Exploring the properties of formocresol in dentistry---a comprehensive review

Due to concerns about formocresol’s mutagenic and genotoxic potential, its use as a pulpotomy medication is currently debatable. The current paper aimed to review the properties of formocresol and concerns regarding its safety as a pulpotomy medicament for primary teeth. With reference to the context of the recently published literature, the alternatives to formocresol are discussed, together with their benefits and drawbacks. A literature search was conducted using multiple databases comprising of MEDLINE (via PubMed), EMBASE, and Web of Science. The terms used for the search were “formocresol”, “pulpotomy”, and “primary teeth”. In total, 364 articles were obtained from the analysis of the databases. Unrelated articles from the available full text of 174 articles were excluded. The main reasons for excluding the articles were: they were usage and precautionary guidelines. A total of 68 studies were finally included in the review. The literature review in this paper supports the notion that formocresol continues to be the most often utilized pulp dressing agent in primary teeth pulpotomies despite offering no advantages over other pulp dressing chemicals that are currently on the market.

Chemical; Dental; Formaldehyde; Primary teeth; Pulpotomy

[1] Ozcelik O, Haytac MC, Akkaya M. Iatrogenic trauma to oral tissues. Journal of Periodontology. 2005; 76: 1793–1797.

[2] Chandrashekhar S, Shashidhar J. Formocresol, still a controversial material for pulpotomy: a critical literature review. Journal of Dental Research. 2014; 2: 114–124.

[3] Al-Dlaigan YH. Pulpotomy medicaments used in deciduous dentition: an update. The Journal of Contemporary Dental Practice. 2015; 16: 486–503.

[4] Schwartz EA. Formocresol vital pulpotomy on permanent dentition. Journal of the Canadian Dental Association. 1980; 46: 570–577.

[5] Buckley JP. Rational treatment of decomposing pulps. The Dental Register. 1904; 58: 609–613.

[6] Havale R, Anegundi RT, Indushekar K, Sudha P. Clinical and radio-graphic evaluation of pulpotomies in primary molars with formocresol, glutaraldehyde and ferric sulphate. Oral Health and Dental Management. 2013; 12: 24–31.

[7] Winters J, Cameron AC, Widmer RP. Pulp therapy for primary and immature permanent teeth. Handbook of Pediatric Dentistry. 2013; 30: 103–122.

[8] Myers DR, Pashley DH, Whitford GM, McKinney RV. Tissue changes induced by the absorption of formocresol from pulpotomy sites in dogs. Pediatric Dentistry. 1983; 5: 6–8.

[9] Casas MJ, Kenny DJ, Judd PL, Johnston DH. Do we still need formocresol in pediatric dentistry? Journal of the Canadian Dental Association. 2005; 71: 749–751.

[10] Yoon RK, Chussid S, Davis MJ, Bruckman KC. Preferred treatment methods for primary tooth vital pulpotomies. A survey. New York State Dental Journal. 2008; 74: 47–49.

[11] Moher D, Shamseer L, Clarke M, Ghersi D, Liberati A, Petticrew M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Systematic Reviews. 2015; 4: 1.

[12] Verma P, Chandra A, Yadav R. Endodontic emergencies: your medication may be the cause. Journal of Conservative Dentistry. 2009; 12: 77.

[13] Lewis B. The obsolescence of formocresol. British Dental Journal. 2009; 207: 525–528.

[14] Goyal S, Indushekar KR. Use of formocresol by the pediatric dentists across India—a questionnaire survey. Journal of Evolution of Medical and Dental Sciences 2013; 2: 5943–5951.

[15] Pannu R. Formocresol in dental domain: a review. International Journal of Science and Research. 2019; 8: 719–722.

[16] Milnes AR. Is formocresol obsolete? A Fresh look at the evidence concerning safety issues. Journal of Endodontics. 2008; 34: S40–S46.

[17] Ranly DM. Assessment of the systemic distribution and toxicity of formaldehyde following pulpotomy treatment: part one. ASDC Journal of Dentistry for Children. 1985; 52: 431–434.

[18] Kahl J, Easton J, Johnson G, Zuk J, Wilson S, Galinkin J. Formocresol blood levels in children receiving dental treatment under general anesthesia. Pediatric Dentistry. 2008; 30: 393–399.

[19] Jayaraman J, Nagendrababu V, Pulikkotil SJ, Veettil SK, Dhar V. Effectiveness of formocresol and ferric sulfate as pulpotomy material in primary molars: a systematic review and meta-analysis with trial sequential analysis of randomized clinical trials. Quintessence International. 2020; 51: 38–48.

[20] Hamaguchi F, Tsutsui T. Assessment of genotoxicity of dental antiseptics: ability of phenol, guaiacol, p-phenolsulfonic acid, sodium hypochlorite, p- chlorophenol, m-cresol or formaldehyde to induce unscheduled DNA synthesis in cultured Syrian hamster embryo cells. Japanese Journal of Pharmacology. 2000; 83: 273–276.

[21] Inci M, Zararsız I, Davarci M, Gorur S. Toxic effects of formaldehyde on the urinary system. Turkish Journal of Urology. 2013; 39: 48–52.

[22] Heck DA, Casanova M, Starr TB. Formaldehyde toxicity—new understanding. Critical Reviews in Toxicology. 1990; 20: 397–426.

[23] Merk O, Speit G. Significance of formaldehyde-induced DNA-protein crosslinks for mutagenesis. Environmental and Molecular Mutagenesis. 1998; 32: 260–268.

[24] Crosby RM, Richardson KK, Craft TR, Benforado KB, Liber HL, Skopek TR. Molecular analysis of formaldehyde-induced mutations in human lymphoblasts and E. coli. Environmental Mutagenesis. 1988; 12: 155–166.

[25] Hauptmann M, Lubin JH, Stewart PA, Hayes RB, Blair A. Mortality from lymphohematopoietic malignancies among workers in formaldehyde industries. J Natl Cancer Inst. 2003; 95: 1615-1623.

[26] Lu Z-S, Yan Y, Y Qiao, HC Yao, X Yang. Studies on genotoxicity of gaseous formaldehyde on human buccal cells. China Environmental Science. 2003; 23: 566–569.

[27] Quievryn G, Zhitkovich A. Loss of DNA-protein crosslinks from formaldehyde-exposed cells occurs through spontaneous hydrolysis and an active repair process linked to proteosome function. Carcinogenesis. 2000; 21: 1573–1580.

[28] Zarzar PA, Rosenblatt A, Takahashi CS, Takeuchi PL, Costa Júnior LA. Formocresol mutagenicity following primary tooth pulp therapy: an in vivo study. Journal of Dentistry. 2003; 31: 479–485.

[29] Ribeiro DA, Scolastici C, de Lima PLA, Marques MEA, Salvadori DMF. Genotoxicity of antimicrobial endodontic compounds by single cell gel (comet) assay in Chinese hamster ovary (CHO) cells. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology. 2005; 99: 637–640.

[30] Kreiger RA, Garry VF. Formaldehyde-induced cytotoxicity and sister-chromatid exchanges in human lymphocyte cultures. Mutation Research Letters. 1983; 120: 51–55.

[31] Hagiwara M, Watanabe E, Barrett JC, Tsutsui T. Assessment of genotoxicity of 14 chemical agents used in dental practice: ability to induce chromosome aberrations in Syrian hamster embryo cells. Mutation Research/Genetic Toxicology and Environmental Mutagenesis. 2006; 603: 111–120.

[32] Nishimura H, Higo Y, Ohno M, Tsutsui TW, Tsutsui T. Ability of root canal antiseptics used in dental practice to induce chromosome aberrations in human dental pulp cells. Mutation Research/Genetic Toxicology and Environmental Mutagenesis. 2008; 649: 45–53.

[33] Block RM, Lewis RD, Sheats JB, Burke SG. Antibody formation to dog pulp tissue altered by formocresol uithin the root canal. Oral Surgery, Oral Medicine, and Oral Pathology. 1978; 45: 282–292.

[34] Morse DR. Immunologic aspects of pulpal-periapical diseases. Oral Surgery, Oral Medicine, Oral Pathology. 1977; 43: 436–451.

[35] Cambruzzi JV, Greenfeld RS. Necrosis of crestal bone related to the use of excessive formocresol medication during endodontic treatment. Journal of Endodontics. 1983; 9: 565–567.

[36] Kopczyk RA, Cunningham CJ, Abrams H. Periodontal implications of formocresol medication. Journal of Endodontics. 1986; 12: 567–569.

[37] Syed M, Chopra R, Sachdev V. Allergic reactions to dental materials-a systematic review. Journal of Clinical and Diagnostic Research. 2015; 9: ZE04–9.

[38] Ding YJ, Song H, Liu JH, Wang GH. Brain injury due to anaphylactic shock as a result of formocresol used during root canal treatment. International Endodontic Journal. 2013; 46: 999–1005.

[39] Dilley GJ, Courts FJ. Immunological response to four pulpal medica-ments. Pediatric Dentistry. 1981; 3: 179–183.

[40] Rölling I, Hasselgren G, Tronstad L. Morphologic and enzyme histo-chemical observations on the pulp of human primary molars 3 to 5 years after formocresol treatment. Oral Surgery, Oral Medicine, Oral Pathology. 1976; 42: 518–528.

[41] Doi S, Suzuki S, Morishita M, Yamada M, Kanda Y, Torii S, et al. The prevalence of IgE sensitization to formaldehyde in asthmatic children. Allergy. 2003; 58: 668–671.

[42] Dilsiz A. Self-inflicted oral soft-tissue burn due to local behavior and treatment. Journal of Clinical and Experimental Dentistry. 2010; 2: e51–e54.

[43] Sooranagi RM, Dayakar M, Pai P, Vijayan V, Waheed A. Chemical burns of gingiva and its management. SRM Journal of Research in Dental Sciences. 2018; 9: 174.

[44] Issrani R, Prabhu N, Alam M. Iatrogenic injury of facial skin due to formocresol: a case report. Journal of Cutaneous and Aesthetic Surgery. 2020; 13: 240.

[45] Girish MS, Anandakrishna L, Chandra P, Nandlal B, Srilatha KT. Iatrogenic injury of oral mucosa due to chemicals: a case report of formocresol injury and review. IOSR Journal of Dental and Medical Sciences (IOSR-JDMS). 2015; 14: 01–05.

[46] Shumayrikh NM, Adenubi JO. Clinical evaluation of glutaraldehyde with calcium hydroxide and glutaraldehyde with zinc oxide eugenol in pulpotomy of primary molars. Endodontics & Dental Traumatology. 1999; 15: 259–264.

[47] Fuks AB, Jones PC, Michaeli Y, Bimstein E. Pulp response to collagen and glutaraldehyde in pulpotomized primary teeth of baboons. Pediatric Dentistry. 1991; 13: 142–150.

[48] Godhi B. Success rate of MTA pulpotomy on vital pulp of primary molars: a 3-year observational study. International Journal of Clinical Pediatric Dentistry. 2016; 9: 222–227.

[49] Fuks AB. Vital pulp therapy with new materials for primary teeth: new directions and treatment perspectives. Journal of Endodontics. 2008; 34: S18–S24.

[50] Holan G, Eidelman E, Fuks AB. Long-term evaluation of pulpotomy in primary molars using mineral trioxide aggregate or formocresol. Pediatric Dentistry. 2005; 27: 129–136.

[51] Farsi N, Alamoudi N, Balto K, Mushayt A. Success of mineral trioxide aggregate in pulpotomized primary molars. Journal of Clinical Pediatric Dentistry. 2005; 29: 307–311.

[52] Fernández CC, Martínez SS, Jimeno FG, Lorente Rodríguez AI, Mercadé M. Clinical and radiographic outcomes of the use of four dressing materials in pulpotomized primary molars: a randomized clinical trial with 2-year follow-up. International Journal of Paediatric Dentistry. 2013; 23: 400–407.

[53] Fuks AB, Holan G, Davis JM, Eidelman E. Ferric sulfate versus dilute formocresol in pulpotomized primary molars: long-term follow up. Pediatric Dentistry. 1997; 19: 327–330.

[54] Fei AL, Udin RD, Johnson R. A clinical study of ferric sulfate as a pulpotomy agent in primary teeth. Pediatric Dentistry. 1991; 13: 327–332.

[55] Prabhu NT, Munshi AK. Clinical, radiographic and histological observa-tions of the radicular pulp following “feracrylum” pulpotomy. Journal of Clinical Pediatric Dentistry. 1997; 21: 151–156.

[56] Markovic D, Zivojinovic V, Vucetic M. Evaluation of three pulpotomy medicaments in primary teeth. European Journal of Paediatric Dentistry. 2005; 6: 133–138.

[57] Heilig J, Yates J, Siskin M, McKnight J, Turner J. Calcium hydroxide pulpotomy for primary teeth: a clinical study. The Journal of the American Dental Association. 1984; 108: 775–778.

[58] Waterhouse PJ, Nunn JH, Whitworth JM. An investigation of the relative efficacy of Buckley’s formocresol and calcium hydroxide in primary molar vital pulp therapy. British Dental Journal. 2000; 188: 32–36.

[59] Kaya C, Elbay ÜŞ, Elbay M, Uçar G. The comparison of calcium hydroxide + biostimulation, calcium hydroxide, formocresol, and MTA pulpotomies without biostimulation in primary teeth: 12-months clinical and radiographic follow-up. Lasers in Medical Science. 2022; 37: 2545–2554.

[60] Yildiz E, Tosun G. Evaluation of formocresol, calcium hydroxide, ferric sulfate, and MTA primary molar pulpotomies. European Journal of Dentistry. 2014; 08: 234–240.

[61] Vargas KG, Packham B, Lowman D. Preliminary evaluation of sodium hypochlorite for pulpotomies in primary molars. Pediatric Dentistry. 2006; 28: 511–517.

[62] Kola SR, Reddy NV, Sneha T, Reddy MA, Niharika P, Kumar PJ. A histopathological comparison of pulpal response to formocresol and sodium hypochlorite used as pulpotomy medicaments: in primary teeth—a clinical trial. Journal of the Indian Society of Pedodontics and Preventive Dentistry. 2019; 37: 198–204.

[63] Mack RB, Dean JA. Electrosurgical pulpotomy: a retrospective human study. ASDC Journal of Dentistry for Children. 1993; 60: 107–114.

[64] El-Meligy O, Abdalla M, El-Baraway S, El-Tekya M, Dean J. Histolog-ical evaluation of electrosurgery and formocresol pulpotomy techniques in primary teeth in dogs. Journal of Clinical Pediatric Dentistry. 2002; 26: 81–85.

[65] Oztas N, Ulusu T, Oygür T, Cokpekin F. Comparison of electrosurgery and formocresol as pulpotomy techniques in dog primary teeth. Journal of Clinical Pediatric Dentistry. 1994; 18: 285–289.

[66] Moeintaghavi A, Emtiazi M, Hosseini G, Bahrololoomi Z. Clinical and radiographic comparison of primary molars after formocresol and electrosurgical pulpotomy: a randomized clinical trial. Indian Journal of Dental Research. 2008; 19: 219.

[67] Elliott RD, Roberts MW, Burkes J, Phillips C. Evaluation of the carbon dioxide laser on vital human primary pulp tissue. Pediatric Dentistry. 1999; 21: 327–331.

[68] Juneja P, Kulkarni S. Clinical and radiographic comparison of biodentine, mineral trioxide aggregate and formocresol as pulpotomy agents in primary molars. European Archives of Paediatric Dentistry. 2017; 18: 271–278.

[69] Malhotra R, Ahuja S, Kumar D, Gandhi K, Kapoor R, Surabhi K. Comparative evaluation of success of biodentine and mineral trioxide aggregate with formocresol as pulpotomy medicaments in primary molars: an in vivo study. International Journal of Clinical Pediatric Dentistry. 2020; 13: 167–173.

[70] Jasani B, Musale P, Jasani B. Efficacy of biodentine versus formocresol in pulpotomy of primary teeth: a systematic review and meta-analysis. Quintessence International. 2022; 53: 698–705.

[71] Sabbarini J, Mohamed A, Wahba N, El-Meligy O, Dean J. Comparison of enamel matrix derivative versus formocresol as pulpotomy agents in the primary dentition. Journal of Endodontics. 2008; 34: 284–287.

[72] Ranly DM. Pulpotomy therapy in primary teeth: new modalities for old rationales. Pediatric Dentistry. 1994; 16: 403–409.

[73] Jose B, Ratnakumari N, Mohanty M, Varma HK, Komath M. Calcium phosphate cement as an alternative for formocresol in primary teeth pulpotomies. Indian Journal of Dental Research. 2013; 24: 522.

[74] Haghgoo R, Abbasi F. A histopathological comparison of pulpotomy with sodium hypochlorite and formocresol. Iranian Endodontic Journal. 2012; 7: 60–62.