Registration Dossier

Toxicological information

Genetic toxicity: in vivo

Currently viewing:

Administrative data

Endpoint:
in vivo mammalian germ cell study: cytogenicity / chromosome aberration
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Published study
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
publication
Title:
Cytogenetic Studies of sodium fluoride in mice
Author:
Zeiger E, Gulati DK, Kaur P, Mohamed AH, Revazova J & Deaton TG
Year:
1994
Bibliographic source:
Mutagenesis, 1994, 9(5), 467

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
The study was performed in the mouse and investigated the incidence of chromosomal aberrations in bone marrow cells and the incidence of micronuclei in erythrocytes.
GLP compliance:
not specified
Type of assay:
other: combined chromosomal aberration and micronucleus assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
No further details

Test animals

Species:
mouse
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
No further information given.

Administration / exposure

Route of administration:
oral: drinking water
Vehicle:
The test substance was administered in the water.
Details on exposure:
The cytogenetic effects of sodium fluoride (NaF) were measured in mice following administration in the drinking water for 6 weeks.
Duration of treatment / exposure:
Sodium fluoride was administered in the drinking water for 6 weeks.
Frequency of treatment:
Sodium fluoride, administered in the drinking water was available ad libitum for 6 weeks.
Post exposure period:
No post exposure period.
Doses / concentrations
Remarks:
Doses / Concentrations:
200, 400 mg/L
Basis:
nominal in water
Control animals:
yes, concurrent no treatment
Positive control(s):
A concurrent postive control was used.

Examinations

Tissues and cell types examined:
Micronuclei were measured in peripheral blood erythrocytes following 1 and 6 weeks of administration. Bone marrow cell preparations were examined for the presence of chromosome aberrations following 6 weeks of treatment.
Details of tissue and slide preparation:
Micronuclei were measured in peripheral blood erythrocytes following 1 and 6 weeks of NaF administration. Bone marrow cell preparations were examined for the presence of chromosome aberrations following 6 weeks of treatment; metaphase and anaphase cells were examined. Anaphase cells were scored in three independent laboratories, two of which also scored metaphase cells from the same slides.
Evaluation criteria:
No evaluation criteria.
Statistics:
Not relevant

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative
Remarks:
No evidence of micronuclei in erythrocytes or cheomosomal aberrations in bone marrow cells.
Toxicity:
yes
Remarks:
Mortality at 400 mg/L; bodywieght effects at 200 and 400 mg/L
Vehicle controls valid:
yes
Negative controls valid:
not applicable
Positive controls valid:
yes
Additional information on results:
Bone fluoride levels were determined and showed a dose-related incorporation of fluoride. No increases in micronuclei were seen in peripheral erythrocytes at either time point, and no increases in chromosome aberrations were seen in bone marrow cells when metaphase or anaphase cells were examined.

Any other information on results incl. tables

Bone fluoride levels were determined and showed a dose-related incorporation of fluoride. No increases in micronuclei were seen in peripheral erythrocytes at either time point, and no increases in chromosome aberrations were seen in bone marrow cells when metaphase or anaphase cells were examined. A concurrent positive control, cyclophosphamide, produced significant increases in peripheral blood cell micronuclei and in chromosome aberrations in bone marrow cells in metaphase. No increases in aberrations were seen in the same cyclophosphamide-treated mice when anaphase cells were examined.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
Sodium fluoride did not cause any cytogenetic effects in mice under the conditions of this study
Executive summary:

The potential for sodium fluoride to cause chromosomal effects was investigated in a drinking-water study in mice. Mice were exposed for 1 or 6 weeks to sdoium fluoride. No evidence of micronuclei formation was seen in peripheral blood erythrocytes afer 1 or 6 weeks; no evidence of chromosomal aberration was seen in bone marrow cells after exposure for 6 weeks. Marked toxicity (including mortality) was seen at the highest dose level in this study.