Chlorodimethylsilane

Genetic toxicity: in vitro

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

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1978

Report date:

1978

Reference 2

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

Test material information

Constituent 1

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

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:

N-dimethylnitrosamine

Remarks:

(with activation)

Controls 3

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

methylmethanesulfonate

Remarks:

(without activation)

Controls 4

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 , .