Trichloro(2,4,4-trimethylpentyl)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

Study period:

2000-11-02 to 2001-02-06

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was conducted according to the appropriate OECD test guideline, and in compliance with GLP. It is considered that read-across to the registered substance is scientifically justified.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2001

Report date:

2001

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of assay:

in vitro mammalian chromosome aberration test

Test material

Test material information

Constituent 1

Reference substance name:

Triethoxy(2,4,4-trimethylpentyl)silane

EC Number:

252-558-1

EC Name:

Triethoxy(2,4,4-trimethylpentyl)silane

Cas Number:

35435-21-3

IUPAC Name:

triethoxy(2,4,4-trimethylpentyl)silane

Method

Species / strain

Species / strain / cell type:

Chinese hamster lung fibroblasts (V79)

Metabolic activation:

with and without

Metabolic activation system:

Beta-Napthoflavone and Phenobarbital induced rat liver S9

Test concentrations with justification for top dose:

500, 2000, 5000 µg/ml (expt 1 -S9), 50, 200, 5000 µg/ml (expt 1 +S9); 50, 200, 500 µg/ml (expt 2, -S9)

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: Cell culture medium. The test substance was prepared and diluted in cell culture mediu, Freshly prepared solutions (applied within 1 h after preparation) were used.

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:

cyclophosphamide

Remarks:

with activation

Details on test system and experimental conditions:

ACTIVATION: S9 mix contained0.75 mg/ml protein and NADP as cofactor. 50 µl were added to test organisms, test or control substance and medium in each chamber of Quadriperm dishes.

METHOD OF APPLICATION: in medium

DURATION

- Exposure duration: 4 hours with and without S9 (exp 1); 20 hours without S9 (exp 2)

- Expression time (cells in growth medium): 16 hours (exp 1); 20 hours (exp 2)

- Selection time (if incubation with a selection agent): 2 days

- Fixation time (start of exposure up to fixation or harvest of cells): 17.5 hours

SPINDLE INHIBITOR (cytogenetic assays): colcemide

STAIN (for cytogenetic assays): giesma

NUMBER OF REPLICATIONS: 2

NUMBER OF CELLS EVALUATED: At least 200 per concentration

DETERMINATION OF CYTOTOXICITY

- Method: mitotic index; relative total growth

OTHER EXAMINATIONS:

- Determination of polyploidy: determined in 100 cells per culture of each test group

Evaluation criteria:

A positive result is determined by a dose related increase in the number of cells with aberration, and a biologically relevant positive response for at least one of the test points.

The number of aberrations found in the negative control should be between 0 % and 4.5 %. The positive control should produce biologically relevant increases in the number of cells with structural chromosome 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:

500 μg/ml (exp 2, 20h treatment without activation)

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Additional information on results:

TEST-SPECIFIC CONFOUNDING FACTORS

- Precipitation: noted in experiment 2 at 5000 μg/ml, so 500 μg/ml selected as top concentration.

COMPARISON WITH HISTORICAL CONTROL DATA: Results were within range of historical control data

Remarks on result:

other: strain/cell type: Chinese hamster lung fibroblasts (V79)

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

Table 2: Results of chromosome analysis Experiment 1, 4h treatment without activation (total count from 2 cultures)

		Solvent* Control	Positive Control	Low dose 500 μg/ml	Medium dose 2000 μg/ml	High dose 5000 μg/ml
Cytotoxicity		No	No	No	No	No
		Mean
Chromatid aberrations	gaps	3	4	0	1	2
	deletions	0	1	1	0	1
	interchanges	0	21	0	1	2
Chromosome	gaps	-	-	-	-	-
	deletions	0	0	0	0	0
	interchanges	0	4	0	0	0
Mitotic index		100 %	103 %	140 %	116 %	86 %
Polyploidy		6	7	1.5	1	4
Endo reduplication		ND	ND	ND	ND	ND

 *Solvent control with culture medium

ND not determined

Table 3: Results of chromosome analysis Experiment 1, 4h treatment with activation (total count from 2 cultures)

		Solvent* Control	Positive Control	Low dose 250 μg/ml	Medium dose 2000 μg/ml	High dose 5000 μg/ml
Cytotoxicity		No	No	No	No	No
		Mean
Chromatid aberrations	gaps	2	4	4	2	0
	deletions	0	1	0	0	0
	interchanges	2	17	1	1	1
Chromosome	gaps	-	-	-	-	-
	deletions	0	0	0	0	0
	interchanges	0	0	0	0	0
Mitotic index		100 %	126 %	93 %	95 %	83 %
Polyploidy		3.5	5	3.5	3.5	2
Endo reduplication		ND	ND	ND	ND	ND

 *Solvent control with culture medium

ND not determined

Table 4: Results of chromosome analysis Experiment 2, 20h treatment without activation (total count from 2 cultures)

		Solvent* Control	Positive Control	Low dose 50 μg/ml	Medium dose 200 μg/ml	High dose 500 μg/ml
Cytotoxicity		No	Yes	No	No	Yes
		Mean
Chromatid aberrations	gaps	1	11	3	1	0
	deletions	0	2	1	0	0
	interchanges	0	35	0	0	0
Chromosome	gaps	-	-	-	-	-
	deletions	0	0	0	0	0
	interchanges	0	2	0	0	0
Mitotic index		100 %	51 %	91 %	85 %	29 %
Polyploidy		3.5	2.5	4.5	1.5	3
Endo reduplication		ND	ND	ND	ND	ND

 *Solvent control with culture medium

ND not determined

Applicant's summary and conclusion

Conclusions:

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

Triethoxy(2,4,4-trimethylpentyl)silane has been tested in a valid and reliable test performed according to OECD 473, under GLP. The test substance did not induce structural chromosomal aberrations in the V79 Chinese hamster cell line. It si concluded that the test substance is negative for the induction of chromosome aberrations under the conditions of the test.