Chlorotrimethylsilane

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study was conducted according to a test protocol that is similar to the appropriate OECD test guideline. It was not compliant with GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1978

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 replicates

Principles of method if other than guideline:

Method: other: In accordance with 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:

Chlorotrimethylsilane

EC Number:

200-900-5

EC Name:

Chlorotrimethylsilane

Cas Number:

75-77-4

Molecular formula:

C3H9ClSi

IUPAC Name:

chloro(trimethyl)silane

Method

Species / strain

Species / strain / cell type:

other: L5178Y Fischer mouse lymphoma cell line

Metabolic activation:

with and without

Metabolic activation system:

mouse liver S9

Test concentrations with justification for top dose:

0.02, 0.04, 0.08, 0.16, and 0.32 µL/mL, equivalent to approximately 20, 40, 80, 160 and 320 µg/ml

Vehicle / solvent:

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

- Justification for choice of solvent/vehicle: none given in report

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)

Details on test system and experimental conditions:

Litton Bionetics standard procedure: Screening Program for the Identification of Potential Mutagens and Carcinogens. Protocol Number : DMT 100

The test substance was added the cells and growth medium for 4 hours and then divided into 2 aliquots. One aliquot was allowed to express for 3 days prior to determination of the number of revertants

Cells incubated in selection medium for 10 days before determining surviving cell populations by plating in nonselective growth medium.

The control and test substances were administered once.  Negative controls (tissue culture medium or EtOH, as appropriate) were included.

Metabolic Activation: Yes, both with and without Species and cell type:  Rat liver Quantity: 100 µl of a 9000 x g supernatant of mouse liver homogenate 
per  ml of reaction mixture Induced or not induced: Not induced

Evaluation criteria:

Responses (numbers of revertants; percent change in elution) to the test substance were compared to concurrent negative and positive controls.

Statistics:

Mutation index determined by deriving a mutation index (clones in selective medium/cells in non-selective medium, then comparing the mutation index derived for diffent doses of test substance and for positive and solvent controls.

Results and discussion

Test results

Test results 1

Species / strain:

mouse lymphoma L5178Y cells

Metabolic activation:

without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

0.32 µl/ml, equivalent to approx 320 µg/ml

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Test results 2

Species / strain:

mouse lymphoma L5178Y cells

Metabolic activation:

with

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

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

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

The following results were obtained:

Point Mutation:

Test 1: Summary of Mouse Lymphoma (L5178Y) Results

Test	Total Mutant Clones	Total Viable Clones	Percent Relative Growth^1	Mutant Frequency^2 x 10E-6
Non-activation
Solvent control	50.5	1355	100	37.3
Negative control	55.0	223.0	119.9	24.7
EMS	290.0	89.0	21.4	325.8
Test compound (μL/mL)
0.02	76.0	230.0	144.5	33.0
0.04	72.0	275.0	143.9	26.2
0.08	36.0	472.0	187.9	7.6
0.16	60.0	246.0	179.9	24.4
0.32	157.0	313.0	2.8	50.2
Activation
Solvent control	42.5	129.0	100.0	32.9
Negative control	72.0	235.0	157.2	30.6
DMN	102.0	78.0	5.9	130.8
Test compound (μL/mL)
0.02	66.0	257.0	157.9	25.7
0.04	75.0	201.0	142.0	37.3
0.08	27.0	173.0	115.5	15.6
0.16	76.0	174.0	141.7	43.7
0.32	94.0	305.0	144.8	30.8

¹(Relative suspension growth x relative cloning efficiency)/100

²(Mutant clones/Viable clones) x 10E-4

Test 2: Summary of Mouse Lymphoma (L5178Y) Results

Test	Total Mutant Clones	Total Viable Clones	Percent Relative Growth^1	Mutant Frequency^2 x 10E-6
Non-activation
Solvent control	31.0	202.0	100.0	15.0
Negative control	38.0	180.0	85.7	21.1
EMS	473.0	173.0	35.0	273.4
Test compound (μL/mL)
0.16	68.0	237.0	80.9	28.7
0.24	68.0	209.0	76.6	32.5
0.32	42.0	181.0	84.0	23.2
0.64	27.0	102.0	0.0	26.5
Activation
Solvent control	34.5	328.0	100.0	10.0
Negative control	54.0	322.0	101.7	16.8
DMN	524.0	99.0	5.0	529.3
Test compound (μL/mL)
0.16	52.0	193.0	43.5	26.9
0.32	19.0	135.0	26.2	14.1
0.48	44.0	164.0	50.7	26.8
0.64	58.0	169.0	35.2	34.3

¹(Relative suspension growth x relative cloning efficiency)/100

²(Mutant clones/Viable clones) x 10E-4

The test substance did not induce forward mutation in L5178Y mouse lymphoma cells either without activation or in the presence of the mouse liver S9 activation system (Test 1).  A second trial (Test 2) was conducted in order to test the compound at less than 50% survival in the presence of the S9 activation system.  This trial supported the observations in Trial 1.  Although the four levels were approximately 2.5 times the solvent control, no increase in the absolute number of mutants was observed; the solvent control value was at the lower end of the normal range, and these trends were not reproducible from trial to trial.

Applicant's summary and conclusion

Conclusions:

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

Chlorotrimethylsilane was tested in a reliable and reproducible test according to a protocol that is similar to OECD 476. Appropriate concurrent negative and positive controls were included and the expected responses were observed. The test substance, Chlorotrimethylsilane (CAS No. 75-77-4), did not induce significant forward mutation. The test substance is considered negative for mutagenicity in L5178Y mouse lymphoma cells under the conditions of the test.