Trimethoxy(2-methylpropyl)silane

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro cytogenicity / chromosome aberration study in mammalian cells

Remarks:

Type of genotoxicity: chromosome aberration

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 study was conducted according to an appropriate OECD test guideline, with acceptable restrictions. The restrictions were that there was no information on cytotoxicity, and only .

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)

Version / remarks:

1983

Deviations:

yes

Remarks:

no information on cytotoxicity

GLP compliance:

yes

Type of assay:

in vitro mammalian chromosome aberration test

Test material

Test material information

Constituent 1

Reference substance name:

Triethoxyisobutylsilane

EC Number:

402-810-3

EC Name:

Triethoxyisobutylsilane

IUPAC Name:

Triethoxyisobutylsilane

Constituent 2

Reference substance name:

017980-47-1

Cas Number:

017980-47-1

IUPAC Name:

017980-47-1

Method

Species / strain

Species / strain / cell type:

Chinese hamster lung fibroblasts (V79)

Metabolic activation:

with and without

Metabolic activation system:

Aroclor induced rat liver S9

Test concentrations with justification for top dose:

25-150 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

Migrated to IUCLID6: 500 µg/ml

Controls 2

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

cyclophosphamide

Remarks:

with activation

Migrated to IUCLID6: 5 µg/ml

Details on test system and experimental conditions:

ACTIVATION Aroclor induced rat liver S9 containing NADP as cofactor, final concentration ca 1.5% S9-mix/culture

METHOD OF APPLICATION: in medium


DURATION

- Exposure duration: 3 or 21 hours

- Expression time (cells in growth medium): 15 hours after exposure (3 h treatment)

- Fixation time (start of exposure up to fixation or harvest of cells):21 hours


SPINDLE INHIBITOR (cytogenetic assays): 0.25 ml colcemid solution (10 µg/ml) added 2.5 h before end of incubation time

STAIN (for cytogenetic assays): Giesma


NUMBER OF REPLICATIONS: duplicate cultures


NUMBER OF CELLS EVALUATED: 5000 cells/culture (mitotic index); 100/culture (chromosome analysis)


DETERMINATION OF CYTOTOXICITY

- Method: mitotic index


OTHER EXAMINATIONS:

- Determination of polyploidy: yes

- Determination of endoreplication: yes

Evaluation criteria:

Substance considered positive when parallel cultures at one dose level repeatedly produce aberrations in more than 10% analyzed cells (gaps excluded). Dose dependency may provide further evidence for clastogenicity.

Statistics:

Only done if there was a significant increase in the number of aberrations

Results and discussion

Test results

Species / strain:

Chinese hamster lung fibroblasts (V79)

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

at 200 µg/ml in preliminary test

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 1 Results of preliminary cytotoxicity assay

Concentration µg/ml	Mitotic Index
Solvent control	+MA	-MA
Positive control	115.8	151.6
50.0	88.6	116.4
100.0	109.2	128.8
200.0	48.6	91.2
400.0	0	0
600.0	0	0
800.0	0	0
1000.0	0	0
1250.0	0	0
2500.0	0	0
1500.0	0	0

Table 2 Results of chromosomal aberration test with cultured mammalian cells (V79)

Treatment group µg/ml	Activation	Exposure time hrs	% Cells with aberrations + gaps	% Cells with aberrations - gaps
Solvent control	-	21	4.0	0.5
Positive control	-	21	28.0	14.5
25	-	21	8.5	1.0
50	-	21	6.0	2.0
100	-	21	5.0	0.0
150	-	21	8.5	1.5
Solvent control	+	3	12.5	3.0
25	+	3	8.5	0.5
50	+	3	10.5	2.0
100	+	3	10.0	2.0
150	+	3	8.0	2.0
Solvent control	+	3	14.5	2.5
25	+	3	11.0	3.5
50	+	3	1.5	0.5
100	+	3	9.5	3.5
150	+	3	9.5	3.0
Solvent control	+	3	11.5	2.5
Positive control	+	3	32.5	16.5
25	+	3	12.5	3.5
50	+	3	7.5	2.5
100	+	3	10.0	3.0
150	+	3	8.5	1.5

The incorporation of an additional experiment using recovery times longer than 1.5 cell cycles (maybe 40-48 hours) would have been a beneficial add-on to this study since some chemicals have the ability to cause mitotic arrest, which may lead to a genotoxic result.

Applicant's summary and conclusion

Conclusions:

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

Triethoxyisobutylsilane has been tested in a valid study according to OECD 473 and under GLP, up to concentrations that could be expected to be cytotoxic.. No increase in the number of cells with aberrations was observed either with or without activation. Solvent and positive controls gave expected results. It is concluded that the test substance is negative for the induction of chromosome aberrations under the conditions of this study.