Collaborative Study by Anesthesia and Dentistry Confirms Routine Use of Formocresol in Pediatric Dentistry
from Practice Update, Winter 2007
Introduction and Background
Some concern has been expressed in the last 25 years regarding the use of formocresol for vital pulpotomy treatment of primary molars due primarily to its mutagenic, carcinogenic and toxic potential when used in high concentrations and under specific conditions. Studies demonstrated that high systemic doses (0.0285mg/kg of formaldehyde, which is approximately 500 times the expected dose from one pulpotomy in a 10 kg test subject) administered intravenously to dogs can lead to liver, kidney and cardiac pathology. Despite the controversy, formocresol continues to be the standard of care primarily because of its high clinical success rate in vital pulpotomies and failure to show any systemic effects when used in much lower concentrations in humans.
The two active ingredients in formocresol are formaldehyde and cresol. Most formaldehyde exists in a bound (unavailable) form in many common sources, including soap products, food preservatives, building products and automobile exhaust. Formaldehyde that enters the body is rapidly metabolized (half life: one to 1.5 minutes). Metabolites of formaldehyde are incorporated into macromolecules via one-carbon pathways or are eliminated in the expired air and urine. Of primary concern is the belief that formaldehyde that escapes metabolism can react with macromolecules, in particular form DNA-protein cross links, and thereby cause mutations.
Cresol, the second active ingredient in formocresol, has received little attention in biological circles, probably because it has no other dental or medical applications. No data currently exist regarding the metabolism of cresol, environmental sources of cresol, or the mean plasma concentration of cresol in the pediatric or adult population.
Study Purpose: To determine the existence, if any, and time-based plasma concentration of formocresol in children undergoing comprehensive oral rehabilitation involving pulp therapy under general anesthesia.
Method
The study sample consisted of 30 children from two years to 6.4 years. A total of 85 pulpotomies were performed. The number of pulpotomies performed ranged from one to five with the mean number of pulpotomies being four. Patients were categorized as receiving a high dose of formocresol (four or more pulpotomies) or low dose (three or less pulpotomies). Nine children treated fell into the high dose pulpotomy group and 21 children fell into the low dose group. Although the potential to perform 20 primary tooth pulpotomies under general anesthesia exists, this number of pulpotomies is uncommon.
Pulpotomies were performed on primary teeth. After pulpal access and coronal pulp extirpation, hemostasis was achieved by placing a sterile dry cotton pellet in the pulp chamber for one to five minutes. The radicular pulp stumps were then treated with two previously prepared sterile pellets that had been placed in formocresol solution. The pellets were removed after five minutes and the pulp chamber was sealed and the tooth restored.
Up to 12 timed blood samples were obtained. A preoperative blood sample was taken. Once treatment was initiated, further sampling was performed after the first formocresol pulpotomy had been completed at 30 minute intervals until the last pulpotomy was complete. After completion of the final pulpotomy, samples were taken at five, 15, 30, 60, 90 and 120 minutes. A final sample was taken immediately prior to patient discharge. Collected samples were then analyzed for formaldehyde and cresol levels using a specific and validated gas chromatography method with mass spectrometry detection.
Analysis and Conclusion
A total of 312 blood samples were collected for the study. Analysis revealed that formaldehyde and cresol were undetectable in all samples.
The absence of free formaldehyde in all blood samples collected in the study corroborates previous studies that demonstrated that the formaldehyde upon exiting the pulpotomy site is rapidly metabolized to formate and enters one carbon metabolism. As such it presents little or no risk to the subjects. Cresol was also undetectable in all of the blood samples collected in the study.
A coincidental detection of benzyl alcohol (a byproduct of tricresol oxidation) in samples taken after vital pulpotomy treatment suggests that the potential exists for cresol to enter systemic circulation. However, free cresol is undetectable in all of the samples and the level of benzyl alcohol present is far below the FDA allowable daily allowance. Based on the results presented in the study, it is highly unlikely that formocresol, used in the doses typically employed for the vital pulpotomy procedure, poses any risk to children.
The study was supported by grant M01 RR00069, General Clinical Research Centers Program, National Centers for Research Resources, NIH. For additional information about this study, contact Jeffrey Galinkin, MD, at 303-861-6226.
