Registration Dossier

Toxicological information

Genetic toxicity: in vitro

Currently viewing:

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

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1978
Report date:
1978
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 guidelineopen allclose all
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
Qualifier:
according to guideline
Guideline:
other: DMT-106
Deviations:
no
GLP compliance:
not specified
Type of assay:
mammalian cell gene mutation assay

Test material

Constituent 1
Chemical structure
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.
Controlsopen allclose all
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
ethylmethanesulphonate
Remarks:
without activation
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.