Ethoxytrimethylsilane

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:

2002-05-07 to 2002-08-29

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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)

Remarks:

Freie und Hansestadt Hamburg, Behörde für Arbeit, Gesundheit uns Soziales, Germany

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Ethoxytrimethylsilane

EC Number:

217-370-6

EC Name:

Ethoxytrimethylsilane

Cas Number:

1825-62-3

Molecular formula:

C5H14OSi

IUPAC Name:

ethoxytrimethylsilane

Details on test material:

- Name of test material (as cited in study report): Silan M3-Ethoxy
- Stability under test conditions: at +4°c in the dark: > 1 day
- Storage condition of test material: cool, dark, dry

Method

Target gene:

His operon

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, 316, 1000, 3160 and 5000 µg/plate with and without metabolic activation

Vehicle / solvent:

- Vehicle/solvent used: ethanol

- Justification for choice of solvent/vehicle: Solubility properties and relative non-toxicity to bacteria

Controls

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

9-aminoacridine

2-nitrofluorene

sodium azide

cyclophosphamide

methylmethanesulfonate

other: 2-anthracene amide

Details on test system and experimental conditions:

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

DURATION

- Preincubation period: 60 minutes

- Exposure duration: 48 hours

NUMBER OF REPLICATIONS: 3 plates for each test concentration in two independent experiments

DETERMINATION OF CYTOTOXICITY
- Method: Background lawn assessment, revertant count

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.

Cytotoxicity is defined as a reduction in the number of colonies by >50% compared with the solvent control and/or a sparse background lawn.

Statistics:

MANN and WHITNEY and Spearman’s rank.

Results and discussion

Test results

Test results 1

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

at 3160 (only preincubation method) and 5000 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Test results 2

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

at 3160 (only preincubation method) and 5000 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Test results 3

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

at 3160 (only preincubation method) and 5000 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Test results 4

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

at 3160 (only preincubation method) and 5000 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Test results 5

Species / strain:

S. typhimurium TA 102

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

at 3160 (only preincubation method) and 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

Any other information on results incl. tables

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

	TA100
Conc. (µg/plate)	Plate 1	Plate 2	Cytotoxic (yes/no)
0*	137	147	No
0.316	133	130	No
1	126	114	No
3.16	118	132	No
10	130	122	No
31.6	153	121	No
100	181	126	No
316	170	175	No
1000	151	172	No
3160	124	118	No
5000	133	123	Yes

*solvent control with Ethanol

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*	41	38.7	No	131.7	128.7	No	292	294.3	No
100	40	31.7	No	172	113	No	266.7	268.3	No
316	45.7	37.7	No	150.7	136.3	No	279	262	No
1000	40.7	34.7	No	154.7	131.7	No	281	246.7	No
3160	45.7	36.7	No	162	148.3	No	278	287	No
5000	37	32.7	Yes	146.3	161.3	Yes	272.7	274.3	Yes
Positive control	1169.3	1177.3	No	1105.7	1134.3	No	1177.7	1095	No

*solvent control with ethanol

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*	15	13.3	No	7.3	7.3	No
100	14	14.7	No	4	7	No
316	16.7	14.7	No	3.7	4.7	No
1000	16.3	15	No	4.3	7	No
3160	13.7	16	No	4	6.3	No
5000	13.7	15.7	Yes	5	6	Yes
Positive control	575.3	584.3	No	579.3	581	No

*solvent control with ethanol

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*	38.3	36.3	No	136	165.7	No	295	282.7	No
100	36	38	No	137.7	167	No	291	291.7	No
316	31.7	40.3	No	138.3	164.3	No	303.3	280.7	No
1000	30	37.7	No	133.7	164	No	286	279.3	No
3160	28.7	41.3	Yes	159	155	Yes	287.7	294.3	Yes
5000	29.3	44.7	Yes	143.3	145	Yes	292.3	284.3	Yes
Positive control	1292	1255.7	No	1163.7	1191	No	1137.7	1218	No

*solvent control with ethanol

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*	15.3	15	No	4.7	5.3	No
100	14	14	No	3	3.7	No
316	14	13	No	4.3	5	No
1000	12	13	No	4	3	No
3160	15	13.3	Yes	3.7	3.7	Yes
5000	14.3	13	Yes	4	5	Yes
Positive control	565.3	566	No	566.3	563	No

*solvent control with ethanol

MA: Metabolic Activation

Applicant's summary and conclusion

Conclusions:

In a reliable test, conducted under OECD 471, with GLP, no mutagenic effect was observed for the test substance tested up to cytotoxic concentration in any of the test strains in two independent experiments without and with metabolic activation. The test substance is non-mutagenic in test strains used.