Registration Dossier

Administrative data

Endpoint:
in vitro gene mutation study in bacteria
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
04 Aug 2006
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2006
Report date:
2006

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Version / remarks:
Intermediate summary report with no details provided on the materials and methods.
Deviations:
not specified
Principles of method if other than guideline:
Intermediate summary report with no detail provided on the materials and methods. The main information indicate that the study seems to follow the OECD guidline.
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay

Test material

Constituent 1
Chemical structure
Reference substance name:
N,N'-[dithiobis[2-(2-hydroxyethyl)-1-methylvinylene]]bis[N-[(4-amino-2-methyl-5-pyrimidinyl)methyl]formamide
EC Number:
200-644-4
EC Name:
N,N'-[dithiobis[2-(2-hydroxyethyl)-1-methylvinylene]]bis[N-[(4-amino-2-methyl-5-pyrimidinyl)methyl]formamide
Cas Number:
67-16-3
Molecular formula:
C24H34N8O4S2
IUPAC Name:
N-[(4-amino-2-methylpyrimidin-5-yl)methyl]-N-[(2E)-3-{[(2E)-2-{N-[(4-amino-2-methylpyrimidin-5-yl)methyl]formamido}-5-hydroxypent-2-en-3-yl]disulfanyl}-5-hydroxypent-2-en-2-yl]formamide
Test material form:
solid: particulate/powder
Specific details on test material used for the study:
No detail provided.

Method

Target gene:
not specified
Species / strainopen allclose all
Species / strain / cell type:
S. typhimurium, other: TA 7001 to 7006
Additional strain / cell type characteristics:
not specified
Species / strain / cell type:
S. typhimurium TA 98
Additional strain / cell type characteristics:
not specified
Metabolic activation:
with and without
Metabolic activation system:
Not specified
Test concentrations with justification for top dose:
156 to 5000 µg/ml
Vehicle / solvent:
DMSO
Controls
Untreated negative controls:
not specified
Negative solvent / vehicle controls:
not specified
True negative controls:
not specified
Positive controls:
not specified
Positive control substance:
not specified

Results and discussion

Any other information on results incl. tables

Identification of Gédéon database : Amendment N°73

Preliminary toxicity assay(on theMixedstrains only, with and without metabolic activation):

Compound

Tested Concentrations

Unit

10036 AMINOET

0 (DMSO)

79

157

313

625

1250

2500

5000 (c)

(µg/ml)

5007 TDS HYDRATE SEC

0 (DMSO)

79

157

313

625

1250

2500

5000 (c)

(µg/ml)

3341 UREE

0 (DMSO)

79

157

313

625

1250

2500

5000 (c)

(µg/ml)

PYRIMIDYL-2',1 PIPERAZINE

0 (DMSO)

79

157

313

625

1250

2500

5000 (c)

(µg/ml)

9490 S BENZYLOXY PTS

0 (DMSO)

79

157

313

625

1250

2500

5000 (c)

(µg/ml)

3341 UREE

0 (DMSO)

79

157

313

625

1250

2500

5000 (c)

(µg/ml)

RESULTS:  

 

 

 

 

 

 

 

 

 

Genotoxicity assay (onMixedandTA98):

All the criteria for a valid test were met.

Compound

Tested Concentrations and Induction Factors (Significance)

Conclusion

 

+ S9

156

313

625

1250

2500

5000 (c)

2-AA

Negative

10036 AMINOET

Mixed

0.5

0.5

1.0

2.0

1.3

1.3

35.0

Assay 1

 

 

 

 

 

 

(**)

 

TA98

2.0

1.7

1.7

1.7

2.3

2.3

48.0

 

 

 

 

 

 

 

(**)

Batch:

- S9

156

313

625

1250

2500

5000 (c)

4NQO+2NF

Negative

534301/002

Mixed

1.3

0.5

1.3

0.5

0.3

0.5

36.0

 

 

 

 

 

 

 

(**)

Serie: 10036

TA98

0.7

1.0

1.7

1.0

1.0

0.0

48.0

 

 

 

 

 

 

 

(**)

Vehicle: DMSO

Discussion :No presence of colonies nor changes in the colour of the wells was observed.

Compound

Tested Concentrations and Induction Factors (Significance)

Conclusion

 

+ S9

156

313

625

1250

2500

5000 (c)

2-AA

Negative

5007 TDS HYDRATE SEC

Mixed

1.3

1.7

0.7

1.0

2.0

0.7

46.3

Assay 1

 

 

 

 

 

 

(**)

 

TA98

1.0

1.0

1.5

0.8

2.0

1.5

36.0

 

 

 

 

 

 

 

(**)

Batch:

- S9

156

313

625

1250

2500

5000 (c)

4NQO+2NF

Negative

544681/014

Mixed

0.3

1.0

0.3

2.0

1.3

0.0

48.0

 

 

 

 

 

 

 

(**)

Serie: 5007

TA98

1.3

1.0

1.0

0.7

0.7

0.7

48.0

 

 

 

 

 

 

 

(**)

Vehicle: DMSO

Discussion :No presence of colonies nor changes in the colour of the wells was observed.

Compound

Tested Concentrations and Induction Factors (Significance)

Conclusion

 

+ S9

20

39

78

156

313

625 (e)

2-AA

Negative

3341 UREE

Mixed

0.9

0.9

0.7

0.7

1.0

1.1

18.7

Assay 1

 

 

 

 

 

 

(**)

 

TA98

0.7

0.5

0.5

1.7

0.3

1.3

24.0

 

 

 

 

 

 

 

(**)

Batch:

- S9

2.6

7.8

23

70

209

625 (e)

4NQO+2NF

Negative

544641/001

Mixed

0.3

1.0

0.7

0.3

0.7

0.7

47.7

 

 

 

 

 

 

 

(**)

Serie: 3341

TA98

2.3

2.3

2.7

0.0

0.3

0.3

48.0

 

 

 

 

 

 

 

(**)

Vehicle: DMSO

Discussion :No presence of colonies nor changes in the colour of the wells was observed.

 


 

Compound

Tested Concentrations and Induction Factors (Significance)

Conclusion

 

 

+ S9

156

313

625

1250

2500

5000 (c)

2-AA

Negative

 

PYRIMIDYL-2',1 PIPERAZINE

Mixed

0.8

0.5

0.8

1.3

0.8

2.5

34.8

 

Assay 1

 

 

 

 

 

 

(**)

 

 

TA98

1.2

0.8

1.4

0.6

0.2

1.2

28.8

 

 

 

 

 

 

 

 

(**)

 

Batch:

- S9

156

313

625

1250

2500

5000 (c)

4NQO+2NF

Negative

 

M02413/001

Mixed

0.7

1.3

1.7

1.3

0.7

0.7

47.7

 

 

 

 

 

 

 

 

(**)

 

Serie: 495

TA98

0.3

0.7

1.0

1.3

1.3

2.7

48.0

 

 

 

 

 

 

 

 

(**)

 

Vehicle: DMSO

Discussion :No presence of colonies nor changes in the colour of the wells was observed.

 

Compound

Tested Concentrations and Induction Factors (Significance)

Conclusion

 

 

+ S9

156

313

625

1250

2500

5000 (c)

2-AA

Negative

 

9490 S BENZYLOXY PTS

Mixed

0.3

0.7

1.0

2.0

1.3

1.3

43.3

 

Assay 1

 

 

 

 

 

 

(**)

 

 

TA98

1.0

1.3

1.3

1.7

3.0

1.0

48.0

 

 

 

 

 

 

 

 

(**)

 

Batch:

- S9

15

44

133

398

1193

3594 (d)

4NQO+2NF

Negative

 

543401/005

Mixed

0.3

0.7

0.7

0.7

0.7

0.0

48.0

 

 

 

 

 

 

 

 

(**)

 

Serie: 9490

TA98

1.3

1.3

1.5

0.8

0.3

0.0

36.0

 

 

 

 

 

 

 

 

(**)

 

Vehicle: DMSO

Discussion :No presence of colonies nor changes in the colour of the wells was observed.

 

Compound

Tested Concentrations and Induction Factors (Significance)

Conclusion

 

 

+ S9

7.4

22

67

201

603

1800 (e)

2-AA

Negative

 

3341 UREE

Mixed

0.5

1.0

1.0

0.8

1.8

1.8

33.8

 

Assay 1

 

 

 

 

 

 

(**)

 

 

TA98

0.8

1.8

1.0

1.5

1.0

1.8

36.0

 

 

 

 

 

 

 

 

(**)

 

Batch:

- S9

7.4

22

67

201

603

1800 (e)

4NQO+2NF

Negative

 

544641/002

Mixed

1.8

0.8

1.0

0.5

1.0

1.3

35.8

 

 

 

 

 

 

 

 

(**)

 

Serie: 3341

TA98

0.8

0.8

1.5

0.8

1.5

1.5

36.0

 

 

 

 

 

 

 

 

(**)

 

Vehicle: DMSO

Discussion :No presence of colonies nor changes in the colour of the wells was observed.

 

 

(a): highest concentration limited by the solubility in the solvent

 

(b): highest concentration limited by the available amount of the compound

 

(c): highest maximum recommended concentration

 

(d): highest concentration limited by toxicity

 

(e): highest concentration limited by precipitate

 

(**): statistical significance (p<0.01)

 

4NQO: 4-Nitroquinoline N-oxyde (500 ng/ml)

 

2NF: 2 Nitrofluorene (2000 ng/ml)

 

2-AA: 2-anthramine (5 µg/ml)

 

DMSO : Dimethyl Sulfoxide

Applicant's summary and conclusion

Conclusions:
No presence of colonies nor changes in the colour of the wells was observed.
Executive summary:

No presence of colonies nor changes in the colour of the wells was observed in an intermediate study report.