2,8,9-Trioxa-5-aza-1-silabicyclo[3.3.3]undecane, 1,1'-(dithiodi-3,1-propanediyl)bis-

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:

2007-12-14 - 2008-03-18

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was conducted according to an appropriate test guideline and in compliance with GLP.

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)

Version / remarks:

1997

Deviations:

no

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

477-700-1

EC Name:

-

Cas Number:

883794-93-2

Molecular formula:

Hill formula: C18H36N2O6S2Si2 CAS formula: C18H36N2O6S2Si2

IUPAC Name:

1-{3-[(3-{2,8,9-trioxa-5-aza-1-silabicyclo[3.3.3]undecan-1-yl}propyl)disulfanyl]propyl}-2,8,9-trioxa-5-aza-1-silabicyclo[3.3.3]undecane

Method

Target gene:

histidine-tryptophan requiring strains

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:

S9-mix (rat liver homogenate)

Test concentrations with justification for top dose:

first experiment: 0; 62; 185; 556; 1667; 5000 µg/plate
second experiment: 0; 1000; 2000; 3000; 4000; 5000 µg/plate

Vehicle / solvent:

DMSO

Controls

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

no

Positive controls:

yes

Positive control substance:

9-aminoacridine

2-nitrofluorene

sodium azide

benzo(a)pyrene

other: 4-nitroquinoline-1-oxide, 2-amioanthracene

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation)

DURATION
- Exposure duration: 48 h at 37°C

DETERMINATION OF CYTOTOXICITY: counting of bacteria colonies

NUMBER OF REPLICATIONS: 2 tests, for each strain and concentration three plates

Evaluation criteria:

A test substance producing no biologically relevant positive response in any one of the bacterial strains tested is considered to be non-mutagenic in this system. A biological relevant response is present if the number of revertants is at least twice the spontaneous reversion rate in one of the strains and/or if there is a concentration related increasing number of revertants over the range tested.

Statistics:

Student's t-test

Results and discussion

Test results

Test results 1

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

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Test results 2

Species / strain:

E. coli WP2 uvr A

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Additional information on results:

COMPARISON WITH HISTORICAL CONTROL DATA: The positive control substances induced clear increases in revertant colonies (more than twice the
spontaneous rate of the respective negative control

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

Table 1: Results of the Main Experiment 1 with and without S9

Dose [µg/plate]	Mean revertants / plate
	Without S9					With S9
	TA 1535	TA 1537	TA 98	TA 100	WP2 uvrA	TA 1535	TA 1537	TA 98	TA 100	WP2 uvrA
Solvent control	16±4	10±3	28±3	120±7	25±5	27±3	11±3	41±4	160±6	36±5
62	18±1	7±3	30±1	135±22	20±3	23±4	10±4	41±1	149±22	37±5
185	21±5	8±2	25±3	110±8	27±3	23±5	8±5	33±3	146±6	35±12
556	12±5	9±4	25±7	120±8	21±4	24±2	9±2	39±5	161±13	36±7
1667	21±6	±1	31±5	155±44	25±2	24±5	12±1	35±5	168±20	36±1
5000	19±5	8±3	24±6	120±13	27±1	29±5	8±2	39±5	173±11	37±2
Positive control*	549±40	367±60	397±72	1000±0	1000±0	149±15	58±10	1000±0	1000±0	255±54

* without S9: sodium azide (TA 1535 and TA 100); 9-aminoacridine (TA 1537); 2-nitroflurene (TA 98); 4-nitroquinoline-1-oxide (WP2 uvrA)

with S9: 2 -aminoanthracene (TA 1535, TA 1537, TA 100 and WP2 uvrA); Benzo(a)pyrene (TA 98)

Table 2: Results of the Main Experiment 2 with and without S9

Dose [µg/plate]	Mean revertants / plate
	Without S9					With S9
	TA 1535	TA 1537	TA 98	TA 100	WP2 uvrA	TA 1535	TA 1537	TA 98	TA 100	WP2 uvrA
Solvent control	24±5	7±3	38±3	127±13	26±5	26±5	7±3	42±7	150±24	33±7
62	20±4	8±1	32±3	123±8	25±3	32±7	6±1	34±3	130±12	38±3
185	25±1	7±0	30±3	121±8	25±2	25±7	7±2	39±3	159±7	34±9
556	23±3	8±5	32±2	118±13	24±2	29±5	10±1	42±2	147±24	34±4
1667	25±1	10±1	36±1	133±19	33±7	30±2	7±2	34±2	150±9	33±13
5000	22±4	7±1	37±6	123±9	28±1	25±3	6±2	30±9	141±7	39±6
Positive control*	571±28	447±146	626±95	1000±0	1000±0	421±64	579±72	1000±0	1000±0	247±63

* without S9: sodium azide (TA 1535 and TA 100); 9-aminoacridine (TA 1537); 2-nitroflurene (TA 98); 4-nitroquinoline-1-oxide (WP2 uvrA)

with S9: 2 -aminoanthracene (TA 1535, TA 1537, TA 100 and WP2 uvrA); Benzo(a)pyrene (TA 98)

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative

The test substance was not mutagenic under the test conditions neither in the absence nor in the presence of S9 supplementation.