Lithium fluoride

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1987

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods with acceptable restrictions

Data source

Reference

Reference Type:

publication

Title:

Sodium fluoride and chromosome damage (MI vitro human lymphocyte and in vivo micronucleus assays)

Author:

Albanese, R.

Year:

1987

Bibliographic source:

Mutagenesis 2(6): 497-499, 1987

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

Deviations:

yes

Remarks:

Only two dose levels and one treatment were performed.

GLP compliance:

not specified

Type of assay:

other: mammalian micronucleus test

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

Test animals

Species:

rat

Strain:

Wistar

Remarks:

Alpk:APfSD

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 90 - 140 g
- Assigned to test groups randomly: yes
- Fasting period before study: at least 7 days
- Housing: groupwise
- Diet: ad libitum, pelleted NDD diet (Special Diet Services)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 7 days

Administration / exposure

Route of administration:

oral: drinking water

Vehicle:

- Vehicle(s)/solvent(s) used: water
- Concentration of test material in vehicle: 500 and 1000 mg/kg
- Amount of vehicle (if gavage or dermal): 10 mL/kg

Duration of treatment / exposure:

24 and 48 hours

Frequency of treatment:

once

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

500 mg/kg bw (total dose)

Doses / concentrations 2

Dose / conc.:

1 000 mg/kg bw (total dose)

No. of animals per sex per dose:

5/group/sample time

Control animals:

yes, concurrent vehicle

Positive control(s):

Cyclophosphamide (CP)
- Justification for choice of positive control(s): Substance known to cause chromosome aberrations in bone marrow and micronucleated peripheral blood erythrocytes.
- Route of administration: gavage

Examinations

Tissues and cell types examined:

Bone marrow and peripheral blood

Details of tissue and slide preparation:

DETAILS OF SLIDE PREPARATION:
Slides were prepared of bone marrow cells using the paint brush technique.

METHOD OF ANALYSIS:
The number of normochromatic erythrocytes in 1000 polychromatic erythrocytes (PE) and the incidence of micronucleated polychromatic erythrocytes (MPE) in 2000 PE was assessed on each slide.

Results and discussion

Test results

Key result

Sex:

male

Genotoxicity:

negative

Toxicity:

yes

Remarks:

4 out of 5 rats of the high dose group were found dead prior to 48 h sampling.

Vehicle controls validity:

valid

Negative controls validity:

not examined

Positive controls validity:

valid

Any other information on results incl. tables

Table 1 Results

Sample time (hours after dosing)	Treatment and dose	MPE/1000 PE (based on 2000 PE assessed per animal)
		Individual animal results	Mean ± SD
24	Distilled water 10 mL/kg (vehicle control	3, 1, 0, 1, 1	1.2 ± 1.0
	NaF 1000 mg/kg	1, 1, 1, 0, 1	0.8 ± 0.4
	NaF 500 mg/kg	1, 0, 2, 1, 1	1.0 ± 0.7
	Cyclophosphamide 20 mg/kg	19, 11, 20, 32, 25	21.4 ± 7.7
48	Distilled water 10 mL/kg (vehicle control	1, 1, 1, 1, 0	0.8 ± 0.4
	NaF 1000 mg/kg	1 (a)	-
	NaF 500 mg/kg	2, 0, 0, 2, 2	1.2 ± 1.0
	Cyclophosphamide 20 mg/kg	9, 15, 13, 8, 8	10.6 ± 3.2

(a) 4 out of 5 dosed animals were found dead before 48 hour sampling

Applicant's summary and conclusion

Conclusions:

No significant increase in the frequency of micronucleated polychromatic erythrocytes in bone marrow was observed after a single oral treatment of male rats with 500 and 1000 mg/kg bw.

Executive summary:

In a Wistar rat bone marrow micronucleus assay equivalent to OECD guideline 474, 5 male rats /group/sampling time were treated orally with sodium fluoride at doses of 0, 500 and 1000 mg/kg bw (Albanese, 1987). Bone marrow cells were harvested at 24 and 48 hours post treatment. The vehicle was distilled water. The test substance was applied by gavage as a single dose.

4 out of 5 animals died before the second harvest point (48 hours). No signs of abnormal behaviour were observed in the remaining animals. As the ratio between normochromatic and polychromatic erythrocytes was nearly 1:1 in the control and treated animals, cytotoxicity for sodium fluoride was excluded. There was no a significant increase in the frequency of micronucleated polychromatic erythrocytes in bone marrow after any treatment time.