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Topical Fluoride Therapy: Discussion of Some Aspects of Toxicology, Safety, and Efficacy
E. Newbrun J DENT RES 1987 66: 1084 DOI: 10.1177/00220345870660052001 The online version of this article can be found at: http://jdr.sagepub.com/content/66/5/1084

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Topical Fluoride Therapy: Discussion of Some Aspects of Toxicology, Safety, and Efficacy
E. NEWBRUN
Department of Stomatology, University of California, San Francisco, San Francisco, California 94143-0512

Although ingestion of an acute toxic dose offluoride is extremely rare in dental treatments, practitioners should be familiar with the signs and symptoms and with emergency measures of treating accidental overdosage. The amount offluoride ingested chronically from the use of self-applied topical fluoride can be reduced to safe limits by instructing parents to dispense small amounts of toothpaste for their young children and to ensure thatfluoride dentifrices and mouthrinses are fully expectorated. Similarly, when custom-fitted trays are used, only minimal amounts of fluoride gels are necessary. The minimal amount of such gels that can be dispensed appears to be influenced by their viscosity. Clinical efficacy does not support a reduction in the concentration offluoride in commercial dentifrices.

Blood chemistry:

Acidosis, hypocalcemia, and hypomagnesemia.

J Dent Res 66(5):1084-1086, May, 1987

The symposium speakers have carefully reviewed the amounts of fluoride used in topical therapy, and the absorption, deposition, and excretion of that portion of the fluoride that is ingested from such topical therapy. I wish very briefly to amplify some aspects of these presentations.

The treatment for acute fluoride toxicity depends in part upon the dosage. If fewer than 5.0 mg/kg have been ingested, oral administration of calcium in the form of milk or lime water may suffice. However, higher dosages require prompt hospitalization and, in the absence of vomiting, gastric lavage. In addition, cardiac monitoring should begin, and preparations should be made for endotracheal intubation to assist respiration and for direct current cardioversion, if necessary. Blood samples need to be monitored for calcium, magnesium, potassium, and pH. Intravenous infusion, as needed, of fluids to restore blood volume and of calcium gluconate and magnesium to restore calcium and magnesium levels to normal ranges should be instituted. Alkaline diuresis can speed the excretion of fluoride.

Chronic fluoride ingestion.

Chronic ingestion of fluoride in greater-than-optimal amounts as a consequence of self-application of topical fluoride, be it in the form of dentifrice, mouthrinse, or topical gel, is a real possibility in very young children but does not appear to present any problems for adults at high risk of caries who require self-application of topical fluoride agents. That increased ingestion of fluoride occurs after topical fluoride application is well-substantiated (Baxter, 1980; Birkeland, 1973; Einwag, 1983a, b; Ekstrand and Koch, 1980; Glass et al., 1975; Ekstrand et al., 1983; LeCompte and Doyle, 1982; Owen et al., 1979; Wei and Kanellis, 1983). Unfortunately, as pointed out by Goldhaber (1985), there seems to be a "fluorosis bandwagon" in the dental research community. However, the data documenting increased dental fluorosis in children as a result of ingestion of fluoride from topical agents are weak, mostly anecdotal (Leverett, 1982) and do not warrant alarm. It should be emphasized that this reported increase in fluorosis is mostly of the very mild or mild type, and does not constitute an esthetic or health problem. Furthermore, a survey of several fluoridated communities in Illinois found little evidence of a change in the prevalence of dental fluorosis during the past 40 years (Horowitz et al., 1984).

Acute toxicity.
There is no question that fluoride taken in high enough amounts is toxic and can be fatal. However, it is important to place this fact into perspective. The most common cause of fatalities due to acute fluoride toxicity is attempted suicide (Hodge and Smith, 1965). During the interval 1956-1966, a total of 344 accidental deaths due to fluoride were reported in U.S. Vital Statistics, of which 294, or 88%, were suicides (F.A. Smith, personal communication). Less frequently, fatalities have resulted from industrial accidents, and from an unusual instance of a cooking mistake at a mental hospital where roach poison, kept in a container nearly identical to one for powdered milk, was stirred into a batch of scrambled eggs (Lidbeck et al., 1943). Dentally related fatalities are extremely rare. In fact, only two such instances have been recorded, one of which resulted from the misuse of topical fluoride agents in the dental office (Church, 1976) and the other when a threeyear-old child swallowed 200 tablets of a fluoride supplement containing 1 mg fluoride (Eichler et al., 1982). Heifetz and Horowitz (1984) correctly stated that practitioners should be familiar with emergency measures for treating accidental overdosage. The signs and symptoms of acute fluoride toxicity are as follows: Gastrointestinal: Nausea, vomiting, diarrhea, abdominal pain, and cramps. Neurological: Paresthesia, paresis, tetany, central nervous system depression, and
coma.
Cardiovascular system:

Topical fluoride therapy and salivary enzymatic activity.

Most of the extensive review by Whitford et al. (1987) on the effect of fluoride on various enzymatic activities concerned in vitro or animal studies and was not relevant to the effects of topical fluoride in vivo in humans. However, their claim of a 36% increase in salivary amylase activity after application of APF requires comment. It is well known that salivary protein concentrations depend on flow rate (Dawes. 1969). Furthermore, in human parotid saliva, amylase activity shows a significant positive correlation with flow rate (Blomfield et al., 1976). Without careful control of flow rate, the claim by Whitford et al. (1987), that topical fluoride alters salivary amylase

Weak pulse, hypotension, pallor, shock, cardiac irregularities and ultimately failure.

Presented during the Symposium entitled "Topical Fluorides: Optimizing Safety and Efficacy", held during the 63rd General Session of the International Association for Dental Research, March 23, 1985, in Las Vegas, Nevada 1084

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Vol. 66 No. 5

TOXICOLOGY, SAFETY, AND EFFICACY OF TOPICAL FLUORIDES

1085

activity, may be invalid. Most probably, the application of the topical gel acted as an additional stimulus, increasing salivary flow rates and causing increased discharge of zymogen granules, just as isoproterenol does.

Relation of fluoride concentration to efficacy in topical agents.

Data documenting that topical fluoride agents containing lower concentrations of fluoride than are currently in use are as effective in preventing caries as are agents containing the higher levels of fluoride are sparse and unconvincing (Koch et al., 1982). In one study comparing the efficacy of fluoride dentifrices containing 250 and 1000 ppm fluoride, the caries increment on occlusal and buccolingual surfaces was similar in children using either concentration of fluoride. However, the approximal caries increment was greater in the children using 250 ppm fluoride than in those using 1000 ppm fluoride. Most fluoride dentifrice studies indicate that higher concentrations of available fluoride give greater caries protection (Table 1). The extensive clinical trials comparing the old formulation of Crest dentifrice with the new formulation clearly showed that the latter had 15% to 20% greater efficacy (Beiswanger et al., 1981; Zacherl, 1981). Although these two formulations differ with respect to other ingredients, such as the abrasive system and the form of the fluoride agent used, the important point is that the original formulation of Crest provided approximately 260 ppm of available fluoride, whereas the new formulation provides almost five times as much, 1100 ppm available fluoride. Similarly, a double-blind comparison of two dentifrices containing 250 and 1000 ppm fluoride, as sodium monofluorophosphate, showed significantly less benefit with the lower fluoride concentration. The authors concluded that the dentifrice containing the lower concentration of fluoride was less effective in reducing dental caries (Mitropoulos et al., 1984). The commercial dentifrice called "1 tot 4", which contains 250 ppm fluoride and is marketed in The Netherlands for young children, was introduced without any basis of proven clinical

efficacy. I agree with Heifetz and Horowitz (1984) that studies to date of dentifrices with lower fluoride potency are few and inconclusive, but I disagree with the recommendation of Whitford et al. (1987) that currently available commercial dentifrices containing 1000 ppm fluoride should bear a warning label that they not be used by children under six years of age. However, all fluoride dentifrices, especially those with higher fluoride concentrations, should state on the label that for children under six years of age, only a pea-sized amount should be applied on the brush and that the dentifrice should be expectorated. For young children, it is prudent that the use of fluoride dentifrices be supervised to conform to these guidelines.

Reducing ingestion of fluoride.

The symposium speakers have amply discussed the amounts of fluoride contained in various forms of therapy used in the office and in self-applied fluoride toothpaste and mouthrinses. For completeness, we should also include the amounts of fluoride used in the daily self-application of gels in custom-fitted trays. The amount of gel used depends upon the size of the tray, the type of gel used, and the person dispensing the gel. When this method was originally introduced, only 5 to 10 drops per tray, or a total of approximately 1.4 mL, were used (Englander et al., 1967). Other investigators have dispensed 2 or 5 mL per tray, representing a total exposure of 4 and 10 mL per daily treatment, respectively (Ekstrand and Koch, 1980; LeCompte and Doyle, 1982). I have tested various commercial products marketed for self-application that contained either 1. 1% sodium fluoride or 0.4% stannous fluoride and found, even when I was attempting to use a minimal amount of the gel, that those products that contained more bulking agent and did not flow readily required more of the agent (Table 2). However, with some of the less viscous, freely flowing gels, one can limit the amount dispensed to approximately 1 g per tray, or a total of 2 g per treatment. This represents a daily exposure of 10 mg fluoride from the 1.1% sodium fluoride gels, or 2 mg fluoride from the 0.4% stannous fluoride gels, of which in

Study
Reed (1973) Forsman (1974)

Hodge et al. (1980)

Koch et al. (1982) Buhe et al. (1984)

TABLE 1 DOSE/RESPONSE EFFICACY OF FLUORIDE DENTIFRICES IN REDUCING Fluoride Diagnostic Duration Supervised Fluoride in ppm Use Radiographs Dose/Response (years) (agents) + + 2 0/250/500/1000 (NaF) + 2 0/250/1000 (MFP & NaF) + + 3 0/1000/1450 (MFP & NaF)

CARIES

Comment
Used Ca2P,07 abrasive, F only partly available Supervised use of 0.2% NaF rinse biweekly, relatively low caries increments Girls demonstrated efficacy more dramatically than boys and had better oral

Mitropoulos et al. (1984)

Diodati et at. (1986)

250/1000 (MFP & NaF) 0/1000/1500 (MFP) 250/1000 (MFP) 1000/1450/2000 (MFP & NaF)
1000/2500 (MFP & NaF)

3 3
2.7
+

+
+
+

3 3
3
+

hygiene Insufficient sample size, chance of not detecting differences Increasing F level resulted in increased efficacy Reducing F level resulted in lower efficacy Increased efficacy at higher F levels, no significant difference between the higher
levels Poor compliance, dentifrice distasteful

Ripa et al. (1987)

Stephen et al. (1987)

1000/1500/2500
(MFP)

Increased efficacy at higher F levels

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1086

NEWBRUN TABLE 2 VARIATION OF GEL DISPENSED Manufacturer Unitek Cooper North Pacif. Dent. Hoyt Cooper Scherer Dunhall Du-More

J Dent Res May 1987

Product F gelution Gel II Pride Prevident Stop Gel Kam Omni Gel Easy Gel

Weight (g) 3.1 1.8 1.3 0.8 - 1.1 2.5 2.2 1.2 1.0

either case some 25% may be swallowed. Comparison of the efficacy of these products with respect to caries reduction is lacking.

Conclusions.
There is good justification for recommending to patients, parents and children, and indeed also to dentists and dental hygienists, that when dispensing topical fluoride agents, be it gels or dentifrices, the important message is to KEEP IT SMALL. That is, a pea-sized amount of fluoride gel (from 1 to 1.5 g) should be used in trays. Similarly, for young children (under six years of age), only pea-sized amounts of fluoride dentifrice should be applied on the brush, and the dentifrice should be expectorated. Proposed changes in the concentration of fluoride to be used in such topical agents are not supported on the basis of clinical efficacy in reducing caries, and are not justified based on present knowledge.
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