Departments of Oral Rehabilitation and Stomatology, School of Dentistry, University of Otago, Dunedin, New Zealand.
Root-canal-filling materials are either placed directly onto vital periapical tissues or may leach through dentine. The tissue response to these materials therefore becomes important and may influence the outcome of endodontic treatment. This paper is a review of the biocompatibility of contemporary orthograde and retrograde root-canal-filling materials.
Departments of Oral Rehabilitation and Stomatology, School of Dentistry, University of Otago, Dunedin, New Zealand.
Solid filling materials.
Gutta-percha.
Gutta-percha is the main filling material used in rootcanal treatment although it only forms about 20% of the composition of modern gutta-percha cones. Zinc oxide is the main component (60-70%) of the cone and provides a major part of the radiopacity. The remaining 10% is not specified, as it is proprietary information but consists of a mixture of resins, waxes and metal sulphates (Spngberg1999).
Gutta-percha is considered to have acceptable biocompatibility with a low degree of toxicity, a view based on findings in animal studies involving implanted pieces of gutta-percha (Spngberg 1969a, Wolfson & Seltzer 1975). These studies describe the formation of a collagenous capsule around the implants with very little or no inflammatory host response. Gutta-percha cones have however, been shown to be cytotoxic in in vitro tests. Spngberg (1969a) suggested that toxic agents bound to water-insoluble substances are responsible for the toxicity of gutta-percha cones. These substances are set free when gutta-percha is dispersed into small particulate fractions.
Wolfson& Seltzer (1975) found that with the exception of a calcium hydroxide and a chloroform-containing product, the toxic effects of natural occurring guttapercha (trans-polyisoprene) are similar to those of commercial gutta-percha. Munaco et al. (1978) and Pascon & Spngberg (1990) regarded the cytotoxic effect of commercial gutta-percha to be due to the high content of zinc oxide. Contrary to this belief, results from the study by Sunzel et al. (1997) showed that the addition of zinc reduced the toxicity of rosin and resin acid and appeared to be cytoprotective.
Complement activation was applied as a parameter to determine the inflammatory potential of four different brands of gutta-percha and nine ingredients of one of those products (ZnO,TiO2, BaSO4) in vitro (Serene et al. 1988). Each investigated brand of gutta-percha and all individual gutta-percha components stimulated the complement system. It was concluded from this data that overextension of gutta-percha might contribute to pain and periapical inflammation although this has never been shown clinically.
Holland et al. (1982) investigated the long-term reaction of rat connective tissue to silver and gutta-percha points over a period of1 year. One brand of gutta-percha and the silver points were well tolerated. The other brand of gutta-percha points caused pronounced effects with thick fibrous capsules and severe chronic inflammation of the surrounding connective tissue. This observation is in line with the inflammatory potential of guttapercha as shown in the study by Serene et al. (1988).
In a study by Sjogren et al. (1995) the tissue reaction to gutta-percha in the form of large, fine and rosin-chloroform- dissolved particles was tested. Large gutta-percha particles were well encapsulated and the surrounding tissue was free of inflammation. Fine particles and those treated by rosin-chloroform evoked an intense, localized tissue response, characterized by the presence of macrophages and multinucleated giant cells. The authors concluded that the size and surface character of guttapercha determine the tissue reaction to the material.
Calcium hydroxide-containing gutta-percha points and their efficacy comparable with calcium hydroxide pastes have been demonstrated (Holland et al. 1996). In an in vitro study by Podbielski et al. (2000) calciumhydroxide containing gutta-percha points demonstrated good inhibitory action on the bacterial growth of three of the four test organisms. Iodoform gutta-percha cones, introduced by Martin & Martin (1999) had a negligible effect on Enterococcus faecalis, but demonstrated a significant inhibitory effect on Streptococcus sanguis (Silver et al.2000).
Warm gutta-percha techniques impose the additional complication of heat generated during obturation which may have a deleterious effect on the periodontium. A temperature rise of 10 8C above normal body temperature is regarded as a critical level at which irreversible damage to periodontal tissues can occur (Gutmann et al.1987, Saunders1990). Studies have shown that the temperature hardly ever exceeded an increase of 10 8C at the external root surface during themoplasticized gutta-percha obturation techniques (Gutmann et al. 1987, Silver et al.1999, Sweatman et al.2001) and as such should not pose a problem.
Obturation with gutta-percha requires the use of sealing cement and although gutta-percha has been shown to be cytotoxic, the sealers are normally the most toxic element of the filling.
These sealers are simply zinc oxide-eugenol (ZnOE) cements modified for endodontic use. The liquid for these materials is eugenol whilst the powder contains finely sifted ZnO to enhance the flow of the cement. In a study by Serene et al. (1988), it was found that ZnOE sealers activated the complement system and thus an inflammatory reaction. Additionally, Guigand et al. (1999) found these sealers to be severely cytotoxic in fibroblast cultures. These properties are mainly attributed to the eugenol component. However, ZnOE sealers easily lend themselves to the addition of chemicals, which may contribute to its cytotoxicity. Rosin or Canada balsam is added for greater dentine adhesion, paraformaldehyde for antimicrobial and mummifying effects, germicides for antiseptic action and corticosteroids for suppression of inflammation.
Rosins are derived from a variety of conifers and are composed ofapproximately90%resinacids.Theremaining parts are volatile and non-volatile compounds such as terpene alcohol, aldehydes and hydrocarbons. The carbon group of resin acids is lipophilic, affecting the lipids in cell membranes and increasing the cell membrane permeability. The resin acids are both antimicrobial and cytotoxic (Soderberg1990).
Zinc oxide is effective as an antimicrobial agent (Sunzel et al.1990) and has been shown to provide cytoprotection to tissue cells. Interactive toxic effects between zinc and rosin or resin acid was investigated using human polymorphonuclear leucocytes and gingival fibroblasts. Rosin and resin acids were highly cytotoxic depending on the concentration. The addition of zinc clearly reduced rosin and resin acid toxicity proportionally with increasing zinc concentration (Sunzel et al. 1997). Non-specific histocompatibility tests showed that eugenol-based sealers elicited pronounced tissue irritation (Kolokuris et al.1998a, Gulati et al.1991).Two ZnOE sealers (Sealite; Pierre Rolland Co., Merignac, France), Kerr Pulp Canal Sealer (Kerr, Romulus, MI, USA) were, however, rated biocompatible, based on histologic response, when implanted into the mandibular bone of rabbits (Pertot et al.1992). Kolokuris et al. (1998a) found that subcutaneous injection of a ZnOE sealer (Roth 811 (Roth Drug Co., Chicago, IL)) into rats affected the normal concentrations of Zn, Ca & Cu in various organs, e.g. heart, brain, liver and kidney. These results suggest that ZnOE sealers may release considerable amounts of these compounds, which are then deposited in vital organs.
A comparative study on the effects of one calcium phosphate cement (CPC) and two ZnOE sealers was performed with intentional overfilling in monkeys over a 6-month period. The CPC caused only mild inflammatory periapical reactions in the initial study period whereas both ZnOE sealers (Grossman’s sealer; Pharmacy, Glasgow, Royal Infirmary, UK) and N2 (Indrag- Agsa, Losone, Switzerland) were severely irritating over the full 6-month duration (Hong et al.1991). Despite the antimicrobial effect of rosin and zinc oxide on facultative bacteria, zinc-releasing materials such as gutta-percha and ZnOE sealers, especially those releasing paraformaldehyde, have been associated with maxillary sinus aspergillosis (Beck-Mannagetta&Necek1986,Kobayashi 1995, Odell & Pertl1995). It was hypothesized that paraformaldehyde penetrates the sinus through overfilled sealer and may cause tissue irritation and local necrosis of the sinus mucosa. Subsequently, zinc oxide is released from the sealer, which may then promote growth of inhaled Aspergillus conidia (Beck-Mannagetta & Necek 1986).
The setting of zinc oxide-eugenol cements [such as Rickert’s sealer (Kerr, Romulus, MI, USA), U/P-Grossman’s sealer (Pharmacy, Glasgow, Royal Infirmary, UK), Tubli-seal (Kerr, Romulus, MI, USA)] is a chemical process combined with physical embedding of zinc oxide in a matrix of zinc eugenolate. Analyses of the release of eugenol from set ZnOE cement showed that the oil is available only as the result of surface hydrolysis of the chelate (Wilson & Batchelor 1970, Becker et al. 1983, Hume1984). Samples of ZnOE placed into saline showed an immediate release of eugenol from the ZnOE surface with the highest rate of release in the first seconds after contact, the release rate declined exponentially thereafter. In contrast, the release rate through intervening dentine was found to be entirely different. The release of eugenol was found to be much slower and could only be detected after several hours, it peaked after about a day and then declined slowly over several weeks. A sustained release occurred with the establishment of a relatively stable concentration gradient across the dentine which persisted for several months (Hume 1988). On the basis of data on this concentration gradient, Hume (1988) predicted the various pharmacological and toxicological actions of eugenol. In the dentine immediately beneath the ZnOE, the concentration of eugenol is sufficient to inhibit bacterial metabolism whilst the concentration in more remote dentine would be below the threshold for killing mammalian cells but at a sufficient level to exhibit pharmacological properties for which eugenol is renowned such as inhibition of nerve action potential (Brodin & Prstavik 1983) and prostaglandin synthesis (Dewhirst 1980). If ZnOE contacts wetter tissue the release is more rapid, leading to the development of concentrations sufficient to kill cells. This explains the toxic effects of ZnOE when applied to wet tissues or to cells in culture.
The toxic potency of eugenol has been demonstrated by Araki et al. (1993a, 1994) who found that the sealer, Canals (Syowa Yakuhin Kako Ltd., Tokyo, Japan), with eugenol as the liquid component was significantly more cytotoxic in permanent L929 cells and primary human periodontal ligament fibroblasts than the material, Canals-N (SyowaYakuhin Kako Ltd., Tokyo, Japan),with an identical powder as Canals but with fatty acids replacing eugenol as the liquid component. Similarly, it has been shown that the eugenol component of a sealer was highlycytotoxic to primary human periodontal ligament fibroblasts whereas the other sealer ingredients TiO2, ZnO and BaSO4 caused only slight toxic effects (Klaiber et al. 1981). The effect of eugenol on the adherence of immunocompetent cells to substrate was studied with peritoneal macrophages from Wistar rats. Even high dilutions (1:1000) of this phenol derivative significantly reduced the adhesion of macrophages. Thus, eugenol could inhibit macrophage function and may influence inflammatory reactions in the periapical tissues (Segura & Jmenez-Rubio 1998). The pronounced antibacterial effect of the ZnOE sealer is very likely due to eugenol (Al-Khatib et al.1990, Mickel &Wright1999). Fora long time, it has been common to mix formaldehyde into some endodontic sealers (Endomethasone (Septodont, Saint-Maur, France) and N2 (Indrag-Agsa, Losone, Switzerland)). Formaldehyde adds to the already toxic effect of eugenol and prevents or inhibits healing.
Calcium hydroxide-containing sealers Several sealers, e.g. Sealapex (Kerr, Romulus, MI, USA), CRCS (Hygenic, Akron, USA) and Apexit (Vivadent Schaan, Liechtenstein) have been marketed which claim the benefits of the biological effects of added Ca(OH)2. In order to be therapeutically effective, calcium hydroxide must be dissociated into Ca2+ and OH- ions. Therefore, to be therapeutic an endodontic sealer based on calcium hydroxide must release these ions which may affect the structural integrity of the sealer and compromise the long-term seal.
In a study of diffusion of hydroxyl ions into surrounding dentine after root filling with Sealapex and Apexit, no traces were found in teeth filled with Apexit. Some hydroxyl ions could be detected in the dentine close to the root filling with Sealapex (Staehle et al. 1995). In a similar study of calcium and hydroxyl ion release from Sealapex and CRCS, negligible release was noted from CRCS, whilst Sealapex released more ions but disintegrated in the process (Tagger et al. 1988). In vivo studies have demonstrated that Sealapex and CRCS easily disintegrate in the tissue (Soares et al. 1990), and both may cause chronic inflammation (Tronstad et al. 1988).
Calcium hydroxide sealers are generally characterized as having good cytocompatibility (Feiglin 1987, Beltes et al. 1995, Economides et al. 1995, Vajrabhaya & Sithisan 1997, Vajrabhaya et al. 1997, Geurtsen et al. 1998, Osorio et al. 1998, Telli et al. 1999, Ersev et al. 1999). However, unsatisfactory results were found with CRCS in several studies (Tronstad et al. 1988, Yesilsoy et al. 1988, Boiesen & Brodin 1991, Bezerra et al. 1997). CRCS is considered a standard ZnOE sealer by various authors though it also contains Ca(OH)2. The Ca(OH)2- containing sealer Apexit showed nomutagenic potential in a study by Schweikl & Schmalz (1991).
Nonspecific histocompatibility tests on calcium hydroxide-based sealers were variable after subcutaneous implantation or intraperitoneal injection in mice. Inflammation and tissue necrosis were especially prominent during the initial period after application. Neurotoxic effects were investigated with isolated nerves in vitro. Rat phrenic nerves were treated for 1.5- 30 minwith two calciumhydroxide-containing sealers, CRCS and Sealapex. Short-term contact resulted in a reversible inhibition of the nerves whereas neural conduction was irreversibly inhibited after 30 min by both sealers (Boiesen & Brodin1991).
Specific histocompatibility was tested in dog root canals to compare the periapical reaction to four Ca(OH)2-containing sealers (Leonardo et al.1997).After 6 months, no inflammatory lesions and complete sealing of the apical region of the root canals were found with Sealapex. However, incomplete sealing of the filled canals and periapical inflammation were identified when CRCS, Apexit or Sealer 26 (Dentsply, Petro. polis, RJ, Brazil) were used. The inflammatory reactions were related to an incomplete adaptation of the root-canal fillings (Leonardo et al. 1997). These results indicate that an incomplete adaptation may increase in vivo degradation of the sealer with subsequent periapical irritation due to elevated quantities of released substances, or it may favour microbial leakage contributing to periapical inflammation.
Finally, calciumhydroxide and Sealapex impaired the status of the periapical tissue when the materials were extruded through the apex. No adverse effects were found with root fillings terminating at the anatomical foramen. These observations suggest that mechanical stimuli of the periapical tissue may influence the compatibility of a root-canal filling in vivo (Sonat et al.1990). Formaldehyde-containing sealers
A large group of sealer/cements, including the commonly used Endomethasone (Deproco UK Ltd., Surrey, UK), Riebler’s paste (Amubarut; Wera Karl, Biesingen, Germany) and N2 (Indrag-Agsa, Losone, Switzerland) contain substantial amounts of paraformaldehyde. Of these, N2 has been most studied. The contents of N2 are not much different from other paraformaldehyde containing sealers as far as toxicity is concerned and it is basically a zinc oxide-eugenol sealer, the exact composition of which has changed over the years. Thus, the significant lead oxide content (England et al. 1980), as well as the smaller amounts of organic mercury that were formerly major components ofN2areoftenmissing from modern formulations although it still contains large amounts (4-8% v/v) of formaldehyde. It loses substantial volume when exposed to fluid (Grossman1978) with this volume loss being exacerbated when it also contains hydrocortisone (e.g. Endomethasone; Septodont, St Maur, France). N2 seals well when used with a core (Brown et al.1979). It has been found to bevery toxic, both in vitro (Spngberg & Langeland 1973) and in vivo (Spngberg 1969a, 1974). Coagulation necrosis is normally observed within a very short time period and reaches a maximum in less than 3 days. Since the tissue is impregnated with formaldehyde, repair of the necrosis is a slow process, often taking months to occur. In time, the formaldehyde is flushed from the necrotic tissue (Block et al. 1980, Araki et al. 1993b), followed by either bacterial invasion or, if the blood supply to the tissue is still adequate, repair (Spngberg 1969 a,1974). In clinical setting, this untoward tissue reaction can be seen as localized inflammatory reactions in the periapical tissue (Engstrom & Spngberg1969b).
Cases of hypersensitivity reactions, presumably as a result of systemic exposure to formaldehyde, have been reported following root-canal treatment (Forman & Ord 1986, Fehr et al. 1992). In addition to its cytotoxic properties, formaldehyde is known to be both mutagenic (Goldmacher & Thilly 1983) as well as carcinogenic (Swenberg et al.1980), though these effects have not been attributed to formaldehyde release from endodontic materials (Lewis & Chestner1981). Some epoxy resin sealers have been reported to release formaldehyde when freshly prepared and during setting (Koch 1999) and these will be discussed under resin sealers.
Chloroform-based sealers such as rosin-chloroform (Callahan1914), Chloropercha (Tanrac Ltd., Gavle, Sweden), Kloropercha (Svenska AB, Stockholm, Sweden) and Kloroperka N-P (Union Broach Corp., Long Island City, NY, USA) are common. Chloropercha consists of white gutta-percha and chloroform and derives its toxicity from the chloroform component. Rosin chloroform contains 5-8% of various rosins that are toxic. Thus, after the evaporation/absorption of chloroform, theresin continues to be irritating (Spngberg & Langeland 1973, Sjogren et al. 1995). Kloroperka N-P powder contains approximately 20% white gutta-percha and 50% zinc oxide. The remaining components are Canada balsam and rosins which may act as irritants after the loss of the chloroform. However, the combination with zinc oxide should provide a significant level of cytoprotection in clinical use (Soderberg1990).
The general use of chloroform has been substantially curtailed in recent years due to concerns about its toxicity, however, the amount normally used in endodontics is insignificant and poses no health hazard. Nevertheless, it is important to reduce the vaporization during use because chloroform is highly volatile. When used for softening of gutta-percha during the removal of old root-canal fillings or for the chloroform dip root-canal- filling technique the chloroform should be dispensed through a syringe and hypodermic needle (Donelly 1993). For other uses the exposure time, amount used and chloroform surface exposed should be minimized.
Halothane and turpentine may be used as chloroform substitutes. Halothane is less effective than chloroform in softening gutta-percha, is hepatotoxic like chloroform and has a higher local toxicity than chloroform. Turpentine is not carcinogenic but may cause allergies, it has high local toxicity and dissolves gutta-percha poorly. Several other chloroform substitutes have been described for use in endodontic treatment procedures (Uemura et al.1997, Hansen1998). However, with careful workplace hygiene there is little risk associated with the use of chloroform in endodontics (Barbosa et al. 1994).
Polymers.
Most of the newer sealers on the market are polymers. They include epoxy resin sealers, e.g. AH26 and AHPlus (DeTrey Dentsply, Konstanz, Germany), methacrylate based sealers, e.g. polyhydroxy-ethylmethacrylate (Hydron, NPD Dental Systems Inc., New Brunswick, NJ, USA), polyvinyl-based sealers (Diaket-A, ESPE-Premier, Norristown, PA, USA) and polydimethylsiloxane (Roeko- Seal, Langenau, Germany). Like most sealers AH26 (DeTrey Dentsply) is very toxic when freshly prepared (Spngberg 1969b, Pascon et al. 1991). The toxicity of AH26 sealer is attributed to the release of a very small amount of formaldehyde as a result of the chemical setting process. This amount of brief release of formaldehyde, however, is thousands times lower than the longterm release from conventional formaldehyde-containing sealers such as N2 (Spngberg et al.1993) but signifi- cantly higher than the amount released by AH Plus (Spngberg et al.1993, Cohen et al.1998, Leonardo et al. 1999a).
AH26 contains a catalyst/disinfective agent, hexamethylenetetramine (methenamine), which is hydrolysed to ammonia and formaldehyde. It is a very hydrophilic material and formaldehyde is processed only by hydrolytic cleavage of hexamethylenetetramine (methenamine). The surface of the freshly mixed material in contact with water apparently determines the amount of formaldehyde released (Koch 1999). Koch (1999) studied the formaldehyde release from three different rootcanal sealers (AH26, Amubarut a phenol resin, and N2), and demonstrated that all materials showed the highest release of formaldehyde in the freshly mixed samples. The release of formaldehyde decreased after setting for 48 h. No further decreasewas seen after storage for 2 weeks in the case of N2, whilst AH26 released only insignificant amounts after 2 weeks.
After the initial setting, AH26 exerts little toxic effect in vitro and in vivo (Bergdahl et al. 1974, Wennberg et al. 1974, Pascon & Spngberg 1990). Azar et al. (2000) demonstrated early cytotoxic effects of AH26 on fibroblasts lasting for1week followed by a substantial reduction in cytotoxicity. The cytotoxicity of AH Plus was confined to the early period of the experiment and was no longer detectable after 4 h after mixing. AH26 and AHPlus have been rated as highly, moderately or slightly toxic in various studies involving different tests (Klaiber et al. 1981, Meryon & Brook 1990, Vajrabhaya et al. 1997, Geurtsen et al.1998, Koulaouzidou et al. 1998,Telli et al. 1999, Cohen et al.2000).AH Plus exhibited a lower cytotoxicity potential compared to AH26 in the study by Huang et al. (2002).
Schweikl et al. (1995) studied the genotoxicityofAH26 and its components using theV79/hprt mammalian cell mutation assay. Unset sealer was clearly genotoxic, however, the mutation frequency decreased proportionally to increased setting time. Both AH26 and AH Plus caused a dose-dependent increase in genotoxicity in the study by Huang et al.2002).AH26liquidwas also distinctly mutagenic. It was concluded that two mutagenic ingredients - bisphenol-A-diglycidyl-ether and formaldehyde - were the causative agents. Silver-free AH26 revealedaweak positive mutagenic response to the Ames test (Ersev et al. 1999). Other investigators found AH26 to be mutagenic up to 1 month after setting (Stea et al. 1994, Heil et al.1996, Jukic et al.2000). It was speculated that this ‘long-term’ genotoxic action was due to a derivative of bisphenol-A-diglycidyl-ether. Contradictory data have been reported about the mutagenic potential of AHPlus inthe unset and set condition. A comprehensive screening using four in vitro and in vivo assays (umu, Ames, DIT, AFE) yielded no indication that this sealer may cause mutagenicity in the set condition (Leyhausen et al.1999). However, using theAmes test, a weak mutagenic activity was found in the unset condition and up to 1 day after mixing (Schweikl et al. 1998, Jukic et al. 2000).
In a long-term specific histocompatibility study in baboons by Pascon et al. (1991),AH26 caused severe periapical inflammation after 1-7 days. After periods of 2- 3 years, however, AH26 was found to cause only slight irritation. An in vivo study in dogs’premolars (Leonardo et al.1999b) demonstrated hard tissue formation apically to the AH Plus in14 of the16 roots analysed. Inflammatory cells or areas of necrosis were not associated with AH Plus. AH26 was found to be markedly antimicrobial particularly against Porphyromonas endodontalis, an effect that was ascribed to the formaldehyde release during the initial period after mixing (Spngberg et al. 1993).
Diaket is a polyketone compound containing vinyl polymers mixed with zinc oxide and bismuth phosphate (Schmitt 1951). In the studies by Spngberg (1969a,b,c,d) it was found highly toxic in vitro, causing extensive tissue necrosis and long-lasting irritation. Olsson et al. (1981a,b) have shown data suggesting mild tissue reactions after longer periods of time and Olsson & Wennberg (1985) suggested marked reduction in tissue irritating effect after 2 weeks. Results from the study by Prstavik & Mjor (1988) also showed Diaket to have a favourable biocompatibility especially in comparison to the other tested sealers. Diaket showed no mutagenic potential in the study by Schweikl & Schmalz (1991). Biocompatibility has been assessed when the material was embedded in bone. Nencka et al. (1995) implanted Diaket into the tibia of rats and observed that it caused a severe inflammatory reaction at 3 days, with a gradual decrease in intensity until no reaction was seen at 180 days.These results suggest that Diaket has acceptable biocompatibility.
Glass ionomer sealers.
Glass ionomer cements have been introduced as endodontic sealers (e.g. Ketac-Endo, ESPE GMBH & Co., KG, Seefeld/Oberbay, Germany), as root-end-filling materials (Zetterqvist et al.1991, Jessle. n et al.1995) and as a perforation repair material (Alhadainy & Himel1993).
Ketac-Endo (ESPE GMBH & Co.), a glass ionomer cement modified for endodontic use, is known to cause minor tissue irritation (Zetterqvist et al.1987, Zetterqvist et al.1988) and low toxicity in vitro (Pissiotis et al.1991). Kolokuris et al. 1996) implanted Ketac-Endo in Teflon tubes into the subcutaneous tissue of Wistar-Furth rats. A mild inflammatory reaction was seen after 5 days of implantation. The intensity of the inflammatory reaction diminished by the15thdayand this reduction continued progressively through the 60th and 120th day, thus showing good biocompatibility and confirming the findings of Zetterqvist et al. (1987,1988). It had little cytotoxic effect on L-929 cells after a setting time of 24 h and 1week, respectively, and showed nomutagenic potency in the Ames test (Ersev et al. 1999). Ketac-Endo showed antibacterial activity to Enterococcus faecalis after 24 h with an increased activity after 7 days (Heling & Chandler1996). Ina study by Leonardo et al. (2000), Ketac-Endo was antibacterial to all seven tested bacterial strains.
Gutta-percha.
The use of gutta-percha to fill root-end preparations has been described but limited clinical reports on its effectiveness are available (Reit & Hirsch1986). Gutta-percha with sealer may be cold condensed (Weine & Gerstein 1976) or chloroform softened (Reit & Hirsch 1986). The introduction of thermoplasticized gutta-percha has also led to greater investigation into the clinical use of gutta-percha for root-end filling (Dawood & Pitt Ford 1989, Sultan & Pitt Ford 1995). Biocompatibility of gutta-percha has been discussed previously.
Zinc oxide-eugenol.
Zinc oxide-eugenol cements have been recommended for root-end fillings by clinicians for many decades (Garcia 1937, Nicholls 1965). Dorn & Gartner (1990) showed that root-end fillings with two versions of zinc oxide- eugenol hada significantly higher success rate than with amalgam. Ina recent series of histological investigations (Pitt Ford et al. 1994, 1995a,b), Super-EBA (Harry J Bosworth Co., Skokie, IL, USA) and IRM(L.D. Caulk Co., Milford, DE, USA) were found to be more biocompatible than other formulations of zinc oxide-eugenol. These fortified versions also have low solubility (Owadally & Pitt Ford 1994), good antibacterial action (Chong et al. 1994, Torabinejad et al.1995c) with minimal dye leakage (O’Connor et al.1995). A frequent finding on histological examination has been the presence of giant cells on the surface of the root-end-filling material (Pitt Ford et al. 1994, 1995 a, b). However, Pantschev et al. (1994) did not support the superiority of root-end filling with fortified zinc oxide-eugenol cement (Stailine EBA) over amalgam.
Polymers.
Diaket (ESPE-Premier, Norristown, PA, USA), mixed to a thicker consistency than for use as a root-canal sealer, has been advocated as a root-end-filling material (Tetsch 1986).When used as a root-end filling in the study by Williams & Gutmann 1996), the overall healing of the periradicular tissues was found to be favourable. Furthermore, Walia et al. (1995) demonstrated in a leakage study that Diaket provided a better seal than either IRM or EBA in both1and 3-mm-deep root-end preparations.
Glass ionomer cements.
When used as a root-end-filling material the antibacterial effect of glass ionomer cements has been reported as variable (DeSchepper et al. 1989, Chong et al. 1994) and their sealing ability has been questioned (Pitt Ford & Roberts 1990, Chong et al. 1991). However, a favourable periapical tissue response has been reported in the absence of infection in the root canal (Callis & Santini 1987, Pitt Ford & Roberts 1990, Zetterqvist et al. 1991). Glass ionomers were found to inhibit the growth of gingival fibroblasts and periodontal ligament cells (Peltola et al. 1992, Makkawy et al. 1998). This is especially relevant when glass ionomers are used as root perforation materials and are in contact with the periodontium for prolonged periods of time. It has, however, been demonstrated that tissue irritation is not a problem after a period of time (Kolokuris et al.1996).
Amalgam has been the most widely used root-end-filling material for many years (Von Hippel 1914, Block & Bushell 1982, Gutmann & Harrison 1985, Friedman 1991)mainly because dentists are familiar with its handling and because it is radiopaque. In recent years, its continued use has been questioned for reasons such as leakage, biocompatibility, corrosion, staining and overall poor performance (Dorn & Gartner 1990, Pitt Ford et al. 1995a). It has come under increasing criticism because of the mercury hazard (Eley&Cox1993).The tissue response to amalgam root-end fillings has been shown to be unfavourable and associated with inflammation in short-term studies with time periods ranging from2 weeks to5 months following placement (PittFord et al. 1994, Torabinejad et al. 1995b, 1997). Histological staining for mercury has shown traces of amalgam in the tissue some distance from the root-end. These amalgam particles were also associated with inflammation (Pitt Ford et al.1994). In histological studies of root-end fillings amalgam has been associated with the most severe and extensive inflammation of all materials tested including IRM, Super-EBA, Kalzinol (De Trey, Dentsply, Konstanz, Germany),Vitrebond (3M, St. Paul, MN, USA), and Proroot TMMTA(Dentsply, Konstanz, Germany) (Pitt Ford et al. 1994, 1995b, Torabinejad et al. 1995a, 1997, Chong et al. 1997). Polymorphonuclear leucocytes (PMN) were the predominant cells at the 2-5-week time period and lymphocytes the predominant cells at the 10-18-week time period (Torabinejad et al. 1995a). No fibrous capsule tissue was seenateither of these time periods. Torabinejad et al. (1997) sacrificed experimental monkeys 5 months after surgery and found that lymphocytes were the predominant inflammatory cell in the bulk of the lesions. PMN leucocytes were frequently observed close to the amalgam and a fibrous tissue capsule was present over most amalgam root-end fillings. Clinical and radiographic healing of periapical lesions following apicectomy and amalgam root-end fillings was found to increase from 57% at 1-year recall to 72% at later recalls (2-15 years) (Rud et al.1972).However, Jessle. n et al. (1995) found that the clinical and radiographic success rate after the placement of amalgam retro fillings decreased from 90% at 1 years to 85% at 5 years, although this effect may not have been due solely to the amalgam. Overall, studies suggest that amalgam shows poor tissue biocompatibility reactions in the short term with improvement in biocompatibility over a longer observation period.
Composite resin.
Conventional composite resins contain a polymerizable organic matrix, inorganic reinforcing fillers and a silane-coupling agent which bridges the organic and inorganic components (Ferracane 1995). The organic matrix consists of several (co)monomers (e.g. Bis-GMA, UDMA, EGDMA, TEGDMA, etc.) and various additives which function as (co)initiators, stabilizers or inhibitors. Various factors determine the biocompatibility of a resin-based material, particularly the amount and nature of leachable components (Geurtsen 2000). All organic ingredients of a composite resin are extractable by organic solvents after polymerization. A few components are, however, also leached into an aqueous medium. In particular, considerable amounts of TEGDMA may be released into water. Several composite resins were also found to liberate formaldehyde into water in amounts sufficient to cause local allergic reactions (Pysad et al.1988, Koch & Staehle1997).
Geurtsen et al. (1998) investigated the cytotoxic effects of 35 single monomers and additives of composite resins in permanent 3T3 cells and primary human oral fibroblasts. With in the groups of (co)monomers and (co)initiators, high or moderate cytotoxic reactions were observed. Proliferation of Streptococcus sobrinus and Lactobacillus acidophilus was inhibited, promoted or not influenced in a dose-dependent manner by single-resin components in solid-a s well as liquid-phase systems (Updegraff et al.1971, Hansel et al.1998). Generally, only very small amounts of these hydrophobic substances are released into an aqueous environment and should not have microbial effects. The severely cytotoxic (co)monomers EGDMA and TEGDMA significantly promoted growth of cariogenic pathogens (Spahl et al. 1998). The cytotoxic properties of these (co)monomers together with their microbial growth promotion may contribute to pulpal injury. It has been reported that methylmethacrylate (MMA) may be teratogenic and can cause adverse cardiovascular effects in animals (Phillips et al. 1971, Singh et al.1972, Karlsson et al.1995).
Composite resin in combination with a dentine-bonding agent used for root-end filling in a saucer-type preparation has achieved good short- and long-term healing results in clinical studies (Rud et al. 1991, 1996 a, b). Clinical investigations including patient recalls of up to 9 and 12 years after treatment with Retroplast TM (Retroplast Trading, RUnne, Denmark) and Gluma1 (BayerAG, Leverkusen, Germany), respectively, showed complete radiographic bone healing over time in a high percentage of cases (Rud et al. 1996b, 2001). In vivo studies in both monkeys and humans comparing the Retroplast and Gluma combination revealed the absence of inflammatory cells around the root-end filling, with fibroblast and collagen fibres present immediately adjacent to the filling (Rud et al. 1996a). In many cases, cementum deposition with Sharpeys fibres were found in intimate contact with the restoration, suggesting a cementogenesis potential for these materials. Unfortunately, absence of complete healing has been found in conjunction with poor haemostatic control during treatment (Rud et al.1991).
More recent composite systems support many of the ideal characteristics for root-end-filling materials and are consequently one of the more common options available for root-end filling. Many resin materials are, however, not suitable for periradicular use and care must be exercised in choosing the right material.
Mineral trioxide aggregate.
Mineral trioxide aggregate (MTA) has been proposed as a compound to seal off the pathway of communication between the root-canal system and the periapical tissue and has been shown to have less leakage than amalgam or zinc oxide-eugenol materials in leakage tests (Torabinejad et al.1994, 1995 a, b). Other properties that have been investigated include antibacterial effects (Torabinejad et al.1995c), biocompatibility in cell culture (Torabinejad et al. 1995d) and when embedded in bone (Torabinejad et al. 1995e), its cytotoxicity with the agar overlay and radium chromium release method (Torabinejad et al.1995d) and also in histological examinations of the periapical area associated with root-end fillings in dogs and monkeys (Torabinejad et al. 1995a, 1997) and with lateral root perforations in dogs (Holland et al. 2001). These tests demonstrated that MTA has good biocompatibity.
The use of MTA as a root-end-filling material in dogs and monkeys provided superior results with considerably less periradicular inflammation compared with amalgam and the production of new cementum over the root-end filling of all the long-term specimens (Torabinejad et al. 1995a, 1997). The consistency of response has been unparalleled with other materials. Clinical reports of five cases indicate that MTA may have clinical advantages over other sealers, such as Ca(OH)2-based materials, in the treatment of severe endodontic problems such as root fracture and perforation (Schwartz et al.1999). Histological analysis of the healing of intentional root perforations repaired with MTA (Holland et al. 2001) showed no inflammation, with deposition of cementum over MTA in the majority of specimens. All the specimens that were restored with Sealapex exhibited chronic inflammation and only three cases showed slight deposition of cementum over the restorative material.
MTA has also been used as a pulp-capping material for mechanically exposed pulps (Pitt Ford et al. 1996), for root-end induction (Tittle et al.1996, Witherspoon & Ham 2001), repair of root perforation (Lee et al. 1993, Pitt Ford et al. 1995c), and as a barrier during internal bleaching of endodontically treated teeth (Cummings & Torabinejad1995).
Alhadainy HA, Himel VT (1993) Evaluation of the sealing ability of amalgam, Cavit and glass ionomer cement in the repair of furcation perforation. Oral Surgery, Oral Medicine and Oral Pathology 75,362-6.
Al-Khatib ZZ, Baum RH, Morse DR, Yesilsoy C, Bhambhani S, Furst ML (1990) The antimicrobial effect of various endodontic sealers. Oral Surgery, Oral Medicine and Oral Pathology 70,784-90.
ArakiK, IsakaH, IshiiT, SudaH(1993b) Excretionof14C-formaldehyde distributed systemically through root canal following pulpectomy. Endodontics and Dental Traumatology 9,196-9.
Araki K, Suda H, Barbosa SV, Spngberg LS (1993a) Reduced cytotoxicity of a root canal sealer through eugenol substitution. Journal of Endodontics 19,554-7.
Araki K, Suda H, Spngberg LS (1994) Indirect longitudinal cytotoxicity of root canal sealers on L929 cells and human periodontal ligament fibroblasts. Journal of Endodontics 20, 67-70.
Azar NG, Heidari M, Bahrami ZS, Shokri F (2000) In vitro cytotoxicity of a new epoxy resin root canal sealer. Journal of Endodontics 26, 462-5.
Barbosa SV, Burkard DH, Spngberg LSW (1994) Cytotoxic effects of gutta-perch solvents. Journal of Endodontics 20, 6-8.
Becker RM, Hume WR, Wolinsky LE (1983) Release of eugenol from mixtures of ZnOE in vitro. Journal of Pedodontics 8,71-7.
Beck-Mannagetta J,Necek D (1986) Radiologic findings in aspergillosis of the maxillary sinus. Oral SurgeryOralMedicineOral Pathology 62,345-9.
Beck-Mannagetta J, Necek D, Grasserbauer M (1986) Dental aspects of solitary maxillary sinus aspergillosis. A clinical, microanalytical and experimental study. Zeitschrift fur Stomatologie. 83, 283-315.
Beltes P, Koulaouzidou E, KotoualaV, Kortsaris AH (1995) In vitro evaluation of the cytotoxicity of calcium hydroxide-based root canal sealers. Endodontics and Dental Traumatology 11, 245-9.
Bergdahl M, Wennberg A, Spngberg L (1974) Biologic effect of polyisobutylene on bony tissue in guinea pigs. Scandinavian Journal of Dental Research 82,618-21.
Bezerra Silva LA, Leonardo MR, Faccioloi LH, Figueiredo F (1997) Inflammatory responses to calcium hydroxide-based root canal sealers. Journal of Endodontics 23, 86-90.
Block RM, Bushell A (1982) Retrograde amalgam procedures for mandibular posterior teeth. Journal of Endodontics 8,107-12.
Block RM, Lewis RD, Hirsch J, Coffey J, Langeland K (1980) Systemic distribution of N2 paste containing 14C paraformaldehyde following root canal therapy in dogs. Oral Surgery, Oral Medicine and Oral Pathology 50,350-60.
Boiesen J, Brodin P (1991) Neurotoxic effect of two root canal sealers with calcium hydroxide on rat phrenic nerve in vitro. Endodontics and Dental Traumatology 7, 242-5.
Brodin P, Prstavik D (1983) Effects of therapeutic and pulp protecting materials in nerve transmisiion in vitro. Scandinavian Journal of Dental Research 91, 46-50.
Brown BD, Kafrawy AH, Patterson SS (1979) Studies of Sargenti technique of endodontics - autoradiographic and scanning electron microscope studies. Journal of Endodontics 5,13-9.
CallahanJR (1914) Rosin solution for the sealing of the dentinal tubuli and as an adjuvant in the filling of root canals. Journal of Allied Dental Society 9,53-63.
Callis PD, Santini A (1987) Tissue response to retrograde fillings in the ferret canine: a comparison of glass ionomer cement and gutta percha with sealer. Oral Surgery, Oral Medicine and Oral Pathology 64,475-9.
Chong BS, Owadally ID, Pitt Ford TR, Wilson RF (1994)Antibacterial activity of potential retrograde root filling materials. Endodontics and Dental Traumatology 10,66-70.
Chong BS, Pitt Ford TR, Kariyawasam SP (1997) Tissue resonse to potential root-end-fillingmaterials in infected root canals. International Endodontic Journal 30,102-14.
Chong BS, Pitt Ford TR, Watson TF (1991) The adaptation and sealing ability of light-cured glass ionomer retrograde fillings. International Endodontic Journal 24, 223-32.
Cohen BI, Pagnillo MK, Musikant BL,DentschAS (1998)Evaluationof the release of formaldehyde for three endodontic filling materials. Oral Health 88,37-9.
Cohen BI, Pagnillo MK, Musikant BL, Deutsch AS (2000) An in vitro study of the cytotoxicity of two root canal sealers. Journal of Endodontics 26, 228-9.
Cummings GR, Torabinejad M (1995) Mineral trioxide aggregate (MTA) as an isolating barrier for internal bleaching [Abstract #53]. Journal of Endodontics 21, 228.
Dawood AJ, Pitt Ford TR (1989) Surgical approach to the obturation of apically flared root canals with thermoplasticized gutta-percha. International Endodontic Journal 22,138-41.
DeSchepper EJ, White RR, Von der Lehr W (1989) Antibacterial effects of glass ionomers. American Journal of Dentistry 2, 50-6. Dewhirst FE (1980) Structure-activity relationships for inhibition of prostaglandin cyclooxy-oxygenase by phenolic compounds. Prostaglandins 20, 209-22.
Donelly JC(1993) Usinga1-ml syringe for the chloroformdiproot canal filling technique. Journal of Endodontics19, 478.
Dorland's Illustrated Medical Dictionary (1981), 26th edn. Piladelphia, USA:W.B. Saunders Company, p.355.
Dorn SO, Gartner AH (1990) Retrograde filling materials: a retrospective success-failure study of amalgam, EBA, and IRM. Journal of Endodontics16,391-3.
Economides N, Kotsaki-Kovatsi VP, Poulopoulus A, Kolokuris I, RozosG, ShoreR(1995) Experimental study of the biocompatibility of four root canal sealers and their influence on the zinc and calcium content of several tissues. Journal of Endodontics 21,122-7.
Eley BM, Cox SW (1993) The release, absorption and possible health effects of mercury from dental amalgam: a review of recent findings. British Dental Journal 175,355-62.
England MC, West NM, Safavi K, Green DB (1980) Tissue lead levels in dogs with RC-2B root canal fillings. Journal of Endodontics 6, 728-30.
Engstrom B, Spngberg L (1969) Effect of root canal filling material N2 when used for filling after partial pulpectomy. Svensk Tandlakare Tidskrift 62,815-29.
Ersev H, Schmalz G, Bayirli G, Schweikl H (1999) Cytotoxic and mutagenic potencies of various root-canal-filling materials in eukaryotic and prokaryotic cells in vitro. Journal ofEndodontics 25,359-63.
Fehr B, Huwyler T,Wuthrich B (1992) Formaldehyd-a nd paraformaldehyd allergie. Schweizerische Monatschrift fur Zahnmedizin102,94- 6.
Feiglin B (1987) Effect of some endodontic sealers on cell migration in experimental granulomas. Oral Surgery ,Oral Medicine and Oral Pathology 63,371-4.
FerracaneJL (1995) Current trends in dental composites. Critical Reviews in Oral Biology and Medicine 6,302-18.
Forman GH, Ord RA(1986)Allergic endodontic angiooedema in response to periapical Endomethasone. British Dental Journal 160,348-50.
Friedman S (1991) Retrograde approaches in endodontic therapy. Endodontics and Dental Traumatology 7,97-107. Garcia GF (1937) Apicectomia experimental. Revista Odontologica 2,145-60.
Geurtsen W (2000) Biocompatibility of resin-modified filling materials. Critical Reviews of Oral Biology and Medicine 11, 333-55.
GeurtsenW, Leinenbach F, Krage T, Leyhausen G (1998) Cytotoxicity of four root canal sealers in permanent 3T3 cells and primary human periodontal ligament fibroblast cultures. Orals Surgery, Oral Medicine, Oral Pathology, Oral Radiology and Endodontics 85,592-7.
Goldmacher VS, Thilly WG (1983) Formaldehyde is mutagenic for cultured human cells. Mutation Research116, 417-22.
Grossman LI (1978) Solubility of root canal cements. Journal of Dental Research 57,927.
Guigand M, Pellen-Mussi P, Le Goff A,Vulcain J-M, Bonnaure- Mallet M (1999) Evaluation of the cytocompatibility of three endodontic materials. Journal of Endodontics 25, 419-23.
Gulati N, Chandra S, Aggarwal PK, Jaiswal JN, Singh M (1991) Cytotoxicity of eugenol in sealer containing zinc oxide. Endodontics and Dental Traumatology 7,181-5.
Gutmann JL, Harrison JW(1985) Posterior endodontic surgery: anatomical considerations and clinical techniques. International Endodontic Journal18,8-34.
Gutmann JL, Rakusin H, Powe R, Bowles WH (1987) Evaluation of heat transfer during root canal obturation with thermoplasticized gutta-percha. Part II. In vivo response toheat levels generated. Journal of Endodontics13, 441-8.
Hansel C, Leyhausen G, Mai UEH, GeurtsenW (1998) Effects of various resin composite (Co) monomers and extracts on two caries-associated micro-organisms in vitro. Journal of Dental Research 77,60-7.
Hansen MG (1998) Relative efficiency of solvents used in endodontics. Journal of Endodontics 24,38-40.
Heil J, Reifferscheid G,Waldmann P, Leyhausen G, GeurtsenW (1996) Genotoxicity of dental materials. Mutation Research 368,181-94.
Heling I, Chandler NP (1996) The antimicrobial effect within dentinal tubules of four root canal sealers. Journal ofEndodontics 22, 257-9.
Holland R, Filho JA, de SouzaV, NeryMJ, Bernabe PF, Dezan E Jr (2001) Mineral trioxide aggregate repair of lateral root perforations. Journal of Endodontics 27, 281-4.
Holland R, Desouza V, Nery MJ, De Mello W, Bernabe. PFE, Otoboni Filho JA (1982) Reaction of rat connective tissue to gutta-percha and silver points. A long-term histological study. Australian Dental Journal 27, 224-6.
Holland R, Murata SS, Dezan E, Garlipp O (1996) Apical leakage after root canal filling with an experimental calcium hydroxide gutta-percha point. Journal of Endodontics 22,71-3.
Hong YC, Wang JT, Hong CY, Brown WE, Chow LC (1991) The periapical tissue reactions to a calcium phosphate cement in teeth of monkeys. Journal of Biomedical and Material Research 25, 485-98.
Huang FM, Tai K-W, Chou M-Y, Chang Y-C (2002) Cytotoxicity of resin-, zinc oxide-eugenol-, and calcium hydroxide-based root canal sealers on human periodontal ligament cells and permanent V79 cells. International Endodontic Journal 35, 153-8.
HumeWR (1984) An analysis of the release and the diffusion through dentin of eugenol from zinc oxide-eugenol mixtures. Journal of Dental Research 63,881-4.
Hume WR (1988) In vitro studies on the local pharmacodynamics, pharmacology and toxicology of eugenol and zinc oxide-eugenol. International Endodontic Journal 21,130-4.
Jessle. n P, Zetterqvist L, Heimdahl A (1995) Long-term results of amalgam versus glass ionomer cement as apical sealant after apicectomy. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology and Endodontics 79,101-3.
Jukic S,Miletic I, Anic I, Britvic S, Osmak M, Sistig S (2000) The mutagenic potential of AHþand AH26 by Salmonella/microsome assay. Journal of Endodontics 26,321-4.
Karlsson J, Wendling W, Chen D, Zelinsky J, Jeevanandam V, Hellman S, et al. (1995) Methylmethacrylate monomer produces direct relaxation of vascular smooth muscle in vitro. Acta Anaesthesiologica Scandinavica 39,685-9.
Klaiber B, Mittermayer C, Kaden P, Schwechten I (1981)Determination of the toxicity of root-canal-filling materials and their separate components in cell cultures. Deutsche Zahnarztliche Zeitschrift 36, 212-6.
Kobayashi A (1995) A symptomatic aspergillosis of the maxillary sinus associated with foreign body of endodontic origin. Journal of Oral and Maxillofacial Surgery 24, 243-4.
Koch MJ (1999) Formaldehyde release from root-canal sealers: influence of method. International Endodontic Journal 32, 10-6. Koch MJ, Staehle HJ (1997) Formaldehyde release from dental materials. Deutsche Zahnarztliche Zeitskrift 52, 778-82.
Kolokuris I, Beltes P, Economides N, Vlemmas I (1996) Experimental study of the biocompatibility of a new glass ionomer root canal sealer (Ketac-Endo). Journal of Endodontics 22, 395-8.
Kolokuris I, Economides N, Beltes P, Vlemmas I (1998a) In vivo comparison of the biocompatibility of two root canal sealers implanted into the subcutaneous connective tissue of rats. Journal of Endodontics 24,82-5.
Kolokuris I, Katsaki-Kovatsi VP, Economides N, Pouloloulos A, Razos G, Vlemmas I (1998b) Influence of zinc oxide and eugenol sealer on concentration of zinc, calciumand copper in rat tissues. Endodontics and Dental Traumatology 14, 210-3.
Koulaouzidou EA, Papazisis KY, Geromichalas GD (1998) Cytotoxicity of three resin-based root canal sealers implanted into the subcutaneous connective tissue of rats. Endodontics and DentalTraumatology14,182-5.
Lee SJ, Monsef M, Torabinejad M (1993) Sealing ability of a mineral trioxide aggregate for repair of lateral root perforations. Journal of Endodontics19,541-4.
Leonardo MR, da Silva LAB, Filho MT, da Silva RS (1999a) Release of formaldehyde by 4 endodontic sealers. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology and Endodontics 88, 221-5.
Leonardo MR, da Silva LA, Almeida WA, Utrilla LS (1999b) Tissue response to an epoxy resin-based root canal sealer. Endodontics and Dental Traumatology 15, 28-32.
Leonardo MR, da Silva LA, Tanomaru Filho M, Bonifacio KC, Ito IY (2000) In vitro evaluation of antimicrobial activity of sealers and pastes used in endodontics. Journal of Endodontics 26,391-4.
LeonardoMR, Silva LA, Utrilla LS, Assed S, Ether SS (1997) Calcium hydroxide root canal sealers - histopathologic evaluation of apical and periapical repair after endodontic treatment. Journal of Endodontics 23, 428-32.
Lewis BB, Chestner SB (1981) Formaldehyde in dentistry: a review of mutagenic and carcinogenic potential. Journal of the American Dental Association103, 429-34.
Leyhausen G, Heil J, Reifferscheid G, Waldmann Geurtsen W (1999) Genotoxicity and cytotoxicity of the epoxy resin-based root canal sealer AH Plus. Journal of Endodontics 25,109-13.
Makkawy HA, Koka S, Lavin MT, Ewoldsen NO (1998) Cytotoxicity of root perforation repair materials. Journal of Endodontics 24, 477-9.
Martin H, Martin T (1999) Iodoform gutta percha: MGP, a new endodontic paradigm. DentistryToday18 (4). Meryon SD, Brook AM (1990) In vitro comparison of the cytotoxicity of twelve endodontic materials using a new technique. International Endodontic Journal 23, 203-10.
Mickel AK, Wright ER (1999) Growth inhibition of Streptococcus anginosus (milleri) by three calcium hydroxide sealers and one zinc oxide-eugenol sealer. Journal of Endodontics 25, 34-7.
Munaco FS, Miller WA, Everett MM (1978) A study of long-term toxicity of endodontic materials with use of an in vitro model. Journal of Endodontics 4,151-7.
Nencka D, Walia HD, Austin BP (1995) Histologic evaluation of the biocompatibility of Diaket [Abstract#716]. Journal of Dental Research 74,101.
Nicholls E (1965) The role of surgery in endodontics. British Dental Journal 59-67.
O'Connor RP, Hutter JW, Roahen JO (1995) Leakage of amalgam and Super-EBA root-end fillings using two preparation techniques and surgical microscopy. Journal of Endodontics 21, 74-8.
Odell E, PertlCH(1995) Zinc as a growth factor for Aspergillus sp. & the antifungal effects of root canal sealers. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology and Endodontics 79,82-7.
Olsson B, Siwkowski A, Langeland K (1981a) Subcutaneous implantation inthe biological evaluation of endodonticmaterial. Journal of Endodontics 7,355-8.
Olsson B, Siwkowski A, Langeland K (1981b) Intraosseus implantation for biological evaluation of endodontic materials. Journal of Endodontics 7, 253-65.
Olsson B, WennbergA (1985) Early tissue reaction to endodontic filling materials. Endodontics and Dental Traumatology 1, 138-41.
Prstavik D, Mjor IA (1988) Histopathology and X-ray microanalysis of the subcutaneous tissue response to endodontic sealers. Journal of Endodontics14,13-23.
Osorio RM, HeftiA, Vertucci FJ, Shawley AL(1998) Cytotoxicity of endodontic materials. Journal of Endodontics 24,91-6.
Owadally ID, Pitt Ford TR (1994) Effect of addition of hydroxyapatite on the physical properties of IRM. International Endodontic Journal 27, 227-32.
Pysæd H, Ruyter IE, Kleven S (1988) Release of formaldehyde from dental composites. Journal of Dental Research 67, 1289-94.
PantschevA, Carlsson AP, Andersson L (1994) Retrograde root filling with EBA cement or amalgam. A comparative clinical study. Oral Surgery, Oral Medicine and Oral Pathology 78, 101-4.
Pascon EA, Leonardo MR, Safavi K, Langeland K (1991) Tissue reaction to endodontic materials: methods, criteria, assessment, and observations. Oral Surgery, Oral Medicine and Oral Pathology 72, 222-37.
Pascon EA, Spngberg LS (1990) In vitro cytotoxicity of rootcanal-fi lling materials. Part 1. Gutta-percha. Journal of Endodontics 16, 429-33.
PeltolaM, SaloT, Oikarinen K (1992) Toxic effects of various retrograde root filling materials on gingival fibroblasts and rat sarcoma cells. Endodontics and Dental Traumatology 8, 120-4.
PertotWJ, Camps J, RemusatM, Proust JP (1992) In vivo comparison of the biocompatibility of two root canal sealers implanted into the mandibular bone of rabbits. Oral Surgery, Oral Medicine and Oral Pathology 73,613-20.
Phillips H, Cole PV, Lettin AW (1971) Cardiovascular effects of implanted acrylic bone cement. British Medical Journal 3 (772), 460-1.
Pissiotis E, Sapounas G, Spngberg LS (1991) Silver glass ionomer cement as a retrograde filling material: a study in vitro. Journal of Endodontics 17, 225-9.
Pitt Ford TR, Andreasen JO, Dorn SO, Kariyawasam SP (1994) Effect of IRM root end fillings on healing after replantation. Journal of Endodontics 20,381-5.
Pitt Ford TR, Andreasen JO, Dorn SO, Kariyawasam SP (1995a) Effect of various zinc oxide materials as root-end fillings on healing after replantation. International Endodontic Journal 28, 273-8.
Pitt Ford TR, Andreasen JO, Dorn SO, Kariyawasam SP (1995b) Effect of super-EBA as a root end filling on healing after replantation. Journal of Endodontics 21,13-5.
Pitt FordTR, Roberts GJ (1990) Tissue response to glass ionomer retrograde root fillings. International Endodontic Journal 23, 233-8.
Pitt Ford TR,Torabinejad M, Abedi HR, Bakland LK, Kariyawasam SP (1996) Mineral trioxide aggregate as a pulp capping material. Journal of the American Dental Association 127, 491-4.
Pitt Ford TR, Torabinejad M, Hong CU, Kariyawasam SP (1995c) Use of mineral trioxide aggregate for repair of furcal perforations. Oral Surgery, Oral Medicine and Oral Pathology 79, 756-63.
Podbielski A, Boeckh C, Haller B (2000) Growth inhibitory activity of gutta-percha points containing root canal medications on common endodontic bacterial pathogens as determined byanoptimized quantitative in vitro assay. Journal of Endodontics 26, 398-403.
Reit C,HirschJ (1986) Surgical endodontic retreatment. International EndodonticJournal19,107-12.
Rud J, Andreasen JO, Moller Jensen JE (1972) A follow-up study of 1000 cases treated by endodontic surgery. International Journal of Oral Surg ery1, 215-28.
Rud J, Munksgaard EC, Andreasen JO, RudV, Asmussen E (1991) Retrograde root filling with composite and a dentin-bonding agent. Part1. Endodontics and Dental Traumatology 7,118-25.
Rud J, Rud V, Munksgaard EC (1996a)Retrograde root filling with composite and a dentin-bonding agent. Part 2. Endodontics and Dental Traumatology 7,126-31.
Rud J, Rud V, Munksgaard EC (1996b) Long-term evaluation of retrograde root filling with dentin-bonding agent. Endodontics and DentalTraumatology 22,90-3.
Rud J, RudV, Munksgaard EC (2001) Periapical healing of mandibular molars after root-end sealing with dentine-bonded composite. International Endodontic Journal 34, 285-92.
Saunders EM (1990) In vivo findings associated with heat generation during thermomechanical compaction of guttapercha. Part I. Temperature levels at the external surface of the root. International EndodonticJournal 23, 268-74.
Schmitt W (1951) Die chemischengrundlagennder erhartenden wurzelfullungen. ZahnarztlicheWelt 5,560.
Schwartz RS, Mauger M, Clement DJ, Walker WA (1999)Mineral trioxide aggregate: a new material for endodontics. Journal of the American Dental Association 130,967-75.
Schweikl H, Schmalz G (1991) Evaluation of the mutagenic potential of root canal sealers using the Salmonella/microsome assay. Journal of Material Science: Materials in Medicine 2,181-5.
Schweikl H, Schmalz G, Federlin M (1998) Mutagenicity of the root canal sealer AHplus in the Ames test. Clinical Oral Investigations 2,125-9.
Schweikl H, Schmalz G, StimmelmayrH, Bey B (1995) Mutagenicity of AH26 in an in vitro mammalian cell mutation assay. Journal of Endodontics 21, 407-10.
Segura JJ, Jmenez-Rubio A (1998) Effect of eugenol on macrophage adhesion in vitro to plastic surfaces. Endodontics and DentalTraumatology14,72-4.
Serene TP,Vesely J, Boackle RJ (1988) Complement activation as a possible in vitro indication of the inflammatory potential of endodontic materials. Oral Surgery, Oral Medicine and Oral Pathology 65,354-7.
Silver GK, Love RM, Purton DG (1999) Comparison of two root canal obturation techniques: vertical condensation and System B. International Endodontic Journal 32, 287-95.
Silver GK,Taylor TL, Simon JHS (2000) Antimicrobial effect of iodoform gutta-percha cones on Streptococcus sanguis and Enterococcus faecalis. New Zealand Endodontic Journal 26,1-3.
Singh AR, LawrenceWH, Autian J (1972) Embryonic-fetal toxicity and teratogenic effects of a group of methacrylate esters in rats. Journal of Dental Research 51,1632-8.
Sjogren U, Sundqvist G, Nair PNR (1995) Tissue reaction to gutta-percha particles of various sizes when implanted subcutaneously in guinea pigs. European Journal of Science 103, 313-21.
Soares I, Goldberg F, Massone EJ, Soares IM(1990) Periapical tissue response to two calciumhydroxide-containing endodontic sealers. Journal of Endodontics16,166-9.
Soderberg TA (1990) Effects of zinc oxide, rosin and resin acids and their combinations on bacterial growth and inflammatory cells. Scandinavian Journal of Plastic Reconstructive Surgery and Hand Surgery 24 (S22), 1-87.
Sonat B, Dalat D, Gunhan O (1990) Periapical tissue reaction to root fillings with Sealapex. International Endodontic Journal 23, 46-52.
SpahlW, Budzikiewicz H, GeurtsenW (1998) Determination of leachable components from four commercial dental composites by gas and liquid chromatography/mass spectrometry. Journal of Dentistry 26,137-45.
Spngberg L (1969a) Biological effects of root-canal-filling materials. Part 7. Reaction of bony tissue to implanted rootcanal-filling material in guinea pigs. Odontologisk Tidskrift 77,133-59.
Spngberg L (1969b) Biological effects of root-canal-filling materials. Part 2. Effect in vitro of water-soluble components of root-canal-filling materials on HeLa cells. Odontologisk Revy 20,133-45.
Spngberg L (1969c) Biological effects of root-canal-filling materials. Part 5. Toxic effect of root-canal-filling materials on HeLa cells and human skin fibroblasts. Odontologisk Revy 20, 427-36.
Spngberg L (1969d)Biological effects of root-canal-filling materials. Part 4. Effect in vitro of water-soluble components of root-canal-filling materials on HeLa cells. Odontologisk Revy 20, 289-99.
Spngberg L (1974) Biologic effects of root-canal-filling materials. The effect on bone tissue of two formaldehyde-containing root canal filling pastes: N2 and Riebler's paste. Oral Surgery, Oral Medicine and Oral Pathology 38, 934-44.
Spngberg L (1999) Endodontic treatment of teeth without apical periodontitis. In: Prstavik, D, Pitt Ford, TR, eds. Essential Endodontology, 2nd edn. Cambridge, UK: Blackwell Science, p. 228.
Spngberg LSW, Barbosa SV, Lavigne GD (1993) AH26 releases formaldehyde. Journal of Endodontics 19,596-8.
Spngberg L, Langeland K (1973) Biologic effects of dental materials. 1. Toxicity of root-canal-filling materials on HeLa cells in vitro. Oral Surgery, Oral Medicine and Oral Patholoy 35, 402-14.
Staehle HJ, Spiess V, Heinecke A, Muller HP (1995) Effect of rootcanal-filling materials containing calcium hydroxide on the alkalinity of root dentin. Endodontics and Dental Traumatology 11,163-8.
Stea S, Savarino L, Ciabetti G, Cenni E, Stea StTrotta F, Morozzi G, Pizzoferrato A (1994) Mutagenic potential of root canal sealers: evaluation through Ames testing. Journal of Biomedical and Material Research 28, 319-28.
Sultan M, Pitt Ford TR (1995) Ultrasonic preparation and obturation of root-end cavities. International Endodontic Journal 28, 231-8.
Sunzel B, Lazek J, Soderberg TA, ElmrosT, Hallmans G, HolmSE (1990) The effect of zinc oxide on Staphylococcus aureus and polymorphonuclear cells in a tissue cage model. Scandinavian Journal of Plastic and Reconstructive Hand Surgery 24,31-5.
Sunzel B, Soderberg TA, Johansson A, Hallmans G, Gref R (1997) The protective effect of zinc on rosin and resin acid toxicity in human polymorphonuclear leukocytes and human gingival fibroblasts in vitro. Journal of Biomedical Material Research 37, 20-8.
Sweatman TL, Baumgartner JC, Sakaguchi RL (2001) Radicular temperature associated with thermoplasticized guttapercha. Journal of Endodontics 27,512-5.
Swenberg JA, Kerns WD, Mitchell RE, Gralla EJ, Parkow KL (1980) Induction of squamous cell carcinomas of the rat nasal cavity by inhalation exposure to formaldehyde vapors. Cancer Research 40,3398-402.
Tagger M, Tagger E, Kfir A (1988) Release of calcium and hydroxyl ions from set endodontic sealers containing calcium hydroxide. Journal of Endodontics14,588-91.
Telli C, Serper A, Dogan AL, Guc D (1999) Evaluation of the cytotoxicity of calcium phosphate root canal sealers by MTT assay. Journal of Endodontics 25,811-3.
Tetsch P (1986) Wurzelspitzenresektionen, Munich, Hanser. pp. 96-99.
Tittle KW, Farley J, Linkhardt T, Torabinejad M (1996) Apical closure induction using bone growth factors and mineral trioxide aggregate [Abstract#41]. Journal of Endodontics 22,198.
Torabinejad M, Falah Rastegar A, Kettering JD, Pitt Ford TR (1995b) Bacterial leakage of mineral trioxide aggregate as a root-end-filling material. Journal of Endodontics 21,109-12.
Torabinejad M, Higa RK, McKendry DJ, Pitt Ford TR (1994) Dye leakage of four root-end-filling materials: effects of blood contamination. Journal of Endodontics 20,159-63.
Torabinejad M, Hong C-U, Lee S-J, Monsef M, Pitt FordTR (1995a) Investigation of mineral trioxide aggregate for root-end filling in dogs. Journal of Endodontics 21,603-8.
Torabinejad M, Hong CU, Pitt Ford TR, Kariyawasam SP (1995e) Tissue reaction to implanted Super-EBA and mineral trioxide aggregate in the mandible of guinea pigs: a preliminary report. Journal of Endodontics 21,569-71.
Torabinejad M, Hong CU, Pitt Ford TR, Kettering JD (1995c)Antibacterial effects of some root-end-filling materials. Journal of Endodontics 21,403-6.
Torabinejad M, Hong CU, Pitt Ford TR, Kettering JD (1995 d) Cytotoxicity of four root-end-filling materials. Journal of Endodontics 21, 489-92.
TorabinejadM, Pitt FordTR,McKendry DJ, Abedi HR,Miller DA, KariyawasamSP (1997) Histologic assessment of mineral trioxide aggregate as a root-end filling in monkeys. Journal of Endodontics 23, 225-8.
Tronstad L, Barnett F, Flax M (1988) Solubility and biocompatibility of calcium hydroxide-containing root canal sealers. Endodontics and Dental Traumatology 4,152-9.
UemuraM, HataG,TodaT,Weine FS (1997) Effectiveness of eucalyptol and d-limonene as gutta-percha solvents. Journal of Endodontics 23,739-41.
Updegraff DM, Chang RWH, Joos RW(1971) Antibacterial activity of dental restorative materials. Journal of Dental Research 50,382-7.
Vajrabhaya L, Sithisan P (1997) Multilayer and monolayer cell cultures in a cytotoxicity assay of root canal sealers. International Endodontic Journal 30,141-4.
Vajrabhaya L, Sithisan P,Wilairat P, Leelaphiwat S (1997) Comparison between Sulphorhodamine-B dye staining and 51Cr-release method in cytotoxicity assay of endodontic sealers. Journal of Endodontics 23, 355-7.
Von Hippel R (1914) Zur Technik der Granulomoperation. Deutsche Monatsschrifte Furzahnheilkunde 32, 255-65.
Walia HD, Newlin S, Austin BP (1995) Electrochemical analysis of retrofilling microleakage in extracted human teeth [Abstract#719]. Journal of Dental Research 74,101.
Weine FS, Gerstein H (1976) Periapical surgery. In: Endodontic Therapy, 2nd edn. St. Louis, USA: Mosby, 287-351.
Wennberg A, Bergdahl M, Spngberg L (1974) Biologic effect of polyisobutylene on HeLa cells and on subcutaneous tissue in guinea pigs. Scandinavian Journal of Dental Research 82, 613-7.
Williams SS, Gutmann JL (1996) Periradicular healing in response toDiaket root-end-filling material with and without tricalcium phosphate. International Endodontic Journal 29, 84-92.
Wilson AD, Batchelor RF (1970) Zinc oxide-eugenol cements. Part II. Study of erosion and disintegration. Journal of Dental Research 49,593-8.
Witherspoon DE, Ham K (2001) One-visit apexification: technique for inducing root-end barrier formation in apical closures. Practical Proceedings of Aesthetic Dentistry13, 455-60.
Wolfson EM, Seltzer S (1975) Reaction of rat connective tissue to some gutta-percha formulations. Journal of Endodontics 1, 395-402.
Yesilsoy C, Koren LZ, Morse DR, Kobayashi C (1988) A comparative tissue toxicity evaluation of established and newer root canal sealers. Oral Surgery, Oral Medicine and Oral Pathology 65, 459-67.
Zetterqvist L, Anneroth G, Danin J, Roding K (1988)Microleakage of retrograde fillings - a comparative investigation between amalgam and glass ionomer cement in vitro. International Endodontic Journal 21,1-8.
Zetterqvist L, Anneroth G, Nordenram A (1987) Glass-ionomer cement as retrograde filling material: an experimental investigation in monkeys. International Journal of Oral and Maxillofacial Surgery16, 459-64.
Zetterqvist L, Hall G, Holmlund A (1991) Apicectomy: a clinical comparison of amalgam and glass ionomer cement as apical sealants. Oral Surgery, Oral Medicine and Oral Pathology 71, 489-91.