[3-(2,3-epoxypropoxy)propyl]dimethoxymethylsilane

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro cytogenicity / chromosome aberration study in mammalian cells

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2004-04-26 to 2004-2004-05-24

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

The study was conducted according to the appropriate OECD test guideline, and in compliance with GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)

Deviations:

no

GLP compliance:

yes

Type of assay:

in vitro mammalian chromosome aberration test

Test material

Test material information

Constituent 1

Reference substance name:

[3-(2,3-epoxypropoxy)propyl]diethoxymethylsilane

EC Number:

220-780-8

EC Name:

[3-(2,3-epoxypropoxy)propyl]diethoxymethylsilane

Cas Number:

2897-60-1

Molecular formula:

C11H24O4Si

IUPAC Name:

Diethoxy-methyl-[3-(oxiran-2-ylmethoxy)propyl]silane

Constituent 2

Reference substance name:

[3-(2,3-epoxypropoxy)propyl]diethoxy(methyl)silane

IUPAC Name:

[3-(2,3-epoxypropoxy)propyl]diethoxy(methyl)silane

Method

Species / strain

Species / strain / cell type:

lymphocytes: Human blood

Metabolic activation:

with and without

Metabolic activation system:

phenobarbitone and naphthoflavone induced rat liver S9

Test concentrations with justification for top dose:

9.7, 19.41, 38.81, 77.63, 155.25*, 310.5*, 621*, 1242, 1863, 2484 µg/ml (* analysed concentrations)

Vehicle / solvent:

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

- Justification for choice of solvent/vehicle: Solubility properties and relative non-toxicity to bacteria

Controls

Controls 1

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

cyclophosphamide

Remarks:

(with activation)

Controls 2

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

mitomycin C

Remarks:

(without activation)

Details on test system and experimental conditions:

METHOD OF APPLICATION: in medium

ACTIVATION: 1ml of 20 % S9 mix ( ie 2 % final concentration of S9 in standard co-factors) was added to the cultures.

DURATION

- Exposure duration: 4 hours
- Expression time (cells in growth medium): 20 hours

SPINDLE INHIBITOR (cytogenetic assays): Colcemid

STAIN (for cytogenetic assays): Gurrs Giemsa


NUMBER OF REPLICATIONS: 2 cultures per dose level


NUMBER OF CELLS EVALUATED: 950 in total. (150 for positive control, 200 for treatments and vehicle control)


DETERMINATION OF CYTOTOXICITY
- Method: mitotic index, relative total growth


OTHER EXAMINATIONS:
- Determination of polyploidy: mean frequency % for experiment 1

Evaluation criteria:

A positive response was recorded if the % of cells with aberrations, excluding gaps, markedly exceeded that seen in the concurrent control, with or
without a clear dose-relationship. For modest increases in aberration frequency a dose response relationship is generally required and appropriate
statistical tests may be applied in order to record a positive response

Results and discussion

Test results

Test results 1

Species / strain:

lymphocytes: human blood

Metabolic activation:

without

Genotoxicity:

positive

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

50% mitotic inhibition at 310.5 μg/ml

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Test results 2

Species / strain:

lymphocytes: human blood

Metabolic activation:

with

Genotoxicity:

positive

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

73% mitotic inhibition at 2484 μg/ml

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Additional information on results:

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

Any other information on results incl. tables

Table 3: Results of chromosome analysis Experiment 1, 4h treatment without activation (total count from 2 cultures)

		Solvent* Control**	Positive Control***	621 μg/ml**	310.5 μg/ml**	155.25 μg/ml**
Cytotoxicity		No	Yes	No	Yes	Yes
		Mean
Chromatid aberrations	gaps	2	20	33	14	8
	breaks	1	25	36	10	5
	interchanges	1	33	28	1	0
Chromosome aberrations	gaps	NR	NR	NR	NR	NR
	breaks	0	2	4	3	1
	interchanges	0	1	0	0	0
Mitotic index (%)		100	49	16	50	80
Polyploidy (% mean freq.)		0.5	0	0	0.5	0
Endo reduplication		NR	NR	NR	NR	NR

 *Solvent control with DMSO

** Per 200 cells

*** Per 150 cells

NR not reported

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

		Solvent* Control**	Positive Control***	621 μg/ml**	1242 μg/ml**	1863 μg/ml**	2484 μg/ml***
Cytotoxicity		No	Yes	No	No	No	Yes
		Mean
Chromatid aberrations	gaps	0	39	8	8	26	27
	breaks	0	47	1	4	25	42
	interchanges	0	33	0	3	7	14
Chromosome aberrations	gaps	NR	NR	NR	NR	NR	NR
	breaks	1	3	1	3	5	5
	interchanges	0	0	0	0	0	1
Mitotic index (%)		100	19	117	70	57	27
Polyploidy (% mean freq.)		0	0	0	0	1.5	0
Endo reduplication		NR	NR	NR	NR	NR	NR

 *Solvent control with DMSO

** Per 200 cells

*** Per 100 cells

NR not reported

Applicant's summary and conclusion

Conclusions:

I[3-(2,3-epoxypropoxy)propyl]diethoxy(methyl)silane has been tested in a study carried out according OECD 473 and in compliance with GLP. The test material induced a statistically significant dose-related increase in the frequency of cells with chromosome aberrations in both the absence and presence of metabolic activation. Appropriate solvent and positive controls were included and gave expected results. The test material was therefore considered to be clastogenic to human lymphocytes in vitro under the conditions of the study.