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Diss Factsheets

Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Bacterial reverse mutation assay: tetradecamethylhexasiloxane was negative, with and without metabolic activation in S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102 (OECD 471, 1997) (BSL Bioservice, 2014).
Mammalian cytogenicity assay: tetradecamethylhexasiloxane was negative, with and without metabolic activation in Chinese hamster lung fibroblasts (V79) (OECD 473, 1997) (Bioservice, 2015).
Mammalian mutagenicity assay: tetradecamethylhexasiloxane was negative, with and without metabolic activation in mouse lymphoma L5178Y cells (OECD476, 1997) (Eurofins, 2015).

Link to relevant study records

Referenceopen allclose all

Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
23 September 2014 to 03 November 2014
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:
adopted 21st July 1997
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.5100 - Bacterial Reverse Mutation Test (August 1998)
Qualifier:
according to guideline
Guideline:
other: EC No. 440/2008 B.13/14:"Mutagenicity - Reverse Mutation Test using Bacteria"
GLP compliance:
yes (incl. QA statement)
Type of assay:
bacterial reverse mutation assay
Target gene:
histidine operon
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102
Metabolic activation:
with and without
Metabolic activation system:
phenobarbital (80 mg/kg bw) and β-naphthoflavone (100 mg/kg bw) induced rat liver S9
Test concentrations with justification for top dose:
0.0316, 0.100, 0.316, 1.0, 2.5, 5.0 µL/plate
Vehicle / solvent:
ethanol
Untreated negative controls:
yes
Remarks:
distilled water
Negative solvent / vehicle controls:
yes
Remarks:
ethanol
True negative controls:
no
Positive controls:
yes
Remarks:
dissolved in distilled water
Positive control substance:
sodium azide
Remarks:
-MA; TA 100, TA 1535; 10 µg/plate
Untreated negative controls:
yes
Remarks:
distilled water
Negative solvent / vehicle controls:
yes
Remarks:
ethanol
True negative controls:
no
Positive controls:
yes
Remarks:
dissolved in DMSO
Positive control substance:
other: 4-nitro-o-phenylene-diamine
Remarks:
-MA; 10 µg/plate TA 98; 40 µg/plate TA 1537
Untreated negative controls:
yes
Remarks:
distilled water
Negative solvent / vehicle controls:
yes
Remarks:
ethanol
True negative controls:
no
Positive controls:
yes
Remarks:
dissolved in distilled water
Positive control substance:
methylmethanesulfonate
Remarks:
-MA; TA 102; 1 µL/plate
Untreated negative controls:
yes
Remarks:
distilled water
Negative solvent / vehicle controls:
yes
Remarks:
ethanol
True negative controls:
no
Positive controls:
yes
Remarks:
dissolved in DMSO
Positive control substance:
other: 2-aminoanthracene
Remarks:
+MA; all strains; 2.5 µg/plate, 10 µg/plate for TA 102
Details on test system and experimental conditions:
METHOD OF APPLICATION: in agar (plate incorporation), pre-incubation

ACTIVATION:
Protein concentrations in S9 preparation:
- 34.7 mg/mL phenobarbital
- 33 mg/mL ß-naphthoflavone

S9 mix included 5% S9 and the following cofactors: 8 mM MgCl₂; 33 mM KCl; 5 mM glucose-6-phosphate; 4 mM NADP. The final concentration of S9 in the plates was approximately 1%.

DURATION
- Preincubation period: 60 min at 27°C
- Exposure duration: after solidification, the plates were inverted and incubated at 37°C for at least 48 h in the dark

SELECTION AGENT: histidine deficient agar

NUMBER OF REPLICATIONS: triplicate plates. The inital plate incorporation assay was repeated using the preincubation method.

DETERMINATION OF CYTOTOXICITY
- Method: other: clearing or diminuation of background bacterial lawn/reduction in number of revertants down to a mutation faction of approximately ≤0.5 in relation to the solvent control


Evaluation criteria:
A test item is considered as mutagenic if:
- a clear and dose-related increase in the number of revertants occurs and/or
- a biologically relevant positive response for at least one of the dose groups occurs
in at least one test strain with or without metabolic activation.
A biologically relevant increase is:
- if in tester strains TA 98, TA 100 and TA 102 the number of reversions is at least twice as high
- if in test strains TA 1537 and TA 1535 the number of reversions is at least three times higher than the reversion rate of the solvent control.
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102
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
Remarks on result:
other:
Remarks:
No mutagenic potential observed

Plate incorporation test: number of revertant colonies per plate (mean of 3 plates)

Dose/plate

TA 98

TA 100

TA 1535

TA 1537

TA 102

+ MA

- MA

+ MA

- MA

+ MA

- MA

+ MA

- MA

+ MA

- MA

Distilled water

29

21

121

83

8

6

6

9

313

268

Ethanol

31

21

103

90

6

5

4

8

261

258

0.0316 µL

27

25

117

96

7

11

4

6

367

305

0.100 µL

30

25

111

102

8

7

11

11

369

300

0.316 µL

32

27

110

105

7

12

6

6

397

305

1.000 µL

32

26

121

103

6

6

7

8

337

290

2.50 µL

34

23

122

100

10

6

7

9

338

324

5.0 µL

34

21

111

86

7

6

7

7

369

279

4-NOPD 10 µg

-

283

-

-

-

-

-

51

-

-

2-AA 2.5 µg

2822

-

2300

-

157

-

285

-

964

-

NaN310 µg

-

-

-

482

-

463

-

-

-

-

MMS 1 µL

-

-

-

-

-

-

-

-

-

2395

 

Plate-incubation test: number of revertant colonies per plate (mean of 3 plates)

Dose/plate

TA 98

TA 100

TA 1535

TA 1537

TA 102

+ MA

- MA

+ MA

- MA

+ MA

- MA

+ MA

- MA

+ MA

- MA

Distilled water

32

19

82

81

16

17

5

7

236

187

Ethanol

29

21

97

61

11

9

5

4

208

198

0.0316 µL

35

20

93

92

16

18

10

7

212

198

0.100 µL

28

19

92

81

14

11

7

6

185

164

0.316 µL

31

21

77

74

14

14

7

7

151

136

1.000 µL

26

19

89

62

12

10

8

7

142

109

2.50 µL

28

23

92

77

16

17

10

8

182

134

5.0 µL

28

21

100

94

15

15

11

6

232

197

4-NOPD 10 µg

-

291

-

-

-

-

-

84

-

-

2-AA 2.5 µg

2908

-

1124

-

92

-

179

-

567

-

NaN310 µg

-

-

-

226

-

1226

-

-

-

-

MMS 1 µL

-

-

-

-

-

-

-

-

-

2199

 

4-NOPD = 4-nitro-o-phenylene-diamine

2-AA = 2-aminoanthracene

NaN3= sodium azide

MMS = methylmethanesulfonate

Conclusions:
Tetradecamethylhexasiloxane has been tested for mutagenicity to bacteria, in a study which was conducted according to the OECD TG 471, compliant with GLP. No evidence of a test-substance related increase in the number of revertants was observed with or without metabolic activation in Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA 1537 or TA 102. in the initial plate incorporation assay or the repeat experiment using the preincubation method, up to limit concentrations. Appropriate positive, solvent and negative (water) controls were included and gave the 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
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2014-08-25 to 2014-09-15
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)
Deviations:
no
GLP compliance:
yes
Type of assay:
in vitro mammalian chromosome aberration test
Species / strain / cell type:
Chinese hamster lung fibroblasts (V79)
Details on mammalian cell type (if applicable):
- Type and identity of media:
Culture medium: MEM (minimum essential medium) supplemented with 10% FBS (fetal bovine serum)
Treatment medium: MEM (minimum essential medium) without FBS
- Properly maintained: yes
- Periodically checked for Mycoplasma contamination: yes
Metabolic activation:
with and without
Metabolic activation system:
phenobarbital (80 mg/kg bw) and β-naphthoflavone (100 mg/kg bw) induced rat liver S9
Test concentrations with justification for top dose:
Experiment I:
without and with metabolic activation: 0.0313, 0.0625, 0.125, 0.25, 0.5, 1 and 2 μL/mL
Experiment II:
without metabolic activation: 0.0625, 0.125, 0.25, 0.5, 1, 2 and 4 μL/mL
with metabolic activation: 0.125, 0.25, 0.375, 0.75, 1.25, 1.5, 2.5 and 3 μL/mL
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: MEM + 0 % FBS
- Justification for choice of solvent/vehicle: The nature of the test material does not allow the use of solvents. Based on the results of the solubility test the best suited vehicle was MEM cell culture medium
Untreated negative controls:
yes
Remarks:
treatment medium
Negative solvent / vehicle controls:
no
True negative controls:
no
Positive controls:
yes
Positive control substance:
ethylmethanesulphonate
Remarks:
without metabolic activation
Untreated negative controls:
yes
Remarks:
treatment medium
Negative solvent / vehicle controls:
no
True negative controls:
no
Positive controls:
yes
Positive control substance:
cyclophosphamide
Remarks:
with metabolic activation
Details on test system and experimental conditions:
ACTIVATION: The S9 supernatant was mixed with S9 cofactor solution to result in concentration of 0.75 mg/mL of S9 mix that was added to the cultures. The cofactors added were: 8 mM MgCl2, 33 mM KCl, 5 mM Glucose-6-phosphate, 5 mM NADP in 100 mM sodium-phosphate-buffer pH 7.4.

METHOD OF APPLICATION: in medium

DURATION
- Preincubation period: 48 hours
- Exposure duration:
Experiment I: 4 hours with and without metabolic activation
Experiment II: 4 hours with metabolic activation; 20 hours without metabolic activation
- Expression time (cells in growth medium):
Experiment I: 20 hours after the treatment
Experiment II: straight after exposure (without metabolic activation); 20 hours ( 4-hour exposure with metabolic activation).
- Selection time (if incubation with a selection agent): hypotonic solution (0.4% KCl) for 15-20 min
- Fixation time (start of exposure up to fixation or harvest of cells): after 20 hours the cells were fixed with 3 + 1 methanol + glacial acetic acid

SPINDLE INHIBITOR (cytogenetic assays): Colcemid (0.2 μg/mL culture medium) was added 17.5 hours after the start of the treatment.
STAIN (for cytogenetic assays): Giemsa

NUMBER OF REPLICATIONS: Duplicate lymphocyte cultures

NUMBER OF CELLS EVALUATED: 1000

DETERMINATION OF CYTOTOXICITY
- Method: mitotic index and reduction of degree in cell count

OTHER EXAMINATIONS:
- Determination of polyploidy: yes
Evaluation criteria:
- a clear and dose-related increase in the number of cells with aberrations,
- a biologically relevant response for at least one of the dose groups, which is higher than the laboratory negative control range (up to 4.0% aberrant cells without and 4.3% with metabolic activation)
Statistics:
A statistical evaluation was used as an aid for interpretation of the results. Statistical significance at the 5% level (p< 0.05) was evaluated by the Fischer´s exact test. The p value was used as a limit in judging for significance levels in comparison with the corresponding negative control.
Species / strain:
Chinese hamster lung fibroblasts (V79)
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Untreated negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: pH of suspension was 7.0 ± 0.4
- Effects of osmolality: osmolality was 293 mOsmol/kg
- Precipitation: precipitation was observed at concentrations of 1 μl/ml and higher with and without metabolic activation in experiment I. In experiment II precipitation was observed from 0.5 μl/ml without metabolic activation, and from 1.5 μl/ml with metabolic activation.

RANGE-FINDING/SCREENING STUDIES: Little cytotoxicity was observed in the pre-test, but precipitation was observed.

COMPARISON WITH HISTORICAL CONTROL DATA: The results of positive and solvent controls were within the range of historical controls.

No biologically relevant increase in the frequencies of polyploid cells was found after treatment with the test item.
Remarks on result:
other:
Remarks:
No mutagenic potential observed

Table 1. Summary, Experiment I and II, with and without metabolic activation

 

Dose

Group

Concentration

µg/mL

Relative Mitotic Index

(%)

RICC

(%)

Mean % Aberrant Cells

Historical Laboratory Negative Control Range

Precipitation

Including

Gaps

Excluding Gaps

Experiment I and II, without metabolic activation

Experiment I

4 hour treatment, 20 hour preparation interval

C

0

100

100

3.5

0.5

0.0% - 4.0 %

aberrant cells

-

5

0.5

120

113

2.5

2.0

-

6

1

113

97

3.0

1.5

+

7

2

124

121

1.5

1.5

+

EMS

900

127

89

13.0

9.0

-

 

Experiment II

20 hour treatment, 20 hour preparation interval

C

0

100

100

2.5

0.5

0.0 % - 4.0 %

aberrant cells

-

3

0.25

99

106

4.5

2.0

-

4

0.5

102

98

2.5

0.5

+

5

1

98

103

2.5

1.0

+

6

2

95

105

6.5

2.5

+

7

4

92

100

6.5

3.0

+

EMS

400

80

81

13.5

10.5

-

Experiment I and II, with metabolic activation

Experiment I

4 hour treatment, 20 hour preparation interval

C

0

100

100

3.5

2.0

0.0 % - 4.3 %

aberrant Cells

 

 

 

 

0.0 % - 4.0 %

aberrant cells

-

5

0.5

96

144

2.0

1.0

-

6

1

92

111

2.5

1.5

+

7

2

97

119

4.0

2.0

+

CPA

1.1

96

108

18.5

15.5

-

 

 

Experiment II

20 hour treatment, 20 hour preparation interval

C

0

100

100

4.5

2.5

-

5

0.75

109

100

8.5

4.0

-

6

1.5

99

98

3.5

1.0

+

7

2.5

102

97

3.0

1.5

+

CPA

0.83

90

88

18.5

10.5

-

C: Negative Control (Culture Medium)

CPA: Cyclophosphamide

- without precipitation, + with precipitation

Conclusions:
Tetradecamethylhexasiloxane has been tested in a valid study according to OECD 473 and under GLP, up to precipitating concentrations. No increase in the number of cells with aberrations was observed either with or without metabolic activation in Chinese hamster lung fibroblast (V79) cells. Appropriate negative (treatment medium) and positive controls were included and gave expected results. It is concluded that the test substance is negative for the induction of chromosome aberrations under the conditions of this study.
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:
2015-03-09 to 2015-06-05
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)
Version / remarks:
1997
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: complete culture medium
- Properly maintained: yes
Metabolic activation:
with and without
Metabolic activation system:
phenobarbital (80 mg/kg bw) and ß-naphthoflavone (100 mg/kg bw) induced S9 mix
Test concentrations with justification for top dose:
Experiment I:
0.0010, 0.0025, 0.005, 0.010, 0.025, 0.05, 0.10, 0.25 and 0.5 μL/mL, with and without metabolic activation
Experiment II:
0.0015, 0.003, 0.008, 0.015, 0.03, 0.08, 0.15 and 0.5 μL/mL, with metabolic activation
0.0025, 0.005, 0.010, 0.025, 0.05, 0.10, 0.25 and 0.5 μL/mL, without metabolic activation
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: ethanol
- Justification for choice of solvent/vehicle: The solvent was compatible with the survival of the cells and the S9 activity.
Untreated negative controls:
yes
Remarks:
treatment medium
Negative solvent / vehicle controls:
yes
Remarks:
ethanol
True negative controls:
no
Positive controls:
yes
Positive control substance:
ethylmethanesulphonate
Remarks:
without metabolic activation
Untreated negative controls:
yes
Remarks:
treatment medium
Negative solvent / vehicle controls:
yes
Remarks:
ethanol
True negative controls:
no
Positive controls:
yes
Positive control substance:
methylmethanesulfonate
Remarks:
without metabolic activation
Untreated negative controls:
yes
Remarks:
treatment medium
Negative solvent / vehicle controls:
yes
Remarks:
ethanol
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: benzo[a]pyrene
Remarks:
with metabolic activation
Details on test system and experimental conditions:
ACTIVATION SYSTEM: S9 cofactor solution included S9 at a concentration of 0.75 mg/ml in the cultures. Cofactors added to the S9 mix were: 8 mM MgCl2, 33 mM KCl, 5 mM Glucose-6-phosphate, 5 mM NADP in 100 mM sodium-phosphate-buffer pH 7.4.

METHOD OF APPLICATION: in complete culture medium

DURATION
- Exposure duration:
Experiment I: 4 hours, with and without metabolic activation
Experiment II: 4 hours, with metabolic activation; 24 hours, without metabolic activation
- Expression time (cells in growth medium): 2 days
- Selection time (if incubation with a selection agent): 14 days
- Determination of cloning efficiency: cells were incubated for 6 days to determine cloning efficiency

SELECTION AGENT (mutation assays): selective medium with TFT

NUMBER OF REPLICATIONS: duplicate cultures

DETERMINATION OF CYTOTOXICITY
- Method: cloning efficiency
Evaluation criteria:
The test item was considered mutagenic if the following criteria were met:
- The induced mutant frequency meets or exceeded the Global Evaluation factor (GEF) of 126
mutants per 106 cells
- A dose-dependent increase in mutant frequency was detected.
Statistics:
Mean values and t-test.
Species / strain:
mouse lymphoma L5178Y cells
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:
PRECIPITATION: Precipitation was observed at 0.5 μL/mL in experiment I and II, with and without metabolic activation

ADDITIONAL INFORMATION ON CYTOTOXICITY: No growth inhibition was observed in experiment I and II, with and without metabolic activation
Remarks on result:
other:
Remarks:
No mutagenic potential observed

Table 1. Experiment I, without metabolic activation

 

Test Group

Concentrations

µL/ml

RCE %

RTG %

MF

(mutants/106cells)

IMF (mutants/106cells)

GEF exceeded

Statistical Significant Increase

 

 

 

 

 

Experiment I: without metabolic activation

C1

0

103.0

97.2

88.6

/

/

/

C2

0

115.2

105.1

88.6

/

/

/

S1

0

100.0

100.0

73.9

/

/

/

S2

0

100.0

100.0

73.9

/

/

/

2

0.0010

119.0

108.5

65.8

-8.2

-

-

3

0.0025

95.5

85.5

97.9

23.9

-

+

4

0.005

104.7

90.9

60.5

-13.4

-

-

5

0.010

99.9

87.1

76.5

2.6

-

-

6

0.025

103.0

99.7

67.9

-6.1

-

-

7

0.05

106.3

87.3

54.9

-19.0

-

-

8

0.10

113.3

104.2

61.8

-12.1

-

-

9

0.25

123.2

106.9

78.6

4.7

-

-

10

0.5

137.2

137.8

41.6

-32.4

-

+

EMS

300 μg/mL

76.8

52.6

967.7

893.8

+

+

MMS

10 μg/mL

80.2

58.7

582.5

508.5

+

+

Table 2. Experiment II, without metabolic activation

 

Test Group

Concentrations

µL/ml

RCE %

RTG %

MF

(mutants/106cells)

IMF (mutants/106cells)

GEF exceeded

Statistical Significant Increase

 

 

 

 

 

Experiment II: without metabolic activation

C1

0

88.8

97.6

68.0

/

/

/

C2

0

90.1

105.3

68.0

/

/

/

S1

0

100.0

100.0

86.0

/

/

/

S2

0

100.0

100.0

86.0

/

/

/

3

0.0025

113.9

99.1

72.1

-13.9

-

-

4

0.005

88.8

76.7

89.1

3.2

-

-

5

0.010

122.9

122.0

57.2

-28.8

-

-

6

0.025

88.8

77.6

97.6

11.6

-

-

7

0.05

100.8

103.9

91.8

5.9

-

-

8

0.10

93.0

91.1

90.0

4.1

-

-

9

0.25

90.1

90.5

97.8

11.9

-

-

10

0.5

106.1

104.7

92.1

6.1

-

-

EMS

200 μg/mL

52.7

31.0

2366.9

2281.0

+

+

MMS

8 μg/mL

58.3

36.1

1081.3

995.4

+

+

Table 3. Experiment I, with metabolic activation

 

Test Group

Concentrations

µL/ml

RCE %

RTG %

MF

(mutants/106cells)

IMF (mutants/106cells)

GEF exceeded

Statistical Significant Increase

 

 

 

 

 

Experiment I: with metabolic activation

C1

0

102.1

86.1

73.6

/

/

/

C2

0

125.6

122.4

73.6

/

/

/

S1

0

100.0

100.0

82.0

/

/

/

S2

0

100.0

100.0

82.0

/

/

/

2

0.0010

121.4

140.4

63.9

-18.2

-

-

3

0.0025

117.5

120.0

75.3

-6.8

-

-

4

0.005

105.2

116.7

64.4

-17.7

-

-

5

0.010

113.8

119.6

60.9

-21.2

-

-

6

0.025

108.5

117.5

93.0

11.0

-

-

7

0.05

112.0

123.1

67.8

-14.3

-

-

8

0.10

119.4

137.3

69.4

-12.6

-

-

9

0.25

134.7

146.4

70.7

-11.3

-

-

10

0.5

113.8

123.8

77.3

-4.7

-

-

B[a]P

3.5 μg/mL

68.2

23.3

656.5

574.5

+

+

Table 4. Experiment II, with metabolic activation

 

Test Group

Concentrations

µL/ml

RCE %

RTG %

MF

(mutants/106cells)

IMF (mutants/106cells)

GEF exceeded

Statistical Significant Increase

 

 

 

 

 

Experiment II: with metabolic activation

C1

0

102.7

91.1

64.6

/

/

/

C2

0

91.1

92.7

64.6

/

/

/

S1

0

100.0

100.0

66.1

/

/

/

S2

0

100.0

100.0

66.1

/

/

/

3

0.0015

104.3

102.0

71.0

4.8

-

-

4

0.003

93.8

87.5

70.2

4.0

-

-

5

0.008

109.3

105.0

61.6

-4.5

-

-

6

0.015

120.5

113.6

49.0

-17.1

-

-

7

0.03

111.0

115.1

59.4

-6.8

-

-

8

0.08

96.6

102.9

47.7

-18.4

-

-

9

0.15

105.9

104.6

57.4

-8.7

-

-

10

0.5

91.1

89.5

79.7

13.6

-

-

B[a]P

3.5 μg/mL

99.6

62.4

576.2

510.1

+

+

C: Negative Controls

S: Solvent Controls

Relative Cloning Efficiency, RCE = [(CE dose group / CE of corresponding controls) x 100]

Cloning Efficiency, CE = ((-LN (((96 - (mean P1,P2)) / 96)) / 1.6) x 100)

Relative Total Growth, RTG = (RSG x RCE)/100

Mutant Frequency, MF = {-ln [negative cultures/total wells (selective medium)] / -ln [negative cultures/total wells (non selective medium)]}x800

Induced Mutant Frequency, IMF = mutant frequency sample – mean value mutant frequency corresponding controls

Global Evaluation Factor, GEF (126); +: GEF exceeded, -: GEF not exceeded

Statistical significant increase in mutant frequency compared to solvent controls (Mann Whitney test , p<0.05).

+: significant; -not significant

EMS: Ethylmethanesulfonate [200 μg/mL and 300 μg/mL]

MMS: Methylmethanesulfonate [8 μg/mL and 10 μg/mL]

B[a]P: Benzo[a]pyrene [3.5 μg/mL]

Conclusions:
Tetradecamethylhexasiloxane has been tested in a valid study according to OECD 476 and under GLP. No statistically and biologically significant increase in the mutant frequency was observed with or without metabolic activation when tested up to precipitating concentrations in mouse lymphoma L5178Y cells. Appropriate solvent, negative (treatment medium) and positive controls were included and gave expected results. It is concluded that the test substance is negative for mutagenicity to mammalian cells under the conditions of the test.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Tetradecamethylhexasiloxane has been tested in a valid bacterial reverse mutation assay, according to the OECD TG 471, and under GLP, using Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA 1537 or TA 102 (BSL Bioservice, 2014).

No increase in the number of revertants was observed in any test strain, with or without metabolic activation, when tested up to limit concentration. Appropriate negative, positive and solvent controls were added and gave expected results. It is concluded that the test substance is negative for mutagenicity to bacteria under the conditions of the test. The study was considered reliability 1.

Tetradecamethylhexasiloxane has been tested for ability to cause chromosome aberrations in Chinese hamster lung fibroblasts (V79) according to OECD TG 473 and under GLP (Bioservice, 2015). No increase in the number of cells with aberrations was observed either with or without metabolic activation in Chinese hamster V79 cells, when tested up to precipitating concentrations. Appropriate negative (treatment medium) and positive controls were included and gave expected results. It is concluded that the test substance is negative for the induction of chromosome aberrations under the conditions of this study. The study was considered reliability 1.

Tetradecamethylhexasiloxane has been tested for mutagenicity in mouse lymphoma L5178Y cells according to OECD TG 476, and under GLP (Eurofins, 2015). No test-substance induced increase in the number of mutations was observed, when tested up to precipitating concentrations. Appropriate solvent, negative (treatment medium) and positive controls were included and gave expected results. It is concluded that the test substance is negative for mutagenicity to mammalian cells under the conditions of the study. The study was considered reliability 1.

Tetradecamethylhexasiloxane contains no structural elements which may be of concern for potential mutagenic activity. In vitro tests are negative, including a bacterial mutagenicity, mammalian cytogenicity and mammalian mutagenicity studies, therefore in vivo testing is not required.




Justification for classification or non-classification

Based on the available data for tetradecamethylhexasiloxane, no classification is required for genetic toxicity according to Regulation (EC) No 1272/2008.