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Toxicological information

Genetic toxicity: in vitro

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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:
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

Reference
Name:
Unnamed
Type:
Constituent

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.
Controlsopen allclose all
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)
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
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
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 resultsopen allclose all
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
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
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
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
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
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
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
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..