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EC number: 217-370-6 | CAS number: 1825-62-3
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Endpoint summary
Administrative data
Key value for chemical safety assessment
Genetic toxicity in vitro
Description of key information
Gene mutation (Bacterial reverse mutation assay/ Ames test): negative in S. typhimurium strains TA 98, TA 100, TA 102, TA 1535 and TA 1537 with and without metabolic activation (according to OECD 471)
Mutagenicity in mammalian cells: negative in mouse lymphoma cells (according to OECD 490)
Cytogenicity in mammalian cells: negative in Chinese hamster V79 fibroblasts (according to OECD 473)
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:
- 2002-05-07 to 2002-08-29
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- Freie und Hansestadt Hamburg, Behörde für Arbeit, Gesundheit uns Soziales, Germany
- Type of assay:
- bacterial reverse mutation assay
- Target gene:
- His operon
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Species / strain / cell type:
- S. typhimurium TA 102
- Metabolic activation:
- with and without
- Metabolic activation system:
- Aroclor induced rat liver S9
- Test concentrations with justification for top dose:
- 100, 316, 1000, 3160 and 5000 µg/plate with and without metabolic activation
- Vehicle / solvent:
- - Vehicle/solvent used: ethanol
- Justification for choice of solvent/vehicle: Solubility properties and relative non-toxicity to bacteria - Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 9-aminoacridine
- 2-nitrofluorene
- sodium azide
- cyclophosphamide
- methylmethanesulfonate
- other: 2-anthracene amide
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in agar (plate incorporation); preincubation
DURATION
- Preincubation period: 60 minutes
- Exposure duration: 48 hours
NUMBER OF REPLICATIONS: 3 plates for each test concentration in two independent experiments
DETERMINATION OF CYTOTOXICITY
- Method: Background lawn assessment, revertant count - Evaluation criteria:
- A result is positive if the number of revertants is significantly increased compared with the solvent control to at least 2-fold of the solvent control for TA 98, TA 100 and TA 102 and 3-fold of the solvent control for TA 1535 and TA 1537 in both experiments.
Positive results have to be reproducible and the histidine independence of the revertants has to be confirmed by streaking on histidine-free agar plates.
Cytotoxicity is defined as a reduction in the number of colonies by >50% compared with the solvent control and/or a sparse background lawn. - Statistics:
- MANN and WHITNEY and Spearman’s rank.
- Species / strain:
- S. typhimurium TA 1535
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- at 3160 (only preincubation method) and 5000 µg/plate
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 1537
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- at 3160 (only preincubation method) and 5000 µg/plate
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 98
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- at 3160 (only preincubation method) and 5000 µg/plate
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- at 3160 (only preincubation method) and 5000 µg/plate
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 102
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- at 3160 (only preincubation method) and 5000 µg/plate
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Additional information on results:
- COMPARISON WITH HISTORICAL CONTROL DATA: Results were within range of historical control data
- Conclusions:
- In a reliable test, conducted under OECD 471, with GLP, no mutagenic effect was observed for the test substance tested up to cytotoxic concentration in any of the test strains in two independent experiments without and with metabolic activation. The test substance is non-mutagenic in test strains used.
- 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:
- 29 July 2016
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- OGYÉI National Institute of Pharmacy and Nutrition, Budapest, Hungary
- Type of assay:
- in vitro mammalian cell gene mutation tests using the thymidine kinase gene
- Target gene:
- thymidine kinase locus
- Species / strain / cell type:
- mouse lymphoma L5178Y cells
- Details on mammalian cell type (if applicable):
- CELLS USED
- Source of cells: American Type Culture Collection (Manassas, Virginia, USA)
MEDIA USED
- Type and identity of media including CO2 concentration if applicable: Growth medium, RPMI-10 medium, consisted of 10% v/v horse serum (heat inactivated); 0.01 mL/mL antibiotic-antimycotic solution; 0.5 mg/mL Pluronic-F68; and 0.2 mg/mL pyruvic acid. Treatment medium RPMI-5 medium, was the same as growth medium except 5% v/v horse serum. At the end of the expression period, RPMI-20 was used and consisted of: 20% v/v horse serum (heat inactivated); 0.01 mL/mL antibiotic-antimycotic solution; and 0.2 mg/mL pyruvic acid.
- Properly maintained: yes
- Periodically checked for Mycoplasma contamination: yes - Metabolic activation:
- with and without
- Metabolic activation system:
- phenobarbital/β-naphtholflavone induced rat liver S9-mix
- Test concentrations with justification for top dose:
- Assay 1, 3-hour treatment with metabolic activation: 2000, 1000, 500, 250, 125, 62.5, 31.25, 15.625, 7.813 and 3.906 µg/mL,
Assay 1, 3-hour treatment without metabolic activation: 2000, 1000, 500, 250, 125, 62.5, 31.25, 15.625, 7.813 and 3.906 µg/mL,
Assay 2, 3-hour treatment with metabolic activation: 2000, 1000, 500, 250, 125, 62.5, 31.25, 15.625, 7.813 and 3.906 µg/mL,
Assay 2, 24-hour treatment without metabolic activation: 2000, 1000, 500, 250, 125, 62.5, 31.25, 15.625, 7.813 and 3.906 µg/mL. - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: acetone
- Justification for choice of solvent/vehicle: Acetone was selected based on the solubility of the test material. - Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 4-nitroquinoline-N-oxide
- cyclophosphamide
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in medium
- Cell density at seeding: 2x10E5 cells/mL
DURATION
- Exposure duration: 3 or 24 h
- Expression time (cells in growth medium): 2 days
- Selection time (if incubation with a selection agent): 12 days
SELECTION AGENT (mutation assays): trifluorothymidine (TFT)
NUMBER OF REPLICATIONS: 2
NUMBER OF CELLS EVALUATED: four 96-well plates at a density of approximately 2x10E3 cells per well.
DETERMINATION OF CYTOTOXICITY
- Method: mitotic index; cloning efficiency; relative total growth; other: suspension growth (SG; the number of times the cell number increased from the starting cell density); relative total growth (RTG; the product of the relative suspension growth [RTG] and the relative cloning efficiency [RCE]) - Evaluation criteria:
- The assay was considered valid if all of the following criteria were met:
1. The mutant frequency in the negative (vehicle/solvent) control cultures fell within the normal range (50-170 mutants per 10E6 viable cells).
2. The positive controls met at least one of the following two criteria: (1) The positive control chemical demonstrated an absolute increase in total MF that is, an increase above the spontaneous background MF of at least 300 x 10E-6. At least 40% of the IMF reflected in the small colony MF; and (2) the positive control substance had an increase in the small colony MF of at least 150 x 10E-6 above that seen in the concurrent untreated/vehicle control (a small colony IMF of 150 x 10-6).
3. The cloning efficiency (PEviability) of the negative (vehicle) controls was within the range of 65% to 120% at the end of the expression period.
4. At least four test concentrations were present, where the highest concentration produced approximately 80-90% toxicity (measured by RTG), resulted in precipitation, or it was 2 mg/mL, 2 µL/mL or 0.01 M (whichever was the lowest), or it was the highest practical (achievable) concentration.
The test item was considered to be clearly positive (mutagenic) in this assay if all the following criteria were met:
1. At least one concentration exhibited a statistically significant increase (p < 0.05) compared with the concurrent negative (vehicle) control and the increase was biologically relevant higher than the corresponding negative (vehicle/solvent) control value.
2. The increases in mutation frequency were reproducible between replicate cultures and/or between tests.
3. The increase was concentration-related (p ≤ 0.05) as indicated by the linear trend analysis.
The test item was considered clearly negative (non-mutagenic) in this assay if in all experimental conditions examined there was no concentration related response or, if there is an increase in MF, but it did not exceed the Global Evaluation Factor (GEF). - Species / strain:
- mouse lymphoma L5178Y cells
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- not applicable
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: There were no large changes in pH.
- Effects of osmolality: There were no large changes in osmolality .
- Precipitation: No precipitation was detected in the samples. - Conclusions:
- In conclusion, no mutagenic effect of ethoxy(trimethyl)silane was observed in the presence or in the absence of metabolic activation system under the conditions of this Mouse Lymphoma Assay.
- Endpoint:
- in vitro cytogenicity / chromosome aberration 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 473 (In Vitro Mammalian Chromosome Aberration Test)
- Version / remarks:
- 2016
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- OGYÉI National Institute of Pharmacy and Nutrition, Budapest, Hungary
- Type of assay:
- in vitro mammalian chromosome aberration test
- Target gene:
- not applicable
- Species / strain / cell type:
- Chinese hamster lung fibroblasts (V79)
- Details on mammalian cell type (if applicable):
- CELLS USED
- Source of cells: ECACC (European Collection of Authenticated Cells Cultures)
- Suitability of cells: stability of karyotype and morphology makes it suitable for genetic toxicity assays with low background aberrations.
- Cell cycle length, doubling time or proliferation index: doubling time = 12-14 h
- Number of passages: not more than 5 before test started
- Modal number of chromosomes: diploid number, 2n=22
MEDIA USED
- Type and identity of media including CO2 concentration if applicable: Dulbecco’s Modified Eagle’s Medium supplemented with 2 mM L-glutamine, 1% (v/v) Antibiotic-antimycotic solution (standard content: 10000 NE/mL penicillin, 10 mg/mL streptomycin and 25 μg/mL amphotericin-B) and 10% (v/v) heat-inactivated fetal bovine serum (DMEM-10, culture medium); approximately 5%CO2
- Properly maintained: yes
- Periodically checked for Mycoplasma contamination: yes
- Periodically checked for karyotype stability: yes
- Periodically 'cleansed' against high spontaneous background: not specified - Additional strain / cell type characteristics:
- not applicable
- Cytokinesis block (if used):
- Colchicine (0.2 μg/mL)
- Metabolic activation:
- with and without
- Metabolic activation system:
- cofactor-supplemented post-mitochondrial S9 fraction prepared from activated (phenoparbital and β-naphthoflavone) rat liver
- Test concentrations with justification for top dose:
- 12.35, 37.04, 111.1, 333.3, and 1000 µg/mL for 3-hour treatment with and without S9 mix
concentration selection was based on cytotoxicity assays performed with ten test concentrations between 2000 and 3.906 µg/mL - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: acetone
- Justification for choice of solvent/vehicle: the test item was insoluble at 200 mg/mL concentration using dimethyl sulfoxide (DMSO) or distilled water as vehicles. However, the 400 mg/mL concentration was achievable using acetone as vehicle (solvent). Acetone was selected for vehicle (solvent) of the study. The vehicle was compatible with the survival of the cells and the S9 activity. - Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- cyclophosphamide
- ethylmethanesulphonate
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in medium
DURATION
- Exposure duration: 3 or 20 hours
- Expression time (cells in growth medium): 20 hours (approximately 1.5 normal cell cycles)
- Fixation time (start of exposure up to fixation or harvest of cells): 20 hours
SPINDLE INHIBITOR (cytogenetic assays): Colchicine (0.2 μg/mL) was added 2-2.5 hours prior to harvesting
STAIN (for cytogenetic assays): 5% Giemsa solution
NUMBER OF REPLICATIONS: 2
METHODS OF SLIDE PREPARATION AND STAINING TECHNIQUE USED: 2-2.5 hours prior to harvesting, cell cultures were treated with Colchicine (0.2 μg/mL). The cells were swollen with 0.075 M KCl hypotonic solution for 4 minutes, then were washed in fixative (methanol : acetic acid 3 : 1 (v : v) mixture) until the preparation became plasma free (4 washes). Then, a suspension of the fixed cells* was dropped onto clean microscope slides and air-dried. The slides were stained with 5% Giemsa solution, air-dried and coverslips were mounted. Three slides were prepared for each culture.
NUMBER OF CELLS EVALUATED: at least 150
NUMBER OF METAPHASE SPREADS ANALYSED PER DOSE (if in vitro cytogenicity study in mammalian cells): At least 150* metaphases with 22 ± 2 chromosomes (centromeres) from each culture (replicate) will be examined for the presence or absence of chromosomal aberrations (approximately 1000x magnification), where possible. Chromatid and chromosome type aberrations (gaps, deletions and exchanges) will be recorded separately.
*Note: The examination of slides from a culture was halted when 25 or more metaphases with aberrations (excluding gaps) have been recorded for that culture.
DETERMINATION OF CYTOTOXICITY
- Method: At the scheduled harvesting time, the number of surviving cells was determined using a haemocytometer. Results are expressed compared to the negative (vehicle) control as RICC (Relative Increase in Cell Counts)
OTHER EXAMINATIONS:
- Determination of polyploidy: yes
- Determination of endoreplication: yes - Evaluation criteria:
- The assay is considered valid, if the following criteria are met:
- The negative (vehicle) control data are within the laboratory’s normal range for the spontaneous aberration frequency.
- The positive controls induce increases in the aberration frequency, which are significant.
The test item is considered to have shown clastogenic activity in this study if all of the following criteria are met:
- Increases in the frequency of metaphases with aberrant chromosomes are observed at one or more test concentrations (only data without gaps will be considered).
- The increases are reproducible between replicate cultures and between tests (when treatment conditions were the same).
- The increases are statistically significant.
- The increases are not associated with large changes in pH or osmolality of the treated cultures.
The historical control data for this laboratory were also considered in the evaluation. Evidence of a dose-response relationship (if any) was considered to support the conclusion.
The test item is concluded to have given a negative response if no reproducible, statistically significant increases are observed. - Statistics:
- For statistical analysis, Fisher’s exact test was used. The parameter evaluated for statistical analysis was the number of cells with one or more chromosomal aberrations excluding gaps.
- Key result
- Species / strain:
- Chinese hamster lung fibroblasts (V79)
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity, but tested up to precipitating concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: none
- Effects of osmolality: none
- Evaporation from medium: not relevant
- Water solubility: insolubility (oily film/minimal oily film) was detected at the end of the treatment period in the final treatment medium in the 1000-333.3 μg/mL concentration range with and without metabolic activation
- Precipitation: see above
RANGE-FINDING/SCREENING STUDIES: Based on the available solubility information (trial formulations of the test item performed at the Test Facility), acetone at 400 mg/mL concentrations was selected for vehicle (solvent) of the study. The highest examined concentration in the preliminary test was 2000 μg/mL.
Two Concentration Selection Cytotoxicity Assays (Assay A: 3-hour treatment with and without metabolic activation, 20-hour harvesting time; and Assay B: 20-hour treatment without metabolic activation, 20-hour harvesting time) were performed as part of the study to establish an appropriate concentration range for the Chromosome Aberration Assays. A total of ten test concentrations between 2000 and 3.906 μg/mL were used to evaluate toxicity in the presence and absence of metabolic activation in each cytotoxicity assay. Detailed results of the cytotoxicity assays are presented in the attached Tables 2,
3 and 4. Treatment concentrations for the chromosome aberration assays were selected on the basis of results of the performed Concentration Selection Cytotoxicity Assays according to the OECD guideline instructions (up to the maximum recommended concentration and/or up to the solubility limit).
CYTOKINESIS BLOCK (if used)
- Distribution of mono-, bi- and multi-nucleated cells: not reported
HISTORICAL CONTROL DATA (with ranges, means and standard deviation and confidence interval (e.g. 95%)
- Positive historical control data: see attached Tables
- Negative (solvent/vehicle) historical control data: see attached Tables
ADDITIONAL INFORMATION ON CYTOTOXICITY:
- Measurement of cytotoxicity used: RICC see attached Table 5 to 8 - Conclusions:
- In conclusion, the test substance did not induce a significant level of chromosome aberrations in Chinese hamster V79 cells in the performed experiments with and without metabolic activation. Therefore, the test substance was considered as not clastogenic in this test system.
Referenceopen allclose all
Table 2: Dose range-finding study Number of revertants per plate (2 plates)
|
TA100 |
||
Conc. |
Plate 1 |
Plate 2 |
Cytotoxic |
0* |
137 |
147 |
No |
0.316 |
133 |
130 |
No |
1 |
126 |
114 |
No |
3.16 |
118 |
132 |
No |
10 |
130 |
122 |
No |
31.6 |
153 |
121 |
No |
100 |
181 |
126 |
No |
316 |
170 |
175 |
No |
1000 |
151 |
172 |
No |
3160 |
124 |
118 |
No |
5000 |
133 |
123 |
Yes |
*solvent control with Ethanol
Table 3: Experiment 1 Plate incorporation Number of revertants per plate (mean of 3 plates)
|
TA98 |
TA100 |
TA102 |
||||||
Conc. |
— MA |
+ MA |
Cytotoxic |
— MA |
+ MA |
Cytotoxic |
— MA |
+ MA |
Cytotoxic |
0* |
41 |
38.7 |
No |
131.7 |
128.7 |
No |
292 |
294.3 |
No |
100 |
40 |
31.7 |
No |
172 |
113 |
No |
266.7 |
268.3 |
No |
316 |
45.7 |
37.7 |
No |
150.7 |
136.3 |
No |
279 |
262 |
No |
1000 |
40.7 |
34.7 |
No |
154.7 |
131.7 |
No |
281 |
246.7 |
No |
3160 |
45.7 |
36.7 |
No |
162 |
148.3 |
No |
278 |
287 |
No |
5000 |
37 |
32.7 |
Yes |
146.3 |
161.3 |
Yes |
272.7 |
274.3 |
Yes |
Positive control |
1169.3 |
1177.3 |
No |
1105.7 |
1134.3 |
No |
1177.7 |
1095 |
No |
*solvent control with ethanol
Table 3: Experiment 1 Plate incorporation Number of revertants per plate (mean of 3 plates)
|
TA1535 |
TA1537 |
||||
Conc. |
— MA |
+ MA |
Cytotoxic |
— MA |
+ MA |
Cytotoxic |
0* |
15 |
13.3 |
No |
7.3 |
7.3 |
No |
100 |
14 |
14.7 |
No |
4 |
7 |
No |
316 |
16.7 |
14.7 |
No |
3.7 |
4.7 |
No |
1000 |
16.3 |
15 |
No |
4.3 |
7 |
No |
3160 |
13.7 |
16 |
No |
4 |
6.3 |
No |
5000 |
13.7 |
15.7 |
Yes |
5 |
6 |
Yes |
Positive control |
575.3 |
584.3 |
No |
579.3 |
581 |
No |
*solvent control with ethanol
Table 4: Experiment 2 Preincubation Number of revertants per plate (mean of 3 plates)
|
TA98 |
TA100 |
TA102 |
||||||
Conc. |
— MA |
+ MA |
Cytotoxic |
— MA |
+ MA |
Cytotoxic |
— MA |
+ MA |
Cytotoxic |
0* |
38.3 |
36.3 |
No |
136 |
165.7 |
No |
295 |
282.7 |
No |
100 |
36 |
38 |
No |
137.7 |
167 |
No |
291 |
291.7 |
No |
316 |
31.7 |
40.3 |
No |
138.3 |
164.3 |
No |
303.3 |
280.7 |
No |
1000 |
30 |
37.7 |
No |
133.7 |
164 |
No |
286 |
279.3 |
No |
3160 |
28.7 |
41.3 |
Yes |
159 |
155 |
Yes |
287.7 |
294.3 |
Yes |
5000 |
29.3 |
44.7 |
Yes |
143.3 |
145 |
Yes |
292.3 |
284.3 |
Yes |
Positive control |
1292 |
1255.7 |
No |
1163.7 |
1191 |
No |
1137.7 |
1218 |
No |
*solvent control with ethanol
Table 4: Experiment 2 Preincubation Number of revertants per plate (mean of 3 plates)
|
TA1535 |
TA1537 |
||||
Conc. |
— MA |
+ MA |
Cytotoxic |
— MA |
+ MA |
Cytotoxic |
0* |
15.3 |
15 |
No |
4.7 |
5.3 |
No |
100 |
14 |
14 |
No |
3 |
3.7 |
No |
316 |
14 |
13 |
No |
4.3 |
5 |
No |
1000 |
12 |
13 |
No |
4 |
3 |
No |
3160 |
15 |
13.3 |
Yes |
3.7 |
3.7 |
Yes |
5000 |
14.3 |
13 |
Yes |
4 |
5 |
Yes |
Positive control |
565.3 |
566 |
No |
566.3 |
563 |
No |
*solvent control with ethanol
MA: Metabolic Activation
Summary tables of the main experiments (table 9 to 12) are attached.
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Genetic toxicity in vivo
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Bacterial mutagenicity
The Ames study on ethoxy(trimethyl)silane was conducted in compliance with GLP and according to OECD 471. Ethoxy(trimethyl)silane was examined in 5 Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100, and TA 102 in two independent experiments, each carried out without and with metabolic activation. The first experiment was carried out as a plate incorporation test and the second as a pre-incubation test. Five concentrations ranging from 100 to 5000 µg/plate of the test substance were applied. No increase in the number of revertants was observed in any strain and in any test. In the plate incorporation test cytotoxicity was noted at the top concentration of 5000 µg/plate in all test strains carried out without and with metabolic activation. Whereas in the pre-incubation test without metabolic activation cytotoxicity was noted at concentration of 3160 µg/plate ethoxy(trimethyl)silane in test strains TA 100, TA 102, TA 1535 and TA 1537 and at the top concentration of 5000 µg/plate in all test strains. In the experiment with metabolic activation cytotoxicity was noted at concentration of 3160 and 5000 µg/plate ethoxy(trimethyl)silane in all test strains. Appropriate solvent and positive controls were included into the test and gave the expected results. Hence, the test item was considered to be not mutagenic to bacteria under the conditions of the test.
Mammalian mutagenicity
Ethoxy(trimethyl)silane has been tested for mutagenicity to mammalian cells in a study conducted according to OECD 490 and in compliance with GLP (Citoxlab, 2018). An in vitro mammalian cell assay was performed in mouse lymphoma L5178Y TK+/- cells at the tk locus to test the potential of ethoxy(trimethyl)silane to cause gene mutation and/or chromosome damage. Treatment was performed for 3 hours with and without metabolic activation (±S9 mix) and for 24 hours without metabolic activation (-S9 mix). Acetone was used as vehicle. Concentrations up to 2000 µg/mL were tested. No precipitation was detected in the samples and there were no large changes in pH or osmolality after treatment. Following a 3-hour treatment with and without metabolic activation, no marked cytotoxicity of the test item was observed. No statistically significant or biologically relevant increase in the mutation frequency was noted at any of the evaluated concentrations. No dose-response relationship was observed. The same results were found following a 24 -hour treatment without metabolic activation. The experiments were performed using appropriate untreated, negative (vehicle/solvent) and positive control samples in all cases. The spontaneous mutation frequency of the negative (vehicle/solvent) controls was in the appropriate range. The positive controls gave the anticipated increases in mutation frequency. The plating efficiencies for the negative (vehicle) controls at the end of the expression period were acceptable in all assays. The evaluated concentration ranges were considered to be adequate. The number of test concentrations met the acceptance criteria. Therefore, the study was considered to be valid.
In conclusion, no mutagenic effect of ethoxy(trimethyl)silane was observed in the presence or in the absence of metabolic activation system under the conditions of this Mouse Lymphoma Assay.
Mammalian cytogenicity
Ethoxy(trimethyl)silane was tested for cytogenicity to mammalian cells in a study conducted according to OECD 473 and in compliance with GLP (Citoxlab, 2018). No test-substance related increase in the number of cells with aberrations was observed when Chinese hamster V79 lung fibroblasts were treated with 12.35, 37.04, 111.1, 333.3, and 1000 μg/mL of test substance in the presence and absence of metabolic activation. Insolubility (oily film/minimal oily film) was detected at the end of the treatment period in the final treatment medium in the 1000-333.3 μg/mL concentration range with and without metabolic activation. There were no large changes in the pH and osmolality. No cytotoxicity was observed in any sample. None of the treatment concentrations caused a biologically or statistically significant increase in the number of cells with structural chromosome aberrations in either assay with or without metabolic activation when compared to the appropriate negative (vehicle) control values. Polyploid metaphases (1-8) were found in some cases in the negative (vehicle) control, positive control or test item treated samples in the performed experiments. No endoreduplicated metaphases were detected in the performed experiments. The negative (vehicle) control data were within the acceptable range for the spontaneous aberration frequency, the positive control substances caused a statistically significant increase in the number of structural aberrations excluding gaps in the experiments with or without metabolic activation demonstrating the sensitivity of the test system.
In conclusion, ethoxy(trimethyl)silane did not induce a significant level of chromosome aberrations in Chinese hamster V79 cells in the performed experiments with and without metabolic activation. Therefore, ethoxy(trimethyl)silane was considered as not clastogenic in this test system.
Based on the above results the test substance is considered to have no genetic toxicity potential.
Justification for classification or non-classification
The available data on genetic toxicity of the test substance do not meet the criteria for classification according to Regulation (EC) No 1272/2008, and are therefore conclusive but not sufficient for classification.
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