*This study was made possible, in part by research grant D 70 from the United States
Public Health Service, U, S. Department of Health, Education and Welfare, and in part
by a grant from the New Jersey Dental Research Association, Inc.

Enziflur@ tablets were supplied for this study by Ayerst Laboratories, 22 East 40th Street, New York. Sodium monoflurophosphate for the study was supplied by Ozark-Mahoning Company, Tulsa Oklahoma.

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Summary

Data is presented showing exact quantity of known fluoride that was ingested by gravid women and the amount recovered in placental tissue and in fetal blood. No definite correlation between concentrations in placental and blood could be demonstrated. The quantity recovered of lower levels when using sodium monofluorophosphate than when using the calcium or sodium fluoride salts.

The effects of fluoride on the blood pictures of’ children who had been using the tablets for varying periods of time revealed no unusual effects or differences.

One per cent out of 1100 cases presented evidence of undesirable side effects from the fluoride therapy. Skin rashes, headaches, epigastric distress, varying from slight discomfort to bloody vomiting were among the symptoms. The lowered threshold of allergic patients to allergens or intoxicants such as fluoride is discussed. It is pointed out that if fluoride is the allergen or intoxicant, by the tablet method of administration, the source is readily removed by discontinuance of the therapy. This cannot be readily accomplished when. communal water supplies are the source.

Clinically, at present, beneficial results to the dentitions are reported as a result of ingestion of fluorides during the first two trimesters of pregnancy. Dental fluorosis of deciduous teeth is reported.

Beneficial effects to cases with hypersensitive teeth due to imperfect development is reported, with sensitivity relieved after but two weeks of therapy.

A marked delay in the eruption of the teeth was noted and the possible cause is cited.

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… The investigation reported here, however, was aimed at determining the effects of fluorides, when given in measured, accurate, daily doses in tablet form to pregnant women and in children through the age of eight, during that period when tooth crown formation is under way.

This progress report pertains to the placental storage and transfer of fluoride ingested in
sodium monofluorophosphate tablets, each tablet containing 825 micrograms, the effects of NaF and CAF₂ on the blood picture of children, and the untoward reactions and beneficial results occurring with the use of fluoride salts. In the future, after sufficient time has elapsed to evaluate the permanent dentitions, a final analysis will be prepared…

Fluoride Administration During Pregnancy

Based on the known characteristics of tooth enamel, a long range study has been instituted involving the administration of fluoride to the expectant mother during pregnancy and to the child until his permanent tooth crowns have fully matured. These fluoride tablets are of three fluoride salts: calcium fluoride (Enziflur®), sodium fluoride, and sodium monoflurophosphate, each yielding one milligram of the fluoride ion. These tablets are prescribed for gravid women and for children old enough to understand and follow instructions. Infants and young children unable to properly dissolve the tablet in the mouth receive the drug in fruit juice, vitamin drops, or water.

Patients are Instructed – Each patient is carefully instructed as to the dosage, including the warning that the prescription is a poison if more than one is ingested daily. Eight years of use with the first two enumerated tablets has been without a single case of overdosage. Poisoning by excessive ingestion has not occurred in over a thousand cases…

Passage of Fluorides from Mother to the Fetus – A correlation between water-borne fluorides and excretion in the urine⁶ and; placental storage⁷ has been demonstrated. A progress report on this study⁸ showed the same correlation when the fluoride is given as CaF2 and/or NaF in tablet form plus a transplacental passage of fluorides from the mother to the fetus.

Placental and Fetal Blood Concentration

Table l shows the results obtained from the analysis of placental tissue and fetal blood of seventeen cases who were given one monoflurophosphate tablet daily during pregnancy.
As pointed out in an earlier progress report, there is no definite correlation between the placental and cord blood concentrations. The placental concentration varied between 18.6 and 340 micrograms fluorine (F-) per 100 grams ·of placental tissue. Cord blood concentrations varied between 4.7 and 83.8 micrograms fluorine (F-) per 100 milliliters of fetal blood.

Average Concentration Resembles Previous Controls – It is interesting to note that the average concentration more closely resembles the controls previously reported.⁸ Furthermore, these results seem to indicate that the fluoride derived from sodium monoflurophosphate does not pass the placental barrier as readily as does  fluoride from calcium fluoride or sodium fluoride…

Undesirable Effects

Out of the 601 cases in the adult group, six have shown undesirable side effects from the fluoride supplement. Five out of the 495 children have presented evidence of undesirable reactions. This is 1 per cent incidence of side effects.

Reactions in Adults – Included in the adult cases are three cases previously reported. (9) Because the three patients were within two weeks of their expected date of confinement, it was not possible to investigate thoroughly the causes and relationship of the fluoride therapy and the symptoms: two cases of vomiting and one of urticaria. At the time the cases were reported, it was concluded that these symptoms were not the result of the fluoride ingestion, but a reaction to the binder used in the tablets.

Fluoride Possible Source of Side Effects – More recent cases which are reported here seem to indicate, however, that the fluoride itself was the source of the reactions.

Case 1

The patient was a seven-year old white child with an itchy skin rash, headache, epigastric distress, generalized weakness, and listlessness. Her discomfort was such that most of her time in school was spent in the nurse’s room. When the tablets were withdrawn, symptoms disappeared but returned again when therapy was reinstituted. Again withdrawal resulted in disappearance of symptoms. The patient has been symptom free since. The parents of this child refused to allow further experimentation.

Case 2

A report from a physician concerning an experience with a white male child, two and a half years of age when treatment was instituted, states: “Beginning in his first year of life, after an episode of measles, the child developed an atopic dermatitis, at first, involving the entire skin of the body and with usual treatment receding to a controllable state. He was placed on fluoride, 1 milligram, every day. Approximately three days after ingestion of the daily dose, he developed a generalized vesicular type of rash associated with marked pruritus. Upon cessation of the drug, the rash markedly improved in ten days when he was again placed on the fluoride which again resulted with a rash of the same general appearance. After this second episode the use of fluoride was terminated”

Case 3

A 23-year-old well-oriented primipara in the fourth month of pregnancy was admitted to the prenatal clinic on January 7, 1955. She was placed on fluoride tablets, one daily, slowly dissolved in the mouth. After one week the drug was stopped because she developed a rash on her face. The rash looked like chapped blotches of various sizes and shapes, it was scaly and itchy, and covered the entire forehead, right cheek, and chin. The rash did not occur on the left cheek or chin.

Fluoride discontinued – The patient’s face cleared up in three days on discontinuing the fluoride. Upon resuming the tablets the rash recurred in two days, this time accompanied by nausea. Tablets were again withdrawn and symptoms disappeared. Two weeks later the patient returned to the clinic and was directed to take the tablets again.

Development of Serious Symptoms – The patient took the tablets for three days, the rash reappeared and she developed serious symptoms including vomiting with blood showing in the vomitus. The fluoride description was discontinued. The patient then continued an uneventful pregnancy and delivered a healthy baby.

General Conclusions from Case Histories

The cases described indicate that certain patients react unfavorably to fluoride therapy. Whether the fluorine acts as an allergen after short term use or whether the fluorine acts as an intoxicant after many months of use, is unknown and should be determined.

Possible Association with Allergy – It has been reported that cases of fluorine intoxication occur in persons with a history of allergy. It is emphasized that a lower threshold in tolerance to drugs in allergic patients must be reckoned with. (10)

Termination of Undesirable Effects Simple – Whatever the mechanism involved it is simple to terminate the undesirable reaction of fluoride dosage by discontinuing the ingestion of the tablets. If the source of the fluoride is the public water supply, the problem is more complicated.

Additional Investigation Needed – Much has yet to be learned and understood regarding the metabolism and physiologic actions of this element and its salts.