Octaphenylcyclotetrasiloxane

Genetic toxicity: in vitro

Administrative data

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:

2011-08-08 to 2011-09-26

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

There were minor deviations

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2011

Report date:

2011

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Version / remarks:

1997

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: NIER 2010-29

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Octaphenylcyclotetrasiloxane

EC Number:

208-904-9

EC Name:

Octaphenylcyclotetrasiloxane

Cas Number:

546-56-5

Molecular formula:

C48H40O4Si4

IUPAC Name:

octaphenyl-1,3,5,7,2,4,6,8-tetraoxatetrasilocane

Method

Target gene:

histidine operon - Salmonella strains, tryptophan operon - E.coli strain

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 induced rat liver S9

Test concentrations with justification for top dose:

312.5, 625, 1250, 2500 and 5000 µg/plate

Vehicle / solvent:

acetone

Controls

Controls 1

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

sodium azide

Remarks:

-MA, TA 1535 (0.5 µg/plate)

Controls 2

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

9-aminoacridine

Remarks:

-MA, TA 1537 (80 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-(2-furyl)-3-(5-nitro-2-furyl)acrylamide

Remarks:

-MA, TA 98 (0.1 µg/plate) TA 100 (0.01 µg/plate) WP2 uvrA (0.01 µg/plate)

Controls 4

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 2-aminoanthracene

Remarks:

+MA, TA 98 (0.5 µg/plate) TA 100 (1.0 µg/plate) TA 1535 (2.0 µg/plate) TA 1537 (2.0 µg/plate) WP2 uvrA (10 µg/plate)

Details on test system and experimental conditions:

ACTIVATION:
Content of 1 mL S9 mix:
- 0.1 mL S9
- 8 µmol MgCl2
- 33 µmol KCl
- 5 µmol Glucose-6-phosphate
- 4 mol NADPH
- 4 µmol NADH
- 100 µmol Sodium phosphate buffer (pH 7.4)

METHOD OF APPLICATION: plate incorporation

DURATION
- Preincubation period:
- Exposure duration:
- Expression time (cells in growth medium):

SELECTION AGENT (mutation assays): histidine tryptophan deficient agar

NUMBER OF REPLICATIONS: 3

DETERMINATION OF CYTOTOXICITY
- Method: other: clearing of diminution of background lawn, the appearance of micro-colonies, and/or the decrease more than 50% in the number of colonies compared to the vehicle control.

Evaluation criteria:

Results were judged to be positive if there was a reproducible increase in the number of colonies in a dose-dependant manner, at least in one test strain with or without the metabolic system, clearly exceeding 2 times of that of control.

Results and discussion

Test results

Test results 1

Key result

Species / strain:

S. typhimurium TA 1535

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

Positive controls validity:

valid

Test results 2

Key result

Species / strain:

S. typhimurium TA 1537

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

Positive controls validity:

valid

Test results 3

Key result

Species / strain:

S. typhimurium TA 98

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

Positive controls validity:

valid

Test results 4

Key result

Species / strain:

S. typhimurium 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

Positive controls validity:

valid

Test results 5

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

Positive controls validity:

valid

Remarks on result:

other: No mutagenic potential

Any other information on results incl. tables

Plate incorporation: number of revertant colonies (mean of 3)

Dose (μg/plate)	TA 98		TA 100		TA 1535		TA 1537		WP2 uvrA
	- MA	+ MA	- MA	+ MA	- MA	+ MA	- MA	+ MA	- MA	+ MA
0	13	18	90	88	10	10	6	9	28	33
50	14	16	86	86	8	8	5	9	32	32
100	12	17	83	87	8	12	7	7	29	30
500	14	14	79	88	11	10	5	7	31	31
1000	10	12	85	85	9	11	7	8	28	32
5000	8	12	80	80	6	9	7	7	27	31
Positive control	353	329	416	462	312	200	712	260	316	320

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative with and without metabolic activation

Octaphenylcyclotetrasiloxane 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 E. coli WP2 uvrA in the initial or the repeat experiments up to cytotoxic/limit concentrations. Appropriate positive and solvent 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.