Triethoxysilane

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Link to relevant study records

Reference

Reference 1

Endpoint:

in vitro gene mutation study in mammalian cells

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

from 08-04-1994

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

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

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Type of assay:

mammalian cell gene mutation assay

Target gene:

TK Locus

Species / strain / cell type:

mouse lymphoma L5178Y cells

Details on mammalian cell type (if applicable):

- Type and identity of media: Fischers's Medium for Leukemic Cells of Mice with 0.1 % Pluronics, supplemented with 10 % horse serum and 4 mM L-glutamine.
- Properly maintained: yes
- Periodically checked for Mycoplasma contamination: yes
- Periodically checked for karyotype stability: yes
- Periodically "cleansed" against high spontaneous background: yes

Metabolic activation:

with and without

Metabolic activation system:

cofactor supplemented post-mitochondrial fraction (S9 mix), prepared from the livers of rats treated with Aroclor 1254.

Test concentrations with justification for top dose:

313, 625, 1250, 2500 and 5000 µg/mL

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: Ethanol.

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

7,12-dimethylbenzanthracene

Remarks:

+ S9: 5.0 and 2.5 µL/mL in ethanol.

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

ethylmethanesulphonate

Remarks:

-S9: 0.5 and 0.25 µL/mL in ethanol.

Details on test system and experimental conditions:

METHOD OF APPLICATION: in medium.

DURATION
- Exposure duration: 4 hours.
- Expression time (cells in growth medium): 2 days
- Selection time (if incubation with a selection agent): 10-12 days.

SELECTION AGENT (mutation assays): 3 µg/mL trifluorothymidine (TFT)

NUMBER OF REPLICATIONS: 2


DETERMINATION OF CYTOTOXICITY
- Method: cloning efficiency and relative total growth.

OTHER: Small and large colonies were differentiated, as small colonies are capable to indicate chromosomal mutations.
Cofactors: 11.25 mg DL-Isocitric acid and 6.0 mg nicotinamide adenine dinucleptide phosphate (NADP), pH 7.0.
Metabolic activation: Adult male Sprague-Dawley rats were induced by a single intraperitoneal injection of Aroclor-1254 at a dosage of 500 mg/kg body weight five days prior to sacrifice.

Evaluation criteria:

In evaluation of the data, increases in mutant frequencies which occurred only at highly toxic concentrations (i.e., less than 10% total growth) were not considered biologically relevant. All conclusions were based on sound scientific judgement; however, as a guide to interpretation of the data, the test article was considered to induce a positive response if a concentration- related increase in mutant frequency was observed and more than one dose level was 10% or greater total growth exhibited a mutant frequency two-fold greater than the solvent control. A doubling above background at one or more dose levels with 10% or greater total growth with no evidence of a dose-response was considered to be equivocal. Test articles not producing a doubling above background at one or more dose levels with 10 % or greater growth was concluded to be negative.

Species / strain:

mouse lymphoma L5178Y cells

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

> 2500 µg/mL

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Additional information on results:

RANGE-FINDING/SCREENING STUDIES: The preliminary toxicity test conducted on triethoxysilane indicated 94% toxicity at 5000 µg/mL for the non-activated cultures and 65% toxicity at 5000 µg/mL for the S-9 activated cultures. The cultures treated with 140 µl of ethanol exhibited average suspension growths of 91% of control in the absence of S-9 and 87 % of control in the presence of S-9. The osmolality of the solvent control was 457 mOsm (530 mOsm/kg for 140 µl ethanol) and the osmolality of the top dose, 5000 µg/mL, was 463 mOsm/kg. Based on the results of the initial toxicity test, the doses chosen for the mutagenesis assay ranged from 5000 to 39 µg/mL for both the non-activated cultures and for the S-9 activated cultures.

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Table 1. Total compound toxicity data in the absence of exogenous metabolic activation (-S9):

Concentration [µg/ mL]	Cloning efficiency [%]	Relative Total Growth [%]	Mutants per 1E+06 cells	Mutation factor
-S9
5000 A	79	8	44	11
5000 B	81	18	52	19
2500 A	85	30	42	9
2500 B	88	16	41	8
1250 A	91	62	30	-3
1250 B	84	53	34	1
625 A	90	79	34	1
625 B	72	71	42	9
313 A	68	61	48	15
313 B	92	87	35	2
140 µl Ethanol	100	98	31	-2
140 µl Ethanol	91	83	41	8
Ethanol 1			29
Ethanol 2			23
Ethanol 3			49
Ethanol 4			32
Ethyl Methanesulfonate (µl/mL)
0.50	43	23	1206	1164
0.25	64	47	602	560
Solvent 1			41
Solvent 2			42

Table 2. Total compound toxicity data in the presence of exogenous metabolic activation (+S9):

Concentration [µg/ mL]	Cloning efficiency [%]	Relative Total Growth [%]	Mutants per 1E+06 cells	Mutation factor
+ S9
5000 A	77	17	85	35
5000 B	95	36	51	1
2500 A	85	43	67	17
2500 B	85	47	53	3
1250 A	106	101	48	-2
1250 B	95	84	42	-8
625 A	95	98	51	1
625 B	113	120	42	-8
313 A	102	114	46	-4
313 B	115	120	49	-1
140 µl Ethanol	104	103	45	-5
140 µl Ethanol	94	92	63	13
Ethanol 1			62
Ethanol 2			45
Ethanol 3			43
Ethanol 4			49
Ethyl Methanesulfonate (µl/mL)
0.50	35	35	417	360
0.25	71	71	179	132
Solvent 1			40
Solvent 2			54

Conclusions:

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

In a mammalian mutagenicity assay in mouse lymphoma L5178Y cells conducted according to OECD 476 and in compliance with GLP, triethoxysilane was found to be non-mutagenic in the absence or presence of metabolic activation.

Reference 2

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:

from 02-02-1995

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The study was conducted according to the appropriate EU test guideline, and in compliance with GLP and is therefore considered to be reliability 1. Read-across of the study itself is considered to be reliability 2. Further information on read-across is given in the endpoint summary.

Justification for type of information:

Please refer to the attached justification below and the overall justification for grouping of substances attached in IUCLID Section 13.

Qualifier:

according to guideline

Guideline:

EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)

Deviations:

no

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Target gene:

His operon (S. typhimurium strains)
Trp operon (E. coli strains)

Species / strain / cell type:

other: Salmonella typhimurium TA 98, TA 100, TA 1535, TA 1537; Escherichia coli WP2 and WP2 uvrA

Metabolic activation:

with and without

Metabolic activation system:

cofactor supplemented post-mitochondrial fraction (S9 mix), prepared from the livers of rats treated with Aroclor 1254.

Test concentrations with justification for top dose:

100, 333, 1000, 3333, and 5000 µg/plate

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: the solvent was chosen based on solubility of the test article and compatibility with the target cells.

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

2-nitrofluorene

Remarks:

TA 98 (without metabolic activation)

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

sodium azide

Remarks:

TA 100, TA 1535 (without metabolic activation)

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

9-aminoacridine

Remarks:

TA 1537 (without metabolic activation)

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

methylmethanesulfonate

Remarks:

WP2, WP2uvrA (without metabolic activation)

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 2-Aminoanthracene

Remarks:

All strains (with metabolic activation)

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: Sterigmatocystin

Remarks:

All strains (with metabolic 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 to 72 hours

NUMBER OF REPLICATIONS: 2 plates per test concentration

DETERMINATION OF CYTOTOXICITY
- Method: relative total growth; background lawn assessment

Evaluation criteria:

The test article is evaluated as positive when it causes a dose-related increase in mean revertants per plate of at least one tester strain with a minimum of two increasing concentrations of test article.

Statistics:

Positive controls and tester strains with revertant counts greater than 100 were counted with a colony counter (Mini Count) and those less than 100 were counted manually.

Species / strain:

other: Salmonella typhimurium TA 98, TA 100, TA 1535, TA 1537; Escherichia coli WP2 and WP2 uvrA

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Remarks:

> 5000 µg/plate

Vehicle controls validity:

not specified

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Additional information on results:

TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: none recorded
- Effects of osmolality: none recorded
- Evaporation from medium: not reported
- Precipitation: Slight precipitation at higher concentrations did not affect assay
- Other confounding effect: In first two tests, a variation in the precipitation pattern was observed, so the tests were repeated. The findings from the initial two experiments are not recorded.

RANGE-FINDING/SCREENING STUDIES:
No toxicity observed

COMPARISON WITH HISTORICAL CONTROL DATA:
The results of the controls lie within the range of the historical control data.

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

 

Table 1 Preliminary toxicity test

	TA 100			WP2 uvrA (pKM101)
Concentration (μg/Plate)	Plate 1 + MA	Plate 2 - MA	Cytotoxic (Yes/No)	Plate 1 + MA	Plate 2 - MA	Cytotoxic (Yes/No)
0	199	174	no	250	208	no
6.7	180	173	no	234	187	no
10	165	157	no	241	210	no
33	174	163	no	200	198	no
67	179	197	no	228	185	no
100	196	152	no	195	217	no
333	177	170	no	186	184	no
667	175	175	no SP	230	214	no SP
1000	169	156	no SP	138	168	no SP
3333	199	174	no SP	221	169	no SP
5000	174	158	no SP	247	180	no SP

SP Slight precipitate

 

Table 2: Experiment 1 Plate incorporation assayNumber 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)
0*	13	17	no	95	144	no	10	11	no
100	13	17	no	89	127	no	9	11	no
333	13	18	no	86	135	no	8	11	no
1000	14	16	no	85	116	no	9	11	no
3333	17	21	no	97	116	no	6	14	no
5000	13	21	no	95	111	no	7	13	no
Positive Control	1304	1050	-	581	997	-	497	124	-

*solvent control with DMSO

 

Table 2: Experiment 1 Plate incorporation assayNumber of revertants per plate (mean of 3 plates)

	TA1537			WP2 uvrA (pKM101)			WP2 (pKM101)
Conc. (µg/plate)	-MA	+ MA	Cytotoxic (yes/no)	-  MA	+ MA	Cytotoxic (yes/no)	- MA	+ MA	Cytotoxic (yes/no)
0*	4	6	no	226	263	no	65	64	no
100	4	10	no	236	295	no	54	64	no
333	3	5	no	239	258	no	87	60	no
1000	6	8	no	210	294	no	62	53	no
3333	5	8	no	213	273	no	67	64	no
5000	5	6	no	197	247	no	67	61	no
Positive Control	215	130	-	1554	1262	-	1476	499	-

 

 

*solvent control withDMSO

 

Table 3: Experiment 2 Pre incubation assayNumber 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)
0*	15	24	no	102	129	no	11	10	no
50	26	24	no	112	122	no	10	11	no
160	21	20	no	105	116	no	11	9	no
500	24	14	no	101	120	no	12	10	no
1600	23	17	no	110	128	no	9	12	no
5000	19	18	no	100	123	no	10	11	no
Positive Control	764	909	-	527	902	-	433	117	-

*solvent control with DMSO

 

Table 3: Experiment 2 Pre incubation assayNumber of revertants per plate (mean of 3 plates)

	TA1537			WP2 uvrA (pKM101)			WP2 (pKM101)
Conc. (µg/plate)	-MA	+ MA	Cytotoxic (yes/no)	-  MA	+ MA	Cytotoxic (yes/no)	- MA	+ MA	Cytotoxic (yes/no)
0*	5	7	no	204	334	no	23	21	no
100	5	5	no	274	278	no	25	21	no
333	5	5	no	173	316	no	26	25	no
1000	5	6	no	208	296	no	26	22	no
3333	5	4	no	206	285	no	31	28	no
5000	5	6	no	214	283	no	28	24	no
Positive Control	250	119	-	2225	1304	-	358	1222	-

 

*solvent control withDMSO

 

Conclusions:

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

In a bacterial reverse mutation assay according to OECD 471 and GLP, the structural analogue substance trimethoxysilane (CAS:2487-90-3) was concluded to be negative in the Salmonella typhimurium/E. coli preincubation mutagenicity assay with a confirmatory assay. The test substance is non-mutagenic in strains used for this study.

Genetic toxicity in vivo

Link to relevant study records

Reference

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

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

Adequacy of study:

key study

Study period:

1982-04-21 to 1982-05-14

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The study was conducted according to an appropriate OECD test guideline with minor deviations and in compliance with GLP for the structural analogue substance trimethoxysilane (CAS: 2487-90-3). Read-across to the registered substance is considered scientifically justified.

Justification for type of information:

Please refer to the attached justification below and the overall justification for grouping of substances attached in IUCLID Section 13.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

Deviations:

yes

Remarks:

1000 cells scored

Principles of method if other than guideline:

Micronucleus test in vivo: Matter and Schmid, 1971, Mut. Res. 12: 417-425.

GLP compliance:

yes

Type of assay:

micronucleus assay

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Spartan Research Laboratories, Inc. Harlet, MI
- Weight at study initiation: 100 to 175 grams
- Housing: Animals housed individually
- Diet (e.g. ad libitum): PURINA Rodent Laboratory Chow (ad libitum)
- Water (e.g. ad libitum): ad libitum

Route of administration:

inhalation

Vehicle:

- Vehicle(s)/solvent(s) used: air
- Concentration of test material in vehicle: 100 ppm

Details on exposure:

TYPE OF INHALATION EXPOSURE: nose only

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: specially constructed glass chamber
- System of generating particulates/aerosols: vapours were generated by bubbling clean, dry air through the liquid test material

Duration of treatment / exposure:

4 hour(s)

Frequency of treatment:

Single 4 hour exposure

Post exposure period:

30 hours

Remarks:

Doses / Concentrations:
100 ppm
Basis:
nominal conc.

No. of animals per sex per dose:

5 animals per dose level

Control animals:

yes, concurrent no treatment

Positive control(s):

triethylenemelamine

- Route of administration: split-dose intraperitoneal injection (0 and 24 hours)
- Doses / concentrations: 0.5 mg/kg/dose

Tissues and cell types examined:

Animals were exposed to the test article by acute inhalation. They were sacrificed, the bone marrow is extracted and smear preparations made and stained. Polychromatic erythrocytes are scored for micronuclei under the microscope. Both positive and negative (solvent) controls are used in each experiment.

Details of tissue and slide preparation:

At sacrifice the adhering soft tissue and epiphyses of both tibiae were removed. The marrow was aspirated from the bone and transferred to centrifuge tubes containing 5 ml fetal calf serum (one tube for each animal). Following centrifugation to pellet the tissue, the supernatant was drawn off and portions of the pellet was spread on slides and air-dried. The slides were then stained in May-Gruenwald Solution and Giemsa. A thousand polychromatic erythrocytes (PCEs) per animal were scored. The frequency of micronucleated was expressed as percent micronucleated cells based on the total PCEs present in the scored optic field.

Evaluation criteria:

In the normal animal, the normocytes/PCE's is approximately 2. If an agent inhibits the proliferation of erythroblasts the proportion of PCE's is generally reduced. If the agent promotes chromosome breakage or acts as a spindle poison, generally the proportion of red normocytes increases.

Statistics:

Mean normocyte and polychromatic erythrocytes calculated as well as ratio of normocytes to PCE's

Sex:

female

Genotoxicity:

negative

Toxicity:

yes

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

RESULTS OF RANGE-FINDING STUDY

- Dose range: 100 ppm

- Clinical signs of toxicity in test animals: To ensure that the Micronucleus Assay was perfomed on animals exposed to a lethal concentration of the test material (Group A), a second group of animals (Group B) was simultaneously exposed to the chemical via inhalation as a positive control for lethality. The data demonstrates that both groups (A&B) were exposed to a lethal concentration of the test material. All five animals in Group B experienced weight loss and died within the 14 day observation period. At autopsy all five animals showed extensive lung damage with hemorrhage and atelectasis. Animals exposed via inhalation to the test material all showed slight to moderate evidence of lung damage in the form of petechial hemorrhage and focal altelectasis. Some evidence of kidney congestion was noted in several animals. No abnormal pathology was evident in either the positive control (C) or negative control (D) groups.

- Evidence of cytotoxicity in tissue analyzed: The ratio of of normocytes to PCE's obtained with both the test material treatment (Group A = 10.64) and the negative control (Group D = 10.28) closely approximate the normal expected ratio and were fairly consistent. The mean normocyte count from the positive control group was elevated (Group C = 19.4) indicating that the animals responded to a known clastogen (chromosome breaking agent). This same trend verified by the increase in percentage of micronucleated PCEs in the positive control group.

- Harvest times: Group A (Treatment group): 30 hours after exposure. Group B (Toxicity Control): 14 days. Group C (Positive Control): 30 hours. Group D (Negative Control): 30 hours.

- High dose with and without activation: 100 ppm

RESULTS OF DEFINITIVE STUDY

- Induction of micronuclei (for Micronucleus assay): Within normal range for all groups

- Ratio of PCE/NCE (for Micronucleus assay): Within normal range for all groups

- Statistical evaluation: Comparison of the study groups by Student T-test using a SAS computer program confirms their is no difference between the mean PCE micronucleus count for study groups A and D (test article and negative control) (<.0001) while the positive control is definitely positive (p>0.5) compared to the former groups.

 The following table indicates that the amimals responded to the positivecontrol substance. Both Normocytes/PCE **  ratio and % of micronucleated PCEs weresignificantly increased in the positive control group when compared to test material-treated group.

Table 3 : Mean Results of in vivo micronucleus test with mouse bone marrow

		Test Group (A)	Positive Control (C)	Negative Control (D)
Number of cells evaluated		1000	1000	1000
Sampling time (h)		30h	30h	30h
Number of erythro-cytes	Normocytes / Field	10.64	19.4	10.28
	PCE / Field	4.36	4.56	4.36
	Micronuclei / 1000 PCE	6.8	39.2	5.6
Ratio of erythro­cytes	Normochromatic / polychromatic	2.52	4.38	2.39
	% Micronucleated PCE	0.68	3.92	0.56

 

Conclusions:

Interpretation of results (migrated information): negative
In a rat micronucleus assay according to OECD 474 and to GLP, the structural analogue substance trimethoxysilane (CAS: 2487-90-3) did not induce chromosome breakage or act as a spindle poison in the rodent micronucleus assay even when animals were exposed to lethal concentrations. There is no evidence from this study that the mechanism of kill at toxic levels of exposure involves genotoxicity. The test substance is non-mutagenic in Sprague-Dawley rats in this mammalian micronucleus assay.

Additional information

Only a reliable mammalian mutagenicity study is available for triethoxysilane (CAS: 998-30-1), however, reliable data are available for the structural analogue substance trimethoxysilane (CAS: 2487 -90 -3). An in vitro bacterial mutagenicity assay and an in vivo chromosome aberration assay in mammalian cells is available for the structural analogue substance trimethoxysilane. Triethoxysilane and trimethoxysilane hydrolyse in contact with water generating silanetriol and ethanol or methanol. Both substances generate the same silanol hydrolysis product, silanetriol, and it is therefore considered that read-across between the substances is appropriate. The other products of hydrolysis, methanol and ethanol, are not genotoxic.

Studies were chosen as key when the available study was of relevance and of sufficient quality for classification, labelling and for risk assessment.

A key reliable bacterial reverse mutation assay according to EU method B.13/14 and GLP is available for the structural analogue substance trimethoxysilane (CAS: 2487 -90-3) (Wagner, V.O. 1995).  No evidence for a test-substance related increase in the number of revertants was observed in Salmonella typhimurium TA 98, TA 100, TA 1535, TA 1537 and Escherichia coli WP2 and WP2 uvrA.  The strains were treated with doses of 100 to 5000 µg/plate with and without metabolic activation system. Appropriate positive and solvent controls were included and gave expected results. Under the conditions of this study, trimethoxysilane was concluded to be non-mutagenic in the Salmonella typhimurium/E. coli strains.

A key reliable mammalian cell gene mutation assay according to OECD TG 476 and GLP is available for triethoxysilane (DCC 1995g). Triethoxysilane was tested in the L5178Y/TK^+/- Mouse Lymphoma Mutagenesis Assay in the absence and presence of Aroclor induced rat liver S-9. The cultures selected for cloning were treated with doses of 5000 to 313 µg/ml in both the absence and presence of metabolic activation and exhibited total growths from 8% to 87% for the non-activated cultures and from 17% to 120% for the activated cultures. No cultures exhibited a mutant frequency which was at least twice the mean mutant frequency of the solvent controls.Appropriate positive and solvent controls were included and gave expected results.Triethoxysilane was negative for mutagenicity to L178Y cells in both the absence and presence of exogenous metabolic activation.

A key reliable in vivo micronucleus assay equivalent or similar to OECD TG 474 and to GLP is available for the structural analogue substance trimethoxysilane (CAS: 2487-90-3) (Isquith, A.J; Groh, C.L 1982). Under the applied test conditions, trimethoxysilane did not induce chromosome breakage or act as a spindle poison in the rodent micronucleus assay even when animals were exposed to lethal concentrations. There is no evidence from this study that the mechanism of kill at toxic levels of exposure involves genotoxicity.  The test substance is non-mutagenic in Sprague-Dawley rats in this mammalian micronucleus assay.

 

Short description of key information:
In vitro:

Only a reliable mammalian mutagenicity study is available for the registered substance triethoxysilane (CAS: 998-30-1), however, reliable data are available for the structural analogue substance trimethoxysilane (CAS: 2487-90-3) for in vitro bacterial mutagenicity and in vivo chromosome aberration in mammalian cells.

Gene mutation (Bacterial reverse mutation assay/ Ames test): read-across from structural analogue substance trimethoxysilane (CAS: 2487-90-3): negative with and without metabolic activation in S. typhimurium TA 100, TA 98, TA 1535, TA 1537, Escherichia coli WP2 and WP2 uvrA (according to EU Method B.13/14 (Mutagenicity–Reverse Mutation Testing Using Bacteria).

Mammalian gene mutation (mouse lymphoma L5178Y cell gene mutation assay): Negative with and without metabolic activation (according to OECD TG 476).

In vivo:

Chromosome aberration (rat micronucleus assay): read-across from structural analogue substance trimethoxysilane (CAS: 2487-90-3): negative (equivalent or similar to OECD TG 474, inhalation).

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on the available in vitro and in vivo data on mutagenicity of the registered substance and the structural analogue substances, trimethoxysilane (CAS: 2487-90-3) and trichlorosilane (CAS 10025 -78 -2), triethoxysilane is not classified for mutagenicity according to Regulation (EC) 1272/2008 or Directive 67/548/EEC.