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Toxicological information

Exposure related observations in humans: other data

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Administrative data

Endpoint:
exposure-related observations in humans: other data
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non-standard study reported in the literature

Data source

Reference
Reference Type:
publication
Title:
Dissolution of calcium fluoride tablets in vitro and bioavailability in man
Author:
Afseth J, Ekstrand J & Hagelid P
Year:
1987
Bibliographic source:
Scand J Dent Res. 1987 Apr;95(2):191-2

Materials and methods

Type of study / information:
Toxicokinetics: absorption and bioavailability
Endpoint addressed:
basic toxicokinetics
Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
The dissolution rate of calcium fluoride tablets in vitro and the degree of fluoride absorption in vivo after tablet intake in man were investigated.
GLP compliance:
no
Remarks:
: published literature study

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Calcium fluoride tablets (1.1 mg); A.S. Farmaceuutisk Indutri, Oslo, Norway.

Method

Ethical approval:
not specified
Details on study design:
A total of 8 volunteers were administered either Ca2F or NaF tablets. The dissolution of tablets was also investigated in vitro in de-ionised water, simulated gastric juice (0.1 M HCl) or simulated intestinal fluid (phosphate buffer, pH 6.8).
Exposure assessment:
measured
Details on exposure:
In vitro: fluoride analysis was performed in duplicate using a fluoride electrode (450 ul samples).

Volunteers took 4 mg fluoride as sodium fluoride or calcium fluoride tablets

In vivo: venous blood samples were taken prior to, and at 0.5, 0.75, 1.0, 1.25, 1.5, 2.0, 4.0 and 6.0 hours after dosing. Fluoride analysis was performed in duplicate using a fluoride electrode.

Results and discussion

Results:
An increase in plasma fluoride was seen in all subjects administered sodium fluoride; no increase was seen in the volunteers administered calcium fluoride. Dissolution of the calcium fluoride tablets was modest (~50%) in simulated gastric fluid and was negligible in water of buffer.

Any other information on results incl. tables

In spite of the moderate dissolution of the calcium fluoride tablets seen in vitro in simulated gastric fluid, no absorption of fluoride was apparent in human volunteers as measured by plasma levels; values at all timepoints were ~20 ng/mL plasma. In contrast, a marked elevation of plasma fluoride levels (~5 -6 times pre-dosing levels) to ~100 -120 ng/mL plasma was seen in the volunteers administered sodium fluoride.

Applicant's summary and conclusion

Conclusions:
The bioavailability of fluoride from calcium fluoride in vivo is shown to be very low.
Executive summary:

The dissolution rate of calcium fluoride tablets in vitro and the degree of fluoride absorption in vivo after calcium fluoride and sodium fluoride tablet intake in man were investigated. The calcium fluoride tablets were more than 50% dissolved after 1 hour in simulated gastric fluid, but were negligibly soluble in water or phosphate buffer. In spite of the moderate dissolution of the calcium fluorid tablets seen in vitro in simulated gastric fluid, no absorption of fluoride was apparent in human volunteers as measured by plasma levels; values at all timepoints were ~20 ng/mL plasma. In contrast, a marked elevation of plasma fluoride levels (~5 -6 times pre-dosing levels) to ~100 -120 ng/mL plasma was seen in the volunteers administered sodium fluoride. The bioavailability of fluoride from calcium fluoride in vivo is therefore shown to be very low.