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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 from handbook or collection of data

Data source

Reference
Reference Type:
publication
Title:
In vitro gene toxicity study for test chemical in Salmonella Typhimurium TA98, TA 100, TA 1535 and 1537 by AMES test.
Author:
National Toxicology Program
Year:
2018
Bibliographic source:
NTP, Chemical effects in biological system

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Principles of method if other than guideline:
To evaluate the mutagenic potential of test chemical in Salmonella Typhimurium TA98,TA 100,TA 1535 and TA 1537 by AMES test.
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 2-Amino-4-nitrophenol
- Molecular formula (if other than submission substance): C6H6N2O3
- Molecular weight (if other than submission substance): 154.13gm/mole
- Substance type: organic

Method

Target gene:
Histidine
Species / strain
Species / strain / cell type:
other: TA98,TA 100,TA 1535 and TA 1537
Details on mammalian cell type (if applicable):
not specified
Additional strain / cell type characteristics:
not specified
Cytokinesis block (if used):
not specified
Metabolic activation:
with and without
Metabolic activation system:
RLI = induced male Sprague Dawley rat liver S9 HLI = induced male Syrian hamster liver S9
Test concentrations with justification for top dose:
0,10,30,100, 333,1000 and 3333µg/plate
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: 95% Ethanol
- Justification for choice of solvent/vehicle: The test substance is soluble in 95% Ethanol.
Controls
Untreated negative controls:
not specified
Negative solvent / vehicle controls:
yes
Remarks:
95% Ethanol
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
other: -S9 mix;4 nitro-O phenylenediamine (TA 98), Sodium azide (TA1535and TA 100) and 9-Aminoacridine(TA1537) +S9 mix; 2-Aminoanthracene(all strains)
Details on test system and experimental conditions:
Details on test system and conditions
METHOD OF APPLICATION: Pre incubation method
NUMBER OF REPLICATIONS: Duplicate
Evaluation criteria:
The plates were observed for revertents mutants colonies per plates
Statistics:
Yes, SD ± Mean was observed.

Results and discussion

Test results
Key result
Species / strain:
other: TA100, TA1535, TA98 and TA1537
Metabolic activation:
with and without
Genotoxicity:
positive
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
valid
Untreated negative controls validity:
not specified
Positive controls validity:
valid
Remarks on result:
other: Mutagenic effect were observed

Any other information on results incl. tables

Strain: TA100

 

Dose

No Activation 
(Negative)

No Activation 
(Negative)

10% RLI 
(Negative)

10% RLI 
(Weakly Positive)

10% HLI 
(Positive)

10% HLI 
(Weakly Positive)

Protocol

Preincubation

Preincubation

Preincubation

Preincubation

Preincubation

Preincubation

ug/Plate

Mean

±SEM

Mean

±SEM

Mean

±SEM

Mean

±SEM

Mean

±SEM

Mean

±SEM

 0         

139

7.8

107

4

142

4.3

112

7.9

129

6.9

163

8.8

10         

121

5.4

146

3.2

33         

135

9.5

114

4.7

133

4.9

162

7.7

164

10.3

156

8.4

100         

145

8.4

117

11.8

132

14.2

169

10.2

210

8.7

223

11

333         

142

6.2

101

7.4

134

10

191

6.4

268

2.9

247

9

1000         

146

10.3

97

11.6

122

2.7

180

3.5

289

17.3

282

5.9

3333         

86 s

49.7

t

0 s

0

0 s

0

Positive Control

434

3.7

407

18.7

690

15.4

551

3.5

1290

45.3

1796

23.7

 

Strain: TA1535

Dose

No Activation 
(Negative)

10% RLI 
(Negative)

10% HLI 
(Negative)

Protocol

Preincubation

Preincubation

Preincubation

ug/Plate

Mean

±SEM

Mean

±SEM

Mean

±SEM

 0         

27

.9

46

3.8

42

4.5

33         

29

3.7

28

1.7

41

2.1

100         

25

3.5

21

1.8

36

.3

333         

27

3

16

1.2

37

2.2

1000         

28

5.2

0 s

0

32

3.5

3333         

9 s

3.1

t

0 s

0

Positive Control

427

7.1

277

7.1

536

12.8

 

Strain: TA1537

Dose

No Activation 
(Negative)

10% RLI 
(Negative)

10% HLI 
(Negative)

Protocol

Preincubation

Preincubation

Preincubation

ug/Plate

Mean

±SEM

Mean

±SEM

Mean

±SEM

 0         

5

.9

10

1

5

.6

33         

6

1

7

1.2

12

2.8

100         

6

1.7

7

.9

12

4

333         

6

.3

11

1.2

15

1.3

1000         

10

2

12

2.3

10

2

3333         

5

.3

9

1.7

0 s

0

Positive Control

172

4.7

167

14.8

500

5.5

 

Strain: TA98

Dose

No Activation 
(Negative)

No Activation 
(Positive)

10% RLI 
(Negative)

10% RLI 
(Positive)

10% HLI 
(Positive)

10% HLI 
(Positive)

Protocol

Preincubation

Preincubation

Preincubation

Preincubation

Preincubation

Preincubation

ug/Plate

Mean

±SEM

Mean

±SEM

Mean

±SEM

Mean

±SEM

Mean

±SEM

Mean

±SEM

 0         

21

2

29

2.2

40

1.7

37

3.5

37

3.7

37

4.3

10         

27

1.5

44

1.3

33         

26

3.1

52

7.2

38

4.2

53

.7

50

3

54

3.2

100         

30

2.7

64

4.6

50

2.3

57

1.9

67

3.6

62

3.7

333         

17

2.3

64

6.6

55

3.5

75

6.8

94

4.7

86

.3

1000         

17

1

84

7.1

56

4.7

83

1.2

242

19.6

113

13.5

3333         

t

0 s

0

t

0 s

0

Positive Control

724

34

724

7.1

425

15.3

382

27

1514

107.5

1027

53.1

 

Abbreviations:
RLI = induced male Sprague Dawley rat liver S9
HLI = induced male Syrian hamster liver S9
s = Slight Toxicity; p = Precipitate; x = Slight Toxicity and Precipitate; t = Toxic;

Applicant's summary and conclusion

Conclusions:
Test chemical was evaluated for its mutagenic potential in Salmonella typhimurium TA100, TA1535, TA98 and TA1537 by AMES test. The test result was considered to be positive in all strain in the presence and absence of metabolic activation S9.
Executive summary:

Genetic toxicity in vitro study was assessed for test chemical. For this purpose AMES test was performed .The test material was exposed to Salmonella typhimurium TA100, TA1535, TA98 and TA1537in the presence and absence of metabolic activation S9. The concentration of test material used in the presence and absence of metabolic activation were 0, 10, 30,100, 333, 1000 and 3333 µg/plate. Mutagenic effects were observed in all strains, in the presence and absence of metabolic activation. Therefore test chemical was considered to be mutagenic in Salmonella typhimurium TA100, TA1535, TA98 and TA1537by AMES test. Hence the substance can be classified as gene mutant in vitro.