Potassium hydrogendifluoride

Genetic toxicity: in vitro

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 for cross-reference:

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 B6C3F1 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

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

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

IUPAC Name:

sodium fluoride

Details on test material:

Sodium fluoride

Method

Species / strain

Species / strain / cell type:

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 / solvent:

No vehicle

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

no

True negative controls:

no

Positive controls:

yes

Details on test system and experimental 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 / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Additional information on results:

No additional information

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

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.