Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

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

Referenceopen allclose all

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

Table 2: Experiment 1 Preliminary toxicity assay, Number of revertants per plate

 

TA98

TA100

TA1535

Conc.
(
µg/plate)

— MA

+ MA

Cytotoxic
(yes/no)

 MA

+ MA

Cytotoxic
(yes/no)

MA

+ MA

Cytotoxic
(yes/no)

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.
(
µg/plate)

— MA

+ MA

Cytotoxic
(yes/no)

— MA

+ MA

Cytotoxic
(yes/no)

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.
(
µg/plate)

— MA

+ MA

Cytotoxic
(yes/no)

MA

+ MA

Cytotoxic
(yes/no)

MA

+ MA

Cytotoxic
(yes/no)

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.
(
µg/plate)

— MA

+ MA

Cytotoxic
(yes/no)

— MA

+ MA

Cytotoxic
(yes/no)

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.
(
µg/plate)

— MA

+ MA

Cytotoxic
(yes/no)

 MA

+ MA

Cytotoxic
(yes/no)

 MA

+ MA

Cytotoxic
(yes/no)

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.
(
µg/plate)

— MA

+ MA

Cytotoxic
(yes/no)

— MA

+ MA

Cytotoxic
(yes/no)

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

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

Table 2: Dose range-finding study Number of revertants per plate (mean of 3 plates)

 

TA100

TA1535

E coli WP2 uvrA

Conc.
(
µg/plate)

-MA

+ MA

Cytotoxic
(yes/no)

-MA

+ MA

Cytotoxic
(yes/no)

-MA

+ MA

Cytotoxic
(yes/no)

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.
(
µg/plate)

-MA

+ MA

Cytotoxic
(yes/no)

-MA

+ MA

Cytotoxic
(yes/no)

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.
(
µg/plate)

-MA

+ MA

Cytotoxic
(yes/no)

-MA

+ MA

Cytotoxic
(yes/no)

-MA

+ MA

Cytotoxic
(yes/no)

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.
(
µg/plate)

-MA

+ MA

Cytotoxic
(yes/no)

-MA

+ MA

Cytotoxic
(yes/no)

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.
(
µg/plate)

-MA

+ MA

Cytotoxic
(yes/no)

-MA

+ MA

Cytotoxic
(yes/no)

-MA

+ MA

Cytotoxic
(yes/no)

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.
(
µg/plate)

-MA

+ MA

Cytotoxic
(yes/no)

-MA

+ MA

Cytotoxic
(yes/no)

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

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

 

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

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

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

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

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

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.
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
Reference
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

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

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.
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.