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Registration Dossier
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EC number: 240-040-8 | CAS number: 15901-40-3
Endpoint summary
Administrative data
Key value for chemical safety assessment
Genetic toxicity in vitro
Description of key information
Bacterial reverse mutation assay:
N,N’,N’’-tricyclohexyl-1-methylsilanetriamine was negative with and
without activation in S. typhimurium strains TA 98, TA100, TA1535,
TA1537 and TA 1538 (OECD TG 471).
Cytogenicity in mammalian cells:
N,N’,N’’-tricyclohexyl-1-methylsilanetriamine was negative in Chinese
hamster ovary cells (OECD TG 473).
Mutagenicity in mammalian cells:
N,N’,N’’-tricyclohexyl-1-methylsilanetriamine was negative with and
without activation in L5178Y mouse lymphoma cells (OECD TG 476).
Link to relevant study records
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1989-05-10 to 1989-12-08
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study with acceptable restrictions
- Remarks:
- The restrictions were that the range of strains tested does not comply with the current guideline.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Version / remarks:
- 1981
- Deviations:
- yes
- Remarks:
- the range of strains tested does not include a strain to detect cross-linking mutations
- GLP compliance:
- yes
- Type of assay:
- bacterial reverse mutation assay
- Target gene:
- histidine operon
- Species / strain / cell type:
- other: TA 98, TA 100, TA 1535, TA 1537, TA 1538
- Metabolic activation:
- with and without
- Metabolic activation system:
- biphenyl polychlorides-activated rat liver S9
- Test concentrations with justification for top dose:
- 0.1, 0.5, 1.0, 2.5, 5.0 μl/plate
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: acetone
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- acetone
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: amino-2-anthracene
- Remarks:
- TA 98, TA 100, TA 1535, TA 1537, TA 1538, with metabolic activation
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- acetone
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- ethylmethanesulphonate
- Remarks:
- TA 1535, without metabolic activation
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- acetone
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- methylmethanesulfonate
- Remarks:
- TA 100, without metabolic activation
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- acetone
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 9-aminoacridine
- Remarks:
- TA 1537, without metabolic activation
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- acetone
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 2-nitrofluorene
- Remarks:
- TA 98, without metabolic activation
- Details on test system and experimental conditions:
- ACTIVATION: Cofactors were added to the S9 mix to reach the following concentrations: 8 mM MgCl2, 33 mM KCl, 5 mM Glucose-6-phosphate, 4 mM NADP in 100 mM potassium-phosphate-buffer pH 7.4. The concentration of S9 in the mix was 5%, and 0.5 ml of S9 mix were added to test substance, overlay agar and bacterial suspension giving a final concentration of approximately 1% S9 in the plates.
METHOD OF APPLICATION: Vigel-Bonner agar medium, plate incorporation
DURATION
- Exposure duration: 48 hours
- Expression time (cells in growth medium): no data
SELECTION AGENT (mutation assays): agar medium
NUMBER OF REPLICATIONS: triplicate plates, experiment repeated
DETERMINATION OF CYTOTOXICITY
- Method: reduction in number of revertants; condition of background lawn. - Evaluation criteria:
- If the number of colonies apparent in presence of test article is greater than or equal to twice the number of colonies apparent in the negative control group, the result is considered to be positive.
- Statistics:
- Relevant statistics (st.dev, mean) were calculated
- Key result
- Species / strain:
- other: TA 98, TA 100, TA 1535, TA 1537, TA 1538
- 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
- Conclusions:
- N,N’,N’’-Tricyclohexyl-1-methylsilanetriamine has been tested for mutagenicity to bacteria, in a study which was conducted according to the OECD TG 471 (1989), compliant with GLP. No evidence of a test-substance related increase in the number of revertants was observed with or without metabolic activation in Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA 1537 or TA 3538 in the initial or the repeat experiments using the plate incorporation method up to limit concentrations. Appropriate positive and solvent (acetone) and controls were included and gave the expected results. It is concluded that the test substance is negative for mutagenicity to bacteria under the conditions of the test.
- Endpoint:
- in vitro cytogenicity / chromosome aberration study in mammalian cells
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2015-06-02 to 2015-12-07
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
- Version / remarks:
- 2014-09-26
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- in vitro mammalian chromosome aberration test
- Species / strain / cell type:
- Chinese hamster lung fibroblasts (V79)
- Details on mammalian cell type (if applicable):
- - Type and identity of media: minimum essential medium (MEM)
- Properly maintained: yes - Metabolic activation:
- with and without
- Metabolic activation system:
- phenobarbital (80 mg/kg bw) and β-naphthoflavone (100 mg/kg bw) S9 mix
- Test concentrations with justification for top dose:
- Experiment I:
without metabolic activation: 2, 5, 10, 20, 50, 100, 200 μg/mL
with metabolic activation: 50, 100, 200, 500, 1000, 2000 μg/mL
Experiment II:
without metabolic activation: 1, 2, 5, 10, 25, 50, 75, 100 μg/mL - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: tetrahydrofurane (THF)
- Justification for choice of solvent/vehicle: According to the results of the solubility test, the test item was dissolved in tetrahydrofurane (THF). - Untreated negative controls:
- yes
- Remarks:
- treatment medium
- Negative solvent / vehicle controls:
- yes
- Remarks:
- tetrahydrofurane (THF)
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- ethylmethanesulphonate
- Remarks:
- without metabolic activation
- Untreated negative controls:
- yes
- Remarks:
- treatment medium
- Negative solvent / vehicle controls:
- yes
- Remarks:
- tetrahydrofurane (THF)
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- cyclophosphamide
- Remarks:
- with metabolic activation
- Details on test system and experimental conditions:
- ACTIVATION: Cofactors were added to the S9 mix to reach the following concentrations: 8 mM MgCl2, 33 mM KCl, 5 mM Glucose-6-phosphate, 5 mM NADP in 100 mM sodium-phosphate-buffer pH 7.4.
METHOD OF APPLICATION: in medium MEM
DURATION
- Preincubation period: 2 days
- Exposure duration:
Experiment I: 4 hours, with and without metabolic activation
Experiment II: 21 hours, without metabolic activation
- Expression time (cells in growth medium): 21 hours
- Selection time (if incubation with a selection agent): hypotonic solution (0.4% KCl) for 15-20 min
- Fixation time (start of exposure up to fixation or harvest of cells): 21 hours
STAIN (for cytogenetic assays): Giemsa
NUMBER OF REPLICATIONS: duplicate cultures
NUMBER OF CELLS EVALUATED: 1000 cells/culture; 150 metaphases were scored per culture
DETERMINATION OF CYTOTOXICITY
- Method: mitotic index; RICC
OTHER EXAMINATIONS:
- Determination of polyploidy: yes - Evaluation criteria:
- A test chemical is considered to be clearly positive if, in any of the experimental conditions examined:
a) at least one of the test concentrations exhibits a statistically significant increase compared with the concurrent negative control,
b) the increase is dose-related when evaluated with an appropriate trend test,
c) any of the results are outside the distribution of the historical negative control data - Statistics:
- Relative statistics used (mean, statistical significance p<0.05).
- Key result
- Species / strain:
- Chinese hamster lung fibroblasts (V79)
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- ADDITIONAL INFORMATION ON CYTOTOXICITY: No biologically relevant increase in the frequencies of polyploid cells was found after treatment with the test item.
- Conclusions:
- N,N’,N’’-Tricyclohexyl-1-methylsilanetriamine has been tested in a valid study according to OECD 473 and under GLP, up to precipitating concentrations. No increase in the number of cells with aberrations was observed either with or without metabolic activation in Chinese hamster V79 cells. Appropriate solvent, negative (treatment medium) and positive controls were included and gave expected results. It is concluded that the test substance is negative for the induction of chromosome aberrations under the conditions of this study.
- Endpoint:
- in vitro gene mutation study in mammalian cells
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2015-06-02 to 2016-01-26
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- other: OECD guideline 490 ("In vitro Mammalian Cell Gene Mutation Tests Using the Thymidine Kinase Gene") 2015-07-28
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- mammalian cell gene mutation assay
- Target gene:
- Thymidine Kinase (TK) locus
- Species / strain / cell type:
- mouse lymphoma L5178Y cells
- Details on mammalian cell type (if applicable):
- - Type and identity of media: medium without methotrexate but thymidine, hypoxanthine and glycine
- Properly maintained: yes - Metabolic activation:
- with and without
- Metabolic activation system:
- phenobarbital (80 mg/kg bw) and ß-naphthoflavone (100 mg/kg bw) S9 mix
- Test concentrations with justification for top dose:
- 0.0025, 0.005, 0.010, 0.025, 0.05, 0.10, 0.25 and 0.50 mg/mL
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: tetrahydrofuran (THF)
- Justification for choice of solvent/vehicle: According to the results of the solubility test the test item was dissolved in tetrahydrofuran (THF). - Untreated negative controls:
- yes
- Remarks:
- treatment medium
- Negative solvent / vehicle controls:
- yes
- Remarks:
- tetrahydrofuran (THF)
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- ethylmethanesulphonate
- Remarks:
- without metabolic activation
- Untreated negative controls:
- yes
- Remarks:
- treatment medium
- Negative solvent / vehicle controls:
- yes
- Remarks:
- tetrahydrofuran (THF)
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- methylmethanesulfonate
- Remarks:
- without metabolic activation
- Untreated negative controls:
- yes
- Remarks:
- treatment medium
- Negative solvent / vehicle controls:
- yes
- Remarks:
- tetrahydrofuran (THF)
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- benzo(a)pyrene
- Remarks:
- with metabolic activation
- Details on test system and experimental conditions:
- METABOLIC ACTIVATION: Cofactors were added to the S9 mix to reach the concentrations below: 8 mM MgCl2, 33 mM KCl, 5 mM Glucose-6-phosphate, 5 mM NADP in 100 mM sodium-phosphate-buffer pH 7.4.
METHOD OF APPLICATION: in medium
DURATION
- Preincubation period:
- Exposure duration: 4 hours
- Expression time (cells in growth medium): 2 days at 37 °C
- Selection time (if incubation with a selection agent): 6 days
- Fixation time (start of exposure up to fixation or harvest of cells):
SELECTION AGENT (mutation assays): selective medium
NUMBER OF REPLICATIONS:
NUMBER OF CELLS EVALUATED: 2000 cells/well
DETERMINATION OF CYTOTOXICITY
- Method: cloning efficiency - Evaluation criteria:
- The test item is considered mutagenic if the following criteria are met:
-The induced mutant frequency meets or exceeds the Global Evaluation factor (GEF) of 126 mutants per 106 cells
- A dose-dependent increase in mutant frequency is detected. - Statistics:
- t-test
- Key result
- Species / strain:
- mouse lymphoma L5178Y cells
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Conclusions:
- N,N’,N’’-Tricyclohexyl-1-methylsilanetriamine has been tested in a valid study according to OECD 490 and under GLP. No statistically and biologically significant increase in the mutant frequency was observed with or without activation when tested up to precipitation concentrations in mouse lymphoma L5178Y cells. It is concluded that the test substance is negative for mutagenicity to mammalian cells under the conditions of the test.
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Version / remarks:
- 1997
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- bacterial reverse mutation assay
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9 microsomal fraction of Phenobarbital and β-Naphthoflavone induced rat livers
- Test concentrations with justification for top dose:
- Experiment I, with and without metabolic activation:
- TA 98, TA 100: 31.6, 100, 316, 1000, 2500, 5000 µg/plate
- TA 1535, TA 1537, TA 102: 10, 31.6, 100, 316, 1000, 2500 µg/plate
Experiment II, with and without metabolic activation: 62.5, 125, 250, 500, 1000, 3000 µg/plate - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: ethanol
- Justification for choice of solvent/vehicle: the solvent was compatible with the survival of the bacteria and S9 activity - Untreated negative controls:
- yes
- Remarks:
- untreated
- Negative solvent / vehicle controls:
- yes
- Remarks:
- ethanol
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- sodium azide
- Remarks:
- TA 1535, TA 100, without metabolic activation
- Untreated negative controls:
- yes
- Remarks:
- untreated
- Negative solvent / vehicle controls:
- yes
- Remarks:
- ethanol
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: 4-nitro-o-phenylene-diamine
- Remarks:
- TA 1537, TA 98, without metabolic activation
- Untreated negative controls:
- yes
- Remarks:
- untreated
- Negative solvent / vehicle controls:
- yes
- Remarks:
- ethanol
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- methylmethanesulfonate
- Remarks:
- TA 102, without metabolic activation
- Untreated negative controls:
- yes
- Remarks:
- untreated
- Negative solvent / vehicle controls:
- yes
- Remarks:
- ethanol
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: 2-aminoanthracene
- Remarks:
- TA 1535, TA1537, TA 98, TA 100, TA 102, with metabolic activation
- Details on test system and experimental conditions:
- ACTIVATION: The protein concentration in the S9 preparation was 36 mg/ml. The S9 mix contained the following co-factors: 8 mM MgCl2, 33 mM KCl, 5 mM glucose-6-phosphate, 5 mM NADP in 100 mM sodium-orthophosphate-buffer, pH 7.4, and 8.5 parts of cofactor solution were added to 1.5 parts of S9. 0.5 ml S9 mix was added to 0.1 ml test solution and 2 ml of overlay agar, giving a final concentration of approximately 3% S9 in the plates.
METHOD OF APPLICATION: in agar: plate incorporation
DURATION
- Exposure duration: 48 hours
- Expression time (cells in growth medium): 48 hours
SELECTION AGENT (mutation assays): histidine deficient agar
NUMBER OF REPLICATIONS: triplicate plates were used, and an independent repeat experiment was conducted.
DETERMINATION OF CYTOTOXICITY
- Method: condition of bacterial lawn/reduction in number of revertants - Evaluation criteria:
- A test item is considered mutagenic when: a dose related increase in the number of revertants occurs; a reproducible biologically relevant positive response for at least one of the dose groups occurs in at least one strain with or without metabolic activation.
- Statistics:
- Relative statistics (standard deviation, mean) were calculates.
- Key result
- Species / strain:
- S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- from 316 µg/plate, TA 102 without metabolic activation
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- ADDITIONAL INFORMATION ON CYTOTOXICITY:
Experiment I:
- TA 1535, TA 1537, TA 100, TA 98: 2500 µg/plate and higher, with and without metabolic activation
- TA 102: at 316 µg/plate and higher, without metabolic activation; at 2500 µg/plate, with metabolic activation
Experiment II:
- TA 1535, TA 1537, TA 100, TA 98: at 3000 µg/plate, with and without metabolic activation
- TA 102: at 1000 and higher µg/plate, without metabolic activation; at 3000 µg/plate, with metabolic activation
PRECIPITATION
No precipitation of test item was observed. - Conclusions:
- 1,1-Dimethyl-N,N'-bis(1-methylpropyl)silanediamine has been tested for mutagenicity to bacteria, in a study which was conducted according to the OECD TG 471, in compliance with GLP. No evidence of a test-substance related increase in the number of revertants was observed with or without metabolic activation in Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA 1537 or TA 102 in the initial or the repeat experiments using the plate incorporation method up to limit concentrations. Appropriate positive, solvent and negative controls were included and gave the expected results. It is concluded that the test substance is negative for mutagenicity to bacteria under the conditions of the test.
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Version / remarks:
- 1997
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- bacterial reverse mutation assay
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102
- Metabolic activation:
- with and without
- Metabolic activation system:
- phenobarbital (80 mg/kg bw) and β-naphthoflavone (100 mg/kg bw) S9 mix
- Test concentrations with justification for top dose:
- Experiment I:
10, 31.6, 100, 316, 1000, 2500, 5000 µg/plate
Experiment II:
150, 300, 500, 900, 1500, 3000, 5000 µg/plate - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: ethanol
- Justification for choice of solvent/vehicle: The solvent was compatible with the survival of the bacteria and S9 activity. - Untreated negative controls:
- yes
- Remarks:
- untreated
- Negative solvent / vehicle controls:
- yes
- Remarks:
- ethanol
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- sodium azide
- Remarks:
- TA 1535, TA 100, without metabolic activation
- Untreated negative controls:
- yes
- Remarks:
- untreated
- Negative solvent / vehicle controls:
- yes
- Remarks:
- ethanol
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: 4-nitro-o-phenylene-diamine
- Remarks:
- TA 1537, TA 98, without metabolic activation
- Untreated negative controls:
- yes
- Remarks:
- untreated
- Negative solvent / vehicle controls:
- yes
- Remarks:
- ethanol
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- methylmethanesulfonate
- Remarks:
- TA 102, without metabolic activation
- Untreated negative controls:
- yes
- Remarks:
- untreated
- Negative solvent / vehicle controls:
- yes
- Remarks:
- ethanol
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: 2-aminoanthracene
- Remarks:
- TA 1535, TA 1537, TA 98, TA 100, TA 102, with metabolic activation
- Details on test system and experimental conditions:
- ACTIVATION: The protein concentration in the S9 mx was 36 mg/ml. The S9 mix contained the following co-factors: 8 mM MgCl₂, 33 mM KCl, 5 mM glucose-6-phosphate, 5 mM NADP in 100 mM sodium ortho-phosphate-buffer, pH 7.4
METHOD OF APPLICATION: in agar (plate incorporation); preincubation
DURATION
- Preincubation period: 60 min
- Exposure duration: 48 hours
SELECTION AGENT (mutation assays): Vogel-Bonner Medium E agar plates
NUMBER OF REPLICATIONS: triplicate plates were used, and the experiment repeated. The initial experiment used the plate incorporation method, the repeat experiment used preincubation.
DETERMINATION OF CYTOTOXICITY
- Method: condition of bacterial lawn/ reduction in number of revertants - Evaluation criteria:
- The results is considered positive when: a dose related increase in the number of revertants occurs and/or a reproducible biological relevant positive response for at least one of the dose groups occurs in at least one strain with or without metabolic activation.
- Statistics:
- Relative statistics (standard deviation, mean) were calculated.
- Key result
- Species / strain:
- S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- from 1000 µg/plate (TA 1535 with metabolic activation)
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- ADDITIONAL INFORMATION ON CYTOTOXICITY:
Experiment I:
- TA 1537, TA 100, TA 102, TA 98: toxic effect at 2500 µg/plate and higher, with and without metabolic activation
- TA 1535: toxic effect at 2500 µg/plate and higher, without metabolic activation; toxic at 1000 µg/plate, with metabolic activation
Experiment II:
- TA 98, TA 100, TA 102, TA 1535: toxic effect at 1500 µg/plate, without metabolic activation and 3000 µg/plate, with metabolic activation
- TA 1537: toxic effect at 3000 µg/plate with and without metabolic activation
PRECIPITATION
No precipitation was observed in the study. - Conclusions:
- N,N', N''-Tributyl-1-methylsilanetriamine has been tested for mutagenicity to bacteria, in a study which was conducted according to the OECD TG 471, compliant with GLP. No evidence of a test-substance related increase in the number of revertants was observed with or without metabolic activation in Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA 1537 or TA 102 in the initial plate incorporation experiment or the repeat assay using the preincubation method up to limit concentrations. Appropriate positive, solvent (ethanol) and negative (untreated) controls were included and gave the expected results. It is concluded that the test substance is negative for mutagenicity to bacteria under the conditions of the test.
Referenceopen allclose all
Table 1. Results for main study no 1, mean revertants, with and without metabolic activation
Concentration μl/dish |
TA 1535 |
TA 1537 |
TA 1538 |
TA 100 |
TA 98 |
|||||
+MA |
-MA |
+MA |
-MA |
+MA |
-MA |
+MA |
-MA |
+MA |
-MA |
|
0 |
10.7 |
8.3 |
10.3 |
10.0 |
43.0 |
41.3 |
101.0 |
95.3 |
28.0 |
24.0 |
0.1 |
9.3 |
9.0 |
12.7 |
10.3 |
39.3 |
38.7 |
120.3 |
86.7 |
34.0 |
23.7 |
0.5 |
7.3 |
9.7 |
8.0 |
10.7 |
39.3 |
34.7 |
93.0 |
103.0 |
38.0 |
20.3 |
1.0 |
12.3 |
8.0 |
9.7 |
13.0 |
33.0 |
32.7 |
87.3 |
88.3 |
35.0 |
21.3 |
2.5 |
8.7 |
6.7 |
9.0 |
11.7 |
37.7 |
21.0 |
110.7 |
87.3 |
31.7 |
22.7 |
5.0 |
7.7 |
1.0 |
9.7 |
1.3 |
27.0 |
2.3 |
112.7 |
86.0 |
32.7 |
22.0 |
SR |
11.0 |
8.3 |
8.7 |
9.3 |
44.0 |
39.0 |
102.0 |
|
27.3 |
25.7 |
2 NF 0.001 |
|
|
|
|
|
|
|
|
|
551.5 |
2A |
185.0 |
|
93.5 |
|
1258.0 |
|
1538.0 |
|
1135.5 |
|
MMS 0.1 |
|
|
|
|
|
|
|
308.5 |
|
|
EMS 10 |
|
1002.5 |
|
|
|
|
|
|
|
|
9 AA 0.05 |
|
|
|
331.9 |
|
|
|
|
|
|
2 NF 0.001 |
|
|
|
|
|
240.0 |
|
|
|
|
Table 2. Results for main study no 2, mean revertants, with and without metabolic activation
Concentration μl/dish |
TA 1535 |
TA 1537 |
TA 1538 |
TA 100 |
TA 98 |
|||||
+MA |
-MA |
+MA |
-MA |
+MA |
-MA |
+MA |
-MA |
+MA |
-MA |
|
0 |
11.7 |
11.3 |
7.7 |
11.3 |
45.7 |
31.3 |
107.0 |
109.0 |
24.3 |
30.0 |
0.1 |
12.0 |
8.3 |
11.0 |
8.7 |
43.3 |
28.7 |
95.0 |
90.7 |
27.3 |
21.3 |
0.5 |
9.7 |
13.3 |
7.7 |
9.0 |
35.0 |
30.7 |
105.3 |
115.3 |
28.3 |
32.7 |
1.0 |
12.0 |
11.0 |
8.7 |
6.7 |
37.0 |
30.0 |
119.7 |
129.7 |
30.0 |
22.3 |
2.5 |
11.0 |
17.0 |
10.3 |
6.0 |
32.0 |
0.7 |
128.0 |
96.7 |
19.0 |
10.0 |
5.0 |
6.0 |
7.0 |
6.3 |
0.7 |
16.3 |
0.0 |
101.7 |
52.0 |
8.0 |
0.0 |
SR |
11.3 |
10.0 |
6.3 |
11.0 |
40.3 |
27.7 |
110.0 |
83.3 |
30.0 |
23.0 |
2 NF 0.001 |
|
|
|
|
|
|
|
|
|
408.5 |
2A |
133.0 |
|
62.5 |
|
1193.0 |
|
1118.5 |
|
1106.6 |
|
MMS 0.1 |
|
|
|
|
|
|
|
293.5 |
|
|
EMS 10 |
|
1295.5 |
|
|
|
|
|
|
|
|
9 AA 0.05 |
|
|
|
216.5 |
|
|
|
|
|
|
2 NF 0.001 |
|
|
|
|
|
291.0 |
|
|
|
|
SR: spontaneous revertants
2 NF: 2 -nitrofluorene (mg/dish)
2A: 2 -aminoanthracene (mg/dish)
MMS: methyl metanesulphonate (mg/dish)
EMS: ethyl metanesulphonate (mg/dish)
9 -AA: 9 -aminoacridine (mg/dish)
Table 1 Results of chromosomal aberration test with cultured mammalian cells (V79)
|
Dose Group |
Concentration µg/mL |
Relative Mitotic Index (%) |
RICC (%) |
Mean % Aberrant Cells |
Historical Laboratory Negative Control Range |
Precipitation |
||
Including Gaps |
Excluding Gaps |
||||||||
Experiment I and II, without metabolic activation |
|||||||||
Experiment I 4 hour treatment, 21 hour preparation interval |
C |
0 |
113 |
105 |
1.0 |
0.3 |
0.0% - 4.0 % aberrant cells |
- |
|
S |
0 |
100 |
100 |
1.0 |
0.3 |
- |
|||
3 |
10 |
107 |
93 |
0.7 |
0.3 |
- |
|||
4 |
20 |
116 |
93 |
1.3 |
0.0 |
- |
|||
5 |
50 |
103 |
92 |
0.3 |
0.3 |
+ |
|||
EMS |
900 |
107 |
72 |
11.3 |
9.0 |
- |
|||
|
|||||||||
Experiment II 21 hour treatment, 21 hour preparation interval |
C |
0 |
96 |
113 |
2.7 |
0.7 |
0.0 % - 4.0 % aberrant cells |
- |
|
S |
0 |
100 |
100 |
3.0 |
1.3 |
- |
|||
5 |
25 |
108 |
89 |
3.3 |
2.0 |
- |
|||
6 |
50 |
94 |
79 |
1.3 |
0.0 |
- |
|||
7 |
75 |
86 |
87 |
1.3 |
1.3 |
+ |
|||
EMS |
600 |
55 |
73 |
34.4 |
30.4 |
- |
|||
Experiment I, with metabolic activation |
|||||||||
Experiment I 4 hour treatment, 21 hour preparation interval |
C |
0 |
89 |
103 |
2.3 |
0.7 |
0.0 % - 4.3 % aberrant Cells |
- |
|
S |
0 |
100 |
100 |
0.7 |
0.7 |
- |
|||
1 |
50 |
109 |
108 |
2.3 |
0.3 |
- |
|||
2 |
100 |
82 |
91 |
2.0 |
1.3 |
- |
|||
3 |
200 |
106 |
87 |
1.7 |
1.7 |
+ |
|||
CPA |
1.5 |
89 |
90 |
8.3 |
5.5 |
- |
|||
C: Negative Control (Culture Medium)
S: Solvent Control (THF)
EMS: Ethylmethanesulfonate
CPA: Cyclophosphamide
RICC: Relative Increase in Cell Count
+ : with precipitation
- : without precipitation
Table 1. Results Experiment I, with and without metabolic activation
|
Test Group |
Conc. |
RCEa[%] |
RTGb[%] |
MFc[mutants/ 106cells] |
IMFd[mutants/ 106cells] |
GEFeexceeded |
Statistical Significant Increasef |
Precipitate |
[mg/mL] |
|||||||||
Exp I without metabolic activation
|
C1 |
0 |
91.3 |
101.1 |
110.7 |
/ |
/ |
/ |
- |
C2 |
109.8 |
129.3 |
/ |
/ |
/ |
- |
|||
S1 |
0 |
100.0 |
100.0 |
121.1 |
/ |
/ |
/ |
- |
|
S2 |
/ |
/ |
/ |
- |
|||||
4 |
0.0025 |
116.0 |
115.7 |
111.5 |
-9.6 |
- |
- |
- |
|
5 |
0.005 |
95.8 |
93.2 |
123.9 |
2.7 |
- |
- |
- |
|
6 |
0.010 |
111.8 |
115.3 |
104.7 |
-16.4 |
- |
- |
- |
|
7 |
0.025 |
94.3 |
92.0 |
119.0 |
-2.1 |
- |
- |
- |
|
8 |
0.05 |
89.9 |
85.0 |
125.1 |
3.9 |
- |
- |
- |
|
9 |
0.10 |
85.8 |
78.8 |
127.4 |
6.2 |
- |
- |
- |
|
10 |
0.25 |
94.3 |
74.8 |
100.5 |
-20.6 |
- |
- |
- |
|
11 |
0.50 |
89.9 |
46.1 |
122.5 |
1.4 |
- |
- |
+ |
|
EMS |
300 µg/mL |
79.6 |
68.5 |
1029.8 |
908.7 |
+ |
+ |
- |
|
MMS |
10 µg/mL |
67.8 |
58.3 |
798.9 |
677.7 |
+ |
+ |
- |
|
|
|||||||||
Exp I with metabolic activation
|
C1 |
0 |
108.1 |
110.1 |
126.6 |
/ |
/ |
/ |
- |
C2 |
99.8 |
106.0 |
/ |
/ |
/ |
- |
|||
S1 |
0 |
100.0 |
100.0 |
118.3 |
/ |
/ |
/ |
- |
|
S2 |
/ |
/ |
/ |
- |
|||||
4 |
0.0025 |
108.1 |
114.3 |
108.4 |
-9.9 |
- |
- |
- |
|
5 |
0.005 |
109.9 |
105.5 |
110.4 |
-7.8 |
- |
- |
- |
|
6 |
0.010 |
85.9 |
91.7 |
117.3 |
-0.9 |
- |
- |
- |
|
7 |
0.025 |
111.7 |
107.8 |
96.5 |
-21.7 |
- |
- |
- |
|
8 |
0.05 |
92.5 |
89.5 |
122.0 |
3.7 |
- |
- |
- |
|
9 |
0.10 |
93.9 |
92.6 |
107.8 |
-10.5 |
- |
- |
- |
|
10 |
0.25 |
111.7 |
118.3 |
107.6 |
-10.7 |
- |
- |
- |
|
11 |
0.50 |
101.4 |
91.2 |
83.4 |
-34.9 |
- |
- |
+ |
|
B[a]P |
3.5 µg/mL |
93.9 |
68.8 |
572.7 |
454.4 |
+ |
+ |
- |
|
C: Negative Controls
S: Solvent Controls (THF 0.5% v/v)
a: Relative Cloning Efficiency, RCE = [(CEdose group/ CEof corresponding controls) x 100
Cloning Efficiency, CE = ((-LN (((96 - (mean P1,P2)) / 96)) / 1.6) x 100)
b: Relative Total Growth, RTG = (RSG x RCE)/100
c: Mutant Frequency,
MF = {-ln [negative cultures/total wells (selective medium)] / -ln [negative cultures/total wells (non selective medium)]}x800
d: Induced Mutant Frequency, IMF = mutant frequency sample – mean value mutant frequency corresponding controls
e: Global Evaluation Factor, GEF (126); +: GEF exceeded, -: GEF not exceeded
f: statistical
significant increase in mutant frequency compared to solvent controls
(Mann Whitney test , p<0.05).
+: significant; -not significant
EMS: Ethylmethanesulfonate [300 µg/mL]
MMS: Methylmethanesulfonate [10 µg/mL]
B[a]P: Benzo[a]pyrene [3.5 µg/mL]
Table 1. Experiment I, plate incorporation, revertant colonies per plate (mean of three plates), with and without metabolic activation
Concentration μg/plate |
TA 1535 |
TA 1537 |
TA 100 |
TA 98 |
TA 102 |
|||||
+MA |
-MA |
+MA |
-MA |
+MA |
-MA |
+MA |
-MA |
+MA |
-MA |
|
A dest |
15 |
18 |
24 |
16 |
139 |
100 |
25 |
27 |
237 |
293 |
Ethanol |
16 |
20 |
24 |
15 |
120 |
122 |
37 |
30 |
237 |
237 |
31.6 |
19 |
19 |
28 |
18 |
139 |
97 |
31 |
41 |
219 |
212 |
100 |
22 |
14 |
21 |
19 |
140 |
111 |
22 |
37 |
175 |
251 |
316 |
27 |
16 |
21 |
17 |
116 |
105 |
27 |
41 |
165 |
249 |
1000 |
25 |
19 |
16 |
16 |
81 |
106 |
28 |
33 |
260 |
225 |
2500 |
16 |
15 |
21 |
13 |
59 |
72 |
14 |
25 |
235 |
234 |
5000 |
6 |
7 |
3 |
3 |
0 |
0 |
0 |
0 |
118 |
219 |
4-NOPD 10 |
|
|
|
|
|
|
|
798 |
|
|
4-NOPD 40 |
|
|
|
199 |
|
|
|
|
|
|
2-AA 2.5 |
190 |
|
147 |
|
1296 |
|
1269 |
|
|
|
2-AA 10 |
|
|
|
|
|
|
|
|
558 |
|
Sodium azide 10 |
|
1163 |
|
|
|
1121 |
|
|
|
|
MMS 1μL |
|
|
|
|
|
|
|
|
|
2136 |
Table 2. Experiment II, plate incorporation, revertant colonies per plate (mean of three plates), with and without metabolic activation
Concentration µg/plate |
TA 1535 |
TA 1537 |
TA 100 |
TA 98 |
TA 102 |
|||||
+MA |
-MA |
+MA |
-MA |
+MA |
-MA |
+MA |
-MA |
+MA |
-MA |
|
A dest |
14 |
14 |
18 |
14 |
118 |
109 |
37 |
19 |
214 |
311 |
Ethanol |
20 |
18 |
15 |
11 |
117 |
119 |
45 |
28 |
216 |
273 |
62.5 |
18 |
14 |
22 |
12 |
119 |
95 |
41 |
29 |
212 |
254 |
125 |
15 |
12 |
17 |
14 |
123 |
109 |
41 |
33 |
207 |
284 |
250 |
17 |
13 |
23 |
14 |
114 |
118 |
34 |
25 |
214 |
291 |
500 |
17 |
19 |
17 |
13 |
122 |
116 |
33 |
29 |
187 |
268 |
1000 |
19 |
16 |
18 |
10 |
107 |
97 |
40 |
27 |
202 |
189 |
3000 |
2 |
9 |
7 |
0 |
71 |
40 |
22 |
16 |
98 |
190 |
4-NOPD 10 |
|
|
|
|
|
|
|
1339 |
|
|
4-NOPD 40 |
|
|
|
228 |
|
|
|
|
|
|
2-AA 2.5 |
233 |
|
239 |
|
2227 |
|
1756 |
|
|
|
2-AA 10 |
|
|
|
|
|
|
|
|
521 |
|
Sodium azide 10 |
|
1324 |
|
|
|
1348 |
|
|
|
|
MMS 1μL |
|
|
|
|
|
|
|
|
|
1819 |
4 -NOPD: 4-nitro-o-phenylene-diamine
2 -AA: 2-aminoanthracene
MMS: methylmethanesulphonate
Table 1. Experiment 1, plate incorporation, revertant colonies per plate (mean of three plates), with and without metabolic activation
Concentration μg/plate |
TA 1535 |
TA 1537 |
TA 100 |
TA 98 |
TA 102 |
|||||
+MA |
-MA |
+MA |
-MA |
+MA |
-MA |
+MA |
-MA |
+MA |
-MA |
|
A dest |
11 |
11 |
14 |
12 |
110 |
98 |
31 |
28 |
177 |
286 |
Ethanol |
16 |
13 |
13 |
15 |
101 |
102 |
36 |
37 |
205 |
266 |
10 |
21 |
16 |
14 |
16 |
126 |
110 |
38 |
28 |
203 |
276 |
31.6 |
16 |
15 |
14 |
14 |
130 |
123 |
36 |
31 |
215 |
245 |
100 |
15 |
15 |
19 |
12 |
109 |
131 |
42 |
40 |
206 |
261 |
316 |
14 |
18 |
15 |
14 |
105 |
100 |
31 |
27 |
194 |
200 |
1000 |
12 |
15 |
13 |
14 |
106 |
96 |
32 |
31 |
180 |
192 |
2500 |
0 |
9 |
4 |
2 |
75 |
0 |
23 |
0 |
73 |
89 |
5000 |
0 |
3 |
2 |
0 |
27 |
0 |
0 |
0 |
0 |
47 |
4-NOPD 10 |
|
|
|
|
|
|
856 |
|
|
|
2-AA 2.5 |
103 |
|
85 |
|
2306 |
|
1947 |
|
|
|
Sodium azide 10 |
|
1213 |
|
|
|
1131 |
|
|
|
|
MMS 1μL |
|
|
|
|
|
|
|
|
|
1789 |
2-AA 10 |
|
|
|
|
|
|
|
|
742 |
|
4-NOPD 40 |
|
|
|
185 |
|
|
|
|
|
|
Table 2. Experiment 2, preincubation, revertant colonies per plate (mean of three plates), with and without metabolic activation
Concentration µg/plate |
TA 1535 |
TA 1537 |
TA 100 |
TA 98 |
TA 102 |
|||||
+MA |
-MA |
+MA |
-MA |
+MA |
-MA |
+MA |
-MA |
+MA |
-MA |
|
A dest |
14 |
16 |
9 |
11 |
110 |
64 |
38 |
32 |
198 |
343 |
Ethanol |
16 |
14 |
13 |
8 |
113 |
109 |
38 |
35 |
231 |
294 |
150 |
21 |
14 |
12 |
17 |
139 |
101 |
44 |
37 |
218 |
292 |
300 |
23 |
17 |
13 |
14 |
89 |
83 |
41 |
29 |
220 |
291 |
500 |
23 |
18 |
12 |
10 |
100 |
80 |
40 |
34 |
231 |
269 |
900 |
25 |
13 |
11 |
12 |
136 |
94 |
50 |
36 |
172 |
259 |
1500 |
21 |
6 |
13 |
13 |
114 |
69 |
36 |
24 |
188 |
188 |
3000 |
0 |
2 |
4 |
0 |
17 |
0 |
3 |
0 |
37 |
0 |
5000 |
0 |
0 |
1 |
0 |
7 |
0 |
0 |
0 |
6 |
0 |
4-NOPD 10 |
|
|
|
|
|
|
|
528 |
|
|
2-AA 2.5 |
140 |
|
105 |
|
941 |
|
592 |
|
|
|
Sodium azide 10 |
|
1402 |
|
|
|
1222 |
|
|
|
|
MMS 1μL |
|
|
|
|
|
|
|
|
|
1849 |
4-NOPD 40 |
|
|
|
130 |
|
|
|
|
|
|
2-AA 10 |
|
|
|
|
|
|
|
|
810 |
|
4 -NOPD: 4-nitro-o-phenylene-diamine
2 -AA: 2-aminoanthracene
MMS: methylmethanesulphonate
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Additional information
N,N’,N’’-Tricyclohexyl-1-methylsilanetriamine has been tested in a valid bacterial reverse mutation assay, according to the OECD TG 471 (1989), and in compliance with GLP, using Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA 1537 or TA 3538 (Hazleton, 1989). No increase in the number of revertants was observed in any test strain, with or without metabolic activation. Appropriate positive and solvent controls were added and gave expected results. It is concluded that the test substance is negative for mutagenicity to bacteria under the conditions of the test. The study was considered reliability 2, because the range of strains tested did not include a strain to detect cross-linking mutagens.
In order to provide data for the ability of the registered (target) substance to act as a cross-linking mutagen data on two source substances are provided.
N,N', N''-Tributyl-1-methylsilanetriamine has been tested for mutagenicity to bacteria, in a study which was conducted according to the OECD TG 471, compliant with GLP (Bioservice, 2004a). No evidence of a test-substance related increase in the number of revertants was observed with or without metabolic activation in Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA 1537 or TA 102 in the initial plate incorporation experiment or the repeat assay using the preincubation method up to limit concentrations. Appropriate positive, solvent (ethanol) and negative (untreated) controls were included and gave the expected results. It is concluded that the test substance is negative for mutagenicity to bacteria under the conditions of the test. The study was considered reliability 1.
1,1-Dimethyl-N,N'-bis(1-methylpropyl)silanediamine has been tested for mutagenicity to bacteria, in a study which was conducted according to the OECD TG 471, in compliance with GLP (Bioservice, 2004b). No evidence of a test-substance related increase in the number of revertants was observed with or without metabolic activation in Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA 1537 or TA 102 in the initial or the repeat experiments using the plate incorporation method up to limit concentrations. Appropriate positive, solvent and negative controls were included and gave the expected results. It is concluded that the test substance is negative for mutagenicity to bacteria under the conditions of the test. The study was considered reliability 1.
N,N’,N’’-Tricyclohexyl-1-methylsilanetriamine has been tested for ability to cause chromosome aberrations in Chinese hamster ovary cells according to OECD TG 473 and in compliance with GLP (Eurofins, 2015). No increase in the number of cells with aberrations was observed either with or without metabolic activation in Chinese hamster V79 cells. Appropriate solvent, negative (treatment medium) and positive controls were included and gave expected results. It is concluded that the test substance is negative for the induction of chromosome aberrations under the conditions of this study.
N,N’,N’’-Tricyclohexyl-1-methylsilanetriamine has been tested for mutagenicity in mouse lymphoma L5178Y cells according to OECD TG 490, and in compliance with GLP (Eurofins, 2016). No test-substance induced increase in the number of mutations was observed. Appropriate solvent, negative (treatment medium) and positive controls were included and gave expected results. It is concluded that the test substance is negative for mutagenicity to mammalian cells under the conditions of the study. The study was considered reliability 1.
Read across justification
No data are available for mutagenicity to a bacterial strain capable of detecting cross-linking or oxidising mutagens, therefore data are read-across from the related substances 1,1-dimethyl-N,N'-bis(1-methylpropyl)silanediamine (CAS 93777-98-1) and N,N',N''-tributyl-1-methylsilanetriamine (CAS 16411-33-9). Non-testing methods including read-across from surrogate substances are able to provide information on genetic toxicity (REACH Guidance part 07a, R.7.7.3). In the case of genetic toxicity the presence or absence of functional groups that are known to be related to genetic toxicity is considered important, as the presence or absence of reactive groups and molecular substructures is associated with mutagenic and carcinogenic properties of chemicals (Benigni and Bossa, 2006). Consideration is therefore given to the structural similarity, particularly presence or absence of structural alerts for genetic toxicity, when selecting surrogate substances for genetic toxicity endpoints.
Read-across hypothesis
The hypothesis is that the source (read-across) substances and target (registration) substance have similar systemic toxicological properties because they hydrolyse to similar silanol hydrolysis products (methylsilanetriol and dimethylsilanediol) and alkylamines (cyclohexylamine for the target substance, and n-butylamine and sec-butylamine for the source substances). None of the substances or hydrolysis products have structural alerts for genetic toxicity.
Read-across justification
(a) Structural similarity of parent substances and silicon-containing hydrolysis products
The registration and read-across substances are structurally similar in that they are all silylamines with one or two methyl groups and two or three alkylamine groups bound to a central silicon atom. The target substance has one methyl group and three cyclohexylamine groups bound to silicon. The first source substance (CAS 16411-33-9) has one methyl group and three n-butylamine groups bound to silicon. The difference between this read-across substance and the target substance is that the three cyclohexyl groups in the target substance are replaced by three n-butyl groups in the source substance. The second source substance (CAS93777-98-1) has two methyl groups and two sec-butylamine groups bound to silicon. The differences between this read-across substance the target substance are that (i) there are two methyl groups and two amine groups in the source substance and one methyl group and three amine groups in the target substance, and (ii) the amine groups are sec-butylamine in the source substance and cyclohexylamine in the target substance.
All three substances hydrolyse very rapidly to methylsilanetriol or dimethylsilanediol and an alkylamine.
The registered substance, N,N',N''-tricyclohexyl-1-methylsilanetriamine CAS 15901-40-3 hydrolyses rapidly (hydrolysis half-lives at 25°C, < 3 min at pH 4; < 2 min at pH7 and 5.1 min at pH9). The products of hydrolysis are the amine-functional leaving group, cyclohexylamine (CAS 108-91-8) and the silanol, methylsilanetriol (CAS 2445-53-6).
N,N',N''-Tributyl-1-methylsilanetriamine CAS 16411-33-9 hydrolyses rapidly (hydrolysis half-lives at 25°C, < 2 min at pH 4, 7 and 9). The products of hydrolysis are the amine-functional leaving group, n-butylamine (CAS 109-73-9) and the silanol, methylsilanetriol (CAS 2445-53-6).
1,1-Dimethyl-N,N'-bis(1-methylpropyl)silanediamine CAS 93777-98-1 hydrolyses rapidly (hydrolysis half-lives at 25°C, < 2 min at pH 4, 7 and 9). The products of hydrolysis are the amine-functional leaving group, sec-butylamine (CAS 13952-84-6) and the silanol, dimethylsilanediol (CAS 1066-42-8).
The substances and their hydrolysis products are shown in the table below (see attachment for structures).
|
Target |
Source1 |
Source2 |
Parent |
N,N',N''-tricyclohexyl-1- methylsilanetriamine CAS 15901-40-3
|
N,N',N''-Tributyl-1- methylsilanetriamine CAS 16411 -33 -9 |
1,1-Dimethyl-N,N'-bis(1-methylpropyl)silanediamine CAS93777-98-1 |
Silanol hydrolysis product |
Methylsilanetriol CAS2445-53-6 |
Methylsilanetriol CAS2445-53-6 |
Dimethylsilanediol CAS 1066-42-8 |
Amine hydrolysis product |
Cyclohexylamine CAS108-91-8 |
n-butylamine CAS109-73-9 |
sec-butylamine CAS13952-84-6 |
(b) Lack of structural alerts
None of the substances or hydrolysis products has structural alerts for genotoxicity (Benigni et al., 2008).
(c) Lack of genetic toxicity of the silanol hydrolysis product
Dimethylsilanediol is not mutagenic in a study which included an appropriate 5th strain (unpublished data). No data are available for methylsilanetriol, but other substances which also hydrolyse to methylsilanetriol give negative results in appropriate strains.
(d) Lack of genetic toxicity of the non-silicon hydrolysis product
The non-silicon hydrolysis product of the registered product, cyclohexylamine does not have data in the disseminated dossier from a bacterial mutagenicity study which tested an appropriate strain. However, a wide range of in vitro and in vivo data are presented which conclude that the substance is not a genetic toxin. In addition, the registered substance has been tested for mutagenicity and cytogenicity to mammalian cells, and no evidence for genetic toxicity has been observed. The data available for the rapidly hydrolysing read-across substances indicates that n-butylamine and sec-butylamine are not of concern for genetic toxicity
Benigni and Bossa (2006). Current Computer-Aided Drug Design 2, (2),
169-176. Benigni et al (2008). The Benigni/Bossa rule base for
mutagenicity and carcinogenicity JR Scientific report EUR 23241 EN.
Justification for classification or non-classification
N,N’,N’’-Tricyclohexyl-1-methylsilanetriamine contains no structural elements which may be of concern for potential mutagenic activity.
In vitro tests are negative, including bacterial mutagenicity, mammalian cytogenicity and mammalian mutagenicity studies.
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