1,1,1,3,5,5,5-heptamethyl-3-[(trimethylsilyl)oxy]trisiloxane

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:

2001

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2001

Report date:

2001

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

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.

Test guideline 2

Qualifier:

equivalent or similar to guideline

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

Test material

Test material information

Constituent 1

Reference substance name:

1,1,1,3,5,5,5-heptamethyl-3-[(trimethylsilyl)oxy]trisiloxane

EC Number:

241-867-7

EC Name:

1,1,1,3,5,5,5-heptamethyl-3-[(trimethylsilyl)oxy]trisiloxane

Cas Number:

17928-28-8

Molecular formula:

C10H30O3Si4

IUPAC Name:

2,2,4,6,6-pentamethyl-4-[(trimethylsilyl)oxy]-3,5-dioxa-2,4,6-trisilaheptane

Constituent 2

Reference substance name:

017928-28-8

Cas Number:

017928-28-8

IUPAC Name:

017928-28-8

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:

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.

Controls

Controls 1

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

Controls 2

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

Controls 3

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

Controls 4

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.

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

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

Applicant's summary and conclusion

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.