Lithium fluoride

Exposure related observations in humans: other data

Administrative data

Endpoint:

exposure-related observations in humans: other data

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1998

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

Cytogentic effects on lymphocytes in osteoporotic patients on long-term fluoride therapy

Author:

van Asten, P., Firouz D., Adaqaplam, T.N., Ido J.T., Symen A.D.

Year:

1998

Bibliographic source:

Pharmacy World & Science 20(5): 214-218

Materials and methods

Type of study / information:

Genotoxicity (chromosome aberrations, micronuclei) in osteoporosis patients under fluoride treatment.

Endpoint addressed:

genetic toxicity

Test guideline

Qualifier:

no guideline followed

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Sodium fluoride

EC Number:

231-667-8

EC Name:

Sodium fluoride

Cas Number:

7681-49-4

Molecular formula:

FNa

IUPAC Name:

sodium fluoride

Test material form:

solid

Method

Ethical approval:

confirmed and informed consent free of coercion received

Details on study design:

Lymphocytes of 14 non smoking female volunteers were assessed in a double blind way. 7 volunteers were treated with fluoride containing formulations in the form of sodium fluoride (NaF) and disodium monofluorophosphate (MFP) for a period of 15 months up to 49 months. All volunteers of the treatment group are osteoporosis patients. 7 female volunteers of a comparable age range served as control group and remained untreated. The serum fluoride concentrations of the test group were checked every three months. Fluoride serum concentrations were kept within a range of 0.1 to 0.2 mf F-/L.

Exposure assessment:

measured

Details on exposure:

TYPE OF EXPOSURE: Fluoride was applied orally in form of tablets.

TYPE OF EXPOSURE MEASUREMENT: Biomonitoring of blood every three months.

EXPOSURE LEVELS: 100 mg MFP (equivalent to 26.4 mg F- ion); 25 mg NaF (equivalent to 22.6-33.9 mg F- ion)

EXPOSURE PERIOD: MFP was applied two times daily for a period of 19 to 21 months. NaF was applied two to three times daily for 15 months up to 49 months.

Results and discussion

Results:

Chromosome aberrations
Chromosome aberrations were not induced in patients treated with fluoride and were comparable with the results of the untreated control group.
The mean percentage of aberrant lymphocytes was 3.4 ± 1.7 and 2.9 ± 1.6 for fluoride-treated patients and control group, respectively. Predominantly observed aberrations included chromatid gaps, chromosome and chromatid breaks. Chromosomal aberrations of sodium fluoride-treated patients did not differ from the control group; mean values for chromosome breaks were 0.4 ± 0.5 and 0.5 ± 0.7, respectively.

Micronuclei
Results did not differ significantly for patients and control volunteers.

Fluoride ions do not have any clastogenic potential in human peripheral lymphocytes as can be seen from the above results.

Applicant's summary and conclusion

Conclusions:

Fluoride ions do not have any clastogenic potential in human peripheral lymphocytes in vivo.

Executive summary:

In the publication of van Asten et. al. (1998) the lymphocytes of 14 female volunteers were investigated. 7 volunteers were included in the test group and exposed to fluoride containing formulations (i.e. sodium fluoride and disodium monofluorophosphate) for a period of 15 months up to 49 months. The peripheral blood lymphocytes of these patients were stimulated to divide in vitro. Biological endpoints included the frequencies of chromosomal aberrations and micronuclei in binucleated cells. 7 female volunteers of a comparable age range served as control group and remained untreated.

Chromosome aberrations as well as micronuclei were not induced in patients treated with fluoride and were comparable with the results of the untreated control group. Thus, fluoride ions did not show any clastogenic potential in vivo in humans.