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Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Bacterial reverse mutation assay: the substance trimethoxy(methyl)silane and its reaction products with [3-(2,3-epoxypropoxy)propyl]trimethoxysilane and 3-(trimethoxysilyl)propylamine (EC 701 -408 -8) was negative with and without activation in S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2 (OECD Test Guideline 471) (Dow Corning Corporation, 1990).

Cytogenicity in mammalian cells: the substance trimethoxy(methyl)silane and its reaction products with [3-(2,3-epoxypropoxy)propyl]trimethoxysilane and 3-(trimethoxysilyl)propylamine was negative with or without metabolic activation in Chinese hamster ovary cells (OECD Test Guideline 473) (BioReliance, 2001)

Mutagenicity in mammalian cells: the substance trimethoxy(methyl)silane and its reaction products with [3-(2,3-epoxypropoxy)propyl]trimethoxysilane and 3-(trimethoxysilyl)propylamine was negative without metabolic activation and positive with metabolic activation in L5178Y mouse lymphoma cells (OECD Test Guideline 490) (Charles River Laboratories, 2017).

Link to relevant study records

Referenceopen allclose all

Endpoint:
in vitro gene mutation study in bacteria
Type of information:
experimental study
Adequacy of study:
key study
Study period:
August 8, 1990 to September 10, 1990
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to guideline
Guideline:
EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
Version / remarks:
1984
Deviations:
not specified
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2
Additional strain / cell type characteristics:
other: Genetic identity: RFA mutation using crystal violet; R factor (ampicillin resistance) using ampicillin disc's, UVR B deletion by exposing the strains to ultraviolet light and the histidine requirement by culturing the strains with and without histidines.
Metabolic activation:
with and without
Metabolic activation system:
Mammalian activation mixture (S-9 mix).
Test concentrations with justification for top dose:
Five concentrations of the test material (312.5, 625, 1250, 2500 and 5000 µg/plate), separated by half-log intervals, were evaluated with and without metabolic activation.
Vehicle / solvent:
Dimethylsulfoxide (DMSO)
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
Positive controls:
yes
Positive control substance:
9-aminoacridine
2-nitrofluorene
sodium azide
other: N-methyl-N-nitro-N-nitrosoguanidine; 2-anthramin
Details on test system and experimental conditions:
Strains details:
TA-1535, TA-98, TA-1537 and TA-100 from Department of Biochemistry, University of California, Berkeley, USA
Escherichia coli WP2 from MRC Cell Mutation Unit, University of Sussex, Falmer. Brighton, England

The genetic identity of each bacterial tester strain is verified at the time that the master plates are made. Genetic identity is verified by testing for the following: RFA mutation using crystal violet; R factor (ampicillin resistance) using ampicillin disc's, UVR B deletion by exposing the strains to ultraviolet light and the histidine requirement by culturing the strains with and without histidines.

The bacterial strains are cultured in Oxoid media #2. The selective medium is Minimal Agar Davis (Difco) with 22 glucose and the overlay agar is 0.6% purified agar with either 0.05 mM histidine for the Salmonella strains or 0.05 mM tryptophan for the E, coli, 0.05 mM biotin and 0.1 M sodium chloride.

Activation System:
Bacteria were exposed to the test substance both in the presence and absence of a mammalian activation mixture (S-9 mix). S-9 mix is prepared in accordance with published procedures (Ames, et al, 1975; Matsushima, et al, 1976), using a 9,000 x g supernatant prepared from Sprague-Dawley adult male rat liver induced by AROCLOR® 1254 five days prior to kill (Organon Teknika Corporation, Durham, NC).

Study System:
Five concentrations of the test material, separated by half-log intervals, were evaluated with and without metabolic activation. Concentration of test chemical (see above) and appropriate tester strain were added to 2 ml top agar held at 45˚C, which was then pour-plated immediately on the surface of hardened minimal agar. In the nonactivation assay, 0.5 ml phosphate buffer was added just prior to plating while 0.5 ml S-9 activation mix was added for the activation assay.

Positive and negative control assays were conducted with each experiment and consisted of direct-acting mutagens for nonactivation assays and mutagens that require metabolic biotransformation in activation assays. Negative controls consisted of the test article solvent in the overlay agar together with the other essential components. Plates were incubated for 72 hours and counted. All testing was done in triplicate.
Evaluation criteria:
The data are presented as the number of revertant colonies per plate. The number of revertant colonies on both negative (solvent) and positive control plates are also presented. The mean (X) number of revertants per plate and standard deviation are also given.
Statistics:
No data.
Key result
Species / strain:
S. typhimurium TA 1535
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not determined
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Key result
Species / strain:
S. typhimurium TA 1537
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not determined
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Key result
Species / strain:
S. typhimurium TA 98
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not determined
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Key result
Species / strain:
S. typhimurium TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not determined
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Key result
Species / strain:
E. coli WP2
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not determined
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
No toxicity or precipitate was noted. There was no evidence of genetic activity observed in any of the tests.
Conclusions:
Trimethoxy(methyl)silane and its reaction products with [3-(2,3-epoxypropoxy)propyl]trimethoxysilane and 3-(trimethoxysilyl)propylamine has been tested in a valid bacterial reverse mutation assay, conducted according to OECD Test Guideline 471 (1989), and in compliance with GLP, using S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2. 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.
Endpoint:
in vitro gene mutation study in mammalian cells
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 490 (In Vitro Mammalian Cell Gene Mutation Tests Using the Thymidine Kinase Gene)
Version / remarks:
2016
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of assay:
other: in vitro mutagenicity in mammalian cells
Specific details on test material used for the study:
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: At room temperature, protect from moisture/water as well as heat and ignition sources
- Stability under test conditions: The test material was stable in dimethyl sulfoxide.
- Solubility and stability of the test substance in the solvent/vehicle: A solubility test was performed based on visual assessment. The test item was dissolved in dimethyl sulfoxide, to which molecular sieve (0.4 nm) beads were added to absorb the water.
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: Not applicable

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: The test item was dissolved in dimethyl sulfoxide, to which molecular sieve (0.4 nm) beads were added to absorb the water. Test item concentrations were used within 1 hour of preparation. The final concentration of the solvent in the exposure medium was 1.0% (v/v). The pH and the osmolarity of the culture medium containing the highest, non-precipitating concentration were recorded.
- Preliminary purification step (if any): No correction factor required
- Final dilution of a dissolved solid, stock liquid or gel: not applicable
- Final preparation of a solid: not applicable
Target gene:
Thymidine kinase
Species / strain / cell type:
mouse lymphoma L5178Y cells
Details on mammalian cell type (if applicable):
CELLS USED
- Source of cells: American Type Culture Collection, (ATCC, Manassas, USA)
(2001)
- Suitability of cells: Recommended in Test Guideline
- Cell cycle length, doubling time or proliferation index: not stated
- Sex, age and number of blood donors if applicable: not applicable
- Whether whole blood or separated lymphocytes were used if applicable: not applicable
- Number of passages if applicable: not applicable
- Methods for maintenance in cell culture if applicable: Stock cultures of the cells were stored in liquid nitrogen (-196°C)
- Modal number of chromosomes: not stated
- Normal (negative control) cell cycle time: not stated

MEDIA USED
- Type and identity of media including CO2 concentration if applicable: horse media
- Properly maintained: yes
- Periodically checked for Mycoplasma contamination: yes
- Periodically checked for karyotype stability: yes
- Periodically 'cleansed' against high spontaneous background: yes
Metabolic activation:
with and without
Metabolic activation system:
Rat S9 homogenate, Sprague Dawley rats
Test concentrations with justification for top dose:
In order to select appropriate dose levels for mutagenicity testing, cytotoxicity data were obtained by treating 8 x 106 cells (106 cells/ml for 3 hour treatment) with a number of test item concentrations increasing by approximately half log steps. The test item was tested in the absence and presence of S9-mix. The highest tested concentration was 5000 µg/ml exposure medium.
Mutation experiment dose concentrations: 100, 1000, 2000, 3000, 3500, 4000, 4500, 5000 µg/ml without metabolic activation
Mutation experiment dose concentrations: 25, 50, 100, 250, 500, 1000, 3000 µg/ml with metabolic activation

Vehicle / solvent:
- Vehicle(s)/solvent(s) used: dimethyl sulfoxide
- Justification for choice of solvent/vehicle: A solubility test was performed based on visual assessment
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
Remarks:
dimethyl sulfoxide
True negative controls:
no
Positive controls:
yes
Positive control substance:
cyclophosphamide
methylmethanesulfonate
Details on test system and experimental conditions:
ACTIVATION: S9-mix was prepared immediately before use and kept on ice. S9-mix components contained per ml physiological saline: 1.63 mg MgCl2.6H2O; 2.46 mg KCl; 1.7 mg glucose-6-phosphate; 3.4 mg NADP; 4 µmol HEPES. The above solution was filter (0.22 µm)-sterilized. To 0.5 ml S9-mix components 0.5 ml S9-fraction was added (50% (v/v) S9-fraction) to complete the S9-mix. The concentration of the S9-fraction in the exposure medium was 4% (v/v).

METHOD OF APPLICATION: in medium

DURATION
- Exposure duration: 3 hours with or without metabolic activation at 37.0 ± 1.0 °C and 145 rpm
- Expression time (cells in growth medium): 2 days
- Selection time (if incubation with a selection agent): Incubation for 11 or 12 days with TFT-selective medium
- Fixation time (start of exposure up to fixation or harvest of cells): not specified

SELECTION AGENT (mutation assays): TFT-selective medium

NUMBER OF REPLICATIONS: single culture for test group and duplicate cultures for solvent and positive controls.

METHODS OF SLIDE PREPARATION AND STAINING TECHNIQUE USED: stained for 2 hours, by adding 0.5 mg/ml 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) (Sigma).

NUMBER OF CELLS EVALUATED: 2000 cells

DETERMINATION OF CYTOTOXICITY
- Method: relative total growth; relative cloning efficiency; mutation frequency
- Any supplementary information relevant to cytotoxicity: not specified

OTHER EXAMINATIONS:
- Determination of polyploidy: not determined
- Determination of endoreplication: not determined
Evaluation criteria:
A test item is considered positive (mutagenic) in the mutation assay if it induces a mutation frequency of more than the mutation frequency of controls + 126 in a dose-dependent manner. An observed increase should be biologically relevant and will be compared with the historical control data range.
Statistics:
A Cochran Armitage trend test (p < 0.05) was performed to test whether there is a significant trend in the induction.
Key result
Species / strain:
mouse lymphoma L5178Y cells
Metabolic activation:
without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
In the absence of S9-mix, the dose levels of 100 to 4000 μg/ml showed no cytotoxicity. Cytotoxicity was observed at 4500 and 5000μg/ml.
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Key result
Species / strain:
mouse lymphoma L5178Y cells
Metabolic activation:
with
Genotoxicity:
positive
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
at 1000 and 3000 µg/ml
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Additional information on results:
TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: In the solubility test the pH at a concentration of 1250 μg/ml was 7.51.
- Effects of osmolality: In the solubility test the osmolarity at a concentration of 1250 μg/ml was 0.451 Osm/kg.
- Evaporation from medium: not specified
- Water solubility: not specified
- Precipitation: During the solubility test the test item precipitated in the exposure medium at concentrations of 2500 and 5000 μg/ml at the start of the treatment. After 3 hour treatment, the test item precipitated in the exposure medium at the concentration of 5000 μg/ml only. Based on these solubility findings, 5000 μg/ml was selected as the maximum final concentration for the dose range finding test. In the main test the test item precipitated in the exposure medium at test item concentrations 3500 µg/ml and above.
- Definition of acceptable cells for analysis: not specified
- Other confounding effects: not specified

RANGE-FINDING/SCREENING STUDIES: The relative suspension growth was 16% at the test item concentration of 5000 μg/ml compared to the relative suspension growth of the solvent control in the absence of metabolic activation. The relative suspension growth was 29% at the test item concentration of 5000 μg/ml compared to the relative suspension growth of the solvent control in the presence of metabolic activation.

HISTORICAL CONTROL DATA (with ranges, means and standard deviation and confidence interval (e.g. 95%)
- Positive historical control data: Positive control chemicals, methyl methanesulfonate and cyclophosphamide, both produced significant increases in the mutation frequency. In addition, the mutation frequency found in the positive control cultures was within the 95% control limits of the distribution of the historical positive control database.
- Negative (solvent/vehicle) historical control data: The mutation frequency found in the solvent control cultures was within the acceptability criteria of this assay and within the 95% control limits of the distribution of the historical negative control database.

ADDITIONAL INFORMATION ON CYTOTOXICITY:
- Measurement of cytotoxicity used: In the absence of S9-mix, the dose levels of 100 to 4000 μg/ml showed no cytotoxicity and the relative total growth of the highest test item concentration was 37% compared to the total growth of the solvent controls. In the presence of metabolic activation the dose levels of 1000 to 3000 μg/ml showed similar cell growth delay. Therefore, the dose level of 2000 µg/ml was not regarded relevant for mutation frequency measurement. The dose levels of 4000 to 5000 μg/ml were not used for mutation frequency measurement, since these dose levels were too toxic for further testing. The relative total growth of the highest test item concentration was 7% compared to the total growth of the solvent controls, see study plan deviation.

Table 1: Mutation Experiment: Cytotoxic and Mutagenic Response of the test item in the Mouse Lymphoma L5178Y Test System

dose

(µg/ml)

RSG

(%)

CE day2

(%)

RCE       

(%)

RTG

(%)

mutation frequency

per 106 survivors total (small large )

Without metabolic activation

 

3-hour treatment

 

 

 

SC1

100

 

118

 

100

100

96

SC2

 

 

131

 

 

 

77

100

 

137

118

95

130

77

1000

 

145

98

 

79

114

94

2000

 

150

127

 

102

153

96

3000

 

144

101

 

81

117

125

3500 (1)

 

111

116

 

94

104

69

4000 (1)

 

87

113

 

91

79

91

4500 (1)

 

73

120

 

96

70

88

5000 (1)

 

46

101

 

81

37

132

MMS

120

60

49

58

1201

With metabolic activation

 

3-hour treatment

 

 

 

SC1

 

100

86

100

100

53

SC2

 

 

58

 

 

90

25

88

78

108

95

83

50

65

97

134

87

64

100

60

79

109

66

146

250

57

85

118

67

347

500

30

64

89

27

681

1000

18

33

46

8

1318

3000

13

41

56

7

1230

CP

34

16

23

8

2860

RSG = Relative Suspension Growth; CE = Cloning Efficiency; RCE = Relative Cloning Efficiency; RTG = Relative Total Growth;

SC = Solvent control = DMSO; MMS = Methylmethanesulfonate; CP = Cyclophosphamide

(1)   = the test item precipitated in the exposure medium

Conclusions:
Trimethoxy(methyl)silane and its reaction products with [3-(2,3-epoxypropoxy)propyl]trimethoxysilane and 3-(trimethoxysilyl)propylamine has been tested for mutagenicity in Mouse lymphoma L5178Y cells conducted according to OECD Test Guideline 490 and in compliance with GLP. No test-substance induced increase in the number of mutations was observed when the substance was test in the absence of metabolic activation. The test item induced an 18-fold and 9.5-fold dose related increase in the mutation frequency at concentrations of 1000 and 500 µg/ml, respectively, in the presence of metabolic activation. This increase was above the 95% control limits of the distribution of the historical negative control database and also above the GEF + MF(controls). Appropriate solvent and positive controls were included and gave expected results. It is concluded that the test substance is positive for mutagenicity to mammalian cells under the conditions of the study.
Endpoint:
in vitro cytogenicity / chromosome aberration study in mammalian cells
Type of information:
experimental study
Adequacy of study:
key study
Study period:
07 August 2001 to 22 September 2001
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:
1998
Deviations:
no
GLP compliance:
yes
Type of assay:
other: chromosome aberration in mammalian cells
Specific details on test material used for the study:
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: at room temperature
- Stability under test conditions: stable
- Solubility and stability of the test substance in the solvent/vehicle: The test material was dissolved in ethanol.
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: not applicable

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: The test material was dissolved in ethanol.
- Preliminary purification step: none
- Final dilution of a dissolved solid, stock liquid or gel: not applicable
- Final preparation of a solid: not applicable
Species / strain / cell type:
Chinese hamster Ovary (CHO)
Details on mammalian cell type (if applicable):
CELLS USED
- Source of cells: American Type Culture Collection, Manassas, VA
- Suitability of cells: recommended in guideline
- Cell cycle length, doubling time or proliferation index: 10-14 hours
- Modal number of chromosomes: 20


MEDIA USED
- Properly maintained: yes
- Periodically checked for Mycoplasma contamination: yes
- Periodically checked for karyotype stability: yes
- Periodically 'cleansed' against high spontaneous background: yes
Metabolic activation:
with and without
Metabolic activation system:
Arochlor 1254-induced rat liver S9
Test concentrations with justification for top dose:
A preliminary toxicity assay was performed to select dose levels for the chromosome aberration test.
- 4-hour without metabolic activation: 125, 250, 500, 1000, 2000, 3000, 4000 µg/mL
- 20-hour without metabolic activation: 125, 250, 500, 1000, 2000, 3000, 4000 µg/mL
- 4-hour with metabolic activation: 500, 1000, 2000, 5000 µg/mL
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: ethanol
- Justification for choice of solvent/vehicle: A solubility test was performed to select solvent. The solvent was chosen based on solubility of the test material and compatibility with the target cells.
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
Remarks:
ethanol
True negative controls:
no
Positive controls:
yes
Positive control substance:
cyclophosphamide
mitomycin C
Details on test system and experimental conditions:
METHOD OF APPLICATION: in medium suspension
- Cell density at seeding (if applicable): 5x10⁵ cells/25 cm²

ACTIVATION: Prior to use, the S9 was mixed with a cofactor solution containing 2mM magnesium chloride, 6mM potassium chloride, 1mM glucose-6-phosphate, 1mM nicotinamide adenine dinucleotide phosphate (NADP) and 20 µL S9 per milliliter medium.

DURATION
- Preincubation period: 16-24 hours
- Exposure duration: 4 hours with or without metabolic activation or 20 hours without metabolic activation
- Expression time (cells in growth medium): 16 hours following 4-hour exposure with or without metabolic activation
- Selection time (if incubation with a selection agent): 2 hours
- Fixation time (start of exposure up to fixation or harvest of cells): at the end of exposure

SPINDLE INHIBITOR (cytogenetic assays): Colcemid

STAIN (for cytogenetic assays): Giemsa

NUMBER OF REPLICATIONS: Duplicate cultures

NUMBER OF METAPHASE SPREADS ANALYSED PER DOSE (if in vitro cytogenicity study in mammalian cells): 200 metaphase spreads were examined

DETERMINATION OF CYTOTOXICITY
- Method: mitotic index; cloning efficiency; relative total growth

Rationale for test conditions:
A preliminary toxicity assay was performed to select dose levels for the chromosome aberration test.
Evaluation criteria:
The test article was considered to induce a positive response when the percentage of cells with aberrations is increased in a dose-responsive manner with one or more concentrations being statistically significant.
Statistics:
Statistical analysis of the percentage of aberrant cells was performed using Fisher's exact test. When Fisher's test was positive at any test article dose level, the Cochran-Armitage test was used to measure dose responsiveness.
Key result
Species / strain:
Chinese hamster Ovary (CHO)
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
at 4000µg/mL (4-hour, without S9 mix), at 5000µg/mL (4-hour, with S9mix), at 3000µg/mL (20-hour, without S9 mix)
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Additional information on results:
TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: 7.5 of highest concentration
- Effects of osmolality: 317 mmol/kg of highest concentration
- Evaporation from medium: not examined
- Water solubility: not examined
- Precipitation: not observed

RANGE-FINDING/SCREENING STUDIES: The cells were exposed to 9 concentration of the test item ranging from 0.5 to 5000 µg/mL in the absence and presence of S9 mix. Cell growth inhibition relative to the solvent control was 100% in the non-activated 4 and 20-hour exposure groups at 5000 µg/mL. Cell growth inhibition relative to the solvent control was 21% at 5000 µg/mL in the activated 4-hour exposure groups. Based on these results the following dose levels were selected for the main test:
- 4-hour without metabolic activation: 125, 250, 500, 1000, 2000, 3000, 4000 µg/mL
- 20-hour without metabolic activation: 125, 250, 500, 1000, 2000, 3000, 4000 µg/mL
- 4-hour with metabolic activation: 500, 1000, 2000, 5000 µg/mL


HISTORICAL CONTROL DATA (with ranges, means and standard deviation and confidence interval (e.g. 95%)
- Positive historical control data: within the ranges of positive control data
- Negative (solvent/vehicle) historical control data: within the ranges of negative control data

ADDITIONAL INFORMATION ON CYTOTOXICITY:
- Measurement of cytotoxicity used: cell viability, cell growth index, cell growth inhibition

Table 1: Summary of chromosome aberration results

Experiment type

Concentration

µg/mL

Relative Mitotic Index

(%)

Cells with aberrations

Cells with aberrations

Precipitation

 

 

 

Numerical %

Structural %

 

Experiment I

Ethanol

13.2

2.0

0.0

 

4- hour exposure

500

10.7

2.5

1.0

 

16-hour fixation time

2000

8.8

1.0

1.0

 

Without metabolic activation

4000

6.3

1.0

1.5

 

 

MMC 0.2

10.1

2.5

14.5**

 

 

 

 

 

 

 

 

 

 

 

 

 

Experiment II

Ethanol

12.3

0.0

0.0

 

4-hour treatment

500

11.4

0.5

0.0

 

16-hour fixation time

2000

10.5

0.5

1.0

 

Withmetabolic activation

4000

6.5

0.5

2.5*

 

 

CP 10

11.5

1.5

14.0**

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Experiment I

 

Ethanol

12.9

0.35

0.0

 

20-hour treatment

500

12.3

1.0

0.0

 

20-hour fixation time

2000

12.1

2.5

1.5

 

Without metabolic activation

4000

6.8

0.0

0.5

 

 

MMC 0.2

8.1

1.5

14.5**

 

*: p < 0.05

**: p < 0.01

Conclusions:
Trimethoxy(methyl)silane and its reaction products with [3-(2,3-epoxypropoxy)propyl]trimethoxysilane and 3-(trimethoxysilyl)propylamine has been tested for ability to cause chromosome aberrations in Chinese hamster ovary cells according to OECD Test Guideline 473 and in compliance GLP. No increase in the number of cells with aberrations was observed either with or without metabolic activation in Chinese hamster ovary cells. Appropriate solvent 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 conclusion
Endpoint conclusion:
adverse effect observed (positive)

Genetic toxicity in vivo

Description of key information

There are no available in vivo studies for the test substance. An in vivo mammalian cell study examining DNA damage and/or repair has been proposed and awaits approval by ECHA. When further information is available, this section will be updated accordingly.

Endpoint conclusion
Endpoint conclusion:
no study available (further information necessary)

Additional information

Trimethoxy(methyl)silane and its reaction products with [3-(2,3-epoxypropoxy)propyl]trimethoxysilane and 3-(trimethoxysilyl)propylamine has been tested in a valid bacterial reverse mutation assay, conducted according to OECD Test Guideline 471 (1989), and in compliance with GLP, using S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2 (Dow Corning Corporation, 1990). 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.

Trimethoxy(methyl)silane and its reaction products with [3-(2,3-epoxypropoxy)propyl]trimethoxysilane and 3-(trimethoxysilyl)propylamine has been tested for ability to cause chromosome aberrations in Chinese hamster ovary cells according to OECD Test Guideline 473 and in compliance GLP (Bioreliance, 2001). No increase in the number of cells with aberrations was observed either with or without metabolic activation in Chinese hamster ovary cells. Appropriate solvent 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.

Trimethoxy(methyl)silane and its reaction products with [3-(2,3-epoxypropoxy)propyl]trimethoxysilane and 3-(trimethoxysilyl)propylamine has been tested for mutagenicity in Mouse lymphoma L5178Y cells, conducted according to OECD Test Guideline 490, and in compliance with GLP (Charles River Laboratories, 2017). No test-substance induced increase in the number of mutations was observed when the substance was tested in the absence of metabolic activation. The test item induced an 18-fold and 9.5-fold dose related increase in the mutation frequency at concentrations of 1000 and 500 µg/ml, respectively, in the presence of metabolic activation. This increase was above the 95% control limits of the distribution of the historical negative control database and also above the GEF + MF (controls). Appropriate solvent and positive controls were included and gave expected results. It is concluded that the test substance is positive for mutagenicity to mammalian cells under the conditions of the study.

Justification for classification or non-classification

Based on the in vitro data, additional testing is required to investigate whether classification is needed. Therefore, a comet assay (OECD 489) is proposed.