Trimethoxyoctylsilane

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

In an in vitro bacterial reverse mutation assay / Ames test toxicity study, conducted according to OECD Test Guideline 471 and in compliance with GLP, trimethoxy(octyl)silane was negative in the presence and absence of metabolic activation (Dow Corning Corporation (2003).

In an in vitro cytogenicity in mammalian cells toxicity study, conducted according to OECD 473 and in compliance with GLP, triethoxy(octyl)silane was negative in Chinese hamster ovary cells (Bioservices, 1997).

In an in vitro mutagenicity in mammalian cells toxicity study, conducted according to OECD Test Guideline 476 and in compliance with GLP, triethoxy(octyl)silane was negative for mutagenicity in mouse lymphoma L5178Y cells (BSL Bioservice, 2012).

Link to relevant study records

Reference

Reference 1

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2003-03-19 to 2003-04-01

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Version / remarks:

1997

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Target gene:

Histidine operon

Species / strain / cell type:

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

Species / strain / cell type:

E. coli WP2 uvr A

Metabolic activation:

with and without

Metabolic activation system:

Phenobarbital and Beta-Naphthoflavone induced rat liver S9

Test concentrations with justification for top dose:

3 µg/plate - 5000 µg/plate

Vehicle / solvent:

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

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

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) 10 µg/plate

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 10 µg/plate in TA 98, 50 µg/plate in TA 1537

Remarks:

TA 1537, TA 98 (without activation)

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

methylmethanesulfonate

Remarks:

WP2 uvrA (without activation) 4 µl/plate

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 2-aminoanthracene 2.5 µg/plate (TA 1535, TA 1537, TA 98, TA 100), 10 µg/plate (WP2 uvrA)

Remarks:

All strains (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: Background lawn assessment, revertant colony counts

Evaluation criteria:

A result is considered 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 WP2 uvrA and 3-fold of the solvent control for TA 1535 and TA 1537 in both experiments.

A dose dependent increase is considered biologically relevant if the threshold is exceeded at more than one concentration. An increase exceeding the threshold at only one concentration is judged as biologically relevant if reproduced in an independent experiment.

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:

No statistical evaluation of the data is required

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:

valid

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with

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

Key result

Species / strain:

S. typhimurium TA 100

Metabolic activation:

without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

5000 μg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

5000 μg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

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

Key result

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

5000 μg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Key result

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:

valid

Positive controls validity:

valid

Additional information on results:

COMPARISON WITH HISTORICAL CONTROL DATA: With metabolic activation, the number of colonies did not quite reach the lower limit of historical control data in strain TA 1537, (negative and solvent control, exp 1), and in strain WP2 uvrA (negative control exp 1and 2, solvent control exp 1). Since these deviations are rather small, these effects are considered to be based upon biologically irrelevant fluctuations in the number of colonies.

Table 2:  Pre-toxicity test

	TA98			TA100			TA1535
Conc. (µg/plate)	— MA	+ MA	Cytotoxic (yes/no)	— MA	+ MA	Cytotoxic (yes/no)	— MA	+ MA	Cytotoxic (yes/no)
Negative control	23	29	No	108	107	No	10	12	No
0*	26	29	No	134	113	No	9	13	No
3	16	30	No	101	106	No	13	9	No
10	19	30	No	114	127	No	14	9	No
33	21	26	No	115	104	No	12	13	No
100	19	28	No	88	121	No	12	10	No
333	20	27	No	68	81	No	9	10	No
1000	16	26	No	76	84	No	9	10	No
2500	18	23	No	73	67	No	8	7	No
5000	17	20	No	52	58	Yes	5	6	Yes
Positive control	228	1495	No	1068	1629	No	697	211	No

*solvent control with acetone

Table 2:  Pre-toxicity test

	TA1537			E. coli WP2 uvrA
Conc. (µg/plate)	— MA	+ MA	Cytotoxic (yes/no)	— MA	+ MA	Cytotoxic (yes/no)
Negative control	7	6	No	31	32	No
0*	4	5	No	29	31	No
3	3	5	No	28	25	No
10	5	5	No	28	34	No
33	5	5	No	27	33	No
100	4	7	No	32	34	No
333	3	4	No	30	27	No
1000	2	3	No	30	35	No
2500	3	3	No	31	32	No
5000	1	2	Yes	18	35	No
Positive control	50	226	No	804	215	No

*solvent control with acetone

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

	TA98			TA100			TA1535
Conc. (µg/plate)	— MA	+ MA	Cytotoxic (yes/no)	— MA	+ MA	Cytotoxic (yes/no)	— MA	+ MA	Cytotoxic (yes/no)
Negative control	23	29	No	108	107	No	10	12	No
0*	26	29	No	134	113	No	9	13	No
33	21	26	No	115	104	No	12	13	No
100	19	28	No	88	121	No	12	10	No
333	20	27	No	68	81	No	9	10	No
1000	16	26	No	76	84	No	9	10	No
2500	18	23	No	73	67	No	8	7	No
5000	17	20	No	52	58	Yes	5	6	Yes
Positive control	228	1495	No	1068	1629	No	697	211	No

*solvent control with acetone

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

	TA1537			E. coli WP2 uvrA
Conc. (µg/plate)	— MA	+ MA	Cytotoxic (yes/no)	— MA	+ MA	Cytotoxic (yes/no)
Negative control	7	6	No	31	32	No
0*	4	5	No	29	31	No
33	5	5	No	27	33	No
100	4	7	No	32	34	No
333	3	4	No	30	27	No
1000	2	3	No	30	35	No
2500	3	3	No	31	32	No
5000	1	2	Yes	18	35	No
Positive control	50	226	No	804	215	No

*solvent control with acetone

Table 4: Experiment 2 Pre-incubation number of revertants per plate (mean of 3 plates)

	TA98			TA100			TA1535
Conc. (µg/plate)	— MA	+ MA	Cytotoxic (yes/no)	— MA	+ MA	Cytotoxic (yes/no)	— MA	+ MA	Cytotoxic (yes/no)
Negative control	30	38	No	148	184	No	20	18	No
0*	28	35	No	154	187	No	17	17	No
33	30	40	No	150	199	No	17	19	No
100	28	40	No	146	214	No	17	16	No
333	23	32	No	177	198	No	18	16	No
1000	24	37	No	195	216	No	17	17	No
2500	28	35	No	188	242	No	21	15	No
5000	31	44	No	207	215	No	16	17	No
Positive control	239	1465	No	1536	1207	No	1479	299	No

*solvent control with acetone

Table 4: Experiment 2 Pre-incubation number of revertants per plate (mean of 3 plates)

	TA1537			E. coli WP2 uvrA
Conc. (µg/plate)	— MA	+ MA	Cytotoxic (yes/no)	— MA	+ MA	Cytotoxic (yes/no)
Negative control**	9	11	No	38	33	No
0*	9	11	No	36	38	No
33	10	13	No	28	35	No
100	7	11	No	39	36	No
333	5	14	No	42	46	No
1000	6	10	No	31	46	No
2500	6	11	No	41	46	No
5000	5	12	No	40	41	No
Positive control	77	227	No	444	346	No

*solvent control with acetone

Conclusions:

The substance RMS 808 MC has been tested according to OECD 471 and under GLP. No increase in the number of revertants was observed for the test substance tested up to cytotoxic or limit concentrations in any of the test strains either with or without metabolic activation in either the initial plate incorporation assay or the independent pre-incubation experiment . It is concluded that the test substance is not mutagenic to bacteria under the conditions of the test.

Reference 2

Endpoint:

in vitro cytogenicity / chromosome aberration study in mammalian cells

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1994.11.07 - 1997.12.24

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)

Deviations:

no

GLP compliance:

yes

Type of assay:

in vitro mammalian chromosome aberration test

Species / strain / cell type:

Chinese hamster Ovary (CHO)

Details on mammalian cell type (if applicable):

- Type and identity of media:
- Properly maintained: yes/no
- Periodically checked for Mycoplasma contamination: yes
- Periodically checked for karyotype stability: yes/no
- Periodically "cleansed" against high spontaneous background: yes/no

Metabolic activation:

with and without

Metabolic activation system:

Aroclor 1254 induced rat liver S-9

Test concentrations with justification for top dose:

0.016 - 157 µg/ml

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: ethanol
- Justification for choice of solvent/vehicle: no information provided

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Remarks:

Ethanol

True negative controls:

no

Positive controls:

yes

Positive control substance:

benzo(a)pyrene

Remarks:

used with S9 metabolic activation 30 µg/ml

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Remarks:

Ethanol

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: N-methyl-N-nitro-N-nitrosoguanidine (MNNG) dosed at 2 µg/ml

Remarks:

used without S9 activation

Details on test system and experimental conditions:

METHOD OF APPLICATION: in medium

DURATION
- Exposure duration: 6 hours with and without S9 metabolic activation or up to 24 and 48 hours without S9
- Expression time (cells in growth medium): 18 hours
- Fixation time (start of exposure up to fixation or harvest of cells):

SPINDLE INHIBITOR (cytogenetic assays): Colcemid
STAIN (for cytogenetic assays): 5% Giemsa

NUMBER OF REPLICATIONS: 2

NUMBER OF CELLS EVALUATED: 200 per dose level

DETERMINATION OF CYTOTOXICITY
- Method: mitotic index; cell growth inhibition

Statistics:

Fisher's exact test and the Cochran-Armitage test

Key result

Species / strain:

Chinese hamster Ovary (CHO)

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

at 20 µg/ml (_MA); 50 µg/ml (+MA)

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

COMPARISON WITH HISTORICAL CONTROL

Chromosome aberration assay
Treatment µg/ml	S9 activation	Treatment /Harvest Time	Mitotic index*	Metaphase cells scored for aberrations	Cells with aberrations (200 cells evaluated)
					Numerical      Structural
Negative control	-	24	7.2	200	2.5	0.5
Solvent control	-	6/24	6.1	200	2.5	0.5
A-137
8.5	-	6/24	6.8	200	1.0	1.0
11.3	-	6/24	8.2	200	2.0	0.5
15	-	6/24	8.5	200	0.5	2.0
20	-	6/24	3.9	155	0.6	0.0
Positive control	-	6/24	5.2	200	1.5	27.0**
Negative control	+	24	10.9	200	3.0	0.5
Solvent control	+	6/24	8.2	200	5.0	0.5
A-137
21.3	+	6/24	9.5	200	5.0	0.5
28.3	+	6/24	9.4	200	5.0	0.0
37.6	+	6/24	6.6	200	8.0	1.5
50	+	6/24	3.2	200	3.5	1.0
Positive control	+	6/24	3.0	200	8.5	43.0**
Negative control	-	24	12.1	200	0.5	0.5
Solvent control	-	24/24	9.1	200	0.0	1.0
A-137
8.5	-	24/24	7.6	200	0.0	1.0
11.3	-	24/24	11.6	200	1.0	1.0
15	-	24/24	11.7	200	1.5	1.0
20	-	24/24	1.7	37	0.0	0.0
Positive control	-	24/24	5.9	200	1.5	20.5**
Negative control	-	48	5.0	200	0.0	0.5
Solvent control	-	48/48	4.0	200	0.0	1.5
A-137
8.5	-	48/48	4.1	200	0.0	2.0
11.3	-	48/48	3.1	200	0.0	0.0
15	-	48/48	2.0	200	1.0	0.0
20	-	48/48	2.0	200	0.5	2.0
Positive control	-	48/48	2.2	200	1.0	18.0**

* Number of cells evaluated for MI not indicated in report.

** Aberration frequency statistically significant

Conclusions:

Triethoxyoctylsilane has been tested in a reliable in vitro cytogenetic assay according to OECD TG 473 and under GLP. The test substance did not induce statistically and biologically significant increases in the chromosomal aberration frequency of CHO (chinese hamster ovary) cells. It is concluded that the test substance is negative for the induction of chromosome aberrations (not clastogenic) in vitro under the conditions of the test.

Reference 3

Endpoint:

in vitro gene mutation study in mammalian cells

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2011-12-21 to 2012-03-20

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.17 (Mutagenicity - In Vitro Mammalian Cell Gene Mutation Test)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.5300 - In vitro Mammalian Cell Gene Mutation Test

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: IWGT Recommendations

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

(Bayerisches Landesamt für Gesundheit und Lebensmittelsicherheit, Germany)

Type of assay:

mammalian cell gene mutation assay

Target gene:

Thymidine kinase

Species / strain / cell type:

mouse lymphoma L5178Y cells

Details on mammalian cell type (if applicable):

- Type and identity of media: RPMI
- Properly maintained: Yes
- Periodically checked for Mycoplasma contamination: yes
- Periodically "cleansed" against high spontaneous background: yes

Metabolic activation:

with and without

Metabolic activation system:

Liver S9 of Wistar Phenobarbital and ß-Naphthoflavone-induced rat liver S9 mix

Test concentrations with justification for top dose:

Pre-expt I: 0.2, 0.5, 2.5, 5.0, 7.5 and 10.0 mM (+/-MA); Pre-expt II: 0.01, 0.1, 1.0, 2.0, 5.0, 10.0 mM (-MA, 24 h exp); Expt I: 0.1, 0.2, 0.5, 1.0, 2.5, 5.0, 7.5 and 10.0 mM (+/-MA); Expt II: 0.15, 0.3, 0.7, 2.0, 4.0, 6.0, 8.0 and 10.0 mM (+MA); 0.001, 0.002, 0.005, 0.01, 0.02, 0.05, 0.10 and 0.20 mM (-MA)

Vehicle / solvent:

THF was used as solvent (0.35% THF v/v in the samples). To reach a final concentration of 0.35% THF v/v in the samples the test item stock solution was diluted in RPMI + 5% HS for short-term exposure or RPMI + 7.5% HS for long-term exposure. After adding the THF stock solution to cell culture medium precipitate formed.
The solvent was compatible with the survival of the cells and the activity of the S9 mix.

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Remarks:

THF

True negative controls:

no

Positive controls:

yes

Positive control substance:

benzo(a)pyrene

Remarks:

with metabolic activation 3.5 µg/mL

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

ethylmethanesulphonate

Remarks:

without metabolic activation 200 µg/mL and 300 µg/mL

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

methylmethanesulfonate

Remarks:

without metabolic activation 10 µg/mL

Details on test system and experimental conditions:

METHOD OF APPLICATION: dissolved in THF (0.35% THF v/v in the samples)
DURATION: 4 h (short-term exposure), 24 h (long-term exposure)
Expression time (cells in growth medium): 48 h
Selection time (if incubation with selection agent): about 14 days

SELECTION AGENT ( mutation assay) 5 µg/ml trifluorothymidine
NUMBER OF REPLICATIONS: two separate experiments (I+II) with single exposure; cells were seeded in 4 plates and evaluated
NUMBER OF CELLS SEEDED: 2000 cells per well
DETERMINATION OF CYTOTOXICITY: relative total growth (RTG)

ACTIVATION: S9 mix contained glucose-6-phosphate and NADP as co-factors, and sufficient S9 to give a final protein concentration in the cultures of 0.75 mg/ml

Evaluation criteria:

The test item is considered mutagenic if following criteria are met:
-The induced mutant frequency meets or exceeds the Global Evaluation factor (GEF) of 126 per 10^6 cells
- A dose-dependent increase in mutant frequency is detected.

Besides, combined with a positive effect in the mutant frequency, an increased occurrence of small colonies (≥40% of total colonies) is an indication for potential clastogenic effects and/or chromosomal aberrations.
According to the OECD guideline, the biological relevance is considered first for the interpretation of results. Statistical methods might be used as an aid in evaluation the test result.
A test item is considered to be negative if the induced mutant frequency is below the GEF and the trend test is negative.

Statistics:

The non-parametric Mann-Whitney test is applied to the mutation data to prove the dose groups for any significant difference in mutant frequency compared to the negative /solvent controls.

Key result

Species / strain:

mouse lymphoma L5178Y cells

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

RTG of 14.6% and 9.7% without metabolic activation.

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Pre-experiment for toxicity with and without metabolic activation

Concentration (mM)	Number of cells 4 h after treatment		Number of cells 24 h after treatment		Number of cells 48 h after treatment		Suspension growth		Relative suspension growth
	+S9	-S9	+S9	-S9	+S9	-S9	+S9	-S9	+S9	-S9
Negative control	271000	278000	946000	948000	1600000	1570000	15.1	14.9	89.8	103.6
	307000	356000	105000	115000	1510000	1540000	15.9	17.7	94.1	123.3
Solvent control	307000	256000	104000	807000	1560000	1570000	16.2	12.7	100.0	100.0
	339000	313000	112000	101000	1560000	1590000	17.5	16.1
0.2	284000	271000	77000	593000	1540000	1480000	11.9	8.8	70.4	61.1
0.5	307000	252000	876000	377000	1490000	1190000	13.1	4.5	77.5	31.2
2.5	289000	220000	728000	186000	1620000	637000	11.8	1.9	70.0	13.3
5.0	316000	225000	798000	137000	1550000	286000	12.4	0.9	73.4	6.0
7.5 (P)	303000	271000	650000	239000	1590000	850000	10.3	2.6	61.3	17.8
10.0 (P)	305000	244000	728000	183000	1580000	481000	11.5	1.4	68.3	10.0

Summary: Experiment 1 and 2 with metabolic activation

	Treatment (mM)	RTG (%)	MF (mutants/10^6cells)	IMF (mutants/10^6cells)	Precipitate
	Negative control	103.5	125.6	/	-
		98.1		/	-
	Solvent control	100.0	135.2	/	-
				/	-
	0.1	72.3	142.3	7.2	-
Exp 1	0.2	73.5	143.3	8.1	-
	0.5	84.9	97.1	-38.1	-
	1.0	63.7	182.8	47.6	-
	2.5	67.1	144.4	9.2	-
	5.0	87.2	117.6	-17.6	-
	7.5	78.1	154.8	19.6	-
	10.0	74.3	130.3	-4.8	+
	Positive control	38.4	918.4	783.2	-
	Treatment (mM)	RTG (%)	MF (mutants/10^6cells)	IMF (mutants/10^6cells)	Precipitate
	Negative control	98.9	116.5	/	-
		111.8		/	-
	Solvent control	100.0	116.7	/	-
				/	-
	0.15	111.4	105.1	-11.6	-
Exp 2	0.3	96.2	131.1	14.4	-
	0.7	75.7	128.5	11.8	-
	2.0	42.3	220.5	103.8	-
	4.0	72.7	138.8	22.2	-
	6.0	58.9	170.6	53.9	-
	8.0	74.1	134.6	17.9	+
	10.0	76.4	154.9	38.2	+
	Positive control	50.5	1141.0	1024.3	-

MF - mutant frequency

IMF = induced mutant frequency

RTG = relative total growth

Summary: Experiment 1 and 2 without metabolic activation

	Treatment (mM)	RTG (%)	MF (mutants/10^6cells)	IMF (mutants/10^6cells)	Precipitate
	Negative control	122.0	142.0	/	-
		129.6		/	-
	Solvent control	100.0	144.3	/	-
				/	-
	0.1	100.3	177.2	32.9	-
Exp 1	0.2	87.3	157.4	13.0	-
	0.5	98.4	186.0	41.6	-
	1.0	49.2	190.1	45.7	-
	2.5	37.8*	179.4	35.1	-
	5.0	37.2	179.3	35.0	-
	7.5	17.1	224.1	79.8	+
	10.0	14.6	264.7	120.4	+
	Positive control 1	75.1	817.6	673.2	-
	Positive control 2	85.2	564.1	419.7	-
	Treatment (mM)	RTG (%)	MF (mutants/10^6cells)	IMF (mutants/10^6cells)	Precipitate
	Negative control	145.4	110.6	/	-
		122.8		/	-
	Solvent control	100.0	109.3	/	-
				/	-
	0.001	114.6	108.6	-0.8	-
Exp 2	0.002	99.3	94.7	-14.6	-
	0.005	103.4	120.0	10.6	-
	0.01	62.1	121.8	12.5	-
	0.02	82.5	160.0	50.6	-
	0.05	98.6	108.4	-0.9	-
	0.10	16.8	173.0	63.6	-
	0.20	0.9	119.1	9.7	-
	Positive control 1	21.3	2373.6	2264.2	-
	Positive control 2	14.7	1826.6	1717.3	-

Conclusions:

Triethoxyoctylsilane has been tested for mutagenicity to mammalian cells in a reliable study conducted according to OECD TG 476 and in compliance with GLP. No biologically relevant increase in mutation rate was found in mouse lymphoma L5178Y cells with or without metabolic activation in either the initial or the repeat experiment, up to limit and cytotoxic concentrations. The global evaluation factor was not exceeded at any concentration. In addition, colony sizing showed no clastogenic effects in either experiment. Appropriate solvent and positive 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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Data are available for trimethoxy(octyl)silane (CAS 3069-40-7) from a reliable in vitro study for bacterial mutagenicity (Dow Corning Corporation 2003). An additional bacterial mutagenicity study is also available (Anawa Bioservice, 1996). The results of both experiments were in agreement. No further data are available for the registered substance, however, reliable data are available for the related substance triethoxy(octyl)silane, CAS 2943-75-1 from in vitro studies on cytogenicity and mutagenicity to mammalian cells. Both the structurally-analogous substance, triethoxy(octyl)silane, CAS 2943-75-1 and the registered substance, trimethoxy(octyl)silane, CAS 3069-40-7, hydrolyse to octylsilanetriol. Hydrolysis is likely to occur under the conditions of the studies and also in vivo. The other products of hydrolysis, methanol and ethanol, are not genotoxic OECD (2004a and OECD 2004b).

 

Triethoxy(octyl)silane was chosen as read-across substance as it has the same hydrolysis product as trimethoxy(octyl)silane, and neither substance has any functional groups that are associated with genetic toxicity. Additional information is given in a supporting report (PFA (2013aa)) attached in Section 13.

 

Trimethoxy(octyl)silane has been tested for mutagenicity to bacteria in a study conducted according to OECD Test Guideline 471 and in compliance with GLP (Dow Corning Corporation (2003). No increase in the number of revertants was observed for the test substance tested up to cytotoxic or limit concentrations in any of the test strains either with or without metabolic activation in either the initial plate incorporation assay or the independent pre-incubation experiment. Appropriate solvent and positive controls were included and gave expected results. It is concluded that the test substance is not mutagenic to bacteria under the conditions of the test.

 

Additional evidence for lack of mutagenicity to bacteria is available from a study conducted according to a protocol similar to OECD Test Guideline 471 (Anawa Bioservice, 1996). No evidence of mutagenicity was observed with or without metabolic activation when trimethoxyoctylsilane was tested in Salmonella typhimurium strains TA98, TA 100, TA 1535, TA1537 and TA 1538.

 

In a cytogenicity study conducted according to OECD Test Guideline 473 and in compliance with GLP, no evidence of the induction of chromosome aberration was observed when the analogous substance, triethoxy(octyl)silane, was tested with or without metabolic activation in CHO K1 cells (MA Bioservices 1997).

 

The structural analogue triethoxy(octyl)silane has been tested for mutagenicity to mammalian cells in a reliable study conducted according to OECD Test Guideline 476 and in compliance with GLP (BSL Bioservice, 2012). No biologically relevant increase in mutation rate was found in mouse lymphoma L5178Y cells with or without metabolic activation in either the initial or the repeat experiment, up to limit and cytotoxic concentrations. The global evaluation factor was not exceeded at any concentration. In addition, colony sizing showed no clastogenic effects in either experiment. It is concluded that the test substance is negative for mutagenicity under the conditions of the test.

 

There is no justification from in vitro results for testing in vivo.

See attachment to Section 13 for justification of read-across.

 

Justification for classification or non-classification

Based on the available in vitro genotoxicity data, trimethoxy(octyl)silane is not classified for mutagenicity according to Regulation (EC) No 1272/2008.