Hydroxytrimethylsilane

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:

1978-06-13 to 1978-08-01

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1978

Report date:

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 duplicates

Principles of method if other than guideline:

Modification of 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:

Hydroxytrimethylsilane

EC Number:

213-914-1

EC Name:

Hydroxytrimethylsilane

Cas Number:

1066-40-6

Molecular formula:

C3H10OSi

IUPAC Name:

hydroxytrimethylsilane

Method

Target gene:

thymidine kinase

Species / strain

Species / strain / cell type:

mouse lymphoma L5178Y cells

Details on mammalian cell type (if applicable):

- Type and identity of media: Fischer's medium for Leukemic cells of mice with 10% horse serum and sodium pyruvate

Metabolic activation:

with and without

Metabolic activation system:

Non induced mouse liver S9

Test concentrations with justification for top dose:

0.16, 0.32, 0.64, 1.25, 2.5 µl/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:

other: 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

Evaluation criteria:

METHOD OF APPLICATION: in medium

DURATION
- Preincubation period:
- Exposure duration: 4 hours
- Expression time (cells in growth medium): 3 days
- Selection time (if incubation with a selection agent): 10 days
- Fixation time (start of exposure up to fixation or harvest of cells):


SELECTION AGENT (mutation assays): BUdR

NUMBER OF REPLICATIONS: 3

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

Statistics:

Cloning efficiency, relative growth and mutant frequency were calculated from cell counts. There was no statistical treatment of results.

Results and discussion

Test results

Species / strain:

mouse lymphoma L5178Y cells

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

1.25 - 2.5 μl/ml

Vehicle controls validity:

valid

Positive controls validity:

valid

Additional information on results:

See table 1

Remarks on result:

other: No mutagenic potential

Any other information on results incl. tables

Table 1: Results of Mammalian Mutagenicity assay with tester strain L5178Y (mean of 3 plates)

Concentration µl/ml	Mutant* Frequency	Mutant* Frequency	Relative cloning eff. % of control	Relative cloning eff. % of control	Cytotoxicity (yes/no)
-	— MA	+ MA	— MA	+ MA	-
Solvent Control**	20.4	24	100	100	No
0.16	21.8	22.3	88.3	120	No
0.32	17.9	24.9	89.2	94	No
0.64	22.5	30	105.5	100.9	No
1.25	12.1	8.9	115.3	71.9	Yes
2.5	10.7	4.8	99	79.6	Yes
Positive Control	687.1	162.6	41.3	72.8	No

*Per 10⁶surviving cells

**solvent control with ethanol

Applicant's summary and conclusion

Conclusions:

Trimethylsilanol has been tested for mutagenicity in mouse lymphoma cells up to cytotoxic concentrations. No increase in mutant frequency was observed in either the absence or presence of exogenous metabolic activation. Appropriate controls were included and gave expected results. It is concluded that the test substance is not mutagenic in mouse lymphoma L5178Y cells under the conditions of the test.