Registration Dossier

Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Gene mutation (Bacterial reverse mutation assay / Ames test): negative with and without metabolic activation in Salmonella typhimurium strains TA98, TA100, TA1535 and TA1537 Escherichia coli WP2 (similar to OECD TG 471) (Sarwar, G. (2001a).  Cytogenicity in mammalian cells: negative with and without metabolic activation in Chinese hamster CHL/IU cells (OECD TG 473) (Sarwar, G. (2001b).  

Mutagenicity in mammalian cells: negative with and without metabolic activation in L5178Y mouse lymphoma cells (OECD TG 490) (Charles River, 2019).

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:
2001
Reliability:
1 (reliable without restriction)
Qualifier:
according to
Guideline:
JAPAN: Guidelines for Screening Mutagenicity Testing Of Chemicals
Version / remarks:
Ministry of Health and Welfare Ordinance No 1604: November 1, 1999 was followed as reference.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
yes
Remarks:
duplicate not triplicate plates
GLP compliance:
no
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:
Phenobarbital and 5,6-benzoflavone activated rat liver S9
Test concentrations with justification for top dose:
156.3, 312.5, 625, 1250, 2500 and 5000 µg/plate
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: Acetone
- Justification for choice of solvent/vehicle: According to the sponsor, the test substance was insoluble in water and DMSO, whereas soluble and stable in acetone.
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-nitro-2-furyl) AF-2
Remarks:
TA98 (0.1 µg/plate), TA 100 and WP2uvrA (0.01 µg/plate) 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 1535 without metabolic activation: 0.5 µg/plate
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: 2-aminoanthracene - 2-AA
Remarks:
TA98 - 0.5 µg/plate, TA100 - 1.0 µg/plate, TA1535 and TA1537 - 2.0 µg/plate, WP2uvrA - 10.0 µg/plate with 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: 80.0 µg/plate
Details on test system and experimental conditions:
METHOD OF APPLICATION: preincubation

ACTIVATION: S9 mix contained glucose-6-phosphate, NADPH and NADH as co-factors, 0.5 ml of S9 mix containing 10% S9 was added to 2 ml top agar, 0.05 ml of test solution and 0.1 ml tester strain, giving a final concentration of approximately 2% S9.

DURATION
- Preincubation period: Not stated in translated study report
- Exposure duration: 48 hr at 37ºC

SELECTION AGENT (mutation assays): histidine deficient agar

NUMBER OF REPLICATIONS: duplicate plates, test repeated

DETERMINATION OF CYTOTOXICITY
- Method: other: condition of background lawn
Evaluation criteria:
The test substance was judged positive when the number of revertant colonies in the test substance treated plate increased dose dependently and became 2-fold compared to that of the negative control.
Statistics:
The statistical analysis was not done for the judgement.
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

Reverse mutation - dose determination test - pre-incubation method (mean of two plates)

Concentration µg/plate

Mean number of revertants/plate

TA 100

TA 1535

WP2uvrA

TA 98

TA 1537

-S9

+S9

-S9

+S9

-S9

+S9

-S9

+S9

-S9

+S9

Solvent control

131

127

10

11

27

30

23

27

10

15

5

124

139

10

8

23

29

22

36

9

15

10

122

121

11

11

27

26

21

32

11

14

50

110

111

17

14

30

29

19

34

10

16

100

117

121

10

11

30

34

17

38

9

15

500

130

126

11

17

27

35

19

31

10

15

1000

116

115

12

9

23

40

16

42

10

17

5000

116

119

13

13

33

31

19

33

12

17

Positive control

523

779

473

223

166

792

468

495

514

202

Pre-incubation test - revertants per plate (mean of two plates)

Concentration µg/plate

Mean number of revertants/plate

TA 100

TA 1535

WP2uvrA

TA 98

TA 1537

-S9

+S9

-S9

+S9

-S9

+S9

-S9

+S9

-S9

+S9

Solvent control

142

147

10

12

30

31

20

29

6

11

156.3

133

165

11

9

33

33

17

27

6

12

312.5

153

147

8

10

35

37

23

25

7

12

625

127

136

8

9

35

35

26

28

8

13

1250

141

166

13

13

33

34

20

35

6

13

2500

145

152

9

13

31

33

21

40

9

10

5000

137

155

12

8

29

36

19

38

7

14

Positive control

551

949

563

209

226

1019

519

502

496

236

Conclusions:
1,1,1,3,5,5,5-heptamethyl-3-[(trimethylsilyl)oxy]trisiloxane has been tested for mutagenicity to bacteria, in a study which was conducted according to a Japanese guideline similar to OECD TG 471, not in compliance with GLP. No evidence of a test substance related increase in the number of revertants was observed with or without metabolic activation in the initial or the repeat experiment, both of which used the pre-incubation method. Appropriate controls were included and gave expected results. It is concluded that the test substance is negative for mutagenicity to bacteria under the conditions of the test.
Endpoint:
in vitro cytogenicity / chromosome aberration study in mammalian cells
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2001
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods
Qualifier:
according to
Guideline:
other: Japanese ministry of health and welfare ordinance No. 1604: November 1, 1999
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
GLP compliance:
no
Type of assay:
in vitro mammalian chromosome aberration test
Species / strain / cell type:
other: Chinese hamster lung cells (CHL/IU, fibroblast cell line)
Details on mammalian cell type (if applicable):
- Type and identity of media: Eagle's minimum essential medium
- Properly maintained: yes
- Periodically checked for Mycoplasma contamination: yes
Metabolic activation:
with and without
Metabolic activation system:
Phenobarbital and 5,6-benzoflavone activated rat liver S9
Test concentrations with justification for top dose:
777, 1554 and 3107 µg/ml
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: 1% CMC-Na (carboxymethyl cellulose sodium salt)
- Justification for choice of solvent/vehicle: According to the sponsor, the test substance was insoluble and stable in water and DMSO. So, 1% CMC-Na was selected as solvent and used in the test,
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
mitomycin C
Remarks:
without metabolic activation: 0.001 mg/ml
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
benzo(a)pyrene
Remarks:
with metabolic activation : 0.02 mg/ml
Details on test system and experimental conditions:
METHOD OF APPLICATION: in medium

ACTIVATION: S9 mix contained NADP and glucose-6-phosphate as co-factors, 0.3 ml of S9 fraction and pure water in each ml of mixture. Concentration of S9 in cultures not stated in translated report.

DURATION
- Preincubation period:
- Exposure duration: 6 hrs with and without S9, 24 and 48 hrs without S9
- Expression time (cells in growth medium): 18 hrs with and without S9, 24 and 48 hrs without S9


SPINDLE INHIBITOR (cytogenetic assays): Colcemid
STAIN (for cytogenetic assays): 1.5% Giemsa solution

NUMBER OF REPLICATIONS: 2 per dose level

NUMBER OF CELLS EVALUATED: 200 per dose level

DETERMINATION OF CYTOTOXICITY
- Method: cell growth inhibition test

OTHER EXAMINATIONS:
- Determination of polyploidy: yes
- Determination of endoreplication: not examined
Evaluation criteria:
The test substance was judged positive if the incidence of chromosomal aberrations increased dose dependently as compared with those of the concurrent negative control or a reproducible increase in the incidence of chromosomal aberrations at one or more concentrations and the others were judged negative.
Statistics:
No statistical analysis was followed for analysis
Key result
Species / strain:
other: Chinese hamster lung cells (CHL/IU, a fibroblast cell line)
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

Chromosomal aberration test results - all treatment times

Treatment time (h)

+ or – MA

Concentration (mg/ml)

Number of observed cells

Mean % of cells showing

structural chromosomal aberrations

Chromosomal damage %

Chromosome gap %

Cell growth index %

6-18*

-

Solvent control

200

1.0

0.5

100

6-18

-

0.777

200

1.0

0.0

100

6-18

-

1.554

200

0.0

0.0

93

6-18

-

3.107

200

0.5

0.0

86

6-18

-

Positive control

200

16.5

1.5

-

6-18

+

Solvent control

200

0.5

0.5

100

6-18

+

0.777

200

0.5

0.0

102

6-18

+

1.554

200

0.0

0.0

94

6-18

+

3.107

200

0.0

0.0

89

6-18

+

Positive control

200

47.0

4.5

-

24

-

Solvent control

200

0.5

0.5

100

24

-

0.777

200

0.0

0.0

97

24

-

1.554

200

0.5

0.0

99

24

-

3.107

200

0.5

0.0

99

24

-

Positive control

200

45.0

3.5

-

48

-

Solvent control

200

0.5

1.0

100

48

-

0.777

200

0.5

0.0

99

48

-

1.554

200

0.5

0.5

98

48

-

3.107

200

0.0

0.5

99

48

-

Positive control

200

55.5

4.5

-

*6 -18 indicates 6 h treatment followed by 18 h incubation

Conclusions:
1,1,1,3,5,5,5-heptamethyl-3-[(trimethylsilyl)oxy]trisiloxane has been tested for cytogenicity with mammalian cells, in a study which was conducted according to a Japanese guideline similar to OECD 473, not compliant with GLP. No evidence of a test substance related increase in chromosomal aberrations was observed with or without metabolic activation, in Chinese hamster CHL/IU cells. Appropriate controls were included and gave expected results. It is concluded that the test substance is negative for cytogenicity 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:
2018-01-29 to 2018-03-12
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 490 (In Vitro Mammalian Cell Gene Mutation Tests Using the Thymidine Kinase Gene)
Version / remarks:
2005
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of assay:
in vitro mammalian cell gene mutation tests using the thymidine kinase gene
Specific details on test material used for the study:
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature
- Stability under test conditions: stable
- Solubility and stability of the test substance in the solvent/vehicle: Acetone - soluble
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: The test substance was stable in the vehicle, acetone.

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: The test item was dissolved in acetone to give the test concentrations.
- Preliminary purification step (if any): No correction was made for the purity/composition of the test item.
- Final dilution of a dissolved solid, stock liquid or gel: n/a
- Final preparation of a solid: n/a
Species / strain / cell type:
mouse lymphoma L5178Y cells
Details on mammalian cell type (if applicable):
CELLS USED
- Type and source of cells: L5178Y mouse lymphona cells
- Suitability of cells: sensitive indicators of mutagenic activity.

For cell lines:
- Absence of Mycoplasma contamination: yes
- Methods for maintenance in cell culture: in cell medium
- Periodically checked for karyotype stability: not specified
- Periodically ‘cleansed’ of spontaneous mutants: yes

MEDIA USED
- Type and composition of media, CO2 concentration, humidity level, temperature, if applicable: RPMI 1640 HEPES buffered medium (Dutch modification) containing penicillin/streptomycin (50 U/mL and 50 μg/mL, respectively), 1 mM sodium pyruvate and 2 mM L-glutamin. Growth medium contained of basic medium supplemented with 10% (v/v) heat-inactivated horse serum (=R10 medium). All incubations were carried out in a humid atmosphere (80 - 100%, actual range 70 - 97%) containing 5.0 ± 0.5% CO2 in air in the dark at 37.0 ± 1.0°C (actual range 35.7 - 37.5°C).
Additional strain / cell type characteristics:
not applicable
Metabolic activation:
with and without
Metabolic activation system:
Due to migration, the value was transferred to one of the current document's attachments
Test concentrations with justification for top dose:
3-hour mutation assay with and without metabolic activation: 0.24, 0.49, 0.98, 1.95, 3.9, 7.8, 15.6 and 31.3 μg/mL
24-hour mutation assay without metabolic activation: 0.24, 0.49, 0.98, 1.95, 3.9, 7.8, 15.6 and 31.3 μg/mL
Since the test item was not toxic but difficult to dissolve in aqueous solutions, the highest concentration was determined by the solubility in the culture medium. The highest test item concentrations showed a slight precipitate in the exposure medium.
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: acetone

- Justification for choice of solvent/vehicle: The test substance is insoluble in water and DMSO whereas soluble and stable in acetone.

- Justification for percentage of solvent in the final culture medium: 0.25% (v/v)
Untreated negative controls:
not specified
Negative solvent / vehicle controls:
yes
Remarks:
acetone
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
cyclophosphamide
Remarks:
with metabolic activation
Untreated negative controls:
not specified
Negative solvent / vehicle controls:
yes
Remarks:
acetone
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
methylmethanesulfonate
Remarks:
without metabolic activation
Details on test system and experimental conditions:
NUMBER OF REPLICATIONS:
- Number of cultures per concentration (single, duplicate, triplicate) : Solvent and positive control groups were cultured in duplicate. Single cultures for test groups were used.
- Number of independent experiments : two experiments: In the first experiment, cell cultures were exposed for 3 hours to the test item in exposure medium (R5-medium) in the absence and presence of S9-mix. In the second experiment, cell cultures were exposed to the test item in exposure medium (R10-medium) for 24 hours in the absence of S9-mix.

METHOD OF TREATMENT/ EXPOSURE:
- Cell density at seeding (if applicable): 8 x 10⁶ cells (10⁶ cells/mL for 3 hour treatment) or 6 x 10⁶ cells (1.25 x 10⁵ cells/mL for 24 hour treatment) were used.
- Test substance added in medium

TREATMENT AND HARVEST SCHEDULE:
- Preincubation period, if applicable: not applicable
- Exposure duration/duration of treatment: 3 hours or 24 hours
- Harvest time after the end of treatment (sampling/recovery times): not applicable

FOR GENE MUTATION:
- Expression time (cells in growth medium between treatment and selection): For expression of the mutant phenotype, the remaining cells were cultured for 2 days after the treatment period. During this culture period at least 4 x 10⁶ cells (where possible) were subcultured every day in order to maintain log phase growth. Two days after the end of the treatment with the test item the cells were plated for determination of the cloning efficiency (CEday2) and the mutation frequency (MF).
- Selection time (if incubation with a selective agent): 11 or 12 days
- Fixation time (start of exposure up to fixation or harvest of cells): n/a
- Method used: Microwell plates
- Selective agent: 5 µg/mL of Triflourothymidine (TFT). All groups except from the positive control group contained TFT and following incubation, the plates for the TFT-selection were stained for 2 hours, by adding 0.5 mg/mL MTT to each well.
- Number of cells seeded and method to enumerate numbers of viable and mutants cells: For determination of the mutation frequency, a total number of 9.6 x 105 cells per concentration were plated in five 96-well microtiter plates, each well containing 2000 cells in selective medium (TFT-selection), with the exception of the positive control groups where a total number of 9.6 x 105 cells/concentration were plated in ten 96-well microtiter plates, each well containing 1000 cells in selective medium (TFT-selection). The microtiter plates for CEday2 and MF were incubated for 11 or 12 days. Following the incubation period, the plates for the TFT-selection were stained for 2 hours, by adding 0.5 mg/mL MTT to each well. The plates for the CE day2 and MF were scored with the naked eye or with the microscope.
- Criteria for small (slow growing) and large (fast growing) colonies: The small colonies are morphologically dense colonies with a sharp contour and with a diameter less than a quarter of a well. A well containing more than one small colony was classified as one small colony. The large colonies are morphologically less dense colonies with a hazy contour and with a diameter larger than a quarter of a well. A well containing more than one large colony is classified as one large colony. A well containing one small and one large colony was classified as one large colony.
Evaluation criteria:
The result was considered positive when:
- The absolute cloning efficiency of the solvent controls (CEday2) is between 65 and 120% in order to have an acceptable number of surviving cells analyzed for expression of the TK mutation.
- The spontaneous mutation frequency in the solvent control is ≥ 50 per 10⁶ survivors and ≤ 170 per 10⁶ survivors.
- The suspension growth (SG) over the 2-day expression period for the solvent controls should be between 8 and 32 for the 3 hour treatment, and between 32 and 180 for the 24 hour treatment.
- The positive control should demonstrate an absolute increase in the total mutation frequency i.e. an increase above the spontaneous background MF (an induced MF) of at least 300 x 10⁻⁶. At least 40% of the IMF should be reflected in the small colony MF. And/or, the positive control has an increase in the small colony MF of at least 150 x 10⁻⁶ above that seen in the concurrent solvent control (a small colony IMF of 150 x 10⁻⁶).
Statistics:
Not stated
Key result
Species / strain:
mouse lymphoma L5178Y cells
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not determined
Vehicle controls validity:
valid
Untreated negative controls validity:
not specified
Positive controls validity:
valid
Additional information on results:
TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation and time of the determination: The test item did not precipitate directly in the exposure medium at a concentration of 2000 μg/mL. However, moderate precipitation was observed in the exposure medium after 24 hours. An additional solubility experiment was performed where the test item precipitated in the exposure medium at concentrations of 31.3 μg/mL and above. The test item was tested beyond the limit of the solubility to obtain adequate cytotoxicity data, the concentration used as the highest test item concentration for the dose-range finding test was 62.5 μg/mL.

RANGE-FINDING/SCREENING STUDIES
In the dose-range finding test, L5178Y mouse lymphoma cells were treated with a test item concentration range of 1.95 to 62.5 µg/mL in the absence of S9-mix with 3 and 24 hour treatment periods and in the presence of S9-mix with a 3 hour treatment period.
Both in the absence and presence of S9-mix, no toxicity in the relative suspension growth was observed up to and including the highest test item concentration of 62.5 μg/mL compared to the suspension growth of the solvent control. The test item precipitated in the culture medium at the dose levels of 31.3 and 62.5 μg/mL.
No toxicity in the relative suspension growth was observed up to and including the highest
test item concentration of 62.5 μg/mL compared to the suspension growth of the solvent
control. The test item precipitated in the culture medium at the dose levels of 31.3 and
62.5 μg/mL.

STUDY RESULTS
- Concurrent vehicle negative and positive control data : Positive and negative controls were considered to be valid.

For all test methods and criteria for data analysis and interpretation:
- Concentration-response relationship where possible : No biologically relevant increase in the mutation frequency at the TK locus was observed after
3 and 24 hour treatment with the test item neither in the absence nor presence of S9-mix.
- Statistical analysis: there was no statistically significant increase in mutant colonies
- Any other criteria: There was no statistically significant increase in mutation frequency at any of the test concentrations.

Gene mutation tests in mammalian cells:
- Results from cytotoxicity measurements: No toxicity was observed and all dose levels were evaluated in the absence and presence of
S9-mix in both experiments.
o Relative total growth (RTG) was comparable to that of the negative control

- Genotoxicity results:
o When using the thymidine kinase gene on L5178Y cells: The
numbers of small and large colonies in the test item treated cultures were comparable to the numbers of small and large colonies of the solvent controls. No biologically relevant increase in the mutation frequency at the TK locus was observed after 3 and 24 hour treatment with the test item neither in the absence nor presence of S9-mix.No toxicity was observed and all dose levels were evaluated in the absence and presence of
S9-mix in both experiments.


HISTORICAL CONTROL DATA (with ranges, means and standard deviation, and 95% control limits for the distribution as well as the number of data)
- Positive historical control data: Positive control chemicals, methyl methanesulfonate and cyclophosphamide, both produced
significant increases in the mutation frequency. In addition, the mutation frequency found in the positive control cultures was within the 95% control limits of the distribution of the
historical positive control database
- Negative (solvent/vehicle) historical control data:The mutation frequency found in the solvent control cultures was within the acceptability criteria of this assay and within the 95% control limits of the distribution of the historical
negative control database

Table 1 - Historical Control Data of the Spontaneous Mutation Frequencies per 106survivors

of the Solvent Controls for the Mouse Lymphoma Assay

 

  - S9-mix

- S9-mix

+ S9-mix

 

3 hour treatment

24 hour treatment

3 hour treatment

Mean

96

92

96

SD

29

30

29

n

268

248

285

Upper control limit

(95% control limits)

160

152

160

Lower control limit

(95% control limits)

32

31

32

SD = Standard deviation

n = Number of observations

Distribution historical negative control data from experiments performed between November 2014 and November 2017. 

Table 2 - Historical Control Data of the Mutation Frequencies  per 106survivors

of the Positive Controls for the Mouse Lymphoma Assay

 

  - S9-mix

- S9-mix

+ S9-mix

 

3 hour treatment

24 hour treatment

3 hour treatment

Mean

808

684

1669

SD

239

206

843

n

136

124

146

Upper control limit

(95% control limits)

1465

1222

4196

Lower control limit

(95% control limits)

152

146

-859

SD = Standard deviation

n = Number of observations

Distribution historical positive control data from experiments performed between November 2014 and November 2017. 

Table 3a - Cytotoxic and Mutagenic Response of 1,1,1,3,5,5,5-Heptamethyl 3[(trimethylsilyl)oxy]trisiloxane in the Mouse Lymphoma L5178Y Test System– Without metabolic activation 3 h treatment

Dose (µg/ml)

RSG (%)

CE day2 (%)

RCE (%)

RTG (%)

Mutation

 

Total

 

Frequency

survivors

Small

per 106

 

Large

 

SC1

 100

99

  100

  100

108

61

41

SC2

100

101

100

100

134

55

71

0.24

112

88

87

98

116

34

76

0.49

102

108

108

110

125

56

61

0.98

114

95

95

108

120

64

49

1.95

103

116

116

120

127

63

55

3.9

107

86

86

92

149

98

43

7.8

98

102

102

100

138

88

41

15.6

97

101

101

98

114

65

43

31.3

98

108

108

106

123

57

57

MMS

60

50

50

30

1186

670

354

 

Table 3b - Cytotoxic and Mutagenic Response of 1,1,1,3,5,5,5-Heptamethyl 3[(trimethylsilyl)oxy]trisiloxane in the Mouse Lymphoma L5178Y Test System– With metabolic activation 3 h treatment

Dose (µg/ml)

RSG (%)

CE day2 (%)

RCE (%)

RTG (%)

Mutation

 

Total

 

Frequency

survivors

Small

per 106

 

Large

 

SC1

 100

84

 100

 100

136

85

44

SC2

100

91

100

100

93

61

28

0.24

86

107

122

105

92

49

39

0.49

102

101

115

117

136

92

36

0.98

100

91

104

104

90

70

17

1.95

103

110

125

129

95

54

35

3.9

92

97

110

102

103

73

27

7.8

97

101

115

112

130

65

57

15.6

88

101

115

101

112

74

32

31.3

88

98

112

99

90

55

32

MMS

46

45

52

24

2126

1036

616

Note: all calculations were made without rounding off RSG = Relative Suspension Growth; CE = Cloning Efficiency; RCE = Relative Cloning Efficiency; RTG = Relative Total Growth; SC = Solvent control = Acetone; MMS = Methylmethanesulfonate; CP = Cyclophosphamide (1) = the test item precipitated in the exposure medium

Table 4 - Cytotoxic and Mutagenic Response of 1,1,1,3,5,5,5-Heptamethyl-3[(trimethylsilyl)oxy]trisiloxane in the Mouse Lymphoma L5178Y Test System – without metabolic activation – 24 h treatment

Dose (µg/ml)

RSG (%)

CE day2 (%)

RCE (%)

RTG (%)

Mutation

 

Total

 

Frequency

survivors

Small

per 106

 

Large

 

SC1

 100

86

 100

 100

123

66

50

SC2

100

90

100

100

131

66

57

0.24

111

101

114

127

109

52

51

0.49

118

85

96

113

97

47

46

0.98

123

99

113

139

107

48

53

1.95

143

95

108

155

98

46

48

3.9

130

98

111

145

77

34

40

7.8

119

99

113

135

77

28

46

15.6

130

83

94

121

78

42

34

31.3

116

75

85

98

97

43

51

MMS

107

77

87

93

843

458

258

Note: all calculations were made without rounding off RSG = Relative Suspension Growth; CE = Cloning Efficiency; RCE = Relative Cloning Efficiency; RTG = Relative Total Growth; SC = Solvent control = Acetone; MMS = Methylmethanesulfonate (1) = the test item precipitated in the exposure mediu

Conclusions:
1,1,1,3,5,5,5-Heptamethyl-3-[(trimethylsilyl)oxy]trisiloxane has been tested for mutagenicity in mouse lymphoma L5178Y cells according to OECD TG 490, and in compliance with GLP. No test-substance induced increase in the number of mutations was observed when tested with and without metabolic activation. Appropriate solvent and positive controls were included and gave the expected results. It is concluded that the test substance is negative for mutagenicity to mammalian cells under the conditions of the study.
Executive summary:

1,1,1,3,5,5,5-Heptamethyl-3-[(trimethylsilyl)oxy]trisiloxane does not have a mutagenic potential in L5178Y mouse lymphona cells, neither in the absence nor in the presence of a metabolic system (S9-mix).

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

Genetic toxicity in vivo

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

1,1,1,3,5,5,5 -Heptamethyl-3-[(trimethylsilyl)oxy]trisiloxane has been tested for mutagenicity to bacteria, in a study which was conducted according to a Japanese guideline similar to OECD TG 471, not in compliance with GLP (Sarwar, G. (2001a)). No evidence of a test substance related increase in the number of revertants was observed with or without metabolic activation in the initial or the repeat experiment, both of which used the pre-incubation method, in Salmonella typhimurium strains TA 98, TA 100, TA 1535 and TA 1537, and E.coli WP2 uvrA. Appropriate positive and solvent controls were included and gave expected results. It is concluded that the test substance is negative for mutagenicity to bacteria under the conditions of the test.

1,1,1,3,5,5,5-Heptamethyl-3-[(trimethylsilyl)oxy]trisiloxane has been tested for cytogenicity with mammalian cells, in a study which was conducted according to a Japanese guideline similar to OECD 473, not compliant with GLP (Sarwar, G (2001b)). No evidence of a test substance related increase in chromosomal aberrations was observed with or without metabolic activation in CHL/IU cells, tested to cytotoxic concentrations. Appropriate positive and solvent controls were included and gave expected results. It is concluded that the test substance is negative for cytogenicity to mammalian cells under the conditions of the test.

1,1,1,3,5,5,5-Heptamethyl-3-[(trimethylsilyl)oxy]trisiloxane has been tested for mutagenicity in mouse lymphoma L5178Y cells according to OECD TG 490, and in compliance with GLP (Charles River, 2019). No test-substance induced increase in the number of mutations was observed when tested with and without metabolic activation. Appropriate solvent and positive controls were included and gave the expected results. It is concluded that the test substance is negative for mutagenicity to mammalian cells under the conditions of the study.


Justification for classification or non-classification

Based on the available in vitro genotoxicity data, 1,1,1,3,5,5,5-heptamethyl-3-[(trimethylsilyl)oxy]trisiloxane is not classified for mutagenicity according to Regulation (EC) No 1272/2008.