3-(triethoxysilyl)propiononitrile

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2003-10-21 to 2003-12-02

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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 471 (Bacterial Reverse Mutation Assay)

Version / remarks:

1998

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

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

Molecular formula:

C9H19NO3Si

IUPAC Name:

3-(triethoxysilyl)propanenitrile

Method

Species / strain

Species / strain 1

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Species / strain 2

Species / strain / cell type:

E. coli WP2 uvr A

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: Sponsors request and compatability 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:

other: 2-aminoanthracene

Remarks:

All strains (with activation)

Controls 2

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

2-nitrofluorene

Remarks:

TA 98 (without activation)

Controls 3

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

sodium azide

Remarks:

TA 100, TA 1535 (without activation)

Controls 4

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

9-aminoacridine

Remarks:

TA 1537 (without activation)

Controls 5

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

methylmethanesulfonate

Remarks:

WP2uvrA (without activation)

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation); preincubation

DURATION

- Preincubation period: 60 minutes

- Expression time (cells in growth medium): 48 to 72 hours

NUMBER OF REPLICATIONS: 3 plates for each test concentration

DETERMINATION OF CYTOTOXICITY
- Method: relative total growth; background lawn

Evaluation criteria:

For the test article to be evaluated positive, it must cause a dose-related increase in the mean revertants per plate of at least one tester strain over a minimum of two increasing concentrations. For TA1535 and TA1537 there must be a 3 fold increase. For TA98, TA100 and WP2uvrA, there must be a 2 fold increase.

Statistics:

Mean and Standard deviation of the number of revertants per plate were calculated and reported.

Results and discussion

Test results

Test results 1

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

TA 1535 (-MA) 3333 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Test results 2

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Test results 3

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not valid

Positive controls validity:

valid

Test results 4

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Test results 5

Species / strain:

E. coli WP2 uvr A

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

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 2 : Experiment 1 Preliminary toxicity assay Number of revertants per plate

Strain	TA98			TA100			TA1535
Conc. (µg/plate)	— MA	+ MA	Cytotoxic (yes/no)	— MA	+ MA	Cytotoxic (yes/no)	— MA	+ MA	Cytotoxic (yes/no)
0*	12	18	No	136	186	No	15	12	No
6.7	13	18	No	117	138	No	13	11	No
10	14	16	No	134	126	No	10	9	No
33	13	13	No	121	105	No	12	12	No
67	11	13	No	107	128	No	8	10	No
100	12	15	No	124	112	No	11	13	No
333	15	17	No	114	101	No	13	14	No
667	11	11	No	115	109	No	13	9	No
1000	10	15	No	122	121	No	14	10	No
3333	10	17	No	119	168	No	9	10	No
5000	16	19	No	134	117	No	6	11	Yes

*solvent control with DMSO

 

Table 3 : Experiment 1 Preliminary toxicity assay Number of revertants per plate

Strain	TA1537			WP2uvrA
Conc. (µg/plate)	— MA	+ MA	Cytotoxic (yes/no)	— MA	+ MA	Cytotoxic (yes/no)
0*	7	6	No	10	12	No
6.7	6	5	No	13	11	No
10	10	3	No	14	10	No
33	6	8	No	11	14	No
67	5	6	No	12	10	No
100	7	8	No	10	11	No
333	8	3	No	14	12	No
667	4	4	No	13	13	No
1000	6	7	No	10	8	No
3333	6	5	No	10	13	No
5000	4	5	No	12	15	No

*solvent control with DMSO

 

Table 4: Experiment 2 Plate incorporation assay, Number of revertants per plate (mean of 3 plates)

Strain	TA98			TA100			TA1535
Conc. (µg/plate)	— MA	+ MA	Cytotoxic (yes/no)	— MA	+ MA	Cytotoxic (yes/no)	— MA	+ MA	Cytotoxic (yes/no)
0*	17	22	No	184	196	No	8	11	No
100	13	21	No	147	226	No	10	10	No
333	18	18	No	193	206	No	10	12	No
1000	19	23	No	158	196	No	9	10	No
3333	24	21	No	172	179	No	7	8	No
5000	16	25	No	186	208	No	9	6	No
Positive control	157	873	No	645	1002	No	194	264	No

*solvent control with DMSO

 

Table 5: Experiment 2 Plate incorporation assay, Number of revertants per plate (mean of 3 plates)

Strain	TA1537			WP2uvrA
Conc. (µg/plate)	— MA	+ MA	Cytotoxic (yes/no)	— MA	+ MA	Cytotoxic (yes/no)
0*	8	6	No	11	11	No
100	9	8	No	12	11	No
333	9	4	No	12	11	No
1000	8	5	No	13	12	No
3333	6	6	No	13	12	No
5000	8	6	No	12	12	No
Positive control	400	72	No	230	82	No

*solvent control with DMSO

 

Table 6: Experiment 3 Preincubation assay, Number of revertants per plate (mean of 3 plates)

Starin	TA98			TA100			TA1535
Conc. (µg/plate)	— MA	+ MA	Cytotoxic (yes/no)	— MA	+ MA	Cytotoxic (yes/no)	— MA	+ MA	Cytotoxic (yes/no)
0*	14	18	No	152	180	No	21	12	No
100	13	21	No	157	242	No	15	11	No
333	14	15	No	165	180	No	21	10	No
1000	15	18	No	170	208	No	11	11	No
3333	10	14	No	166	190	No	11**	12	Yes
5000	9	12	No	168	208	No	8**	11	Yes
Positive control	394	904	No	486	1105	No	270	70	No

*solvent control with DMSO

**Moderate reduction in background lawn

 

Table 7: Experiment 3 Preincubation assay, Number of revertants per plate (mean of 3 plates)

Starin	TA1537			WP2uvrA
Conc. (µg/plate)	— MA	+ MA	Cytotoxic (yes/no)	— MA	+ MA	Cytotoxic (yes/no)
0*	4	4	No	11	12	No
100	5	5	No	11	10	No
333	5	4	No	14	9	No
1000	4	5	No	12	13	No
3333	3	6	No	11	8	No
5000	2	4	Yes	12	8	No
Positive control	220	126	No	205	614	No

*solvent control with DMSO

 

Applicant's summary and conclusion

Conclusions:

In a reliable and valid study, conducted in accordance with OECD Test Guideline 471 and in compliance with GLP, 3-(triethoxysilyl)propiononitrile did not induce mutagenic activity in Salmonella and E.coli strains. The test substance was concluded to be negative for mutagenicity to bacteria under the conditions of the test.