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63]

Review Article

Formocresol, still a controversial

material for pulpotomy: A critical
literature review
Shashidhar Chandrashekhar, Jyothi Shashidhar1
Departments of Conservative and Endodontics, and 1Pedodontics, Modern Dental College and Research Center, Indore, Madhya Pradesh, India

Address for correspondence: Dr. Shashidhar Chandrashekhar, 1663/56, 11th Main Road, Bank Colony, Siddaveerappa Extension, Davangere ‑ 577 004, Karnataka,
India. E‑mail: shashiendo6@gmail.com

ABSTRACT This paper reviews the history, clinical success and concerns regarding the safety of formocresol
as a primary molar pulpotomy medicament. The alternatives to formocresol are discussed and their
advantages and disadvantages are evaluated.

Keywords: Electrosurgical pulpotomy, formocresol, glutaraldehyde, laser surgery

INTRODUCTION success as well as compatibility between pulp and

surrounding tissue physiologically.[5]
If any field in pediatric dentistry is more controversial
than others, it is pediatric endodontics.[1] Pulp tissue is Formocresol
a highly specialized connective tissue necessary for the Formocresol has been used in dentistry since 100 years
immune competence and sensation within a tooth, long and for deciduous teeth pulpotomy since 80  years.
after dentinogenesis is completed.[2] The tissue, located The reparative, biologic approach to pediatric pulp
in a specific rigid environment, has a complex blood therapy is either devitalization approach of formocresol
flow[3] and is rich in cellular and neural elements. It is pulptomy or pulpectomy. Formocresol was introduced
very difficult for clinicians to diagnose the level of pulpal to treat non‑vital permanent teeth in the United States
inflammation.[2] by Buckley in 1904.[1] In 1930, Sweet introduced the
formocresol pulpotomy technique. Formocresol has
This is the reason why pulp therapy in dentistry, subsequently become a popular pulpotomy medicament
particularly the pulpotomy procedure in pediatric for primary teeth. Initially, the technique involved five
dentistry, has remained a controversial issue. The ideal visits. Sweet reduced the number of visits over the
pulp dressing material after pulpotomy should leave years, because of economic and behavior management
radicular pulp vital, healthy and enclosed within an considerations.[1] Doyle et al.[6] used a two‑visit procedure
odontoblastic‑lined dentine chamber,[4] but such material in their comparison study of formocresol and calcium
has not been found till now. An effective pulpotomy hydroxide. Within a few years, Spedding et al.[7] and
medicament should show clinical and radiographic Redig[8] reported the results of a 5‑min formocresol
protocol, and since that time, complete mummification
Access this article online has been abandoned by the profession.
Quick Response Code:
Website: By 1960, a single visit procedure was advocated.[9] Studies
www.jresdent.org
have shown formocresol therapy to have a success rate
between 70% and 90%.[10] Histologic results have been
DOI: variable in contrast to the high clinical success rate.
10.4103/2321-4619.143594 Formocresol is still considered a gold standard by which
all new modalities are compared.[5]

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Composition Internal resorption may also result in teeth treated

The composition of Buckley’s formocresol is 19% with formocresol might be due to the severe damage
formaldehyde and 35% tricresol, 15% glycerin and to the residual tissue, also destroying its capacity to
31% water base.[11] Glycerine is added to prevent the reabsorb. This may be attributed to inflammation of
polymerization of formaldehyde to para‑formaldehyde. the residual pulp. On the other hand, pulpotomy
The presence of para‑formaldehyde causes clouding of treatment with formocresol in monkeys has been
the solution.[5] One‑fifth dilution of Buckley’s formocresol associated with the formation of reparative dentin.[17,18]
can be prepared by adding 30 ml of Buckley’s formocresol, Human studies have not reported the finding of
90 ml of glycerol and 30 ml of water.[11] reparative dentin in association with the formocresol
pulpotomy. [19,20] This might be possibly due to the
MECHANISM OF ACTION production of reparative dentine on light stimulation
like any type of trauma, including formocresol of the
Formocresol acts through the aldehyde group of pulpal tissue of monkeys.[17]
formaldehyde, forming bonds with the side groups of the
amino acids of both the bacterial proteins and those of the PHARMACOKINETICS OF FORMOCRESOL
remaining pulp tissue. It is therefore both a bactericidal
and devitalizing agent. It kills off and converts bacteria In addition to the clinical response, biologic effects
and pulp tissue into inert compounds.[11] Its function of formocresol should also be studied. Formocresol
is to fasten the live pulps, maintaining them inert and is toxic to living tissues because of the formaldehyde
facilitating the conservation of deciduous tooth until component. Formocresol applied to vital pulp tissue
their physiologic fall. It has a potent antibacterial action is absorbed readily into the systemic circulation and
that justifies its use in long curative in endodontic distributed throughout the body.[21] A portion of the
treatment. absorbed formocresol is metabolized and excreted by
the kidney and lungs.[21,22] The remaining formocresol
With formocresol as the pulptomy medicament, a zone is tissue‑bound with the liver, kidney and lungs  the
of fixation usually is evident where the pulp is in direct predominant sites of tissue binding.
contact with the medicament. Coagulation necrosis of
the tissue occurs at the amputation site and is supported
by the fact that true coagulation necrosis is produced
Pharmacokinetics of formaldehyde
Formaldehyde exposure occurs daily as it is
by poisons such as phenol, formaldehyde or mercuric
present in air, water and food. The World Health
chloride, which denatures the protein of the cells.[12] It has
Organization (WHO) has estimated daily consumption of
also been shown that formocresol inactivates the oxidative
enzymes in the pulp tissue adjacent to the amputation formaldehyde to be approximately 1.5-14 mg/day (mean,
site. It may also have some effect on hyaluronidase 7.8 mg/day).[23] Assuming a contribution of 9.4 mg/day
action. Therefore, the protein‑binding properties and the from food, 1 mg/day from inhalation and 0.15 mg/day
inhibition of the enzymes that can break the pulp tissue from water, an adult takes in 10.55 mg of formaldehyde
down together result in ‘fixation’ of the pulp tissue by per day.[24] The estimated formaldehyde dose associated
formocresol and render it inert and resistant to enzymatic with 1 pulpotomy procedure, assuming a 1:5 dilution of
breakdown.[11] Farther away, where the concentration of formocresol placed on a no. 4 cotton pellet that has been
formocresol is decreased, there is a zone of poor cellular squeezed dry, is approximately 0.02-0.10 mg.[25]
definition and necrosis. Apical to this is a zone of chronic
inflammation, which blends into normal tissue.[6,13,14] In Hileman has shown that endogenous levels of
contrast, Berger reported complete loss of vitality with metabolically produced formaldehyde range from
fibrous granulation tissue in the apical third of the root approximately 3-12  ng/g tissue.[26] This formaldehyde
canal.[15] In a study to know the effect of formocresol on is produced by amino acid metabolism, oxidative
polymorphonuclear cells  (PMNs), the lysis of PMNs d e m e t h yl a t i o n , a n d p u r i n e a n d p y r i m i d i n e
was observed with high concentrations of formocresol. metabolism.[27] Exogenous formaldehyde is taken up
An interesting finding with low concentrations of into the human body via ingestion, inhalation and
formocresol was the significant stimulation of PMN dermal exposure. Inhaled formaldehyde appears to
adherence. The authors postulate that stimulation of be readily absorbed by the upper respiratory tract, but
PMNs by pulpotomy medicaments may contribute to the it is not distributed throughout the body because it is
chronic inflammatory changes seen with their use. Initial rapidly metabolized.[28] Ingested formaldehyde is readily
stimulation followed by depressions is a well‑known absorbed by the gastrointestinal tract and exhibits little
response of PMNs following activation by various subacute toxicity after oral exposure.[29] Exogenous
stimuli. Same activation‑deactivation phenomenon was formaldehyde has a biologic half‑life of 1-1.5  minutes
observed clearly with formocresol.[16] and is quickly cleared from human plasma.[30]

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Human cells manage formaldehyde exposure data exist regarding cresol metabolism or elimination in
physiologically through multiple pathways of humans or other mammals, and about environmental
oxidation of formaldehyde to formate. Cytosolic sources of cresol to which humans might be exposed.
alcohol dehydrogenase, mitochondrial aldehyde
dehydrogenase, and glutathione‑dependent and Benzyl alcohol is a by‑product of tricresol oxidation.[38]
glutathione‑independent dehydrogenases are Benzyl alcohol is oxidized rapidly to benzoic acid,
important enzymes in the metabolism of formaldehyde conjugated with glycine in the liver, and excreted as
in hepatocytes, oral mucosa and nasal respiratory hippuric acid. It has no carcinogenic or mutagenic
mucosa.[25] Formate is the principal oxidative product potential, and the allowable daily intake, as established
of formaldehyde. Formate is further oxidized to by WHO is 5 mg/kg.[39,40]
c a r b o n d i o x i d e a n d wa t e r b y t h e a c t i o n o f
formyl‑tetrahydrofolate synthetase.[25] Formate might Concerns about formocresol
be converted to a soluble sodium salt via alternative Concerns about the safety of formocresol have been
pathways and excreted in the urine, or it might appearing in the dental and medical literature for more
be incorporated into biologic macromolecules via than 20  years. Formaldehyde, a primary component
tetrahydrofolate‑dependent, 1‑carbon biosynthetic in formocresol, is a hazardous substance.[31] National
pathways.[25] Single C‑atoms are released during the Institute for Occupational Safety and Health in USA
metabolism of formaldehyde and formate. These states if formaldehyde exposure occurs at a concentration
C‑atoms deposit in 1 C‑atom pool, which in turn is used of 20 ppb  (parts per billion) or higher, it is instantly
in the biosynthesis of purine, pyrimidine and proteins. dangerous to health and life.[41]

Histological studies demonstrate the true biological Studies on formocresol therapy have put the clinical
damage after formocresol treatment. Physiologically, success rate between 70% and 90%. [5] But variable
with the vascular damage, the balance between osmotic histologic results were also reported in contrast to the
pressure and hydrostatic pressure is disrupted in tissue. clinical success rate. Instead of preserving vital pulpal
As a result, there is absorption of inflammatory fluid tissue, chronic inflammation and necrotic tissue were
insult by pulp tissue and decrease in the osmotic pressure. found.[5,14] Another problem with formocresol is its
So hemostatic balance is re‑established.[31‑33] When this systemic distribution from the pulpotomy site. Pruhs
occurs, the constricted pulp cavity must dissipate the et al. found a relationship between primary teeth
pressure changes. If this does not occur, pressure necrosis treated with formocresol and enamel defects in the
of the pulp occurs. In addition, lymphatic and venous permanent successors. The allergenic and mutagenic
vascular flow from the coronal pulp must dissipate this properties of formaldehyde have been demonstrated
excess inflammatory fluid. This excess is distributed in animal models, but not in humans. Cysts have also
apically and to regional vascular vessels. Therefore, the been found to be associated with the pulpotomized
local insult results in systemic distribution. teeth.[5]

Studies report that formaldehyde labeled with radioactive The study suggests that full strength formocresol (48.5%
carbon  (14C) was apparently distributed among the of formaldehyde) absorbed from multiple pulpotomy
muscle, liver, kidney, heart, spleen and lungs. The sites may initiate tissue injury in kidney and liver
quantities of radiolabeled chemical detected, however, of experimental animals. The author suggests that a
were very small (1% of the total administered dose).[22,34] longitudinal study is needed to determine whether the
Myers et al.[21] and Pashley et al.[35] concluded that [14C] injured kidney and liver cells would recover as there is
formaldehyde is absorbed systemically from pulpotomy only cell injury, and no evidence of onset of inflammatory
sites and formaldehyde is distributed to distant sites, but reaction. This study cannot make any direct clinical
did not determine if the labeling of tissues occurred by implications regarding toxicity of formocresol.[22]
metabolic incorporation of the [14C] moiety of the labeled
formaldehyde into macromolecules. Mutagenicity, genotoxicity and cytotoxicity
Exposure of cells to formaldehyde leads to the formation
Pharmacokinetics of cresol of DPX (DNA-protein cross‑links). The most common
The second active ingredient in formocresol, cresol, has types of DNA damage induced by formaldehyde
received little attention in investigations of formocresol are clastogenic lesions, including sister chromatid
efficacy. Cresol has poor solubility, so it is assumed that exchanges  (SCEs), micronuclei and chromosomal
it does not enter systemic circulation.[36] Cresol is highly aberrations, and deletions. It has been proposed that
lipophilic and has been shown to completely destroy formaldehyde could induce the development of DPX
cellular integrity. This would allow deeper tissue fixation at distant sites, but no convincing evidence has been
by the formaldehyde component of formocresol.[36,37] No obtained from in vivo experimental studies.[24]

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The recent research by Heck and Casanova showed Carcinogenicity

the development of DPX in nasal tissues and It is concluded that cancer develops after inhalation
upper respiratory tract associated with high dose of air with large concentrations of formaldehyde. The
exposure of formaldhehyde.[42] DPX does not persist cancer can occur after a long‑term direct contact with
in tissues for more than few hours and undergoes susceptible tissues. The toxic effects on initial contact
spontaneous hydrolysis or active repair by proteolytic sites like ulceration, hyperplasia and squamous
degradation of cross‑linked proteins. So role of DPX metaplasia may subsequently contribute to cancer.[50]
in formaldehyde‑induced carcinogenesis is again These high‑dose responses are unlikely to occur at
questionable.[43] sites distant from the point of initial formaldehyde
contact (such as the bone marrow). Formaldehyde is
Cytogenetic studies of lymphocytes from rodents not delivered to these distant sites. Those who have
following formaldehyde inhalation with exposures argued against the continued use of formocresol in
ranging from 0.5-1.5 ppm for 6 h/day for 5 days failed pediatric dentistry on the basis that “formaldehyde
to detect either chromosomal aberrations or SCEs at any causes cancer” have failed to recognize this very
of the formaldehyde concentrations.[44] important distinction.[25]

In vitro experiments with a Chinese hamster cell line Health Canada and the Organization for Economic
found that DPX and SCE, as a result of formaldehyde Cooperation and Development have stated on the basis
exposure, were associated with cytotoxicity, not of CIIT (Chemical Industry Institute for Toxicology
mutation.[45] In addition, no mutagenesis occurred in Centers for Health Research) research models that
cultured human lymphocytes below a formaldehyde “taking into account the extensive information on
threshold of 5 µg/mL in the culture medium.[46] its mode of action, formaldehyde is not likely to be
a potent carcinogen to humans under low exposure
In one of the dental studies that do not support conditions.”[51]
formaldehyde is a mutagenic, Zarzar et al. performed
formocresol pulpotomy on 20 children by using Two large American studies from National Cancer
Buckley’s original formula. Blood samples were Institute (NCI) of epidemiological investigations failed
collected from each child immediately before and 24 to show any causal relationship between formaldehyde
hours after the pulpotomy. No statistically significant and leukemia.[52,53]
differences were found between the two groups in
terms of chromosomal aberrations, chromatid breaks In 2004, International Agency for Research on
or chromatid gaps. Also, Zarzar et al. concluded that Cancer  (IARC) reclassified formaldehyde as a known
formocresol is not mutagenic.[47] carcinogen from human probable carcinogen,[54] but
according to them, it is an agent that can increase the
Ribeiro et al. reported two studies that assessed the risk of cancer at some doses. They do not undertake
mutagenic potential of formocresol. With a mouse the dose response analyses and possible threshold. The
lymphoma cell line, cultured human fibroblasts and a possibility that inhaled or ingested formaldehyde might
series of formocresol dilutions similar to clinical doses, induce cancer at sites distant from the respiratory or
these authors found that formocresol did not produce gastrointestinal tracts has been investigated in numerous
detectable DNA damage and should not be considered long‑term toxicity studies performed in rodents. [49]
genotoxic.[48] Experimental and epidemiologic research do not support
the theory that inhaled or ingested formaldehyde might
The investigations of root canal sealers that contain induce distant site toxicity.[25]
formaldehyde and produce cytotoxicity are not
comparable with formocresol pulpotomy studies. The facts are that formaldehyde occurs naturally
Because large quantities of formaldehyde are produced throughout the body, there are multiple pathways
from sealers than pulpotomy, large quantities of sealers for detoxification, and only microgram quantities
are used. Root canal sealer remains in root canal and of formaldehyde are applied to pulp tissues during
forms part of restoration and may lead to further release pulpotomy procedures for mere minutes. Considering
of formaldehyde.[49] these facts, exposure of children to the formaldehyde
component of formocresol during a pulpotomy is
It is summarized that DPX development demonstrated insignificant and inconsequential.
only after a prolonged exposure to formaldehyde at
specific contact sites such as nasopharynx. A  minute Immune sensitization
quantity used in pulpotomy for few minutes that will Pulpotomy in dogs demonstrated that histological
produce distant site genotoxicity is not evidence‑based.[25] changes where foreign pulp protein is present, host’s

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necrotic tissues were produced by pulp tissue on reaction effects of formocresol and glutaraldehyde pulpotomies
with formocresol. The B cells may produce antibodies in various exposed vital human primary molars.[65] The
to foreign pulp protein and host necrotic tissue. 2% glutaraldehyde compound was promising when
Further, non‑specific pro‑inflammatory mediators and compared to ferric sulfate and formocresol in an in vivo
chemotactic cytokines can illicit further immune factor study. The only limitations of glutaraldehyde are
responses. One response is osteogenic activating factor instability due to short shelf‑life and it has to be freshly
that destroys bone. This has not been quantified in either prepared. In this study, the clinical and radiographic
children or adults.[55] success of formocresol, glutaraldehyde and ferric
sulfate were compared as a pulpotomy medicament in
Experiment on dogs showed that formocresol produces primary molars at 3‑month intervals over 1 year. Internal
antigenic activity in pulp tissue.[56] Rolling and Thulin resorption was found in all the medicaments. Clinical
found no increase in either immune response or success was higher than the radiological success.[66]
allergic reactions in 128 children who had undergone
formocresol pulpotomy.[57] A Canadian study of urea One study failed to justify recommendation of 2%
formaldehyde foam insulation from products in the buffered glutaraldehyde solution as a substitute to
homes of asthmatic subjects found that its long‑term formocresol as failure was observed within 6  months
exposure had no effect on immunologic responses.[58] of treatment and failure rate was increased even after
Doi et al. found that there is no clinical relevance of and up to 25 months. Internal resorption and external
formaldehyde‑specific immunoglobulin E. Hence, the resorption were listed as failures. Resorption rate of
suggestion that formocresol “sensitizes” children has pulpotomized teeth was similar to that of other teeth.[67]
not been supported.[59]
Long‑term (36  months) success rates of four different
Comparing formocresol with other materials glutaraldehyde preparations  (2%‑buffered and
Formocresol versus glutaraldehyde unbuffered, 5%‑buffered and unbuffered) as a pulpotomy
In recent years, glutaraldehyde has been proposed as an agent in pulp exposed primary molars were evaluated.
alternative to formocresol based on its superior fixative The 5% buffered solution group showed highest success
properties, self‑limiting penetration, low antigenicity, rate, whereas 5% unbuffered solution showed the lowest,
low toxicity and elimination of cresol.[1] It is a colorless but as such there was no significant difference found
solution that has a mild odor and a boiling point of 183°C among the four groups. The canal obliteration was noted
to 187°C, is soluble in water, and produces mild acidity in 22 treated teeth. The relative high failure rate in this
on contamination.[9] Glutaraldehyde is a chemically long‑term follow‑up indicates that clinicians should be
bifunctional reagent, which forms strong intra‑  and cautious before extensively using glutaraldehyde as
intermolecular protein bonds, leading to superior pulpotomy agent.[68]
fixation by cross‑linkage.[9] Glutaraldehyde produces a
zone of tissue fixation where it is in direct contact with FORMOCRESOL VERSUS
the pulp, while apical to this is a zone of normal tissue ELECTROSURGICAL PULPOTOMY
with few inflammatory cells.[60,61] It has been observed
that inadequate fixation leaves a deficient barrier to Another form of non‑chemical devitalization developed
sub‑base irritation, resulting in internal resorption.[62,63] is electrosurgical pulpotomy.[69] It is a method of cutting
Penetration into the surrounding peri‑apical tissue is and coagulating soft tissues by means of high‑frequency
limited primarily by protein cross‑linkage formation. radio waves passing through the tissue cells. The
Thus, systemic distribution of glutaraldehyde is advantages of electrosurgical pulpotomy are similar.[70]
limited.[64] Glutaraldehyde is less necrotic, dystrophic, The self‑limiting, pulpal penetration is only a few cell
cytotoxic and antigenic, is a better bactericide, and fixes layers deep. There is good visualization and homeostasis
the tissue instantly.[9] without chemical coagulation or systemic involvement.
It is less time‑consuming than the formocresol approach.
Glutaraldehyde appears to produce tissue fixation Electrocautery carbonizes and heat denatures pulp and
without causing tissue necrosis at high concentrations. bacterial contamination. It may not be suitable if apical
Although it depresses PMN adherence at intermediate root resorption has occurred.[71] Remarkably, Mack
concentrations, it does not seem to stimulate PMN and Dean[70] reported a very high success rate with the
adherence and cause inflammatory tissue damage at technique.
low concentrations.[16]
Studies show that there is no significant difference
Prakash et al. concluded that glutaraldehyde is better between clinical and radiographic success rates for
fixative and less toxic agent than formocresol. In this electrosurgical and formocresol pulpotomies.[72,73] But
study, they compared the clinical and radiological electrosurgery is considered as sensitive technique.[74]

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Oztas et al. reported that formocresol pulpotomy technique laser treatment was at least as effective in minimizing
is histopathologically superior to electrosurgery post‑treatment inflammation as the formocresol
pulpotomy technique, as they found presence of treatment. Second, there was no statistically significant
inflammation, fibrosis, necrosis and resorption. recovery from inflammation between the 28‑ and 90‑day
[74]
On the other hand, El‑Meligy et al. showed that observation period in either the laser or formocresol
teeth treated by electrosurgery pulpotomy exhibited group. Third, there was a strong and statistically
less histopathological reaction than formocresol significant inverse correlation between the energy used
pulpotomy.[20] during the respective laser pulpotomies and the degree
of inflammation observed at 28 days.[76]
Electrosurgery pulpotomy with either mechanical
coronal pulp removal or electrical coronal pulp The histological response of dental pulp after different
removal induces formation of reparative dentin. This types of laser irradiation was evaluated in some studies.
is in the form of bridging at the pulpal amputation The results revealed that laser irradiation caused
sites or along the canal walls. It indicates the present carbonization, necrosis and infiltration of inflammation
healthy vital pulp efforts to heal the area of insult.[17,74] cells, edema and hemorrhage in the pulp tissue.[77,78]
This technique also increases the fibroblastic activity
at the middle and apical portions of roots with early The pulp can predictably heal itself when the temperature
resorption,[17,74] as pulp tissue tries to renew itself with does not raise more than 5.5oC above physiological
proliferation of fibroblasts. baseline. The higher energy created a thicker char layer
over the remaining pulp, which in some way had a
On the basis of the use of electrosurgical current favorable effect in reducing the initial inflammatory
intensity, there is a chance of peri‑apical or furcal response in residual pulp.[79]
involvement. Ruemping et al. used low intensity
current for electrosurgical pulpotomy during Laser irradiation was effective for the growth of fibroblast
their research so there was no peri‑apical or furcal and induced suppressive effects for macrophage. In
involvement.[18] addition, effects of laser irradiation on vital pulpotomy
were investigated. It was observed that laser irradiation
In case of electrosurgery, internal resorption was noted induced enhancement of calcification in wound surface
after 4  weeks. This is due to the excess amount of and stimulated formation of calcified tissue. These
lateral heat that can accumulate, causing necrosis and observations indicate that laser irradiation is a useful
resorption. Heat transfer through accessory canals on method for vital pulpotomy.[80]
pulpal chamber floor of molars was responsible for
internal resorption. Later, intense inflammatory cells FORMOCRESOL VERSUS FERRIC SULFATE
were observed at coronal third of pulp canals and
complete healing cannot be achieved in the absence of Monsel’s solution, which is a 20% ferric sub‑sulfate, is
dentinal bridges.[20] widely used as a strong styptic agent in skin and mucosal
biopsies.[66] Ferric sulfate is a non‑aldehyde chemical.
FORMOCRESOL VERSUS LASER SURGERY It controls the pulpal hemorrhage and thus prevents
the problems encountered due to clot formation and
The carbon dioxide laser has wide applications in oral minimizes the inflammation and internal resorption.
and general surgery procedures involving soft tissue.[75] Shaw et al. (   1987) also found reversible damage to the
The laser emits an infrared beam at a wavelength of connective tissue adjacent to the sulcular gingiva after
10.6  m, has an affinity for water, and is capable of application of ferric sulfate. In contact with the blood,
producing well‑localized cautery to soft tissue. Tissue ferric ions form a ferric complex and the membrane of
is removed by ablation through conversion of the laser this complex seals the cut blood vessels mechanically
beam to heat.[76] Based on these characteristics the carbon and provides hemostasis and an agglutinated protein
dioxide laser appears to have promise as an alternative complex, which produces a blood clot that occludes the
for pulpotomy therapy. capillary orifices. The hemostatic properties of ferric
sulfate and the favorable pulpal response make it a
A study conducted to evaluate the response of the promising medicament for pulpotomy.[5]
human primary pulp to the carbon dioxide laser and
formocresol for vital pulp therapy showed that there A clinical research was done by Fie et al. to compare
were no significant differences between the formocresol the clinical and radiographic success of ferric sulfate
and laser groups with respect to symptomatic, clinical and formocresol as pulpotomy medicaments. They
or radiographic findings. The histologic observations in demonstrated that ferric sulfate was clinically and
this study revealed three interesting effects. First, the radiographically successful as a pulpotomy medicament

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Chandrashekhar and Shashidhar: Formocresol‑A review

in primary teeth. At the one‑year recall, the success rate and the effect of ferric sulfate is unclear apart from
of the ferric sulfate group was actually greater than that hemostatic properties.
of the traditional formocresol pulpotomy group. In this
study, samples were small and recall period was short. This study suggested that the primary teeth appear to be
Although the ferric sulfate technique appeared successful clinically functional and not associated with radiographic
histologically, the long‑term effect of this drug on the changes even though pathological changes can be
teeth and the rest of the body was not addressed.[5] seen histologically. Both ferric sulfate and formocresol
pulpotomies produce favorable clinical results in human
In this study, they used zinc oxide eugenol as a base primary teeth, which is clear from clinical studies.[5,86,87]
material over treated pulp stumps but it is not an ideal The highest clinical and radiographic success rate (100%)
choice as eugenol may irritate the underlying pulpal of ferric sulfate was reported by Prabhu and Munshi.[88]
tissue. Since formocresol is said to “mummify” or fix Another short‑term  (20  months) study showed 100%
the pulpal tissue in root canals, pulp tissue under this clinical and 97.2% radiographic success rate for both
agent may not be affected by the zinc oxide eugenol. ferric sulfate and formocresol.[89]
Garcia‑Godoy et al. found less severe inflammation when
zinc oxide eugenol was placed on formocresol‑treated There is a study comparing the effects of ferric sulfate
pulps.[81] Ferric sulfate may function passively. Since and full strength formocresol as pulpotomy agents in
ferric sulfate is not a fixative agent, the base in direct primary human molars in a long‑term (4 years) follow‑up
contact with the pulpal surface may play an important clinical trial, which assessed the succedaneous premolar
role in the healing process. Bases that are inert may teeth for any decalcification, abnormal morphology or
stimulate pulp cell attachment and provide more rapid any other defects as well. They found overall success rate
and less inflammatory wound healing.[82] The possible of ferric sulfate was almost similar to formocresol and
combination of ferric sulfate with different base materials no delay in eruption of premolars and abnormality were
is certainly worthy of further investigation. observed. So the authors concluded that ferric sulfate is
a nontoxic agent to replace formocresol.[90]
In case of chronic coronal pulpitis, even though tooth is
a good candidate for pulpotomy clinically, inflammation It has been stated that success rates may be more
extension makes it questionable for the procedure. At that dependent upon the correct choice of teeth, assessment
time, formocresol because of its property of mummifying of bleeding from amputated pulp stumps and adequate
the remaining pulpal tissue makes the tooth to retain it coronal seal as a candidate for vital pulpotomies than
for a longer time. Ferric sulfate is nonfixative but has on other factors. Inconsistencies of technique and
bacteriostatic properties and may not act on underlying microleakage of the restorative material (IRM) may also
inflammatory tissue. Thus, it may not be beneficial in limit the success of pulpotomy.
similar situation.[83]
In most of the studies, zinc oxide eugenol is used as
Additional histologic studies are needed to determine a sub‑base. Zinc oxide is in direct contact with pulpal
pulpal response to this material. Studies should tissue, which may cause chronic inflammation and
determine the potential effects on underlying permanent necrosis. This may lead to internal resorption. Hume
teeth and the nature of any absorption and systemic stated that formocresol would fix tissue that may act as a
distribution of ferric sulfate from pulpal tissues.[5] barrier to the eugenol, but with ferric sulfate the clot is the
only entity separating the eugenol from vital tissues.[91]
Jones and Duggal compared the pulpal reactions to
ferric sulfate and formocresol pulpotomies in primary Some authors have stated that formocresol pulpotomies
molars with inflamed pulps of baboons. This study has could be considered clinically successful therapies,
shown that both pulpotomy agents produced apparently as they preserve extremely carious primary molars
successful vital pulpotomies, but both were associated until their normal exfoliation.[91,92] The main objective
with pulp necrosis and apical abscesses at a histological of pulpotomies must be to maintain the vitality of the
level. No literature has given specific guidelines for majority of the radicular pulp. The authors who advocate
histological success after pulpotomy.[84] pulpotomies should be to keep the pulp of primary teeth
vital until their normal physiological resorption, rather
Ideally, healing in primary pulp should be good. The than just “maintaining” teeth.[93]
pulps of primary teeth are known to be quite resilient
and are cell rich and fiber poor.[85] The most important Formocresol versus calcium hydroxide
part of healing of an exposed pulp is formation of a Calcium hydroxide was the first agent used in
dentinal bridge. Such finding is rare in the above study pulpotomies that demonstrated any capacity to
as formocresol destroys those cells that produce healing, induce regeneration of dentin. [94] The high pH of

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Chandrashekhar and Shashidhar: Formocresol‑A review

calcium hydroxide wounds the pulp in a manner Formocresol versus mineral trioxide
that permits the intrinsic reparative cascade to begin. aggregate
Unfortunately, the stimulus evoked by this compound Mineral trioxide aggregate (MTA) is a fine hydrophilic
is delicately balanced between one of repair and powder developed by Mahmoud Torabinejad in Loma
resorption. The study by Magnusson demonstrated Linda University. It consists of tricalcium silicate,
how often the balance is tilted toward the destructive tricalcium aluminate, tricalcium oxide, silicate oxide and
pathway.[95] bismuth oxide.[100] The US Food and Drug Administration
approved MTA in 1998 as a therapeutic endodontic
Schröder emphasized on the importance of avoiding material for humans.[101]
a blood clot between the amputation site and calcium
hydroxide for clinical success.[96] Calcium hydroxide Torabinejad et al., Bates et al. and Fischer et al. evaluated
adequately controls pulpal hemorrhage, to permit the sealing ability of MTA in root canals.[101] MTA is
good contact between medicament and pulpal tissue. currently being used in pulp therapy and has been
This seems to be important in the prevention of internal shown to provide an enhanced seal over the vital pulp
resorption, post‑pulpotomy.[97] and is nonresorbable. Furthermore, MTA has superior
biocompatibility and is less cytotoxic than other materials
A study conducted to compare the clinical and currently used in pulp therapy.
radiological outcomes following single‑visit vital pulp
therapy techniques, using two different materials, Previous studies showed that MTA stimulated the
formocresol and calcium hydroxide in cariously exposed release of cytokines and production of interleukin
primary molar teeth. This investigation confirms the and induced hard tissue formation. Schmitt et al.
clinical efficacy of a one‑fifth dilution of Buckley’s reported that Tulsa Dental provides MTA as ProRoot.
formocresol as an agent in pulp treatment of cariously The material can be placed in the tooth with the Tulsa
exposed, vital primary molar teeth. However, calcium carrier, an amalgam carrier, Messing gun or a hand
hydroxide in its pure, powder form is a clinically instrument.[101] Advantage of MTA is that it needed less
acceptable alternative when combined with strict time for procedures.[102] Some of the main disadvantages
selection criteria for this method of restorative care. There are discoloration,[103] costs and accessibility, which
was a statistically insignificant difference in successful may block worldwide distribution of MTA where
clinical and radiological outcome between the two formocresol is relatively inexpensive and have global
treatment groups.[98] accessibility. MTA has also shown to revascularize and
promote dentin‑like tissue formation in several clinical
situations.[63‑65]
The status of radicular pulp tissue may have more
bearing upon the clinical outcome following calcium
A study comparing three pulpotomy agents in preschool
hydroxide pulp therapy, since this agent relies on the
children suggested MTA success rates were less than
tissue itself being able to recover sufficiently to heal, with
100%. Success rates of 100% can be attributed to smaller
or without the formation of a calcific barrier. Therefore,
sample size or wider range of patients (5-12 years), which
calcium hydroxide may be more technique sensitive
can reduce validity and reliability of results. Younger
than formocresol. The inflammatory status of radicular patients showed high radiographic failure rates after 12
pulp tissue at the time of treatment, providing effective months such as external resorption. This is due to wider
coronal seal, is thought to be important to a successful pulp canals in younger teeth, which can facilitate the
outcome. transfer of stimulatory factors.[100]

Markovic et al. reported the presence of a dentine A histological study to know the effects of gray
bridge above the pulp amputation site radiographically and white MTA on amputated pulp tissue, along
in 47% of pulpotomized teeth using calcium with formocresol as a gold standard suggests that it
hydroxide. [99] Heilig et al. was performed calcium preserves and regenerates both hard and soft tissues.
hydroxide pulpotomy in 17 carious primary molars The nearly normal pulp architecture was found to
using alternative method of hemorrhage control be intact and continuous odontoblastic layer was
i.e., aluminum chloride. This study suggests that the seen. While cases treated with white MTA showed
aluminum chloride‑calcium hydroxide pulpotomy dentine bridge formation along with inflammatory
may be a viable alternative to formocresol pulpotomies cells and areas of partial necrosis, more clinical and
in the primary dentition. Although these findings radiographic failures were seen with white MTA. The
encourage continued research, including a long‑term minor difference in composition between gray and
follow‑up, a histologic study is indicated.[97] white groups accounts for the differences in pulpotomy

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Chandrashekhar and Shashidhar: Formocresol‑A review

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