2,4,6-trimethyl-2,4,6-tris(3,3,3-trifluoropropyl)cyclotrisiloxane

Genetic toxicity: in vitro

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2011

Report date:

2011

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

2,4,6-trimethyl-2,4,6-tris(3,3,3-trifluoropropyl)cyclotrisiloxane

EC Number:

219-154-7

EC Name:

2,4,6-trimethyl-2,4,6-tris(3,3,3-trifluoropropyl)cyclotrisiloxane

Cas Number:

2374-14-3

Molecular formula:

C12H21F9O3Si3

IUPAC Name:

2,4,6-trimethyl-2,4,6-tris(3,3,3-trifluoropropyl)cyclotrisiloxane

Constituent 2

Reference substance name:

002374-14-3

Cas Number:

002374-14-3

IUPAC Name:

002374-14-3

Method

Species / strain

Species / strain 1

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Species / strain 2

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.

Controls

Controls 1

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

Controls 2

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

Controls 3

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

Controls 4

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

Controls 5

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

Results and discussion

Test results

Test results 1

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

Test results 2

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

Any other information on results incl. tables

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

Applicant's summary and conclusion

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 Test Guideline 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.