2-(3,4-epoxycyclohexyl)ethyltrimethoxysilane

Genetic toxicity: in vitro

Administrative data

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:

1978-06-05 to 1978-06-07

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study was conducted according to an appropriate national standard method, with acceptable restrictions. The restrictions were, insufficient concentration levels and no duplicates were used

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1978

Report date:

1978

Reference 2

Reference Type:

publication

Title:

Evaluation of the Developmental Toxicity of beta-(3,4-Epoxycyclohexyl)ethyltrimethoxysilane in Fischer 344 Rats and New Zealand White Rabbits

Author:

Tyl W et al

Year:

1988

Bibliographic source:

Fund. Appl.Tox. 10: 439-452

Materials and methods

Test guideline

Test guideline 1

Qualifier:

equivalent or similar to guideline

Guideline:

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

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: DMT-106

Deviations:

no

GLP compliance:

not specified

Type of assay:

mammalian cell gene mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

2-(3,4-epoxycyclohexyl)ethyltrimethoxysilane

EC Number:

222-217-1

EC Name:

2-(3,4-epoxycyclohexyl)ethyltrimethoxysilane

Cas Number:

3388-04-3

Molecular formula:

C11H22O4Si

IUPAC Name:

trimethoxy[2-(7-oxabicyclo[4.1.0]hept-3-yl)ethyl]silane

Method

Target gene:

TK

Species / strain

Species / strain / cell type:

mouse lymphoma L5178Y cells

Metabolic activation:

with and without

Metabolic activation system:

S9 rat liver with Aroclor

Test concentrations with justification for top dose:

0.02-2.00 µl/ml

Vehicle / solvent:

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

- Justification for choice of solvent/vehicle: Non toxic to mouse lymphoma cells.

Controls

Controls 1

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

ethylmethanesulphonate

Remarks:

without activation

Controls 2

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: Dimethylnitrosamine

Remarks:

with activation

Details on test system and experimental conditions:

METHOD OF APPLICATION: in medium and soft agar with BrdU

DURATION
- Preincubation period: 4 hours

- Expression time (cells in growth medium): 3 days

SELECTION AGENT (mutation assays): bromodeoxyuridine (BrdU)


NUMBER OF REPLICATIONS: 3


DETERMINATION OF CYTOTOXICITY
- Method: cloning efficiency; relative total growth


- Selection time (if incubation with a selection agent): 10days

Evaluation criteria:

The test substance is considered positive if a dose-response is observed over 3 of the 4 dose levels employed and the minimum increase at the high level of dose-response curve is at least 2.5 times greater than the solvent and/or negative control values.

The solvent and negative control data should be within the normal range of the spontanious background for the TK locus.

Results and discussion

Test results

Species / strain:

mouse lymphoma L5178Y cells

Metabolic activation:

with and without

Genotoxicity:

positive

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

Cytotoxic at 1.25 µl/ml without activation and 0.020 µl/ml with activation.

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

Table 2:  Results of Mammalian Mutagenicity Assay with tester strain L5178Y

Concentration µl/ml	Mutant Frequency *		Relative cloning efficiency (% of Control)		Cytotoxicity (yes/no)
	-       MA	+ MA	-       MA	+ MA
Solvent Control**	20	19	100	100	No
Negative Control	6.1	12.9	150.7	107.6	No
0.020	-	24.5	-	111	No
0.040	-	39.7	-	81.2	No
0.080	-	59.4	-	99.5	No
0.160	-	39.4	-	113.8	No
0.640	25.1	-	115.9	-	No
1.250	46.9	-	134.4	-	No
1.500	41.3	-	134.4	-	No
1.700	64.7	-	88.5	-	No
2.000	145.3	-	74.9	-	No
Positive Control	358	1850	88.1	2.7	No

*  Mutantfrequency per 10⁶ surviving cells.

** Solvent: DMSO

Applicant's summary and conclusion

Conclusions:

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

The test material produced a dose related increase in cytotoxicity / mutant frequency, both with and without metabolic activation. The test material was mutagenic in the mouse lymphoma forward mutation assay. The mutagenic response was greater under non activated conditions.