Octamethyltrisiloxane

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:

2007-12-28 - 2008-01-23

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Octamethyltrisiloxane

EC Number:

203-497-4

EC Name:

Octamethyltrisiloxane

Cas Number:

107-51-7

Molecular formula:

C8H24O2Si3

IUPAC Name:

2,2,4,4,6,6-hexamethyl-3,5-dioxa-2,4,6-trisilaheptane

Constituent 2

Reference substance name:

105-51-7

IUPAC Name:

105-51-7

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, 1500 and 5000 µg/plate

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: Acetone
- Justification for choice of solvent/vehicle: none given

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 1 µg/plate

Remarks:

TA98, TA100, TA1535 and TA1537 with metabolic activation

Controls 2

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 2-aminoanthracene 10 µg/plate

Remarks:

WP2 uvrA with metabolic activation

Controls 3

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

2-nitrofluorene

Remarks:

TA98 without metabolic activation: 1 µg/plate

Controls 4

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

sodium azide

Remarks:

TA100 and TA1535 without metabolic activation: 1 µg/plate

Controls 5

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

9-aminoacridine

Remarks:

TA1537 without metabolic activation: 75 µg/plate

Controls 6

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

methylmethanesulfonate

Remarks:

WP2 uvrA without metabolic activation: 1000 µg/plate

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation)

ACTIVATION: S9 mix contained 10% S9, and glucose-6-phosphate and NADP as co-factors. 0.5 ml S9 mix was added to 2.0 ml top agar giving a final concentration of approximately 2% S9.
DURATION
- Exposure duration: 48 - 72 hours

NUMBER OF REPLICATIONS: experiment 1 - duplicate plates, experiment 2 - triplicate plates


DETERMINATION OF CYTOTOXICITY
- Method: other: condition of background lawn

Evaluation criteria:

A result is positive if the mean of each positive control exhibits at least a 3-fold increase in the number of revertants over the mean value of the respective vehicle control. A minimum of three non-toxic dose levels were required to evaluate assay data. Strains TA1535 and TA1537 were judged positive if there was a 3-fold increase in the number of revertants compared with the mean vehicle control value and a 2-fold increase for Salmonella typhimurium strains TA98, TA100 and E. coli WP2 uvrA.

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

Additional information on results:

TEST-SPECIFIC CONFOUNDING FACTORS


COMPARISON WITH HISTORICAL CONTROL DATA: Historical negative and positive control values included in report

ADDITIONAL INFORMATION ON CYTOTOXICITY: Cytotoxicity was not evident at any concentration

Any other information on results incl. tables

Plate incorporation – average number of revertants per plate (mean of 2 plates).

Experiment 1

Treatment µg/plate	TA98		TA100		TA1535		TA1537		WP2 uvrA
	-S9	+S9	-S9	+S9	-S9	+S9	-S9	+S9	-S9	+S9
Solvent control	15	13	147	164	16	13	4	8	21	18
1.5	17	13	160	147	18	12	6	6	18	18
5.0	16	14	164	175	19	9	1	8	22	24
15	16	17	140	120	15	11	8	4	19	14
50	13	14	177	156	17	13	6	5	19	21
150	15	18	155	156	22	12	7	6	24	24
500	12	15	172	171	15	12	8	9	24	18
1500	14	17	149	153	11	7	4	9	23	20
5000	14	16	179	175	15	9	7	5	21	21
Positive control	144	454	540	553	369	121	923	131	166	242

 

Plate incorporation – average number of revertants per plate (mean of 3 plates).

Experiment 2

Treatment µg/plate	TA98		TA100		TA1535		TA1537		WP2 uvrA
	-S9	+S9	-S9	+S9	-S9	+S9	-S9	+S9	-S9	+S9
Solvent control	31	17	183	184	20	17	10	8	23	23
50	18	18	189	173	16	16	6	10	21	19
150	28	16	199	172	16	18	11	11	27	24
500	24	12	171	180	12	18	11	7	25	20
1500	26	17	189	193	18	16	6	10	22	25
5000	28	19	167	198	16	20	6	10	20	23
Positive control	194	666	607	660	436	125	1154	185	127	278

 

Applicant's summary and conclusion

Conclusions:

Octamethyltrisiloxane 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 with Salmonella typhimurium strains TA 98, 100, 1535, 1537 and E.coli WP2 uvrA. Appropriate positive and solvent controls were tested and gave expected results. It is concluded that the test substance is negative for mutagenicity to bacteria under the conditions of the test.