Good Morning!

FORMOCRESOL AND
ITS
CONTROVERSIES
Presented by:
Dr.Reena Rani
PG final Year
Department of Pedodontics and
Preventive Dentistry
 Contents
•Introduction
•Composition
Buckley’s Formocresol
Preparation
•Mechanism of Action
•Functions
•Histological changes in tooth with formocresol
•Toxicity, carcinogenicity and mutagenicity
•Concerns about Formocresol
•Pharamacokinetics of formocresol
•Pharamacokinetics of formaldehyde
. •Dosage and Administration
•Conclusion

3
 INTRODUCTION

▸ Formocresol was introduced to treat non-vital permanent teeth in the

United States by Buckley in 1904 as a root canal medication

J. Todd milledge. Endodontic therapy for primary teeth. In: Ingle J, Bakland L, editors. Endodontics. 6th ed. Hamilton: BC
Deker; 2008.Vol 1, p. 1400-30
4
▸ Sweet in 1930 advocated the first pulpotomy technique as a
multi- visit technique, for vital as well as for non- vital teeth.

▸ The aim of the treatment was to sterilize the pulp chamber by a

rotation of drugs before filling it with zinc oxide eugenol.

▸ He had started with five appointments which were later

reduced to three. By the year 1955, he had shown a clinical
success rate of 97% in 16,551 cases.
J. Todd milledge. Endodontic therapy for primary teeth. In: Ingle J, Bakland L, editors. Endodontics. 6th ed. Hamilton: BC Deker; 2008.Vol 1, p. 1400-
30
5
▸ Massler & Mansukhani(1959)- investigated the histologic
effects of formocresol on dental pulp. The other histologic study
carried out at the same time was by Emmerson and his co-
workers in 1959.

6
▸ Doyle et al (1962) reduced it to two visits, complex devitalization.

▸ Spedding (1965) recommended the one appointment, 5-minute

protocol, resulting in partial devitalization.

▸ Venham (1967) gave the 15 sec protocol but it is not preferred.

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▸ Loos and Han (1971) reported comparable tissue fixations
with 1:4 or in 1 in 5 dilutions as with full strength.

▸ The current technique followed is the use of diluted

Buckley’s formacresol technique for 5 minutes in a single
visit.
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 Composition

▸ Buckley contended that equal parts of formalin and tricresol

would react chemically with the intermediate and end
products of pulp inflammation to form a ‘new’, colorless,
and non-infective compound of a harmless nature.

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 FDI RECOMMENDATION

Formocresol (Full Strength)

▸ Formaldehyde:48.5%
▸ Cresol: 48.5%
▸ Glycerine:3%

Buckley’s Formocresol 1/5th strength.

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 Buckley’s Formocresol

Water
31%
Glycerin
15%

Tricresol 35%

Formaldehyde
19%

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 Preparation of Buckley’s Formocresol

▸ One-fifth dilution of Buckley’s formocresol can be prepared by

adding 30ml of Buckley’s formocresol, 90 ml of glycerol and 30
ml of water to obtain 150mL of dilute formocresol. i.e. 1/5th
strength.
▸ Glycerine prevent the polymerization formaldehyde
to para-formaldehyde.

▸ The presence of para-formaldehyde causes clouding of the

solution.
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 MECHANISM OF ACTION

▸ Formocresol is both a devitalizing agent and bactericidal.It

converts pulp tissue and bacteria into inert compounds.

▸ It acts through the aldehyde group of formaldehyde, forming

bonds with the side groups of the amino acids of both the
bacterial proteins and those of the remaining pulp tissue.

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 Functions
▸ Its function is to fasten the live pulps, maintaining them inert
and facilitating the conservation of deciduous tooth until their
physiologic exfoliation.

▸ It has a potent antibacterial action that justifies its use in long

curative in endodontic treatment.

▸ With formocresol as the pulptomy medicament, a zone of

fixation usually is evident where the pulp is in direct contact
with the medicament.
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 Functions
▸ Inactivates the oxidative enzymes in the pulp tissue adjacent to
the amputation site.

▸ Effect on hyaluronidase action- The protein-binding properties

and the inhibition of the enzymes that can break the pulp tissue
down together result in ‘fixation’ of the pulp tissue by
formocresol and render it inert and resistant to enzymatic
breakdown.

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Histological changes in tooth
with formocresol

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▸ Coagulation necrosis of the tissue occurs at the amputation site
and is supported by the fact that true coagulation necrosis is
produced by poisons such as phenol, formaldehyde or mercuric
chloride, which denatures the protein of the cells.
Chandrashekhar S, Shashidhar J. Formocresol, still a controversial material for pulpotomy: A critical literature review. J Res
Dent 2014;2:114-24

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▸ Farther away, where the concentration of formocresol is
decreased, there is a zone of poor cellular definition and necrosis.
Apical to this is a zone of chronic inflammation, which blends
into normal tissue, demonstrated by Mass and Zilbermann in
1993 and also by Massler and Mansukhani in 1959.
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▸ In contrast, Berger reported complete loss of vitality with
fibrous granulation tissue in the apical third of the root canal.

Chandrashekhar S, Shashidhar J. Formocresol, still a controversial material for pulpotomy: A critical literature
review. J Res Dent 2014;2:114-24

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▸ Massler & Mansukhani (1959) concluded that formocresol
produced a progressive fixation and degeneration of pulpal
tissue.
▸ The progressive fixation was considered destructive and it
was suggested that formocresol be placed for two to three
days followed by a more palliative dressing so as to allow for
pulpal healing.
▸ As a result, they recommended that to prevent progressive
fixation formocresol should be applied for less than seven
days.
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▸ Doyle and his co-workers, in 1962, performed two-stage
formocresol pulpotomies in which amputated pulps received a
four to seven day application of formocresol prior to the second
appointment where the teeth received a dressing of zinc-oxide-
eugenol and formocresol.
▸ In five cases, the formocresol containing cotton pledget
remained in place for periods of eight to 42 days. Histologic
evaluations took place on teeth extracted anywhere from four to
380 days after treatment.

21
▸ Berger (1965) observed internal resorption and subsequent
repair by reparative dentin apical to the advancing front of
granulation tissue.

▸ There was also a consistent observation of a slight

accumulation of inflammatory cells at the junction of the
granulation and necrotic tissues.

22
▸ Internal resorption due to formocresol might be due to the
severe damage to the residual tissue, also destroying its capacity
to reabsorb. This may be attributed to inflammation of the
residual pulp.

Shulman ER, McIver FT, Burkes EJ Jr. Comparison of electrosurgery and formocresol as pulpotomy techniques in monkey primary teeth. Pediatr
Dent 1987;9:189-94

23
▸ From 1975 to 1978, Rolling studied formocresol pulpotomies
for a period of up to 36 months. She used full-strength
formocresol and also added formocresol to her ZOE base. The
results of her study found that there was a success rate of 90%
after 3 months and an overall success rate of 70% after 3 years.

▸ Concluded that formocresol pulpotomy should be considered a

temporary procedure for primary teeth.

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▸ In 1975, Ranly performed a study to determine if formocresol
added to the ZOE base was adequate to treat the pulp, allowing
the clinician to skip the step of placing the formocresol pellet.

▸ His study showed that formocresol leached out of the ZOE in

adequate amounts and concluded that the use of a medicated
pellet prior to the placement of the base was unnecessary.

25
▸ Cox et al. (1978) studied the bactericidal potential of materials
used in primary tooth pulpotomies. They found that plain zinc
oxide did not have any inhibitory effect on the bacteria tested.

▸ When formocresol or paraformaldehyde was added to the zinc

oxide–eugenol–zinc acetate cement, there was an even greater
inhibitory effect

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 ▸ Barefield, in 1985, reported that formocresol in the sub-base
alone exerted the same pulpal effect as the initial five-minute
formocresol application and offered the possible advantage of
lower levels of formocresol exposure systemically

Strange DM et al. Outcome of formocresol/ZOE sub-base pulpotomies utilizing alternative radiographic success
criteria.Scientific Article, American Academy of Pediatric Dentistry. 2001; 23:3

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 Controversies of Formocresol Uses

• Toxicity
• Carcinogenicity
• Mutagenicity

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▸ The use of formocresol in dentistry has become a
controversial issue due to its widespread distribution in the
body following systemic injection.

▸ Formocresol is toxic to living tissues because of the

formaldehyde component. Formocresol applied to vital pulp
tissue is absorbed readily into the systemic circulation and
distributed throughout the body.

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▸ Toxicity: Formocresol and formaldehyde have shown to be
cytotoxic, mutagenic and carcinogenic in animal experiments by
Lewis in 1981.

▸ But Ranly calculated that, over 3000 pulpotomies must be

performed in the same individual for formocresol to reach toxic
level.

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 Pharmacokinetics of Formocresol

▸ A portion of the absorbed formocresol is metabolized and

excreted by the kidney and lungs.

▸ The remaining formocresol is tissue-bound with the liver,

kidney and lungs ,the predominant sites of tissue binding.

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 Pharmacokinetics of formaldehyde

▸ Formaldehyde exposure occurs daily as it is present in air, water

and food.

▸ The World Health Organization (WHO) has estimated daily

consumption of formaldehyde to be approximately 1.5-14
mg/day (mean, 7.8 mg/day).

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▸ The estimated formaldehyde dose associated with 1 pulpotomy
procedure, assuming a 1:5 dilution of formocresol placed on a no.
4 cotton pellet that has been squeezed dry, is approximately
0.02-0.10 mg.

▸ Exogenous formaldehyde has a biologic half-life of 1-1.5 minutes

and is quickly cleared from human plasma.

Milnes AR. Is formocresol obsolute? A fresh look at the evidence concerning safety issues. J Endod 2008;34:S40-6

33
 Carcinogenicity

“
It is concluded that cancer develops after inhalation
of air with large concentrations of formaldehyde.

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 How cancer develops?

▸ The cancer can occur after a long-term direct contact with

susceptible tissues.
▸ The toxic effects on initial contact sites like ulceration,
hyperplasia and squamous metaplasia may subsequently
contribute to cancer.
▸ These high-dose responses are unlikely to occur at sites distant
from the point of initial formaldehyde contact (such as the bone
marrow). Formaldehyde is not delivered to these distant sites.

35
▸ Those who have argued against the continued use of
formocresol in pediatric dentistry on the basis that
“formaldehyde causes cancer” have failed to recognize this
very important distinction.

Chandrashekhar S, Shashidhar J. Formocresol, still a controversial material for pulpotomy: A critical literature review. J
Res Dent 2014;2:114-24.

36
 Concerns about Formocresol

▸ Concerns about the safety of formocresol have been

appearing in the dental and medical literature for more
than 20 years.

▸ National Institute for Occupational Safety and Health in USA

states if formaldehyde exposure occurs at a concentration of 20
ppb (parts per billion) or higher, it is instantly dangerous to
health and life.

37
Health Canada and the Organization for Economic
Cooperation and Development have stated on the basis of CIIT
(Chemical Industry Institute for Toxicology Centers for Health
Research) research models that “taking into account the extensive
information on its mode of action, formaldehyde is not likely to be a
potent carcinogen to humans under low exposure conditions.”

38
▸ In 2004, International Agency for Research on Cancer (IARC) re-
classifed formaldehyde as a known carcinogen from human probable
carcinogen,but according to them, it is an agent that can increase the
risk of cancer at some doses. They do not undertake the dose
response analyses and possible threshold.

▸ The possibility that inhaled or ingested formaldehyde might induce

cancer at sites distant from the respiratory or gastrointestinal tracts
has been investigated in numerous long-term toxicity studies
performed in rodents.

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▸ IARC (June 2004) classified formocresol as carcinogen that
has potency to cause leukemia and nasopharyngeal carcinoma.

▸ Eugenia (2007) reported dentigerous cyst associated with a

formocresol pulpotomized deciduous molar.

Kumar Praveen NH et al. Pulpotomy Medicaments: Continued Search for New Alternatives- A Review. OHDM 2014; 13(4):883-
890

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▸ There is little work investigating the effects of formocresol

when used as a pulp medicament in human subjects. Its use in

normal therapy should be investigated, in vivo, because of the
suggested cumulative mutagenic effects,which may cause
damage to children and future generations.

P.A. Zarzar et al. Formocresol mutagenicity following primary tooth pulp therapy: an in vivo study.Journal
of Dentistry · September 2003).

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 Mutagenicity
▸ Brazilian National Research Council (CNPq),The Claude
Bernard Institute,and the Research Support Foundation of
Ceara(FUNCAP) 2008 concluded that Formocresol induced
a significant increase in micronucleus frequencies and DNA –
protein cross links at the highest dilution only at 24 hours after
administration

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 So is it safe ?
▸Experimental and epidemiologic research do not support the
theory that inhaled or ingested formaldehyde might induce distant
site toxicity.

▸The facts are that formaldehyde occurs naturally throughout the

body, there are multiple pathways for detoxification, and only
microgram quantities of formaldehyde are applied to pulp tissues
during pulpotomy procedures for mere minutes.

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▸ Considering these facts, exposure of children to the
formaldehyde component of formocresol during a
pulpotomy is insignifcant and inconsequential

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DOSAGE AND ADMINISTRATION

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▸ No data exist to verify the actual amount of formocresol
delivered to the pulp during the performance of a formocresol
pulpotomy.

Milnes, Is Formocresol Obsolete? A Fresh Look at the Evidence Concerning Safety Issues, Volume 34, Number 7S, July 2008,40-46

46
▸ The dose of formaldehyde from a single cotton pellet has been
determined.
▸ Wesley DJ, Marshall FJ and Rosen S stated that a drop of
formocresol weighs approximately 24.7 mg; clinically the dose of
formocresol in a no. 4 cotton pellet squeezed dry weighs 4.86 mg
(1/5 th drop) which is approximately twice the least effective dose
(1/10 th drop)
Goyal S, Abuwala T, Joshi K, Mehta J, Indushekar KR, Hallikerimath S. The Clinical, Radiographic and
Histological evaluation of three different concentrations of Formocresol as a pulpotomy agent. J Int Oral Health
2014;6(2):118-25.

47
 ▸ While Milnes has calculated that a no. 4 cotton pellet soaked
in full-strength formocresol and then squeezed dry could
theoretically deliver a dose of 0.1 to 0.5 mg formocresol to
the dental pulp.

Goyal S, Abuwala T, Joshi K, Mehta J, Indushekar KR, Hallikerimath S. The Clinical, Radiographic and
Histological evaluation of three different concentrations of Formocresol as a pulpotomy agent. J Int Oral Health
2014;6(2):118-25.

48
▸ In a study done by S Goyal, has calculated the formaldehyde
dose from a no. 1 foam pellet twice squeezed dry (Voco,
PeleTim, Germany).
▸ The mean formaldehyde dose from fullstrength was 2.73 mg,
1.65 mg from 1:5 diluted formocresol and 0.70 mg from 1:25
diluted formocresol.

Goyal S, Abuwala T, Joshi K, Mehta J, Indushekar KR, Hallikerimath S. The Clinical, Radiographic and
Histological evaluation of three different concentrations of Formocresol as a pulpotomy agent. J Int Oral Health
2014;6(2):118-25.

49
▸ A survey was conducted among pedodontic faculty (ISPPD
members) and postgraduates of pedodontics attending the
ISPPD convention in the year 2013, showed 61% of
respondents used formocresol for primary tooth vital
pulpotomies in which 28% used undiluted formocresol and 33%
used diluted formocresol.

▸ The results of this survey suggest that the majority of dentists

who used formocresol were not concerned with any adverse
effects.
S Goyal, KR Indushekar. Use of formocresol by the Pediatric Dentists across India- A questionnaire survey. J Evol
Med Dent Sci. 2013;2(32):5943–5951. 50
 Intracanal disinfection in permanent teeth:

▸ Isolate the tooth with a rubber dam

▸ Clean, de-bride and instrument the canals.
▸ Rinse and dry the canal spaces.
▸ Moisten a small cotton pellet with formocresol.
▸ Blot or wring any excess liquid from the pellet. Place the cotton
pellet in the pulp chamber and seal the access cavity with a
temporary filling material.
▸ Recall the patient after a minimum of 48 hours and remove the
pellet. Complete the endodontic treatment and restore
Nikhil Marwah,Textbook of pedodontics and preventive dentistry,ed:3rd

51
 Formocresol pulpotomy in primary teeth:
▸ Isolate the tooth with a rubber dam.
▸ Remove visible caries.
▸ Remove the coronal pulp with an excavator or bur leaving the
radicular pulp.
▸ Achieve hemostasis.
▸ Moisten small cotton pellets with fomocresol. Blot or wring any
excess liquid from the pellet.
▸ Place the pellets directly on the radicular pulp stumps for 5
minutes. Place a base or a core in the tooth and restore

52
 Where Do We Go From Here?

▸ On the basis of the evidence presented in this seminar, it is

highly unlikely that formocresol, judiciously used, is genotoxic
or immunotoxic or poses a cancer risk to children who
undergo one or more formocresol pulpotomy procedures.

▸ Definitive data to support this hypothesis are lacking,

however, and such evidence is needed before definitive
conclusions can be reached

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▸ It is important to put this discussion into a broader perspective.
Antibiotics are used in dentistry at least as often as
formocresol, and each year numerous children and adults are
injured or die as a result of allergic or anaphylactic reactions to
antibiotics , yet there has been no call for the elimination of
antibiotics from dental practice.

54
▸ In fact, there is an acceptance that an allergic reaction is both
a possibility and a risk in the treatment of dental infection.

▸ Singling out one chemical such as formocresol for elimination

from practice protocols in the face of a complete lack of
human experimental data identifying a clear risk is intellectual
tomfoolery

55
▸ Research has indicated that a minority of pediatric dentists
use dilute formocresol because it is not available
commercially, so perhaps it is time for the manufacturers to
develop and market dilution of this medicament to replace the
“full-strength”

56
 Conclusion
On the basis of the evidence presented in this seminar, the risk
of cancer, mutagenesis or immune sensitization associated with
the proper use of formocresol in pediatric pulp therapy can be
considered inconsequential. Until a biologic and reparative
alternative has been identifed that is clearly Place
andyourreproducibly
screenshot here

superior to formocresol, there are no scientifc or toxicologic

reasons to discontinue its use in pediatric dentistry. When used
judiciously, formocresol is a safe medicament.

57
 TAKE HOME MESSAGE

▸ JUDICIAL USE OF BUCKLEY’S FORMOCRESOL

▸ COTTON PELLET WITH FORMOCRESOL IN THE PULP
CHAMBER FOR LONGER SPAN SHOULD BE AVOIDED
▸ FOR PERMANENT IT SHOULDN’T EXCEED MORE THAN
48 HOURS
▸ FOR PRIMARY 1-5 MINUTES

58
 Thanks!

To that end, a 1:5 dilution of Buckley’s

formocresol is recommended

You can find me at reenachouhan521@gmail.com

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 Refernces

▸J. Todd milledge. Endodontic therapy for primary teeth. In: Ingle’s Endodontics, editors.
Endodontics. 6th ed. Hamilton: BC Deker; 2008.Vol 1, p. 1400-30
▸Chandrashekhar S, Shashidhar J. Formocresol, still a controversial material for pulpotomy: A
critical literature review. J Res Dent 2014;2:114-24
▸Verma P, Chandra A, Yadav R. Endodontic emergencies: Your medication may be the cause. J
Conserv Dent 2009;12:77-9
▸Milnes AR. Is formocresol obsolute? A fresh look at the evidence concerning safety issues. J
Endod 2008;34:S40-6
▸Shulman ER, McIver FT, Burkes EJ Jr. Comparison of electrosurgery and formocresol as
pulpotomy techniques in monkey primary teeth. Pediatr Dent 1987;9:189-94
▸S Goyal, KR Indushekar. Use of formocresol by the Pediatric Dentists across India- A
questionnaire survey. J Evol Med Dent Sci. 2013;2(32):5943–5951.

60