Registration Dossier

Diss Factsheets

Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

A valid Ames test according OECD TG 471 with Salmonella typhimurium strains TA1535, TA1537, TA98 and TA100 and Escherichia coli strain WP2uvrAis available.The test was negative with and without metabolic activation.

Link to relevant study records
Reference
Endpoint:
in vitro gene mutation study in bacteria
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Experimental start date: 31 May 2017, Experimental completion date: 08 August 2017.
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
GLP compliance:
yes (incl. QA statement)
Type of assay:
bacterial reverse mutation assay
Specific details on test material used for the study:
Identification: 2,2,4-Trimethyl-1-oxa-4-aza-2-silacyclohexane
CAS No: 10196-49-3
CAS name: 1-Oxa-4-aza-2-silacyclohexane, 2,2,4-trimethyl-
EC name: 2,2,4-trimethyl-1-oxa-4-aza-2-silacyclohexane
EC number: 233-487-5
Empirical Formula: C6H15NOSi
Molecular Mass: 145.3 g/mol
Physical state/Appearance: Clear colourless liquid
Expiry Date: 09 December 2030
Storage Conditions: Room temperature in the dark
Target gene:
Histidine locus
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Species / strain / cell type:
E. coli WP2 uvr A
Metabolic activation:
with and without
Metabolic activation system:
Phenobarbital/β-naphthaflavone induced rat liver was used at the metabolic activation system
Test concentrations with justification for top dose:
Experiment 1: 1.5, 5, 15, 50, 150, 500, 1500 and 5000 µg/plate. The maximum concentration was 5000 µg/plate as this is the maximum recommended dose level.

Experiment 2: 15, 50, 150, 500, 1500, 5000 µg/plate. There was no visible reduction in the growth of the bacterial background lawn at any dose level, either in the presence or absence of metabolic activation (S9-mix), in the first mutation test (plate incorporation method) and consequently the same maximum dose level was used in the second mutation test
Vehicle / solvent:
The test item was fully miscible in sterile distilled water and dimethyl sulphoxide at 50 mg/mL in solubility checks performed in–house. Sterile distilled water was selected as the vehicle for the study. The test item was found to be stable at 4 and 24 hours when stored at room temperature in the light, the formulations were also found to be homogeneously prepared.
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
Remarks:
Sterile distilled water
True negative controls:
no
Positive controls:
yes
Remarks:
2 µg/plate for WP2uvrA, 3 µg/plate for TA100, 5 µg/plate for TA1535
Positive control substance:
N-ethyl-N-nitro-N-nitrosoguanidine
Remarks:
without metabolic activation
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
Remarks:
sterile distilled water
True negative controls:
no
Positive controls:
yes
Remarks:
80 µg/plate for TA1537
Positive control substance:
9-aminoacridine
Remarks:
without metabolic activation
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
Remarks:
sterile distilled water
True negative controls:
no
Positive controls:
yes
Remarks:
0.2 µg/plate for TA98
Positive control substance:
4-nitroquinoline-N-oxide
Remarks:
without metabolic activation
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
Remarks:
sterile distilled water
True negative controls:
no
Positive controls:
yes
Remarks:
1 µg/plate for TA100, 2 µg/plate for TA1535 and TA1537, 10 µg/plate for WP2uvrA
Positive control substance:
other: 2-Aminoanthracene
Remarks:
with metabolic activation
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
Remarks:
Sterile distilled water
True negative controls:
no
Positive controls:
yes
Remarks:
5 µg/plate for TA98
Positive control substance:
benzo(a)pyrene
Remarks:
with metabolic activation
Details on test system and experimental conditions:
Test Item Preparation and Analysis
The test item was accurately weighed and, on the day of each experiment, approximate half-log dilutions prepared in sterile distilled water by mixing on a vortex mixer and sonication for 5 minutes at 40 °C Formulated concentrations were adjusted to allow for the stated impurity content (1.4%) of the test item. All formulations were used within four hours of preparation. Analysis for concentration of the test item formulations is not a requirement of the test guidelines and was, therefore, not determined. This is an exception with regard to GLP and has been reflected in the GLP compliance statement.

Test for Mutagenicity: Experiment 1 - Plate Incorporation Method
Dose selection
The test item was tested using the following method. The maximum concentration was 5000 µg/plate (the maximum recommended dose level). Eight concentrations of the test item (1.5, 5, 15, 50, 150, 500, 1500 and 5000 µg/plate) were assayed in triplicate against each tester strain, using the direct plate incorporation method.
Without Metabolic Activation
0.1 mL of the appropriate concentration of test item, solvent vehicle or appropriate positive control was added to 2 mL of molten, trace amino-acid supplemented media containing 0.1 mL of one of the bacterial strain cultures and 0.5 mL of phosphate buffer. These were then mixed and overlayed onto a Vogel Bonner agar plate. Negative (untreated) controls were also performed on the same day as the mutation test. Each concentration of the test item, appropriate positive, vehicle and negative controls, and each bacterial strain, was assayed using triplicate plates.
With Metabolic Activation
The procedure was the same as described previously except that following the addition of the test item formulation and bacterial culture, 0.5 mL of S9 mix was added to the molten, trace amino-acid supplemented media instead of phosphate buffer.
Incubation and Scoring
All of the plates were incubated at 37 ± 3 °C for approximately 48 hours and scored for the presence of revertant colonies using an automated colony counting system. The plates were viewed microscopically for evidence of thinning (toxicity).

Test for Mutagenicity: Experiment 2 – Pre-Incubation Method
As the result of Experiment 1 was deemed negative, Experiment 2 was performed using the pre-incubation method in the presence and absence of metabolic activation.
Dose selection
The dose range used for Experiment 2 was determined by the results of Experiment 1 and was 15, 50, 150, 500, 1500, 5000 µg/plate.
Six test item dose levels per bacterial strain were selected in the second mutation test in order to achieve both a minimum of four non-toxic dose levels and the potential toxic limit of the test item following the change in test methodology from plate incorporation to
pre-incubation.
Without Metabolic Activation
0.1 mL of the appropriate bacterial strain culture, 0.5 mL of phosphate buffer and 0.1 mL of the test item formulation or solvent vehicle or 0.1 mL of appropriate positive control were incubated at 37 ± 3 °C for 20 minutes (with shaking) prior to addition of 2 mL of molten, trace amino-acid supplemented media and subsequent plating onto Vogel Bonner plates. Negative (untreated) controls were also performed on the same day as the mutation test employing the plate incorporation method. All testing for this experiment was performed in triplicate.
With Metabolic Activation
The procedure was the same as described previously except that following the addition of the test item formulation and bacterial strain culture, 0.5 mL of S9 mix was added to the tube instead of phosphate buffer, prior to incubation at 37 ± 3 °C for 20 minutes (with shaking) and addition of molten, trace amino-acid supplemented media. All testing for this experiment was performed in triplicate.
Incubation and Scoring
All of the plates were incubated at 37 ± 3 °C for approximately 48 hours and scored for the presence of revertant colonies using an automated colony counting system. The plates were viewed microscopically for evidence of thinning (toxicity). Due to a hardware failure, Ames study manager and sorcerer system suffered an extended downtime, resulting in manual counts being performed on all of the plates produced for Experiment 2.






Evaluation criteria:
There are several criteria for determining a positive result. Any, one, or all of the following can be used to determine the overall result of the study:
1. A dose-related increase in mutant frequency over the dose range tested (De Serres and Shelby, 1979).
2. A reproducible increase at one or more concentrations.
3. Biological relevance against in-house historical control ranges.
4. Statistical analysis of data as determined by UKEMS (Mahon et al., 1989).
5. Fold increase greater than two times the concurrent solvent control for any tester strain (especially if accompanied by an out of historical range response (Cariello and Piegorsch, 1996)).
A test item will be considered non-mutagenic (negative) in the test system if the above criteria are not met.
Although most experiments will give clear positive or negative results, in some instances the data generated will prohibit making a definite judgment about test item activity. Results of this type will be reported as equivocal.
Statistics:
Statistical significance was confirmed by using Dunnetts Regression Analysis (* = p < 0.05) for those values that indicate statistically significant increases in the frequency of revertant colonies compared to the concurrent solvent control.
Key result
Species / strain:
S. typhimurium TA 1535
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Key result
Species / strain:
S. typhimurium TA 1537
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Key result
Species / strain:
S. typhimurium TA 98
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Key result
Species / strain:
S. typhimurium TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Key result
Species / strain:
E. coli WP2 uvr A
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
Prior to use, the master strains were checked for characteristics, viability and spontaneous reversion rate (all were found to be satisfactory). The amino acid supplemented top agar and the S9-mix used in both experiments was shown to be sterile. The test item formulation was also shown to be sterile.

Results for the negative controls (spontaneous mutation rates) were considered to be acceptable. These data are for concurrent untreated control plates performed on the same day as the Mutation Test.

The vehicle (sterile distilled water) control plates gave counts of revertant colonies within the normal range. All of the positive control chemicals used in the test induced marked increases in the frequency of revertant colonies, both with or without metabolic activation fell within prescribed historical control ranges. Thus, the sensitivity of the assay and the efficacy of the S9-mix were validated.

The maximum dose level of the test item in the first experiment was selected as the maximum recommended dose level of 5000 µg/plate. There was no visible reduction in the growth of the bacterial background lawn at any dose level, either in the presence or absence of metabolic activation (S9-mix), in the first mutation test (plate incorporation method) and consequently the same maximum dose level was used in the second mutation test. Similarly, there was no visible reduction in the growth of the bacterial background lawn at any dose level, either in the presence or absence of metabolic activation (S9-mix), in the second mutation test (pre-incubation method).

No test item precipitate was observed on the plates at any of the doses tested in either the presence or absence of S9-mix.

There were no biologically relevant increases in the frequency of revertant colonies recorded for any of the bacterial strains, with any dose of the test item, either with or without metabolic activation (S9-mix) in Experiment 1 (plate incorporation method). Similarly, no increases in the frequency of revertant colonies were recorded for any of the bacterial strains, with any dose of the test item, either with or without metabolic activation (S9-mix) in Experiment 2 (pre incubation method). Small, statistically significant increases in revertant colony frequency were observed in Experiment 1 at 5000 µg/plate (TA1535 dosed in the absence of S9) and 150 µg/plate (TA1537 dosed in the presence of S9-mix). These increases were considered to be of no biological relevance because there was no evidence of a dose-response relationship or reproducibility. Furthermore, the individual revertant counts at the statistically significant dose levels were within the in-house historical untreated/vehicle control range for each tester strain and the mean maximum fold increase was only 1.9 times the concurrent vehicle controls.

Spontaneous Mutation Rates (Concurrent Negative Controls)

Experiment 1

Number of revertants (mean number of colonies per plate)

Base-pair substitution type

Frameshift type

TA100

TA1535

WP2uvrA

TA98

TA1537

104

 

17

 

25

 

16

 

15

 

84

(87)

22

(17)

11

(24)

16

(16)

11

(12)

72

 

12

 

36

 

15

 

9

 

Experiment 2

Number of revertants (mean number of colonies per plate)

Base-pair substitution type

Frameshift type

TA100

TA1535

WP2uvrA

TA98

TA1537

63

 

14

 

18

 

20

 

12

 

65

(67)

14

(14)

25

(19)

19

(17)

6

(9)

72

 

13

 

13

 

13

 

9

 

 

 

Test Results: Experiment 1 – Without Metabolic Activation

Test Period

From: 10 July 2017

To: 13 July 2017

S9-Mix

(-)

Dose Level

Per Plate

Number of revertants (mean) +/- SD

Base-pair substitution strains

Frameshift strains

TA100

TA1535

WP2uvrA

TA98

TA1537

Solvent Control

(Water)

71

77

82

(77)

5.5#

12

9

10

(10)

1.5

21

27

23

(24)

3.1

13

27

20

(20)

7.0

18

18

22

(19)

2.3

1.5 µg

93

74

87

(85)

9.7

10

10

13

(11)

1.7

20

23

20

(21)

1.7

16

13

19

(16)

3.0

12

10

8

(10)

2.0

5 µg

82

79

95

(85)

8.5

12

13

18

(14)

3.2

23

20

17

(20)

3.0

16

33

13

(21)

10.8

24

15

14

(18)

5.5

15 µg

90

91

79

(87)

6.7

15

15

14

(15)

0.6

24

19

17

(20)

3.6

20

15

17

(17)

2.5

14

23

13

(17)

5.5

50 µg

85

81

81

(82)

2.3

17

10

8

(12)

4.7

17

18

28

(21)

6.1

13

19

25

(19)

6.0

14

13

30

(19)

9.5

150 µg

83

85

83

(84)

1.2

18

14

20

(17)

3.1

23

26

20

(23)

3.0

25

21

24

(23)

2.1

9

21

16

(15)

6.0

500 µg

92

98

90

(93)

4.2

24

19

7

(17)

8.7

25

22

30

(26)

4.0

25

25

23

(24)

1.2

15

6

10

(10)

4.5

1500 µg

90

74

109

(91)

17.5

18

20

12

(17)

4.2

17

20

19

(19)

1.5

17

21

21

(20)

2.3

10

17

20

(16)

5.1

5000 µg

77

88

80

(82)

5.7

22

24

14

*

(20)

5.3

19

35

31

(28)

8.3

19

27

28

(25)

4.9

16

20

15

(17)

2.6

Positive controls

S9-Mix

(-)

Name

Dose Level

No. of Revertants

ENNG

ENNG

ENNG

4NQO

9AA

3 µg

5 µg

2 µg

0.2 µg

80 µg

300

481

425

(402)

92.7

77

72

100

(83)

14.9

402

299

279

(327)

66.0

249

284

288

(274)

21.5

103

77

148

(109)

35.9

ENNG        N-ethyl-N'-nitro-N-nitrosoguanidine

4NQO         4-Nitroquinoline-1-oxide

9AA           9-Aminoacridine

*               p0.05

#         Standard deviation

Test Results: Experiment 1 – With Metabolic Activation

Test Period

From: 10 July 2017

To: 13 July 2017

S9-Mix

(+)

Dose Level

Per Plate

Number of revertants (mean) +/- SD

Base-pair substitution strains

Frameshift strains

TA100

TA1535

WP2uvrA

TA98

TA1537

Solvent Control

(Water)

72

81

85

(79)

6.7#

9

13

19

(14)

5.0

23

33

40

(32)

8.5

26

25

25

(25)

0.6

8

14

8

(10)

3.5

1.5 µg

102

86

80

(89)

11.4

10

10

11

(10)

0.6

22

30

29

(27)

4.4

25

11

20

(19)

7.1

13

12

9

(11)

2.1

5 µg

71

83

85

(80)

7.6

9

21

9

(13)

6.9

24

22

20

(22)

2.0

23

14

27

(21)

6.7

18

14

11

(14)

3.5

15 µg

74

88

94

(85)

10.3

15

21

12

(16)

4.6

25

23

20

(23)

2.5

12

13

19

(15)

3.8

12

11

10

(11)

1.0

50 µg

88

91

84

(88)

3.5

16

9

11

(12)

3.6

26

16

43

(28)

13.7

18

16

22

(19)

3.1

13

16

11

(13)

2.5

150 µg

82

83

84

(83)

1.0

15

8

11

(11)

3.5

36

32

25

(31)

5.6

14

18

23

(18)

4.5

16

16

21

*

(18)

2.9

500 µg

71

90

107

(89)

18.0

9

17

9

(12)

4.6

25

28

32

(28)

3.5

19

21

14

(18)

3.6

11

13

7

(10)

3.1

1500 µg

84

87

83

(85)

2.1

9

9

10

(9)

0.6

33

29

32

(31)

2.1

22

21

19

(21)

1.5

20

15

10

(15)

5.0

5000 µg

86

92

113

(97)

14.2

10

7

9

(9)

1.5

22

26

28

(25)

3.1

20

12

17

(16)

4.0

13

15

15

(14)

1.2

Positive controls

S9-Mix

(+)

Name

Dose Level

No. of Revertants

2AA

2AA

2AA

BP

2AA

1 µg

2 µg

10 µg

5 µg

2 µg

732

1479

1516

(1242)

442.3

214

229

227

(223)

8.1

235

208

217

(220)

13.7

185

209

204

(199)

12.7

248

279

319

(282)

35.6

BP          Benzo(a)pyrene

2AA        2-Aminoanthracene

*               p0.05

#            Standard deviation

 

 

Test Results: Experiment 2 – Without Metabolic Activation

Test Period

From: 01 August 2017

To: 04 August 2017

S9-Mix

(-)

Dose Level

Per Plate

Number of revertants (mean) +/- SD

Base-pair substitution strains

Frameshift strains

TA100

TA1535

WP2uvrA

TA98

TA1537

Solvent Control

(Water)

78

68

68

(71)

5.8#

12

16

13

(14)

2.1

24

21

18

(21)

3.0

24

22

27

(24)

2.5

9

8

16

(11)

4.4

15 µg

69

65

65

(66)

2.3

10

9

14

(11)

2.6

20

25

12

(19)

6.6

18

22

22

(21)

2.3

11

9

9

(10)

1.2

50 µg

65

67

69

(67)

2.0

18

16

14

(16)

2.0

14

14

18

(15)

2.3

24

27

16

(22)

5.7

9

9

10

(9)

0.6

150 µg

81

79

61

(74)

11.0

16

21

12

(16)

4.5

24

15

25

(21)

5.5

17

22

14

(18)

4.0

12

11

9

(11)

1.5

500 µg

67

69

64

(67)

2.5

11

11

13

(12)

1.2

24

12

24

(20)

6.9

16

18

21

(18)

2.5

9

14

13

(12)

2.6

1500 µg

80

65

66

(70)

8.4

12

10

17

(13)

3.6

20

15

18

(18)

2.5

11

16

15

(14)

2.6

3

16

14

(11)

7.0

5000 µg

81

70

69

(73)

6.7

18

7

14

(13)

5.6

16

19

14

(16)

2.5

21

17

21

(20)

2.3

19

9

7

(12)

6.4

Positive controls

S9-Mix

(-)

Name

Dose Level

No. of Revertants

ENNG

ENNG

ENNG

4NQO

9AA

3 µg

5 µg

2 µg

0.2 µg

80 µg

799

833

798

(810)

19.9

1457

1692

1480

(1543)

129.5

553

527

459

(513)

48.5

295

306

302

(301)

5.6

359

246

317

(307)

57.1

ENNG        N-ethyl-N'-nitro-N-nitrosoguanidine

4NQO         4-Nitroquinoline-1-oxide

9AA           9-Aminoacridine

#         Standard deviation

 

 

Test Results: Experiment 2 – With Metabolic Activation

Test Period

From: 01 August 2017

To: 04 August 2017

S9-Mix

(+)

Dose Level

Per Plate

Number of revertants (mean) +/- SD

Base-pair substitution strains

Frameshift strains

TA100

TA1535

WP2uvrA

TA98

TA1537

Solvent Control

(Water)

86

68

62

(72)

12.5#

15

21

19

(18)

3.1

21

24

19

(21)

2.5

28

29

18

(25)

6.1

15

8

6

(10)

4.7

15 µg

68

67

65

(67)

1.5

20

21

16

(19)

2.6

27

19

27

(24)

4.6

25

17

21

(21)

4.0

9

12

15

(12)

3.0

50 µg

66

72

64

(67)

4.2

17

12

16

(15)

2.6

19

16

24

(20)

4.0

31

13

16

(20)

9.6

11

11

7

(10)

2.3

150 µg

65

65

64

(65)

0.6

18

19

13

(17)

3.2

19

20

18

(19)

1.0

24

19

17

(20)

3.6

8

9

10

(9)

1.0

500 µg

69

60

65

(65)

4.5

18

19

11

(16)

4.4

18

13

20

(17)

3.6

21

21

27

(23)

3.5

15

9

11

(12)

3.1

1500 µg

61

64

63

(63)

1.5

12

13

23

(16)

6.1

16

14

21

(17)

3.6

28

23

31

(27)

4.0

11

10

9

(10)

1.0

5000 µg

73

72

64

(70)

4.9

23

18

21

(21)

2.5

26

25

24

(25)

1.0

22

30

24

(25)

4.2

9

11

16

(12)

3.6

Positive controls

S9-Mix

(+)

Name

Dose Level

No. of Revertants

2AA

2AA

2AA

BP

2AA

1 µg

2 µg

10 µg

5 µg

2 µg

902

907

898

(902)

4.5

194

186

205

(195)

9.5

192

166

197

(185)

16.6

141

156

180

(159)

19.7

337

368

386

(364)

24.8

BP          Benzo(a)pyrene

2AA        2-Aminoanthracene

#            Standard deviation

Conclusions:
2,2,4-Trimethyl-1-oxa-4-aza-2-silacyclohexane (CAS no. 10196-49-3) was considered to be non-mutagenic under the conditions of this test.
Executive summary:

  Introduction

The test method was designed to be compatible with the guidelines for bacterial mutagenicity testing published by the OECD Guidelines for Testing of Chemicals No. 471 "Bacterial Reverse Mutation Test".

 Methods

Salmonella typhimuriumstrains TA1535, TA1537, TA98 and TA100 andEscherichia colistrain WP2uvrAwere treated with2,2,4-Trimethyl-1-oxa-4-aza-2-silacyclohexaneusing both the Ames plate incorporation and pre-incubation methods at up to eight dose levels, in triplicate, both with and without the addition of a rat liver homogenate metabolizing system (10% liver S9 in standard co-factors). The dose range for Experiment 1 (plate incorporation method) was predetermined and was 1.5 to 5000 mg/plate. The experiment was repeated on a separate day (Experiment 2, pre-incubation method) using fresh cultures of the bacterial strains and fresh test item formulations. The dose range for Experiment 2 was amended, following the results of Experiment 1, and was 15 to 5000 µg/plate. Six test item concentrations were selected in Experiment 2 in order to achieve both four non‑toxic dose levels and the potential toxic limit of the test item following the change in test methodology.

Results

The vehicle (sterile distilled water) control plates gave counts of revertant colonies within the normal range. All of the positive control chemicals used in the test induced marked increases in the frequency of revertant colonies, both with or without metabolic activation. Thus, the sensitivity of the assay and the efficacy of the S9-mix were validated.

The maximum dose level of the test item in the first experiment was selected as the maximum recommended dose level of 5000 µg/plate. There was no visible reduction in the growth of the bacterial background lawn at any dose level, either in the presence or absence of metabolic activation (S9-mix), in the first mutation test (plate incorporation method) and consequently the same maximum dose level was used in the second mutation test. Similarly, there was no visible reduction in the growth of the bacterial background lawn at any dose level, either in the presence or absence of metabolic activation (S9-mix), in the second mutation test (pre-incubation method). 

No test item precipitate was observed on the plates at any of the doses tested in either the presence or absence of S9-mix.

There were no biologically relevant increases in the frequency of revertant colonies recorded for any of the bacterial strains, with any dose of the test item, either with or without metabolic activation (S9-mix) in Experiment 1 (plate incorporation method). Similarly, no increases in the frequency of revertant colonies were recorded for any of the bacterial strains, with any dose of the test item, either with or without metabolic activation (S9-mix) in Experiment 2 (pre‑incubation method). Small, statistically significant increases in revertant colony frequency were observed in Experiment 1 at 5000 µg/plate (TA1535 dosed in the absence of S9) and 150 µg/plate (TA1537 dosed in the presence of S9-mix). These increases were considered to be of no biological relevance because there was no evidence of a dose-response relationship or reproducibility. Furthermore, the individual revertant counts at the statistically significant dose levels were within the in-house historical untreated/vehicle control range for each tester strain and the mean maximum fold increase was only 1.9 times the concurrent vehicle controls.

Conclusion

2,2,4-Trimethyl-1-oxa-4-aza-2-silacyclohexanewas considered to be non-mutagenic under the conditions of this test.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

The Ames test (key-study) with S. typ. TA1535, TA1537, TA98, TA100 and E. coli WP2uvrA was negative.

According to Regulation EC No. 1272/2008, no classification and labelling for mutagenicity is required.

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