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Chelating Agents-Review Paper Hulsman Et Al IEJ 2003

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RE V IE W

Chelating agents in root canal treatment: mode of


action and indications for their use
M. Hulsmann, M. Heckendorff & A. Lennon
Department of Operative Dentistry, Preventive Dentistry and Periodontology, University of Gottingen, Gottingen, Germany

Abstract
Hulsmann M, Heckendorff M, Lennon A. Chelating
agents in root canal treatment: mode of action and indications for
their use ^ a review. International Endodontic Journal, 36, 810^830,
2003.

Chelating agents were introduced into endodontics as


an aid for the preparation of narrow and calcied root
canals in1957 by Nygaard-stby. A liquid solution of ethylenediaminetetraacetic acid (EDTA) was thought to
chemically soften the root canal dentine and dissolve the
smear layer, as well as to increase dentine permeability.
Although the ecacy of EDTA preparations in softening
root dentine has been debated, chelator preparations have

Historical development of chelators


The term `chelate'originates from the Greek word `chele'
(crab claw). Chelates are particularly stable complexes
of metal ions with organic substances as a result of
ring-shaped bonds. This stability is a result of the bond
between the chelator, which has more than one pair of
free electrons, and the central metal ion (Grossman
et al.1988, Zeeck et al.1992; Fig. 1). The ability of chelators
to bind and inactivate metallic ions is widely exploited
in medicine. Chelators can be used to bring about excretion of dangerous ions in the case of metal poisoning or
in the treatment of copper metabolism disturbances
(Zeeck et al. 1992).
In1951, the rst reports on the demineralizing eect of
ethylenediaminetetraacetic acid (EDTA) on dental hard
Correspondence: Professor Dr M. Hulsmann, Department of
Operative Dentistry, Preventive Dentistry and Periodontology,
Zentrum ZMK, Robert-Koch-Str. 40,37075 Gottingen, Germany
(Tel.: 49 551 392855; fax: 49 551 392037; e-mail: michael.
huelsmann@med.uni-goettingen.de).

810

International Endodontic Journal, 36, 810^830, 2003

regained popularity recently. Almost all manufacturers


of nickel^titanium instruments recommend their use as
a lubricant during rotary root canal preparation.Additionally, a nal irrigation of the root canal with 15^17% EDTA
solutions to dissolve the smear layer is recommended in
many textbooks.This paper reviews the relevant literature
on chelating agents, presents an overview of the chemical
and pharmacological properties of EDTA preparations
and makes recommendations for their clinical use.
Keywords: chelators, dentine hardness, dentine permeability, EDTA, root canal treatment, smear layer.
Received13 March 2003; accepted 2 September 2003

tissues were published (Hahn & Reygadas1951, Screebny


& Nikiforuk 1951). Chelators were rst introduced to
endodontics by Nygaard-stby (1957), who recommended the use of a 15% EDTA solution (pH 7.3) with
the following composition:
 Disodium salt of EDTA (17.00 g)
 Aqua dest. (100.00 mL)
 5 M sodium hydroxide (9.25 mL)
A few years later, a detergent was added in order to
increase the cleaning and bactericidal potential of the
EDTA solution, the new composition being known as
EDTAC (Von der Fehr & Nygaard-stby 1963). EDTAC is
produced when EDTA is mixed with 0.84 g of a quarternary ammonium compound (Cetavlon; Goldberg &
Abramovich 1977). This addition is aimed at reducing
the surface tension of the irrigant, facilitating the wetting of the entire root canal wall and thereby increasing
the abilityof the chelators to penetrate the dentine. EDTA
in its pure form already has a lower surface tension than
1 or 5% sodium hypochlorite (NaOCl), saline solution
or distilled water (Tasman et al. 2000). Furthermore,
EDTAC should have a greater antimicrobial eect than

2003 Blackwell Publishing Ltd

Hulsmann et al. Chelators ^ a review

Figure 1 Chemical structure and


mechanism of EDTA binding.

EDTA, although it also causes greater inammatory


reactions in soft tissue (Weine 1988). In contrast to this,
no dierence in the eectiveness of EDTAC and EDTA
has been reported (Weinreb & Meier 1965).
Initially, chelators were used as liquids for irrigation
during mechanical instrumentation of the root canal
system. In 1969, Stewart et al. presented RC-Prep (premier Dental; Philadelphia, PA, USA), probably the best
known paste-type chelatingagent. Although the ecacy
of liquid and paste-type EDTA preparations in softening
root dentine has beena point of controversy, chelator preparations have been advocated frequently as adjuncts
for root canal preparation, especially in narrow and
calcied root canals (Serene 1976, Stock & Nehammer
1985, Stewart 1986, 1995, Weine 1988, Lovdahl &
Gutmann 1997), and for removal of the smear layer
(McComb & Smith 1975, Goldman et al. 1985, Berg et al.
1986, Baumgartner & Mader 1987, Ciucchi et al. 1989,
Aktener & Bilkay1993, Garberoglio & Becce1994, Hottel
et al. 1999, Calt & Serper 2000, Di Lenarda et al. 2000,
O'Connell et al. 2000, Scelza et al. 2000). Recently,
paste-type chelators have regained popularity as almost
all manufacturers of nickel^titanium instruments
recommend their use as a lubricant during rotary root
canal preparation, presumably to reduce the risk of
instrument separation.

Chelator preparations
Liquid chelators
The most common liquid chelator preparations and their
main ingredients are:
 Calcinase (lege artis, Dettenhausen, Germany) is a
liqiud chelator preparation and contains17% sodium edetate, sodium hydroxide as a stabilizor and puried water.
 REDTA (Roth International, Chicago, IL., USA) is a17%
EDTA solution with the addition of 0.84 g Cetyl-trimethyl ammonium bromide (Cetrimide) to reduce surface tension. The other ingredients are 9.25 mL 5 M
sodium hydroxide and 100 mL distilled water.
 EDTAC and DTPAC are solutions of EDTA (15%) and
diethyl-triamine-penta acetic acid (DTPA) at pH 8.When
0.75 g of the detergent Cetyl-tri-methyl ammonium

2003 Blackwell Publishing Ltd

bromide is added to 100 mL of these solutions, respectively, two new solutions named EDTAC and DTPAC are
produced (Pawlicka et al. 1981, 1982).
 EDTA-T (Formula & Acao Farmacia, Sao Paulo, Brazil)
consists of 17% EDTA plus sodium lauryl ether sulfate
(Tergentol) as a detergent (Scelza et al. 2000).
 EGTA (Sigma, St Louis, MO, USA) is a chelator whose
main component is ethylene glycol bis (b-amino-ethyl
ether)-N,N,N0,N0-tetra acetic acid. It is reported to bind
Ca more specically than EDTA (Calt & Serper 2000).
 CDTA (experimental solution) is a 1% solution of
cyclohexane-1,2-diaminetetraacetic acid (Cruz-Filho
et al. 2001).
 Largal Ultra (Septodont, Paris, France) contains a15%
EDTA solution as a disodium salt,0.75% Cetyl-tri-methyl
ammonium bromide (Cetrimide) and sodium hydroxide
to adjust the pH value to 7.4.
 Salvizol (Ravens, Konstanz, Germany) is based on a 5%
aminoquinaldinumdiacetate in propylene glycol and
has a pH of 6.6 (Kaufman et al. 1978).
 Decal (Veikko Auer, Helsinki, Finland) has a pH value of
3.4 and is composed of 5.3% oxyl-acetate,4.6% ammonium
oxyl-acetate and 0.06% Cetyl-tri-methyl ammonium
bromide (Cetrimide), thereby combining the eects of a
chelator complex and dissolution by an acid component.
 Tubulicid Plus (Dental Therapeutics, Nacka, Sweden)
contains1.5 g Amphoteric-2 (38%),0.5 g benzalkonichloride, 3 g disodium EDTA dihydrate, phosphate buer solution pH 7.3 q.s.,100 g distilled water and 50% citric acid.
 Hypaque (experimental solution) is composed of 5%
NaOCl, 17% EDTA and hypaque, a high-contrast injectable dye for angiography and arteriography (Scarfe
et al.1995). Hypaque is an aqueous solution of two iodine
salts, diatrizoate meglumine and sodium iodine. It is
water soluble and has a pH of 6.7^7.7. This agent is
intended to visualize the complexity of the root canal
system and thus to combine the solving potential
of EDTA and NaOCl and the radiopacity of the contrast
solution (Ruddle 2002).
Paste-type chelators
Whilst the literature reports predominantly on the mode
of action of liquid chelator solutions for root canal irriga-

International Endodontic Journal, 36, 810^830, 2003

811

Chelators ^ a review Hulsmann et al.

tion, the chelators recommended for use during rotary


root canal preparation have a paste or gel consistency.
The best known paste chelators include the following
substances:
 Calcinase slide (lege artis, Dettenhausen, Germany)
contains 15% sodium EDTA and 58^64% water, but no
peroxides, colourants or preservatives (self-preserving).
The preparation has an alkaline pH value of 8^9, which
remains stable under clinical conditions. According to
the manufacturer, no EDTA precipitation occurs in combination with the commonly used irrigants. Furthermore, the gel can be mixed with water and therefore
can be easily rinsed out of the root canal system. Because
of its thixotropic nature, the gel is rm at room temperature and develops a creamy consistency when agitated.
In this way, the EDTA preparation not only adheres well
to the working instrument, but also disperses well inside
the root canal. The manufacturers do not claim a pharmacological eect as such, because the complex eect
of EDTA is only seen after the removal of the EDTA-softened surface dentine layer using mechanical instrumentation. Intermittent use in combination with a
NaOCl solution is recommended.
 RC-Prep (Premier Dental, Philadelphia, PA, USA) is a
combination of10% urea peroxide,15% EDTA and glycol
in an aqueous ointment base. Oxygen is set free by the
reaction of RC-Prep with a NaOCl irrigant so that pulpal
remnants and blood coagulates can be easily removed
from the root canal wall (Stewart et al.1969). The manufacturer claims that discoloured teeth can be bleached
in this way. Urea peroxide retains its antibacterial action
in the presence of blood (Stewart et al. 1961). The glycol
component of RC-Prep serves as a lubricant for instruments and is thought to inhibit the oxidation of EDTA
by urea peroxide.
 Glyde le (DeTrey Dentsply, Konstanz, Germany) is
composed of15% EDTAand10% urea peroxide in aqueous
solution, and its viscosity is dependent on storage conditions. It was developed for use with NaOCl irrigants,
because the oxygen release from urea peroxide caused
eervescence and this is claimed to facilitate the removal
of dentine particles and pulpal remnants. In addition to
this, internal bleaching is claimed to take place.
 FileCare EDTA (VDWAntaeos, Munich, Germany) also
is composed of 15% EDTA and 10% urea peroxide.
 File-EZE (Ultradent Products, SouthJordan, UT, USA) is
a chelating agent in an aqueous water-soluble solution
containing 19% EDTA.
It should be noted that some of the chelator preparations listed above are distributed under dierent names
in some countries.

812

International Endodontic Journal, 36, 810^830, 2003

Demineralization
Nygaard-stby (1957) used the principle of a constant
solubility product to explain the demineralization of
dental hard tissue by EDTA and its sodium salt. An equilibrium is established between the saturated salt solution and the consolidated precipitate because ions from
the precipitate constantly go into solution, whilst at the
same time, ions from the solution are precipitated as
solids. The concentration of the salt remains constant,
and therefore the product of the concentrations of the
ions in solution at a given temperature (the solubility
product) remains stable.
According to Nygaard-stby (1957), even lyophobic
substances such as dentine, the mineral components of
which are mainly phosphate and calcium, are soluble
in water.When the disodium salt of EDTA is added to this
equilibrium, calcium ions are removed from the solution. This leads to the dissolution of further ions from
dentine so that the solubility product remains constant.
Thus, chelators cause decalcication of dentine. A normal concentration of EDTA can remove 10.5 g from
100 g calcium (Pawlicka et al. 1981).
In the rst study of Nygaard-stby (1957), the EDTA
(15% (pH 7.3))-treated samples were analysed using
polarized microscopy. The root canal lumen was
encircled by a clearly dened zone of demineralized dentine.The extension of the demineralized zone was dependent on the working time (20 min 96 h). These
experiments demonstrated that EDTAC had a rapid
demineralizing eect. EDTAC is thought to have a lower
surface tension than EDTA because of the addition of a
detergent, thereby increasing the ability to penetrate
deeper into the dentine. A 20^30-mm demineralized
zone was apparent after 5 min. This increased to 30^
40 mm after 30 min and to 50 mm after a working time
of 24^48 h. This layer was separated from the deeper
unchanged dentine by a clearly dened smooth demarcation line. Therefore, the solution did not permeate diffusely into the dentine and the eect was thought to be
self-limiting because the demineralization did not
extend beyond 50 mm evenaftera relativelylongworking
time (Nygaard-stby 1957).
Chelators such as EDTA form a stable complex with calcium.When all available ions have been bound, an equilibrium is formed and no further dissolution takes place.
Using gravimetrical analyses, Seidberg & Schilder (1974)
showed that the properties of EDTA were self-limiting.
This limitation is thought to be because of pH changes
during demineralization of dentine. Under neutral conditions, most chelators have a pH near the neutral value,

2003 Blackwell Publishing Ltd

Hulsmann et al. Chelators ^ a review

99% of the EDTA is present as EDTAHNa3. The exchange


of calcium from the dentine by hydrogen results in a subsequent decrease in pH. Because of the release of acid,
the eciency of EDTA decreases with time; on the other
hand, the reaction of the acid with hydroxyapatite aects
the solubility of dentine.
Chemically, two coexisting reactions can be distinguished: complex formation (Eqn. 1) and protonation
(Eqn. 2; Perez et al. 1989):
EDTAH3 Ca2 EDTACa2 H

EDTAH3 H EDTAH2 2

As this reaction proceeds, acid accumulates and protonation of EDTA prevails (Eqn. 2), thus decreasing the
rate of demineralization. EDTA has four carboxyl groups,
and the dissociation takes place in four steps each with
its own dissociation constant (pK), ranging from
pK1 2.0 for the rst to pK4 10.26 for the fourth step.
This means that the dissolution of EDTA takes place over
a broad range of dierent pH values (Sand 1961).
In contrast, Patterson (1963) concluded from his studies that EDTA induced decalcication, which was not
self-limiting and proceeded for up to 5 days, although
the maximum penetration was 28 mm. The demineralization proceeds until all chelators have formed complexes with calcium. Dentine demineralization is
observed at pH values of 4^5, but enamel is not aected.
The dierence in solubilitycan be explained by the dierences in apatite crystal size, the presence of tubules in
dentine and the favourable proportion of calcium to
EDTA. Although dentine demineralization was thought
not to be pH-dependent (Seidberg & Schilder 1974,
Schmidt1968), a neutral or alkaline EDTA solution gives
an optimal eect (Screebny & Nikiforuk 1951, Nikiforuk
& Screebny 1953, Rubin et al. 1979, Serper & Calt 2002).
This is supported by a study showing that the optimum
pH for demineralization of dentine is between 5.0 and
6.0 (Cury et al.1981).The demineralizing eect, measured
as the amount of released phosphorus is stronger for
solutions with a pH of 7.5 as compared to solutions with
a pHof 9.0 (Serper & Calt 2002). Inthe coronal and middle
parts of the root canal, EDTA, with a neutral pH, dissolves signicantly more calcium and phosphorus than
RC-Prep (Verdelis et al. 1999). The authors concluded
from their study that RC-Prep mainly decalcied and
removed the loosely attached part of the supercial
smear layer, but was not able to modify the subsurface
dentine. Besides the low pH of RC-prep, insucient wetting of the dentine and possible side interactions are discussed as possible reasons.

2003 Blackwell Publishing Ltd

Further studies have shown that mechanical preparation in combination with EDTA could remove more calcium than instrumentation with physiological saline,
but slightly less than preparation with 20% hydrochloric
acid (Heling et al. 1965).
In a recent study (Hulsmann & Heckendor 2002), the
weight loss of dentine discs was measured after 3, 6
and 9 min of application of the chelator pastes Calcinase
slide, RC-Prep and Glyde File Prep.There were signicant
dierences between the control group (no chelating
agent) and the chelator pastes, and between the dierent
application times. No signicant dierence was found
between the chelator pastes after 3 min. Calcinase slide
caused greater mineral loss than RC-Prep after 6 and
9 min and Glyde File Prep was superior to RC-Prep after
6 min. Measuring the amount of liberated phosphorus
at dierent intervals after exposure to EDTA solutions
(1^15 min) with dierent concentrations (10 and 17%)
and pH (7.5 and 9.0), the pH did not play any signicant
role, whereas time of exposure and concentration signicantly inuenced the demineralization of root dentine.
Nevertheless, solutions with a pH of 7.5 performed more
eciently than those with a pH of 9.0 (Serper & Calt
2002). root canal dentine showed severe peritubular
and intratubular erosions after 10 min irrigation with a
liquid EDTA chelator (17%), whereas a 1-min exposure
was eective in removing the smear layer (Calt & Serper
2002). After 3,10 and15 min of exposure, no dierences
in the amount of extracted Ca could be found between
17% EDTA and 10% citric acid, whereas EDTA-T showed
worse results (Scelza et al. 2003). Following irrigation
with15% EDTA for 2 or 3 min and subsequent irrigation
with 6% NaOCl for 2 or 3 min, erosion was found to be
more pronounced than following irrigation with EDTA
alone, suggesting that 6% NaOCl accelerates erosion of
the dentinal tubules (Niu et al. 2002).
More recent results have shown that a neutral EDTA
solution reduces the mineral and noncollagenous protein (NCP) component of dentine, leading to surface softening but not to erosion of the surface dentine layer
(Kawasaki et al. 1999, Verdelis et al. 1999). EDTA can
remove not only calcium ions but also water-soluble
NCP and phosphoproteins at a neutral pH (Kuboki et al.
1979). Thus, not only calcium ions but also calcium
bonded to the extracted fractions of NCPs is removed
by EDTA. As the content of noncollagenous organic
matrix decreases in the apical part of the root dentine,
this may explain the lower degree of decalcication in
this part of the root.
The use of EDTA followed by NaOCl irrigation signicantly changes the calcium and phosphate content of

International Endodontic Journal, 36, 810^830, 2003

813

Chelators ^ a review Hulsmann et al.

root dentine in contrast to irrigation with EDTA and RCPrep alone, whereas the magnesium content increases
(Dogan & Calt 2001). Although not denitely claried,
the authors suggest that magnesium replaces calcium
in dentine. On the other hand, earlier clinical, experimental and histological investigations cast doubt on
the eciency of EDTA for dentine demineralization
under clinical conditions (Wandelt 1961, 1965, Ram
1980, Dow 1984). Fraser (1974) calculated that 0.02 mL
of EDTA decalcied only about 0.35 mm2 of dentine.
EDTA solution seems to be limited in its ability to demineralize because each relatively large chelator molecule
can only bind a single calcium ion.When all molecules
are bound, the reaction stops.Wandelt (1961,1965) stated
that the desired eect can only be achieved when a suciently large amount of active substance for the respective surface area and enough time are available to
allow the complex formation to take place. The author
concluded from the results of his studies that the eect
of chelators depends on the width of the root canal and
that only an insucient amount of active substance
can be introduced into narrow canals.

Changes in dentine hardness


The hardness value of unaected root dentine is between
40 and 75 kg mm 2 (Vickers hardness; Patterson 1963,
Komiya & Kroncke 1968). Dentine hardness increases
characteristically from the root canal lumen towards
the cemento-dentinal junction, whereas the values in
the apical-third are lower than inthe middle and cervical
sections of the root (Patterson 1963). In contrast, the
hardness of the root canal wall is almost constant with
a Vickers hardness of 88.78 kg mm 2 at the entrance to
the root canal and 94.68 kg mm 2 at the apex (Fromme
et al. 1970, Pawlicka et al. 1981).
Pawlicka (1982) reported that chelators can change
the root dentine hardness by about 20 HV (Vickers
hardness), whereby the greatest dierences are to be
found in dentine immediately adjacent to the root canal
lumen. The eect of the chelator is already apparent
after 5 min and cannot be signicantly increased by
extending the working time to 24 h. No dierence in
the change could be found between the chelators used:
EDTA, EDTAC, DTPA and DTPAC. This was conrmed
further by studies (Weinreb & Meier 1965) when it was
demonstrated that chelators have the ability to soften
dentine. The hardness of untreated dentine was
25 Knoop hardness number (KHN) near to the dentine^cement junction, reached a maximum of over
70 KHN and decreased again to 42 KHN in the immedi-

814

International Endodontic Journal, 36, 810^830, 2003

ate area of the root canal lumen. After 9 min treatment


with EDTAC, the dentine hardness decreased from 60
to 45 KHN and after 24 h, the average hardness of the
treated dentine was 7 KHN (Patterson1963). EGTA solutions (1,3 and 5%) signicantly reduce dentine hardness
when compared to distilled water; the degree of softening is dependent on the concentration of the chelating
agent (Cruz-Filho et al. 2002). A comparative study of
15% EDTAC,1% CDTAand1% EGTAusing the same technique revealed no signicant dierences between the
three solutions investigated (Cruz-Filho et al. 2001).
Fromme et al. (1970) used the chelator preparation
Largal Ultra and found that the reduction in hardness
took place in wide sections of the canal and at the
canal entrance and not at the root tip or in narrow sections of the root. In general, these authors concluded
that chelators showed a demineralizing eect on dental
hard tissue, but were ineective in narrow sections
of the root. They believed that this was because of the
diculty in providing sucient volume of material
and exchanging used material within roots having a
narrow lumen. Fraser (1974) also doubted the usefulness
of chelators during root canal preparation. Whilst
Fromme et al. (1970) applied chelators through the
root canal entrance, the chelators used by Fraser
(1974) ^ RC-Prep, Largal Ultra and Decal ^ were applied
directly to the canal wall for 15 min. Whilst chelators
have been shown to have a softening eect on dentine
in the cervical- and middle-third of the root (20^
40 mm deep depending on the preparation used), little
or no eect has been shown in narrow areas of the
apical section of the root (Hampson & Atkinson 1964,
Wandelt 1965, Fromme et al. 1970, Fraser 1974). This is
not only because of the diculty in providing a sucient
amount of chelator to this part of the root canal, but also
reects the dierences in structure between the middle,
coronal and apical dentine (Pashley et al. 1985, Mjor
et al. 2001).

Changes in dentine permeability


The diameter of dentine tubules decreases from1.2 mm at
the pulp^dentine junction to 0.4 mm at the cementodentinal junction (Pashley 2002).The number of tubules
per square millimeter is also greater near to the pulp
(58000 mm 2) than further away from the pulp
(10000 mm 2; Mjor et al. 2002). As the tubule density
reduces towards the apex, so does the dentine permeability (Fraser 1974). Furthermore, root dentine is not uniformly mineralized. Apical dentine is more frequently
sclerosed, and is more mineralized (Vasiliadis et al.

2003 Blackwell Publishing Ltd

Hulsmann et al. Chelators ^ a review

1983). Intratubular mineralization can lead to narrowing of the dentine canal lumen (Schroeder 1992).
Dentine permeability is directly dependent on the area
of the tubule lumina and in reverse proportionto the wall
thickness of the root canal (Reeder et al. 1978). After
mechanical preparation, the wall thickness of the root
canal is reduced whilst the surface area of the lumen is
increased. Additionally, the smear layer acts as a diusion barrier, reducing dentine permeability by 25^49%
(Pashley 1984, Pashley & Depew 1986, Pashley et al.
1988, Fogel & Pashley 1990).
Dentine permeability is increased (Cohen et al. 1970,
Brannstrom 1984, Guignes et al. 1996) and a reduction
in microleakage between the denitive root canal lling
and the canal wall dentine is achieved (Cergneux et al.
1987, Petschelt et al. 1987, Wennberg & rstavik 1990,
Behrend et al. 1996) after smear layer removal with the
aid of EDTA. In addition, it is possible to obturate a
greater number of lateral canals (Goldberg et al. 1986).
SEM investigations show that the use of EDTA during
preparation leads to enlargement of the dentinal tubule
openings (Goldberg & Abramovich 1977, Hottel et al.
1999). Furthermore, EDTA produces an increase in root
dentine permeability, which in turn, results in an
increase in the activity of endodontic medicaments
(Hampson & Atkinson 1964).
Tao et al. (1991) point out the importance of root
cementum in dentine permeability. Instrumentation of
the root canal in cases with intact root cementum did
not lead to a change in permeability. Therefore, root
canal instrumentation does not necessarily result in
an increase in permeability in cases where external root
resorption has not taken place. Dissolution of the smear
layer by EDTA had no signicant eect on permeability
(Tao et al. 1991). The rate of diusion fell initially after
smear layer removal and increased signicantly again
after storing the extracted teeth for 2 months in deionized water (Galvan et al.1994). The authors presumed
that crystals formed during the dissolution of the smear
layer by EDTA caused a precipitation of calcium phosphate crystals inside the dentinal tubules. After storage
in water, these calcium phosphate crystals appeared to
have dissolved, and the rate of diusion increased again.

Removal of smear layer


A 1^5-mm thick smear layer is the result of the direct
action of the endodontic instrument on the root canal
wall (Mader et al. 1984, Goldman et al. 1985, Kockapan
1995). McComb & Smith (1975) were the rst to describe
the smear layer on instrumented root canal walls. The

2003 Blackwell Publishing Ltd

depth of the dentinal tubule plug can be between 6 and


40 mm (Mader et al. 1984, Petschelt & Oberschachtsiek
1985). The smear layer consists of ground dentine and
predentine, pulpal remnants, odontoblast processes,
remnants of the irrigant and, in the case of infected
teeth, bacteria (McComb & Smith 1975, Mader et al.
1984, Kockapan 1995, Sen et al. 1995, Torabinejad et al.
2002; Fig. 2a^c). There is controversy as to whether the
smear layer should be removed or not before obturation
of the root canal. Microorganisms can remain in or
migrate into dentine despite thorough chemomechanical preparation (Shovelton1964, Brannstrom & Johnson
1974, Bystrom & Sundqvist 1981, 1983). Some authors
propose that the smear layer acts as a barrier to bacterial
metabolites, preventing the bacterial invasion of the
dentinal tubules, and not as a preferred site for bacterial
colonization (Vojinovic et al. 1973, Michelich et al. 1980,
Diamond & Carrel 1984). However, bacteria not only
remain, but also survive and multiply in the smear layer
(Brannstrom & Nyborg 1973, Baker et al. 1975, Yamada
et al.1983, Brannstrom1984) and can also penetrate into
dentinal tubules (Olgart et al. 1974, Akpata & Blechman
1982, Williams & Goldman 1985, Meryon et al. 1986,
Meryon & Brook 1990). The antimicrobial action of
medicaments in the dentinal tubules can be delayed or
hindered by the smear layer (Goldberg & Abramovich
1977, Brannstrom & Nordervall 1978, Wayman et al.
1979,Yamada et al.1983, Brannstrom1984, Baumgartner
& Mader 1987, rstavik & Haapasalo 1990, Drake et al.
1994). This would appear to make smear layer removal
advisable. Moreover, the ability of the sealer to penetrate
the dentinal tubules and thereby the adaptation of the
root canal lling to the root canal wall is much improved
after removal of the smear layer (Diamond & Carrel
1984,White et al. 1984, 1987,Wennberg & rstavik 1990,
Oksan et al.1993). Some investigators found that root lling impermeability is signicantly higher after smear
layer removal (Kennedy et al. 1986, Cergneux et al. 1987,
Petschelt et al.1987), whilst others showed no dierences
(Madison & Krell 1984, Goldberg et al. 1985, Evans &
Simon 1986).
Electron microscopy has shown that the smear layer
contains both organic and inorganic substances
(Yamada et al. 1983, Pashley 1984, Kockapan 1987). It
appears, however, to consist mostly of inorganic components as root canal irrigation with NaOCl has little eect
on removal of this layer. Partial if not complete smear
layer removal is achieved only with the aid of acids and
chelators (Yamada et al. 1983, Kockapan 1987). As the
components of the smear layer are small particles with
a large surface/mass ratio, they are highly soluble in

International Endodontic Journal, 36, 810^830, 2003

815

Chelators ^ a review Hulsmann et al.

acids (Pashley 1992). Numerous studies have reported


that irrigation with a 17% EDTA solution has a good
cleaning eect on the root canal walls (McComb & Smith
1975, Goldberg & Abramovich 1977, Goldman et al.
1985, Berg et al. 1986, Baumgartner & Mader 1987,
Cergneux et al. 1987, Meryon et al. 1987, Ciucchi et al.
1989, Aktener & Bilkay 1993, Garberoglio & Becce 1994,
Hottel et al. 1999, Calt & Serper 2000, Di Lenarda et al.
2000, O'Connell et al. 2000, Scelza et al. 2000). Following
smear layer removal, the root canal walls are clean and

the dentinal tubules are clearly recognizable (McComb


& Smith 1975, Goldberg & Abramovich 1977, Ram 1977,
Pawlicka et al. 1981, Goldman et al. 1985, Cergneux et al.
1987, Aktener & Bilkay 1993, Liolios et al. 1997, Calt &
Serper 2000; Fig. 3a^b). The tubule orices are enlarged
because of dissolution of peritubular dentine (Goldberg
& Abramovich 1977, Cergneux et al. 1987, Meryon et al.
1987, Hottel et al.1999, Calt & Serper 2000; Fig. 4). Some
studies even detected erosion of the dentinal tubules
(Calt & Serper 2002, Niu et al. 2002, Torabinejad et al.

Figure 2 (a) Following


instrumentation, the root canal wall
is covered by debris and smear layer
(magnication 250). (b) Following
instrumentation of the root canal, the
dentine surface is covered with smear
layer (magnication 3000). (c) The
smear layer is pressed into the
dentinal tubules (magnication
8500).

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International Endodontic Journal, 36, 810^830, 2003

2003 Blackwell Publishing Ltd

Hulsmann et al. Chelators ^ a review

Figure 2 continued

2002; 2003a,b; Fig. 5). Whilst Pawlicka et al. (1981)


reported that the root canal wall is clean along its entire
length after use of EDTA preparations, other authors
found that the cleaning action is reduced towards the
apex and therefore more ecient in the coronal- and
middle-third of the root (Baker et al. 1975, McComb &
Smith 1975, Chow 1983, Ciucchi et al. 1989, Abbott et al.
1991, Aktener & Bilkay1993, O'Connell et al.2000, Scelza
et al. 2000, Hulsmann & Heckendor 2002, Lim et al.
2003). The number of visible tubule openings reduces
from coronal to apical (Scelza et al. 2000). In a comparative study, a carbon dioxide or Er:YAG laser removed
the smear layer more eciently than EDTA (Takeda
et al.1999). A new irrigant, composed of tetracycline isomer, an acid and a detergent (MTAD) showed similar
results but less erosion than EDTA (Torabinejad et al.
2003a,b).

Combined use of EDTA, sodium


hypochlorite and ultrasonics
Because EDTA acts by dissolving the inorganic components of the smear layer, several authors have recommended its use in combination with NaOCl (0.5^5.25%)
in order to remove organic remnants (Goldman et al.
1982, Yamada et al. 1983, Baumgartner & Mader 1987,
Cengiz et al.1990, Abbott et al.1991, Stewart1998,Tatsuta
et al. 1999, Brandt et al. 2001). Both the cleaning action
(Baumgartner & Mader 1987, Stewart 1998, Lim et al.
2003,Yamashita et al. 2003) and the antimicrobial eect

2003 Blackwell Publishing Ltd

(Bystrom & Sundqvist 1985) are greater when these irrigants are used in combination rather than alone. It has
been shown that EDTA retained its ability to chelate calcium inthe presence of NaOCl, whereas the tissue-dissolving ability of NaOCl was reduced (Grawehr et al. 2003).
The content of available chlorine was drastically reduced
from 0.50 to 0.06% when EDTA was added to a NaOCl
solution; nevertheless, the antibacterial ecacy against
Candida albicans and Enterococcus faecalis was the
same for 8.5% EDTA and a17% EDTA/1% NaOCl solution
(Grawehr et al. 2003). The authors concluded that both
solutions therefore should be used separately. Ultrasonically supported irrigation with EDTA does not improve
the cleaning eect of EDTA (Ciucchi et al. 1989, Abbott
et al. 1991). Possibly, ultrasound waves produced by the
vibrating instrument reduce the demineralizing eect
of the chelator by reducing the working time, as EDTA
only develops its full eectiveness after a certain working
time (Abbott et al.1991). In contrast, a superior root canal
cleanliness is achieved following ultrasonically agitated
irrigation with NaOCl (1^4%) and EDTAC when compared to ultrasonically agitated irrigation with distilled
water or NaOCl alone (Cameron 1995, Guerisoli et al.
2002).
Pawlicka et al. (1981) compared the cleaning eect of
dierent chelator preparations and found that the eciency of EDTA and DTPA could be further improved by
the addition of a detergent (EDTAC and DTPAC). The
observation that Salvizol can dissolve both organic and
inorganic components of the smear layer and has a

International Endodontic Journal, 36, 810^830, 2003

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Chelators ^ a review Hulsmann et al.

Figure 3 (a) root canal wall after


removal of smear layer using RC-Prep
(magnication1000). (b) root canal
wall after removal of smear layer
using Calcinase slide (magnication
500).

superior cleaning action than EDTAC (Kaufman et al.


1978, Spngberg et al. 1978), however, could not be conrmed (Velvart 1987). Neither Salvizol, Largal Ultra nor
Decal were able to dissolve both organic and inorganic
substances (Koskinen et al. 1980).
Tubulicid Plus and Largal Ultra both removed the
smear layer resulting in a surface with open dentinal
tubules (Liolios et al. 1997). A comparison of EDTA, RCPrep and Salvizol showed that EDTAwas the most eective solution to remove the smear layer (Ram 1977). A
neutral solution of EDTA had a better cleaning action

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International Endodontic Journal, 36, 810^830, 2003

than RC-Prep and allowed visualization of the dentinal


tubules (Verdelis et al. 1999). EGTA has been recommended as an alternative to EDTA for dissolution of the
smear layer because it does not cause erosion of the dentinal tubules unlike EDTA (Calt & Serper 2000).
The cleaning eect of Calcinase Slide, RC-Prep and
Glyde File Prep after 5 min application in alternating
rinses with H2O2 and NaOCl were compared in a recent
study (Hulsmann & Heckendor 2002). Calcinase Slide
cleaned signicantly better than the other preparations
in the coronal- and middle-third of the canal. No dier-

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Hulsmann et al. Chelators ^ a review

Figure 4 (a) Enlarged tubule openings


following the use of a paste-type
chelating agent (magnication
1000). (b) Some tubule openings are
surrounded by a decalcied zone of
peritubular dentine (magnication
1000).

ence could be found between the preparations in the apical-third of the canal. A reduction in root canal-wall
cleanliness towards the apex was also observed.
Irrigation with17% EDTA resulted in better root canal
cleanliness than the use of Glyde File during rotary preparation with Lightspeed NiTi instruments (Ahn & Yu
2000). The use of Glyde File or irrigation with17% EDTA
removed the smear layer more eectively than NaOCl
(Lim et al. 2003). Comparing root canal preparation with
rotary ProFile NiTi instruments, root canal cleanliness

2003 Blackwell Publishing Ltd

proved to be superior following preparation with the


paste-type chelator Glyde File Prep and 2.5% NaOCl as
an irrigant when compared to preparation with NaOCl
or physiological solution alone (Grandini et al. 2002).
Nevertheless, complete removal of the smear layer could
not be achieved, which is conrmed by several studies
on NiTi preparation in combination with a paste-type
chelator and NaOCl (Peters et al.1997, Peters & Barbakow
2000, Hulsmann et al. 2001, Schafer & Lohmann 2002,
Versumer et al. 2002).

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Chelators ^ a review Hulsmann et al.

Figure 5 Following the use of a chelator


paste for 5 min, some dentinal
tubules showed erosion of peritubular
dentine (arrow; magnication
1000).

Comparing dierent sequences of irrigation, the


sequence EDTAC > NaOCl > EDTAC proved to be more
ecient in smear layer removal than the sequence
NaOCl > EDTAC > NaOCl (Abbott et al. 1991). The additional use of ultrasound did not enhance cleaning ability
of these irrigants.

Working time of chelators


Still, the optimal working time of chelating agents is
unknown. Acertain cleaning eect is achieved after chelator application for a few minutes. According to Goldberg & Spielberg (1982), the optimal cleaning eect is
onlyachieved after15 min. In contrast, McComb & Smith
(1975) were able to show a better eect when the chelator
preparation was left in the root canal for14 h. In a study
using autoradiographic tracings of 45Ca-labelled EDTA,
no signicant dierence in penetration depth could be
found after 15-min and 24-h working time (Nicholson
et al.1968). Additionally, quantity of smear layer removal
is related both to the pH and to the length of time for
which the chelating agent has been exposed (Morgan &
Baumgartner 1997). Several studies conrmed that
mineral loss, changes in dentine hardness and cleanliness of the root canal walls depend on the working time
(Nygaard-stby 1957, Hulsmann & Heckendor 2002,
Serper & Calt 2002).
Several studies have reported a good cleaning ecacy of liqiud or paste-type EDTA after working times
between 1 and 5 min (Yamada et al. 1983, Cergneux
et al. 1987, Calt & Serper 2000; 2002, Hu lsmann &
Heckendor 2002, Scelza et al. 2003). In a recent study,

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International Endodontic Journal, 36, 810^830, 2003

1-min exposure to 10 mL EDTA was sucient to


remove the smear layer, whereas an exposure for
10 min caused excessive peritubular and intratubular
erosion (Calt & Serper 2002). This kind of erosion has
been proposed because of the result of the combined
use of EDTA and NaOCl rather than EDTA alone
(Niu et al. 2002). Nevertheless, at present, no denite
recommendation can be given on the optimal amount
and working time for a paste or liquid chelator under
clinical conditions.

Biocompatibility of chelating agents


There is much discussion as to whether and what degree
of inammatory tissue reaction can be caused by chelating agents passing through the apical foramen.
Nygaard-stby (1957) investigated the eect of a 15%
EDTA solution (pH 7.3) on human periapical tissue as
well as on pulpal tissue under clinical conditions in cases
with vital and necrotic pulps. No periapical tissue
damage could be detected after a period of action of up
to 14 months, even though EDTA was intentionally
forced through the apical constriction using a le. The
histological examination revealed normally regenerated
alveolar bone and new functional periodontal ligament
bres. In addition, clinical studies showed that placement of EDTA for up to 28 days after pulpotomy failed
to produce any pulpal tissue necrosis.
In an investigation of the tissue reaction in rats after
intramuscular implantation and injection of EDTA
and EDTAC (15%), the latter caused much greater tissue
irritation after implantation and after injection than

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Hulsmann et al. Chelators ^ a review

10% EDTA (Patterson 1963). No periapical tissue irritation or damage of any kind occurred in 200 clinical
cases where EDTA was used as an irrigant. Acute
exacerbation did not seem to occur more frequently
than with other irrigants. Further studies have indicated that EDTA is not capable of destroying collagen
(Lindemann et al. 1985). When the dentine is intact,
the eect on the pulp seems to be negligible (Lindemann
et al. 1985) so that EDTA can also be recommended as
a conditioning agent prior to application of dentine
bonding (Cao et al. 1992).
In contrast to previous ndings, Collet et al. (1981) concluded that a 15% sodium (Na)-EDTA solution has toxic
eects in vitro. Complete prevention of cell growth was
detected after in vitro use of EDTA-T (Scelza et al. 2001).
Additionally, 15% solutions of EDTA and EDTAC at
pH 7.3 have the potential to cause severe irritation
(Koulaouzidou et al. 1999). These authors found that 15
and17% EDTA solutions and 2.25% NaOCl solutions produce severe cytotoxic eects, whilst1% solutions of both
agents evoked only moderate reactions.
Extrusion of even a low concentration of EDTA solution through the apical constriction results not only in
an irreversible decalcication of periapical bone, but
can also have consequences for neuroimmunological
regulatory mechanisms (Segura et al. 1996). These
authors investigated the eect of EDTA and EGTA on
the binding of vasoactive intestinal peptides (VIP) to
macrophages.VIPs act not onlyas vasoactive substances,
but also play an important role as neuropeptides in the
communication between nerves and immune cells in
the pulp and periapical tissue by modifying the macrophage function. EDTA inhibits VIP binding to macrophages even in lower concentrations than those used
in endodontics (10%). EDTA can prevent the adhesion
of macrophages to substrate; this is time- and concentration-dependent (Segura et al. 1997). EDTA concentrations measurable in the periapical tissues are capable
of reducing binding by 50%. The degree to which VIP
and substrate control of macrophage function eects
the healing process is not clear. On one hand, changes
in macrophage activity can cause the inammatory
reaction to be more easily initiated; on the other hand,
reduced capacity of phagocytosis can result. In addition,
it has been found that EDTA improves plasma extravasation and mediator action (Segura et al. 1997).
In an investigation of the eects of dental etchants and
chelators on nerve compound action potentials (Cehreli
et al. 2002), RC-Prep and File-EZE were shown to reduce
the compound action potentials afteranapplication time
of 160 min by 61.8 and 62.4%, respectively.

2003 Blackwell Publishing Ltd

Comparing the cytotoxic eects of the three irrigants,


EDTA provoked more cytotoxic eects than oxidative
potential water or NaOCl (Serper et al. 2001). Salvizol
was found to be less cytotoxic than EDTAC (Spngberg
et al.1978). In the light of these results, extrusion of EDTA
into the periapical tissue during chemomechanical root
canal preparation should be avoided.

Antibacterial effects of EDTA


Ethylenediaminetetraacetic acid has a certain, albeit
limited, antibacterial eect (Patterson 1963). This is
thought to be because of the chelation of cations from
the outer membrane of bacteria. The use of a 10% EDTA
solution results in the formation of a zone of inhibition
of bacterial growth similar to creosote. Lower concentrations of EDTA solution (0.03^1%) produce a reduced
eect or no eect at all (Russell 1999). The antibacterial
properties of EDTA depend on concentration and pH
(Kotula & Bordacova 1969). The antibacterial eect of
Na-EDTA is only maintained as longas the chelators have
not formed bonds with metal ions (Hendershot et al.
1960, Kotula & Bordacova 1969).
Bacteriological investigations (Pawlicka & Nowacka
1982) have shown that whilst chelators have an antibacterial eect, it is much less than that of paramonochlorophenol. No dierences could be shown between the
eect of EDTA and DTPA, even after the addition of a
detergent (EDTAC and DTPAC).
In a clinical study, Yoshida et al. (1995) examined
the eectiveness of 15% EDTA solution used in combination with ultrasound. No intracanal dressing was
placed between treatment sessions. After 1 week, no
bacteria could be found in the root canal in 93 of 129
cases. EDTA proved to have a greater antimicrobial
eect than saline. The authors concluded that a negative bacteria culture could only be expected after
removal of the smear layer using EDTA. Furthermore,
the combined use of EDTA and 5% NaOCl has a greater
antimicrobial eect than NaOCl alone (Bystrom &
Sundqvist 1985).
REDTA can only inhibit the growth of some anaerobes
after 60 min to a week. Porphyromonas gingivalis is the
exception, because an eect is seen with a 10% solution
after only 1 min (Ohara et al. 1993). Salvizol is thought
to have fungicidal and broad-spectrum antibiotic activity (Nawrath et al. 1960), with lower tissue toxicity than
EDTAC (Spngberg et al.1978). Further studies show that
RC-Prep has a limited antibacterial eect, depending
on the microorganisms used (Heling & Chandler 1998,
Buck et al. 1999, Steinberg et al. 1999). RC-Prep is more

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Chelators ^ a review Hulsmann et al.

Figure 6 Crystals on the root canal wall


following the use of a paste-type
chelator and irrigation with NaOCl.
These crystals could be observed only
in a limited number of specimens
(magnication1000).

eective against Gram-negative than Gram-positive


aerobes (Heling & Chandler 1998).
Increasing the incubation period from 10 to 45 min
increases the antimicrobial eect of RC-Prep on Staphylococcus aureus and Streptococcus peltzer in dentinal tubules
(Heling et al. 1999). The urea peroxide (10%) content of
RC-Prep is thought to be mainly responsible for its antibacterial eect. Urea peroxide is anoxidizing antibacterial
agent (Block 1991), which retains its eectiveness in the

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International Endodontic Journal, 36, 810^830, 2003

presence of blood (Stewart et al. 1961). Investigations of


more than 100 patients after irrigation with EDTA, urea
peroxide and NaOCl resulted in a negative bacterial culture in 97.2% of cases at the end of the rst appointment.
At the beginning of the second appointment, 94.4% of
the teeth showed no bacterial growth, although no canal
dressing had been used (Stewart et al.1969).
Steinberg et al. (1999) investigated the bacteriostatic
and bactericidal eect of the individual components of

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Hulsmann et al. Chelators ^ a review

RC-Prep on S. sobrinus. The minimum concentration to


yield an inhibitory eect was 0.125% for EDTA, 0.25%
for urea peroxide and 30% for glycol, whilst the minimum concentration for a bactericidal eect was 0.25%
for EDTA, 0.5% for urea peroxide and 50% for glycol. In
contrast to this, rstavik & Haapasalo (1990) questioned
the antibacterial eect and the tubular disinfection produced by a 17% EDTA solution. Whilst the number of
S. sanguis at a depth of 100^300 mm in the dentinal
tubules could be reduced after 5 min incubation with
NaOCl, no disinfection could be achieved using EDTA.
Following irrigation with NaOCl (3.5%) and 0.5 M
EDTA,Yang & Bae (2002) found signicantly less bacteria
(Prevotella nigrescens) adhering to the root dentine than
in root canals where the smear layer had not been
removed or removed after irrigation with only NaOCl
(3.5%).

Effect of EDTA on the quality of root


canal obturation
An increased number of obturated accessory canals is
found after nal irrigation with NaOCl (6%) alone or in
combinationwith EDTAthanafter no irrigation or irrigation with distilled water (Villegas et al. 2002). The root
canals in that study were obturated using the System B
(Analytic Technology, San Diego, CA, USA) and Obtura
II (Texceed Corp., Fenton, MO, USA).
The dentine adhesion of endodontic sealers can be
improved by dentine pretreatment with EDTAC,
although this eect is more pronounced after ER:YAG
laser pretreatment (Pecora et al. 2001, Picoli et al. 2003).
The highest increase in adhesiveness was found for Sealer 26 (Dentsply, Petropolis, Brazil); for calcium hydroxide-containing sealers such as Sealapex (Kerr,
Romulus, Mich, USA), Apexit (Vivadent, Schaan, Liechtenstein) and CRCS (Hygienic, Mahwah, NJ, USA), only
a slight increase was found (Picoli et al. 2003). On the
other hand, both NaOCl and RC-Prep signicantly
reduced the bond strength of resin cement to root dentine (Morris et al.2001).This reduction can be completely
reversed by application of 10% ascorbic acid or 10%
sodium ascorbate. Dental adhesives bound signicantly
better to calcied dentine thanto decalcied dentine pretreated with EDTA (Perdigao et al. 2001).
Although some studies suggest that removal of the
smear layer reduces apical leakage after obturation
(Kennedy et al. 1986, Cergneux et al. 1987, Petschelt et al.
1987), the treatment with EDTA may leave a chelated
layer of dentine at the dentine^root lling interface. Residual EDTA inside the dentinal tubules, which was mea-

2003 Blackwell Publishing Ltd

sured to be up to 3.8% of the originally applied volume


(Zurbriggen et al. 1975), may contribute additionally to
ongoing demineralization, resulting in further increase
of apical leakage (Cooke et al. 1976, Biesterfeld & Taintor
1980). Residual EDTA also may interact with the sealer,
which has been demonstrated for zinc oxide^eugenolcontaining sealers (Biesterfeld & Taintor1980). However,
Madison & Krell (1984), who compared NaOCl, REDTA
and a combination of both, could not detect any inuence of the irrigation solution on the apical seal.

Bleaching effect
In some commerciallyavailable EDTA preparations, urea
peroxide is added to the EDTA. The release of oxygen
results in some eervescence that is not only expected to enhance the cleaning eciency, but also is
claimed to have a bleaching eect. No scientic evidence
exists to support the bleaching eect of such chelators.
Regarding the working time of a chelator under clinical
conditions, no bleaching should be expected as a visible
eect of internal bleaching procedures using urea peroxide can be observed only after 48 h (Matis et al. 1998,
Attin et al., 2003).

Additional findings
1 In some studies, it has been mentioned that crystals
could be observed on the dentine surface following the
use of chelators (Schmidt 1968, Kockapan 1987, Behrens
& Sierra1992, Liolios et al.1997, Hulsmann & Heckendor
2002; Fig. 6a,b). Electron dispersive spectrometer analysis revealed that these crystals contained mainly calcium and phosphorus (Schwarze & Geurtsen 1995,
Liolios et al. 1997). Storage in formaldehyde-containing
liquids has been proposed as one possible reason for
the presence and growth of such crystals (Schwarze &
Geurtsen 1995).
2 In an in vitro study, irrigation with EDTA did not aect
the accuracy of electronic length determination using
the Root ZX (Morita,Tokyo, Japan; Jenkins et al. 2001).
3 The use of EDTAduring root canal preparation caused
less corrosion to stainless steel les than NaOCl (5.25%;
Mueller 1982, Oztan et al. 2002). However, other studies
could not detect any corroding eect of EDTA on steel
instruments (Aten1993). In contrast, the cutting ecacy
of steel les is reduced signicantly by EDTA as a result
of slight corrosion but less than following exposure to
NaOCl (Neal et al. 1983).
4 The release of mercury from amalgam llings was
lower when EDTA was used as an irrigant in combina-

International Endodontic Journal, 36, 810^830, 2003

823

Chelators ^ a review Hulsmann et al.

tion with NaOCl than with NaOCl alone (Rotstein et al.


2001).
5 When curved root canals were instrumented with
NiTi instruments to size 30, maintenance of the original
curvature was better in the group in which no EDTA
was used (Bramante & Betti 2000). Nevertheless, the
number of teeth per group in this study was too small
to draw denite conclusions.
6 It has been hypothesized that the use of EDTA would
substantially increase the retention of posts, but no signicant eect has been found (Burns et al. 1993).
Although smear layer removal would be benecial for
increased retention, the decalcication of the dentine
could actually reduce retention. In contrast, a signicantly increased retention was observed after irrigation
with 17% EDTA and 5.25% NaOCl (Goldman et al.
1984a,b).

Conclusions and clinical recommendations


The critical examination of the extensive literature on
the eectiveness of chelator preparations presented here
indicates that the use of chelators is recommended during root canal preparation. Chelator preparations can
reduce the extent of the smear layer produced during
preparation. The eectiveness of these preparations
depends more on the length of application time than
the specic product chosen and clearly decreases from
the canal orice towards the apex.With careful use, the
risk of damage to the periapical tissues is low. On the
other hand, the antibacterial eect of chelator preparations is low, and uid chelators should not replace NaOCl
as a standard irrigant, although they may improve the
ability of NaOCl to penetrate into the dentine and
increase its antibacterial eect.The degree to which chelators actually facilitate negotiation and preparation of
calcied and narrow root canals is unknown. As the
eectiveness of chelating agents is dependent not only
on the concentration and working time but also on the
relationship between the amount of available chelator
solution and the canal-wall surface area, skepticism is
indicated.
The following clinical recommendations are made
based on the previous discussion:
1 root canal preparation can be carried out with the aid
of a chelator paste. This may be introduced into the root
canal with the preparation instrument. The canals
should rst have been ooded with NaOCl to dissolve
vital or necrotic tissue.
2 A chelator in paste form serves as a lubricant for les
and may reduce the risk of instrument fracture in the

824

International Endodontic Journal, 36, 810^830, 2003

canal, although there is no experimental evidence for


this claim. In relation to this, the NiTi instrument manufacturers' recommendations should be followed, even
though there are no clinical or experimental studies
available on this matter.
3 Preferably, a NaOCl solution should be used during
preparation because of its superior antibacterial and tissue-dissolving properties.
4 A nal intensive rinse with a 17% chelator solution
reduces the extent of the smear layer remaining, which,
in turn, results in a cleaner canal wall and better adaptation of the root lling to the canal wall. The order in
which the NaOCl and the chelator should be used has
not yet been dened.
5 EDTA-containing agents should be used between 1
and 5 min.
6 A liquid EDTA solution may be introduced into the
pulp chamber (pipette, cotton pellet) to identify the
entrance to calcied canals.
7 The dierences in certain properties and modes of
action of individual chelators found in the few comparative studies do not allow the recommendation of any particular chelator preparation.
8 EDTA pretreatment may reduce bond strength of
adhesive materials and obturation materials.
9 There is no evidence for a bleaching eect when using
EDTA preparations containing urea peroxide.
10 Apical extrusion of chelators should be avoided.

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Hulsmann et al. Chelators ^ a review

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