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EC number: 915-748-1 | CAS number: -
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):
read-across from
4,4,13,13-tetraethoxy-3,14-dioxa-8,9-dithia-4,13-disilahexadecane (S2;
CAS 56706-10-6): negative with and without activation in all strains
tested (OECD TG 471)
Gene mutation (Bacterial reverse mutation assay / Ames test):
read-across from Polysulfides, bis[3-(triethoxysilyl)propyl] (CAS
211519-85-6): negative with and without activation in all strains tested
(OECD TG 471)
Cytogenicity in mammalian cells: read-across from
4,4,13,13-tetraethoxy-3,14-dioxa-8,9-dithia-4,13-disilahexadecane (S2;
CAS 56706-10-6): negative in cultured human lymphocytes (similar to OECD
TG 473)
Cytogenicity in mammalian cells: read-across from Polysulfides,
bis[3-(triethoxysilyl)propyl] (CAS 211519-85-6) negative in Chinese
hamster lung fibroblasts (OECD TG 473)
Mutagenicity in mammalian cells: read-across from Polysulfides,
bis[3-(triethoxysilyl)propyl] (CAS 211519-85-6), negative in L5178Y
mouse lymphoma cells (OECD TG 476)
Link to relevant study records
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1999-11-18 to 2000-01-24
- 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
- Type of assay:
- bacterial reverse mutation assay
- 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:
- Aroclor induced rat liver S9
- Test concentrations with justification for top dose:
- 75-5000 µg/plate
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: Sponsor's request and compatibility with target cells. - Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: 2-aminoanthracene
- Remarks:
- All Salmonella Strains, WP2 uvrA (with activation)
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 2-nitrofluorene
- Remarks:
- TA 98 (without activation)
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- sodium azide
- Remarks:
- TA 100, TA 1535 (without activation)
- Untreated negative controls:
- no
- 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:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- methylmethanesulfonate
- Remarks:
- WP2 uvrA (without activation)
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in agar, preincubation
DURATION
- Preincubation period: 60 minutes
- Expression time (cells in growth medium): 48 to 72 hours
- Fixation time (start of exposure up to fixation or harvest of cells): 12 hours
NUMBER OF REPLICATIONS: 3 plates for each test concentration
DETERMINATION OF CYTOTOXICITY
- Method: Background lawn monitoring - Evaluation criteria:
- For the test article to be positive, it must cause a dose-related increase in mean revertants per plate of at least one tester strain with a minimum of two increasing concentrations per test article.
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 WP2 uvrA, and 3-fold of the solvent control for TA 1535 and TA 1537.
Cytotoxicity is defined as a reduction in the number of colonies by >50% compared with the solvent control and/or a sparse background lawn. - Key result
- Species / strain:
- S. typhimurium TA 1535, TA 1537, TA 98 and 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
- Key result
- Species / strain:
- E. coli WP2 uvr A
- 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:
- COMPARISON WITH HISTORICAL CONTROL DATA: Results were within range of historical control data
- Conclusions:
- In a reliable test conducted in compliance with OECD 471, under GLP, the test substance (8.3% Bis(triethoxysilylpropyl) (S1), 65.4% Bis(triethoxysilylpropyl) (S2), 16.6% Bis(triethoxysilylpropyl) (S3)) did not cause a positive response in any of the tester strains with or without metabolic activation in either of the tests. The test substance is non mutagenic in E. coli and Salmonella strains under the conditions of the test.
- Endpoint:
- in vitro gene mutation study in bacteria
- 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 471 (Bacterial Reverse Mutation Assay)
- Version / remarks:
- 1997
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: Japan ministry of labour notifications 67
- Deviations:
- no
- GLP compliance:
- yes
- Type of assay:
- bacterial reverse mutation assay
- 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:
- phenobarbitol and 5,6 benzoflavone induced rat liver S9
- Test concentrations with justification for top dose:
- 4.88-5000 µg/plate (range finding expt), 156-5000 µg/plate main tests (pre-incubation)
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: test substance is insoluble in water - Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: 2(2-furyl)-3-(5-mitro-2-furyl)acrylamide
- Remarks:
- TA 100, TA 98 and E coli WP2 uvrA without activation
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- sodium azide
- Remarks:
- TA 1535 without activation
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: 2-methoxy-6-chloro-9-[3-(2-chloroethyl)-aminopropylamino] acridine
- Remarks:
- TA 1537 without activation
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: 2-aminoacridine
- Remarks:
- all strains with activation
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: preincubation
DURATION
- Preincubation period: 20 min
- Exposure duration: 48 h
- Expression time (cells in growth medium): 48 h
- Fixation time (start of exposure up to fixation or harvest of cells): 48 h
NUMBER OF REPLICATIONS: test concentrations plated in triplicate, experiment repeated
DETERMINATION OF CYTOTOXICITY
- Method: other: inhibition of bacterial growth
- Evaluation criteria:
- An increase in the number of revertants above twice that of the negative (solvent) control was judged to be a positive result.
- Statistics:
- No statistical treatment was done.
- Key result
- Species / strain:
- S. typhimurium TA 1535, TA 1537, TA 98 and 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
- Key result
- Species / strain:
- E. coli WP2 uvr A
- 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:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: hydrolyses in water
- Effects of osmolality: no information
- Evaporation from medium: no information
- Water solubility: hydrolyses in water
- Precipitation: observed at highest concentration
- Other confounding effects: none reported
RANGE-FINDING/SCREENING STUDIES: no cytotoxicity or genotoxicity observed
COMPARISON WITH HISTORICAL CONTROL DATA: comparable with historical data
ADDITIONAL INFORMATION ON CYTOTOXICITY: no inhibition of bacterial growth was observed - Conclusions:
- Bis(3-triethoxysilylpropyl)poly(n=1.6)sulfide has been testing according to OECD TG 471 under GLP. No increase in the number of reversions was observed in any test strain, with and without metabolic activation. 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:
- 17 January 2002 - 19 February 2002
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- test procedure in accordance with national standard methods
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
- Version / remarks:
- Fulfils requirements of Japanese new chemical substance law
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- JAPAN: Guidelines for Screening Mutagenicity Testing Of Chemicals
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- in vitro mammalian chromosome aberration test
- Species / strain / cell type:
- Chinese hamster lung fibroblasts (V79)
- Metabolic activation:
- with and without
- Metabolic activation system:
- phenobarbitone and beta-naphthoflavone induced rat liver S9
- Test concentrations with justification for top dose:
- 5-160 µg/ml +S9 , 1.25-40 µg/ml -S9
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: Ethanol
- 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: Expt 1 - 6h. Expt 2 - 24 and 48 h
- Expression time (cells in growth medium): Expt 1 - 18 h
- Fixation time (start of exposure up to fixation or harvest of cells): Expt 1 - 24h. Expt 2 - 24 and 48 h
SPINDLE INHIBITOR (cytogenetic assays): Colcemid added 2 hours before harvest
STAIN (for cytogenetic assays): Giemsa
NUMBER OF REPLICATIONS: 2
NUMBER OF CELLS EVALUATED: 1000 cells counted to determine mitotic index, 100 cells evaluated for chromosomal aberrations
DETERMINATION OF CYTOTOXICITY
- Method: mitotic index; relative cell count
OTHER EXAMINATIONS:
- Determination of polyploidy: % of cells with 38 or more chromosomes reported
- Determination of endoreplication: included in polyploid cell total number. Dose related increase in endoreplicated cells reported separately - Evaluation criteria:
- A positive response was recorded if the % of cells with aberrations, excluding gaps, markedly exceeded that seen in the concurrent control, with or without a clear dose-relationship. For modest increases in aberration frequency a dose response relationship is generally required and appropriate statistical tests may be applied in order to record a positive response
- Statistics:
- Where necessary, the frequency of cells with aberrations excluding gaps, and the frequency of polyploid cells were compared with the concurrent vehicle control using Fischer's Exact test.
- Key result
- Species / strain:
- Chinese hamster lung fibroblasts (V79)
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Conclusions:
- 4,4,13,13-tetraethoxy-3,14-dioxa-8,9-dithia-4,13-disilahexadecane has been tested according a method similar to OECD 473 and under GLP. The test substance did not induce any statistically significant, dose-related increases in the frequency of cells with chromosomal aberrations either in the presence or absence of metabolic activation or after various exposure times. The test material was therefore considered to be non-clastogenic (negative for the induction of chromosome aberrations) to CHL cells in vitro 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:
- 2000-40-3 to 2000-07-13
- 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:
- 1997
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: Kihatsu No 652 1997
- Deviations:
- no
- GLP compliance:
- yes
- Type of assay:
- in vitro mammalian chromosome aberration test
- Species / strain / cell type:
- mammalian cell line, other: Chinese hamster lung fibroblasts CHL/IU clone no. 11
- Metabolic activation:
- with and without
- Metabolic activation system:
- Phenobarbital and 5,6-benzoflavone activated rat liver S9
- Test concentrations with justification for top dose:
- 50-800 µg/ml (6 h exposure without activation); 50-400 3-5000 µg/ml (6 h exposure with activation); 25-3003-5000 µg/ml (24 h exposure without activation)
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: DMSO (dried)
- Justification for choice of solvent/vehicle: a stable suspension of test substance was obtained at 480 mg/ml. The test substance hydrolyses in water. - Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- mitomycin C
- Remarks:
- without activation
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: cyclophosphamide monohydrate
- Remarks:
- with activation
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in medium; preincubation;
DURATION
- Preincubation period: 6 hours
- Exposure duration: 6 hours short term test, 24 hours continuous
- Expression time (cells in growth medium): 18 hours
- Fixation time (start of exposure up to fixation or harvest of cells): 24 hours
SPINDLE INHIBITOR (cytogenetic assays): colcemid added 2 h before completion of incubation
STAIN (for cytogenetic assays): 2% Giesma
NUMBER OF REPLICATIONS: Duplicate cultures at each dose
NUMBER OF CELLS EVALUATED: 200
DETERMINATION OF CYTOTOXICITY
- Method: mitotic index; inhibition of cell growth
OTHER EXAMINATIONS:
- Determination of polyploidy: yes
- Determination of endoreplication: not recorded - Evaluation criteria:
- A result was judged positive when there is a 10% dose dependent increase in the frequency of cells with structural chromosomal aberration or 5% increase in the frequency of cells with polyploidy.
- Statistics:
- No statistical evaluation of results was carried out.
- Key result
- Species / strain:
- mammalian cell line, other: CHL/IU clone 11
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Remarks:
- at 200 µg/ml
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Conclusions:
- Bis-(3-triethoxysilylpropyo)poly(n=1-6) sulfide has been tested under GLP in an in vitro chromosome aberration assay that is comparable to OECD 473. No substance-related increase in the number of aberrant cells was observed. It is concluded that bis-(3-triethoxysilylpropyo)poly(n=1-6) sulfide is not cytogenic to mammalian cells 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:
- 2009-08-11 to 2009-09-14
- 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)
- Version / remarks:
- 2008
- Deviations:
- no
- GLP compliance:
- yes
- Type of assay:
- mammalian cell gene mutation assay
- Species / strain / cell type:
- mouse lymphoma L5178Y cells
- Metabolic activation:
- with and without
- Metabolic activation system:
- phenobarbital/beta naphthoflavone induced rat liver S9
- Test concentrations with justification for top dose:
- 0.31 to 20 μg/ml (4 and 24 h -S9); 5 to 60 μg/ml (4 h +S9)
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: ethanol
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- ethylmethanesulphonate
- 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; in agar (plate incorporation); preincubation; in suspension; as impregnation on paper disk
DURATION
- Preincubation period: none
- Exposure duration: 4 h (with and without activation) 24 hours (without activation
- Expression time (cells in growth medium): 2 days
- Selection time (if incubation with a selection agent): 10-14 days
SELECTION AGENT (mutation assays): 5-trifluorothymidine
NUMBER OF REPLICATIONS: cell cultures treated in duplicate
DETERMINATION OF CYTOTOXICITY
- Method: relative total growth; other: relative suspension growth; 2 day viability
OTHER: microwells used - Evaluation criteria:
- A substance is judged to be positive if it produces a reproducible, dose-dependent, statistically significant increase in the mutant frequency relative to the vehicle control, by a factor that equals or exceeds the global evaluation value for the microwell method of 126 E-06.
- Key result
- Species / strain:
- mouse lymphoma L5178Y cells
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- 25 µg/ml (4 and 24 h without activation)
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation: at or above 194.19 µg/ml in all exposure groups
COMPARISON WITH HISTORICAL CONTROL DATA: control values were within historical control data - Conclusions:
- Polysulfides, bis[3-(triethoxysilyl)propyl] (CAS 211519-85-6) have been tested for mutagenicity in mouse lymphoma L5178Y cells according to OECD TG 476 and under GLP. No increase in the number of revertants was observed. It is concluded that the test substance is negative for the mutagenicity in mammalian cells under the conditions of the test.
Referenceopen allclose all
Table 2: Experiment 1 Preliminary toxicity assay, Number of revertants per plate
|
TA98 |
TA100 |
TA1535 |
||||||
Conc. |
— MA |
+ MA |
Cytotoxic |
— MA |
+ MA |
Cytotoxic |
— MA |
+ MA |
Cytotoxic |
0* |
NC*** |
30 |
No |
128 |
172 |
No |
15 |
8 |
No |
6.7 |
14 |
29 |
No |
145 |
124 |
No |
19 |
14 |
No |
10 |
18 |
22 |
No |
150 |
171 |
No |
19 |
11 |
No |
33 |
12 |
19 |
No |
142 |
177 |
No |
12 |
13 |
No |
67 |
21 |
28 |
No |
170 |
193 |
No |
16 |
10 |
No |
100 |
9 |
19 |
No |
136 |
189 |
No |
19 |
13 |
No |
333 |
17 |
24 |
No |
138 |
181 |
No |
23 |
23 |
No |
667 |
23 |
23 |
No |
147 |
162 |
No |
15 |
15 |
No |
1000 |
14** |
24** |
No |
132** |
169** |
No |
19** |
25** |
No |
3333 |
15** |
17** |
No |
167** |
184** |
No |
24** |
16** |
No |
5000 |
21** |
26** |
No |
139** |
199** |
No |
23** |
15** |
No |
*solvent control with DMSO
**Non-Interfering Precipitate
***No count due to procedural error in which plate did not receive an aliquot of tester strain
Table 2: Experiment 1 Preliminary toxicity assay, Number of revertants per plate
|
TA1537 |
WP2uvrA |
||||
Conc. |
— MA |
+ MA |
Cytotoxic |
— MA |
+ MA |
Cytotoxic |
0* |
56 |
45 |
No |
14 |
16 |
No |
6.7 |
49 |
42 |
No |
19 |
15 |
No |
10 |
37 |
41 |
No |
12 |
19 |
No |
33 |
49 |
43 |
No |
12 |
17 |
No |
67 |
47 |
40 |
No |
10 |
10 |
No |
100 |
47 |
46 |
No |
13 |
17 |
No |
333 |
37 |
48 |
No |
9 |
12 |
No |
667 |
48 |
39 |
No |
10 |
16 |
No |
1000 |
37** |
67** |
No |
11** |
12** |
No |
3333 |
45** |
52** |
No |
8** |
18** |
No |
5000 |
44** |
55** |
No |
15** |
14** |
No |
*solvent control with DMSO
**Non-Interfering Precipitate
***No count due to procedural error in which plate did not receive an aliquot of tester strain
Table 3: Experiment 2 Preincubation mutagenicity assay, Number of revertants per plate (mean of 3 plates)
|
TA98 |
TA100 |
TA1535 |
||||||
Conc. |
— MA |
+ MA |
Cytotoxic |
— MA |
+ MA |
Cytotoxic |
— MA |
+ MA |
Cytotoxic |
0* |
16 |
21 |
No |
174 |
203 |
No |
13 |
15 |
No |
75 |
9 |
25 |
No |
161 |
217 |
No |
13 |
16 |
No |
200 |
14 |
24 |
No |
166 |
213 |
No |
17 |
16 |
No |
600 |
10 |
18 |
No |
159 |
212 |
No |
17 |
18 |
No |
1800 |
13 |
17 |
No |
169 |
232 |
No |
14 |
16 |
No |
5000 |
9 |
17 |
No |
140 |
209 |
No |
16 |
18 |
No |
Positive control |
981 |
1350 |
No |
626 |
1197 |
No |
370 |
140 |
No |
*solvent control with DMSO
Table 3: Experiment 2 Preincubation mutagenicity assay, Number of revertants per plate (mean of 3 plates)
|
TA1537 |
WP2uvrA |
||||
Conc. |
— MA |
+ MA |
Cytotoxic |
— MA |
+ MA |
Cytotoxic |
0* |
8 |
9 |
No |
12 |
14 |
No |
75 |
4 |
6 |
No |
9 |
12 |
No |
200 |
5 |
5 |
No |
8 |
13 |
No |
600 |
4 |
9 |
No |
9 |
11 |
No |
1800 |
4 |
5 |
No |
9 |
15 |
No |
5000 |
5 |
8 |
No |
9 |
6 |
No |
Positive control |
827 |
149 |
No |
495 |
462 |
No |
*solvent control with DMSO
Table 4: Experiment 2 Preincubation (Repeat) mutagenicity assay,Number of revertants per plate (mean of 3 plates)
|
TA98 |
TA100 |
TA1535 |
||||||
Conc. |
— MA |
+ MA |
Cytotoxic |
— MA |
+ MA |
Cytotoxic |
— MA |
+ MA |
Cytotoxic |
0* |
17 |
16 |
No |
152 |
160 |
No |
11 |
10 |
No |
75 |
14 |
14 |
No |
145 |
171 |
No |
7 |
13 |
No |
200 |
15 |
19 |
No |
135 |
189 |
No |
7 |
15 |
No |
600 |
14 |
10 |
No |
137 |
159 |
No |
10 |
9 |
No |
1800 |
16 |
14 |
No |
143 |
156 |
No |
9 |
12 |
No |
5000 |
15 |
12 |
No |
115 |
173 |
No |
8 |
7 |
No |
Positive control |
409 |
785 |
No |
677 |
759 |
No |
207 |
68 |
No |
*solvent control with DMSO
Table 4: Experiment 2 Preincubation (Repeat) mutagenicity assay, Number of revertants per plate (mean of 3 plates)
|
TA1537 |
WP2uvrA |
||||
Conc. |
— MA |
+ MA |
Cytotoxic |
— MA |
+ MA |
Cytotoxic |
0* |
5 |
6 |
No |
10 |
10 |
No |
75 |
4 |
4 |
No |
12 |
6 |
No |
200 |
4 |
6 |
No |
9 |
8 |
No |
600 |
5 |
5 |
No |
12 |
10 |
No |
1800 |
2 |
7 |
No |
9 |
12 |
No |
5000 |
4 |
5 |
No |
11 |
8 |
No |
Positive control |
719 |
71 |
No |
317 |
75 |
No |
*solvent control with DMSO
Table 2: Dose range-finding study Number of revertants per plate (mean of 3 plates)
|
TA100 |
TA1535 |
E coli WP2 uvrA |
||||||
Conc. |
-MA |
+ MA |
Cytotoxic |
-MA |
+ MA |
Cytotoxic |
-MA |
+ MA |
Cytotoxic |
0* |
110 |
119 |
no |
8 |
11 |
no |
22 |
25 |
no |
4.88 |
111 |
112 |
no |
10 |
11 |
no |
20 |
24 |
no |
19.5 |
111 |
104 |
no |
8 |
11 |
no |
19 |
25 |
no |
78.1 |
100 |
120 |
no |
12 |
8 |
no |
21 |
30 |
no |
313 |
114 |
126 |
no |
13 |
9 |
no |
19 |
27 |
no |
1250 |
116 |
114 |
no |
10 |
14 |
no |
23 |
31 |
no |
+5000 |
117 |
122 |
no |
9 |
7 |
no |
24 |
29 |
no |
Positive control |
329 |
992 |
- |
349 |
153 |
- |
111 |
692 |
- |
*solvent control with DMSO
Table 3: Dose range-finding study, Number of revertants per plate (mean of 3 plates)
|
TA 98 |
TA1537 |
||||
Conc. |
-MA |
+ MA |
Cytotoxic |
-MA |
+ MA |
Cytotoxic |
0* |
19 |
32 |
no |
8 |
16 |
no |
4.88 |
18 |
29 |
no |
9 |
19 |
no |
19.5 |
18 |
34 |
no |
8 |
20 |
no |
78.1 |
21 |
26 |
no |
9 |
20 |
no |
313 |
24 |
27 |
no |
10 |
17 |
no |
1250 |
16 |
31 |
no |
12 |
19 |
no |
+5000 |
24 |
29 |
no |
12 |
15 |
no |
Positive control |
398 |
264 |
- |
22296 |
198 |
- |
*solvent control with DMSO
Table 4: Experiment 1 Preincubation Number of revertants per plate (mean of 3 plates)
|
TA100 |
TA1535 |
E coli WP2 uvrA |
||||||
Conc. |
-MA |
+ MA |
Cytotoxic |
-MA |
+ MA |
Cytotoxic |
-MA |
+ MA |
Cytotoxic |
0* |
110 |
124 |
no |
15 |
12 |
no |
17 |
28 |
no |
156 |
109 |
101 |
no |
17 |
11 |
no |
19 |
23 |
no |
313 |
102 |
95 |
no |
18 |
13 |
no |
22 |
29 |
no |
625 |
118 |
104 |
no |
18 |
14 |
no |
19 |
28 |
no |
1250 |
104 |
91 |
no |
13 |
12 |
no |
21 |
24 |
no |
+2500 |
134 |
132 |
no |
19 |
16 |
no |
23 |
30 |
no |
+5000 |
114 |
131 |
no |
16 |
17 |
no |
26 |
32 |
no |
Positive control |
422 |
912 |
- |
447 |
115 |
- |
121 |
887 |
- |
*solvent control with DMSO
Table 5: Experiment 1 Preincubation Number of revertants per plate (mean of 3 plates)
- |
TA 98 |
TA1537 |
||||
Conc. |
-MA |
+ MA |
Cytotoxic |
-MA |
+ MA |
Cytotoxic |
0* |
15 |
29 |
no |
9 |
15 |
no |
156 |
18 |
34 |
no |
5 |
16 |
no |
313 |
21 |
34 |
no |
6 |
17 |
no |
625 |
19 |
30 |
no |
8 |
10 |
no |
1250 |
20 |
32 |
no |
7 |
15 |
no |
+2500 |
16 |
35 |
no |
8 |
15 |
no |
+5000 |
22 |
35 |
no |
15 |
16 |
no |
Positive control |
384 |
273 |
- |
2814 |
173 |
- |
*solvent control with DMSO
Table 6: Experiment 2 Preincubation Number of revertants per plate (mean of 3 plates)
- |
TA100 |
TA1535 |
E coli WP2 uvrA |
||||||
Conc. |
-MA |
+ MA |
Cytotoxic |
-MA |
+ MA |
Cytotoxic |
-MA |
+ MA |
Cytotoxic |
0* |
112 |
108 |
no |
8 |
6 |
no |
17 |
23 |
no |
156 |
102 |
111 |
no |
11 |
7 |
no |
18 |
21 |
no |
313 |
108 |
101 |
no |
7 |
8 |
no |
18 |
21 |
no |
625 |
100 |
105 |
no |
10 |
8 |
no |
17 |
25 |
no |
1250 |
110 |
114 |
no |
7 |
11 |
no |
14 |
18 |
no |
+2500 |
100 |
110 |
no |
8 |
7 |
no |
18 |
23 |
no |
+5000 |
105 |
109 |
no |
7 |
9 |
no |
23 |
26 |
no |
Positive control |
360 |
908 |
- |
200 |
125 |
- |
111 |
570 |
- |
*solvent control with DMSO
Table 7: Experiment 2 Preincubation Number of revertants per plate (mean of 3 plates)
- |
TA 98 |
TA1537 |
||||
Conc. |
-MA |
+ MA |
Cytotoxic |
-MA |
+ MA |
Cytotoxic |
0* |
15 |
22 |
no |
4 |
12 |
no |
156 |
15 |
21 |
no |
5 |
11 |
no |
313 |
13 |
28 |
no |
6 |
10 |
no |
625 |
15 |
23 |
no |
5 |
10 |
no |
1250 |
17 |
20 |
no |
4 |
11 |
no |
+2500 |
17 |
23 |
no |
6 |
13 |
no |
+5000 |
18 |
24 |
no |
7 |
12 |
no |
Positive control |
354 |
249 |
- |
2665 |
173 |
- |
*solvent control with DMSO
Table 2: Results of chromosome analysis Expt 1, 6h treatment, without activation
|
Solvent* Control |
Positive Control |
Low dose 5 µg/ml |
Mid dose 10 µg/ml |
High dose 20 µg/ml |
|
Cytotoxicity*** |
no |
yes/no |
no |
no |
yes |
|
|
Mean |
|||||
Chromatid aberrations |
gaps |
- |
- |
- |
- |
- |
breaks |
0.5% |
4.5% |
0 |
0 |
1.5% |
|
interchanges |
0 |
10% |
0 |
0 |
0.5% |
|
Chromosome aberrations |
gaps |
0.5% |
11.5% |
2.0% |
1.5% |
3.5% |
breaks |
0 |
0 |
0 |
0 |
0 |
|
interchanges |
0 |
0 |
0.5% |
0 |
0 |
|
Mitotic index |
100 % |
101% |
142% |
92% |
25% |
|
Polyploidy |
0 |
0 |
1% |
1% |
2% |
|
Endo reduplication |
NR** |
NR** |
NR** |
NR** |
NR** |
|
*Solvent control with ethanol
** NR Not recorded
*** Cytotoxicity yes if approximately 50% reduction in cell count
Table 3: Results of chromosome analysis Expt 1, 6h treatment, with activation
|
Solvent* Control |
Positive Control |
Low dose 20 µg/ml |
Mid dose 40 µg/ml |
High dose 80 µg/ml |
|
Cytotoxicity |
no |
no |
no |
no |
no |
|
|
Mean |
|||||
Chromatid aberrations |
gaps |
- |
- |
- |
- |
- |
breaks |
1.5% |
14.7% |
0 |
0.5% |
0.5% |
|
interchanges |
0 |
30% |
0 |
0.5% |
0 |
|
Chromosome aberrations |
gaps |
3.5% |
11.3% |
2% |
2% |
1.5% |
breaks |
0 |
1.3% |
0.5% |
0.5% |
0 |
|
interchanges |
0 |
0.7% |
1.0% |
0.5% |
0 |
|
Mitotic index |
100% |
49% |
102% |
102% |
67% |
|
Polyploidy |
1% |
0 |
0 |
0 |
1% |
|
Endo reduplication |
NR** |
NR** |
NR** |
NR** |
NR** |
|
*Solvent control with ethanol
** NR Not recorded
*** Cytotoxicity yes if greater than 50% reduction in cell count
Table 4: Results of chromosome analysis Expt 2, 24h treatment, without activation
|
Solvent* Control |
Positive Control |
Low dose 2.5 µg/ml |
Mid dose 5 µg/ml |
Mid dose 10 µg/ml |
High dose 15 µg/ml |
|
Cytotoxicity*** |
no |
no |
no |
no |
no |
no |
|
|
Mean |
||||||
Chromatid aberrations |
gaps |
- |
- |
- |
- |
- |
- |
breaks |
0 |
6.3% |
1% |
1% |
0 |
0.5% |
|
interchanges |
0 |
8% |
0 |
0 |
0 |
0 |
|
Chromosome aberrations |
gaps |
4.5% |
9% |
2% |
1% |
2.5% |
2.5% |
breaks |
0 |
1.3% |
0 |
0 |
0 |
0.5% |
|
interchanges |
0.5% |
0.3% |
0.5% |
0.5% |
0.5% |
0 |
|
Mitotic index |
100% |
100% |
108% |
83% |
73% |
42% |
|
Polyploidy |
1% |
0.3% |
1% |
1% |
1.5% |
0.5% |
|
Endo reduplication |
NR** |
NR** |
NR** |
NR** |
NR** |
NR** |
|
*Solvent control with ethanol
** NR Not recorded
*** Cytotoxicity yes if greater than 50% reduction in cell count
Table 5: Results of chromosome analysis Expt 2, 48h treatment, without activation
|
Solvent* Control |
Positive Control |
Low dose 2.5 µg/ml |
Mid dose 5 µg/ml |
High dose 10 µg/ml |
|
Cytotoxicity*** |
no |
no |
no |
no |
no |
|
|
Mean |
|||||
Chromatid aberrations |
gaps |
- |
- |
- |
- |
- |
breaks |
0 |
7.5% |
0 |
1.5% |
0.5% |
|
interchanges |
0 |
2.5% |
0.5% |
0 |
0 |
|
Chromosome aberrations |
gaps |
3.5% |
8.3% |
2.5% |
4.5% |
0 |
breaks |
0 |
2.3% |
0 |
0.5% |
0.5% |
|
interchanges |
0 |
1% |
0 |
1.0% |
0 |
|
Mitotic index |
100% |
118% |
102% |
76% |
70 |
|
Polyploidy |
0% |
0.5% |
1% |
1% |
1% |
|
Endo reduplication |
NR** |
NR** |
NR** |
NR** |
NR** |
|
*Solvent control with ethanol
** NR Not recorded
*** Cytotoxicity yes if greater than 50% reduction in cell count
Numbers in tables indicate the average number of aberrant cells per 100 cells, unless otherwise indicated
Table 2: Results of chromosome analysis: 6h exposure, 18 h recovery, without activation
- |
Solvent Control |
Positive Control |
Low dose 50 µg/ml |
Mid dose 100 µg/ml |
High dose 200 µg/ml |
|
Cytotoxicity |
- |
yes/no |
no |
no |
yes |
|
Precipitation |
- |
- |
no |
yes |
yes |
|
Chromatid aberrations |
gaps |
0 |
1.5 |
0 |
0 |
0 |
breaks |
0 |
23 |
0 |
0 |
0 |
|
interchanges |
0 |
42.5 |
0 |
0 |
0 |
|
Isochromatid aberrations |
gaps |
- |
- |
- |
- |
- |
breaks |
0 |
0.5 |
0 |
0 |
1 |
|
interchanges |
0 |
1.5 |
0 |
0 |
0 |
|
Cell growth index |
100% |
NR |
107.6% |
67.9% |
53.7% |
|
Polyploidy |
1% |
0 |
2% |
0 |
0 |
|
Endo reduplication |
NR |
NR |
NR |
NR |
NR |
|
NR: Not reported
Table 3: Results of chromosome analysis: 6h exposure, 18 h recovery, with activation
- |
Solvent Control |
Positive Control |
Low dose 50 µg/ml |
Mid dose 100 µg/ml |
High dose 150 µg/ml |
|
Cytotoxicity |
- |
yes/no |
no |
no |
yes |
|
Precipitation |
- |
- |
no |
yes |
yes |
|
Chromatid aberrations |
gaps |
1.5 |
1.5 |
0 |
0.5 |
1.0 |
breaks |
0 |
15 |
0 |
0.5 |
3.0 |
|
interchanges |
0.5 |
22.5 |
0 |
2.0 |
2.5 |
|
Isochromatid aberrations |
gaps |
- |
- |
- |
- |
- |
breaks |
0 |
0.5 |
0 |
0 |
0 |
|
interchanges |
0.5 |
0 |
0 |
0 |
0 |
|
Cell growth index |
100% |
NR |
98.6% |
73.4% |
44.2% |
|
Polyploidy |
0.5% |
0 |
2% |
0 |
0 |
|
Endo reduplication |
NR |
NR |
NR |
NR |
NR |
|
NR: Not reported
Table 4: Results of chromosome analysis: continuous exposure
- |
Solvent Control |
Low dose 50 µg/ml |
Mid dose 1 50 µg/ml |
Mid dose 2 75 µg/ml |
High dose 100 µg/ml |
Cytotoxicity |
- |
no |
no |
yes |
yes |
Precipitation |
- |
no |
no |
yes |
yes |
Frequency of aberrant cells - structural |
0 |
0 |
0 |
0 |
0 |
Cell growth index |
100% |
97.1% |
72.3% |
51.8% |
38% |
Polyploidy |
4% |
0 |
0 |
0 |
0 |
Endo reduplication |
NR |
NR |
NR |
NR |
NR |
NR: Not reported
Table 1 Preliminary toxicity test
Dose (μg/ml) |
% RSG (-S9) 4-Hour Exposure |
% RSG (+S9) 4-Hour Exposure |
% RSG (-S9) 24-Hour Exposure |
0* |
100 |
100 |
100 |
12.4 |
74 |
96 |
72 |
24.27 |
90 |
96 |
26 |
48.55 |
83 |
84 |
0 |
97.09 |
100 |
68 |
0 |
194.49 |
95 |
82 |
1 |
388.38 |
94 |
102 |
1 |
776.75 |
108 |
98 |
1 |
1553.5 |
100 |
102 |
4 |
3107 |
97 |
82 |
39 |
* solvent control with ethanol
Table 2 Main experiment Relative suspension growth, relative total growth and mutant frequency
Treatment µg/ml |
4 hours - S9 |
Treatment µg/ml |
4 hours + S9 |
||||
% RSG |
RTG |
MF |
% RSG |
RTG |
MF |
||
0* |
100 |
1.00 |
89.99 |
0* |
100 |
1.00 |
114.53 |
12.5 |
112 |
1.29 |
89.46 |
12.5 |
113 |
1.04 |
91.57 |
25 |
111 |
1.28 |
82.23 |
25 |
106 |
1.20 |
95.58 |
50 |
121 |
1.42 |
89.78 |
50 |
102 |
1.05 |
101.72 |
100** |
110 |
1.28 |
79.77 |
100 |
105 |
1.09 |
93.79 |
150** |
109 |
1.28 |
86.92 |
150** |
104 |
1.10 |
88.74 |
200** |
122 |
1.38 |
86.12 |
200** |
106 |
1.17 |
98.22 |
Positive control |
94 |
0.81 |
710.52 |
Positive control |
65 |
0.29 |
935.61 |
RSG: Relative suspension growth,
RTG: relative total growth and mutant frequency
MF: mutant frequency
*Solvent control with ethanol
**Precipitate observed
Table 3 Main experiment Relative suspension growth, relative total growth and mutant frequency
Treatment µg/ml |
24 hours - S9 |
||
% RSG |
RTG |
MF |
|
0* |
100 |
1.00 |
96.68 |
1.56 |
109 |
NC |
NC |
3.13 |
102 |
0.95 |
108.38 |
6.25 |
101 |
1.29 |
76.85 |
12.5 |
104 |
1.21 |
113.47 |
18.75 |
89 |
1.02 |
93.93 |
25 |
59 |
0.69 |
89.8 |
37.5 |
16 |
0.14 |
141.03 |
50 |
9 |
NC |
NC |
Positive control |
9 |
0.69 |
992.94 |
RSG: Relative suspension growth,
RTG: relative total growth and mutant frequency
MF: mutant frequency
NC not counted
*Solvent control with ethanol
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Genetic toxicity in vivo
Description of key information
Micronucleus assay study (ip administration) in rat: read-across from 4,4,13,13-tetraethoxy-3,14-dioxa-8,9-dithia-4,13-disilahexadecane (S2; CAS 56706-10-6): Negative (OECD TG 474)
Link to relevant study records
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1 September 1998 - 3 October 1998
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- Deviations:
- no
- GLP compliance:
- yes
- Type of assay:
- micronucleus assay
- Species:
- mouse
- Strain:
- NMRI
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Harlan-Winkelmann GmbH, D-33176 Borchen
- Age at study initiation: approx 7 weeks
- Weight at study initiation: males: 27.4-33.8 g; female: 22.0-26.1g
- Assigned to test groups randomly: yes, under following basis: computerised random number generator.
- Fasting period before study:
- Housing: Macrolon cages type II, 1 animal per cage
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 6 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.0-21.5°C
- Humidity (%): 50-57%
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12 hrs dark/12 hrs light
IN-LIFE DATES: From: To: 3 Sept 1998 - Route of administration:
- intraperitoneal
- Vehicle:
- - Vehicle(s)/solvent(s) used: peanut oil
- Lot/batch no. (if required): 1936301 - Details on exposure:
- Route of exposure: intraperitoneal
- Duration of treatment / exposure:
- 46-48 hours
- Frequency of treatment:
- 2 intraperitoneal administrations of 10 ml/kg bw with an interval of approximately 24 hours (test material and negative control group). Positive control group received a single injection of 10 ml/kg bw
- Post exposure period:
- Animals were sacrificed 22-24h after second (test and negative control) or single (positive control) administration.
- Remarks:
- Doses / Concentrations:
2000 mg/kg bw
Basis:
nominal conc. - No. of animals per sex per dose:
- 7
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- - cyclophosphamide
- Justification for choice of positive control(s): standard guideline positive control
- Route of administration: intraperitoneal
- Doses / concentrations: 10 ml/kg bw of 0.9% solution in physiological saline - Tissues and cell types examined:
- See table 2
- Details of tissue and slide preparation:
- CRITERIA FOR DOSE SELECTION: limit dose
TREATMENT AND SAMPLING TIMES ( in addition to information in specific fields):no further information
DETAILS OF SLIDE PREPARATION: centrifuged cells were suspended n a thin layer of serum, and a small drop was smeared on a slide and air-dried overnight. The dried slides were stained using the panoptic stain method of Pappenheim (Queisser W (1978) Das Knochenmark, Georg Thieme Verlag, Stuttgart)
METHOD OF ANALYSIS: microscopic examination. 2000 PCE scored for incidence of polychromatic erythrocytes with micronuclei. Ratio of PCE/NCE was scored based on 1000 erythrocytes (PCE+NCE) - Statistics:
- Frequencies of PCE with micronuclei of test material and of positive control group were compared with those of the negative control group. A Poisson test was applied. Data from each treatment group for each sex and for the sexes combined were compared with appropriate negative control using software from ASTA medica AG and an Alpha computer (Digital Equipment Corp)
- Key result
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- no effects
- Vehicle controls validity:
- valid
- Negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Additional information on results:
- See table 3
RESULTS OF DEFINITIVE STUDY
- Induction of micronuclei (for Micronucleus assay): negative
- Ratio of PCE/NCE (for Micronucleus assay): see table 3. The PCE/NCE ratio was unchanged in treated animals, so there is no evidence that the test substance reached the target tissue.
- Appropriateness of dose levels and route: appropriate dose and route
- Statistical evaluation: no statistically significant induction of micronuclei occurred - Conclusions:
- 4,4,13,13-tetraethoxy-3,14-dioxa-8,9-dithia-4,13-disilahexadecane has been tested in an in vivo mouse micronucleus assay to OECD 474 and under GLP. No evidence of the induction of micronuclei was observed. It should be noted that the PCE/NCE ratio was unchanged in treated animals, so there is no evidence that the test substance reached the target tissue. It is concluded that the test substance is negative for the induction of micronuclei in vivo under the conditions of the test.
Reference
Table 3: Results of in vivo micronucleus test with Silane Si 266
|
Vehicle Control |
Positive control |
2000 mg/kg bw |
|
Number of cells evaluated |
2000 |
2000 |
2000 |
|
Sampling time (h) |
24 |
24 |
24 |
|
Number of erythrocytes per animal |
normochromatic |
NR |
NR |
NR |
polychromatic |
2000 |
2000 |
2000 |
|
polychromatic with micronuclei |
3.4 |
38.1 |
3.4 |
|
Ratio of erythrocytes |
polychromatic / normochromatic |
1.9* |
1.5* |
1.8* |
polychromatic with micronuclei / normochromatic |
NR |
NR |
NR |
|
* Mean calculated from data for individual animals
PCE polychromatic erythrocyte
NR not recorded
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Additional information
No genetic toxicity study results are available for the registered substance, reaction mass of 4,4,15,15-tetraethoxy-3,16-dioxa-8,9,10,11-tetrathia-4,15-disilaoctadecane (CAS 56705 -10 -6) and 4,4,14,14-tetraethoxy-3,15-dioxa-8,9,10-trithia-4,14-disilaheptadecane (CAS 56706 -11 -7)
Data are available for two related substances: 4,4,13,13-tetraethoxy-3,14-dioxa-8,9-dithia-4,13-disilahexadecane (S2; CAS 56706-10-6), which is a constituent of the registered substance;
and Polysulfides, bis[3-(triethoxysilyl)propyl] (CAS 211519-85-6), which is a reaction mass of 4,4,15,15-tetraethoxy-3,16-dioxa-8,9,10,11-tetrathia-4,15-disilaoctadecane (S4) and 4,4,14,14-tetraethoxy-3,15-dioxa-8,9,10-trithia-4,14-disilaheptadecane (S3) and 4,4,13,13-tetraethoxy-3,14-dioxa-8,9-dithia-4,13-disilahexadecane (S2).
The test material used in the in vitro studies on S2 (CAS 56706 -10 -6) contained 8.3% Bis(triethoxysilylpropyl) (S1), 65.4% Bis(triethoxysilylpropyl) (S2) and 16.6% Bis(triethoxysilylpropyl) (S3).
Reliable in vitro studies of bacterial mutagenicity and mammalian cytogenicity are available for S2; CAS 56706-10-6 and Polysulfides; CAS 211519-85 -6.
A reliable in vitro mammalian mutagenicity study is available for Polysulfides CAS 211519 -85 -6. In vivo data are available from a micronucleus study on S2; CAS 56706 -10 -6. The results of all the studies are in agreement, with no evidence of genetic toxicity observed in any study. Further information on the detailed composition of the read-across substance Polysulfides; CAS 211519-85-6 is given in the discussion in the repeated dose toxicity section (CSR Section 5.6.3).
Justification for classification or non-classification
The available information for the related substance indicates that when tested in vitro, 4,4,13,13-tetraethoxy-3,14-dioxa-8,9-dithia-4,13-disilahexadecane (CAS 56706 -10 -6) does not cause mutagenicity in bacteria nor cytogenicity in mammalian cells. The related substance Polysulfides, bis[3-(triethoxysilyl)propyl] (CAS 211519-85-6) does not cause mutagenicity to bacterial or to mammalian cells, and does not induce cytogenicity in mammalian cells. The conclusion reached from these in vitro studies is supported by an in vivo micronucleus study on 4,4,13,13-tetraethoxy-3,14-dioxa-8,9-dithia-4,13-disilahexadecane (CAS 56706 -10 -6).
Therefore it is considered that classification for mutagenicity is not required.
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