Pulp response to temporary restorative materials

Interim filling materials have gained wide acceptance as therapeutic agents, insulating bases, and
temporary restorative materials.
Zinc Oxide Eugenol
Eugenol is a component of clove oil and other essential oils. Eugenol play a prominent role in
dental and oral hygiene preparations. Eugenol is used as flavor, irritant, sensitizer and can
produce local anaesthesia. Eugenol-producing dental materials are used in clinical dentistry.
When zinc oxide- eugenol (ZOE) is applied to a dentinal cavity, small quantities of eugenol
diffuse through the dentin to the pulp.in Lower concentrations, eugenol possess antiinflammatory and local anesthetic effects on the dental pulp. Thus use of ZOE temporary filling
may facilitate pulpal healing; on the other hand, high eugenol concentrations are cytotoxic.
Direct application of eugenol to pulp tissue may result in extensive tissue damage. The ability of
ZOE-based endodontic sealers to influence periapical tissue healing is considered in view of
eugenol's anti-inflammatory and toxic properties. Eugenol- containing dental materials are
frequently used in clinical dentistry. When zinc oxide-eugenol (ZOE) is applied to a dentinal
cavity, small quantities of eugenol diffuse through the dentin to the pulp. Low concentrations of
eugenol exert anti-inflammatory and local anesthetic effects on dental pulp. Eugenol and the
essential oils have also been observed to possess membrane Stabilizing properties on
synaptosomes, erythrocytes and mast cells.
Pavithra B. Eugenol-A Review. Indian J Medical Research. 1981;73:443-51.

Dentists frequently use zinc oxide-eugenol (ZOE) as a temporary filling and as a cement for
provisional restorations. Eugenol-soaked pellets are occasionally placed on vital exposed pulps
as a sedative dressing. These practices are not always successful or without controversy. Both
beneficial and harmful effects have been attributed to eugenol. To date few studies of eugenols
physiologic: effects on the dental pulp have been undertaken. Eugenol and related compounds
have a long history of use by dentists. Eugenol, thymol, and other essential oils have pleasant
smells, germicidal activity and some degree of local anesthetic effects. These com pounds are
related to phenol, which is a weakly acidic alcohol. Phenol also has anesthetic effects and was
one of the first antiseptics used in surgery. Phenol and the closely related compound cresol are
irritating and somewhat caustic to tissue. Eugenol is found in oil of clove, which is primarily
used as a spice and food pre- servative. When eugenol is mixed with zinc oxide, a chelation
reaction occurs and zinc eugenolate is formed. ZOE is a common constituent of temporary
filling, material, cavity base, liners, and root canal sealers. When examined ultrastructurally,
ZOE ce- ment consists of grains of zinc oxide embedded in a zinc eugenolate matrix. Because
separate zinc eu- genolate units are held together by van der Waals forces and particle
interlocking, ZOE cements are weak mechanically.4 Products such as IBM (L.D. Caulk, Milford,
Del.) are reinforced ZOE cements with improved mechanical properties. When exposed to
aqueous media such as saliva or dentinal fluid, hydrolysis of zinc eugenolate occurs, yielding
eugenoi and zinc hydroxide. Eugenol hber- ated from ZOE can diffuse through dentin and into
the saliva. Hume5 filled occlusal cavities in extracted human teeth with zinc oxide mixed with

tritium- labeled eugenol and found that eugenol was slowly released into the dentin and pulpal
fluid. A schematic diagram illustrating the release and dentinal diffusion of eugenol from a ZOE
filling is shown in Fig. 1. In the dentin below the filling, concentrations of 10m2 mol/L were
reached. Fluid in the pulp space obtained concentrations of 10e4 mol/L. These concentrations
were maintained for more than 1 week. The release of eugenol was not markedly affected by the
zinc oxide/ eugenol mix ratio. The release of eugenol was affected by the thickness of remaining
dentin between the pulp chamber and the ZOE-filled cavity. Meryon et a1.6, 7 found that thick
dentin sections provided a better protective barrier than thin sections. Calcium in the dentinal
tubules chelates eugenol, limiting its ability to diffuse through dentin. Binding of eugenol to the
organic matrix of dentin, especially collagen, also slows diffusion. Modified ZOE cements were
also demonstrated to release less eugenol and exert fewer toxic effects. It has been suggested that
acid-etched dentin may facilitate diffusion of potentially toxic amounts of eugenol to the pul~.~
Flume8 considered ZOE paste a good control deiivery system to deposit pharmacologically
active but subtoxic levels of eugenol to the pulp.

TOXIC EFFECTS OF EUGENOL:

Eugenol is bactericidal at relatively high concentrations ( 10m2 to low3 mol/L). Dentin adjacent
to a ZOE-filled cavity may be exposed to bactericidal eu- genol levels. ZOE fillings act to
prevent bacteria! penetration of dentinal cavities9 This clinically im- portant effect was attributed
to the ability of ZOE to prevent microleakage of contaminated oral fluids. Direct measurements

of leakage suggest that the seal created by ZOE is not particularly tight when com- pared with
other materials. Thus the antibacterial effects of ZOE fillings may contribute to their clini- cal
effectiveness. Brief exposure to l0-3 mol/L eugenol kills mammalian cells. Prolonged exposure to
10-3 mol/L also kills cells. Humes data from these studies show that eugenol concentrations that
diffuse through dentin are not cytotoxic. Even lower concen- trations, however, can inhibit cell
respiration and cell division. Recent studies tested the ability of phenolic compounds to inhibit
enzymes in cultured rat pulp cells. Inhibitory eugenol concentrations were significantly higher
than concentrations that had anti- inflammatory eflrects. I2 Various biochemical mecha- nisms
have been proposed to explain the cytotoxicity of eugenol. For instance, eugenol can be oxidized
by peroxidase enzymes t.o a product that is toxic to rat hepatocytes. I3 Eugenol and related
compounds were shown to have a high affinity for plasma membranes because of their lipid
solubility. This is hypothesized to contribute tso cell damage.14 Cotmore et a1.t5 reported that
eugenol can uncouple oxidative phos- phorylation in mitochondria. These toxic effects of
eugenol may explain why direct application of eu- genol-soaked cotton pellets to pulp tissue
appears to cause an exacerbation of pulpitis symptoms. Direct pulp capping with ZOE evokes
mild to more severe pulpal inflammatory response.5-17 Watts and Pater- son1* tested the effects
of ZOE-containing cements on germ-free rats after sterile pulp exposure. When the ZOE material
was sleparated from the exposed pulp by dentin chips, the pulp exhibited minimal inflammatory change 28 days after pulp capping. Placement of the ZOE materia!l in direct contact with
the pulp tissue resulted in chronic inflammation and necrosis. Because this test was conducted
with a commercial ZOE cement, the possible toxic role of other sub- stances besides zinc oxide
and eugenol must be con- sidered. Severe inflalmmatory reactions to ZOE ce- ments applied to
deep cavities were reported in human teeth by BrannstrGm and Nyborg.19 These studies
highlight an important principle concerning eugenols clinical use. Direct (contact between vital
tissue and eugenol-containing material can cause damage to tissue.
PULPAL INFLAMMATION
Inflammation is the response of tissues to injury and infection. The dental pulp is subject to
bacterial inva- sion from caries and trauma from drilling and other restorative procedures.
Inflammation is charcterized by an increase in blood flow, increase in vascular leakage, and
sensitization of nerve endings. These re- sponses lead to the principal symptoms of inflammation, swelling, and pain. In addition, various blood- borne cells enter inflamed tissue. In most
organs in- flammation serves a useful function, limiting the extent of damage and initiating
healing. In the dental pulp inflammation may lead to a less favorable outcome. The pulp -is
enclosed in the rigid confines of the dental hard tissues and lacks collateral circula- tion. This
low-compliance environment does not allow the pulp to swell during the inflammatory
response.20 Instead, the pulpal tissue pressure increases to an ex- tent that may I.ower pulpal
blood flow. Because of this unique functional property, irreversible damage and even pulp death
are frequent consequences of deep caries and traumatic restorative procedures. The following
sections examine the effects of eugenol on var- ious components of the inflammatory process.
This provides a basis for understanding effects that eugenol has on both pulpal and periapical
tissue.

CLINICAL IMPLICATIONS OF EUGENOLS PROPERTIES

The pharmacologic effects of eugenol are likely to be complex and to depend on the free eugenol
concentration to which the tissue is exposed. Fig. 3 shows that beneficial pharmacologic
responses are most probable when the pulp is exposed to low eugeno! concentrations. These low
concentrations can be ob- tained by eugenol diffusion from a ZOE filling through a layer of
intact dentin. Placement of a ZOE filling after excavation of deep caries should exert a sedative
and anti-inflammatory effect. Clinically this should be manifested by a decrease in sensitivity of
the tooth to cold, hot, and sweets. Alternatively, high concentrations capable of cytotoxic effects
can be de- livered to tissues by placing eugenol or ZOE in direct contact with vital tissue. The
evidence strongly sug- gests that direct pulp capping with eugenol-contain- ing materials should
be avoided if long-term mainte- nance of pulp vitality is to be achieved. Direct place- ment of a
eugenol-soaked pellet over a vital exposure should be done when an endodontic procedure can
be performed within a few days. Like other drugs, eugenol is not a panacea. The ef- fectiveness
of eugenol is limited in the face of severe tissue injury. In some instances deep caries or traumatic tooth preparation may induce irreversible ef- fects not amenable to pharmacologic
intervention. Although eugenol may reduce the response to mild trauma, the nature of the pulps
reaction depends on the severity of the damage. No pharmacologic treat- ment can mitigate the
effect of poor technique. To preserve tooth vitality, there is no substitute for early, conservative,
and atraumatic tooth preparation.
The pulpal and possible apical effects of eugenol suggests that this substance be used
conservatively in clinical practice. On the basis of the re- sults of in vitro studies alone, ZOE
may not be accepted as a restorative material.9 Although less toxic than some materials,22
ZOEs maximal benefit can be obtained by avoiding direct contact with vital tissue. This allows
eugenols analgesic and anti-inflammatory effects to predominate over its toxic potential.
Biologic properties of eugenol and zinc oxide--eugenol A clinically oriented review Kenneth
Markowitz, DDS,( Michael Moynihan, DDS, Mintsai Liu, DDS, MA,b and Syngcuk Kim,
DDS, PhD,C New York, N.Y.

Zinc oxide/eugenol cement is widely used as a temporary filling material, a cavity lining, and a
temporary cement. The reaction of the pulp beneath such cement is widely believed to be
insignificant. l-4 Therefore, in many experimental investigations of the pulpal effect of other
restorative materials, zinc oxide/eugenol cement has been used as a control; it has also been used
in teeth to appraise the long-term effect of the trauma of cavity preparation on the pulp. It is
astonishing that such investiga- tio.ns were performed without use of a protective calcium
hydroxide paste or liner, since reactions can occur under deep zinc oxide/eugenol fillings. In an
earlier in- vestigation of 28 such temporary fillings, considerable loss of odontoblasts was noted
under 11, infiltration of exudate cells under nine, and partial necrosis under two. Zinc
oxide/eugenol has been described as a good cavity sealant, preventing leakage and ingrowth of
bacteria. 6-s It, therefore, appears less likely that diffusion of toxins or ingrowth of bacteria from
the surface of the tooth along the interface of ,the temporary filling and the cavity walls will
cause reactions in the pulp. Two other possibilities should be considered. Bacteria can survive in
grinding debris, which forms a layer 2 to 5 p thick that adheres to the prepared surfaces and
cannot be removed by a water spray . This appears to be the main cause of injury to the pulp
observed under restorative materials, such as zinc phosphate cement and different types of resins.
Contaminated debris may also cause pulpal injury under silicate cement and amalgam. When
zinc oxide/eugenol cement is used, it is possible for bacteria to survive in the grinding debris for
some time after insertion and thus cause reactions in the pulp. (2) The second explanation of
possible reactions is chemical irritation by the material.
Zinc oxide/eugenol fillings are known to provide a good sea16-s It seems reasonable, therefore,
to exclude leakage as a causal factor of pulpal irritation. The observations made in Series 1, in
which it was found that the reactions in the pulp were less frequent under lined cavities indicate
that the liner used in the present study offered some protection against irritation by the filling
material. The reduction in the number of odontoblasts and the presence of cell nuclei in the
tubules frequently observed in teeth with unlined cavities, but not under the lined cavities, may
be attributed not only to the thin remaining dentin and the effect of preparation, but also to the
dehydrating effect of the restorative material. This effect is more severe in unlined cavities filled
with zinc oxide/eugenol cement.ls An accelerated outward flow of fluid through the dentinal
tubules caused by the dehydrating effect of the filling material may explain the presence of cell
nuclei under practically all unlined restorations. However, there is no reason to believe that the
aspiration of cells into the dentinal tubules may result in inflammation.
A comparison of the present results with those obtained in studies of the effect of zinc phosphate
cement applied as a thin film in deep cavities reveals that zinc oxide/eugenol cement might be
more dangerous to the pulp than zinc phosphate cement. The latter material did not seem to
produce any inflammatory reaction in the pulp; the same is true for composite resins.8 It seems
logical to assume that if the eugenol is the cause of the pulpal reaction observed, the results
obtained in the present study dealing with Nobetec might also hold true for other materials with a
zinc oxide/eugenol base. It is known that the dentin is often hypersensitive after the removal of a
temporary crown cemented with a zinc oxide/eugenol cement. It has also been demonstrated that
a dentin surface is more sensitive where an inflammatory reaction has been produced in the

corresponding area of the pulp. The hypersensitive dentin may be caused by the inflammatory
reaction produced by the zinc oxide/eugenol cement.
The pulpal irritation, such as inflammatory reaction and aspiration of pulpal cells, demonstrated
after insertion of the zinc oxide/eugenol cement (Nobetec) seems to warrant the following
recommendations:

A temporary restoration with a zinc oxide/eugenol base should not be inserted in deep
cavities without a protective liner or a calcium hydroxide base covering the exposed
dentinal tubules.
Before the temporary cementing of inlays and crowns with a zinc oxide/eugenol cement,
not only should the dentin be properly cleaned and debris removed, but the prepared
surfaces should be covered with a calcium hydroxide liner.

Pulp reaction cement to a temporary zinc oxide/eugenol Martin BriinnstriSm, Odont.Dr.,*

and Hilding Nyborg, Odont.Dr.** Karolinska Institutet, School of Dentistry, Stockholm,
Sweden, and University of
CAVIT
Langeland has stated that the finding of odontoblastic nuclei in the dentinal tubules
constitutes the only valid evidence of injury to these cells and is a valid indication of a
pathologic reaction having taken place within the p~lp.~ This then can be used as a gauge of
injury experienced by the pulpal tissues and is considered to be the only certain histologic
criterion for evaluation of the degree of injury., g Displaced odontoblasts in this study were
found to be confined to the cut dentinal tubules associated with the restorative materials and
were employed as a measure of pulpal involvement. Swerdlow and Stanleyhave shown that in
cavity preparation procedures the remaining dentin thickness is the most significant factor in determining the degree of pulpal response
when the cavity is restored with a relatively inert material. Stanley has stated that, when the time
interval and remaining dentin thickness are known, most other prob- lems of interpretation due to
biologic variation can be extrapolated. A direct relationship is thought to exist in clinical
specimens between the cavity depth and the degree of pulpal reactions. Sayegh and Reed have
recommended that the depth of remaining dentin in monkey teeth as measured along the shortest
distance from material to pulp be not more than 1 .O mm. In this experiment, the average
remaining dentin in all time frames for zinc oxide-eugenol was 1.1 mm., whereas for Cavit it was
1 .O mm. The application of dehydrating agents has been shown to remove enough water to give
rise to an outward movement of dentinal tubular contents.+ I2 This reduced pressure in the
cavity preparation could result in the displacement of the odontoblastic nuclei into the tubules
beneath the cavity., 5, I3 Cavit and zinc oxide-eugenol are similar in that they both set
hydroscopically. I. I4
They differ, however, in their continuing need for water. Cavit sets only after permeation with
water, with the final set product resulting from a reaction with calcium sulfate and zinc oxidezinc sulfate. Zinc oxide-eugenol undergoes an autocatalytic reaction which is initiated by water.

A by-product of this initial reaction is water, which then allows continuation of the setting
reaction without the need of additional outside water. Since both Cavit and zinc oxide-eugenol
exhibit hydroscopic capability, which could result in the displacement of odontoblastic nuclei, it
seems logical that this might serve as a means of comparison. Although Cavit has a sixfold
greater absorption value than zinc oxide- eugenol, no statistical difference in displacement was
found by analysis in any time frame. This would indicate that Cavit does not initiate a greater
pulpal response than that of zinc oxide eugenol.
Conclusion:
When used in accordance with the manufacturers directions, Cavit may serve as a biologica!ly
acceptable interim filling material. Results obtained in this study indicate no statistically
significant difference bettieen Cavit and zinc oxide-eugenol. It should be pointed out that the
manufacturer suggests that Cavit, when used as a temporary restorative material, should be
placed in a thoroughly cleaned cavity prepara- tion which has been left moist rather than dry.