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EC number: 221-338-7 | CAS number: 3069-40-7
Endpoint summary
Administrative data
Key value for chemical safety assessment
Genetic toxicity in vitro
Description of key information
In an in vitro bacterial reverse mutation assay / Ames test toxicity study, conducted according to OECD Test Guideline 471 and in compliance with GLP, trimethoxy(octyl)silane was negative in the presence and absence of metabolic activation (Dow Corning Corporation (2003).
In an in vitro
cytogenicity in mammalian cells toxicity study, conducted according to
OECD 473 and in compliance with GLP, triethoxy(octyl)silane was negative
in Chinese hamster ovary cells (Bioservices, 1997).
In an in vitro
mutagenicity in mammalian cells toxicity study, conducted according to
OECD Test Guideline 476 and in compliance with GLP,
triethoxy(octyl)silane was negative for mutagenicity in mouse lymphoma
L5178Y cells (BSL
Bioservice, 2012).
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:
- 2003-03-19 to 2003-04-01
- 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
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- bacterial reverse mutation assay
- Target gene:
- Histidine operon
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Species / strain / cell type:
- E. coli WP2 uvr A
- Metabolic activation:
- with and without
- Metabolic activation system:
- Phenobarbital and Beta-Naphthoflavone induced rat liver S9
- Test concentrations with justification for top dose:
- 3 µg/plate - 5000 µg/plate
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: Acetone
- Justification for choice of solvent/vehicle: Solubility properties and relative non-toxicity to bacteria - Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- sodium azide
- Remarks:
- TA 1535, TA 100 (without activation) 10 µg/plate
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: 4-nitro-o-phenylene-diamine 10 µg/plate in TA 98, 50 µg/plate in TA 1537
- Remarks:
- TA 1537, TA 98 (without activation)
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- methylmethanesulfonate
- Remarks:
- WP2 uvrA (without activation) 4 µl/plate
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: 2-aminoanthracene 2.5 µg/plate (TA 1535, TA 1537, TA 98, TA 100), 10 µg/plate (WP2 uvrA)
- Remarks:
- All strains (with activation)
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in agar (plate incorporation); preincubation
DURATION
- Preincubation period: 60 minutes
- Expression time (cells in growth medium): 48 hours
NUMBER OF REPLICATIONS: 3 plates for each test concentration
DETERMINATION OF CYTOTOXICITY
- Method: Background lawn assessment, revertant colony counts - Evaluation criteria:
- A result is considered 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 WP2 uvrA and 3-fold of the solvent control for TA 1535 and TA 1537 in both experiments.
A dose dependent increase is considered biologically relevant if the threshold is exceeded at more than one concentration. An increase exceeding the threshold at only one concentration is judged as biologically relevant if reproduced in an independent experiment.
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:
- No statistical evaluation of the data is required
- Key result
- Species / strain:
- S. typhimurium TA 98
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 100
- Metabolic activation:
- with
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 100
- Metabolic activation:
- without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- 5000 μg/plate
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 1535
- Metabolic activation:
- with
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- 5000 μg/plate
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 1535
- Metabolic activation:
- without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- 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:
- cytotoxicity
- Remarks:
- 5000 μg/plate
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- E. coli WP2 uvr A
- 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:
-
COMPARISON WITH HISTORICAL CONTROL DATA: With metabolic activation, the number of colonies did not quite reach the lower limit of historical control data in strain TA 1537, (negative and solvent control, exp 1), and in strain WP2 uvrA (negative control exp 1and 2, solvent control exp 1). Since these deviations are rather small, these effects are considered to be based upon biologically irrelevant fluctuations in the number of colonies. - Conclusions:
- The substance RMS 808 MC has been tested according to OECD 471 and under GLP. No increase in the number of revertants was observed for the test substance tested up to cytotoxic or limit concentrations in any of the test strains either with or without metabolic activation in either the initial plate incorporation assay or the independent pre-incubation experiment . It is concluded that the test substance is not mutagenic 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:
- 1994.11.07 - 1997.12.24
- 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)
- Deviations:
- no
- GLP compliance:
- yes
- Type of assay:
- in vitro mammalian chromosome aberration test
- Species / strain / cell type:
- Chinese hamster Ovary (CHO)
- Details on mammalian cell type (if applicable):
- - Type and identity of media:
- Properly maintained: yes/no
- Periodically checked for Mycoplasma contamination: yes
- Periodically checked for karyotype stability: yes/no
- Periodically "cleansed" against high spontaneous background: yes/no - Metabolic activation:
- with and without
- Metabolic activation system:
- Aroclor 1254 induced rat liver S-9
- Test concentrations with justification for top dose:
- 0.016 - 157 µg/ml
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: ethanol
- Justification for choice of solvent/vehicle: no information provided - Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- Remarks:
- Ethanol
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- benzo(a)pyrene
- Remarks:
- used with S9 metabolic activation 30 µg/ml
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- Remarks:
- Ethanol
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: N-methyl-N-nitro-N-nitrosoguanidine (MNNG) dosed at 2 µg/ml
- Remarks:
- used without S9 activation
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in medium
DURATION
- Exposure duration: 6 hours with and without S9 metabolic activation or up to 24 and 48 hours without S9
- Expression time (cells in growth medium): 18 hours
- Fixation time (start of exposure up to fixation or harvest of cells):
SPINDLE INHIBITOR (cytogenetic assays): Colcemid
STAIN (for cytogenetic assays): 5% Giemsa
NUMBER OF REPLICATIONS: 2
NUMBER OF CELLS EVALUATED: 200 per dose level
DETERMINATION OF CYTOTOXICITY
- Method: mitotic index; cell growth inhibition - Statistics:
- Fisher's exact test and the Cochran-Armitage test
- Key result
- Species / strain:
- Chinese hamster Ovary (CHO)
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- at 20 µg/ml (_MA); 50 µg/ml (+MA)
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
COMPARISON WITH HISTORICAL CONTROL- Conclusions:
- Triethoxyoctylsilane has been tested in a reliable in vitro cytogenetic assay according to OECD TG 473 and under GLP. The test substance did not induce statistically and biologically significant increases in the chromosomal aberration frequency of CHO (chinese hamster ovary) cells. It is concluded that the test substance is negative for the induction of chromosome aberrations (not clastogenic) in vitro 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
- Study period:
- 2011-12-21 to 2012-03-20
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.17 (Mutagenicity - In Vitro Mammalian Cell Gene Mutation Test)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.5300 - In vitro Mammalian Cell Gene Mutation Test
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: IWGT Recommendations
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- (Bayerisches Landesamt für Gesundheit und Lebensmittelsicherheit, Germany)
- Type of assay:
- mammalian cell gene mutation assay
- Target gene:
- Thymidine kinase
- Species / strain / cell type:
- mouse lymphoma L5178Y cells
- Details on mammalian cell type (if applicable):
- - Type and identity of media: RPMI
- Properly maintained: Yes
- Periodically checked for Mycoplasma contamination: yes
- Periodically "cleansed" against high spontaneous background: yes - Metabolic activation:
- with and without
- Metabolic activation system:
- Liver S9 of Wistar Phenobarbital and ß-Naphthoflavone-induced rat liver S9 mix
- Test concentrations with justification for top dose:
- Pre-expt I: 0.2, 0.5, 2.5, 5.0, 7.5 and 10.0 mM (+/-MA); Pre-expt II: 0.01, 0.1, 1.0, 2.0, 5.0, 10.0 mM (-MA, 24 h exp); Expt I: 0.1, 0.2, 0.5, 1.0, 2.5, 5.0, 7.5 and 10.0 mM (+/-MA); Expt II: 0.15, 0.3, 0.7, 2.0, 4.0, 6.0, 8.0 and 10.0 mM (+MA); 0.001, 0.002, 0.005, 0.01, 0.02, 0.05, 0.10 and 0.20 mM (-MA)
- Vehicle / solvent:
- THF was used as solvent (0.35% THF v/v in the samples). To reach a final concentration of 0.35% THF v/v in the samples the test item stock solution was diluted in RPMI + 5% HS for short-term exposure or RPMI + 7.5% HS for long-term exposure. After adding the THF stock solution to cell culture medium precipitate formed.
The solvent was compatible with the survival of the cells and the activity of the S9 mix. - Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- Remarks:
- THF
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- benzo(a)pyrene
- Remarks:
- with metabolic activation 3.5 µg/mL
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- ethylmethanesulphonate
- Remarks:
- without metabolic activation 200 µg/mL and 300 µg/mL
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- methylmethanesulfonate
- Remarks:
- without metabolic activation 10 µg/mL
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: dissolved in THF (0.35% THF v/v in the samples)
DURATION: 4 h (short-term exposure), 24 h (long-term exposure)
Expression time (cells in growth medium): 48 h
Selection time (if incubation with selection agent): about 14 days
SELECTION AGENT ( mutation assay) 5 µg/ml trifluorothymidine
NUMBER OF REPLICATIONS: two separate experiments (I+II) with single exposure; cells were seeded in 4 plates and evaluated
NUMBER OF CELLS SEEDED: 2000 cells per well
DETERMINATION OF CYTOTOXICITY: relative total growth (RTG)
ACTIVATION: S9 mix contained glucose-6-phosphate and NADP as co-factors, and sufficient S9 to give a final protein concentration in the cultures of 0.75 mg/ml - Evaluation criteria:
- The test item is considered mutagenic if following criteria are met:
-The induced mutant frequency meets or exceeds the Global Evaluation factor (GEF) of 126 per 10^6 cells
- A dose-dependent increase in mutant frequency is detected.
Besides, combined with a positive effect in the mutant frequency, an increased occurrence of small colonies (≥40% of total colonies) is an indication for potential clastogenic effects and/or chromosomal aberrations.
According to the OECD guideline, the biological relevance is considered first for the interpretation of results. Statistical methods might be used as an aid in evaluation the test result.
A test item is considered to be negative if the induced mutant frequency is below the GEF and the trend test is negative. - Statistics:
- The non-parametric Mann-Whitney test is applied to the mutation data to prove the dose groups for any significant difference in mutant frequency compared to the negative /solvent controls.
- Key result
- Species / strain:
- mouse lymphoma L5178Y cells
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- RTG of 14.6% and 9.7% without metabolic activation.
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Conclusions:
- Triethoxyoctylsilane has been tested for mutagenicity to mammalian cells in a reliable study conducted according to OECD TG 476 and in compliance with GLP. No biologically relevant increase in mutation rate was found in mouse lymphoma L5178Y cells with or without metabolic activation in either the initial or the repeat experiment, up to limit and cytotoxic concentrations. The global evaluation factor was not exceeded at any concentration. In addition, colony sizing showed no clastogenic effects in either experiment. Appropriate solvent and positive controls were included and gave 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 2: Pre-toxicity test
|
TA98 |
TA100 |
TA1535 |
||||||
Conc. |
— MA |
+ MA |
Cytotoxic |
— MA |
+ MA |
Cytotoxic |
— MA |
+ MA |
Cytotoxic |
Negative control |
23 |
29 |
No |
108 |
107 |
No |
10 |
12 |
No |
0* |
26 |
29 |
No |
134 |
113 |
No |
9 |
13 |
No |
3 |
16 |
30 |
No |
101 |
106 |
No |
13 |
9 |
No |
10 |
19 |
30 |
No |
114 |
127 |
No |
14 |
9 |
No |
33 |
21 |
26 |
No |
115 |
104 |
No |
12 |
13 |
No |
100 |
19 |
28 |
No |
88 |
121 |
No |
12 |
10 |
No |
333 |
20 |
27 |
No |
68 |
81 |
No |
9 |
10 |
No |
1000 |
16 |
26 |
No |
76 |
84 |
No |
9 |
10 |
No |
2500 |
18 |
23 |
No |
73 |
67 |
No |
8 |
7 |
No |
5000 |
17 |
20 |
No |
52 |
58 |
Yes |
5 |
6 |
Yes |
Positive control |
228 |
1495 |
No |
1068 |
1629 |
No |
697 |
211 |
No |
*solvent control with acetone
Table 2: Pre-toxicity test
|
TA1537 |
E. coli WP2 uvrA |
||||
Conc. |
— MA |
+ MA |
Cytotoxic |
— MA |
+ MA |
Cytotoxic |
Negative control |
7 |
6 |
No |
31 |
32 |
No |
0* |
4 |
5 |
No |
29 |
31 |
No |
3 |
3 |
5 |
No |
28 |
25 |
No |
10 |
5 |
5 |
No |
28 |
34 |
No |
33 |
5 |
5 |
No |
27 |
33 |
No |
100 |
4 |
7 |
No |
32 |
34 |
No |
333 |
3 |
4 |
No |
30 |
27 |
No |
1000 |
2 |
3 |
No |
30 |
35 |
No |
2500 |
3 |
3 |
No |
31 |
32 |
No |
5000 |
1 |
2 |
Yes |
18 |
35 |
No |
Positive control |
50 |
226 |
No |
804 |
215 |
No |
*solvent control with acetone
Table 3: Experiment 1 Plate incorporation number of revertants per plate (mean of 3 plates)
|
TA98 |
TA100 |
TA1535 |
||||||
Conc. |
— MA |
+ MA |
Cytotoxic |
— MA |
+ MA |
Cytotoxic |
— MA |
+ MA |
Cytotoxic |
Negative control |
23 |
29 |
No |
108 |
107 |
No |
10 |
12 |
No |
0* |
26 |
29 |
No |
134 |
113 |
No |
9 |
13 |
No |
33 |
21 |
26 |
No |
115 |
104 |
No |
12 |
13 |
No |
100 |
19 |
28 |
No |
88 |
121 |
No |
12 |
10 |
No |
333 |
20 |
27 |
No |
68 |
81 |
No |
9 |
10 |
No |
1000 |
16 |
26 |
No |
76 |
84 |
No |
9 |
10 |
No |
2500 |
18 |
23 |
No |
73 |
67 |
No |
8 |
7 |
No |
5000 |
17 |
20 |
No |
52 |
58 |
Yes |
5 |
6 |
Yes |
Positive control |
228 |
1495 |
No |
1068 |
1629 |
No |
697 |
211 |
No |
*solvent control with acetone
Table 3: Experiment 1 Plate incorporation - number of revertants per plate (mean of 3 plates)
|
TA1537 |
E. coli WP2 uvrA |
||||
Conc. |
— MA |
+ MA |
Cytotoxic |
— MA |
+ MA |
Cytotoxic |
Negative control |
7 |
6 |
No |
31 |
32 |
No |
0* |
4 |
5 |
No |
29 |
31 |
No |
33 |
5 |
5 |
No |
27 |
33 |
No |
100 |
4 |
7 |
No |
32 |
34 |
No |
333 |
3 |
4 |
No |
30 |
27 |
No |
1000 |
2 |
3 |
No |
30 |
35 |
No |
2500 |
3 |
3 |
No |
31 |
32 |
No |
5000 |
1 |
2 |
Yes |
18 |
35 |
No |
Positive control |
50 |
226 |
No |
804 |
215 |
No |
*solvent control with acetone
Table 4: Experiment 2 Pre-incubation number of revertants per plate (mean of 3 plates)
|
TA98 |
TA100 |
TA1535 |
||||||
Conc. |
— MA |
+ MA |
Cytotoxic |
— MA |
+ MA |
Cytotoxic |
— MA |
+ MA |
Cytotoxic |
Negative control |
30 |
38 |
No |
148 |
184 |
No |
20 |
18 |
No |
0* |
28 |
35 |
No |
154 |
187 |
No |
17 |
17 |
No |
33 |
30 |
40 |
No |
150 |
199 |
No |
17 |
19 |
No |
100 |
28 |
40 |
No |
146 |
214 |
No |
17 |
16 |
No |
333 |
23 |
32 |
No |
177 |
198 |
No |
18 |
16 |
No |
1000 |
24 |
37 |
No |
195 |
216 |
No |
17 |
17 |
No |
2500 |
28 |
35 |
No |
188 |
242 |
No |
21 |
15 |
No |
5000 |
31 |
44 |
No |
207 |
215 |
No |
16 |
17 |
No |
Positive control |
239 |
1465 |
No |
1536 |
1207 |
No |
1479 |
299 |
No |
*solvent control with acetone
Table 4: Experiment 2 Pre-incubation number of revertants per plate (mean of 3 plates)
|
TA1537 |
E. coli WP2 uvrA |
||||
Conc. |
— MA |
+ MA |
Cytotoxic |
— MA |
+ MA |
Cytotoxic |
Negative control** |
9 |
11 |
No |
38 |
33 |
No |
0* |
9 |
11 |
No |
36 |
38 |
No |
33 |
10 |
13 |
No |
28 |
35 |
No |
100 |
7 |
11 |
No |
39 |
36 |
No |
333 |
5 |
14 |
No |
42 |
46 |
No |
1000 |
6 |
10 |
No |
31 |
46 |
No |
2500 |
6 |
11 |
No |
41 |
46 |
No |
5000 |
5 |
12 |
No |
40 |
41 |
No |
Positive control |
77 |
227 |
No |
444 |
346 |
No |
*solvent control with acetone
Chromosome aberration assay |
||||||
Treatment µg/ml |
S9 activation |
Treatment /Harvest Time |
Mitotic index* |
Metaphase cells scored for aberrations |
Cells with aberrations (200 cells evaluated) |
|
Numerical Structural |
||||||
Negative control |
- |
24 |
7.2 |
200 |
2.5 |
0.5 |
Solvent control |
- |
6/24 |
6.1 |
200 |
2.5 |
0.5 |
A-137 |
|
|
|
|
|
|
8.5 |
- |
6/24 |
6.8 |
200 |
1.0 |
1.0 |
11.3 |
- |
6/24 |
8.2 |
200 |
2.0 |
0.5 |
15 |
- |
6/24 |
8.5 |
200 |
0.5 |
2.0 |
20 |
- |
6/24 |
3.9 |
155 |
0.6 |
0.0 |
Positive control |
- |
6/24 |
5.2 |
200 |
1.5 |
27.0** |
|
|
|
|
|
|
|
Negative control |
+ |
24 |
10.9 |
200 |
3.0 |
0.5 |
Solvent control |
+ |
6/24 |
8.2 |
200 |
5.0 |
0.5 |
A-137 |
|
|
|
|
|
|
21.3 |
+ |
6/24 |
9.5 |
200 |
5.0 |
0.5 |
28.3 |
+ |
6/24 |
9.4 |
200 |
5.0 |
0.0 |
37.6 |
+ |
6/24 |
6.6 |
200 |
8.0 |
1.5 |
50 |
+ |
6/24 |
3.2 |
200 |
3.5 |
1.0 |
Positive control |
+ |
6/24 |
3.0 |
200 |
8.5 |
43.0** |
|
|
|
|
|
|
|
Negative control |
- |
24 |
12.1 |
200 |
0.5 |
0.5 |
Solvent control |
- |
24/24 |
9.1 |
200 |
0.0 |
1.0 |
A-137 |
|
|
|
|
|
|
8.5 |
- |
24/24 |
7.6 |
200 |
0.0 |
1.0 |
11.3 |
- |
24/24 |
11.6 |
200 |
1.0 |
1.0 |
15 |
- |
24/24 |
11.7 |
200 |
1.5 |
1.0 |
20 |
- |
24/24 |
1.7 |
37 |
0.0 |
0.0 |
Positive control |
- |
24/24 |
5.9 |
200 |
1.5 |
20.5** |
|
|
|
|
|
|
|
Negative control |
- |
48 |
5.0 |
200 |
0.0 |
0.5 |
Solvent control |
- |
48/48 |
4.0 |
200 |
0.0 |
1.5 |
A-137 |
|
|
|
|
|
|
8.5 |
- |
48/48 |
4.1 |
200 |
0.0 |
2.0 |
11.3 |
- |
48/48 |
3.1 |
200 |
0.0 |
0.0 |
15 |
- |
48/48 |
2.0 |
200 |
1.0 |
0.0 |
20 |
- |
48/48 |
2.0 |
200 |
0.5 |
2.0 |
Positive control |
- |
48/48 |
2.2 |
200 |
1.0 |
18.0** |
* Number of cells evaluated for MI not indicated in report.
** Aberration frequency statistically significant
Pre-experiment for toxicity with and without metabolic activation
Concentration (mM) |
Number of cells 4 h after treatment |
Number of cells 24 h after treatment |
Number of cells 48 h after treatment |
Suspension growth |
Relative suspension growth |
|||||
|
+S9 |
-S9 |
+S9 |
-S9 |
+S9 |
-S9 |
+S9 |
-S9 |
+S9 |
-S9 |
Negative control |
271000 |
278000 |
946000 |
948000 |
1600000 |
1570000 |
15.1 |
14.9 |
89.8 |
103.6 |
307000 |
356000 |
105000 |
115000 |
1510000 |
1540000 |
15.9 |
17.7 |
94.1 |
123.3 |
|
Solvent control |
307000 |
256000 |
104000 |
807000 |
1560000 |
1570000 |
16.2 |
12.7 |
100.0 |
100.0 |
339000 |
313000 |
112000 |
101000 |
1560000 |
1590000 |
17.5 |
16.1 |
|||
0.2 |
284000 |
271000 |
77000 |
593000 |
1540000 |
1480000 |
11.9 |
8.8 |
70.4 |
61.1 |
0.5 |
307000 |
252000 |
876000 |
377000 |
1490000 |
1190000 |
13.1 |
4.5 |
77.5 |
31.2 |
2.5 |
289000 |
220000 |
728000 |
186000 |
1620000 |
637000 |
11.8 |
1.9 |
70.0 |
13.3 |
5.0 |
316000 |
225000 |
798000 |
137000 |
1550000 |
286000 |
12.4 |
0.9 |
73.4 |
6.0 |
7.5 (P) |
303000 |
271000 |
650000 |
239000 |
1590000 |
850000 |
10.3 |
2.6 |
61.3 |
17.8 |
10.0 (P) |
305000 |
244000 |
728000 |
183000 |
1580000 |
481000 |
11.5 |
1.4 |
68.3 |
10.0 |
Summary: Experiment 1 and 2 with metabolic activation
|
Treatment (mM) |
RTG (%) |
MF (mutants/106cells) |
IMF (mutants/106cells) |
Precipitate |
|
Negative control |
103.5 |
125.6 |
/ |
- |
|
98.1 |
/ |
- |
||
|
Solvent control |
100.0 |
135.2 |
/ |
- |
|
/ |
- |
|||
|
0.1 |
72.3 |
142.3 |
7.2 |
- |
Exp 1 |
0.2 |
73.5 |
143.3 |
8.1 |
- |
|
0.5 |
84.9 |
97.1 |
-38.1 |
- |
|
1.0 |
63.7 |
182.8 |
47.6 |
- |
|
2.5 |
67.1 |
144.4 |
9.2 |
- |
|
5.0 |
87.2 |
117.6 |
-17.6 |
- |
|
7.5 |
78.1 |
154.8 |
19.6 |
- |
|
10.0 |
74.3 |
130.3 |
-4.8 |
+ |
|
Positive control |
38.4 |
918.4 |
783.2 |
- |
|
|
|
|
|
|
|
Treatment (mM) |
RTG (%) |
MF (mutants/106cells) |
IMF (mutants/106cells) |
Precipitate |
|
Negative control |
98.9 |
116.5 |
/ |
- |
|
111.8 |
/ |
- |
||
|
Solvent control |
100.0 |
116.7 |
/ |
- |
|
/ |
- |
|||
|
0.15 |
111.4 |
105.1 |
-11.6 |
- |
Exp 2 |
0.3 |
96.2 |
131.1 |
14.4 |
- |
|
0.7 |
75.7 |
128.5 |
11.8 |
- |
|
2.0 |
42.3 |
220.5 |
103.8 |
- |
|
4.0 |
72.7 |
138.8 |
22.2 |
- |
|
6.0 |
58.9 |
170.6 |
53.9 |
- |
|
8.0 |
74.1 |
134.6 |
17.9 |
+ |
|
10.0 |
76.4 |
154.9 |
38.2 |
+ |
|
Positive control |
50.5 |
1141.0 |
1024.3 |
- |
MF - mutant frequency
IMF = induced mutant frequency
RTG = relative total growth
Summary: Experiment 1 and 2 without metabolic activation
|
Treatment (mM) |
RTG (%) |
MF (mutants/106cells) |
IMF (mutants/106cells) |
Precipitate |
|
Negative control |
122.0 |
142.0 |
/ |
- |
|
129.6 |
/ |
- |
||
|
Solvent control |
100.0 |
144.3 |
/ |
- |
|
/ |
- |
|||
|
0.1 |
100.3 |
177.2 |
32.9 |
- |
Exp 1 |
0.2 |
87.3 |
157.4 |
13.0 |
- |
|
0.5 |
98.4 |
186.0 |
41.6 |
- |
|
1.0 |
49.2 |
190.1 |
45.7 |
- |
|
2.5 |
37.8* |
179.4 |
35.1 |
- |
|
5.0 |
37.2 |
179.3 |
35.0 |
- |
|
7.5 |
17.1 |
224.1 |
79.8 |
+ |
|
10.0 |
14.6 |
264.7 |
120.4 |
+ |
|
Positive control 1 |
75.1 |
817.6 |
673.2 |
- |
|
Positive control 2 |
85.2 |
564.1 |
419.7 |
- |
|
|
|
|
|
|
|
Treatment (mM) |
RTG (%) |
MF (mutants/106cells) |
IMF (mutants/106cells) |
Precipitate |
|
Negative control |
145.4 |
110.6 |
/ |
- |
|
122.8 |
/ |
- |
||
|
Solvent control |
100.0 |
109.3 |
/ |
- |
|
/ |
- |
|||
|
0.001 |
114.6 |
108.6 |
-0.8 |
- |
Exp 2 |
0.002 |
99.3 |
94.7 |
-14.6 |
- |
|
0.005 |
103.4 |
120.0 |
10.6 |
- |
|
0.01 |
62.1 |
121.8 |
12.5 |
- |
|
0.02 |
82.5 |
160.0 |
50.6 |
- |
|
0.05 |
98.6 |
108.4 |
-0.9 |
- |
|
0.10 |
16.8 |
173.0 |
63.6 |
- |
|
0.20 |
0.9 |
119.1 |
9.7 |
- |
|
Positive control 1 |
21.3 |
2373.6 |
2264.2 |
- |
|
Positive control 2 |
14.7 |
1826.6 |
1717.3 |
- |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Genetic toxicity in vivo
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Data are available for trimethoxy(octyl)silane (CAS 3069-40-7) from a reliable in vitro study for bacterial mutagenicity (Dow Corning Corporation 2003). An additional bacterial mutagenicity study is also available (Anawa Bioservice, 1996). The results of both experiments were in agreement. No further data are available for the registered substance, however, reliable data are available for the related substance triethoxy(octyl)silane, CAS 2943-75-1 from in vitro studies on cytogenicity and mutagenicity to mammalian cells. Both the structurally-analogous substance, triethoxy(octyl)silane, CAS 2943-75-1 and the registered substance, trimethoxy(octyl)silane, CAS 3069-40-7, hydrolyse to octylsilanetriol. Hydrolysis is likely to occur under the conditions of the studies and also in vivo. The other products of hydrolysis, methanol and ethanol, are not genotoxic OECD (2004a and OECD 2004b).
Triethoxy(octyl)silane was chosen as read-across substance as it has the same hydrolysis product as trimethoxy(octyl)silane, and neither substance has any functional groups that are associated with genetic toxicity. Additional information is given in a supporting report (PFA (2013aa)) attached in Section 13.
Trimethoxy(octyl)silane has been tested for mutagenicity to bacteria in a study conducted according to OECD Test Guideline 471 and in compliance with GLP (Dow Corning Corporation (2003). No increase in the number of revertants was observed for the test substance tested up to cytotoxic or limit concentrations in any of the test strains either with or without metabolic activation in either the initial plate incorporation assay or the independent pre-incubation experiment. Appropriate solvent and positive controls were included and gave expected results. It is concluded that the test substance is not mutagenic to bacteria under the conditions of the test.
Additional evidence for lack of mutagenicity to bacteria is available from a study conducted according to a protocol similar to OECD Test Guideline 471 (Anawa Bioservice, 1996). No evidence of mutagenicity was observed with or without metabolic activation when trimethoxyoctylsilane was tested in Salmonella typhimurium strains TA98, TA 100, TA 1535, TA1537 and TA 1538.
In a cytogenicity study conducted according to OECD Test Guideline 473 and in compliance with GLP, no evidence of the induction of chromosome aberration was observed when the analogous substance, triethoxy(octyl)silane, was tested with or without metabolic activation in CHO K1 cells (MA Bioservices 1997).
The structural analogue triethoxy(octyl)silane has been tested for mutagenicity to mammalian cells in a reliable study conducted according to OECD Test Guideline 476 and in compliance with GLP (BSL Bioservice, 2012). No biologically relevant increase in mutation rate was found in mouse lymphoma L5178Y cells with or without metabolic activation in either the initial or the repeat experiment, up to limit and cytotoxic concentrations. The global evaluation factor was not exceeded at any concentration. In addition, colony sizing showed no clastogenic effects in either experiment. It is concluded that the test substance is negative for mutagenicity under the conditions of the test.
There is no justification from in vitro results for testing in vivo.
See attachment to Section 13 for justification of read-across.
Justification for classification or non-classification
Based on the available in vitro genotoxicity data, trimethoxy(octyl)silane is not classified for mutagenicity according to Regulation (EC) No 1272/2008.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
