Registration Dossier

Diss Factsheets

Toxicological information

Genetic toxicity: in vitro

Currently viewing:

Administrative data

Endpoint:
in vitro gene mutation study in bacteria
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Experiment start date - 16 October 1984; Experiment completion date - 12 November 1984; Study completion date - 29 November 1984.
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:
1984
Report date:
1984

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
no
GLP compliance:
no
Type of assay:
bacterial reverse mutation assay

Test material

Constituent 1
Chemical structure
Reference substance name:
Sodium 3-[[3-methoxy-4-[(4-methoxyphenyl)azo]phenyl]azo]benzenesulphonate
EC Number:
264-129-6
EC Name:
Sodium 3-[[3-methoxy-4-[(4-methoxyphenyl)azo]phenyl]azo]benzenesulphonate
Cas Number:
63405-85-6
Molecular formula:
C20H18N4O5S.Na
IUPAC Name:
sodium 3-({3-methoxy-4-[(4-methoxyphenyl)diazenyl]phenyl}diazenyl)benzenesulfonate
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
None
Specific details on test material used for the study:
Name: FAT 20004/G
Purity: 98.4 %
Batch no: DM 4694/13/1

Method

Target gene:
Histidine gene

Species / strain
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102
Details on mammalian cell type (if applicable):
The bacteria on which the tests were performed were the following histidine-auxotrophic strains of Salmonella typhimurium: TA 98, TA 100, TA 102, TA 1535 and TA 1537 (origin: Prof.B. Ames, Berkeley, U.S.A.).
Additional strain / cell type characteristics:
not specified
Metabolic activation:
with and without
Metabolic activation system:
S9 mix
Test concentrations with justification for top dose:
With and without metabolic activation: 20, 78, 313, 1250 and 5000 µg/0.1 ml.
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: DMSO
Controlsopen allclose all
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: daunorubicin- HCl
Remarks:
for TA 98 without -S9
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
True negative controls:
no
Positive controls:
yes
Positive control substance:
4-nitroquinoline-N-oxide
Remarks:
for TA 100 without -S9
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
True negative controls:
no
Positive controls:
yes
Positive control substance:
mitomycin C
Remarks:
for TA 102: without -S9
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
True negative controls:
no
Positive controls:
yes
Positive control substance:
sodium azide
Remarks:
for TA 1535 without -S9
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: aminoacridine hydrochloride monohydrate
Remarks:
TA 1537 without -S9
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: 2-aminoanthracene
Remarks:
strains TA 98, TA 100, TA 1537, TA 102 with activation mixture
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
cyclophosphamide
Remarks:
with strain TA 1535 with activation mixture

Results and discussion

Test results
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Additional information on results:
In the experiments performed without and with microsomal activation none of the tested concentrations of FAT 20004/G led to an increase in the incidence of histidine-prototrophic mutants in comparison with the controls. After exposure to FAT 20004/G at the highest concentration in the experiments without and with microsomal activation, the number of histidine-prototrophic mutants was reduced, as a result of the inhibitory effect of the substance on the growth of the bacteria.

Any other information on results incl. tables

SALMONELLA/MAMMALIAN-MICROSOME MUTAGENICITY TEST EXPERIMENTS WITHOUT MICROSOMAL ACTIVATION NUMBER OF BACK-MUTANT COLONIES PER PLATE (ARITHMETIC MEAN)

Strain

TA 98

TA 100

TA 102

TA 1535

TA 1537

Control

25

160

285

12

4

20 µg/0.1 ml

23

200

299

9

7

78 µg/0.1 ml

25

181

285

11

6

313 µg/0.1 ml

21

168

301

11

6

1250 µg/0.1 ml

18

164

288

6

7

5000 µg/0.1 ml

14

45

166

8

4

Positive control (Vehicle)

26

168

269

13

9

Positive control

(Concentration 1)

309

916

916

790

43

Positive control

(Concentration 2)

576

1464

2431

1236

835

 

 SALMONELLA/MAMMALIAN-MICROSOME MUTAGENICITY TEST EXPERIMENTS WITH MICROSOMAL ACTIVATION NUMBER OF BACK-MUTANT COLONIES PER PLATE (ARITHMETIC MEAN)

Strain

TA 98

TA 100

TA 102

TA 1535

TA 1537

Control

53

162

406

12

13

20 µg/0.1 ml

66

162

380

12

8

78 µg/0.1 ml

53

155

407

12

9

313 µg/0.1 ml

54

167

393

13

9

1250 µg/0.1 ml

47

154

416

9

8

5000 µg/0.1 ml

36

81

216

13

6

Positive control (Vehicle)

43

143

345

9

7

Positive control

(Concentration 1)

1657

2041

1188

602

249

  

SALMONELLA/MAMMALIAN-MICROSOME MUTAGENICITY TEST EXPERIMENTS WITHOUT MICROSOMAL ACTIVATION NUMBER OF BACK-MUTANT COLONIES PER PLATE (ARITHMETIC MEAN)

Strain

TA 98

TA 100

TA 102

TA 1535

TA 1537

Control

28

131

328

18

7

20 µg/0.1 ml

28

138

291

14

8

78 µg/0.1 ml

26

143

310

18

11

313 µg/0.1 ml

29

165

324

15

8

1250 µg/0.1 ml

27

131

298

14

8

5000 µg/0.1 ml

16

52

140

10

7

Positive control (Vehicle)

26

129

305

16

9

Positive control

(Concentration 1)

572

775

1008

582

66

Positive control

(Concentration 2)

856

1275

1368

813

982

 

 SALMONELLA/MAMMALIAN-MICROSOME MUTAGENICITY TEST EXPERIMENTS WITH MICROSOMAL ACTIVATION NUMBER OF BACK-MUTANT COLONIES PER PLATE (ARITHMETIC MEAN)

Strain

TA 98

TA 100

TA 102

TA 1535

TA 1537

Control

52

141

326

17

19

20 µg/0.1 ml

46

132

309

17

24

78 µg/0.1 ml

60

126

353

13

21

313 µg/0.1 ml

70

123

350

11

25

1250 µg/0.1 ml

55

136

486

12

17

5000 µg/0.1 ml

24

67

133

4

5

Positive control (Vehicle)

50

119

278

22

14

Positive control

(Concentration 1)

1853

1600

1296

614

106

 

Applicant's summary and conclusion

Conclusions:
No evidence of the induction of point mutations by FAT 20004/G or by the metabolites of the substance formed as a result of microsomal activation was detectable in the strains of S. typhimurium used in these experiments.
Executive summary:

FAT 20004/G was tested for mutagenic effects on histidine-auxotrophic mutants of Salmonella typhimurium. This study was conducted according to method equivalent or similar to OECD test guideline 471. The investigations were performed on strains TA 98, TA 100, TA 102, TA 1535 and TA 1537 with the following concentrations of the trial substance without and with microsomal activation: 20, 78, 313, 1250 and 5000 µg/0.1 ml. In order to confirm the results, the experiments were repeated. 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-prototrophism. To ensure that mutagenic effects of metabolites of the test substances 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, treatment of the cultures with the various concentrations of FAT 20004/G did not increase the incidence of back-mutant colonies by comparison with the negative control. Owing to a growth-inhibiting effect of the substance a reduction in the colony count was observed at the highest concentration. No evidence of the induction of point mutations by FAT 20004/G or by the metabolites of the substance formed as a result of microsomal activation was detectable in the strains of S. typhimurium used in these experiments.

Categories Display