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Clinical Oral Investigations

, Volume 12, Issue 1, pp 1–8 | Cite as

In vitro and in vivo studies on the toxicity of dental resin components: a review

  • Michel GoldbergEmail author
Discussion Paper

Abstract

In vitro and in vivo studies have clearly identified that some components of restorative composite resins, adhesives, and resin-modified glass ionomer cements are toxic. The mechanisms of cytotoxicity are related firstly to the short-term release of free monomers occurring during the monomer–polymer conversion. Secondly, long-term release of leachable substances is generated by erosion and degradation over time. In addition, ion release and proliferation of bacteria located at the interface between the restorative material and dental tissues are also implicated in the tissue response. Molecular mechanisms involve glutathione depletion and reactive oxygen species (ROS) production as key factors leading to pulp or gingival cell apoptosis. Experimental animal approaches substantiate the occurrence of allergic reactions. There is a large gap between the results published by research laboratories and clinical reports.

Keywords

Composite resin Resin-modified glass ionomer cement Adhesive Free monomers HEMA TEGDMA Free radicals Cytotoxicity Glutathione Allergy Mutagenicity 

References

  1. 1.
    Accorinte Mde L, Loguercio AD, Reis A, Muench A, de Araujo VC (2005) Adverse effects of human pulps after direct pulp capping with the different components from a total-etch, three-step adhesive system. Dent Mater 21:599–607PubMedCrossRefGoogle Scholar
  2. 2.
    Al-Hiyyasat AS, Darmani H, Elbetieha AM (2004) Leached components from dental composites and their effects on fertility of female mice. Eur J Oral Sci 112:267–272CrossRefGoogle Scholar
  3. 3.
    Arenholt-Bindslev D, Breinholt V, Preiss A, Schmalz G (1999) Time-related bisphenol-A content and estrogenic activity in saliva samples collected in relation to placement of fissure sealants. Clin Oral Investig 3:120–125PubMedCrossRefGoogle Scholar
  4. 4.
    Arnst C, Carey J (1998) Biotech bodies. Business Week July pp. 42–49Google Scholar
  5. 5.
    Bergenholtz G (2000) Evidence for bacterial causation of adverse pulpal responses in resin-based dental restorations. Crit Rev Oral Biol Med 11:467–480PubMedGoogle Scholar
  6. 6.
    Bergenholtz G, Cox CF, Loesche WJ, Syed SA (1982) Bacterial leakage around dental restorations and bacterial growth in cavities. J Oral Pathol 11:439–450PubMedCrossRefGoogle Scholar
  7. 7.
    Blomgren J, Axell T, Sandahi O, Jontell M (1996) Adverse reactions in the oral mucosa associated with anterior composite restorations. J Oral Pathol & Med 25:311–313CrossRefGoogle Scholar
  8. 8.
    Bouilliaguet S, Virgillito M, Wataha J, Ciucchi B, Holz J (1998) The influence of dentine permeability on cytotoxicity of four dentine systems, in vitro. J Oral Rehabil 25:45–51CrossRefGoogle Scholar
  9. 9.
    Burke FJ, Cheung SW, Mjör IA, Wilson NH (1999) Reasons for the placement and replacement of restorations in vocational training practices. Prim Dent Care 6:17–20PubMedGoogle Scholar
  10. 10.
    Carmichael AJ, Gibson JJ, Walls AW (1997) Allergic contact dermatic to bisphenol-A-glycidyldimethacrylate (BIS-GMA) dental resin associated with sensitivity to epoxy resin. Br Dent J 183:297–298PubMedGoogle Scholar
  11. 11.
    Chang H-H, Guo M-K, Kasten FH, Chang M-C, Huang G-F, Wang Y-L, Wang R-S, Jeng J-H (2005) Stimulation of glutathione depletion, ROS production and cell cycle arrest of dental pulp cells and gingival epithelial cells by HEMA. Biomaterials 26:745–753PubMedCrossRefGoogle Scholar
  12. 12.
    Chen CC, Chen RC, Huang ST (2002) Enzymatic response of human deciduous pulpal fibroblasts to dental restorative materials. J Biomed Mater Res 60:452–457PubMedCrossRefGoogle Scholar
  13. 13.
    Cox CF, Hafez AA, Akimoto N, Otsuki M, Suzuki S, Tarim B (1998) Biocompatibility of primer, adhesive and resin composite systems on exposed and exposed pulps of non-human primate teeth. Am J Dent 11(Spec No):S55–S63PubMedGoogle Scholar
  14. 14.
    De Oliveira Mussel RL, De Sa Silva E, Monte Alto Costa A, Mandarim-De-Lacerda CA, (2003) Mast cells in tissue response to dentistry materials: an adhesive resin, a calcium hydroxide and a glass ionomer cement. J Cell Mol Med 7:171–178CrossRefGoogle Scholar
  15. 15.
    De Munck J, Van Landuyt K, Peumans M, Poitevin A, Lambrecht P, Braem M, Van Meerbek B (2005) A critical review of the durability of adhesion to tooth tissue: methods and results. J Dent Res 84:118–132PubMedCrossRefGoogle Scholar
  16. 16.
    Demarco FF, Tarquinio SB, Jargerf MM, de Araujo VC, Matson E (2001) Pulp response and cytotoxicity evaluation of 2 dentin bonding agents. Quintessence Int 32:211–220PubMedGoogle Scholar
  17. 17.
    Engelmann J, Leyhausen G, Leibfritz D, Geurtsen W (2001) Metabolic effects of dental resin components in vitro detected by NMR sprectroscopy. J Dent Res 80:869–875PubMedGoogle Scholar
  18. 18.
    Engelmann J, Leyhausen G, Leibfritz D, Geurtsen W (2002) Effects of TEGDMA on the intracellular glutathione concentration of human gingival fibroblasts. J Biomed Mater Sci 63:746–751CrossRefGoogle Scholar
  19. 19.
    Ferracane JL (1994) Elution of leachable components from composites. J Oral Rehabil 21:441–452PubMedCrossRefGoogle Scholar
  20. 20.
    Finer Y, Jaffer F, Santerre JP (2004) Mutual influence of cholesterol esterase and pseudocholinesterase on the biodegradation of dental composites. Biomaterials 25:1787–1793PubMedCrossRefGoogle Scholar
  21. 21.
    Finer Y, Santerre JP (2004) The influence of resin chemistry on a dental composite's biodegradation. J Biomed Mater Res 69A:233–246CrossRefGoogle Scholar
  22. 22.
    Franz A, Konig F, Anglmayer M, Rausch-fan X, Gille G, Rausch WD, Lucas T, Sperr W, Schedle A (2003) Cytotoxic effects of packable and nonpackable dental composites. Dent Mater 19:382–392PubMedCrossRefGoogle Scholar
  23. 23.
    Franz-Xaver R, Jürgen D, Kai K, Matthias F, Norbert K, Markus S, El-Mahdy K, Reinhard H (2003) Synergistic effects of H2O2 with components of dental restorative materials on glucogenesis in rat kidney tubules. Biomaterials 24:1909–1916PubMedCrossRefGoogle Scholar
  24. 24.
    Fung EY, Ewoldsen NO, St Germain HA Jr, Marx DB, Miaw C-L, Siew C, Chou H-N, Gruninger MS, Meyer DM (2000) Pharmacokinetics of bisphenol A released from a dental sealant. J Am Dent Assoc 131:51–58PubMedGoogle Scholar
  25. 25.
    Geurtsen W (1998) Substances released from dental resin composites and glass ionomer cements. Eur J Oral Sci 106:687–695PubMedCrossRefGoogle Scholar
  26. 26.
    Geurtsen W (2000) Biocompatibility of resin-modified filling materials. Crit Rev Oral Biol Med 11:333–355PubMedGoogle Scholar
  27. 27.
    Geurtsen W, Leyhausen G (2001) Chemical–biological interaction of the resin monomer triethyleneglycoldimetacrylate (TEGDMA). J Dent Res 80:2046–2050PubMedGoogle Scholar
  28. 28.
    Geurtsen W, Lehmann F, Spahl W, Leyhausen G (1998) Cytotoxicity of 35 dental resin composite monomers/additives in permanent 3T3 and three primary fibroblast cultures. J Biomed Mater Res 41:474–480PubMedCrossRefGoogle Scholar
  29. 29.
    Goldberg M, Stanislawski L, Bonte E, Daniau X, Bonte E, Daniau X, Lasfargues J-J (1999) Biocompatibility of glass-ionomer cements. In: Davidson CL, Mjor IA (eds) Advances in glass-ionomer cements, chapter 5. Quintessence Publishing, Chicago, pp 103–120Google Scholar
  30. 30.
    Hamid A, Hume WR (1997) A study of component release from resin pit and fissure sealants in vitro. Dent Mater 13:98–102PubMedCrossRefGoogle Scholar
  31. 31.
    Hamid A, Okamoto A, Iwaku M, Hume WR (1998) Component release from light-activated glass ionomer and compomer cements. J Oral Rehabil 25:94–99PubMedCrossRefGoogle Scholar
  32. 32.
    Hansel C, Leyhausen G, Mai UE, Geurtsen W (1998) Effects of various resin composite (co)monomers and extracts on two caries-associated micro-organisms in vitro. J Dent Res 77:60–67PubMedGoogle Scholar
  33. 33.
    Hashimoto M, Ito S, Tay FR, Svizero NR, Sano H, Kaga M, Pashley DM (2004) Fluid movement across the resin–dentin interface during and after bonding. J Dent Res 83:843–848PubMedGoogle Scholar
  34. 34.
    Hensten-Pettersen A (1998) Skin and mucosal reactions associated with dental materials. Eur J Oral Sci 106:707–712PubMedGoogle Scholar
  35. 35.
    Hume WR, Gerzina TM (1996) Bioavailability of components of resin-based materials which are applied to teeth. Crit Rev Oral Biol Med 7:172–179PubMedCrossRefGoogle Scholar
  36. 36.
    Issa Y, Watts DC, Brunton PA, Waters CM, Duxbury AJ (2004) Resin composite monomers alter MTT and LDH activity of human gingival fibroblasts in vitro. Dent Mater 20:12–20PubMedCrossRefGoogle Scholar
  37. 37.
    Issa Y, Duxbury AJ, Macfarlane TV, Brunton PA (2005) Oral lichenoid lesions related to dental restorative materials. Br Dent J 198:361–366PubMedCrossRefGoogle Scholar
  38. 38.
    Jaffer F, Finer Y, Santerre JP (2002) Interactions between resin monomers and commercial composite resins with human saliva derived esterases. Biomaterials 23:1707–1719PubMedCrossRefGoogle Scholar
  39. 39.
    Kaga M, Noda M, Ferracane JL, Nakamura W, Oguchi H, Sano H (2001) The in vitro cytotoxicity of eluates from dentin bonding resins and their effect on tyrosine phosphorylation of L929 cells. Dent Mater 17:333–339PubMedCrossRefGoogle Scholar
  40. 40.
    Katsuno K, Manabe A, Kurihara A, Itoh K, Hisamitsu H, Wakumoto S, Yoshida T (1998) The adverse effect of commercial dentine-bonding systems on the skin of guinea pigs. J Oral Rehabil 25:180–184PubMedCrossRefGoogle Scholar
  41. 41.
    Kehe K, Reichl FX, Durner J, Walther U, Hickel R, Forth W (2001) Cytotoxicity of dental composite components and mercury compounds in pulmonary cells. Biomaterials 22:317–322PubMedCrossRefGoogle Scholar
  42. 42.
    Khalichi P, Cvitkovitch DG, Santerre JP (2004) Effect of composite resin biodegradation products on oral streptococcal growth. Biomaterials 25:5467–5472PubMedCrossRefGoogle Scholar
  43. 43.
    Kleinsasser NH, Wallner BC, Harréus UA, Kleinjung T, Folwaczny M, Hickel R, Kehe K, Reichl F-X (2004) Genotoxicity and cytotoxicity of dental materials in human lymphocytes as assessed by the single cell microgel electrophoresis (comet) assay. J Dent 32:229–234PubMedCrossRefGoogle Scholar
  44. 44.
    Kleinsasser NH, Schmid K, Sassen AW, Harréus UA, Staudenmaier R, Folwaczny M, Glas J, Reichl F-X (2006) Cytotoxic and genotoxic effects of resin monomers in human salivary gland tissue and lymphocytes as assessed by the single cell microgel electrophoresis (comet) assay. Biomaterials 27:1762–1770PubMedCrossRefGoogle Scholar
  45. 45.
    Lan WH, Lan WC, Wang TM, Lee YL, Tseng WY, Lin CP, Jeng JH, Chang MC (2003) Cytotoxicity of conventional and modified glass ionomer cements. Oper Dent 28:251–259PubMedGoogle Scholar
  46. 46.
    Lefebvre CA, Schuster GS, Rueggeberg FA, Tamareselvy K, Knoernschild KL (1996) Response of oral epithelial cells to dental resin components. J Biomater Sci Polym Ed 7:965–976PubMedCrossRefGoogle Scholar
  47. 47.
    Lefeuvre M, Bourd K, Loriot M-A, Goldberg M, Beaune P, Périanin A (2004) TEGDMA modulates glutathione-S-transferase P1 activity in gingival fibroblasts. J Dent Res 83:914–919PubMedGoogle Scholar
  48. 48.
    Lefeuvre M, Amjaad W, Goldberg M, Stanislawski L (2005) TEGDMA induces mitochondrial damage and oxidative stress in human gingival fibroblasts. Biomaterials 26:5130–5137PubMedCrossRefGoogle Scholar
  49. 49.
    Mjör IA, Jokstad A, Qvist V (1990) Longevity of posterior restorations. Int Dent J 40:11–17PubMedGoogle Scholar
  50. 50.
    Munksgaard EC, Hansen EK, Engen T, Holm U (1996) Self-reported occupational dermatological reactions among Danish dentists. Eur J Oral Sci 104:396–402PubMedCrossRefGoogle Scholar
  51. 51.
    Murray PE, Windsor LJ, Hafez AA, Stevenson RG, Cox CF (2003a) Comparison of pulp responses to resin composites. Oper Dent 28:242–250PubMedGoogle Scholar
  52. 52.
    Murray PE, Hafez AA, Smith AJ, Cox CF (2003b) Identification of hierarchical factors to guide clinical decision making for successful long-term pulp capping. Quintessence Int 34:61–70PubMedGoogle Scholar
  53. 53.
    Noda M, Wataha JC, Kaga M, Lockwood PE, Volkmann KR, Sano H (2002) Components of dentinal adhesives modulate heat shock protein 72 expression in heat-stressed THP-1 human monocytes at sublethetal concentrations. J Dent Res 81:265–269PubMedGoogle Scholar
  54. 54.
    Nomura Y, Ishibashi H, Miyahara M, Shinohara R, Shiraishi F, Arizono K (2003) Effects of dental resin metabolites on estrogenic activity in vitro. J Mater Sci Mater Med 14:307–310PubMedCrossRefGoogle Scholar
  55. 55.
    Örtengren U (2000) On composite resin materials—degradation, erosion and possible adverse effects in dentists. Swed Dent J Suppl 141:1–61PubMedGoogle Scholar
  56. 56.
    Örtengren U, Andreasson H, Karlsson S, Meddling B, Barregärd L (1999) Prevalence of self-reported hand eczema and skin symptoma associated with dental materials among Swedish dentists. Eur J Oral Sci 107:496–505PubMedCrossRefGoogle Scholar
  57. 57.
    Peumans M, Van Meerbeek B, Lambrechts P, Vanherle G, Quirynen M (1998) The influence of direct composite addition for the correction of tooth form and/or position on periodontal health. A retrospective study. J Periodontol 69:422–427PubMedGoogle Scholar
  58. 58.
    Ratanasthien S, Watnha JC, Hanks CT, Dennison JB (1995) Cytotoxic interactive effects of dentin bonding components on mouse fibroblasts. J Dent Res 74:1602–1606Google Scholar
  59. 59.
    Reichl FX, Durner J, Mückter H, Elsenhans B, Forth W, Kunzelmann KH, Hickel R, Spahl W, Hume WR, Moes GW (1999) Effects of dental materials on glucogenesis in rat kidney tubules. Arch Toxicol 73:381–386PubMedCrossRefGoogle Scholar
  60. 60.
    Reichl FX, Walther UI, Durner J, Kehe K, Hickel R, Kunzelmann KH, Spahl W, Hume WR, Benschop H, Forth W (2001a) Cytotoxicity of dental composite components and mercury compounds in lung cells. Dent Mater 17:95–101PubMedCrossRefGoogle Scholar
  61. 61.
    Reichl FX, Durner J, Kunzelmann KH, Hickel R, Spahl W, Hume WR, Moes GWH, Kehe K, Walther U, Forth W (2001b) Biological clearance of TEGDMA in guinea pigs. Arch Toxicol 75:22–27PubMedCrossRefGoogle Scholar
  62. 62.
    Reichl FX, Durner J, Hickel R, Kunzelmann KH, Jewett A, Wang MY, Spahl W, Kreppel H, Moes GW, Kehe K, Walther U, Forth W, Hume WR (2001c) Distribution and excretion of TEGDMA in guinea pigs and mice. J Dent Res 80:1412–1415PubMedGoogle Scholar
  63. 63.
    Reichl FX, Durner J, Hickel R, Spah W, Kehe K, Walther U, Gempel K, Liebl B, Kunzelmann KH, Hume W (2002) Uptake, clearance and metabolism of TEGMA in guinea pigs. Dent Mater 18:581–589PubMedCrossRefGoogle Scholar
  64. 64.
    Schmalz G (1998) The biocompatibility of non-amalgam dental filling materials. Eur J Oral Sci 106:696–706PubMedCrossRefGoogle Scholar
  65. 65.
    Schmalz G, Preiss A, Arenholt-Bindslev D (1999) Bisphenol-A content of resin monomers and related degradation products. Clin Oral Investig 3:114–119PubMedCrossRefGoogle Scholar
  66. 66.
    Schuurs AHB, Gruythuysen RJM, Wesselink PR (2000) Pulp capping with adhesive resin-based composite vs.calcium hydroxide: a review. Endod Dent Traumatol 16:240–250PubMedCrossRefGoogle Scholar
  67. 67.
    Schweikl H, Schmalz G, Rackbrandt K (1998) The mutagenic activity of unpolymerized resin monomers in Salmonella typhimurium and V79 cells. Mutat Res 415:119–130PubMedGoogle Scholar
  68. 68.
    Schweikl H, Schmalz G (1999) Triethylene glycol dimetacrylate induces large deletions in the hprt gene of V79 cells. Mutat Res 438:71–78PubMedGoogle Scholar
  69. 69.
    Schweikl H, Schmalz G, Spruss T (2001) The induction of micronuclei in vitro by unpolymerized resin monomers. J Dent Res 80:1615–1620PubMedGoogle Scholar
  70. 70.
    Schweikl H, Spagnuolo G, Schmaltz G (2006) Genetic and cellular toxicology of dental resin monomers. J Dent Res 85:870–877PubMedGoogle Scholar
  71. 71.
    Shajii L, Santerre JP (1999) Effect of filler content on the profile of released biodegradation products in microfilled bis-GMA/TEGDMA dental composite resins. Biomaterials 20:1897–1908PubMedCrossRefGoogle Scholar
  72. 72.
    Six N, Lasfargues J-J, Goldberg M (2000) In vivo study of the pulp reaction to Fuji IX, a glass ionomer cement. J Dent 28:413–422PubMedCrossRefGoogle Scholar
  73. 73.
    Soheili Majd E, Goldberg M, Stanislawski L (2003) In vitre effects of ascorbate and Trolox on the biocompatibility of dental restorative materials. Biomaterials 24:3–9PubMedCrossRefGoogle Scholar
  74. 74.
    Spahl W, Budzikiewicz H, Geursten W (1998) Determination of leachable components from four commercial dental composites by gas and liquid chromatography/mass spectrometry. J Dent 26:137–145PubMedCrossRefGoogle Scholar
  75. 75.
    Stanislawski L, Daniau X, Lauti A, Goldberg M (1999) Factors responsible for pulp cell cytotoxicity induced by resin-modified glass ionomer cements. J Biomed Mater Res 48:277–288PubMedCrossRefGoogle Scholar
  76. 76.
    Stanislawski L, Soheili-Majd E, Perianin A, Goldberg M (2000) Dental restorative biomaterials induce glutathione depletion in cultured human gingival fibroblast: protective effect of N-acetyl cysteine. J Biomed Mater Res 51:469–474PubMedCrossRefGoogle Scholar
  77. 77.
    Stanislawski L, Lefeuvre M, Bourd K, Soheili-Majd E, Goldberg M, Perianin A (2003) TEGDMA-induced toxicity in human fibroblasts is associated with early and drastic glutathione depletion with subsequent production of oxygen reactive species. J Biomed Mater Res 66:476–482CrossRefGoogle Scholar
  78. 78.
    Szep S, Kumkel A, Ronge K, Heidemann D (2002) Cytotoxicity of modern dentin adhesives: in vitro testing on gingival fibroblasts. J Biomed Mater Res 63:53–60PubMedCrossRefGoogle Scholar
  79. 79.
    Tarumi H, Imazoto S, Narimatsu M, Matsuo M, Ebisu S (2000) Estrogenicity of fissure sealants and adhesive resins determined by reporter gene assay. J Dent Res 79:1838–1843PubMedGoogle Scholar
  80. 80.
    Thonemann B, Schmalz G, Hiller KA, Schweikl H (2002) Responses of L929 mouse fibroblasts, primary and immortalized bovine dental papilla-derived cells lines to dental resin components. Dent Mater 18:318–323PubMedCrossRefGoogle Scholar
  81. 81.
    Vamnes JS, Lygre GB, Grönningsæter AG, Gjerdet NR (2004) Four years of clinical experience with adverse reaction unit for dental biomaterials. Community Dent Oral Epidemiol 32:150–157PubMedCrossRefGoogle Scholar
  82. 82.
    Wallenhammar L-M, Örtengren U, Andreasson H, Barregärd L, Björkner B, Karlsson S, Wrangssjö K, Meding B (2000) Contact allergy and hand eczema in Swedish dentists. Contact Dermatitis 43:192–199PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  1. 1.Faculté de Chirurgie DentaireUniversity Paris 5MontrougeFrance

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