Formocresol was first introduced by Buckley as a treatment of non-vital permanent teeth in 1904 [6, 8] and consisted of equal parts of formalin and cresol. It was not until 1930, however, that formocresol was introduced as a pulpotomy medicament for non-vital primary teeth with the formulation of 19 % formaldehyde and 35 % cresol in a vehicle of glycerin or water [7, 9].

A multistep process of four visits was proposed for mummifying the radicular pulp tissue completely, thereby eliminating the likelihood of internal resorption [7]. Microscopic analysis by Emmerson et al. showed that most of the beneficial effects of formocresol was in the first 5 min; moreover, they showed that prolonged exposure caused calcific degeneration [10]. Thus, the original four-visit technique was revised to the currently accepted one-visit, 5-min-application, as introduced by Redig in 1968 [11].

Although this method of application saved time, it rendered the pulp tissue only partially vital leaving the tissue susceptible to abscess formation and/or internal root resorption [11]. In 1971, Loos and Han evaluated the effects of different concentrations of formocresol and found that a 1:5 dilution was as effective as the full strength [12].

Rolling and Lambjerg-Hansen studied histologically teeth that had been successfully treated with formocresol and observed that the remaining radicular pulps had severe inflammation adjacent to the amputation site, and most had areas of necrosis within the remaining pulp tissue without evidence of pulp fixation [13]. From these observations, the authors concluded that the formocresol option should be reserved as a means to keep the affected primary teeth functioning for a limited period of time. Regardless of this outcome, it has been the benchmark against which all other pulpotomy medicaments are measured.

Numerous studies have been conducted since the 1930s and have found success rates varying from 55 to 95 % [7]. These rates vary based on the type of study, criteria for success, and the follow-up period.

Over the years, formocresol has been labeled as being mutagenic, toxic, and carcinogenic [14–16]. However, little to no evidence actually exists to implicate formocresol in any of these allegations [17]. Regardless, the gavel has been swung, the verdict has been delivered, and formocresol as a pulpotomy medicament is becoming less popular. To further compound the issue, the International Agency for Research on Cancer classified formaldehyde as carcinogenic for humans in June 2004 [50]. With this new classification, the need to assess new materials to replace the long-standing formocresol has become crucial.

Glutaraldehyde is a colorless, oily liquid that is used as an antimicrobial agent in water treatment lines, a preservative in cosmetics, and as a cold sterilizing material in the healthcare industry (http://​www.​cdc.​gov/​niosh/​topics/​glutaraldehyde/​).

Glutaraldehyde is a di-aldehyde that has superior fixative properties over formocresol and has self-limiting penetration, low antigenicity, low toxicity, and eliminates cresol. Glutaraldehyde has no bactericidal ability at low pH and therefore must be alkalinized to a pH of between 7.5 and 8.5 before it is effective. This increase in pH renders glutaraldehyde unstable, thus decreasing its shelf life to approximately 14 days [18]. Some formulations increase the life of this product to 1 or 2 weeks [18].

s-Gravenmade [19] proposed glutaraldehyde as an alternative to formocresol in endodontic procedures in 1975. He observed that, unlike formocresol, glutaraldehyde did not diffuse laterally or apically through the root length, making it a safer alternative to formocresol.

In 1980, Kopel et al. introduced glutaraldehyde into primary tooth pulpotomies as an attempt to find a material that was less toxic than formocresol, was self-limiting, and preserved the radicular pulp [20]. The authors used a 2 % glutaraldehyde solution over the amputated pulp stumps and then incorporated a drop of glutaraldehyde into the ZOE paste which was placed in the pulp chamber. Garcia-Godoy et al. used a 2 % formulation with similar findings [21]. The clinical and histological findings of both these studies prompted the proposal that glutaraldehyde was a viable alternative to formocresol as a pulpotomy medicament for primary teeth. The results of a study by Fuks et al. were not so promising and perhaps slowed down the impact that glutaraldehyde was gaining [22, 23].

Histologically, glutaraldehyde is a better fixative at higher concentrations and longer exposure times than formocresol, yet demonstrates less penetration into the subsurfaces, leading to less formation of zones of necrosis and granulation tissue [24]. Lloyd et al. studied various concentrations of glutaraldehyde over differing times in primates and found that the effectiveness of glutaraldehyde was inversely proportional to both the concentration and length of the exposure. The lower the concentration, the longer the glutaraldehyde needed to be in contact with the remaining radicular pulp for effectiveness to be maintained. Their results showed a concentration of 2 % with an exposure time of 10 min to have the most favorable success over time [25].

Several human studies have shown success rates ranging from 82 to 95 % [7], yet, perhaps due to its instability and short life span, glutaraldehyde has not gained the popularity that other materials in this category have.

Ferric sulfate is an agglutinating agent thought to produce hemostasis by blood reaction with both the ferric and sulfate ions as well as with the acidic pH of the solution [26]. The hemostasis achieved by this agglutination is thought to reduce the likelihood of clot breakdown and subsequent inflammatory response [27].

It has been shown that the application of ferric sulfate prior to calcium hydroxide in pulpotomized primate teeth had more favorable results than calcium hydroxide alone [28