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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:
data from handbook or collection of data
Justification for type of information:
Data is from peer reviewed publication

Data source

Reference
Reference Type:
publication
Title:
SALMONELLA MUTAGENICITY TESTS: III. RESULTS FROM THE TESTING OF 255 CHEMICALS
Author:
ZEIGER E, ANDERSON B, HAWORTH S, LAWLOR T, MORTELMANS K AND SPECK W
Year:
1987
Bibliographic source:
ENVIRON. MOL. MUTAGEN. 9(SUPPL.9):1-110, 1987

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Principles of method if other than guideline:
Gene mutation toxicity study was performed to determine the mutagenic nature of Pigment Violet 1 using Salmonella typhimurium strains
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay

Test material

Constituent 1
Chemical structure
Reference substance name:
Xanthylium, 9-(2-carboxyphenyl)-3,6-bis(diethylamino)-, molybdatetungstatephosphate
EC Number:
215-413-3
EC Name:
Xanthylium, 9-(2-carboxyphenyl)-3,6-bis(diethylamino)-, molybdatetungstatephosphate
Cas Number:
1326-03-0
Molecular formula:
C112H127MoN8O23PW
IUPAC Name:
Xanthylium, 9-(2-carboxyphenyl)-3,6-bis(diethylamino)-, molybdatetungstatephosphate
Test material form:
solid: particulate/powder
Details on test material:
- Name of test material: C.I. Pigment Violet 1
- IUPAC name: Xanthylium, 9-(2-carboxyphenyl)-3,6-bis(diethylamino)-, molybdatetungstatephosphate
- Molecular formula: C112H127MoN8O23PW
- Molecular weight (if other than submission substance): 2264.729736 g/mol
- Smiles : CCN(CC)C1=CC2=C(C=C1)C(=C3C=CC(=[N+](CC)CC)C=C3O2)C4=CC=CC=C4C(=O)O.OP(=O)(O)[O-].OS(=O)(=O)O.O=[Mo]=O
- Inchi : 1S/C28H30N2O3.Mo.H3O4P.H2O4S.2O/c1-5-29(6-2)19-13-15-23-25(17-19)33-26-18-20(30(7-3)8-4)14-
16-24(26)27(23)21-11-9-10-12-22(21)28(31)32;;2*1-5(2,3)4;;/h9-18H,5-8H2,1-4H3;;(H3,1,2,3,4);(H2,1,2,3,4);;
- Substance type: Organic
- Physical state: Solid powder (purple)
Specific details on test material used for the study:
- Name of test material: C.I. Pigment Violet 1
- IUPAC name: Xanthylium, 9-(2-carboxyphenyl)-3,6-bis(diethylamino)-, molybdatetungstatephosphate
- Molecular formula: C28H35MoN2O13PS
- Molecular weight (if other than submission substance): 766.573 g/mol
- Smiles : CCN(CC)C1=CC2=C(C=C1)C(=C3C=CC(=[N+](CC)CC)C=C3O2)C4=CC=CC=C4C(=O)O.OP(=O)(O)[O-].OS(=O)(=O)O.O=[Mo]=O
- Inchi : 1S/C28H30N2O3.Mo.H3O4P.H2O4S.2O/c1-5-29(6-2)19-13-15-23-25(17-19)33-26-18-20(30(7-3)8-4)14-
16-24(26)27(23)21-11-9-10-12-22(21)28(31)32;;2*1-5(2,3)4;;/h9-18H,5-8H2,1-4H3;;(H3,1,2,3,4);(H2,1,2,3,4);;
- Substance type: Organic
- Physical state: Solid powder (purple)

Method

Target gene:
Histidine
Species / strain
Species / strain / cell type:
S. typhimurium, other: TA100, TA1535, TA97, TA98
Remarks:
LAB 1
Details on mammalian cell type (if applicable):
Not applicable
Additional strain / cell type characteristics:
not specified
Cytokinesis block (if used):
No data
Metabolic activation:
with and without
Metabolic activation system:
The S-9 fractions of Aroclor 1254-induced, male Sprague-Dawley rat and male Syrian hamster livers were prepared
Test concentrations with justification for top dose:
LAB 1: 0, 33, 100, 333, 1000, 2000, 3333, 5000 or 10000 µg/plate
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: The test chemical was soluble in DMSO
Controls
Untreated negative controls:
not specified
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
9-aminoacridine
sodium azide
other: 2-Aminoanthracene (All strains + S9); 4-Nitro-o-phenylenediamine (TA98; -S9)
Details on test system and experimental conditions:
METHOD OF APPLICATION: preincubation

DURATION
- Preincubation period: 20 mins
- Exposure duration: 48 hrs
- Expression time (cells in growth medium): 48 hrs
- Selection time (if incubation with a selection agent): No data available
- Fixation time (start of exposure up to fixation or harvest of cells): No data available

SELECTION AGENT (mutation assays): No data available
SPINDLE INHIBITOR (cytogenetic assays): No data available
STAIN (for cytogenetic assays): No data available

NUMBER OF REPLICATIONS: Triplicate

NUMBER OF CELLS EVALUATED: No data available

DETERMINATION OF CYTOTOXICITY
- Method: mitotic index; cloning efficiency; relative total growth; other: No data available

OTHER EXAMINATIONS:
- Determination of polyploidy: No data available
- Determination of endoreplication: No data available
- Other:

OTHER: No data available
Rationale for test conditions:
No data
Evaluation criteria:
An individual trial was judged mutagenic (+) if a dose-related increase over the corresponding solvent control was seen, and it was judged weakly mutagenic C+W) if a low-level dose response was seen. A trial was considered questionable (?) if a dose-related increase was judged insufficiently high to justify a call of "+W," if only a single dose was elevated over the control, or if a non-dose-related increase was seen.

The chemical was judged to be mutagenic (+), or weakly mutagenic (+W), if it produced a reproducible, dose-related increase in his+ revertants over the corresponding solvent controls in replicate trials.

It chemical was considered to be questionable (?) if a reproducible increase of his+ revertants did not meet the criteria for either a " + " or " + W," or if only single doses produced an increase in his+ revertants in repeat trials.
Statistics:
No data

Results and discussion

Test results
Species / strain:
S. typhimurium, other: TA100, TA1535, TA97, TA98
Remarks:
LAB 1
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
valid
Untreated negative controls validity:
not specified
Positive controls validity:
valid
Additional information on results:
No data
Remarks on result:
other: No mutagenic potential

Any other information on results incl. tables

Table: Mutagenicity of Pigment violet 1

Lab 1:

Dose (µg/plate)

TA100

-S9

10% HLI

30% HLI

10% RLI

30% RLI

Mean

SEM

Mean

SEM

Mean

SEM

Mean

SEM

Mean

SEM

0

109

11.7

106

2.3

112

9.1

113

3.4

140

2.6

33

108

10.3

 

 

105

1.5

 

 

120

2.5

100

92

2.0

99

3.0

120

8.8

106

4.5

112

10.2

333

105

6.0

91

7.2

129

1.9

95

9.0

124

6.1

1000

82s

10.1

83

7.4

113s

7.9

89

7.3

97s

6.2

2000

 

 

 

 

 

 

 

 

 

 

3333

63s

2.0

66s

7.3

70s

4.7

72s

3.5

77s

3.7

5000

 

 

 

 

 

 

 

 

 

 

10000

 

 

12

2.0

 

 

17

1.8

 

 

Positive control

1196

36.6

1211

41.5

736

7.5

1191

46.2

547

27.1

 

Dose (µg/plate)

TA1535

-S9

5% HLI

10% HLI

30% HLI

5% RLI

10% RLI

30% RLI

Mean

SEM

Mean

SEM

Mean

SEM

Mean

SEM

Mean

SEM

Mean

SEM

Mean

SEM

0

23

1.5

15

1.2

15

2.3

16

2.3

16

5.2

15

1.5

14

2.8

33

 

 

 

 

 

 

13

1.9

 

 

 

 

14

3.0

100

22

3.2

16

2.3

9

1.7

12

2.5

19s

2.3

13

1.5

12

0.7

333

29s

2.9

11

1.5

11s

2.3

13

0.9

17s

1.7

13s

1.8

15

1.8

1000

17s

1.2

18s

2.9

13s

0.9

11

2.1

19s

2.3

17s

1.3

7

1.2

2000

23s

2.7

20s

3.0

14s

3.8

 

 

25s

2.9

19s

4.0

 

 

3333

20s

3.8

23s

1.2

21s

3.9

10s

2.6

19s

0.6

22s

0.3

15s

4.1

5000

15s

2.4

20s

4.1

20s

3.5

 

 

16s

4.4

19s

0.3

15s

4.1

10000

12s

0.7

13s

1.2

10s

0.9

 

 

14s

2.1

11s

0.0

 

 

Positive control

1041

16.2

181

8.0

118

5.8

224

14.9

108

2.1

121

3.6

161

3.7

 

Dose (µg/plate)

TA97

-S9

10% HLI

30% HLI

10% RLI

30% RLI

Mean

SEM

Mean

SEM

Mean

SEM

Mean

SEM

Mean

SEM

0

114

3.7

129

6.7

156

5.5

134

9.0

189

9.7

33

119

6.4

 

 

162

4.8

 

 

185

1.2

100

102

9.3

124

6.8

164

5.4

142

4.6

155

8.5

333

105

10.8

93

2.9

162

10.7

108

3.9

170

3.5

1000

100

10.4

79

4.4

126

2.0

88

5.0

120

8.2

2000

 

 

 

 

 

 

 

 

 

 

3333

11s

7.7

32s

15.5

118s

14.2

51s

2.1

104s

3.8

5000

 

 

 

 

 

 

 

 

 

 

10000

 

 

10

1.0

 

 

15

2.0

 

 

Positive control

797

16.2

747

12.3

542

12.2

902

43.0

548

18.2

 

Dose (µg/plate)

TA98

-S9

10% HLI

30% HLI

10% RLI

30% RLI

Mean

SEM

Mean

SEM

Mean

SEM

Mean

SEM

Mean

SEM

0

16

1.7

34

2.3

34

3.2

37

3.2

34

5.0

33

19

4.9

 

 

29

3.2

 

 

32

5.0

100

11

1.8

44

4.6

31

4.7

36

3.8

32

1.2

333

10

2.0

22

0.6

43

2.1

30

6.4

37

2.8

1000

8

1.3

20

2.0

20

3.2

19

1.0

13

1.2

2000

 

 

 

 

 

 

 

 

 

 

3333

8

3.0

13

2.3

14

1.5

15

1.2

15s

2.3

5000

 

 

 

 

 

 

 

 

 

 

10000

 

 

10

0.9

 

 

7

2.9

 

 

Positive control

1594

95.7

1341

42.6

653

12.2

1397

38.8

449

13.0

 

Lab 2:

Dose (µg/plate)

TA100

TA1535

-S9

10% HLI

30% HLI

-S9

10% RLI

30% RLI

Mean

SEM

Mean

SEM

Mean

SEM

Mean

SEM

Mean

SEM

 

 

0

128

1.5

110

0.7

115

7.2

25

2.2

8

2.0

9

1.9

33

116

12.3

112

5.8

108

4.7

24

3.2

11

2.0

8

1.9

100

100

12.5

133

10.7

122

9.0

31

2.9

5

0.6

11

3.3

333

100

5.0

115

0.3

101

8.2

25

3.8

6

0.9

9

2.1

1000

97

9.4

105

6.9

95

7.5

16

3.8

7

0.9

7

3.0

3333

60

1.5

88

5.9

79

10.5

15

1.5

10

0.3

10

0.6

Positive control

531

0.6

1828

104.6

606

14.9

604

10.2

407

19.1

129

5.6

 

Dose (µg/plate)

TA1537

98

-S9

10% HLI

30% HLI

-S9

10% RLI

30% RLI

Mean

SEM

Mean

SEM

Mean

SEM

Mean

SEM

Mean

SEM

 

 

0

5

1.2

7

1.2

5

1.2

17

0.6

24

3.8

25

3.2

33

11

2.0

27

1.5

29

7.8

15

1.7

30

2.1

29

2.7

100

5

0.7

6

1.5

11

1.5

15

1.7

30

2.1

29

2.7

333

4

0.9

7

2.6

5

0.6

16

0.9

24

2.0

35

1.3

1000

6

1.7

7

0.7

6

1.3

13

1.7

12

1.3

12

2.3

3333

4

0.3

6

3.1

4

0.3

14

1.2

13

0.3

14

0.9

Positive control

630

83.2

204

34.3

125

0.7

864

41.2

1270

51.2

378

23.2

 

s: slight clearing of background lawn

Applicant's summary and conclusion

Conclusions:
Pigment violet 1 did not induce mutation in Salmonella typhimurium strains TA98, TA100, TA 1537 and TA 97 in the presence and absence of S9 metabolic activation system and hence is not likely to classify as a gene mutant in vitro.
Executive summary:

Gene mutation toxicity study was performed to determine the mutagenic nature of Pigment Violet 1 (EC name: Xanthylium, 9-(2-carboxyphenyl)-3,6-bis(diethylamino)-, molybdatetungstatephosphate) using Salmonella typhimurium strains TA100, TA1535, TA97and TA98. Salmonella/microsome test was performed both in the absence and presence of liver S-9 obtained from Aroclor-induced male Sprague-Dawley rats and Syrian hamsters. Preincubation assay was performed at dose levels of 0, 33, 100, 333, 1000, 2000, 3333, 5000, 10000 µg/plate in lab 1. The plates were preincubated for 20 mins and incubated futher for 48 hrs chemical exposure. Concurrent solvent and positive controls were also included in the study. Pigment violet 1did not induce gene mutation in Salmonella typhimurium strains TA98, TA100, TA1535 and TA 97 in the presence and absence of S9 metabolic activation system and hence is not likely to classify as a gene mutant in vitro.

 

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