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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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1982
Report date:
1982

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay

Test material

Constituent 1
Chemical structure
Reference substance name:
3-[[3-(dimethylamino)propyl]amino]propiononitrile
EC Number:
274-159-1
EC Name:
3-[[3-(dimethylamino)propyl]amino]propiononitrile
Cas Number:
69852-45-5
Molecular formula:
C8H17N3
IUPAC Name:
3-{[3-(dimethylamino)propyl]amino}propanenitrile
impurity 1
Chemical structure
Reference substance name:
3,3'-[[3-(dimethylamino)propyl]imino]bispropiononitrile
EC Number:
275-331-9
EC Name:
3,3'-[[3-(dimethylamino)propyl]imino]bispropiononitrile
Cas Number:
71326-27-7
Molecular formula:
C11H20N4
IUPAC Name:
3,3'-{[3-(dimethylamino)propyl]imino}dipropanenitrile
Test material form:
liquid
Remarks:
colorless
Specific details on test material used for the study:
Batch no. Zd 429-10A III

Method

Species / strain
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2
Metabolic activation:
with and without
Metabolic activation system:
Rat liver microsomes and co-factors
Test concentrations with justification for top dose:
5, 10, 50, 100, 500 ,1000 and 5000 µg/0.1 ml
Vehicle / solvent:
Twice distilled water
Controls
Negative solvent / vehicle controls:
yes
Positive controls:
yes
Positive control substance:
9-aminoacridine
2-nitrofluorene
N-ethyl-N-nitro-N-nitrosoguanidine
other: DMSO
Details on test system and experimental conditions:
METHOD OF APPLICATION: Minimum agar, plus salts and glucose.

The plates were incubated for about 48 hours at 37°C in darkness.
Evaluation criteria:
When the colonies had been counted, the arithmetic mean was calculated. The test substance is generally considered to be non-mutagenic if the colony count in relation to the negative control is not doubled at any concentration.

Results and discussion

Test results
Key result
Species / strain:
S. typhimurium TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
valid
Positive controls validity:
valid

Any other information on results incl. tables

Material

Concentration of testing sample

(µg / plate)

Presence of S9 Mix

Back Mutation                 Number of colunies/plate (mean)

Base Conversion Type

Frame Shift Type

TA100

TS1535

WP2UBrA

TA98

TA1537

TA1538

Vehicle Control

 

-

91

15

20

19

15

14

TK12271

 

5

-

87

18

20

28

14

18

10

-

89

20

26

29

14

14

50

-

95

23

15

27

9

12

100

-

100

15

19

25

14

20

500

-

86

15

21

20

13

14

1000

-

83

15

20

25

15

14

5000

-

88

15

19

25

12

14

Vehicle Control

 

+

78

11

16

46

8

33

TK12271

 

5

+

71

12

24

44

7

30

10

+

76

10

21

42

5

29

50

+

83

12

13

44

5

27

100

+

78

12

17

46

12

26

500

+

81

15

18

51

6

30

1000

+

81

12

13

44

6

28

5000

+

69

7

19

45

9

30

Applicant's summary and conclusion

Conclusions:
In the experiments performed without and with microsomal activation, comparison of the number of histidine- or tryptophan-prototrophic mutants in the controls and after treatment with TK 12271 revealed no marked differences.
Executive summary:

TK 12271 was tested for mutagenic effects on histidine-auxotrophic strains of Salmonella typhimirium and on a tryptophan-auxotrophic strain of E. coli. The investigations were performed with the following concentrations of the trial substance without and with microsomal activation: 5, 10, 50, 100, 500, 1000 and 5000 µg/0.1 ml.

These tests permit the detection of point mutations in bacteria induced by chemical substances. Any mutagenic effects of the substances are demonstrable on comparison of the number of bacteria in the treated and control cultures that have undergone back- mutation to histidine- or tryptophan- prototrophism. To ensure that mutagenic effects of metabolites of the test substance formed in mammals would also be detected, experiments were performed in which the cultures were additionally treated with an activation mixture (rat liver microsomes and co-factors).

In the experiments performed without and with microsomal activation, comparison of the number of back-mutant colonies in the controls and the cultures treated with the various concentrations of TK 12271 revealed no marked deviations.

No evidence of the induction of point mutations by TK 12271 or by the metabolites of the substance formed as a result of microsomal activation was detectable in the strains ofS. typhimuriumandE. coliused in these experiments.