Triethoxy(2,4,4-trimethylpentyl)silane

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:

1998-03-24 to 1998-04-06

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1998

Report date:

1998

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:

Triethoxy(2,4,4-trimethylpentyl)silane

EC Number:

252-558-1

EC Name:

Triethoxy(2,4,4-trimethylpentyl)silane

Cas Number:

35435-21-3

Molecular formula:

C14H32O3Si

IUPAC Name:

triethoxy(2,4,4-trimethylpentyl)silane

Method

Species / strain

Species / strain / cell type:

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

Metabolic activation:

with and without

Metabolic activation system:

Phenobarbital and Beta-Naphthoflavone induced rat liver S9

Test concentrations with justification for top dose:

33-5000 µg/plate

Vehicle / solvent:

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

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

Controls

Controls 1

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

sodium azide

Remarks:

TA 1535, TA 100 (without activation)

Controls 2

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 4-nitro-o-phenylene-diamine

Remarks:

TA 1537, TA 98 (without activation)

Controls 3

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

methylmethanesulfonate

Remarks:

TA 102 (without activation)

Controls 4

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 2-aminoanthracene

Remarks:

All strains (with activation)

Details on test system and experimental conditions:

ACTIVATION: Phenobarbital and beta-naphthoflavone induced rat liver S9 mix containing NADP as cofactor: Mix was 15% S9, 500 µl were mixed into a total volume of 2,700 µl prior to pouring giving a final concentration of approximately 1.2% S9.

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. The initial plate incorporation experiment was repeated using the preincubation method.

DETERMINATION OF CYTOTOXICITY
- Method: Background lawn evaluation, revertant colony counts

Evaluation criteria:

The test substance is considered positive if there is a reproducible dose related increase in revertants, or reproducible increase in one test concentration.

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.

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

Results and discussion

Test results

Key result

Species / strain:

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

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:

valid

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

	TA 98			TA 100
Concentration (μg/Plate)	Plate 1 + MA	Plate 2 - MA	Cytotoxic (Yes/No)	Plate 1 + MA	Plate 2 - MA	Cytotoxic (Yes/No)
Negative control*	41	21	No	148	137	No
0**	26	23	No	137	117	No
3	30	20	No	124	107	No
10	33	23	No	106	94	No
33	36	19	No	126	108	No
100	30	23	No	113	114	No
333	30	20	No	116	111	No
1000	36	28	No	153	117	No
2500	24	23	No	147	117	No
5000	34	16	No	156	118	No
Positive control	286	609	No	405	982	No

*negative control with water

**solvent control with DMSO

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)
Negative control*	21	41	No	137	148	No	192	249	No
0**	23	26	No	117	137	No	178	273	No
33	19	36	No	108	126	No	169	209	No
100	23	30	No	114	113	No	163	206	No
333	20	30	No	111	116	No	158	227	No
1000	28	36	No	117	153	No	169	234	No
2500	23	24	No	117	147	No	161	202	No
5000	16	34	No	118	156	No	196	280	No
Positive control	609	286	No	982	405	No	983	1153	No

*negative control with water

**solvent control with DMSO

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)
Negative control*	12	9	No	18	14	No
0**	15	10	No	14	14	No
33	20	14	No	15	17	No
100	19	11	No	12	12	No
333	23	11	No	13	13	No
1000	16	18	No	13	15	No
2500	17	14	No	12	13	No
5000	14	15	No	13	15	No
Positive control	1024	147	No	153	112	No

*negative control with water

**solvent control with DMSO

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)
Negative control*	29	52	No	159	156	No	279	245	No
0**	25	49	No	147	166	No	285	251	No
33	31	54	No	139	169	No	237	231	No
100	30	51	No	137	165	No	275	254	No
333	29	49	No	122	160	No	227	258	No
1000	30	49	No	139	166	No	222	252	No
2500	32	43	No	128	175	No	236	276	No
5000	28	51	No	134	157	No	231	243	No
Positive control	630	267	No	1236	688	No	1496	1049	No

*negative control with water

**solvent control with DMSO

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)
Negative control*	26	16	No	11	25	No
0**	29	13	No	11	22	No
33	22	18	No	10	24	No
100	21	16	No	9	30	No
333	22	16	No	7	23	No
1000	20	18	No	9	18	No
2500	21	11	No	9	16	No
5000	17	17	No	6	18	No
Positive control	847	121	No	128	126	No

*negative control with water

**solvent control with DMSO

Applicant's summary and conclusion

Conclusions:

Triethoxy(2,4,4-trimethylpentyl)silane has been tested for mutagenicity to bacteria in a valid and reliable study conducted according to OECD Test Guideline 471 and in compliance with GLP. No mutagenic effect was observed for the test substance tested up to limit concentration in any of the Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 in a plate incorporation experiment without and with metabolic activation. The result was confirmed in an independent pre-incubation assay. Appropriate positive, negative 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.