2,11-Dioxa-3,10-disiladodecane, 3,3,10,10-tetramethoxy-

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:

19.06.1991 - 01.08.1991

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The study was conducted according to the appropriate OECD test guideline, and in compliance with GLP, with acceptable deviations. The deviations were that only duplicate plates were used instead of triplicate. The report is a certified translation from Japanese (signed Ogura, S. 1997-07-22).

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

JAPAN: Guidelines for Screening Mutagenicity Testing Of Chemicals

Version / remarks:

Japanese MOL 76, 1988

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Reference substance 001

Cas Number:

87135-01-1

Molecular formula:

C12H30O6Si2

Constituent 2

Reference substance name:

3,3,10,10-tetramethoxy-2,11-dioxa-3,10-disiladodecane

EC Number:

617-969-6

Cas Number:

87135-01-1

Molecular formula:

(CH3O)3Si(CH2)6Si(OCH3)3 C12 H30 O6 Si2

IUPAC Name:

3,3,10,10-tetramethoxy-2,11-dioxa-3,10-disiladodecane

Test material form:

other: liquid

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:

Phenobarbitol and benzoflavone induced rat liver S9

Test concentrations with justification for top dose:

313, 625, 1250. 2500 and 5000 µg/plate with and without S9

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: no reason given

Controls

Controls 1

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Remarks:

TA98 and TA100 - 0.1µg/plate, WP2 uvrA - 0.01 µg/plate

Positive control substance:

other: 2-(2-Furyl)-3-(5-nitro-2-furyl)acrylamide (AF-2)

Remarks:

TA100, TA98, WP2 uvrA without metabolic activation

Controls 2

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Remarks:

0.5 µg/plate

Positive control substance:

sodium azide

Remarks:

TA1535 without metabolic activation

Controls 3

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Remarks:

1 µg/plate

Positive control substance:

other: 2-Methoxy-6-chloro-9-(3-(2-chloroethyl)-aminopropylamino)acridine

Remarks:

TA1537 without metabolic activation

Controls 4

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Remarks:

TA100 - 1 µg/plate, TA1535, TA1537 - 2 µg/plate, TA98 - 0.5 µg/plate, WP2 uvrA - 10 µg/plate

Positive control substance:

other: 2-Aminoanthracene

Remarks:

TA100, TA1535, TA98, TA1537, WP2 uvrA with metabolic activation

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation)

ACTIVATION: S9 mix contained glucose-6-phosphate and NADP as co-factors, 0.1 ml of S9 mix containing 10% S9 was added to 2 ml top agar, 0.1 ml bacterial suspension and 0.1 ml of test solution, giving a final concentration of approximately 2% S9.

DURATION

- Exposure duration: 48 hrs at 37°C


SELECTION AGENT (mutation assays): histidine deficient agar


NUMBER OF REPLICATIONS: duplicate plates, initial dose-finding experiment used all strains. The experiment was repeated

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

Evaluation criteria:

The test substance is judged to be positive when the number of revertant colonies is more than twice that of the negative control and is dose-related.

Statistics:

A mean value of two plates was calculated with rounding off a fraction to a decimal point and no statistical analysis was used.

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

Untreated negative controls validity:

not applicable

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

Untreated negative controls validity:

not applicable

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

Untreated negative controls validity:

not applicable

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

Untreated negative controls validity:

not applicable

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

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:

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

1,6-Bis(trimethoxysilyl)hexane has been tested for mutagenicity to bacteria in a study which was conducted according to the Japanese guideline MOL, No 76 (similar to OECD 471) and in compliance with GLP. No evidence for a test-substance related increase in the number of revertants was observed with or without metabolic activation in the initial or repeat experiments using S. typhimurium TA 1535, TA 1537, TA 98 and TA 100 and E. coli WP2 uvr A. 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.