nonapotassium 2,4,6-trihydroxy-4-methyl-3,5-dioxa-2,4,6-trisilaheptane-2,6-bis(olate) 2,6,8-trihydroxy-4,6-dimethyl-3,5,7-trioxa-2,4,6,8-tetrasilanonane-2,4,8-tris(olate) 6-hydroxy-2,4,6-trimethyl-1,3,5,2,4,6-trioxatrisilinane-2,4-bis(olate) dihydroxy(methyl)silanolate {[dihydroxy(methyl)silyl]oxy}(hydroxy)methylsilanolate

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

2002-04-15 to 2002-06-13

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2002

Report date:

2002

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Potassium methylsilanetriolate

EC Number:

250-807-9

EC Name:

Potassium methylsilanetriolate

Cas Number:

31795-24-1

IUPAC Name:

tripotassium methylsilanetriolate

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:

S. typhimurium TA 102

Metabolic activation:

with and without

Metabolic activation system:

Aroclor induced rat liver S9

Test concentrations with justification for top dose:

100-5000 µg/plate

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: water

- Justification for choice of solvent/vehicle: none given in report

Controls

Controls 1

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

Water

True negative controls:

no

Positive controls:

yes

Positive control substance:

sodium azide

Remarks:

TA 1535, TA 100 (without activation)

Controls 2

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

Water

True negative controls:

no

Positive controls:

yes

Positive control substance:

2-nitrofluorene

Remarks:

TA 98 (without activation)

Controls 3

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

Water

True negative controls:

no

Positive controls:

yes

Positive control substance:

9-aminoacridine

Remarks:

TA 1537 (without activation)

Controls 4

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

Water

True negative controls:

no

Positive controls:

yes

Positive control substance:

methylmethanesulfonate

Remarks:

TA 102 (without activation)

Controls 5

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

Water

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 2-anthracene amide

Remarks:

TA 98, TA 102, TA 1537 (with activation)

Controls 6

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

Water

True negative controls:

no

Positive controls:

yes

Positive control substance:

cyclophosphamide

Remarks:

TA 100, TA 1535 (with activation)

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation); preincubation

DURATION

- Preincubation period: 60 minutes

- Expression time (cells in growth medium): 48 hours

NUMBER OF REPLICATIONS: 3 plates for each test concentration

DETERMINATION OF CYTOTOXICITY

- Method: relative total growth; background lawn assessment

Evaluation criteria:

A result is positive if the number of revertants is significantly increased compared with the solvent control to at least 2-fold of the solvent control for TA 98, TA 100 and TA 102 and 3-fold of the solvent control for TA 1535 and TA 1537 in both experiments.

Positive results have to be reproducible and the histidine independence of the revertants has to be confirmed by streaking on histidine-free agar plates.

Statistics:

MANN and WHITNEY and Spearman’s rank.

Results and discussion

Test results

Species / strain:

S. typhimurium, other: S. typhimurium TA 1535, TA 1537, TA 98, TA 102 and TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

TA 1537 without activation only: 5000 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Additional information on results:

COMPARISON WITH HISTORICAL CONTROL DATA: Results were within range of historical control data

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

Table 2: Dose range-finding study (TA 100 – MA) Number of revertants per plate (2 plates)

	TA100
Conc. (µg/plate)	Plate 1	Plate 2	Cytotoxic (yes/no)
0*	135	150	No
0.316	123	122	No
1	123	108	No
3.16	109	124	No
10	115	125	No
31.6	148	114	No
100	108	115	No
316	105	121	No
1000	109	105	No
3160	106	150	No
5000	118	125	No

*Solvent control: Water

Table 3: Experiment 1 Plate incorporation Number of revertants per plate (mean of 3 plates)

	TA98			TA100			TA102
Conc. µg/plate	— MA	+ MA	Cytotoxic (yes/no)	— MA	+ MA	Cytotoxic (yes/no)	— MA	+ MA	Cytotoxic (yes/no)
0*	35.3	32.7	No	133	137.3	No	293.3	280.7	No
100	26.3	39	No	125.3	140.7	No	181.3	325.7	No
316	36.7	32.7	No	136.7	141	No	290.3	317	No
1000	37	43.7	No	139.3	144.3	No	298	319.7	No
3160	30.7	31.3	No	140.3	137.7	No	308.7	315.3	No
5000	37.3	48.7	No	164	143.7	No	317.7	333	No
Positive control	1170.3	1110	No	1139.3	1241.3	No	1094	1066.7	No

*Solvent control: Water

Table 3: Experiment 1 Plate incorporation Number of revertants per plate (mean of 3 plates)

	TA1535			TA1537
Conc. µg/plate	— MA	+ MA	Cytotoxic (yes/no)	— MA	+ MA	Cytotoxic (yes/no)
0*	13.3	17.7	No	7.3	8	No
100	13.7	18.3	No	6	6	No
316	16.7	17	No	6.7	5.3	No
1000	13.7	14.7	No	7	5	No
3160	13.7	14	No	7	7.3	No
5000	15	16	No	5	6.7	No
Positive control	736	921.3	No	885	893.7	No

*Solvent control: Water

Table 4: Experiment 2 Preincubation Number of revertants per plate (mean of 3 plates)

	TA98			TA100			TA102
Conc. µg/plate	— MA	+ MA	Cytotoxic (yes/no)	— MA	+ MA	Cytotoxic (yes/no)	— MA	+ MA	Cytotoxic (yes/no)
0*	30.3	24.3	No	124	135	No	285.7	280.3	No
100	29.7	35.7	No	114.7	132	No	310.3	300	No
316	31	38.3	No	119.3	123.3	No	312.3	309	No
1000	28	34.3	No	120.7	136	No	320.3	296.7	No
3160	31.3	35	No	124.7	136	No	301	289	No
5000	27.7	33.3	No	111.3	143	No	245.7	298	No
Positive control	831.1	1110.7	No	1218	1195.3	No	1150.3	1161.7	No

*Solvent control: Water

Table 4: Experiment 2 Preincubation Number of revertants per plate (mean of 3 plates)

	TA1535			TA1537
Conc. µg/plate	— MA	+ MA	Cytotoxic (yes/no)	— MA	+ MA	Cytotoxic (yes/no)
0*	16	14	No	8	6	No
100	15	11.3	No	4.3	5	No
316	13.3	14.3	No	5	7.3	No
1000	16.3	13	No	5	7	No
3160	17	14	No	6.7	5.7	No
5000	12	16.3	No	4	11.7	Yes
Positive control	884	888.3	No	645.3	627	No

*Solvent control: Water

Applicant's summary and conclusion

Conclusions:

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

In a valid and reliable study conducted in accordance with OECD 471 and under GLP, no mutagenic effect was observed for the test substance tested up to cytotoxic concentration in any of the test strains in a plate incorporation study with and without metabolic activation. The result was confirmed in a pre-incubation study. It is concluded that the test substance is negative for the induction of micronuclei under the conditions of the test.