Registration Dossier

Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Link to relevant study records

Referenceopen allclose all

Endpoint:
in vitro gene mutation study in mammalian cells
Remarks:
Type of genotoxicity: gene mutation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
from 08-04-1994
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to the appropriate OECD and EU test guidelines, and in compliance with GLP.
Qualifier:
according to
Guideline:
OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
Deviations:
no
GLP compliance:
yes
Type of assay:
mammalian cell gene mutation assay
Target gene:
TK Locus
Species / strain / cell type:
mouse lymphoma L5178Y cells
Details on mammalian cell type (if applicable):
- Type and identity of media: Fischers's Medium for Leukemic Cells of Mice with 0.1 % Pluronics, supplemented with 10 % horse serum and 4 mM L-glutamine.
- Properly maintained: yes
- Periodically checked for Mycoplasma contamination: yes
- Periodically checked for karyotype stability: yes
- Periodically "cleansed" against high spontaneous background: yes
Metabolic activation:
with and without
Metabolic activation system:
cofactor supplemented post-mitochondrial fraction (S9 mix), prepared from the livers of rats treated with Aroclor 1254.
Test concentrations with justification for top dose:
313, 625, 1250, 2500 and 5000 µg/mL
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:
7,12-dimethylbenzanthracene
Remarks:
+ S9: 5.0 and 2.5 µL/mL in ethanol.
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
ethylmethanesulphonate
Remarks:
-S9: 0.5 and 0.25 µL/mL in ethanol.
Details on test system and experimental conditions:
METHOD OF APPLICATION: in medium.

DURATION
- Exposure duration: 4 hours.
- Expression time (cells in growth medium): 2 days
- Selection time (if incubation with a selection agent): 10-12 days.

SELECTION AGENT (mutation assays): 3 µg/mL trifluorothymidine (TFT)

NUMBER OF REPLICATIONS: 2


DETERMINATION OF CYTOTOXICITY
- Method: cloning efficiency and relative total growth.

OTHER: Small and large colonies were differentiated, as small colonies are capable to indicate chromosomal mutations.
Cofactors: 11.25 mg DL-Isocitric acid and 6.0 mg nicotinamide adenine dinucleptide phosphate (NADP), pH 7.0.
Metabolic activation: Adult male Sprague-Dawley rats were induced by a single intraperitoneal injection of Aroclor-1254 at a dosage of 500 mg/kg body weight five days prior to sacrifice.
Evaluation criteria:
In evaluation of the data, increases in mutant frequencies which occurred only at highly toxic concentrations (i.e., less than 10% total growth) were not considered biologically relevant. All conclusions were based on sound scientific judgement; however, as a guide to interpretation of the data, the test article was considered to induce a positive response if a concentration- related increase in mutant frequency was observed and more than one dose level was 10% or greater total growth exhibited a mutant frequency two-fold greater than the solvent control. A doubling above background at one or more dose levels with 10% or greater total growth with no evidence of a dose-response was considered to be equivocal. Test articles not producing a doubling above background at one or more dose levels with 10 % or greater growth was concluded to be negative.
Species / strain:
mouse lymphoma L5178Y cells
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
> 2500 µg/mL
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Additional information on results:
RANGE-FINDING/SCREENING STUDIES: The preliminary toxicity test conducted on triethoxysilane indicated 94% toxicity at 5000 µg/mL for the non-activated cultures and 65% toxicity at 5000 µg/mL for the S-9 activated cultures. The cultures treated with 140 µl of ethanol exhibited average suspension growths of 91% of control in the absence of S-9 and 87 % of control in the presence of S-9. The osmolality of the solvent control was 457 mOsm (530 mOsm/kg for 140 µl ethanol) and the osmolality of the top dose, 5000 µg/mL, was 463 mOsm/kg. Based on the results of the initial toxicity test, the doses chosen for the mutagenesis assay ranged from 5000 to 39 µg/mL for both the non-activated cultures and for the S-9 activated cultures.
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Table 1. Total compound toxicity data in the absence of exogenous metabolic activation (-S9):

Concentration
[µg/ mL]

Cloning efficiency [%]

Relative Total Growth [%]

Mutants per 1E+06 cells

Mutation factor

-S9

5000 A

79

8

44

11

5000 B

81

18

52

19

2500 A

85

30

42

9

2500 B

88

16

41

8

1250 A

91

62

30

-3

1250 B

84

53

34

1

625 A

90

79

34

1

625 B

72

71

42

9

313 A

68

61

48

15

313 B

92

87

35

2

140 µl Ethanol

100

98

31

-2

140 µl Ethanol

91

83

41

8

Ethanol 1

 

 

29

 

Ethanol 2

 

 

23

 

Ethanol 3

 

 

49

 

Ethanol 4

 

 

32

 

Ethyl Methanesulfonate (µl/mL)

 

 

 

 

 

0.50

43

23

1206

1164

0.25

64

47

602

560

Solvent 1

 

 

41

 

Solvent 2

 

 

42

 

Table 2. Total compound toxicity data in the presence of exogenous metabolic activation (+S9):

Concentration
[µg/ mL]

Cloning efficiency [%]

Relative Total Growth [%]

Mutants per 1E+06 cells

Mutation factor

+ S9

5000 A

77

17

85

35

5000 B

95

36

51

1

2500 A

85

43

67

17

2500 B

85

47

53

3

1250 A

106

101

48

-2

1250 B

95

84

42

-8

625 A

95

98

51

1

625 B

113

120

42

-8

313 A

102

114

46

-4

313 B

115

120

49

-1

140 µl Ethanol

104

103

45

-5

140 µl Ethanol

94

92

63

13

Ethanol 1

 

 

62

 

Ethanol 2

 

 

45

 

Ethanol 3

 

 

43

 

Ethanol 4

 

 

49

 

Ethyl Methanesulfonate (µl/mL)

 

 

 

 

 

0.50

35

35

417

360

0.25

71

71

179

132

Solvent 1

 

 

40

 

Solvent 2

 

 

54

 

Conclusions:
Interpretation of results (migrated information):
negative with and without metabolic activation

In a mammalian mutagenicity assay in mouse lymphoma L5178Y cells conducted according to OECD 476 and in compliance with GLP, triethoxysilane was found to be non-mutagenic in the absence or presence of metabolic activation.
Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
from 02-02-1995
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The study was conducted according to the appropriate EU test guideline, and in compliance with GLP and is therefore considered to be reliability 1. Read-across of the study itself is considered to be reliability 2. Further information on read-across is given in the endpoint summary.
Justification for type of information:
Please refer to the attached justification below and the overall justification for grouping of substances attached in IUCLID Section 13.
Qualifier:
according to
Guideline:
EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
Deviations:
no
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay
Target gene:
His operon (S. typhimurium strains)
Trp operon (E. coli strains)
Species / strain / cell type:
other: Salmonella typhimurium TA 98, TA 100, TA 1535, TA 1537; Escherichia coli WP2 and WP2 uvrA
Metabolic activation:
with and without
Metabolic activation system:
cofactor supplemented post-mitochondrial fraction (S9 mix), prepared from the livers of rats treated with Aroclor 1254.
Test concentrations with justification for top dose:
100, 333, 1000, 3333, and 5000 µg/plate
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: the solvent was chosen based on solubility of the test article 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:
2-nitrofluorene
Remarks:
TA 98 (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:
TA 100, TA 1535 (without metabolic 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 metabolic activation)
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
methylmethanesulfonate
Remarks:
WP2, WP2uvrA (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:
All strains (with metabolic activation)
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: Sterigmatocystin
Remarks:
All strains (with metabolic activation)
Details on test system and experimental conditions:
METHOD OF APPLICATION: in agar (plate incorporation); preincubation

DURATION

- Preincubation period: 60 minutes
- Expression time (cells in growth medium): 48 to 72 hours

NUMBER OF REPLICATIONS: 2 plates per test concentration

DETERMINATION OF CYTOTOXICITY
- Method: relative total growth; background lawn assessment
Evaluation criteria:
The test article is evaluated as positive when it causes a dose-related increase in mean revertants per plate of at least one tester strain with a minimum of two increasing concentrations of test article.
Statistics:
Positive controls and tester strains with revertant counts greater than 100 were counted with a colony counter (Mini Count) and those less than 100 were counted manually.
Species / strain:
other: Salmonella typhimurium TA 98, TA 100, TA 1535, TA 1537; Escherichia coli WP2 and WP2 uvrA
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
Remarks:
> 5000 µg/plate
Vehicle controls validity:
not specified
Untreated negative controls validity:
not specified
Positive controls validity:
valid
Additional information on results:
TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: none recorded
- Effects of osmolality: none recorded
- Evaporation from medium: not reported
- Precipitation: Slight precipitation at higher concentrations did not affect assay
- Other confounding effect: In first two tests, a variation in the precipitation pattern was observed, so the tests were repeated. The findings from the initial two experiments are not recorded.

RANGE-FINDING/SCREENING STUDIES:
No toxicity observed

COMPARISON WITH HISTORICAL CONTROL DATA:
The results of the controls lie within the range of the historical control data.


Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

 

Table 1 Preliminary toxicity test

 

TA 100

WP2 uvrA (pKM101)

Concentration (μg/Plate)

Plate 1

+ MA

Plate 2

- MA

Cytotoxic (Yes/No)

Plate 1

+ MA

Plate 2

- MA

Cytotoxic (Yes/No)

0

199

174

no

250

208

no

6.7

180

173

no

234

187

no

10

165

157

no

241

210

no

33

174

163

no

200

198

no

67

179

197

no

228

185

no

100

196

152

no

195

217

no

333

177

170

no

186

184

no

667

175

175

no SP

230

214

no SP

1000

169

156

no SP

138

168

no SP

3333

199

174

no SP

221

169

no SP

5000

174

158

no SP

247

180

no SP

SP Slight precipitate

 

Table 2: Experiment 1 Plate incorporation assayNumber 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*

13

17

no

95

144

no

10

11

no

100

13

17

no

89

127

no

9

11

no

333

13

18

no

86

135

no

8

11

no

1000

14

16

no

85

116

no

9

11

no

3333

17

21

no

97

116

no

6

14

no

5000

13

21

no

95

111

no

7

13

no

Positive Control

1304

1050

-

581

997

-

497

124

-

*solvent control with DMSO

 

Table 2: Experiment 1 Plate incorporation assayNumber of revertants per plate (mean of 3 plates)

 

TA1537

WP2 uvrA (pKM101)

WP2 (pKM101)

Conc.
(
µg/plate)

-MA

+ MA

Cytotoxic
(yes/no)

-

 MA

+ MA

Cytotoxic
(yes/no)

-

MA

+ MA

Cytotoxic
(yes/no)

0*

4

6

no

226

263

no

65

64

no

100

4

10

no

236

295

no

54

64

no

333

3

5

no

239

258

no

87

60

no

1000

6

8

no

210

294

no

62

53

no

3333

5

8

no

213

273

no

67

64

no

5000

5

6

no

197

247

no

67

61

no

Positive Control

215

130

-

1554

1262

-

1476

499

-

 

 

*solvent control withDMSO

 

Table 3: Experiment 2 Pre incubation assayNumber 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*

15

24

no

102

129

no

11

10

no

50

26

24

no

112

122

no

10

11

no

160

21

20

no

105

116

no

11

9

no

500

24

14

no

101

120

no

12

10

no

1600

23

17

no

110

128

no

9

12

no

5000

19

18

no

100

123

no

10

11

no

Positive Control

764

909

-

527

902

-

433

117

-

*solvent control with DMSO

 

Table 3: Experiment 2 Pre incubation assayNumber of revertants per plate (mean of 3 plates)

 

TA1537

WP2 uvrA (pKM101)

WP2 (pKM101)

Conc.
(
µg/plate)

-MA

+ MA

Cytotoxic
(yes/no)

-

 MA

+ MA

Cytotoxic
(yes/no)

-

MA

+ MA

Cytotoxic
(yes/no)

0*

5

7

no

204

334

no

23

21

no

100

5

5

no

274

278

no

25

21

no

333

5

5

no

173

316

no

26

25

no

1000

5

6

no

208

296

no

26

22

no

3333

5

4

no

206

285

no

31

28

no

5000

5

6

no

214

283

no

28

24

no

Positive Control

250

119

-

2225

1304

-

358

1222

-

 

*solvent control withDMSO

 

Conclusions:
Interpretation of results (migrated information):
negative with and without activation

In a bacterial reverse mutation assay according to OECD 471 and GLP, the structural analogue substance trimethoxysilane (CAS:2487-90-3) was concluded to be negative in the Salmonella typhimurium/E. coli preincubation mutagenicity assay with a confirmatory assay. The test substance is non-mutagenic in strains used for this study.

Genetic toxicity in vivo

Link to relevant study records
Reference
Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1982-04-21 to 1982-05-14
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The study was conducted according to an appropriate OECD test guideline with minor deviations and in compliance with GLP for the structural analogue substance trimethoxysilane (CAS: 2487-90-3). Read-across to the registered substance is considered scientifically justified.
Justification for type of information:
Please refer to the attached justification below and the overall justification for grouping of substances attached in IUCLID Section 13.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
Deviations:
yes
Remarks:
1000 cells scored
Principles of method if other than guideline:
Micronucleus test in vivo: Matter and Schmid, 1971, Mut. Res. 12: 417-425.
GLP compliance:
yes
Type of assay:
micronucleus assay
Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Spartan Research Laboratories, Inc. Harlet, MI
- Weight at study initiation: 100 to 175 grams
- Housing: Animals housed individually
- Diet (e.g. ad libitum): PURINA Rodent Laboratory Chow (ad libitum)
- Water (e.g. ad libitum): ad libitum
Route of administration:
inhalation
Vehicle:
- Vehicle(s)/solvent(s) used: air
- Concentration of test material in vehicle: 100 ppm
Details on exposure:
TYPE OF INHALATION EXPOSURE: nose only

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: specially constructed glass chamber
- System of generating particulates/aerosols: vapours were generated by bubbling clean, dry air through the liquid test material
Duration of treatment / exposure:
4 hour(s)
Frequency of treatment:
Single 4 hour exposure
Post exposure period:
30 hours
Remarks:
Doses / Concentrations:
100 ppm
Basis:
nominal conc.
No. of animals per sex per dose:
5 animals per dose level
Control animals:
yes, concurrent no treatment
Positive control(s):
triethylenemelamine

- Route of administration: split-dose intraperitoneal injection (0 and 24 hours)
- Doses / concentrations: 0.5 mg/kg/dose
Tissues and cell types examined:
Animals were exposed to the test article by acute inhalation. They were sacrificed, the bone marrow is extracted and smear preparations made and stained. Polychromatic erythrocytes are scored for micronuclei under the microscope. Both positive and negative (solvent) controls are used in each experiment.
Details of tissue and slide preparation:
At sacrifice the adhering soft tissue and epiphyses of both tibiae were removed. The marrow was aspirated from the bone and transferred to centrifuge tubes containing 5 ml fetal calf serum (one tube for each animal). Following centrifugation to pellet the tissue, the supernatant was drawn off and portions of the pellet was spread on slides and air-dried. The slides were then stained in May-Gruenwald Solution and Giemsa. A thousand polychromatic erythrocytes (PCEs) per animal were scored. The frequency of micronucleated was expressed as percent micronucleated cells based on the total PCEs present in the scored optic field.
Evaluation criteria:
In the normal animal, the normocytes/PCE's is approximately 2. If an agent inhibits the proliferation of erythroblasts the proportion of PCE's is generally reduced. If the agent promotes chromosome breakage or acts as a spindle poison, generally the proportion of red normocytes increases.
Statistics:
Mean normocyte and polychromatic erythrocytes calculated as well as ratio of normocytes to PCE's
Sex:
female
Genotoxicity:
negative
Toxicity:
yes
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
RESULTS OF RANGE-FINDING STUDY

- Dose range: 100 ppm

- Clinical signs of toxicity in test animals: To ensure that the Micronucleus Assay was perfomed on animals exposed to a lethal concentration of the test material (Group A), a second group of animals (Group B) was simultaneously exposed to the chemical via inhalation as a positive control for lethality. The data demonstrates that both groups (A&B) were exposed to a lethal concentration of the test material. All five animals in Group B experienced weight loss and died within the 14 day observation period. At autopsy all five animals showed extensive lung damage with hemorrhage and atelectasis. Animals exposed via inhalation to the test material all showed slight to moderate evidence of lung damage in the form of petechial hemorrhage and focal altelectasis. Some evidence of kidney congestion was noted in several animals. No abnormal pathology was evident in either the positive control (C) or negative control (D) groups.

- Evidence of cytotoxicity in tissue analyzed: The ratio of of normocytes to PCE's obtained with both the test material treatment (Group A = 10.64) and the negative control (Group D = 10.28) closely approximate the normal expected ratio and were fairly consistent. The mean normocyte count from the positive control group was elevated (Group C = 19.4) indicating that the animals responded to a known clastogen (chromosome breaking agent). This same trend verified by the increase in percentage of micronucleated PCEs in the positive control group.

- Harvest times: Group A (Treatment group): 30 hours after exposure. Group B (Toxicity Control): 14 days. Group C (Positive Control): 30 hours. Group D (Negative Control): 30 hours.

- High dose with and without activation: 100 ppm

RESULTS OF DEFINITIVE STUDY

- Induction of micronuclei (for Micronucleus assay): Within normal range for all groups

- Ratio of PCE/NCE (for Micronucleus assay): Within normal range for all groups

- Statistical evaluation: Comparison of the study groups by Student T-test using a SAS computer program confirms their is no difference between the mean PCE micronucleus count for study groups A and D (test article and negative control) (<.0001) while the positive control is definitely positive (p>0.5) compared to the former groups.

 The following table indicates that the amimals responded to the positivecontrol substance. Both Normocytes/PCE **  ratio and % of micronucleated PCEs weresignificantly increased in the positive control group when compared to test material-treated group.

Table 3 : Mean Results of in vivo micronucleus test with mouse bone marrow

 

Test Group

(A)

Positive Control (C)

Negative Control (D)

Number of cells evaluated

1000

1000

1000

Sampling time (h)

30h

30h

30h

Number of erythro-cytes

Normocytes / Field

10.64

19.4

10.28

PCE / Field

4.36

4.56

4.36

Micronuclei / 1000 PCE

6.8

39.2

5.6

Ratio of erythro­cytes

Normochromatic / polychromatic

2.52

4.38

2.39

% Micronucleated PCE

0.68

3.92

0.56

 

Conclusions:
Interpretation of results (migrated information): negative
In a rat micronucleus assay according to OECD 474 and to GLP, the structural analogue substance trimethoxysilane (CAS: 2487-90-3) did not induce chromosome breakage or act as a spindle poison in the rodent micronucleus assay even when animals were exposed to lethal concentrations. There is no evidence from this study that the mechanism of kill at toxic levels of exposure involves genotoxicity. The test substance is non-mutagenic in Sprague-Dawley rats in this mammalian micronucleus assay.

Additional information

Only a reliable mammalian mutagenicity study is available for triethoxysilane (CAS: 998-30-1), however, reliable data are available for the structural analogue substance trimethoxysilane (CAS: 2487 -90 -3). An in vitro bacterial mutagenicity assay and an in vivo chromosome aberration assay in mammalian cells is available for the structural analogue substance trimethoxysilane. Triethoxysilane and trimethoxysilane hydrolyse in contact with water generating silanetriol and ethanol or methanol. Both substances generate the same silanol hydrolysis product, silanetriol, and it is therefore considered that read-across between the substances is appropriate. The other products of hydrolysis, methanol and ethanol, are not genotoxic.

Studies were chosen as key when the available study was of relevance and of sufficient quality for classification, labelling and for risk assessment.

A key reliable bacterial reverse mutation assay according to EU method B.13/14 and GLP is available for the structural analogue substance trimethoxysilane (CAS: 2487 -90-3) (Wagner, V.O. 1995).  No evidence for a test-substance related increase in the number of revertants was observed in Salmonella typhimurium TA 98, TA 100, TA 1535, TA 1537 and Escherichia coli WP2 and WP2 uvrA.  The strains were treated with doses of 100 to 5000 µg/plate with and without metabolic activation system. Appropriate positive and solvent controls were included and gave expected results. Under the conditions of this study, trimethoxysilane was concluded to be non-mutagenic in the Salmonella typhimurium/E. coli strains.

A key reliable mammalian cell gene mutation assay according to OECD TG 476 and GLP is available for triethoxysilane (DCC 1995g). Triethoxysilane was tested in the L5178Y/TK+/- Mouse Lymphoma Mutagenesis Assay in the absence and presence of Aroclor induced rat liver S-9. The cultures selected for cloning were treated with doses of 5000 to 313 µg/ml in both the absence and presence of metabolic activation and exhibited total growths from 8% to 87% for the non-activated cultures and from 17% to 120% for the activated cultures. No cultures exhibited a mutant frequency which was at least twice the mean mutant frequency of the solvent controls.Appropriate positive and solvent controls were included and gave expected results.Triethoxysilane was negative for mutagenicity to L178Y cells in both the absence and presence of exogenous metabolic activation.

A key reliable in vivo micronucleus assay equivalent or similar to OECD TG 474 and to GLP is available for the structural analogue substance trimethoxysilane (CAS: 2487-90-3) (Isquith, A.J; Groh, C.L 1982). Under the applied test conditions, trimethoxysilane did not induce chromosome breakage or act as a spindle poison in the rodent micronucleus assay even when animals were exposed to lethal concentrations. There is no evidence from this study that the mechanism of kill at toxic levels of exposure involves genotoxicity.  The test substance is non-mutagenic in Sprague-Dawley rats in this mammalian micronucleus assay.

 

 


Short description of key information:
In vitro:

Only a reliable mammalian mutagenicity study is available for the registered substance triethoxysilane (CAS: 998-30-1), however, reliable data are available for the structural analogue substance trimethoxysilane (CAS: 2487-90-3) for in vitro bacterial mutagenicity and in vivo chromosome aberration in mammalian cells.

Gene mutation (Bacterial reverse mutation assay/ Ames test): read-across from structural analogue substance trimethoxysilane (CAS: 2487-90-3): negative with and without metabolic activation in S. typhimurium TA 100, TA 98, TA 1535, TA 1537, Escherichia coli WP2 and WP2 uvrA (according to EU Method B.13/14 (Mutagenicity–Reverse Mutation Testing Using Bacteria).

Mammalian gene mutation (mouse lymphoma L5178Y cell gene mutation assay): Negative with and without metabolic activation (according to OECD TG 476).

In vivo:

Chromosome aberration (rat micronucleus assay): read-across from structural analogue substance trimethoxysilane (CAS: 2487-90-3): negative (equivalent or similar to OECD TG 474, inhalation).

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on the available in vitro and in vivo data on mutagenicity of the registered substance and the structural analogue substances, trimethoxysilane (CAS: 2487-90-3) and trichlorosilane (CAS 10025 -78 -2), triethoxysilane is not classified for mutagenicity according to Regulation (EC) 1272/2008 or Directive 67/548/EEC.