put life in perspective. My family is most important to me and I
apologize to all of them for the hours of travel and study that have kept me from them.
Formattato: Tipo di
carattere: Non Grassetto
I would also to thank the members of the committee, Prof Piero Tosi, Rector of the
University of Siena, to Prof Alberto Auteri, Dean of the Faculty of Medicine, University of
Siena, to Prof Egidio Bertelli, vice-Dean of the Faculty of Medicine and Director of the
Department of Dental Science, and to Prof Marco Ferrari, Pro-Rector for international
Formattato: Tipo di
carattere: 11 pt
affairs and President of Dental School, University of Siena for their support with this thesis.
Formattato: Tipo di
CURRICULUM VITAE
Gerard Kugel, D.M.D., M.S.,

F.A.C.D., F.I.C.D., F.A.G.D., F.A.D.M. Formattato: Tipo di
171 Burlington Street carattere: (Predefinito) Arial,
Lexington, MA 02173 Non Grassetto
(781) 861-1935 Formattato: Tipo di

carattere: (Predefinito) Arial, 9
pt
Formattato: Tipo di
EDUCATION Tufts University School of Dental Medicine carattere: (Predefinito) Arial
Boston, Massachusetts
Formattato: Tipo di
D.M.D., Ph.D. Program, 1981-1985 carattere: (Predefinito) Arial,
D.M.D., 1985 Grassetto
sinistra, Rientro: Sinistro: 3,6
Sackler School of Graduate Biomedical pt
Sciences
Tabella formattata
Department of Anatomy and Cellular Biology
Formattato: Tipo di
Tufts University carattere: (Predefinito) Arial
Boston, Massachusetts Formattato: Tipo di
M.S., 1993 carattere: (Predefinito) Arial, 8
pt
Eliminato: 214¶
220
Cornell University Graduate School of Formattato: Tipo di
Medical Sciences
Department of Neurobiology
New York, NY
Ph.D. candidate, 1977-1979 (transferred)
Rutgers University Formattato: Tabulazioni:

62,1 pt, Allineato a sinistra +
New Brunswick, NJ Non a 67,5 pt
B.S. Biology and Psychology
1976
WORK EXPERIENCE Associate Dean for Research Formattato: Rientro: Sinistro:
0 pt
Tufts University School of Dental Medicine
March 2001 – Present
Visiting Professor, Restorative Dentistry
University of Siena, Siena, Italy
1993 - Present
Head of the Division of Operative Dentistry

Tufts University School of Dental Medicine
April 1988 – Present
Private Practice
Boston Center for Oral Health
400 Commonwealth Avenue
Boston, Massachusetts 02115
September 1988 – Present
Eliminato: 214¶
221
PUBLICATIONS Kugel G, PapathanasiouA, Williams III A J, Anderson C, Clinical Formattato: A destra 0 ch
Evaluation of Chemical And Light-Activated Tooth Whitening
Systems, Compendium Accepted July 2004. Formattato: Tipo di
Ferrari M, Kugel G, Cagidiaco M C, Barker M L, Gerlach R W, Formattato: Tipo di

Clinical Trial Evaluating the Peroxide Concentration Response of
Whitening Strips Over 28 Days, Am J Dent. In Press
Kugel G, Gerlach R W, Aboushala A, Susana Ferreira-Martin,

Marco Ferrari,The Long term use of 6.5% Hydrogen Peroxide
Bleaching Strips on Tetracycline Stain: A controlled Clinical Study,
J of Esth and Rest Dent, May-04. Accepted
Kugel G, What You Need to Know When Choosing a Material,

Dentist’s Money Digest, pages 24-25, April 2004
Kugel G, Aboushala A, Sharma S, Ferreira S, Anderson C,

Maintenance of Whitening with a Power Toothbrush After
Bleaching Treatment, Compendium, Vol. 25, No. 2, pages 119-
131, February 2004.
Ferreira S, Kugel G, A Simple Review of LED Curing Lights,

Contemporary Esthetics and Restorative Practice, pages 52-56,
November 2003.
Aboushala A, Kugel G, Meta N, Using a Novel Bite Plate to Alleviate

Chronic Bruxism Symtoms, Contemporary Esthetics and Restorative
Practice, Vol 7, No. 10 Pages 72-78, October 2003
Zhang Q, Rosenberg M, Kugel G, Agarwal R, Phillips j, Kumar S,

Effect of Nitrous Oxide on Intracellular Events of GT1-7 GnRH-
secreting Neurons, Anesth Prog 50:53-61, 2003
Zhang Q, Bratton G, Agarwal R, Calise D, Kugel G, Wan Y, Kumar A,

Lead-induced cell singnaling cascades in GT1-7 cells, Brain Research
Bulletin, 61, pages 207-217, 2003
Kugel G, Perry R, Restoring Anterior Maxillary Dentition Using

Alumina and Zirconia –Based, Compendium, Vol. 24, No. 8, pages
569-580, August 2003.
Zhang Q, Bratton G, Agarwal R, Calise D, Kugel G, Wan Y, Kumar A.

Lead-induced cell signaling cascades in GT1-7 cells, Brain Research
Bulletin Vol. 61, No. 207-217, April 2003
Eliminato: 214¶
222
Kugel G, Over-the-Counter Toothwhitening Systems, Compendium
Vol. 24, No 4A. April 2003
Fabianelli A, Kugel G, Ferrari Marco, Efficacy of self-etching primer on

sealing margins of Class II restorations, American Journal of Dentistry
Vol 16, No.1, pages 37-41, February 2003.
Kugel G, Perry R, Direct Composite Resins: An Update,

Compendium. Vol. 23, No. 7. July 2002.
Kugel G, Boghosian A. Impact of the Sonicare® Toothbrush on

Plaque and Gingivitis, Compendium. Vol. 23, No. 7. July 2002.
Suppl. 1
Kugel G, Boghosian A. Effects of the Sonicare® Toothbrush for

Specific Indications, Compendium. Vol. 23, No. 7. July 2002.
Suppl. 1
Papathanasiou A, Kastali S, Perry R, Kugel G, Clinical Evaluation

of a 35% Hydrogen Peroxide In-Office Whitening System,
Compendium. Vol. 23, No. 4. April 2002.
Perry R, Kugel G, Success with Inlays/Onlays: The Seven

Essentials, Compendium. Vol 23, No. 3. March 2002.
Gheewalla E, Perry R., Kugel G, Effects of Three Electric

Toothbrushes on Orthodontic Bracket Retention, Journal of
Clinical Orthodontics, Volume XXXVI No. 2, January 2002
Formattato: Corpo del testo,
Allineato a sinistra, Destro 0 pt
Fabianelli A, Kugel G, Ferrari M. Efficacy of self-etching primer on
sealing margins of CI II restorations. American Journal of Dentistry.
Accepted 2002.
Ferrari M, Cagidiaco M, Kugel G, Dolci G. Evaluation concentration

response after 4 weeks treatment with a flexible, polyethylene
whitening strips. Compendium/Special Issue Volume 22, No. 2,
2001.
Kugel G, Aboushala A, Zhou X, Gerlach R. Daily Use of Whitening

Strips on Tetracycline-Stained Teeth: Comparative Results After 2
Months. Compendium Volume 22, No. 2, 2001.
Eliminato: 214¶
223
Kugel, G., Garcia-Godoy F., Direct Esthetic Adhesive
Restorative Materials A Review. The Indian Dentist, No. 7-13,
21, April – June 2001
Papathanasiou A., Bardwell D, Kugel G., A Clinical Study

Evaluation a New Chairside and Take-Home Whitening System.
Compendium of Continuing Education in Dentistry, Volume 22,
No. 4:289-300, April 2001
Goracci C., Gheewalla R., Kugel G., Ferrari M., Orthodontic-

restorative treatment of chipped or worn incisors. American
Journal of Dentistry, Volume 14, No. 50-55, February, 2001
Kugel G., Provisional Esthetic Enhancements Following Initial

Treatment to Correct Anterior Wear, Esthetic Technique,
Volume 1, No. 1:3-7, April 2001
Leinfelder K, Kugel G., Flowable Compomers, Dialogues in

Esthetic Dentistry, Volume 2, No. 1:7-8, April 2001
Javaheri DS, Kugel G., Janis JN. Current Status of At-Home

Bleaching. Practical Procedures and Aesthetic Dentistry,
Volume 13, No. 1:10-13, January/February 2001
Perry R, Kugel G. Two-Year Clinical Evaluation of a High-

Density Posterior Restorative Material. Compendium of
Continuing Education in Dentistry, Volume 21,No. 12:1067-
1080, December 2000
Weinstock E, Skoulas A, Kugel G, Aboushala A. The Myth of

Dentist-Patient Confidentiality. Compendium of Continuing
Education in Dentistry, Volume 21, No. 12:1056-1064, December
2000
Kugel G. Direct and Indirect Adhesive Restorative Materials: A

Review. American Journal of Dentistry, Volume 13, Special
Issue, No. 35-40, November, 2000.
Eliminato: 214¶
224
Kugel G, Garcia-Godoy F. Direct and Indirect Esthetic Adhesive
Restorative Materials: A Review. Dental News, Volume VII,
Number 3:29-39, 2000
Perry R, Kugel G, Kunzelmann KH, Flessa HP, Estafan D.

Composite Restoration Wear Analysis: Conventional Methods
vs. Three-Dimensional Laser Digitizer. JADA, Vol. 131, No. 10:,
p.1472-1477, October 2000.
Papathanasiou A, Bardwell D, Kugel G. Combining In-Office and

Take-Home Whitening Systems. Contemporary Esthetics and
Restorative Practice. Vol. 4. No. 8: 88, September 2000
Kugel G, Garcia-Godoy, F. Direct Esthetic Adhesive Restorative

Materials: A Review. Contemporary Esthetics and Restorative
Practice. Vol. 4. No. 9: 6-10, September 2000.
Kugel G, Kastali S. Tooth-Whitening Efficacy and Safety: A

Randomized and Controlled Clinical Trial. Compendium 21, S29,
16-21, July 2000
Kugel G. Nontray Whitening. Chairside: Compendium. Vol. 21, No.

6, 524-528, June 2000.
Kugel G, Ferrari M. The Science of Bonding: From First to Sixth

Generation. JADA, Vol. 131:20S-25S, June 2000.
Kugel G, Perry R, Ferrari M, Lalicata P. Disinfection and Communication

Practices: A Survey of U.S. Dental Laboratories. JADA, Vol. 131:786-792, June
2000.
Zervou C, Kugel G, Leone C, Zavras A, Doherty E. Enameloplasty

Effects on Microleakage of Pit and Fissure Sealants Under Load: an
In-Vitro Study. The Journal of Clinical Pediatric Dentistry. 24(4): 279-
285, April 2000
Ferrari M, Mannocci F, Mason PN, Kugel G, In vitro leakage of

resin-bonded all-porcelain crowns. Journal of Adhesive
Dentistry, 1:3:233-242, 1999.
Kugel G, Swift EJ, Sorenson JA, Dunne JT, Tucker JH. A

prospective clinical evaluation of electronically mixed polyvinyl
siloxane impression materials. Compendium, S24:2-22, 1999.
Eliminato: 214¶
225
Petridis H, Hirayama H, Kugel G, Habib C, Garefis P. Shear
bond strength of techniques for bonding esthetic veneers to
metal. Journal of Prosthetic Dentistry, 82:5:608-614, 1999.
Ferrari M, Cagidiaco MC, Kugel G, Davidson CL. Clinical

evaluation of a one-bottle bonding system for desensitizing
exposed roots. American Journal of Dentistry, 12:5:243-249,
1999.
Kugel G, Perry R, Hoang E, Hoang T, Ferrari M. Dyract

Compomer: Comparison of Total Etch vs. No Etch Technique.
Journal of the Academy of General Dentistry, Volume 46,
Number 6:604-606, Nov-Dec 1998.
Kugel G. Clinical Testing of Surefil. Journal of International

Dental Symposia, 5:7, 1998.
Ferrari M, Mason PN, Fabranelli A, Mannocci F, Kugel G,

Davidson CL. Influence of Tissue Characteristics at Margins on
Leakage of Class II Indirect Restorations, Accepted, American
Journal of Dentistry, 1998.
Ferrari M, Kugel G. Handling of Composites in Posterior Teeth,

Compendium, 19:879-892, 1998.
Kugel G, Ferrari M. AelitefloTM. To Base or Not to Base, There

Is No Question!, Restorative Quarterly, 1:7, April 1998.
Karuri AR, Kugel G, Engelking LR, Kumar MSA. Alterations in

Catecholamine Turnover Rate in Specific Regions of the Rat Brain
Following Acute Exposure to Nitrous Oxide, Brain Research
Bulletin, 45:557-561, 1998.
Kugel G, Minimale Präpartion für Frontzahnrestaurationen

(Minimal Preparation for Anterior Restorations), Phillip Journal,
14:383-384, 1997.
Donly K, Vargas M, Meckes M, Sharma A, Kugel G, Hurley E. In-

Vitro Comparison of Restoration Wear and Tensile Strength
Following Extended Brushing with Sonicare and Manual
Toothbrushes, Journal of Clinical Dentistry, 8:1:30-35, 1997.
Zammitti S, Habib C, Kugel G. Use of Environmental Scanning

Electron Microscopy to Evaluate Dental Stain Removal, Journal
of Clinical Dent, 8:1: 20-25, Winter 1997.
Eliminato: 214¶
226
Samadzadeh A, Aboushala A, Hurley E, Kugel G. A Comparison
of Fracture Strength Between PMMA and Resin-Based Provisional
Restorations Reinforced with Plasma-Treated Woven Polyethylene
Fiber, Journal of Prosthetic Dentistry, 78:5:447-450, November
1997.
Kugel G, Perry R, Putignamo A, Ferrari M. Valutazione clinica a due

anni dello spectrumTPH nel restauro di lesioni cariose in cavità di classe
II in denti permanenti.. Quintessence International, Settembre/Ottobre
1997.
Ferrari M, Kugel G. Handling of Composites in Posterior Teeth,

Compendium, 19:879-892, 1998.
Kugel G. Buying Right, Journal of the Massachusetts Dental

Society, 46:2:12-14, October 1997.
Perry RD, Kugel G, Habib CM, McGarry P, Settembrini L. A

Two Year Clinical Evaluation of TPH for Restoration of Class II
Carious Lesions in Permanent Teeth, General Dentistry, 45:
4:344-349, July/August 1997.
Ferrari M, Mannocci F, Cagidiaco MC, Kugel G. Short-Term

Assessment of Leakage of Class V Composite Restorations
Placed In Vivo, Clinical Oral Investigation, 1:2:61-64, June 1997.
Kugel G, Perry R, Hoang E. Effective Tooth Bleaching in 5 Days:

Using a Combined In-Office and At-Home Bleaching System,
Compendium, 18:4:378-383, April 1997.
Abdel-Latif M, Kugel G, Norris L, Kabani S. Nd: Yag Laser and

Conventional Techniques in Bone Surgery, Cairo Dental Journal,
13:1:225-230, 1997.
Kugel G. Classification and Application of Cementation

Alternatives, Signature: The Art and Science of Modern Dentistry,
Fall 1997.
Ferrari, M, Cagidiaco, Kugel G, Davidson CL. Dentin Infiltration by

Three Adhesive Systems in Clinical and Laboratory Conditions,
American Journal of Dentistry, 9:6:240-244, December 1996.
Weiner RS, Weiner LK, Kugel G. Teaching the Use of Bases and
Liners: A Survey of North American Dental Schools, JADA,
127:11:1640-1645, November 1996.
Eliminato: 214¶
227
Kugel G, Perry RD, Habib CM, McGarry P. A Two Year Clinical
Evaluation of Pertac Hybrid for Restoration of Class II Carious
Lesions in Permanent Teeth, Compendium, November 1996.
Ferrari M, Cagidiaco MC, Kugel G. Leakage of Class V Resin

Composite Restorations Placed in Vivo, American Journal of
Dentistry, October 1996.
Aboushala A, Kugel G, Hurley E. Class II Composite Resin

Restorations Using Glass-Ionomer Liners: Microleakage Studies,
Journal of Clinical Pediatric Dentistry, 21:1:67-70, Fall 1996.
Agawal RK, Kugel G, Karuri A, Gwosdow AR, Kumar, MSA.

Effects of Low and High Doses of Nitrous Oxide on
Preproenkephalin on RNA and Its Peptide Methionine
Enkephalin Levels In the Hypothalamus, Brain Research,
730:1,2:47-51, August 1996.
Ferrari M, Cagidiaco MC, Kugel G. All -Ceramic Fixed

Restorations: A Preliminary Clinical Evaluation, Practical
Periodontics Aesthetic Dentistry, 8:1:73-80, Jan-Feb 1996.
Habib C, Smith S, Kugel G, Aboushala A. Dimensional Stability of

Elastomeric Impressions After Long-Term Disinfection, Journal of
Prosthetic Dentistry, January 1996.
Ferrari M, Kugel G. IPS - Empress Crowns: Clinical Reports,

Practical Periodontics and Aesthetic Dentistry, 1996.
Kugel G, Bardwell DN. Restoration of a Class V Lesion Using a

New Compomer Material, Signature: The Art and Science of
Modern Dentistry, 14-17, November 1995.
Kugel G. The Changing Face of Oral Health Care, Feature Article,

Tuftonia, 27, Spring 1994.
Ferrari M, Dalloca L, Kugel G, Bertelli E. An Evaluation of the

Effect of the Adhesive Luting on Microleakage of the IPS Empress
Crowns, Practical Periodontics and Aesthetic Dentistry, 6:4:15-24,
May 1994.
Fischman SL, Kugel G, Truelove RB, Nelson BJ, Cancro LP. The
Motivational Benefits of a Dentifrice Containing Baking Soda and
Hydrogen Peroxide Used, The Journal of Clinical Dentistry, 3:3 88-
92, 1992.
Eliminato: 214¶
228
Russell DA, Kugel G. Preceptor Program: An Alternative Mode of
Instruction for the Slowly Progressing Dental Student, Journal of
Dental Education, 55:1:36-37, January 1991.
Champion MA, Kugel G, Gruskowski C. Evaluation of a New

Intraoral Isolation Device, Operative Dentistry, 16:181-185, 1991.
Kugel G, Zive M, Agawal RK, Beumer JR, Kumar AM. Effects of

Nitrous Oxide on the Concentration of Opioid Peptides, Substance
P, and LHRH in Brain and β-Endorphin in the Pituitary, Anesthesia
Progress, 38:206-211, 1991.
Kugel G, Letelier M, Zive H, King JC. Nitrous Oxide and Infertility,

Anesthesia Progress, 37:4:176-180, July 1990.
Kugel G, Zive M, Norris L. Nitrous Oxide and Occupational

Exposure, Journal of the Society for the Advancement of
Anesthesia in Dentistry, 7:10:266-276, May 1990.
Kugel G, Zive M, Norris L. N2O/O2 - It's No Laughing Matter,

Review Article, Journal of the American Analgesia Society,
24:1:14-16, March 1990.
Kugel G, Norris L, Zive M. Nitrous Oxide; Occupational Exposure:

It's Time to Stop Laughing. Anesthesia Progress, 36:6:252-257,
1989.
King J C, Kugel G, Zahniser D, Wooledge K, Damassa D,

Alexsavich B. 3-D Analyses Reveal Changes in Populations of
LHRH Cell Bodies Following Gonadectomy, Peptides, 8:721-735,
August 1987.
King JC, Lechan RM, Kugel G, Anthony ELP. Acrolein: A Fixative

for - Immunocyto-chemical Localization of Peptides in the Central
Nervous System, The Journal of Histo-chemistry and
Cytochemistry, 31:1:62-68, January 1983.
Formattato: Tipo di
Eliminato: 214¶
229
ABSTRACTS Perry R, Kugel G, Shrama S, Ferreira S, Clinical Evaluation of a LED
Curing Light, Journal of Dental Research, 83: 540 March 2004
Kugel G, Ferreira S, Sharma S, Barker M L, Garlach R W, Comparison of Formattato: Tipo di

Daytime and Nighttime Brush-Applied Whitening Systems, Journal of
Dental Research, 83:1912 March 2004
Papathanasiou A, Kastali S, Clinical Evaluation of a New Adhesive-

Composite System, Journal of Dental Research, 83:538 March 2004
Petkevis J, Alfaro M, Doherty E H, Kugel G, Kanca J, Self-etch adhesive

bond strength at two time intervals, Journal of Dental Research, 83: 465
March 2004
Bedi A, Hirayama H, Kugel G, Forgione A G, Surface Roughness and

Irregularities of Castings using Different Iinvestment Techniques, Journal Formattato: Tipo di
of Dental Research, 83: 1680 March 2004 Non Corsivo
Formattato: Tipo di
Kugel G, Papathanasiou, Clinical Evaluation of Two Different In-office carattere: (Predefinito) Arial
Tooth Whitening Systems, Journal of Dental Research, 28: 897 March Formattato: Tipo di
2003 carattere: (Predefinito) Arial,
Non Corsivo
Aboushala, A, Kugel G, Sharma S, Ferreira S, SonicareToothbrush Formattato: Tipo di

Whitening Effect after Bleaching Treatment, Journal of Dental Research,
Formattato: Tipo di
82: 614, March 2003 carattere: (Predefinito) Arial,
Corsivo
Formattato: Tipo di
Anderson C, Kugel G, Aboushala, A, Sharma S, Ferreira S, Rebound carattere: (Predefinito) Arial
Evaluation of Post-Bleaching Maintenance Utilizing Manual and Electric
Toothbrushes; Quantitative Assessment by Digital Photography, Journal
of Dental Research, 82: 605, March 2003
Kugel G, Aboushala, A, Zhou X, Gerlach R Six-month Continuous Use of

Two At-home Professional Bleaching Systems on Tetracycline Stain,
Journal of Dental Research, 82: 32, March 2003
Anderson C, Kugel G, Ferreira S, Aboushala, A, Sharma S, Six-month

Rebound Evaluation of Subjects Treated with a 15% Carbamide Peroxide
Gel; Quantitative Assessment by Standard Digital Photography, Journal
of Dental Research, 82: 1303, March 2003
Perry R, Papathanasiou A, Kugel G, Davidiian E, A Comparison of Two

Flowable Composite Materials in Posterior Restorations Journal of
Dental Research, 82: 256, March 2003
Eliminato: 214¶
230
Watts R, Joffre E, Doherty E, Kugel G, Shear Bond Strength Investigation
of an Experimental Self-etching Bonding System, Journal of Dental
Research, 82: 566, March 2003
Anderson C, Kugel G, Perry R, Garcia-Godoy F, Evaluation of an

Experimental One-Step Composite Polishing System, Journal of Dental
Anderson C, Sethi S, Kugel G, Perry R, Garcia-Godoy F, Comparison of

Surface Gloss and Time by Three Composite Polishing Systems,
Journal of Dental Research, 81: 1273, March 2002
Kugel G, Aboushala A, Zhou X, Gerlach R W, Use of Whitening Strips

on etracycline: Results after four months, Journal of Dental Research,
81: 2442, March 2002
Kim M S, Reusch B, Hoffmann H, Doherty E H, Kugel G, Surface

Wettability of Saliva and Blood Plasma During Setting of Impression
Materials, Journal of Dental Research, 81: 2660, March 2002
Nguyen T, Doherty E H, Aboushala A, Kugel G, Perry R, Effect of

Chemomechanical Caries Removal System on Microleakage of
Composite Resin Restorations, Journal of Dental Research, 81: 3391,
March 2002
Anderson C, Kugel G, Rebound Evaluation of Tetracycline Stained

Subjects Treated with a 6.5% Hydrogen Peroxide Gel; Quantitative
Assessment by Standard Digital Photography, Journal of Dental
Perry R, Gheewalla E, Kugel G, A Comparison of Three Electric

Toothbrushes on Orthodontic Bracket Retention, Journal of Dental
Research, 80: 590, 2001
Kim MS, Doherty EH, Kugel, G, Flow Under Pressure of Four Impression
Materials Using Shark-Fin Device, Journal of Dental Research, 80: 624,
2001
Kastali S, Papathanasiou A, Perry R, Kugel G, Clinical Evaluation Of A

Light To Heat Activated Bleaching System, Journal of Dental Research,
80: 926, 2001
Eliminato: 214¶
231
Kugel G, Kastali S, Sagel P, Gerlach R, Six-Month Clinical Response
with Whitening Strips: Comparison to Placebo, Journal of Dental
Research, 80: 1174, 2001
Lokko NN, Kugel G, Habib C, Doherty E, Rand W, In Vitro Bond Strength

Evaluation of Resin, Modified Glass Ionomer Cements, Journal of Dental
Research, 80: 1304, 2001
Verdier A, Kugel G, Habib C, Comparison of Surface Finish Produced on

Resin Composites following Extended Brushing With A Manual
Toothbrush and Sonicare, Journal of Dental Research, 80: 1337, 2001
Perry R, Kugel G, Aboushala A, Two-Year Clinical Evaluation of a High-

Density Posterior Restorative, Journal of Dental Research, 79:158, 2000.
Fabianelli A, Vichi A, Kugel G, Ferrari M, Influence of Self-etching

Priming Bonding Systems on Sealing Ability of Class II Restorations:
Leakage and SEM Evaluation, Journal of Dental Research, 79:305, 2000.
Bardwell D, Habib C, Kugel G, Mehta N, Leone C, Microleakage of

Previously Restored Class II Restoratives After Exposure to 10%
Carbamide Peroxide, Journal of Dental Research, 79:306, 2000.
Kastali S, Papathanasiou K, Perry R, Kugel G, Clinical Evaluation of a

New Hybrid Composite, Journal of Dental Research, 79:333, 2000.
Zervou C, Kugel G, Leone C, Zavras A, Doherty E, White G.E.,

Enameloplasty and Load Effects on Microleakage of Sealants (in vitro),
Journal of Dental Research, 79:1688, 2000.
Papathanasiou K, Kastali S, Perry R, Kugel G, Clinical Evaluation of Light

Cured Flowable Compomere in Class V Restorations, Journal of Dental
Research, 79:1735, 2000.
Rassovsky M, Hirayama H, Habib C, Kugel G, The Expansion of Various

Luting Agents Used to Cement Post & Core: An in vitro study, Journal of
Dental Research, 79:2327, 2000.
Naidu K, Kugel G, Habib C, Class II Composite Restorations:

Microleakage Using Three Different Curing Systems, Journal of Dental
Research, 79:2466, 2000.
Eliminato: 214¶
232
Habib C, Kugel G, Effect of Aging on Three Enamel Dentin Adhesive
Systems, Journal of Dental Research, 79:2475, 2000.
Aboushala A, Kugel G, Efthimiadis N, Korchak M, Efficacy of a

Computer-controlled Injection System of Local Anesthesia, in vivo,
Aboushala A, Mehta N, Forgione A, Kugel G, Chapman R. Vertical

Dimension and Electromyography of Masseters in Complete Denture
Patients, Journal of Dental Research, 78:2911, 1999.
Nam C, Kugel G, Habib C. Changes in Enamel Surfaces After Take

Home Bleaching Treatment in vitro, Journal of Dental Research,
78:1695, 1999.
Perry R, Kugel G. One-Year Clinical Evaluation of a High-Density

Posterior Restorative, Journal of Dental Research, 78:1628, 1999.
Lalsingh C, Hurley E, Hassan M, Trushkowsky R, Kugel G,

Leone C. Effects of Curing Lights on Microleakage in Class V
Composite Restorations, Journal of Dental Research 78:1601,
1999.
Papathanasiou A, Kastali G, Kugel G, Bardwell D, Hurley E.

Microleakage Evaluation of Three Class II Composite
Restorative Techniques in vitro, Journal of Dental Research
78:1600, 1999.
Hurley E, Aboushala A, Perry R, Kugel G. Microleakage

in Class II Restorations Using a New Posterior
Composite, Journal of Dental Research 77:487, June
1998.
Drukteinis S, Hurley E, Perry R, Kugel G. The Performance of

Aluminum Oxide and Cojet Microetchant Systems, Journal of
Dental Research 77:506, June 1998.
Gheewalla E, Perry R, Kugel G. Effect of Powered

Toothbrushes on Orthodontic Bracket Adhesion in vivo, Journal
of Dental Research, 77:506, June 1998.
Eliminato: 214¶
233
Kugel G, Karuri A, Kumar MSA. Alterations in the
Cathecholamine Turnover Rate in Specific Regions of Rat Brain
Following Acute Exposure to Nitrous Oxide, Journal of Dental
Research 77:921, June 1998.
Ferrari M, Mason PN, Fabianelli A, Kugel G, Davidson CL.

Influence of Different Margin Substrates on Leakage of Class II
Indirect Restorations, Journal of Dental Research 77:2248,
June 1998.
Aboushala A, Kugel G, Perry R, Leone C. Resin-Ionomer

Restoration of Molar Furcations in Humans, Journal of Dental
Ferrari M, Cagidiaco MC, Kugel G, Davidson CL. Clinical

Evaluation of SB1 Root Desensitization with/without Acid
Etching. Journal of Dental Research 77:2586, June 1998.
Ferrari M, Mannocci F, Innocenti M, Kugel G, Davidson CL.

Clinical Evaluation of Dyract AP and Fuji IX to Build up
Abutments for Porcelain Crowns, Journal of Dental Research
77:2598, June 1998.
Kastali S, Kugel G, Perry R, Papathanassiou A. Combined

In-Office and At-Home Bleaching Systems: An Evaluation,
Journal of Dental Research 77:2604, June 1998.
Perry R, Kugel G, Kastali S. Evaluation of a Non-Hydrogen

Peroxide At-Home Bleaching System, Journal of Dental
Kugel G, Squier C. Fact vs. Fiction: The Transfer of

Scientific Knowledge into the Dental Curriculum, Journal of
Dental Research 77:4, March 1998.
Aboushala A, Mehta N, Forgione A, Kugel G, Chapman R,

Clark RE. Vertical Dimension and Electromyography of
Sternocliedomastoids in Complete Denture Patients, Journal
of Dental Research, 77:456, March 1998.
Chafka A, Mehta N, Kugel G, Hayes C, Forgione A. Effect of

Graded Increases in Vertical Dimension on Cervical Flexor
Strength, Journal of Dental Research 77:735, March 1998.
Kugel G, Lalicata PJ, Perry R. Survey of U.S. Dental

Impression Materials and Techniques, Journal of Dental
Research, 76:1343, March 1997.
Eliminato: 214¶
234
Daryabegi Y, Perry R, and Kugel G. Differences Shear
Bond Strength of Three Dentin Bonding System, Journal of
Dental Research, 76:1387, March 1997.
Fu A, Mehta N, Forgione A, Clark E, Hayes C, Kugel G.

Abdallah E. Maxillomandibular Relationship in TMD Patients
Before and After Short Term Bite Plate Therapy, Journal of
Hoang E, Kugel G. and Perry R. Combined in Office and

Home Applied Bleaching System, Journal of Dental
Perry R, Kugel G, McGarry P, Hurley E. An In Vivo

Subcutaneous Investigation of a Resin-Ionomer, Journal of
Aboushala A, Mehta N, Forgione A, Kugel G. Chapman R.

and Clark RE. Vertical Dimension Effects on
Strenocleidomastoid Strength in Complete Denture Patients,
Journal of Dental Research, 76:3185, March 1997.
Bahram R, Aboushala A, Kugel G, Perry R. Compomer

Effects on Microleakage in Class II Composite Resin
Restorations, Journal of Dental Research, 76:3236, March
1997.
Druktenis S, McGarry P, Aboushala A, Kugel G, Habib C.

Effect of Adhesives on Microleakage Between Dentin and
Light Cured Glass Ionomer Liners, Journal of Dental
Yau L, Perry R, Kugel G. Three Body Wear of Light Cured

Flowable Composites, Journal of Dental Research, 76:3276,
March 1997.
McSweeney T, Perry R, Aboushala A. Kugel G. Different

Liners in Class II Composite Resin Restorations, Journal of
Vaughn V, Kugel G, Perry R, Noonan ST. Measuring Flow

of Elastomeric Impression Materials Using the Shark Fin
Device, Journal of Dental Research, 76:3292, March 1997.
Ferrari M, Cagidiaco MC, Kugel G, Davidson CL. Dentin

Infiltration by Three Adhesive Systems in Clinical and
Laboratory Conditions, American Journal of Dentistry, 9:6,
December 1996.
Eliminato: 214¶
235
Habib C, Smith C, Kugel G, Aboushala A. Comparison of
Dimensional Stability of Elastomeric Impression After
Immersion Disinfection, Journal of Dental Research, 75:357,
March 1996.
Sharma A, Kugel G, Hurley E. Evaluation of the Effect of

Sonic and Manual Toothbrushes on Cemented Crowns,
Samadzadeh A, Aboushala A, Kugel G. A Comparison of

Fracture Strengths Between PMMA and Resin-Based
Provisional Restorations Reinforced with Plasma-Treated
Woven Polyethylene Fiber, Journal of Dental Research,
75:369, March 1996.
Marcus A, Bender G, McGarry P, Kugel G. Comparison of

Dental Cements Shear Bond Strength to a Semi-Precious
Alloy Surface In Vitro, Journal of Dental Research, 75:398,
March 1996.
Vaughn V, Bardwell D, Kugel G, Perilli. Follow-Up

Comparing Three Polishing Systems to Glazed Porcelain
Utilizing Profilometry, Journal of Dental Research, 75:1038,
March 1996.
McSweeney T, Perry R, Kugel G. Profilometry Comparison

of Polished Porcelain. Journal of Dental Research, 75:1039,
March 1996.
Bhatt A, Gheewalla E, Perry R, Kugel G. Comparison of a

Compomer and Resin Cement for Bonding of Orthodontic
Bracket, Journal of Dental Research, 75:1259, March 1996.
Perry R, Kugel G, Kunzelmann KH, Flessa HP, Mehi A,

Hickel R. A Composite Study of Wear Analysis Methods of
In-Vivo Posterior Composite Restorations, Journal of Dental
Lee K, Aboushala A, Kugel G. Microleakage of Class II

Composite Resin Restorations Using Different Placement
and Light Cure Techniques In Vitro, Journal of Dental
Eliminato: 214¶
236
Perry R, Kugel G, Kunzelmann KH, McGarry P. Two-Year
Evaluation of a Hybrid Composite for Posterior Restorations.
Prezioso A, Kugel G, Perry R. Microleakage: A Comparison

of Three Chairside Ceramic Repair Kits In Vitro. Journal of
Hoang E, Perry R, Aboushala A, Kugel G. Comparison of

Microleakage Using Etched and Non-Etched Techniques in
Class V Restorations, Journal of Dental Research, 75:2966,
March 1996.
Vaughn V, Aboushala A, Habib C, Kugel G. Comparison

Between Two Sealants for Reducing Class II Composite Resin
Microleakage In Vitro, Journal of Dental Research, 75:3017,
March 1996.
Beaber W, Arbree N, Kugel G. Pilot study: A Skin Protectant

for Latex-Glove-Induced Dermal Sensitivity Reaction, Journal
Smith N, Sharma A, Habib C, Perry R, Kugel G. Comparison

of a Cordless Curing Light and a Single Unit Curing Light,
Vaughn V, Bardwell D, Kugel G, Perilli R. Comparing Three

Polishing Systems to Glazed Porcelain Utilizing Profilometry,
Resnick S, Prezioso A, Kugel G, Smith C, McGarry P. Effect of

Surface Treatments on Microleakage of Composite - Ceramic
Repair, Journal of Dental Research,. 74:228, March 1995.
Joseph A, Perry R, Kugel G, Smith C. Effects of Varying

Concentrations of 4-META
on Tensile Strength on Bonding Composite to Dentin, Journal
Morrill F, Galburt R, Kugel G, Habib CM. Comparison of Bond

Strength Formed Between Amalgam and Composite by
Varying the Ratio of Spherical to Lathe Cut Particle, Journal of
Dental Research, 74: 743, March 1995.
Zammitti S, Kugel G, Habib C. Environmental Scanning

Electron Microscope Study Evaluating the Efficacy of a Sonic
Toothbrush, Journal of Dental Research, 74:970, March 1995.
Eliminato: 214¶
237
Mehta N, Kugel G, Lamkin J, Bansal S, Forgione A.
Effectiveness of Electronic Anesthesia in Controlling Pain
During Periodontal Scaling, Journal of Dental Research,
74:972, March 1995.
McSweeney T, Perry R, Kugel G. Tensile Strength of Dentin

Bonding Agents With Different Acid Etch Preparations, Journal
Supnet L, Bhatt A, Aboushala A, Bardwell D, Smith C, Kugel G.

Microleakage of Three Experimental Dentin Primers With
Altered HEMA Concentrations, Journal of Dental Research,
74:1112, March 1995.
Perry R, Kugel G, Habib C, McGarry P, Champion M. Two-

Year Evaluation of a Hybrid Composite for Posterior
Restorations, Journal of Dental Research, 74:1224, March
1995.
Kugel G, Court MH, Agarwal RK, Kumar MSA. Effects of

Nitrous Oxide on Preproenkephalia mRNA and Methionine
Enkephalin, Journal of Dental Research, 74:1309, March 1995.
Bahram R, Kugel G, Mclure T, Habib C. Comparison of

Polishability of Three Composite Materials, Journal of Dental
Aboushala A, Kugel G, Habib C. Microleakage Class II

Composite Restorations Using Glass Ionomer Liner, Journal of
Shayegan A, Aboushala A, Kugel G. Microleakage of Class II

Composite Restoration Using a Glass Ionomer, Liner and
Base, Journal of Dental Research, 74:1399, March 1995.
Smith N, Gheewalla E, Kugel G, Habib C. Evaluation of Effects

of a Sonic Toothbrush
on the Bond Strength of Bonded Orthodontic Appliances,
Ferrari M, Kugel G, Davidson CL. In Vivo and In Vitro Hybrid

Layer Formation, IADR-CED Meeting, Lubiana, 1995.
Habib C, Smith C, Kugel G, Aboushala A. Dimensional

Stability of Elastomeric Impressions After Long Term
Disinfection, Journal of Dental Research, 73:409, 1994.
Eliminato: 214¶
238
Morrill F, Galburt R, Kugel G, Zive M, Habib C. Comparison of
Different Shaped Particles of Amalgam Alloy Bonded to
Composite and Dentin with 4-Methacryloxyethyl Trimellitate
Anhydride, Journal of Dental Research, 73:221, 1994.
Bahram R, Kugel G, Zive M, Habib C, Golden M. Comparison

of Bond Strength of Two Dentin Bonding Systems to Radicular
Dentin, Journal of Dental Research, 73:199, 1994.
Mehta N, Kugel G, Al Shuria A, Sands M, Forgione A. Effect of

Electronic Anesthesia T.E.N.S. on T.M.J. and Orofacial Pain,
Kugel G, Smith N, Sharma A, Habib C, Perry R. A Comparison

of a Cordless Curing Light and a Single Unit Curing Light,
Zive M, Champion M, Kugel G. Marginal Microleakage Around

Tooth-Colored Inlay Systems, Journal of Dental Research,
72:307, 1993.
Ghazinouri R, Zammitti S, Zive M, Kugel G, Habib C.

Microleakage Using a New Technique for Posterior Composite
Restorations, Journal of Dental Research, 72:308, 1993.
McGarry P, Kugel G, Habib C, Perry R. Clinical Evaluation of a

Small Particle Composite to Treat Root Caries & Cervical
Erosions, Journal of Dental Research, 72:349, 1993.
Bellucci A, Kugel G, Habib C, Zive M. Adhesion Strengths of

Four Luting Agents with Various Core Buildup Materials,
Habib C, Kugel G, Herr K. Two-Year Evaluation of

Composite Restoration of Root Surface Caries After
Chemo-Mechanical Excavation, Journal of Dental
Research, 72:381, 1993.
Kugel G, Habib C, Zammitti S. Enamel and Dentin

Surfaces After Treatment With Adhesion Conditioners
Using the Environmental SEM, Journal of Dental Research,
72:387, 1993.
Agarwal R, Zive M, Kugel G, Gwosdow A, Kraytsberg G,

Kilpatrick D, Kumar A. Nitrous Oxide Effects on the Expression
of Brain Opiate System, Journal of Dental Research, 71:913A,
March 1992.
Eliminato: 214¶
239
Jong G, Zive M, Kugel G, Habib C. Surface Treatment Effects on
Porcelain Composite Bonding, Journal of Dental Research,
71:1372, March 1992.
Thomas K, Kugel G, Habib CM. Comparison of Dentin Surfaces

after Treatment with Dentin Bonding Primers Using the
Environmental Scanning Electron Microscope, Journal of Dental
Habib C, Kronman J, Kugel G. One-year Evaluation of

Composite Restoration for Root Surface Caries after Chemo-
Mechanical Excavation, Journal of Dental Research, 71:795,
March 1992.
Kugel G, Achour A, Zive M. A Comparison of Marginal

Microleakage Around Porcelain and Resin Inlay Systems,
Journal of Dental Research, 70:990, April 1991.
Habib C, Kronman J, Kugel G, Tutin, R. Dentinal Bonding and

Composite Restoration of Root Surface Caries after Chemo-
Mechanical Excavation, Journal of Dental Research, 70:1025,
April 1991.
Bellucci A, El Alfy H, Kugel G, Chapman R. Fracture

Resistance of Porcelain Related to Polishing and Glazing.
Journal of Dental Research, 70:638, April 1991.
Latif M, Kugel G, Chapman R, Norris L, Kabani S, Washburn B.

Techniques in Bone Surgery. Journal of Dental Research,
70:1956, April 1991.
Kugel G, Rider C, Angelopoulos A, Fakitsas A. Evaluation of the

Nd:YAG Contact Laser in Oral Surgery. Journal of Dental
Zive MA, Kugel G, Beumer J, Kumar MSA. Brain Neuropeptide

Changes in Rats Exposed to N20, Journal of Dental Research,
69:314, March 1990.
Geshnizgani A, Kugel G, Onderdonk A, Delaney M, McDonough

P, Habib C, Cisneros R. Effect of Nitrous Oxide on Oral
Microorganisms, 89th Annual Meeting, American Society for
Microbiology, May 1989.
Kugel G, Letelier C, Atallah H, Zive M. Chronic Low Level

Nitrous Oxide Exposure and Infertility, Journal of Dental
Eliminato: 214¶
240
Kugel G, Norris L, Zive M. Nitrous Oxide: Occupational Eliminato: Blankenau R.
Exposure, Journal of Dental Research, 68:1058, March 1989. Goldstein RE. Haywood VB.
The current status of vital tooth
whitening techniques
[interview].¶
Kugel G, Letelier C, Atallah H, King JC, Gilmore WC. Nitrous Compendium of Continuing
Oxide and Infertility, Journal of Dental Research, 67:380, March Education in Dentistry
(Jamesburg, NJ). 20(8):781-4,
1988. 786, 788 passim; quiz 796,
1999.¶
Caughman WF. Frazier KB.
Kugel G, Rosenberg L. Effects of Nitrous Oxide Exposure on the Haywood VB. Carbamide
Central Nervous System Control of Reproduction in Female Rats, peroxide whitening of nonvital
single discolored teeth: case
Journal of Dental Research, 66:394, March 1987. reports. Quintessence
International. 30(3):155-61,
Mar 1999.¶
King JC, Kugel G, Zahniser D, Wooledge K, Damassa D, Schwachman H, Schuster A:
Alexsavich B. Sex Differences in the Response of LHRH Neurons The tetracyclines applied
pharmacology. Pediat Clin
to Gonadectomy in the Rat: Three-Dimensional Computer North Am 3:295, 1956.¶
Analyses, Society for Neuroscience, 87, May 1984. Mello HS: The mechanism of
tetracycline staining in primary
and permanent teeth. J Dent
King JC, Lechan RM, Kugel G, Anthony ELP. A Fixative for Child 34:478, 1967.¶
Albert A, Rees CW: Avidity of
Immunocyto-Chemical Localization of Peptides, Greater New the tetracyclines for the cations
York Dental Meeting, New York, New York, November 1983. of metals. Nature 177:433,
1956.¶
Finerman GAM, Milch RA: In
vitro binding of tetracyclines to
calcium. Nature 198:486,
1963.¶
Stewart DJ: The effects of
tetracyclines upon the
dentition. Br J Dermat 76:374,
1964. ¶
Stewart RE et al: Pediatric
Dentistry. St Louis, CV Mosby
Co., p.87, 1982.¶
Swift EJ: A method for
bleaching discolored vital
... [172]
Formattato: Tipo di
carattere: 12 pt
Formattato: Tipo di
carattere: 12 pt
Formattato: Tipo di
sinistra
Formattato: Tipo di
Formattato: Tipo di
Formattato: Tipo di
carattere: 12 pt
Formattato: Tipo di
Formattato: Tipo di
carattere: 12 pt
Formattato: Tipo di
Eliminato: 214¶
241
Pagina 4: [1] Formattato gkugel01 28/10/2004 12.00.00
Tipo di carattere: 12 pt
Tipo di carattere: 11,5 pt
Pagina 4: [7] Formattato idesir01 08/11/2004 11.38.00
Rientro: Sporgente 54 pt, Numerazione automatica + Livello:1 + Stile numerazione: 1, 2, 3, … +
Comincia da:6 + Allineamento: A sinistra + Allinea a: 18 pt + Tabulazione dopo: 54 pt + Rientra
di: 54 pt, Tabulazioni: 0 pt, Tabulazione elenco + Non a 18
Interlinea minima 12 pt
Tipo di carattere: (Predefinito) Arial
Normale, Rientro: Sinistro: 0 pt, Interlinea doppia
Tipo di carattere: (Predefinito) Arial, 11,5 pt
Pagina 9: [25] Eliminato tufts 07/06/2004 11.04.00
and for offering treatment

( Kugel, 2000)

also

Tipo di carattere: (Predefinito) Arial, 11 pt
(Harris et al., 2001)

(McMillan et al., 2001).

Technological advances in dentistry make it possible for the practitioner to deliver the highest level
of care in an efficient and often economical way. With t

Rientro: Prima riga: 0 pt
, being promoted as “the future of dentistry,”

awareness and
so-called: “

In 2002 one article and more recently

two

One

study

reported

, whereas

the

,

Reviews of these articles were

in support

4

discredited

findings

5

It is apparent that

t

needs

for

The lack of knowledge is to the detriment of the dentist and patient alike.

need for more knowledge becomes
“up to date” dental office

Allineato a sinistra, Rientro: Prima riga: 0 pt, Spazioprima 0 pt
Bleaching is the most conservative treatment for discolored teeth when compared to resin bonded
composites, porcelain veneers or crowns. It offers a simple and economical approach to changing
the color of teeth. Success of the treatment depends on a careful diagnosis by the practitioner.
Candidates for whitening procedures include patients whose teeth are stained by aging,
chromogenic foods, endodontic treatment, tetracycline use and smoking or use of other tobacco
products.
Acceptable tooth whitening techniques include the in-office technique, dentist-prescribed home-
applied technique, or a combination of the two. The use of hydrogen peroxide (H202) for bleaching
teeth dates back to 1995 6. To reduce

, such as tetracycline stained-teeth,

Most clinicians know that hydrogen peroxide is a bleaching agent that can attain a desired
whitening effect. Bleaching can also be accomplished with Carbamide Peroxide, a lower
concentration of hydrogen peroxide and urea, which breaks down to 3.6% hydrogen peroxide
8,9
.The degree of whitening correlates directly with the amount of contact time and concentration of
the active ingredient, the pH and viscosity 9. The side effects are usually diminished when lower
concentrations are used.

The in-office bleaching treatment using hydrogen peroxide and an accelerating source (heat or
light) were predominant until 1989 when Haywood published the first article on nightguard vital
bleaching using carbamide peroxide 10. Currently, the in-office bleaching technique employs a 15 -
40% hydrogen peroxide bleaching agent (heat activated or not), while the dentist prescribed home-
applied technique most commonly uses a 10 - 15% carbamide peroxide gel.
The advantages of an in-office procedure are twofold. It does not require patient compliance and
immediate results can be accomplished. The disadvantages are the chair side time involved and
the cost to the patient, as the procedure usually requires multiple visits. Light-activated chair side
bleaching systems potentially offer the benefit of being less time-consuming while producing faster
results.

he introduction of very high intensity Plasma Arc lights and Argon Lasers meets the need of an
ever increasing demand for whiter teeth.

Pagina 10: [70] Formattato tufts 07/06/2004 12.01.00
Normale, Giustificato, Spazioprima 0 pt, Non regolare lo spazio tra testo asiatico e in alfabeto
latino, Non regolare lo spazio tra testo asiatico e caratteri numerici, Tabulazioni: Non a 22,5 pt
Tipo di carattere: 11 pt, Non Grassetto
Tipo di carattere: 11 pt, Non Grassetto
Tipo di carattere: 11 pt, Inglese (U.S.A.)
Rientro: Prima riga: 0 pt, Spazioprima 0 pt
Research in vitro has demonstrated that the use of laser-activated hydrogen peroxide did not
produce any perceivable color change 11. Another recent in vitro study, and one which should be of
concern to the practitioner, has shown that the use of these intense lights does elevate
temperature of the bleaching material and as a result caused an increase in intrapulpal
temperature. This may have an impact on post bleaching tooth sensitivity and pulpal health 12.

Non Apice / Pedice
Non Apice / Pedice

Pagina 11: [85] Cambia gkugel01 04/06/2004 7.01.00
Elenchi puntati e numerati formattati
ECHANISM OF ACTION

Rientro: Prima riga: 0 pt
Mokhlis et al. 2000,

Christensen 1989, Sharif et al. 2000,

Haywood et al. 1991, 1992, 1993, 1994, Nathanson et al. 1987, Kugel et al. 1997, Kugel et al.
1998 (abstract), Bardwell et al. 2000 (abstract or unpublished data), Papathanasiou et al. 2000
(abstract or unpublished data)]

appearance within a few weeks. While non-invasive, treatment may need to continue over
an extended period. Some individuals will show favorable response after 3-4 months, after
which treatment may be discontinued. Duration may be difficult to predict, given the
variable clinical manifestations of tetracycline staining. Practitioners and patients should be
advised that optimal bleaching of tetracycline staining may necessitate extended daily at-
home treatment over a period of 3-6 months. The costs, risks, and benefits of the various
treatment options must be considered as part of overall patient management

Pagina 15: [94] Eliminato gkugel01 04/06/2004 12.57.00
Different variations of tetracycline and derivates produce different colors in the tooth. When the
teeth are exposed to the sunlight, they become darker, with a distinct gray/blue tinge. It is
suggested that the reason that the front incisor teeth darken while the molars remain yellow longer
is the different exposure to light 3. The discoloration of the permanent dentition depends on the
amount and duration of tetracycline use4. The portion of the tooth, color and severity of the stains
can be determined by the stage of the tooth development at the time of the drug administration.
Tetracycline is incorporated into dentin during tooth calcification intra and post partum, probably
through chelation with calcium forming tetracycline orthophosphate 5. It can be deposited in fetal
tooth buds when administered in the third trimester of pregnancy or by a child during the
6, 7
development of the tooth (between ages 3 to 4 months and 7 to 8 years) . Colors may vary
intensity of gray, blue, brown and yellow. The different banding can also be attributed to the
variations of the tetracycline derivates.
Clinicians are aware of the results from the use of tetracycline in pregnancy and young children.
Even though physicians and dentists should seek other sources of treatment, tetracycline is still the
drug of choice for treatment of Rocky Mountain spotted fever and it is also the most prescribed
medication for acne.

Tipo di carattere: 12 pt, Non Tutto maiuscole
Tipo di carattere: 12 pt, Non Tutto maiuscole
Pagina 17: [97] Formattato tufts 08/06/2004 18.32.00
Rientro: Prima riga: 0,05 pt, A sinistra -0,01 ch
Bleaching Adverse Effects

Numerazione automatica + Livello:1 + Stile numerazione: 1, 2, 3, … + Comincia da:1 +
Allineamento: A sinistra + Allinea a: 14,4 pt + Tabulazione dopo: 14,4 pt + Rientra di: 14,05 pt
Interlinea 1,5 righe, Numerazione automatica + Livello:1 + Stile numerazione: 1, 2, 3, … +
Comincia da:1 + Allineamento: A sinistra + Allinea a: 14,4 pt + Tabulazione dopo: 14,4 pt +
Burrell KH. ADA supports vital tooth bleaching—but look for the seal. Journal of the American
Dental Association. 128 Suppl:3S-5S, Apr. 1997.
Papathanasiou A., Bardwell D, Kugel G : Combining In Office and Take Home Whitening
Systems. Contemporary Esthetics and Restorative Practrice Vol.4:8; 88-91, September 2000.
Papathanasiou A., Bardwell D, Kugel G : A Clinical Study Evaluating a New Chairside and Take
Home Whitening System. Compendium of Continuing Education in Dentistry, Vol: 22; 4: 289-
298, April 2001.

Haywwod VB, Heymann HO: Nightguard vital bleaching. Quintessence Int 20(3):173-6, 1989.

Bardwell D, Papathanasiou A, Deliperi S: In vitro evaluation of tooth color modifications
utilizing differing hydrogen peroxide concentrations. Unpublished data 2000.
Papathanasiou A, Bardwell D, Kastali S: A clinical study evaluating the efficiency of a
new chairside and take home bleaching system. Unpublished data 2000.
Fuss A, Szajkis S, Tagger M: Tublar permeability to calcium hydroxide and the bleaching
agents. J Endod 15:362-364, 1989.
Goldstein RE, Garber DA: Complete dental bleaching. Quintessence books 1995.

Interlinea 1,5 righe, Numerazione automatica + Livello:1 + Stile numerazione: 1, 2, 3, … +
Comincia da:1 + Allineamento: A sinistra + Allinea a: 14,4 pt + Tabulazione dopo: 14,4 pt +
Allineamento: A sinistra + Allinea a: 14,4 pt + Tabulazione dopo: 14,4 pt + Rientra di: 14,05 pt,
Non regolare lo spazio tra testo asiatico e in alfabeto latino
Tipo di carattere: Arial, 11 pt, Non Grassetto
Tipo di carattere: Arial
Tipo di carattere: Arial, 11 pt
Corpo del testo 3
Tipo di carattere: Arial, 11 pt, Apice
Pagina 111: [124] Formattato idesir01 08/11/2004 11.38.00
Rientro: Sinistro: 0 pt, Numerazione automatica + Livello:1 + Stile numerazione: a, b, c, … +
Comincia da:1 + Allineamento: A sinistra + Allinea a: 18 pt + Tabulazione dopo: 36 pt + Rientra
di: 36 pt, Tabulazioni: Non a 36 pt
Posizione: Orizzontale: 288 pt, Rispetto a: Pg, Verticale: 2,15 pt, Rispetto a: Paragrafo
Pagina 241: [172] Eliminato gkugel01 15/06/2004 10.57.00
Blankenau R. Goldstein RE. Haywood VB. The current status of vital tooth whitening
techniques [interview].
Compendium of Continuing Education in Dentistry (Jamesburg, NJ). 20(8):781-4, 786, 788
passim; quiz 796, 1999.
Caughman WF. Frazier KB. Haywood VB. Carbamide peroxide whitening of nonvital single
discolored teeth: case reports. Quintessence International. 30(3):155-61, Mar 1999.
Schwachman H, Schuster A: The tetracyclines applied pharmacology. Pediat Clin North
Am 3:295, 1956.
Mello HS: The mechanism of tetracycline staining in primary and permanent teeth. J Dent
Child 34:478, 1967.
Albert A, Rees CW: Avidity of the tetracyclines for the cations of metals. Nature 177:433,
1956.
Finerman GAM, Milch RA: In vitro binding of tetracyclines to calcium. Nature 198:486,
1963.
Stewart DJ: The effects of tetracyclines upon the dentition. Br J Dermat 76:374, 1964.
Stewart RE et al: Pediatric Dentistry. St Louis, CV Mosby Co., p.87, 1982.
Swift EJ: A method for bleaching discolored vital teeth. Quint Int 19:607, 1988.
Shafer WG, Hine MK, Levy BL: A textbook of Oral Pathology, 3rd Ed. Philadelphia,
Saunders, 1974.
Jordan RE, Boksman L: Conservative vital bleaching treatment of discolored dentition.
Comp Cont Ed Dent 5(10):803-808, 1984.
Faunce F. Management of discolored teeth. [Review] [30 refs] Dental Clinics of North
America.27(4):657-70, Oct. 1983 .
Nathanson D: Vital tooth bleaching: sensitivity and pulpal considerations. J Am Dent
Assoc., 128(Suppl): 41S-44S, 1997.
Bardwell D, Habib C, Kugel G, Mehta N, Leone L: Microleakage of previously restored
Class II restoratives after exposure to 10% carbamide peroxide. JDR 2000 Special Issue
Vol.79, abstract 306.
P. Yu, A. Aboushala, D. Bardwell. Effect of bleaching on Composite Resin Shear Bond
Strength In Vitro. JDR 1999 Vol.78 special issue, abstract #1445
M. MacKAY, R. PERRY, E. SWIFT, M. VARGAS Effects of two home bleaching systems
on Enamel surfaces. JDR 1997 special issue abstract #1405
Ultradent Products Opalescence Instructions (1996), Ultradent Products, Inc, South
Jordan, UT 84095.
Discus Dental Nite White Instructions (1996), Discus Dental Inc, Los Angeles, CA 90064.
Dentsply Nupro Gold Instructions, Dentsply Preventive Care, York, PA 17405.
Javaheri DS, Janis JN: The efficacy of reservoirs in bleaching trays. Operative Dentistry,
2000, 25, 149-151.
Price RBT, Sedarous M, Hiltz G: The pH of tooth-whitening products. J Can Den Ass,
Sept. 2000, Vol. 66, No. 8, 421-426.
Sun G: The role of lasers in Cosmetic Dentistry Dental Clinics of North America, Vol. 44,
No 4, Oct. 2000, 831-849.
Blankenau R, Goldstein R, Haywood V: The current status of vital tooth whitening
techniques. Compendium of Continuing Education in Dentistry, Aug 1999, Vol. 20, No 8,
781-794.
Haywood VB: Nightguard bleaching: current concepts and research. J Am Den Assoc
128(Suppl):19S-25S, 1997.
Seals NS, McIntosh JE, Taylor AN: Pulpal reaction to bleaching of teeth in dog. J Dent
Res 60:948-953, 1981.
Yiming Li, Toxicological Considerations of Tooth bleaching using peroxide
containing agents. JADA, April 1997; vol.128; 31S-36S
DahlJE, Becher R. Acute Toxicity of carbamide peroxide and commercially available

tooth bleaching agent in rats; Journal of dental Research 1995; 74: 710-714
Schulte J,Morrissette D,Gasior E,Czajewski,M. Clinical Changes on the Gingiva as a

result of at-home bleaching. Compendium 1993, VolXIV, no.11; 1362-1371
Haywood VB, Leonard RH, Chauncy NF, Brunson WD. Effectiveness, Side Effects
and Long Term Status of Nightguard Vital Bleaching. JADA, September 1994
,vol.125pg 1219-1226
Haywood VB History, safety and effectiveness of current bleaching techniques and

applications of the vital bleaching technique. Qunitessence Int 1992; 23:471-488
Michael G Jorgensen, William B. Carroll. Incidence of tooth sensitivity after home

whitening treatment. JADA vol.133 August 2002 ;1076-1082
Pohjola R,Browning WD, Hackman ST, Michael ML, Downey MC. Sensitivity and
Tooth Whitening Agents. Journal of esthetic and Restorative dentistry 2002; vol2,
no.2; 85-91, 2002
Leonard RH, Haywood VB, Phillips C. Risk factors for developing tooth sensitivity and
gingival irritation associated with nightguard vital bleaching. Quintessence International;
1997 vol. 28 no. 8; 527-534
Bartelstone HJ. Radioiodine Penetration through Intact Enamel with Uptake by

Bloodstream and Thyroid Gland. Journal of Dental Research October 1951; 728-733
Gokay O, Tuncbilek M,Ertan R. Penetration of the pulp chamber by carbamide

peroxide bleaching agents on teeth restored with composite resin. J of Endodontics
2000; 27; 92-94
Bowels WH and Ugwuneri Z . Pulp Chamber Penetration by Hydrogen Peroxide

Following Vital Bleaching Procedures. J of Endodontics Aug. 1987vol.13 375-377
Jorgensen MG, Caroll WB.Incidence of tooth sensitivity after home Whitening

treatment, JADA, 2002 Sep; 133(9):1174
Over the Counter

1.HaywoodVB, Heymann HO. Nightguard vital bleaching. Quintessence Int.
1989; 20:173-6
2.Goldstein RE.In-office bleaching: where we came from, where we are today. Jam Dent
Assoc1997;128:11S-15S
3.BurrellKH.ADA supports vital tooth bleaching –but look for the seal. J Am Dent
Assoc1997 128:3S-5S.
4.CrollTP, SasaIS.Carbemide peroxide of teeth with dentiogenisis imperfecta
discoloration: report of a case. Quintessence Int. 1995; 26:683-6
5.Haywood VB. Night guard bleaching to lighten a restored, nonvital discolored tooth.
Compend Continuing Education Dent 1998;19:810-3
6. Frazier KB. Nightguard bleaching to lighten a restored, nonvital discolored tooth.
Compend Contin Educ Dent 1998; 19:810-3
7. Small BW. The application and integration of at-home bleaching into private dental
practice. Compend Contin Educ Dent 1998;19:799-806
8.HaywoodVB, Robinson FG.Vital tooth bleaching with nightgaurd vital bleaching.
Curr.Opin CosmeticDent1997;4:45-52
9.KugelG,PerryRD, Hoang E,Scherer W.Effective tooth bleaching in 5days: using a
combined in office and at home bleaching system . Comp contin Educ Dent
1997 ;18:378-83
10. Kugel G Over the counter tooth whitening Systems Compendium April 2003; 24;4A
376-82
11.Donly KJ, DonlyAS, BaharlooL, et al. Tooth whitening in children, Compend Contin
Edu Dent. 2002; 3:22-27

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A STUDY OF TOOTH WHITENING: SAFETY, EFFICACY AND

A STUDY OF TOOTH WHITENING: SAFETY, EFFICACY AND

diagnosis by the practitioner.

(Dale, esthetic dentistry

among the dental community as the take-home bleaching system.

effective in a variety of regimens, including in-office procedures, dentist-prescribed and

A) Take- home System Eliminato: :

concentrations are 10% to 22% carbamide peroxide.

30% or 35% hydrogen peroxide bleaching agent (heated or non-heated).

requires multiple office visits.

Eliminato: and for offering

teeth 13. Formattato ... [27]

Formattato ... [39]

20, 21 22 23 Formattato ... [44]

Formattato ... [55]

above investigations. Eliminato: ,

unsaturated bonds, resulting in disruption of electron conjugation and a change in the

were taken from marked areas and lightness values determined.

57, 58 Formattato: Non Apice /

and confirmed by a study of

Detailed clinical and radiographic examination, fabrication of a custom-fitted, well- adapted

concentration of active ingredient, viscosity and other salient features.

peroxide demonstrated increased microleakage in the restorations, according to a study which

carbamide peroxide. Microleakage of previously restored Class II restoratives after exposure to

demineralization and erosion may occur with pH less than 5.2 70

Toxicology Formattato: Tipo di

Oral Side Effects Formattati: Elenchi puntati e

agents. JADA, April 1997; vol.128; 31S-36S Formattato ... [100]

340, 343-4 passim; quiz 348

23) Anonymous. Laser-assisted bleaching: an update. ADA Council on Scientific

Update 2(5):82-85, 1991. Formattato: Tipo di

Comp Cont Ed Dent 5(10):803-808, 1984. Formattato: Interlinea 1,5

A Novel Low Dose Tooth-Whitening Delivery System

Efficacy and Safety:

A randomized, single-center, double-blind, parallel-group, placebo controlled trial evaluated the

compared with other at-home bleaching systems.

Association for home whitening.2 Eliminato: 89¶

effect may persist for 3 or more years.

believed to contribute to poor compliance and development of occlusal interferences.

Materials and Methods

Previous participation in a professional or home-use vital bleaching trial, participation in a

The study was a randomized, placebo-controlled, double-blind, parallel-group trial. Subject

of the 2-week treatment period (visit 3).

Crest®,a toothpaste and provided toothbrushes.

performed blinded as to treatment assignment.

baseline and at the end of treatment and included the following:

oropharynx/uvula, buccal mucosa, tongue, floor of mouth, labial mucosa,

mucobuccal/mucolabial folds, and lips.

dentition and restorations.

3. Dentinal hypersensitivity—this parameter was assessed by questioning participants

about tooth hypersensitivity to thermal, air, or other stimuli.

edema; no BOP); 2—moderate inflammation (redness, edema, and glazing; BOP); 3—

severe inflammation (marked redness, edema, ulceration; tendency toward spontaneous

bleeding); 8—ungradable site; 9—missing tooth.

maximum of 36 sites). An average PI score was obtained for each participant, by

Vita® shade score was included as a covariate in the model.

Demographic and Baseline

treated in the active group started at scores of C-2 or whiter.

change of –3.7 ± 0.35, representing an average increase in tooth whiteness of approximately 4

dentinal hypersensitivity assessment were unremarkable. Both groups experienced a

inflammation, and a superficial cervical lesion.

results, is cumbersome and requires an average of 2 to 6 weeks of treatment.2 Stubborn stains

and ΔL, as well as the composite parameter, ΔE.