Abstracted references demonstrating

the cytotoxic nature of Root Filling Cements.

Anything which is placed in a tooth
can be transported throughout the body!

As well as the abstracts below I strongly recommend visiting Sargenti Opposition Society  to understand the dangers of putting formaldehyde in teeth and thus your body.  http://www.sargentipaste.org/index.html
Note that although the material known as N2 is based on the use of para formaldehyde it is not the only material which presents formaldehyde to the body.  One of the most commonly used materials known as AH26 breaks down to various compounds including formaldehyde, Nitrogen Oxides  and Ammonia. The formaldehyde form this source is equally carcinogenic.

Takahara K Onodera A Matsumoto K Toxicity of root canal sealers on rat bone cells in primary culture. Endod Dent Traumatol (1990 Oct) 6(5):200-7

The cytotoxic effects on cultured rat bone cells of newly-developed root canal sealers and commercially available sealers were compared. Various root canal sealers were applied to cultured bone cells obtained from rat calvaria by the enzyme digestion method. Measurement of [3H]-thymidine incorporation, alkaline phosphatase activity, and calcium release were performed after 24 and 48 h. No significant difference was found in cellular DNA synthesis and alkaline phosphatase activity between cells exposed to New B-1, New B- 5 and controls after exposure for 24 and 48 h. Cells in contact with Tubliseal, Diaket and AH-26 demonstrated a significant difference from controls in DNA synthesis and alkaline phosphatase activity. Calcium release at 24 h was significantly different in the cells treated with New B-1 and New B-5 than in controls. No appreciable difference was found, however, between New B-6, Sealapex and controls. At 48 h, cells treated with New B-1, New B-5 and New B-6 showed differed significantly difference from controls, but the cells exposed to Sealapex did not. The newly-developed root canal sealers had lower toxicity in vitro than five types of commercially available root canal sealers.

Arenholt-Bindslev D Horsted-Bindslev P A simple model for evaluating relative toxicity of root filling materials in cultures of human oral fibroblasts. Endod Dent Traumatol (1989 Oct) 5(5):219-26

Standardized test tubes filled with freshly mixed root filling materials (AH26, CRCS, N2, Kloroperka NO, ZOE cement and 2 experimental cements, ECI and ECII) were transferred into tissue culture flasks. Normal human oral fibroblasts were seeded in the flasks. Morphological cell changes were studied up to 15 days after seeding. The size of cell-free zones around the test tubes and the total cell number per culture flask were calculated after 5, 10 and 15 days. The findings showed N2 cement to be by far the most toxic material at all observation periods, whereas no toxic reactions could be seen in relation to tubes filled with Kloroperka NO. Compared with the 5-day observation period, some cell recovery was observed around test tubes with AH26 and ECII, whereas almost full cell recovery was found around test tubes with CRCS, ZOE and ECI. It was concluded that the present model, which allows long-term observations of human cellular reactions to dental materials, can be used as a simple and relatively cheap screening test for initial toxicity testing of dental materials.

Pissiotis E Spangberg LS Toxicity of Pulpispad using four different cell types. Int Endod J (1991 Sep) 24(5):249-57

The cytotoxic effect of a zinc oxide-eugenol-based paste (Pulpispad) was evaluated in vitro after setting for 1 day and 1 week. Target cells were L929 cells, gingival, periodontal ligament and pulpal fibroblasts. The material was incubated with the cells for 4 and 24 hours, and its toxicity was evaluated with the 51Cr-release method. Pulpispad was highly cytotoxic to all cell lines even after setting for 1 week. The use of Pulpispad is not recommended for future clinical application. The various responses among the four cell lines indicated that diploid cell lines can, under certain circumstances, be less sensitive than aneuploid cell lines. It is therefore suggested that in the evaluation of biomaterials the choice of cell lines should be carefully considered, as they can display varying sensitivities.

Lewis BB Chestner SB Formaldehyde In Dentistry: A Review Of Mutagenic And Carcinogenic Potential J Am Dent Assoc (1981) 103(3):429-434 A review of the carcinogenic and mutagenic potential of formaldehyde products used in dentistry is presented.

Dentists performing endodontic therapy may use formocresol and formaldehyde paste. Tissue contact results either directly or by contact with the gaseous formaldehyde phase. While various short-term tests have indicated the mutagenicity of formaldehyde, they are not conclusive for the mammalian species. Clinical studies involving chronic topical application of formalin have demonstrated the induction of leukoplakia and lesions resembling carcinoma in situ. The respiratory tract may be the area for the greatest risk of the development of tumors. Animal studies demonstrate that formaldehyde may affect reproduction potential. Formaldehyde should be considered a potential carcinogen in humans. Formaldehyde poses problems to systemic health via ingestion routes, interaction in air with other aldehydes, and in final breakdown products of formalin in the body. If formaldehyde is clearly not necessary, why is it used at all, particularly in light of its deleterious effects.

Stea S Savarino L Ciapetti G Cenni E Stea S Trotta F Morozzi G Pizzoferrato A Mutagenic potential of root canal sealers: evaluation through Ames testing. J Biomed Mater Res (1994 Mar) 28(3):319-28

The mutagenic potential of 12 commercially available dental cements and of two 'pure substances' (zinc oxide and eugenol) used in root canal filling were examined. The cements were prepared according to the manufacturers' indications and set for defined times. Ames tests were performed in their extracts by using Salmonella typhimurium strains TA 98 and TA 100. The results showed that most cements present strong bactericidal activity that disappears or decreases remarkably in time. One of the tested cements showed mutagenicity with both Salmonella strains. Two cements yielded doubtful results. The remaining cements and the two 'pure substances' showed no mutagenic potential. The authors conclude that it is convenient to examine endodontic cements with the Ames test and to eliminate those that present mutagenicity in time.

Al-Nazhan S Spangberg L Morphological cell changes due to chemical toxicity of a dental material: an electron microscopic study on human periodontal ligament fibroblasts and L929 cells. J Endod (1990 Mar) 16(3):129-34

New endodontic materials with polymer bases may be more difficult to evaluate in cell cultures in vitro than conventional zinc oxide-eugenol cements. In order to study the morphological changes taking place in cells exposed to such materials, L929 cells and human periodontal fibroblasts were observed using scanning electron microscopic and transmission electron microscopic techniques. The morphological changes of the cells were correlated to the quantitative results observed simultaneously in cytotoxicity studies using the radiochromium release method. Results showed there was a relationship between the chromium release and the degree of individual cell damage. The periodontal ligament fibroblasts were more resistant to this kind of chemical injury than the L929 cells. Consequently, it may be proper to use periodontally derived cells for the study of cytotoxic mechanisms of polymer endodontic filling materials. Safavi KE Spangberg LS Costa NS Jr Sapounas G An in vitro method for longitudinal evaluation of toxicity of endodontic sealers. J Endod (1989 Oct) 15(10):484-6 An in vitro method for longitudinal evaluation of root canal sealers was developed and applied. A newly introduced cell culture chamber was used to evaluate the cytotoxic effects of test samples immediately after mixing and for an extended period of time thereafter. A ranking of the test materials, based on their cytotoxicity, was allowed by the method.

Chutich MJ Kaminski EJ Miller DA Lautenschlager EP Risk assessment of the toxicity of solvents of gutta-percha used in endodontic retreatment. J Endod (1998 Apr) 24(4):213-6

Three randomly assigned groups of single-canaled extracted teeth obturated with gutta-percha were retreated using controlled application of one of three organic solvents: chloroform, xylene, or halothane. Two additional groups of teeth served as positive and negative controls. Residual volume of solvent expressed through the apical foramen during retreatment was determined by the difference of pretreatment and posttreatment weights of hermetically sealed receptacles attached to the root surface of the teeth. Results indicate that the amount of solvent that has been determined to have leached out through the apical foramen is several orders of magnitude below the permissible toxic dose. Thus, it is proposed that the use of any of the aforementioned solvents used in the retreatment of root canals would pose negligible risk to the patient.

Mittal M Chandra S Chandra S Comparative tissue toxicity evaluation of four endodontic sealers. Endod (1995 Dec) 21(12):622-4

The tissue toxicity of zinc oxide-eugenol, Tubli seal, Sealapex, and Endoflas F.S. was investigated by injecting them into the subcutaneous connective tissue of the dorsal surface of rats and studying the tissue response histologically. Animals were killed after time intervals of 48 h, 7 days, 14 days, 1 month, and 3 months; tissue sections were taken from the injection sites. Histological examination of the tissue sections revealed that all of the sealers caused some inflammation that decreased with time, except in the case of zinc oxide-eugenol where it increased from the 48th hour to the 7th day and after that showed a decreasing trend. Overall, Sealapex showed the least inflammatory reaction compared with other sealers used, because it showed moderate inflammation at 48 h that became mild in later periods. Zinc oxide-eugenol, Tubli seal, and Endoflas F.S. were severely toxic at 48 h and 7 days. This toxicity decreased gradually in later time periods. No inflammatory reaction was seen at 3 months with any of the sealers used.

Barbosa SV Burkard DH Spangberg LS Cytotoxic effects of gutta-percha solvents. Endod (1994 Jan) 20(1):6-8

Cytotoxicity of commonly used gutta-percha solvents was evaluated. Gutta-percha dissolved by chloroform, halothane, or turpentine was evaluated with the radiochromium release method using L929 mouse fibroblast cells. All solvents were toxic. Turpentine was most toxic followed by halothane and chloroform, which caused similar levels of cell injury.

Helseth DL Jr Tolwin TM Kaminski EJ Osetek EM Incomplete polymerization of Cavalite with the use of recommended photopolymerization times: a warning of possible cytotoxic effects.Oral Surg Oral Med Oral Pathol (1989 Aug) 68(2):223-5

As part of a study of the suitability of new materials for use as a retrofilling material, we examined the polymerization properties of Cavalite, a light-cured, hydroxyapatite and glass ionomer-containing cavity liner. By varying the time of photopolymerization, it was found that polymerization for 20 to 30 seconds according to the manufacturer's recommendations is not sufficient to ensure complete polymerization. The implications of this incomplete polymerization are discussed in terms of possible cytotoxic effects on tissues exposed to unpolymerized Cavalite, both when used in retrofilling situations and as a deep cavity liner.

Yesilsoy C Koren LZ Morse DR Kobayashi C A comparative tissue toxicity evaluation of established and newer root canal sealers.Oral Surg Oral Med Oral Pathol (1988 Apr) 65(4):459-67

Grossman's sealer, eucapercha, Endo-Fill, CRCS, Sealapex, Hypocal, and sterile saline solution (0.3 ml of each) were injected into specific dorsal subdermal tissue sites of 12 guinea pigs. The animals were killed after 6 days, 15 days, and 80 days (four per time period). Analysis of tissue response showed that, overall, Sealapex and Endo-Fill had less severe inflammatory reactions than any of the other test materials. Grossman's sealer, CRCS, and Hypocal showed principally severe inflammatory responses at both 6 and 15 days, but mild reactions at 80 days. Overall, eucapercha showed less severe inflammatory responses than Grossman's sealer, CRCS, and Hypocal. Diffuse calcification was induced by the three calcium hydroxide preparations (CRCS, Sealapex, and Hypocal). Eucapercha and Endo-Fill had minute local areas of calcification. Both Grossman's sealer and CRCS did not have overall favorable histologic reactions; however, Grossman's sealer and CRCS have been used successfully clinically. Further clinical studies are needed.

Wright KJ Barbosa SV Araki K Spangberg LS In vitro antimicrobial and cytotoxic effects of Kri 1 paste and zinc oxide-eugenol used in primary tooth pulpectomies. Pediatr Dent (1994 Mar-Apr) 16(2):102-6

The antimicrobial and cytotoxic effects of Kri 1 paste, an iodoform- based primary tooth filling material, were compared with zinc oxide- eugenol (ZOE), using in vitro techniques. Antimicrobial evaluation involved measuring inhibition zones of Streptococcus faecalis on brain heart agar. Cytotoxicity evaluation involved direct cell- medicament contact experiments of 4-hr and 24-hr duration using fresh and set medicaments, and indirect cell-medicament contact experiments of 24-hr duration using fresh and set medicaments. ZOE produced a greater zone of bacterial inhibition than Kri 1 paste. Kri 1 paste cytotoxicity remained high regardless of the amount of setting time in the 4-hr direct contact experiment, while ZOE cytotoxicity decreased with setting time. Both Kri 1 paste and ZOE had high cytotoxicity regardless of setting time in the 24-hr direct cell- medicament contact test. ZOE cytotoxicity decreased to control levels after only 1 day of setting in the indirect contact experiments, compared with greater than 7 days for Kri 1 paste. The results suggest ZOE has better antimicrobial activity than Kri 1 paste. ZOE also has lower cytotoxicity, although prolonged cell-medicament contact may result in both medicaments having similarly high cytotoxicity.

Lambrecht JT Panzer G [The toxicity of root-canal filling materials in primary osteoclast cell cultures (see comments)]Die Toxizitat von Wurzelfullmaterialien in primaren Osteoklasten- Zellkulturen.Schweiz Monatsschr Zahnmed (1995) 105(7):899-906

Endodontic root-filling material is brought into direct contact with apical tissues when finishing endodontic therapy. Endodontic two- component materials develop cytotoxic effects during the phase, as shown in different in-vitro studies. Insufficient specificity of these tests could be eliminated by using bone cell cultures. The toxicity of seven endodontic root-filling materials towards osteoclasts in primary cell culture were investigated. Osteoclasts initially reacted to freshly mixed endodontic materials by losing their physiological properties (surface adherence), longer exposition on the toxic agents led to cell lysis. To quantify these light- microscopical phenomena, the content of lactate dehydrogenase (LDH) in the adherent cells as well as in the medium of the cultures were determined photometrically. All the examined two-component materials induced a distinct loss of intracellular LDH activity with a proportional uprise in the media. Calibration showed a positive correlation of LDH content and cell number. The results could be interpreted as the survival rate of osteoclasts after incubation with endodontic filling materials. All tested materials--except for gutta- percha--showed a distinct toxicity towards osteoclasts in primary cell culture during the first 24 hours. Osteoclasts proved to be sensitive indicators for cell-adverse toxicity during the in-vitro tests of endodontic root-filling materials.

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