Registration Dossier
Registration Dossier
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EC number: 241-034-8 | CAS number: 16961-83-4
Endpoint summary
Administrative data
Key value for chemical safety assessment
Genetic toxicity in vitro
Description of key information
Hexafluorosilicic acid was negative in a guideline-comparable Ames test. With the read-across compound, sodium hexafluorosilicate, no evidence of mutagenicity was seen in an Ames test, a bacterial mutation screening assay or a Rec assay. Further read-across information for sodium fluoride was also negative in an Ames test, Mammalian gene mutation assay and Chromatid Sister Exchange.
Link to relevant study records
- Endpoint:
- in vitro gene mutation study in bacteria
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Published study, similar to guidelines
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Principles of method if other than guideline:
- Preincubation method
- GLP compliance:
- no
- Type of assay:
- bacterial reverse mutation assay
- Target gene:
- Reversion to histidine independence
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Additional strain / cell type characteristics:
- not applicable
- Species / strain / cell type:
- E. coli WP2 uvr A
- Additional strain / cell type characteristics:
- not applicable
- Species / strain / cell type:
- S. typhimurium TA 1538
- Additional strain / cell type characteristics:
- not applicable
- Metabolic activation:
- with and without
- Metabolic activation system:
- Liver S9 fraction from male Sprague-Dawley rats pre-treated et PCB mixture (KC 500)
- Test concentrations with justification for top dose:
- 1, 5, 10, 50, 100, 500, 1000, 5000 µg/plate
- Vehicle / solvent:
- Water
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- water
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- N-ethyl-N-nitro-N-nitrosoguanidine
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- water
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- benzo(a)pyrene
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- water
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 2-nitrofluorene
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- water
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 4-nitroquinoline-N-oxide
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- water
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 9-aminoacridine
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- water
- True negative controls:
- not specified
- Positive controls:
- no
- Positive control substance:
- other: 2-(2-Furyl)-3-(5-nitro-2-furyl) acrylamide
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- water
- True negative controls:
- not specified
- Positive controls:
- no
- Positive control substance:
- other: 2-aminoantracene
- Details on test system and experimental conditions:
- The preincubation method was used. 0.1mL bacterial strain and 0.5mL of S9 mix or sodium phosphate buffer (pH 7.4) were added to a sterile test tube containing 0.1mL of of hexafluorosilicic acid at the test concentrations. The mixture was then preincubated in a shaker water bath at 37°C for 20 minutes, and then added to 2mL of molten top agar (45°C). The mixture was poured onto a minimal glucose agar plate immediately. The plated were incubated at 37°C for 48 hours.
- Evaluation criteria:
- The number of revertant colonies on each plate was scored with an automated colony counter.
- Statistics:
- No information available
- 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:
- not specified
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- Positive controls validity:
- valid
- Species / strain:
- E. coli WP2 uvr A
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 1538
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 1535
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 1537
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 98
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- Positive controls validity:
- valid
- Additional information on results:
- No further information
- Remarks on result:
- other: all strains/cell types tested
- Conclusions:
- Interpretation of results: negative with and without metabolic activation
A negative result was observed in the Ames test, for hexafluorsilicic acid with and without metabolic activation. - Executive summary:
The mutagenicity of hexafluorosilicic acid was determined in the Ames test using Salmonella typhimurium strains TA98, TA100, TA1535, TA1535 and TA1538 and Escherischia coli WP2uvrA, with and without S9 metabolic activation. The substance was not mutagenic at any of the 8 concentrations tested under the conditions of this assay.
- Endpoint:
- in vitro gene mutation study in bacteria
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Justification for type of information:
- See attached read-across justification
- Reason / purpose for cross-reference:
- read-across source
- Species / strain:
- S. typhimurium, other: TA98, TA100, TA1535, TA1537, TA1538
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 98
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 1535
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 1537
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 1538
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- valid
- Remarks on result:
- other: all strains/cell types tested
- Conclusions:
- Interpretation of results: negative
Read-across substance sodium hexafluorosilicate was not found to be mutagenic under the conditions of this study. - Executive summary:
Cultures of Salmonella typhimurium strains TA98, TA100, TA1535, TA1537 and TA1538 were exposed to read-across substance sodium hexafluorosilicate at concentrations of between 1 -3600 ug/plate in the absence and presence of an exogenous metabolic activation system (Aroclor 1254 -induced Sprague-Dawley rat liver microsomes. No evidence of mutagenicity was seen under the conditions of this study.
- Endpoint:
- in vitro gene mutation study in mammalian cells
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Justification for type of information:
- See attached read-across justification
- Reason / purpose for cross-reference:
- read-across source
- Species / strain:
- Chinese hamster lung fibroblasts (V79)
- Metabolic activation:
- without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- Cytotoxic effects higher at lower pH
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- Positive controls validity:
- valid
- Additional information on results:
- At neutral pH, NaF concentrations or 300µg/mL or more inhibited cell growth for 24 hour following treatment; cells treated with 200, 300, 400 and 500 µg/mL proliferated similarly to controls after 24 hours. In cells treated with NaF at pH4, a larger toxic effect was observed. Inhibition of cell growth was observed during the first 24 hours after treatment even at the lowest concentration (200µg/mL). Growth was inhibited in cells treated with 300µg/mL beyond 24 hours since treatment, and cells treated with 400 and 500µg/mL did not survive. Incubation of cells at reduced pH reduced the level of spontaneous 6-TG mutations. No other significant differences were observed.
- Conclusions:
- Sodium fluoride: Interpretation of results: Cytotoxic at low pH, not mutagenic.
Read-across substance sodium fluoride was highly toxic, but not mutagenic. - Executive summary:
The mutagenic activity of read-across substance sodium fluoride was tested in neutral and acidic conditions in the V79/HGPRT system. Sodium fluoride was found to be cytotoxic at neutral pH, and highly cytotoxic in acidic conditions. Sodium fluoride treatment did not result in any mutagenic activity, and incubation of cells at reduced pH reduced the level of spontaneous mutations. The authors suggest that an acid environment which supports formation of hydrogen fluoride increases toxic but not mutagenic potencies of read-across substance sodium fluoride.
- Endpoint:
- in vitro gene mutation study in mammalian cells
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Justification for type of information:
- See attached read-across justification
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- read-across source
- Species / strain:
- mouse lymphoma L5178Y cells
- Metabolic activation:
- with and without
- Genotoxicity:
- positive
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- Two laboratories were used to test the substance. In the first laboratory, sodium fluoride was positive both with and without Aroclor 1254-induced male Fischer 344 rat liver S9; the effective doses, with and without S9, ranged from 300 to 600 µg/mL. In the second laboratory, sodium fluoride was tested without S9 only and test results were positive in the first trial at 62.5, 125 and 1,000 µg/mL and in the second trial at 800 and 900 µg/mL.
- Conclusions:
- Sodium fluoride: Interpretation of results: positive
Read-across substance sodium fluoride was found to be positive with and without metabolic activation at various concentrations. - Executive summary:
Two laboratories were used to test the read-across substance sodium fluoride. In the first laboratory, sodium fluoride was positive both with and without Aroclor 1254-induced male Fischer 344 rat liver S9; the effective doses, with and without S9, ranged from 300 to 600 µg/mL. In the second laboratory, sodium fluoride was tested without S9 only and test results were positive in the first trial at 62.5, 125 and 1,000 µg/mL and in the second trial at 800 and 900 µg/mL.
- Endpoint:
- in vitro cytogenicity / chromosome aberration study in mammalian cells
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Justification for type of information:
- See attached read-across justification
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- read-across source
- Species / strain:
- Chinese hamster Ovary (CHO)
- Metabolic activation:
- with and without
- Genotoxicity:
- ambiguous
- Remarks:
- : see discussion below
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Conclusions:
- Sodium fluoride: Interpretation of results: ambiguous
The results are inconclusive. The two laboratories used to test the effects of read-across substance sodium fluoride on CHO cells showed conflicting results; one reported a negative result and one reported a positive result for both induction of sister chromatid exchanges (SCE) and chromosomal aberrations (Abs). - Executive summary:
The results are inconclusive. The two laboratories used to test the effects of read-across substance sodium fluoride on CHO cells showed conflicting results; one reported a negative result and one reported a positive result for both induction of sister chromatid exchanges (SCE) and chromosomal aberrations (Abs).
Referenceopen allclose all
Hexafluorosilicic acid did not show any mutagenicity in the Ames test with and without metabolic activation.
No evidence of mutagenicity was seen in this study.
At neutral pH, NaF concentrations or 300µg/mL or more inhibited cell growth for 24 hour following treatment; cells treated with 200, 300, 400 and 500µg/mL proliferated similarly to controls after 24 hours. In cells treated with NaF at pH4, a larger toxic effect was observed. Inhibition of cell growth was observed during the first 24 hours after treatment even at the lowest concentration (200µg/mL). Growth was inhibited in cells treated with 300µg/mL beyond 24 hours since treatment, and cells treated with 400 and 500µg/mL did not survive. Incubation of cells at reduced pH reduced the level of spontaneous 6-TG mutations. No other significant differences were observed.
The table below shows the induction of trifluorothymidine resistance in mouse L5178Y cells by sodium fluoride;
Compound |
Concentration (µg/mL) |
Cloning Efficiency (%) |
Relative Total Growth (%) |
Tft Resistant Cells |
Mutant fraction |
-S9 Trial 1 Distilled water |
|
75.8 ±3.8 |
99.8 ±4.8 |
67.0 ±5.9 |
29.5 ±1.9 |
Sodium fluoride |
200 300 400 500 600 800 |
85.5 ±18.5 85.3 ±4.7 78.7 ±0.9 75.0 ±3.8 79.5 ±3.5 Lethal |
81.5 ±8.5 72.0 ±5.2 41.0 ±4.0 16.7 ±2.7 10.0 ±1.0 |
80.5 ±13.5 133.3 ±22.3 107.7 ±4.9 125.0 ±16.7 196.0 ±3.0 |
32.0 ±2.0 52.7 ±9.4 45.7 ±1.9 55.3 ±4.8 83.0 ±5.0 |
Methyl methanesulfonate |
5 |
66.7 ±2.4 |
70.7 ±5.2 |
489.0 ±43.7 |
244.3 ±13.2 |
-S9 Trial 2 Distilled water |
|
105.7 ±9.1 |
100.0 ±9.1 |
77.0 ±2.5 |
24.3 ±1.9 |
Sodium fluoride |
50 100 200 300 400 500 600 |
91.0 ±7.0 92.0 ±4.0 88.0 ±4.6 89.3 ±10.2 104.0 ±12.0 94.3 ±7.6 Lethal |
86.3 ±2.0 71.5 ±8.5 57.0 ±2.3 49.3 ±3.7 40.0 ±0.0 17.3 ±3.0 |
59.0 ±9.3 75.5 ±3.5 72.7 ±11.1 58.3 ±8.7 112.0 ±25.0 119.0 ±28.4 |
22.0 ±3.1 27.0 ±0 27.3 ±3.0 22.0 ±2.7 35.5 ±4.5 41.3 ±8.5 |
Methyl methanesulfonate |
5 |
66.7 ±2.4 |
70.7 ±5.2 |
489.0 ±43.7 |
140 ±36.5 |
+S9 Trial 3 Distilled water |
|
107.5 ±1.3 |
100.0 ±6.8 |
83.8 ±6.9 |
25.8 ±2.1 |
Sodium fluoride |
100 200 300 400 500 600 |
85 99.7 ±7.8 94.5 ±5.5 106.7 ±7.0 72.3 ±9.2 77.5 ±13.5 |
75 70.7 ±4.9 52.0 ±9.0 41.3 ±2.3 13.3 ±3.8 7.5 ±0.5 |
66 59.7 ±9.9 110.5 ±5.5 121 ±14.1 177.7 ±45.1 206.5 ±24.5 |
26 20.7 ±4.4 39.5 ±4.5 39.0 ±7.6 81.0 ±19.3 94.0 ±27.0 |
Methyl methanesulfonate |
2.5 |
61.3 ±5.2 |
28.0 ±2.1 |
615.0 ±43.3 |
334.7 ±11.9 |
+S9 Trial 3 Distilled water |
|
82.3 ±3.0 |
100.0 ±9.3 |
81.5 ±8.7 |
33.0 ±2.4 |
Sodium fluoride |
50 100 200 300 400 500 600 |
78.0 ±2.9 79.3 ±6.0 85.0 ±13.1 76.3 ±0.3 77.3 ±3.8 74.3 ±3.4 Lethal |
100.0 ±7.8 86.7 ±21.1 83.3 ±6.4 49.7 ±3.3 29.0 ±1.5 21.0 ±3.1 |
63.7 ±4.2 88.7 ±14.0 98.0 ±18.6 119.0 ±11.8 144.7 ±10.3 167.7 ±27.9 |
27.0 ±1.2 37.7 ±6.8 38.0 ±2.0 51.7 ±5.2 62.3 ±2.3 75.7 ±14.3 |
Methyl methanesulfonate |
2.5 |
47.7 ±2.7 |
21.0 ±2.7 |
731.7 ±22.9 |
573.7 ±34.6 |
The table below shows the results obtained for the induction of trifluorothymidine resistance in mouse L5178Y/TK cells by sodium fluoride;
Compound |
Concentration (µg/mL) |
Cloning Efficiency (%) |
Relative Total Growth (%) |
Tft Resistant Cells |
Mutant fraction |
-S9 Trial 1 Fischer’s medium without serum |
|
58.8 ±3.0 |
100.0 ±10.3 |
101 ±14.0 |
58.0 ±9.7 |
Sodium fluoride |
62.5 125 250 500 1000 |
52.5 ±5.5 52.5 ±8.5 59.0 ±4.0 70.0 ±15.0 40.0 ±4.0 |
88.5 ±12.5 78.0 ±4.0 70.0 ±9.0 36.0 ±1.0 8.0 ±3.0 |
162.0 ±0.0 144.0 ±24.0 130.0 ±9.0 161.5 ±18.5 155.5 ±13.5 |
104.5 ±11.5 97.5 ±31.5 73.5 ±0.5 82.5 ±26.5 134.0 ±25.0 |
Methyl methanesulfonate |
15 |
16.5 ±1.5 |
13.0 ±2.0 |
172.0 ±3.0 |
342.5 ±24.5 |
-S9 Trial 2 Fischer's medium without serum |
|
90.5 ±5.72 |
100.0 ±5.3 |
138.3 ±12.8 |
51.0 ±4.1 |
Sodium fluoride |
500 600 700 800 900 1000 |
82.0 ±3.0 87.0 ±10.0 90.5 ±3.5 78.5 ±0.5 78.0 ±2.0 Lethal |
33.0 ±0.0 28.0 ±3.0 25.0 ±0.0 20.0 ±1.0 13.0 ±1.0 |
145.0 ±20.0 148.5 ±0.5 177.0 ±25.0 215.5 ±22.5 445.0 ±22.0 |
58.5 ±5.5 58.0 ±7.0 66.0 ±12.0 91.5 ±9.5 195.5 ±3.5 |
Methyl methanesulfonate |
1552.0 ±4.0 |
52.0 ±4.0 |
35.0 ±1.0 |
77.0 ±14.0 |
49.0 ±5.0 |
Conflicting results were found in the two laboratories testing sodium fluoride on CHO cells for any cytogenetic effects. SCEs were induced in one laboratory at doses of 66.7 and 75 µg/mL without S9 and at doses of 1200 µg/mL and higher with S9. In two of the five cases, the positive results were seen following delayed harvest to allow cells, whose division time was inhibited by the higher doses of sodium fluoride to progress to the second metaphase division to the point where the cells could be scored. The laboratory reporting negative SCE results did not employ extended harvest times and was able to test up to only 50 µg/mL sodium fluoride without S9 and 500 µg/mL with S9. In the tests for the induction of Abs, positive results were reported in one laboratory at doses of 400 µg/mL sodium fluoride and greater without S9. The second laboratory reported negative results without S9, but the highest dose tested was 200 µg/mL. Neither laboratory showed a reproducible increase in chromosomal aberration in the presence of S9.
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Genetic toxicity in vivo
Description of key information
In vivo, no evidence of genotoxicity was seen in a Drosophila assay or a mouse bone marrow micronucleus assay with sodium hexafluorosilicate, whereas with hydrogen fluoride, positive results were seen in Drosophila, Micronucleus test and Dominant Lethal assay. The EU RAR (2001) however concluded that fluoride does not interact directly with DNA and is not genotoxic when administered via an appropriate route (i.e. by oral or inhalation exposure).
Link to relevant study records
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Justification for type of information:
- See attached read-across justification
- Reason / purpose for cross-reference:
- read-across source
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- not specified
- Vehicle controls validity:
- valid
- Negative controls validity:
- not examined
- Remarks on result:
- other: Sodium hexafluorosilicate
- Conclusions:
- Sodium hexafluorosilicate: Interpretation of results: negative
No evidence of mutagencitity was seen under the conditions of this assay. - Executive summary:
The genotoxicity of read-across substance sodium hexafluorosilicate was investigated in a bone marrow micronucleus assay in NMRI mice. Animals (2/sex) were administered two intraperitoneal injections of the test substance at 37.6 mg/kg bw. No evidence of genotoxicity was seen in this study.
Reference
No deaths occurred; signs of toxicity are not reported. The proportion of micronucleated PCEs in treated animals is reported to be 2.0/1000, compared to 2.2/1000 in controls. No evidence of mutagencitity was seen under the conditions of this assay.
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Additional information
Key, weight-of-evidence (WoE) and supporting information was obtained from HFS acid and sourcing substances Sodium hexafluorosilicate, Hydrogen fluoride and Sodium fluoride. Hexafluorosilicic acid will rapidly dissociate in aqueous conditions to the hydronium and fluorosilicate ions, with subsequent hydrolysis of the fluorosilicate to silicate and fluoride. Read-across from water-soluble fluorides such as hydrogen fluoride and sodium fluoride is therefore justified.
Hexafluorosilic acid
No evidence of mutagenicity was seen in a guideline-comparable WoE Ames test using Salmonella typhimurium strains TA98, TA100, TA1535, TA1535 and TA1538 and Escherischia coli WP2uvrA, with and without S9 metabolic activation (Shimizu et al, 1985).
Sodium hexafluorosilicate
No evidence of mutagenicity is reported in a WoE Ames test in S. typhimurium strains TA98, TA100, TA1535, TA1537 and TA1538 (Gocke et al, 1981) or in a supporting screening assay in S.typhimurium strains TA98, TA100, TA1535, TA1537 and TA1538 and E. coli WP2 (Kanematsu et al, 1980).
A negative supporting Rec assay in Bacillus subtilis is also reported (Kanematsu et al, 1980; Kada et al, 1980). In studies in vivo, no evidence of genotoxicity is reported in a supporting Drosophila assay or in a key mouse bone marrow micronucleus assay (Gocke et al, 1981).
Sodium fluoride
Weight-of-Evidence studies were available. No evidence of mutagenicity was seen with sodium fluoride in a Ames test (NTP, 1990). No evidence of mutagenicity was seen in a mammalian cell mutation assay (V79/HPRT) with sodium fluoride. This study was performed only in the absence of metabolic activation, however this deviation is not considered to be critical as the test substance is not metabolised. A positive result with sodium fluoride is reported in a mouse lymphoma assay (NTP, 1990). Sister chromatid exchange and chromosomal aberrations are reported in an additional NTP study.
Hydrogen fluoride
Only supporting studies were available. Gerdes (1971) reported a marginally (but not statistically significant) positive response in a study in Drosophila melanogaster; positive effects in Drosophila are also reported by Mohamed et al (1971). The significance of these results is unclear; the EU RAR for HF considers the findings of these two Drosophila studies to be inconclusive. Zeiger et al (1994) report no evidence of clastogenicity, even at dose levels causing severe toxicity, in a well-conducted mouse study performed with sodium fluoride in which chromosomal aberrations and micronucleus formation was assessed. In contrast, a poorly reported inhalation exposure study performed with HF (Voroshilin et al, 1975) reported clastogenicity in the bone marrow of exposed rats but no dominant lethal effect in exposed mice.
The EU RAR concludes that, while the dataset on the genotoxicity of HF is limited, studies with sodium fluoride are also informative as for both substances target tissues will exposed to fluoride (either free or bound to organic molecules). The EU RAR therefore reviews the available data for NaF and HF and concludes that fluoride does not interact directly with DNA and is not genotoxic when administered via an appropriate route (i.e. by oral or inhalation exposure).
Justification for classification or non-classification
No classification is proposed. The available data indicate that fluoride does not interact directly with DNA and is not genotoxic when administered via an appropriate route (i.e. by oral or inhalation exposure). HFS acid is not predicted to be genotoxic.
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