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 activation in Salmonella typhimurium strains TA98, TA100, TA1535 and TA1537 Escherichia coli WP2 (OECD TG 471) (BioReliance, 2011).
Cytogenicity in mammalian cells; not required: in vivo micronucleus data are available.
Mutagenicity in mammalian cells: negative with and without metabolic activation in mouse lymphoma L5178Y cells (OECD 476) (BSL Bioservice, 2013d).

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:
2011-04-14 to 2011-05-24
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of assay:
bacterial reverse mutation assay
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Species / strain / cell type:
E. coli WP2 uvr A
Metabolic activation:
with and without
Metabolic activation system:
Aroclor 1254-induced rat liver S9
Test concentrations with justification for top dose:
50, 150, 500, 1000, 2500 and 5000 µg/plate
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: ethanol
- Justification for choice of solvent/vehicle: Ethanol was selected based on the 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:
other: 2-aminoanthracene
Remarks:
with metabolic activation -TA98, TA1535, TA1537 - 1.0 µg/plate, TA100 -2.0 µg/plate, WP2 uvrA - 15 µg/plate
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
2-nitrofluorene
Remarks:
without metabolic activation TA98 : 1.0 µg/plate
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
sodium azide
Remarks:
without metabolic activation TA100 and TA1535: 1.0 µg/plate
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
9-aminoacridine
Remarks:
without metabolic activation TA1537: 75 µg/plate
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
methylmethanesulfonate
Remarks:
without metabolic activation WP2 uvrA: 1000 µg/plate
Details on test system and experimental conditions:
METHOD OF APPLICATION: in agar (plate incorporation); preincubation

ACTIVATION: 10% S9 mix contained glucose-6-phosphate and NADP as co-factors and included MgCl and KCI in a phosphate buffer at pH 7.4.
DURATION

- Exposure duration: 48 - 72 hours at 37C

SELECTION AGENT (mutation assays): histidine deficient agar


NUMBER OF REPLICATIONS: triplicate plates, test repeated


DETERMINATION OF CYTOTOXICITY
other: condition of the bacterial background lawn


OTHER:
Evaluation criteria:
For a test article to be evaluated positive, it must cause a dose-related increase in the mean revertants per plate of at least one tester strain over a minimum of two increasing concentrations of test article as specified; TA1535 and TA1537 will be judged positive if the increase in mean revertants at the peak of the dose response is equal to or greater than 3.0 times the mean vehicle control value. TA98, TA100 and WP2 uvrA will be judged positive if the increase in mean revertants at the peak of the dose response is equal to or greater than 2.0 times the mean vehicle control value.
Statistics:
None stated in report
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

Summary of results – mean revertants per plate

Treatment µg/plate

       TA 98

 

TA 100

TA 1535

TA 1537

WP2 uvrA

- S9

+ S9

- S9

+ S9

- S9

+ S9

- S9

+ S9

-S9

+S9

0

21

35

121

155

18

19

5

8

48

38

50

26

36

113

157

22

31

6

7

30

50

150

22

25

137

151

20

19

6

8

55

52

500

25

29

115

186

21

15

5

8

38

43

1000

25

30

136

190

19

20

6

9

33

53

2500

26

18

134

174

28

17

11

11

34

42

5000

19

23

121

196

23

27

6

7

32

52

Pos con

217

323

791

667

761

98

195

45

203

127

Conclusions:
2,4,6-trimethyl-2,4,6-tris(3,3,3-trifluoropropyl)cyclotrisiloxane has been tested for mutagenicity to bacteria, in a study which was conducted according to OECD 471 and in compliance with GLP. No evidence of a test substance related increase in the number of revertants was observed with or without activation in the initial or the repeat experiments. 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.
Endpoint:
in vitro gene mutation study in mammalian cells
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
Qualifier:
according to
Guideline:
EU Method B.17 (Mutagenicity - In Vitro Mammalian Cell Gene Mutation Test)
Qualifier:
according to
Guideline:
EPA OPPTS 870.5300 - In vitro Mammalian Cell Gene Mutation Test
Qualifier:
according to
Guideline:
other: IWGT Recommendations
Deviations:
no
GLP compliance:
yes
Type of assay:
mammalian cell gene mutation assay
Target gene:
thymidine kinase
Species / strain / cell type:
mouse lymphoma L5178Y cells
Details on mammalian cell type (if applicable):
- Type and identity of media: RPMI 1640 supplemented with: 9.0 μg/ml hypoxanthine 15.0 μg/ml thymidine 22.5 μg/ml glycine 0.1 μg/ml methotrexate
- Properly maintained: no information
- Periodically checked for Mycoplasma contamination: yes
- Periodically checked for karyotype stability: no information
- Periodically "cleansed" against high spontaneous background: no information
Metabolic activation:
with and without
Metabolic activation system:
phenobarbital (80 mg/kg bw) and ß-naphthoflavone (100 mg/kg bw) induced rat liver S9
Test concentrations with justification for top dose:
Expt I: 0.002, 0.005, 0.01, 0.02, 0.04, 0.06, 0.08, 0.10 and 0.15 mM (-S9), 0.005, 0.01, 0.02, 0.05, 0.10, 0.20, 0.30 and 0.40 mM(+S9). Expt II: 0.0005, 0.002, 0.005, 0.010, 0.020, 0.025, 0.035, 0.040 mM(-S9), 0.005, 0.01, 0.02, 0.05, 0.06, 0.07, 0.08 and 0.12 mM (+S9)
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: ethanol;
- Justification for choice of solvent/vehicle: A solubility test was performed
- The test item was dissolved in ethanol after treatment with ultrasound for 5 minutes at 37° C, then diluted with RPMI + 5% HS
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
ethylmethanesulphonate
Remarks:
without metabolic activation; 300 μg/ml expt I; 200 μg/ml expt II
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
methylmethanesulfonate
Remarks:
without metabolic activation; 8 μg/ml expt I; 10 μg/ml expt II
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
benzo(a)pyrene
Remarks:
with metabolic activation; 1.5 μg/ml expt I; 2.5 μg/ml expt II
Details on test system and experimental conditions:
METABOLIC ACTIVAION: Sufficient 9 was added to S9 mix to produce a final protein concentration of 0.75 mg/ml. Cofactors were added to the following concentrations: 8 mM MgCl2; 33 mM KCl 5; mM Glucose-6-phosphate; 5 mM NADP

METHOD OF APPLICATION: in medium

DURATION

- Exposure duration: 4 hours (Expt I +/-MA and expt II +MA) 24 hours Expt II -MA.
- Expression time (cells in growth medium): 20 hours (4 h exposure)
- Selection time (if incubation with a selection agent): 14 days


SELECTION AGENT (mutation assays): TFT (trifluorothymidine)

NUMBER OF REPLICATIONS: Single cultures were exposed. Mutant frequency was based on four plates, cloning efficiency on two. The experiment was repeated.

DETERMINATION OF CYTOTOXICITY
- Method: cloning efficiency; relative total growth;

OTHER EXAMINATIONS:
- Other: small and large colony
Evaluation criteria:
The test item is considered mutagenic if following criteria are met:
- The induced mutant frequency meets or exceeds the Global Evaluation factor (GEF) of 126 mutants per 10E+06 cells
- A dose-dependent increase in mutant frequency is detected.

Combined with a positive effect in the mutant frequency, an increased occurrence of small colonies (≥40% of total colonies) is an indication for potential clastogenic effects and/or chromosomal aberrations.
Statistics:
Statistical significance at the 5% level (p < 0.05) was evaluated by means of the non-parametric Mann-Whitney test.
Key result
Species / strain:
mouse lymphoma L5178Y cells
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
Expt I: 0.15 mM (-S9, 4h exposure RTG 9.4%), 0.40 mM (+S9, 4h exposure RTG 11.8%; Expt II: 0.040 mM (-S9, 24h exposure RTG 10.6% ), 0.12 mM (+S9, 4h exposure RTG 16.7%).
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: pH was within the physiological range.

- Effects of osmolality: no information

- Precipitation: Precipitation of the test item was noted in pre-experiment I without metabolic activation at a concentration of 10.0 mM and with metabolic activation at concentrations of 7.5 mM and higher. No precipitation of the test item was noted in experiment I and II without and with metabolic activation and pre-experiment II without metabolic activation.

- Other confounding effects: none

COMPARISON WITH HISTORICAL CONTROL DATA: all control mutant frequencies were within the range of the historical controls.

Summary of results Experiments I and II

Group

Conc.

RCE a [%]

RTG b [%]

MF c [mutants/ 106 cells]

IMF d [mutants/ 106 cells]

GEF e exceeded

Statistical Significance f

Precipitate

Experiment I without metabolic activation, 4 h exposure

C1

0

105.5

114.4

89.1

/

/

/

-

C2

138.3

142.2

/

/

/

-

S1

0

100.0

100.0

98.6

/

/

/

-

S2

/

/

/

-

7

0.002

105.5

98.7

91.0

-7.6

-

-

-

8

0.005

97.7

95.8

81.0

-17.6

-

-

-

9

0.01

94.8

94.7

97.5

-1.1

-

-

-

10

0.02

88.1

75.9

114.9

16.3

-

-

-

11

0.04

102.3

65.0

78.8

-19.8

-

-

-

12

0.06

78.6

38.1

97.0

-1.6

-

-

-

13

0.08

86.9

15.1

92.8

-5.8

-

-

-

14

0.10

80.8

14.0

95.3

-3.3

-

-

-

15

0.15

86.9

9.4

77.2

-21.4

-

-

-

EMS

300 μg/ml

77.4

66.7

870.0

771.4

+

+

-

MMS

8 μg/ml

85.6

78.7

560.8

462.2

+

+

-

Experiment II without metabolic activation, 20 h exposure

C1

0

101.1

115.9

89.1

 

/

/

/

-

C2

138.3

142.2

/

/

/

-

S1

0

100.0

100.0

98.6

/

/

/

-

S2

/

/

/

-

3

0.0005

122.5

106.5

92.0

6.1

-

-

-

5

0.002

89.8

93.2

103.9

18.0

-

-

-

6

0.005

112.8

104.3

68.8

-17.1

-

-

-

7

0.010

82.3

75.8

117.5

31.6

-

-

-

8

0.020

114.6

52.7

73.4

-12.4

-

-

-

9

0.025

89.8

18.5

93.7

7.8

-

-

-

11

0.035

120.5

16.8

90.8

4.9

-

-

-

12

0.040

89.8

10.6

98.3

12.4

-

-

-

EMS

200 μg/ml

62.8

32.8

2382.6

2296.8

+

+

-

MMS

10 μg/ml

52.8

28.7

1293.1

1207.2

+

+

-

Experiment I with metabolic activation, 4 h exposure

C1

0

113.2

105.0

109.3

/

/

/

-

C2

102.2

101.8

/

/

/

-

S1

0

100.0

100.0

135.0

 

/

/

/

-

S2

/

/

/

-

2

0.005

102.2

98.4

100.3

-34.7

-

-

-

3

0.01

124.0

98.5

89.0

-46.0

-

+

-

4

0.02

114.9

100.1

88.9

-46.1

-

+

-

5

0.05

111.5

91.7

116.1

-18.9

-

-

-

6

0.10

106.7

79.9

82.4

-52.6

-

+

-

7

0.20

109.9

28.2

78.7

-56.3

-

+

-

8

0.30

109.9

34.9

82.1

-53.0

-

+

-

9

0.40

75.8

11.8

116.5

-18.5

-

-

-

B[a]P

1.5 μg/ml

120.2

92.1

598.6

463.6

+

+

-

Experiment II with metabolic activation, 4 h exposure

C1

0

97.7

100.9

87.8

/

/

/

-

C2

110.5

110.6

/

/

/

-

S1

0

100.0

100.0

98.5

 

/

/

/

-

S2

/

/

/

-

6

0.005

100.7

106.8

99.8

1.3

-

-

-

7

0.01

105.4

107.6

73.0

-25.4

-

+

-

8

0.02

102.2

112.2

70.4

-28.0

-

+

-

11

0.05

105.4

92.1

92.9

-5.5

-

-

-

12

0.06

93.4

87.9

59.8

-38.7

-

+

-

13

0.07

93.4

68.3

86.8

-11.7

-

-

-

14

0.08

89.4

34.5

84.6

-13.8

-

-

-

15

0.12

75.2

16.7

126.2

27.7

-

-

-

B[a]P

2.5 μg/ml

99.1

84.2

468.5

370.0

+

+

-

C: Negative Controls

S: Solvent Controls

a: Relative Cloning Efficiency, RCE = [(CEdose group/ CEof corresponding controls) x 100]

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

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

c: Mutant Frequency,

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

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

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

f: statistical significant difference in mutant frequency compared to solvent controls (Mann Whitney test , p<0.05).+: significant; -not significant

EMS: Ethylmethanesulfonate [μg/ml]

MMS: Methylmethanesulfonate [μg/ml]

B[a]P: Benzo[a]pyrene [μg/ml]

Conclusions:
F-D3 has been tested in a reliable mammalian mutagenicity study conducted according to OECD 476 and in compliance with GLP. No increase in mutant frequency was observed with or without metabolic activation when L5178Y cells up to cytotoxic concentration in either the initial four hour exposure assay or the repeat experiment in which cells were exposed for four hours with and twenty four hours without metabolic activation. In addition, no evidence of clastogenicity was observed. Appropriate positive, solvent and negative (treatment medium) controls were included and gave expected results.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Genetic toxicity in vivo

Description of key information

Micronucleus assay in mouse (oral administration): negative (OECD TG 474) (BioReliance, 2012).
Rodent dominant lethal: no dominant lethal effect amongst cells at different stages of spermatogenesis observed, but the higher dose induced a mutagenic effect in spermatogonia (Batulin, 1977).

Link to relevant study records
Reference
Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2012-04-02 to 2012-05-10
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
Qualifier:
according to
Guideline:
other: US EPA GLP Standards 40 CFR 792 (TSCA)
GLP compliance:
yes
Type of assay:
micronucleus assay
Species:
mouse
Strain:
ICR
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan, Frederick, MD
- Age at study initiation: 6 weeks old
- Weight at study initiation: 29.4 - 32.5 grams (male) and 23.9 - 28.8 grams (female)
- Assigned to test groups randomly: yes (based on equalization of group mean body weights)
- Housing: Five same sex per rodent Micro-Barrier cage
- Diet (e.g. ad libitum): yes
- Water (e.g. ad libitum): yes
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 72 +/- 3F
- Humidity (%): 50 +/- 20%
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle

IN-LIFE DATES: From: To: 18 - 23 April 2012
Route of administration:
oral: gavage
Vehicle:
- Vehicle(s)/solvent(s) used: corn oil
- Justification for choice of solvent/vehicle: based on Sponsor information
- Concentration of test material in vehicle:
- Amount of vehicle (if gavage or dermal): 80%
- Type and concentration of dispersant aid (if powder):
- Lot/batch no. (if required):
- Purity:
Duration of treatment / exposure:
24 and 48 hours
Frequency of treatment:
Test compounds and controls were administered by a single oral gavage at a dose volume of 10mL/kg body weight.
Post exposure period:
Negative and positive controls and all three dose levels were sacrificed at 24 hours after administration of test substance. The vehicle control and highest dose level were sacrificed 48 hours after administration of test substance.
Dose / conc.:
500 mg/kg bw/day (nominal)
Dose / conc.:
1 000 mg/kg bw/day (nominal)
Dose / conc.:
2 000 mg/kg bw/day (nominal)
No. of animals per sex per dose:
Five
Control animals:
yes, concurrent vehicle
Positive control(s):
- cyclophosphamide
- Justification for choice of positive control(s): standard guideline positive control
- Route of administration: oral gavage
- Doses / concentrations: 50 mg/kg
Tissues and cell types examined:
Bone marrow was collected from all treatment groups and polychromatic erythrocytes (PCE's) and normochromatic erythrocytes (NCE's) were examined for micronuclei.
Details of tissue and slide preparation:
CRITERIA FOR DOSE SELECTION: limit dose

TREATMENT AND SAMPLING TIMES ( in addition to information in specific fields): no further information

DETAILS OF SLIDE PREPARATION: Following euthanasia, the femurs were exposed, and the bone marrow was aspirated into syringe with foetal bovine serum. The bone marrow was centrifuged and the supernatant drawn off. The cell pellet was re-suspended and a small drop of bone marrow suspension was spread onto a clean glass slide (2 slides per mouse). The slides were air dried, fixed in methanol and stained with acridine orange.

METHOD OF ANALYSIS: Slides were coded randomly. Bone marrow cells were evaluated using a fluorescent microscope. 2000 polychromatic erythrocytes (PCEs) were scored for micronuclei per animal. The number of normochromatic erythrocytes (NCEs) and micronucleated NCEs (MNCEs) in the field of 1000 total erythrocytes was determined. The proportion of PCEs to total erythrocytes (ECs) was also determined per 1000 erythrocytes for each animal.

Evaluation criteria:
The test article would have been considered to induce a positive response if the incidence of micronucleated polychromatic erythrocytes at one or more doses is statistically elevated relative to the vehicle control, in a dose dependent manner and exceeding the range of historical vehicle controls.
Statistics:
Statistical significance was determined using the Kastenbaum-Bowman tables which are based on the binomial distribution. All analyses were performed separately for each sex and sampling time.
Key result
Sex:
male/female
Genotoxicity:
negative
Toxicity:
no effects
Remarks:
on PCE/EC ratios
Vehicle controls validity:
valid
Negative controls validity:
not applicable
Positive controls validity:
valid
Additional information on results:
RESULTS OF DETERMINATION OF SYSTEMIC AVAILABILITY:
All animals survived until post-dose collection time point.
Dose concentration, stability and homogeneity were verified by GC/FID methods. The dose solution concentrations were determined to be within the criteria for acceptance, and to be stable for at least two days at room temperature. No extraction of the solutions was carried out prior to determining concentration.
The limit of quantitation of the GC/MS determination of test article content in plasma was 14.4 ng/g. Test article detected in plasma was significantly above the limit of detection for all dose groups at both blood collection time points.
Necroscopy: gross lesions were noted in one animal in the low dose group, these were not attributed to the test article. No gross lesions were observed in any other animal.

Summary of Bone Marrow Micronucleus Analysis

Treatment (10 ml/kg)

Sex and time (hrs)

Mean of PCE/Total erythrocytes

Mean of MPCE/1000 PCE

Number of MPCE/PCE scored

Solvent control

M - 24

0.576

0.2

2 / 1000

F -24

0.574

0.4

4 / 1000

500 mg/kg bw

M - 24

0.556

0.5

5 / 1000

F - 24

0.563

0.2

2 / 1000

1000 mg/kg bw

M - 24

0.412

0.2

2 / 1000

F - 24

0.587

0.4

4 / 1000

2000 mg/kg bw

M - 24

0.522

0.2

2 / 1000

F - 24

0.568

0.5

5 / 1000

Positive control

M - 24

0.500

24.4

**244 / 1000

F - 24

0.488

18.0

**180 / 1000

Solvent control

M - 48

0.579

0.2

2 / 1000

F - 48

0.582

0.3

3 / 1000

2000 mg/kg bw

M - 48

0.447

0.6

6 / 1000

F - 48

0.426

0.3

3 / 1000

** Statistically significant increase compared to vehicle control

Conclusions:
2,4,6-trimethyl-2,4,6-tris(3,3,3-trifluoropropyl)cyclotrisiloxane was tested in an in vivo mouse micronucleus assay conducted according to OECD 474 and in compliance with GLP. No evidence of test substance related induction of micronucleus was observed after oral administration by gavage at doses of 500, 1000 and 2000 mg/kg bw. No test substance related changes in the PCE/NCE ratio were observed, so it was concluded that the test substance did not inhibit erythropoiesis. Appropriate solvent and positive controls were included and gave expected results. It is concluded that the test substance is not genotoxic under the conditions of the test.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Additional information

2,4,6-trimethyl-2,4,6-tris(3,3,3-trifluoropropyl)cyclotrisiloxane has been tested for mutagenicity to bacteria in a study which was conducted according to OECD 471 and in compliance with GLP (BioReliance, 2011). No evidence of a test substance related increase in the number of revertants was observed with or without activation in the initial or the repeat experiments using S. typhimurium TA 1535, TA 1537, TA 98 and TA 100 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. Additional information on mutagenicity to bacteria is provided by three older studies (Dow Corning Corporation, 1978, Dow Corning Corporation, 1979a, Dow Corning Corporation, 1979b). No evidence for genetic toxicity was observed in any of these studies.

2,4,6-trimethyl-2,4,6-tris(3,3,3-trifluoropropyl)cyclotrisiloxane has been tested in a reliable mammalian mutagenicity study conducted according to OECD 476 and in compliance with GLP (BSL Bioservice, 2013d). No increase in mutant frequency was observed with or without metabolic activation when L5178Y cells up to cytotoxic concentration in either the initial four hour exposure assay or the repeat experiment in which cells were exposed for four hours with and twenty four hours without metabolic activation. In addition, no evidence of clastogenicity was observed. Appropriate positive, solvent and negative (treatment medium) controls were included and gave expected results.

2,4,6-trimethyl-2,4,6-tris(3,3,3-trifluoropropyl)cyclotrisiloxane was tested in an in vivo mouse micronucleus assay conducted according to OECD 474 and in compliance with GLP (BioReliance, R., 2012). No evidence of test substance related induction of micronucleus was observed after oral administration by gavage at doses of 500, 1000 and 2000 mg/kg bw. No test substance related changes in the PCE/NCE ratio were observed, so it was concluded that the test substance did not inhibit erythropoiesis. Appropriate solvent and positive controls were included and gave expected results. It is concluded that the test substance is not genotoxic under the conditions of the test.

2,4,6-trimethyl-2,4,6-tris(3,3,3-trifluoropropyl)cyclotrisiloxane has been tested in a rodent dominant lethal study using mice (Batulin, 1977). The publication where these results were presented was in Russian and no translation was available, therefore it was considered to be Reliability 4. No evidence was obtained of a dominant lethal effect amongst cells at different stages of spermatogenesis, but the results indicated a mutant effect in spermatogonia of mice treated with 150 mg/kg bw/day. It is concluded that the test substance has potential for mutagenicity to germ cells.


Justification for classification or non-classification

Based on the available in vitro and in vivo genotoxicity data, 2,4,6-trimethyl-2,4,6-tris(3,3,3-trifluoropropyl)cyclotrisiloxane is not classified for mutagenicity according to Regulation (EC) No 1272/2008.