Registration Dossier

Diss Factsheets

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:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The result was obtained by the valid application of a well-established method. It was not conducted under GLP. Read-across to the registered substance is considered scientifically justified.

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1978
Report date:
1978
Reference Type:
secondary source
Title:
Genotoxicity studies on selected organosilicon compounds: In Vitro assays
Author:
Isquith A, Matheson D, Slesinski R
Year:
1988
Bibliographic source:
Fd Chem Toxic. Vol 26, No. 3, pp. 255 - 261

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
Deviations:
yes
Remarks:
no duplicates though test repeated. Concurrent positive controls did not stain
Principles of method if other than guideline:
The procedure used is a modification of that reported by Clive and Spector (Mutation Research, 31:17-29, 1975).
GLP compliance:
no
Type of assay:
mammalian cell gene mutation assay

Test material

Constituent 1
Chemical structure
Reference substance name:
Dichloro(dimethyl)silane
EC Number:
200-901-0
EC Name:
Dichloro(dimethyl)silane
Cas Number:
75-78-5
Molecular formula:
C2H6Cl2Si
IUPAC Name:
dichloro(dimethyl)silane

Method

Species / strain
Species / strain / cell type:
other: mouse lymphoma (L5178Y)
Metabolic activation:
with and without
Metabolic activation system:
Mouse Liver S9
Test concentrations with justification for top dose:
without activation was 0.02 - 0.32 ul/ml; with activation the dose range used was 0.04 - 0.64 ul/ml
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: Ethanol
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:
N-dimethylnitrosamine
Remarks:
(with activation)
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
methylmethanesulfonate
Remarks:
(without activation)
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
benzo(a)pyrene
Remarks:
(with activation)
Details on test system and experimental conditions:
METHOD OF APPLICATION: in medium; in agar

DURATION

- Exposure duration: 4 hours

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

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

NUMBER OF REPLICATIONS: 3 plates per concentration

DETERMINATION OF CYTOTOXICITY

- Method: loss in growth potential of cells (relative total growth)
Evaluation criteria:
The test substance was evaluated for it's ability to induce point mutations.

Toxicity is defined by a 50 % or greater reduction in growth compared with the solvent control.
Statistics:
Cells counted. Relative suspension growth (% of control), total mutant and viable clones, relative cloning efficiency, % relative growth and mutant frequency calculated.

Results and discussion

Test results
Species / strain:
mouse lymphoma L5178Y cells
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
other: 0.64 ul/ml with activation
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Additional information on results:
COMPARISON WITH HISTORICAL CONTROL DATA: Positive controls were within range of historical control data
Remarks on result:
other: strain/cell type: mouse lymphoma assay (L5178Y)
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

Table 2 : Results of Mammalian Mutagenicity assay  with L5178Y Mouse Lymphoma cells

Concentration µg/ml

Mutant* Frequency

Mutant* Frequency

%Relative

 Growth.

%Relative

 Growth.

Cytotoxicity
(yes/no)

 

— MA

+ MA

— MA

+ MA

-

Solvent Control

13.3

38.8

100

100

No

Negative Control

21.7

12.5

113.2

113.8

No

0.02

16.2

-

114.8

-

No

0.04

29.6

24.6

55

87.5

No

0.08

26.1

27.2

102.7

99.1

No

0.16

14.2

33.7

67

91

No

0.32

23.1

26.3

79.4

103.8

No

0.64

-

21.7

-

23.9

Yes

Positive Control

508.5

221.5

25.7

28.2

Yes

*Per 104 surviving cells

Solvent control with Ethanol

Applicant's summary and conclusion

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

Dimethyldicholrosilane did not induce point mutations at any dose level, with or without metabolic activation. The test substance is non-mutagenic in mouse lymphoma (L5178Y) cells under the conditions of the test , .

Categories Display