3-(trimethoxysilyl)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:

1981-09-14 to 1981-09-19

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1981

Report date:

1981

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: BRRC Standard Operating Procedures 7.4.1. through 7.4.6 and 7.4.12

Version / remarks:

Ames test procedure

GLP compliance:

no

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

3-(trimethoxysilyl)propiononitrile

EC Number:

219-764-3

EC Name:

3-(trimethoxysilyl)propiononitrile

Cas Number:

2526-62-7

Molecular formula:

C6H13NO3Si

IUPAC Name:

3-(trimethoxysilyl)propanenitrile

Method

Target gene:

Histidine operon

Species / strain

Species / strain / cell type:

S. typhimurium, other: TA98, TA100, TA1535, TA1537, TA1538

Metabolic activation:

with and without

Metabolic activation system:

Aroclor induced rat liver S9

Test concentrations with justification for top dose:

0.1 µl/plate - 10 µl/plate

Vehicle / solvent:

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

- Justification for choice of solvent/vehicle: None given in study report.

Controls

Controls 1

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 4-Nitro-o-phenylenediamine 10 µg/plate

Remarks:

TA 98, TA 1538 (without activation)

Controls 2

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): 10 µg/plate

Controls 3

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): 60 µg/plate

Controls 4

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 2-Aminoanthracene 10 µg/plate

Remarks:

All strains (with activation)

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation)

DURATION

- Expression time (cells in growth medium): 24 - 48 hours

NUMBER OF REPLICATIONS: 3 plates for each test concentration

DETERMINATION OF CYTOTOXICITY

- Method: relative total growth; background lawn assessment

Evaluation criteria:

The spontaneous reversion for the solvent controls must be within the laboratory's historical range. Positive controls must demonstrate that the test systems are responsive with known mutagens. A test chemical is considered a bacterial mutagen if the number of revertant colonies is at least twice the solvent control for at least one dose level and there is evidence of a dose-related increase in the number of revertant colonies.

Statistics:

No statistical information is included in the report.

Results and discussion

Test results

Test results 1

Key result

Species / strain:

S. typhimurium TA 98

Metabolic activation:

without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

3 µl/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Test results 2

Key result

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

10 µl/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Test results 3

Key result

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

10 µl/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Test results 4

Key result

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Test results 5

Key result

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

10 µl/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Test results 6

Key result

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Test results 7

Key result

Species / strain:

S. typhimurium TA 1538

Metabolic activation:

without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

10 µl/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Test results 8

Key result

Species / strain:

S. typhimurium TA 1538

Metabolic activation:

with

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

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 Plate incorporation - Number of revertants per plate (mean of 3 plates)

	TA98			TA100			TA1535
Conc. µl/plate	— MA	+ MA	Cytotoxic (yes/no)	— MA	+ MA	Cytotoxic (yes/no)	— MA	+ MA	Cytotoxic (yes/no)
0*	15	23	No	84	78	No	5	8	No
0.1	17	15	No	80	83	No	4	8	No
0.3	12	17	No	70	75	No	8	6	No
1	14	12	No	66	68	No	4	8	No
3	5	22	Yes	42	64	No	5	7	No
10	0	0	Yes	0	80	Yes	5	9	No
Positive control	1147	1709	No	1453	1617	No	1315	159	No

*solvent control with ethanol

Table 2: Experiment 1 Plate incorporation - Number of revertants per plate (mean of 3 plates)

	TA1537			TA1538
Conc. µl/plate	— MA	+ MA	Cytotoxic (yes/no)	— MA	+ MA	Cytotoxic (yes/no)
0*	5	6	No	3	8	No
0.1	6	4	No	3	4	No
0.3	5	4	No	2	5	No
1	3	4	No	3	5	No
3	3	6	No	2	8	No
10	0	5	Yes	0	11	Yes
Positive control	230	207	No	1309	1071	No

*solvent control with ethanol

Applicant's summary and conclusion

Conclusions:

(3-Trimethoxysilyl)propiononitrile has been tested for mutagenicity to bacteria in a valid and reliable study conducted according to a method that is similar to OECD TG 471 and under GLP. No increase in the number of revertants was observed for the test substance tested up to cytotoxic concentration in any of the Salmonella typhimurium strains tested in the presence or absence of metabolic activation. The experiment was not repeated. It is concluded that the test substance is negative for mutagenicity to bacteria..