3-(trichlorosilyl)propiononitrile

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:

experimental study

Adequacy of study:

key study

Study period:

2003-10-16 to 2003-12-05

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. Read across to the registered substance is considered valid and scientifically justifiable.

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-(triethoxysilyl)propiononitrile

EC Number:

213-050-5

EC Name:

3-(triethoxysilyl)propiononitrile

Cas Number:

919-31-3

IUPAC Name:

3-(triethoxysilyl)propanenitrile

Method

Species / strain

Species / strain / cell type:

other: Chinese hamster ovary (CHO-K1) cells

Metabolic activation:

with and without

Metabolic activation system:

Aroclor induced rat liver S9

Test concentrations with justification for top dose:

See table 1

Vehicle / solvent:

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

- Justification for choice of solvent/vehicle: based on information provided by sponsor and compatibility with target cells

Controls

Controls 1

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

mitomycin C

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:

METHOD OF APPLICATION: in medium

DURATION

- Exposure duration: 4 hours (+/- MA); 20 hours (+ MA)

- Expression time (cells in growth medium): 4 hours (+/- MA); 16 hours (+ MA)

- Fixation time (start of exposure up to fixation or harvest of cells): 4 hours (+/- MA); 20 hours (+ MA)

SPINDLE INHIBITOR (cytogenetic assays): Colcemid

NUMBER OF REPLICATIONS: 2 plates for each test concentration

NUMBER OF CELLS EVALUATED: 100 per test concentration

DETERMINATION OF CYTOTOXICITY

- Method: relative total growth

Evaluation criteria:

Toxic effects based on cell growth inhibition and mitotic index relative to solvent control. Number and type of aberrations found recorded. The test substance was considered to induce a positive response when the % of cells with aberrations is increased in a dose-responsive manner with one or more concentrations being statistically significant (p≤0.05).

Statistics:

Cell counts and % viability used to determine cell growth inhibition relative to the solvent control. A minimum of 200 mataphase spreads (100 per duplicate flask) were examined and scored for chromatid-type and chromosome-type aberrations. Statistical analysis of % aberrant cells performed using the Fischer's exact test. In the event of a positive Fischer's exact test at any test substance dose level, the Cochran-Armitage test was used to measure dose-responsiveness.

Results and discussion

Test results

Species / strain:

Chinese hamster Ovary (CHO)

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

other: > 2172 ug/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

Remarks on result:

other: strain/cell type: Chinese hamster ovary (CHO-K1) cells

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

		Solvent* Control***	Positive Control**	543 µg/ml	1086 µg/ml	2172 µg/ml
Cytotoxicity		no	no	no	no	no
		Mean
Chromatidaberrations	gaps	0	0	0	0	0
	breaks	1	19	1	1	1
	exchanges	0	4	0	0	1
Chromosome aberrations	breaks	0	0	0	0	0
	Dic	1	1	1	0	4
	Ring	0	0	0	0	0
Mitotic index		NR	NR	NR	NR	NR
Polyploidy		NR	NR	NR	NR	NR
Endo reduplication		NR	NR	NR	NR	NR

 *Solvent control with DMSO

** Per 50 cells

*** Per 100 cells

NR not reported

 

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

		Solvent* Control***	Positive Control**	543 µg/ml	1086 µg/ml	2172 µg/ml
Cytotoxicity		no	no	no	no	no
		Mean
Chromatidaberrations	gaps	0	0	0	0	0
	breaks	0	4	0	1	1
	exchanges	0	20	0	0	1
Chromosome aberrations	breaks	0	2	0	0	0
	Dic	0	0	0	0	0
	Ring	0	0	0	0	0
Mitotic index		NR	NR	NR	NR	NR
Polyploidy		NR	NR	NR	NR	NR
Endo reduplication		NR	NR	NR	NR	NR

 *Solvent control with DMSO

** Per 50 cells

*** Per 100 cells

NR not reported

 

Table 4: Results of chromosome analysis Experiment 1, 20h treatment without activation (total count from 2 cultures)

		Solvent* Control***	Positive Control**	543 µg/ml	1086 µg/ml	2172 µg/ml
Cytotoxicity		no	no	no	no	no
		Mean
Chromatidaberrations	gaps	0	0	0	0	0
	breaks	0	4	0	0	3
	exchanges	0	10	0	0	1
Chromosome aberrations	breaks	0	3	0	0	1
	Dic	0	1	0	0	2
	Ring	0	0	1	0	2
Mitotic index		NR	NR	NR	NR	NR
Polyploidy		NR	NR	NR	NR	NR
Endo reduplication		NR	NR	NR	NR	NR

 *Solvent control with DMSO

** Per 50 cells

*** Per 100 cells

NR not reported

 

Applicant's summary and conclusion

Conclusions:

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

In a reliable and valid study, conducted in accordance with OECD 473, under GLP conditions, 3-(triethoxysilyl)propanenitrile was concluded to be negative for the induction of structural and numerical chromosome aberrations in CHO cells in both the activated and non- activated test systems.