1,1,1,3,5,5,5-heptamethyl-3-octyltrisiloxane

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:

2001-06-20 to 2001-07-06

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Version / remarks:

1997

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: EEC Directive 2000/32/EEC Method B. 13/14

GLP compliance:

yes

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-octyltrisiloxane

EC Number:

241-881-3

EC Name:

1,1,1,3,5,5,5-heptamethyl-3-octyltrisiloxane

Cas Number:

17955-88-3

Molecular formula:

C15H38O2Si3

IUPAC Name:

2,2,4,6,6-pentamethyl-4-octyl-3,5-dioxa-2,4,6-trisilaheptane

Test material form:

other: liquid

Method

Target gene:

histidine operon

Species / strain

Species / strain / cell type:

other: S. typhimurium TA 97s, TA 98, TA 100, TA 102 and TA 1535

Metabolic activation:

with and without

Metabolic activation system:

phenobarbital and β-naphtoflavone induced rat liver S9

Test concentrations with justification for top dose:

5, 1.6, 0.5, 0.16, 0.05 mg/plate

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: ethanol 95 %
- Justification for choice of solvent/vehicle:

Controls

Controls 1

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

Ethanol

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: ICR 191

Remarks:

TA 97a, without metabolic activation

Controls 2

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

Ethanol

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 4-nitro-o-phenylen-diamine

Remarks:

TA 98, without metabolic activation

Controls 3

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

Ethanol

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: nitrofurantione

Remarks:

TA 100, without metabolic activation

Controls 4

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

Ethanol

True negative controls:

no

Positive controls:

yes

Positive control substance:

sodium azide

Remarks:

TA 1535, without metabolic activation

Controls 5

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

Ethanol

True negative controls:

no

Positive controls:

yes

Positive control substance:

cumene hydroperoxide

Remarks:

TA 102, without metabolic activation

Controls 6

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

Ethanol

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 2-aminoanthracen

Remarks:

TA97a, TA 98, TA 100, TA 1535, with metabolic activation

Controls 7

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

Ethanol

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: danthron

Remarks:

TA 102, with metabolic activation

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation); preincubation
ACTIVATION: no data

DURATION
- Exposure duration:
Experiment 1: 48 hours, all test strains with and without metabolic activation
Experiment 2: 48 hours, all test strains with and without metabolic activation; 48 hours, TA 98 and TA 1535, without metabolic activation

SELECTION AGENT (mutation assays): no data

NUMBER OF REPLICATIONS: triplicate cultures

NUMBER OF CELLS EVALUATED: 150 cells

DETERMINATION OF CYTOTOXICITY
- Method: number of revertants, background lawn, induction rates

Evaluation criteria:

The test item was considered mutagen when there was a concentration effect relationship and the induction rate was >= 2.

Statistics:

The arithmetic mean value and the standard deviation were calculated out of the three replicates of the revertant colony plates.

Results and discussion

Test results

Species / strain:

other: S. typhimurium TA 97s, TA 98, TA 100, TA 102 and 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

Any other information on results incl. tables

Table 1: Experiement 1, mean number of revertants and induction rates of positive controls

Concentration μL/plate	TA 97a		TA 98		TA 1535		TA 100		TA 102
	+MA	-MA	+MA	-MA	+MA	-MA	+MA	-MA	+MA	-MA
5	215	417	45	44	29	31	116	133	710	537
1.6	232	344	41	38	28	36	111	134	730	533
0.5	227	324	48	41	26	45	113	121	557	490
0.16	254	307	36	40	29	32	115	127	688	531
0.05	213	264	28	35	28	36	108	120	659	484
ICR 191 0.5 μg/plate		>4.2
4-nitro-o-phenylen-diamine 0.5 μg/plate				3.0
2-aminoanthracen 2.0 μg/plate	>5.1		>34		4.5		>12.8
nitrofurantione 0.2 μg/plate		2.7						2.7
cumene hydroperoxide 100 μg/plate										>2.8
Danthron 30.0 μg/plate									>2.4
sodium azide 0.25 μg/plate						7.0

Table 2: Experiement 2, mean number of revertants and induction rates of positive controls

Concentration μg/plate	TA 97a		TA 98		TA 1535		TA 100		TA 102
	+MA	-MA	+MA	-MA	+MA	-MA	+MA	-MA	+MA	-MA
5	282	282	37	39	40	37	109	163	631	499
1.6	255	382	48	49	33	32	116	133	563	485
0.5	190	291	31	40	31	33	122	183	675	509
0.16	210	350	33	36	35	30	113	134	629	469
0.05	242	327	36	41	26	32	94	117	631	479
ICR 191 2.0 μg/plate		>4.1
4-nitro-o-phenylen-diamine 0.5 μg/plate				5.1
2-aminoanthracen 2.0 μg/plate	>4.9		>33		4.1		>11.5
nitrofurantione 0.2 μg/plate								2.9
cumene hydroperoxide 100 μg/plate										>2.3
Danthron 30.0 μg/plate									>2.2
sodium azide 0.25 μg/plate						5.4

Applicant's summary and conclusion

Conclusions:

Interpretation of results: negative with and without metabolic activation

1,1,1,3,5,5,5-heptamethyl-3-octyltrisiloxane 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 97a, TA 98, TA 100, TA 1535, or TA 102 in the initial or the repeat experiments up to 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.