Registration Dossier

Toxicological information

Genetic toxicity: in vitro

Currently viewing:

Administrative data

Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
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: NTP study
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
publication
Title:
Technical Report on the Toxicology and Carcinogenesis Studies of Sodium Fluoride in F344/N Rats and B6C3F, Mice.
Author:
NTP
Year:
1990
Bibliographic source:
U. S Department of Health and Human Services. NTP TR 393, NIH Publication No. 91-2848, December 1990.

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Sodium fluoride

Method

Species / strain
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Metabolic activation system:
metabolic enzymes and cofactors from Aroclor 1254-induced male Sprague-Dawley rat or Syrian hamster liver.
Test concentrations with justification for top dose:
Each test consisted of triplicate plates of concurrent positive and negative control and at least five doses of the test chemical. High dose was limited to 10 mg/plate.
Vehicle:
No vehicle
Controls
Negative controls:
yes
Solvent controls:
no
True negative controls:
no
Positive controls:
yes
Details on test system and conditions:
Sodium fluoride was incubated with the Salmonella typhimurium tester strains (TA98, TA100, TA1535, TA1537) either in buffer or S9 mix (metabolic activation enzymes and cofactors from Aroclor 1254-induced male Sprague-Dawley rat or Syrian hamster liver) for 20 minutes at 37 degC prior to the addition of soft agar supplemented with l-histidine and d-biotin and subsequent plating on minimal glucose agar plates. Incubation continued for an additional 48 hours.

Evaluation criteria:
A positive response is defined as a reproducible, dose related increase in histidine-independent (revertant) colonies in any one strain/activation combination. An equivocal response was defined as an increase in revertants that was not dose related, not reproducible or of insufficient magnitude to support a determination of mutagenicity. A negative response was obtained when no increase in revertant colonies was observed following chemical treatment.
Statistics:
none reported.

Results and discussion

Test results
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity:
no
Vehicle controls valid:
yes
Negative controls valid:
not applicable
Positive controls valid:
yes
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.
Additional information on results:
No additional information

Any other information on results incl. tables

Mutagenicity of Sodium Fluoride in Salmonella typhimurium

 

 

Revertants/plate

Strain

Dose

(µg/plate)

-S9

+10% hamster S9

+10% rat S9

Trial 1

Trial 2

Trial 1

Trail 2

Trial 1

Trail 2

TA100

0

70 ±5.4

92 ± 5.9

85 ±7.5

91 ±6.0

100 ±4.4

75 ±7.4

100

119 ±3.6

92 ±6.7

94 ±2.1

95 ±6.8

111 ±6.9

108 ±13.4

333

125 ±6.6

103 ±11.0

86 ±12.1

94 ±4.7

109 ±6.6

104 ±4.5

1000

106 ±10.1

84 ±3.3

89 ±7.1

89 ±7.8

100 ±2.2

94 ±5.9

3333

116 ±8.0

89 ±6.2

91 ±6.4

92 ±8.2

100 ±5.5

94 ±5.0

10000

114 ±1.2

94 ±3.3

85 ±7.8

85 ±7.2

97 ±8.1

96 ±5.4

Trial Summary

Negative

Negative

Negative

Negative

Negative

Negative

Positive control

318 ±21.4

394 ±5.7

428 ±22.9

1492 ±34.2

234 ±10.5

684 ±44.0

TA1535

0

19 ±2.3

8 ±0.6

5 ±0.6

6 ±0.7

12 ±1.8

7 ±0.9

100

24 ±3.8

10 ±2.1

11 ±3.2

9 ±2.3

13 ±1.8

7 ±1.0

333

20 ±5.2

7 ±0.9

10 ±0.3

8 ±2.6

12 ±2.1

7 ±1.5

1000

21 ±3.5

9 ±2.3

11 ±1.7

8 ±3.2

9 ±1.3

8 ±0.0

3333

24 ±2.6

8 ±2.8

9 ±1.7

8 ±0.9

12 ±2.1

7 ±1.0

10000

24 ±0.0

8 ±1.3

7 ±0.7

4 ±0.7

12 ±3.2

10 ±2.7

Trial Summary

Negative

Negative

Negative

Negative

Negative

Negative

Positive control

216 ±8.2

244 ±5.8

293 ±11.9

274 ±6.9

155 ±7.6

189 ±7.5

TA1537

0

6 ±1.3

7 ±1.5

5 ±0.6

6 ±1.0

16 ±1.2

6 ±0.9

100

5 ±1.5

6 ±0.3

21 ±2.9

7 ±1.9

16 ±0.9

11 ±3.0

333

8 ±1.5

4 ±0.9

15 ±1.5

6 ±0.6

15 ±3.2

9 ±2.5

1000

7 ±0.9

6 ±1.9

15 ±2.0

7 ±0.7

17 ±4.3

5 ±1.5

3333

6 ±1.2

4 ±1.8

15 ±2.1

7 ±1.2

15 ±1.5

6 ±1.5

10000

8 ±0.6

4 ±0.6

14 ±2.8

4 ±0.3

15 ±1.2

7 ±0.7

Trial Summary

Negative

Negative

Negative

Negative

Negative

Negative

Positive control

59 ±2.0

107 ±41.0

113 ±6.2

464 ±28.0

239 ±35.2

251 ±18.4

TA98

0

17 ±1.2

14 ±2.1

40 ±12.5

22 ±3.4

25 ±2.2

26 ±3.2

100

20 ±3.8

13 ±3.2

34 ±2.7

19 ±0.9

43 ±3.8

32 ±3.2

333

18 ±0.3

14 ±3.2

38 ±4.0

21 ±4.6

38 ±3.8

23 ±2.2

1000

16 ±0.3

11 ±2.8

30 ±1.7

16 ±3.2

35 ±1.8

21 ±2.0

3333

23 ±2.2

10 ±2.5

33 ±2.3

25 ±2.9

27 ±0.9

15 ±1.5

10000

19 ±2.6

12 ±1.3

29 ±7.0

17 ±0.3

32 ±2.1

18 ±1.0

Trial Summary

Negative

Negative

Negative

Negative

Negative

Negative

Positive control

504 ±20.3

684 ±9.8

265 ±3.8

638 ±104.1

146 ±5.2

180 ±10.4

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative

Sodium fluoride did not induce gene mutations in Salmonella typhimurium when tested with a preincubation protocol at doses of 100 to 10,000 µg/plate in strains TA100, TA1535, TA1537 and TA98
Executive summary:

Sodium fluoride did not induce gene mutations in Salmonella typhimurium when tested with a preincubation protocol at doses of 100 to 10,000 µg/plate in strains TA100, TA1535, TA1537 and TA98; all strains were tested with and without Aroclar 1254 -induced male Sprague-Dawley rat or Syrian hamster liver S9.