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EC number: 201-083-8 | CAS number: 78-10-4
Endpoint summary
Administrative data
Key value for chemical safety assessment
Genetic toxicity in vitro
Description of key information
The genetic toxicity studies for tetraethyl orthosilicate (CAS 78-10-4, EC No. 201-083-8) were conducted according to the appropriate OECD guidelines, or to protocols that are similar to OECD guidelines. The studies were conducted in compliance with GLP, except possibly BRRC 1981 and the published Lionti et al. 2014, for which information on GLP is not available.
Gene mutation assessed as weight of evidence (Bacterial reverse mutation assay / Ames test): negative with and without activation in Salmonella typhimurium TA98, TA100, TA1535, TA1537 and TA1538 (similar to OECD Test Guideline 471) (Hüls AG 1993).
Gene mutation (Bacterial reverse mutation assay / Ames test): negative with and without activation in Salmonella typhimurium strains TA 98, TA 100, TA1535, TA1537 or Escherichia coli WP2 (OECD Test Guideline 471) (Lionti et al. 2014).
Cytogenicity in mammalian cells: negative in CHO cells (OECD Test Guideline 473) (BioReliance 2002).
Mutagenicity in mammalian cells: negative in CHO cells (similar to OECD Test Guideline 476) (BRRC 1981).
Link to relevant study records
- Endpoint:
- in vitro cytogenicity / chromosome aberration study in mammalian cells
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1993-01-29 to 1993-03-22
- 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)
- GLP compliance:
- yes
- Type of assay:
- in vitro mammalian chromosome aberration test
- Target gene:
- Histidine operon (S. typhimurium strains); tryptophan operon (E. coli).
- Species / strain / cell type:
- Chinese hamster Ovary (CHO)
- Metabolic activation:
- with and without
- Metabolic activation system:
- Aroclor induced rat liver S9
- Test concentrations with justification for top dose:
- 125 to 1500 µg/mL (without activation, 4 and 20h exposure), and 500 to 2080 µg/mL (witn activation 4 hour exposure)
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent: based on infomation provided by the Sponsor and compatibility with the target cells. - Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- mitomycin C
- Remarks:
- (without activation)
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- cyclophosphamide
- Remarks:
- (with activation)
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in medium
DURATION
- Exposure duration: 4h / 20h (-S9), 4h (+S9)
- Expression time (cells in growth medium): 20h
- Fixation time (start of exposure up to fixation or harvest of cells): 20h
NUMBER OF REPLICATIONS: duplicate flasks
NUMBER OF CELLS EVALUATED: 200 metaphase spreads (100 per duplicate flask), per concentration.
DETERMINATION OF CYTOTOXICITY
- Method: percentage total growth
- Evaluation criteria:
- Cells examined for numerical and structural aberrations, and statistical significance calculated. For the result to be positive, the increase in aberrations must be statistically significant and dose related.
Toxicity is defined as a 50 % or greater reduction in cell growth. - Statistics:
- The number and type of aberrations found, the percentage of structurally and numerically damaged cells (% aberrant cells) in the total population examined and mean aberrations per cell were calculated for each group. Fisher's exact test was used to compare pairwise the percent aberrant cells of each treatment group with that of the solvent control.
Statistical analysis of the percent aberrant cells was performed using the Fisher's exact test. Fisher's test was used to compare pairwise the percent aberrant cells of each treatment group with that of the solvent control. In the event of a positive Fisher's test at any test article dose level, the Cochran-Armitage test was used to measure dose-responsiveness. - Species / strain:
- Chinese hamster Ovary (CHO)
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- With metabolic activation: 1250 µg/ml; Without metabolic activation: 1250 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: at highest test concentration was 7.4
- Effects of osmolality: checked
RANGE-FINDING/SCREENING STUDIES: Substantial toxicity (i.e., at least 50% cell growth inhibition, relative to the solvent control) was observed at dose level 2080 pg/mL in the non-activated 4 and 20 hour exposure groups and in the S9 activated 4 hour exposure group.
COMPARISON WITH HISTORICAL CONTROL DATA: The percentage of cells with structural aberrations in the test article-treated groups was statistically increased above that of the solvent control at dose level 1250 pg/mL (p - Remarks on result:
- other: No mutagenic potential
- Conclusions:
- Tetraethyl orthosilicate has been tested in a reliable study conducted according to OECD Test Guideline 473 in compliance with GLP (reliability score 1). No increase in the number of structural and numerical chromosome aberrations in CHO cells was observed. Appropriate positive and solvent 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 the test.
- Endpoint:
- in vitro gene mutation study in mammalian cells
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Remarks:
- Tables of results are not included in the copy of the report available to the reviewer.
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
- GLP compliance:
- no
- Type of assay:
- mammalian cell gene mutation assay
- Species / strain / cell type:
- Chinese hamster Ovary (CHO)
- Metabolic activation:
- with and without
- Metabolic activation system:
- Aroclor induced rat liver S9
- Test concentrations with justification for top dose:
- up to 0.15% by volume, equivalent to 1.5 µg/ml
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: DMSO;
- Justification for choice of solvent/vehicle: none given in study report - Untreated negative controls:
- yes
- Remarks:
- cell culture medium
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- N-dimethylnitrosamine
- Remarks:
- with activation
- Untreated negative controls:
- yes
- Remarks:
- cell culture medium
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- ethylmethanesulphonate
- Remarks:
- without activation
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in medium
DURATION
- Exposure duration: 5 hours minimum
- Expression time (cells in growth medium): 7-10 days
- Selection time (if incubation with a selection agent): Not specified
- Fixation time (start of exposure up to fixation or harvest of cells): 9-12 days
SELECTION AGENT (mutation assays):
Not specified
NUMBER OF REPLICATIONS: no information; 10 concentrations tested
DETERMINATION OF CYTOTOXICITY
- Method: relative total growth - Evaluation criteria:
- A dose-related increase in the number of revertants relative to control values was considered positive.
- Statistics:
- Student's t-test
- Species / strain:
- Chinese hamster Ovary (CHO)
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- variable, toxicity observed at several concentrations tested
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- valid
- Additional information on results:
- COMPARISON WITH HISTORICAL CONTROL DATA: mutant frequencies for solvent controls were in an acceptable and low range compared with historical control values,
ADDITIONAL INFORMATION ON CYTOTOXICITY: Percentage survival was dose related for concentrations between 9 - 12 µg/ml. Less cytotoxicity was observed at two higher doses, and no survival was obtained at the highest dose. This unusual response may indicate possible phase separations characteristic of some organosilicon materials in aqueous media. - Remarks on result:
- other: No mutagenic potential
- Conclusions:
- Tetraethyl orthosilicate has been tested in a reliable study according to a protocol that is similar to OECD Test Guideline 476 (reliability score 2). There was no information on GLP compliance. Weak responses (increase in the number of revertants relative to the solvent control ) were obtained at the 1.4 and 1.1 µg/ml concentrations tested without activation in Chinese hamster ovary cells. The biological significance of these results was doubtful because the effects were produced at non-consecutive doses and were within the range of variations observed in historical negative control data. It is therefore considered that the test substance is negative for the induction of mutations in mammalian cells under the conditions of this test.
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 1993-01-29 to 1993-03-22
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study with acceptable restrictions
- Remarks:
- The restrictions are that the range of strains does not comply with current guidelines.
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
- Version / remarks:
- Cited as Directive 84/449/EEC, B.14
- Deviations:
- yes
- Remarks:
- range of stains differs from current guideline
- GLP compliance:
- yes
- Type of assay:
- bacterial reverse mutation assay
- Species / strain / cell type:
- S. typhimurium, other: TA98, TA100, TA1535, TA1537 and TA1538
- Metabolic activation:
- with and without
- Metabolic activation system:
- phenobarbiturate activated S9
- Test concentrations with justification for top dose:
- 8, 40, 200, 1000, 5000 µg/plate
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: DMSO
- Untreated negative controls:
- yes
- Remarks:
- water
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 2-nitrofluorene
- Remarks:
- TA 98, TA 1538 (without activation)
- Untreated negative controls:
- yes
- Remarks:
- water
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: Sodium trinitride
- Remarks:
- TA 100, TA 1535 (without activation)
- Untreated negative controls:
- yes
- Remarks:
- water
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 9-aminoacridine
- Remarks:
- TA 1537 (without activation)
- Untreated negative controls:
- yes
- Remarks:
- water
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- cyclophosphamide
- Remarks:
- TA 100 (with activation)
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in agar; preincubation
DURATION
- Preincubation period: 30 minutes
- Exposure duration: 96 hours
NUMBER OF REPLICATIONS: 3 per test concentration; Plate incorporation test was repeated in two preincubation assays (only two strains tested in final assay)
DETERMINATION OF CYTOTOXICITY
- Method: relative total growth - Evaluation criteria:
- Substances that do not show a mutagenic effect at a concentration of 5000 µg/plate are considered to be non-mutagenic.
- Statistics:
- Revertant colonies counted, and mean / standard deviation calculated using a computer program written by BIOSYS Co.
- 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:
- not applicable
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 100
- 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:
- not applicable
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 1535
- 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:
- not applicable
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 1537
- 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:
- not applicable
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 1538
- 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:
- not applicable
- Positive controls validity:
- valid
- Additional information on results:
- No precipitation or cytotoxicity were observed during the course of the test.
- Remarks on result:
- other: No mutagenic potential
- Conclusions:
- Tetraethyl orthosilicate (CAS No. 78-10-4) has been tested in a reliable study according to an appropriate EU guideline (84/449/EEC B 14), in compliance with GLP (reliability score 2). No evidence of increase in the number of revertants relative to solvent control was observed in Salmonella typhimurium TA98, TA100, TA1535, TA1537 and TA1538, when tested up to limit concentrations. Appropriate concurrent solvent (DMSO), negative (water) and positive controls were included, and the expected responses were observed. It is concluded that the test substance is not mutagenic to bacteria under the conditions of this test.
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 1993-01-29 to 1993-03-22
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study with acceptable restrictions
- Remarks:
- GLP compliance not specified
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- GLP compliance:
- not specified
- Remarks:
- The source of this test is published literature; publications often do not include information on GLP status. Due to the lack of information on GLP status for this test, a weight of evidence approach has been taken for bacterial mutagenicity.
- Type of assay:
- bacterial reverse mutation assay
- Target gene:
- Histidine operon (S. typhimurium strains); tryptophan operon (E. coli).
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2
- Metabolic activation:
- with and without
- Metabolic activation system:
- Phenobarbital/beta-naphthoflavone induced rat liver S9
- Test concentrations with justification for top dose:
- 0, 313, 625, 1250, 2500, 5000 µg/plate
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: DMSO
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 2-nitrofluorene
- Remarks:
- 2 µg/plate TA98 without metabolic activation
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- sodium azide
- Remarks:
- 1 µg/plate TA100 and TA1535 without metabolic activation
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: ICR191
- Remarks:
- 1 µg/plate TA1537 without metabolic activation
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 4-nitroquinoline-N-oxide
- Remarks:
- 0.5 µg/plate E. coli WP2 uvrA (pKM101) without metabolic activation
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: 2-aminoanthracene
- Remarks:
- without metabolic activation; 2.5 µg/plate TA 1535, TA 1537, TA 98, TA 100 and 25 µg/plate E. coli WP2 uvrA (pKM101)
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in agar (plate incorporation)
DURATION
- Exposure duration: no information
SELECTION AGENT (mutation assays): histidine or tryptophan-deficient agar
NUMBER OF REPLICATIONS: triplicate plates
DETERMINATION OF CYTOTOXICITY
- Method: no information; concentrations were based on cytotoxicity evaluation - Evaluation criteria:
- The test substance is considered positive when there is an increase in the number of revertants relative to the solvent control (≥ twofold for TA 98, TA100 and E.coli; ≥ threefold for TA 1535 or TA 1537).
- Statistics:
- Revertant colonies counted, and mean / standard deviation calculated using a computer program written by BIOSYS Co.
- 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:
- not specified
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- not specified
- Species / strain:
- S. typhimurium TA 100
- 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:
- not specified
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- not specified
- Species / strain:
- S. typhimurium TA 1535
- 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:
- not specified
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- not specified
- Species / strain:
- S. typhimurium TA 1537
- 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:
- not specified
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- not specified
- Species / strain:
- E. coli WP2
- 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:
- not specified
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- not specified
- Additional information on results:
- No precipitation or cytotoxicity were observed during the course of the test.
- Remarks on result:
- other: No mutagenic potential
- Conclusions:
- Tetraethyl orthosilicate has been tested for mutagenicity to bacteria in study conducted according to OECD Test Guideline 471 (reliability score 2), up to limit concentrations. No data are available on GLP compliance. No test substance induced increase in the number of revertants was observed in Salmonella typhimurium strains TA 98, TA 100, TA1535, TA1537 or Escherichia coli WP2 in the presence or absence of metabolic activation. Appropriate positive and solvent 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
For the chromosome aberration assay, CHO cells were seeded at approximately 5 x l0 5 cells/25 cm² flask and were incubated at 37+/- 1C in a humidified atmosphere of 5+/-1% CO2 in air for 16-24 hours.
Treatment time: 4hrs,
S9: none, Toxicity at highest dose scored: 52% at 1250 µg/ml;
Mitotic index reduction: 4%
Treatment time: 20 hrs, S9: none,
Toxicity at highest dose scored: 56% at 1250 µg/ml;
Mitotic index reduction: none
Treatment time: 4 hrs, S9: yes,
Toxicity at highest dose scored: 54% at 1250 µg/ml;
Mitotic index reduction: 10%
The percentage of structurally damaged cells in the mitomycin (positive control in non-activated system) treatment (15%) was statistically significant.
The percentage of structurally damaged cells in the cyclophosphamide (positive control in activated system) treatment (14%) was statistically significant.
Table 1 Summary of results (200 cells scored)
Treatment µg/ml |
Metabolic activation |
Treatment time (h) |
Mean mitotic index |
Aberrations per cell (mean (±SD) |
Cells with aberrations % |
|
numerical |
Structural |
|||||
0* |
- |
4 |
15.7 |
0.015 ± 0.122 |
3.0 |
1.5 |
250 |
- |
4 |
16.0 |
0.005 ± 0.071 |
2.5 |
0.5 |
750 |
- |
4 |
15.2 |
0.005 ± 0.071 |
3.0 |
0.5 |
1250 |
- |
4 |
15.0 |
0.000 ± 0.000 |
2.5 |
1.0 |
Positive control |
- |
4 |
15.5 |
0.130 ± 0.484 |
4.0 |
10.0 |
0* |
+ |
4 |
16.6 |
0.000 ± 0.000 |
2.0 |
0.0 |
250 |
+ |
4 |
15.1 |
0.005 ± 0.071 |
2.5 |
0.5 |
750 |
+ |
4 |
15.7 |
0.000 ± 0.000 |
1.5 |
0.0 |
1250 |
+ |
4 |
14.9 |
0.030 ± 0.198 |
3.5 |
2.5 |
Positive control |
+ |
4 |
13.5 |
0.200 ± 0.576 |
3.0 |
14.0 |
0* |
- |
20 |
15.6 |
0.000 ± 0.000 |
2.0 |
1.0 |
250 |
- |
20 |
14.8 |
0.000 ± 0.000 |
3.5 |
0.0 |
750 |
- |
20 |
15.6 |
0.010 ± 0.141 |
2.0 |
0.5 |
1250 |
- |
20 |
15.9 |
0.005 ± 0.071 |
2.5 |
0.5 |
Positive control |
- |
20 |
15.3 |
0.210 ± 0.598 |
3.5 |
15.0 |
* solvent control with DMSO
The test material did not produce a dose-related increase in the frequency of mutants/10 E+06 viable cells over the range of concentrations tested either with or without activation. Two concentrations tested without activation showed a statistically significant mutant frequency relative to solvent control. Small increases in mutant frequency at other dose levels were not considered to be biologically significant because occasional increases of similar magnitude have been obtained in previous tests with solvent or negative controls. The biological significance of the weak responses obtained at the 1.4 and 1.1 µg/ml concentrations tested without activation was doubtful because the effects were produced at non-consecutive doses and were within the range of variations observed in historical negative control data.
Table 2a: Experiment 1 Plate incorporation Number of revertants per plate (mean of 3 plates)
Conc. |
TA 98 |
TA 100 |
TA 1535 |
||||||
- MA |
+ MA |
Cytotoxic |
- MA |
+ MA |
Cytotoxic |
- MA |
+ MA |
Cytotoxic |
|
Negative Control |
28 |
52 |
No |
105 |
120 |
No |
5 |
11 |
No |
0* |
28 |
44 |
No |
87 |
90 |
No |
8 |
10 |
No |
8 |
20 |
42 |
No |
100 |
107 |
No |
9 |
5 |
No |
40 |
20 |
41 |
No |
92 |
97 |
No |
6 |
9 |
No |
200 |
24 |
44 |
No |
97 |
104 |
No |
7 |
10 |
No |
1000 |
26 |
45 |
No |
99 |
107 |
No |
6 |
9 |
No |
5000 |
21 |
30 |
No |
96 |
101 |
No |
10 |
9 |
No |
Positive control |
97 |
- |
No |
450(AZ) 106(CP) |
304 |
No |
367 |
- |
No |
*solvent control with DMSO
Table 2b : Experiment 1 Plate incorporation Number of revertants per plate
Conc. |
TA 1537 |
TA 1538 |
||||
- MA |
+ MA |
Cytotoxic |
- MA |
+ MA |
Cytotoxic |
|
Negative Control |
10 |
17 |
No |
21 |
20 |
No |
0* |
10 |
11 |
No |
24 |
30 |
No |
8 |
10 |
13 |
No |
19 |
31 |
No |
40 |
12 |
12 |
No |
17 |
21 |
No |
200 |
7 |
11 |
No |
21 |
26 |
No |
1000 |
7 |
14 |
No |
20 |
28 |
No |
5000 |
11 |
11 |
No |
21 |
24 |
No |
Positive control |
94 |
- |
No |
82 |
NT |
No |
*solvent control with DMSO
NT: not tested
Table 3a: Experiment 2 Pre incubation Number of revertants per plate (mean of 3 plates
Conc. |
TA 98 |
TA 100 |
TA 1535 |
||||||
- MA |
+ MA |
Cytotoxic |
- MA |
+ MA |
Cytotoxic |
- MA |
+ MA |
Cytotoxic |
|
Negative Control |
218 |
534 |
No |
105 |
103 |
No |
9 |
9 |
No |
0* |
296 |
571 |
No |
92 |
86 |
No |
11 |
9 |
No |
8 |
326 |
622 |
No |
96 |
104 |
No |
11 |
10 |
No |
40 |
314 |
561 |
No |
83 |
88 |
No |
6 |
11 |
No |
200 |
329 |
628 |
No |
98 |
111 |
No |
7 |
13 |
No |
1000 |
422 |
631 |
No |
106 |
98 |
No |
7 |
9 |
No |
5000 |
252 |
258 |
No |
96 |
100 |
No |
5 |
11 |
No |
Positive control |
227 |
- |
No |
442(AZ) 102(CP) |
362 |
No |
371 |
- |
No |
*solvent control with DMSO
Table 3b: Experiment 2 Pre incubation Number ofrevertants per plate
Conc. |
TA 1537 |
TA 1538 |
||||
- MA |
+ MA |
Cytotoxic |
- MA |
+ MA |
Cytotoxic |
|
Negative Control |
9 |
16 |
No |
23 |
25 |
No |
0* |
7 |
13 |
No |
19 |
26 |
No |
8 |
9 |
14 |
No |
21 |
29 |
No |
40 |
8 |
14 |
No |
17 |
24 |
No |
200 |
10 |
13 |
No |
17 |
26 |
No |
1000 |
8 |
15 |
No |
15 |
30 |
No |
5000 |
3 |
18 |
No |
15 |
27 |
No |
Positive control |
109 |
- |
No |
88 |
- |
No |
*solvent control with DMSO
Table 2a: Experiment 1 Plate incorporation Number of revertants per plate (mean of 3 plates)
Conc. |
TA 98 |
TA 100 |
TA 1535 |
||||||
- MA |
+ MA |
Cytotoxic |
- MA |
+ MA |
Cytotoxic |
- MA |
+ MA |
Cytotoxic |
|
Negative Control |
28 |
52 |
No |
105 |
120 |
No |
5 |
11 |
No |
0* |
28 |
44 |
No |
87 |
90 |
No |
8 |
10 |
No |
8 |
20 |
42 |
No |
100 |
107 |
No |
9 |
5 |
No |
40 |
20 |
41 |
No |
92 |
97 |
No |
6 |
9 |
No |
200 |
24 |
44 |
No |
97 |
104 |
No |
7 |
10 |
No |
1000 |
26 |
45 |
No |
99 |
107 |
No |
6 |
9 |
No |
5000 |
21 |
30 |
No |
96 |
101 |
No |
10 |
9 |
No |
Positive control |
97 |
- |
No |
450(AZ) 106(CP) |
304 |
No |
367 |
- |
No |
*solvent control with DMSO
Table 2b : Experiment 1 Plate incorporation Number of revertants per plate
Conc. |
TA 1537 |
TA 1538 |
||||
- MA |
+ MA |
Cytotoxic |
- MA |
+ MA |
Cytotoxic |
|
Negative Control |
10 |
17 |
No |
21 |
20 |
No |
0* |
10 |
11 |
No |
24 |
30 |
No |
8 |
10 |
13 |
No |
19 |
31 |
No |
40 |
12 |
12 |
No |
17 |
21 |
No |
200 |
7 |
11 |
No |
21 |
26 |
No |
1000 |
7 |
14 |
No |
20 |
28 |
No |
5000 |
11 |
11 |
No |
21 |
24 |
No |
Positive control |
94 |
- |
No |
82 |
NT |
No |
*solvent control with DMSO
NT: not tested
Table 3a: Experiment 2 Pre incubation Number of revertants per plate (mean of 3 plates
Conc. |
TA 98 |
TA 100 |
TA 1535 |
||||||
- MA |
+ MA |
Cytotoxic |
- MA |
+ MA |
Cytotoxic |
- MA |
+ MA |
Cytotoxic |
|
Negative Control |
218 |
534 |
No |
105 |
103 |
No |
9 |
9 |
No |
0* |
296 |
571 |
No |
92 |
86 |
No |
11 |
9 |
No |
8 |
326 |
622 |
No |
96 |
104 |
No |
11 |
10 |
No |
40 |
314 |
561 |
No |
83 |
88 |
No |
6 |
11 |
No |
200 |
329 |
628 |
No |
98 |
111 |
No |
7 |
13 |
No |
1000 |
422 |
631 |
No |
106 |
98 |
No |
7 |
9 |
No |
5000 |
252 |
258 |
No |
96 |
100 |
No |
5 |
11 |
No |
Positive control |
227 |
- |
No |
442(AZ) 102(CP) |
362 |
No |
371 |
- |
No |
*solvent control with DMSO
Table 3b: Experiment 2 Pre incubation Number ofrevertants per plate
Conc. |
TA 1537 |
TA 1538 |
||||
- MA |
+ MA |
Cytotoxic |
- MA |
+ MA |
Cytotoxic |
|
Negative Control |
9 |
16 |
No |
23 |
25 |
No |
0* |
7 |
13 |
No |
19 |
26 |
No |
8 |
9 |
14 |
No |
21 |
29 |
No |
40 |
8 |
14 |
No |
17 |
24 |
No |
200 |
10 |
13 |
No |
17 |
26 |
No |
1000 |
8 |
15 |
No |
15 |
30 |
No |
5000 |
3 |
18 |
No |
15 |
27 |
No |
Positive control |
109 |
- |
No |
88 |
- |
No |
*solvent control with DMSO
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Genetic toxicity in vivo
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Information is available for tetraethyl orthosilicate from reliable studies for all the required in vitro endpoints. The results of the standard studies were in agreement and indicate tetraethyl orthosilicate is negative for genotoxicity. There are also results from an in vitro sister chromatid exchange (SCE) assay and from an unscheduled DNA synthesis (UDS) test. No biologically significant induction of SCEs was observed. The results of the UDS assay indicated that DNA damage had occurred as a result of exposure to the test substance. However, it is considered that this finding is not relevant as no effects were observed in the standard studies.
Tetraethyl orthosilicate has been tested in a reliable study according to a now superseded version of an appropriate EU guideline (84/449/EEC B 14), equivalent to OECD Test Guideline 471, in compliance with GLP (Hüls AG 1993). No evidence of increase in the number of revertants relative to solvent control was observed in Salmonella typhimurium TA98, TA100, TA1535, TA1537 and TA1538, when tested up to limit concentrations. Appropriate concurrent solvent (DMSO), negative (water) and positive controls were included, and the expected responses were observed. It is concluded that tetraethyl orthosilicate is not mutagenic to bacteria under the conditions of this test.
Information is available for the registered substance for mutagenicity to a bacterial strain capable of detecting cross-linking or oxidising mutagens from a recently published study in which tetraethyl orthosilicate was tested for mutagenicity to bacteria in study conducted according to OECD Test Guideline 471 (1997), up to limit concentrations (Lionti et al. 2014). No data are available on GLP compliance therefore this study was not chosen as the key study. No test substance induced increase in the number of revertants was observed in Salmonella typhimurium strains TA 98, TA 100, TA1535, TA1537 or Escherichia coli WP2 in the presence or absence of metabolic activation. Appropriate positive and solvent controls were included and gave expected results. It is concluded that tetraethyl orthosilicate is negative for mutagenicity to bacteria under the conditions of the test.
Tetraethyl orthosilicate has been tested in a reliable study conducted according to OECD Test Guideline 473 and in compliance with GLP (BioReliance 2002). No increase in the number of structural and numerical chromosome aberrations in Chinese hamster ovary (CHO) cells was observed. Appropriate positive and solvent controls were included and gave expected results. It is concluded that tetraethyl orthosilicate is negative for the induction of chromosome aberrations under the conditions of the test.
Tetraethyl orthosilicate has been tested in a reliable study conducted according to a protocol that is similar to OECD Test Guideline 476 (BRRC 1981). Weak responses (increase in the number of revertants relative to the solvent control) were obtained at the 1.4 and 1.1 µg/mL concentrations tested without activation in CHO cells. The biological significance of these results was doubtful because the effects were produced at non-consecutive doses and were within the range of variations observed in historical negative control data. It is therefore considered that tetraethyl orthosilicate is negative for the induction of mutations in mammalian cells under the conditions of this test.
Additional information is available from in vitro studies on UDS and SCE (BRRC 1981), with evidence of UDS. However, in the light of the negative results from the standard studies and the lack of genetic toxicity structural alerts, the UDS finding is considered not relevant. According to the guidance, results from the standard mutagenicity studies are generally of higher significance than the result of indicator tests such as UDS.
Justification for classification or non-classification
Based on the available in vitro information, tetraethyl orthosilicate does not require classification for germ cell 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.
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