Registration Dossier

Administrative data

Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1980-03-26 to 1980-05-09
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: scientifically acceptable study report

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1980
Report Date:
1980
Reference Type:
study report
Title:
Unnamed
Year:
1980
Report Date:
1980
Reference Type:
study report
Title:
Unnamed
Year:
1980
Report Date:
1980

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
yes
Principles of method if other than guideline:
according to Ames, B. N.; McCann, J.; Yamasaki, E.: Methods for detecting carcinogens and mutagens with the Salmonella/mammalian-microsome mutagenicity test. Mut. Res. 31, 347 - 364 (1975)
GLP compliance:
no
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent

Method

Species / strainopen allclose all
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Species / strain / cell type:
S. typhimurium TA 1538
Metabolic activation:
with and without
Metabolic activation system:
Aroclor 1254 rat liver S9 fraction
Test concentrations with justification for top dose:
4, 20, 100, 500 and 2500 µg/plate
Vehicle / solvent:
DMSO
Controlsopen allclose all
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
cyclophosphamide
Remarks:
with metaboblic activation, TA100 and TA1535
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: 2-Aminoanthracen
Remarks:
with metabolic activation, TA100, TA98, TA1538, TA1537 and TA1535
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: N-Methyl-N-nitro-N-nitroso-guanidin (MNNG)
Remarks:
without metabolic activation, TA100, TA98, and TA1535
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: 4-Nitro-o-phenylendiamin
Remarks:
without metabolic activation, TA1538
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: 9-Aminoacridiniumchlorid Monohydrat
Remarks:
without metabolic activation, TA1537
Details on test system and experimental conditions:
METHOD OF APPLICATION: in agar (plate incorporation)

DURATION
- Preincubation period: none
- Exposure duration: 48 h

NUMBER OF REPLICATIONS: 4
Evaluation criteria:
A substance is considered positivve if:
- doubling of spontanous colonie numbers
- a dose-effect-relationship can be established
- results are reproducible

Results and discussion

Test resultsopen allclose all
Species / strain:
other: TA 1535, TA 100, TA 98
Metabolic activation:
with and without
Genotoxicity:
positive
Cytotoxicity / choice of top concentrations:
other: A bacteriotoxic effect was not present in the tester strains (with the exception of TA 1535).
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Species / strain:
other: TA 1537, TA 1538
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

Dosis µg/plate

S9 Mix

TA98

TA100

Experiment 1

Experiment 2

Experiment 1

Experiment 2

DMSO

+

40

-

33

35

38

35

41

39

110

105

107

103

139

120

151

128

4

+

38

31

32

39

 

 

99

112

113

115

 

 

 

20

+

41

38

44

64

34

35

36

35

242

157

125

141

297

286

299

251

100

+

78

75

85

61

68

79

74

64

579

330

189

218

709

630

655

626

500

+

109

76

87

92

81

94

104

88

368

181

483

1900

1700

1650

1600

1950

2500

+

118

87

106

114

156

142

132

138

2550

2600

3000

2400

2750

2650

2900

2700

10 2-Aminoanthracen

+

1220

758

1020

1180

1850

1880

1460

1800

2100

2500

2780

1850

2750

3150

2650

3000

500 Cyclophosphamid

+

 

 

 

 

 

 

 

 

260

232

268

338

255

243

218

286

DMSO

-

33

26

25

36

21

28

28

27

123

126

135

122

124

118

137

114

4

-

25

22

28

24

 

 

 

 

136

119

149

113

 

 

 

 

20

-

24

41

37

21

27

26

57

31

153

169

134

125

231

183

208

219

100

-

47

39

30

27

25

28

19

25

475

334

264

162

445

742

533

500

2500

-

53

45

51

41

18

27

22

24

985

710

750

760

1400

1360

1400

1400

500

-

58

40

39

18

29

24

23

28

-

2100

1950

1700

2700

2530

2450

2400

5 MNNG

-

1760

1730

1580

1520

1230

1010

1370

1300

2900

2600

2850

2600

2800

3150

3000

3350

Dosis µg/plate

S9 Mix

TA1535

TA1537

TA1538

Experiment 1

Experiment 2

DMSO

+

13

12

14

12

16

16

18

14

6

7

6

6

22

22

24

21

4

+

34

24

16

26

 

 

 

5

4

11

5

24

23

25

28

20

+

105

110

33

117

265

164

291

279

5

5

9

8

21

19

24

25

100

+

227

377

152

407

895

742

901

707

4

9

7

-

21

20

24

30

500

+

1500

1000

380

600

2050

1700

1950

2000

6

6

8

9

18

23

30

25

2500

+

850

589

B

-

3100

2600

2000

3100

7

7

8

8

16

-

17

19

10 2-Aminoanthracen

+

340

277

251

298

367

360

327

318

103

122

116

163

920

1050

930

670

500 Cyclophosphamid

+

312

212

166

184

178

199

181

182

 

 

 

 

 

 

 

 

DMSO

-

14

12

16

15

18

13

17

18

5

5

7

6

13

14

11

12

4

-

17

29

19

15

 

 

 

 

7

6

6

5

14

15

14

10

20

-

87

141

82

74

206

143

185

166

9

6

9

4

16

14

12

14

100

-

356

284

254

269

750

613

544

620

8

8

5

5

14

12

10

11

500

-

422

-

317

556

1660

1500

1800

1680

5

5

6

8

10

12

15

13

2500

-

960

990

2700

366

2700

2700

2600

2800

7

5

5

9

12

11

9

11

5 MNNG

-

2600

3000

2900

2500

2950

2700

2500

2500

 

 

 

 

 

 

 

 

10 4-Nitro-o-phenylen-diamin

-

 

 

 

 

 

 

 

 

 

 

 

 

268

297

284

342

100 9-Aminoscridinium-chlorid-Monohydrat

-

 

 

 

 

 

 

 

 

332

437

308

421

 

 

 

 

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
positive

The test substance showed a mutagenic potential in the Ames test.
Executive summary:

The test substance was used in an Ames test in S. typhimurium strains TA98, TA100, TA1535, TA1537 and TA1538. Concentrations of 4 - 2500 µg/plate were applied with an without metabolic activation (S9 mix). Mutagenicity was observed in strains TA100 and TA1535 with and without metabolic activation and in TA98 with metabolic activation. The test substance was not mutagenic in TA1537 and TA1538 with and without metabolic activation. Bacteriotoxicity was only detected for TA1535 at 2500 µg/plate in Experiment 1. Thus the test substance showed a mutagenic potential in the Ames test.