Registration Dossier

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:
weight of evidence
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: IV. Results From the Testing of 300 Chemicals
Author:
Errol Zeiger, Beth Anderson, Steve Haworth, Timothy Lawlor, and Kristien Mortelmans
Year:
1988
Bibliographic source:
Environmental and Molecular Mutagenesis Volume 11, Supplement 12: 1-158 (1988)

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:
The test chemical m-Amino benzenesulfonic acid was studied for its ability to induce mutations in strains of Salmonella typhimurium.
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: m-Amino benzenesulfonic acid
- IUPAC name: 3-Aminobenzene sulphonic acid
- Molecular formula: C6H7NO3S
- Molecular weight: 173.1913 g/mol
- Substance type: Organic
Specific details on test material used for the study:
- Name of test material: m-Amino benzenesulfonic acid
- IUPAC name: 3-Aminobenzene sulphonic acid
- Molecular formula: C6H7NO3S
- Molecular weight: 173.1913 g/mol
- Substance type: Organic
- Physical state: No data
- Purity: 99+%
- Impurities (identity and concentrations): No data

Method

Target gene:
Histidine
Species / strain
Species / strain:
other: TA100, TA1535, TA97 and TA98
Details on mammalian cell lines (if applicable):
Not applicable
Additional strain characteristics:
not specified
Cytokinesis block (if used):
No data
Metabolic activation:
with and without
Metabolic activation system:
10% and 30% HLI and RLI S-9 (9,000 g supernatant) fractions were prepared from Aroclor 1254-induced, male Sprague- Dawley rat and male Syrian hamster livers
Test concentrations with justification for top dose:
0, 33, 100, 333, 1000 or 3333 µg/plate
Vehicle:
- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: The test chemical is soluble in DMSO

Controls
Negative controls:
not specified
Solvent controls:
yes
Remarks:
DMSO
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
9-aminoacridine
sodium azide
other: 4-nitro-o-phenylenediamine (TA98; -S9) and 2-aminoanthracene (all strains; +S9)
Details on test system and 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: No data available

OTHER: No data available
Rationale for test conditions:
No data
Evaluation criteria:
Evaluations were made at both the individual trial and overall chemical levels.

Individual trials were judged mutagenic (+), weakly mutagenic (+ W), questionable (?), or nonmutagenic (-), depending on the magnitude of the increase of his+ revertants, and the shape of the dose-response. A trial was considered questionable (?) if the dose-response was judged insufficiently high to support a call of “ +W,” if only a single dose was elevated over the control, or if the increase seen was not dose related. The distinctions between a questionable mutagenic response and a nonmutagenic or weak mutagenic response, and between a weak mutagenic response and mutagenic response are highly subjective. It was not necessary for a response to reach two fold over background for a chemical to be judged mutagenic.

A chemical was judged mutagenic (+) or weakly mutagenic (+ W) if it produced a reproducible dose-related reponse over the solvent control in replicate trials. A chemical was judged questionable (?) if the results of individual trials were not reproducible, if increases in his+ revertants did not meet the criteria for a “+W” response, or if only single doses produced increases in his+ revertants in repeat trials.
Chemicals were judged nonmutagenic (-) if they did not meet the criteria for a mutagenic or questionable response. The chemicals were decoded by the chemical repository only after a determination had been made regarding their mutagenicity or nonmutagenicity.
Statistics:
Mean ± SD

Results and discussion

Test results
Species / strain:
other: TA100, TA1535, TA97 and TA98
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity:
not specified
Vehicle controls valid:
yes
Negative controls valid:
not specified
Positive controls valid:
yes
Remarks on result:
other: No mutagenic potential
Additional information on results:
TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: No data available
- Effects of osmolality: No data available
- Evaporation from medium: No data available
- Water solubility: No data available
- Precipitation: No data available
- Other confounding effects: No data available

RANGE-FINDING/SCREENING STUDIES: All chemicals were tested initially in a toxicity assay to determine the appropriate dose range for the mutagenicity assay. The toxicity assay was performed using TA100. Toxic concentrations were those that produced a decrease in the number of his+ colonies, or a clearing in the density of the background lawn, or both.

COMPARISON WITH HISTORICAL CONTROL DATA: Yes

ADDITIONAL INFORMATION ON CYTOTOXICITY: No data available

Any other information on results incl. tables

Table: Mutagenicity of m-Amino benzene sulfonic acid

Dose (µg/plate)

TA100

-S9

10% HLI

30% HLI

10% RLI

30% RLI

Mean

SEM

Mean

SEM

Mean

SEM

Mean

SEM

Mean

SEM

0

85

0.5

84

3.1

90

3.4

83

0.0

97

6.1

33

72

13.4

79

3.5

97

9.0

102

3.1

95

6.8

100

79

8.0

95

3.2

86

7.5

89

2.1

95

4.5

333

77

0.7

84

9.0

75

4.6

101

11.6

82

6.4

1000

84

4.3

81

4.0

86

6.8

98

3.0

87

4.0

3333

84

4.7

94

7.9

93

5.4

98

6.9

9.4

5.8

Positive control

302

7.2

402

9.5

357

23.1

315

11.3

196

6.8

 

Dose (µg/plate)

TA1535

-S9

10% HLI

30% HLI

10% RLI

30% RLI

Mean

SEM

Mean

SEM

Mean

SEM

Mean

SEM

Mean

SEM

0

15

0.3

12

1.0

11

1.5

10

2.0

10

2.0

33

12

0.9

10

2.9

8

0.3

9

0.7

8

0.3

100

12

0.9

4

1.2

9

1.5

7

0.9

7

1.7

333

12

2.4

9

0.7

6

0.9

9

0.9

8

1.0

1000

13

1.5

7

0.7

10

3.5

8

0.3

8

1.8

3333

7

1.2

12

0.6

9

1.0

10

2.5

9

0.9

Positive control

174

4.9

50

7.5

70

9.2

120

7.0

46

3.2

 

Dose (µg/plate)

TA97

-S9

10% HLI

30% HLI

10% RLI

30% RLI

Mean

SEM

Mean

SEM

Mean

SEM

Mean

SEM

Mean

SEM

0

78

4.4

93

2.8

146

3.8

101

6.2

195

7.0

33

67

5.0

95

4.7

152

4.7

101

8.7

203

2.4

100

71

5.5

91

3.8

154

8.3

123

1.7

188

14.1

333

84

5.0

101

8.0

144

1.2

91

5.8

170

3.7

1000

72

3.5

98

8.0

15

4.7

121

10.0

190

13.7

3333

64

3.4

94

10.9

126

3.5

120

11.9

218

9.0

Positive control

803

66.2

494

17.6

760

9.0

511

22.8

372

21.7

 

Dose (µg/plate)

TA98

-S9

10% HLI

30% HLI

10% RLI

30% RLI

Mean

SEM

Mean

SEM

Mean

SEM

Mean

SEM

Mean

SEM

0

14

1.5

33

9.0

26

5.2

32

2.4

23

2.7

33

11

1.2

38

4.7

26

2.6

34

2.1

19

0.9

100

14

0.9

25

3.8

22

5.0

31

0.7

21

0.3

333

18

0.6

25

1.2

23

2.7

22

1.5

21

2.8

1000

19

3.1

30

5.8

25

2.6

29

0.7

21

0.3

3333

14

2.6

32

6.1

22

3.2

29

2.0

18

2.4

Positive control

147

1.2

106

5.2

175

12.8

86

11.0

59

2.3

 

Applicant's summary and conclusion

Conclusions:
m-Amino benzene sulfonic acid is not mutagenic to the Salmonella typhimurium TA100, TA1535, TA97 and TA98 in the presence and absence of rat and hamster liver S9 metabolic activation system and hence it is not likely to classify as a gene mutant in vitro.
Executive summary:

m-Amino benzenesulfonic acid was studied for its ability to induce mutations in strains of Salmonella typhimurium.

 

The test compound was dissolved in DMSO and was tested at concentration of 0, 33, 100, 333, 1000 or 3333 µg/plate using Salmonella typhimurium TA100, TA1535, TA97 and TA98 in the presence and absence of 10 % and 30 % rat and hamster liver S9 metabolic activation system. Preincubation assay was performed with a preicubation for 20 mins. The plates were observed for histidine independence after 2 days incubation period. Concurrent solvent and positive controls were included in the study.

 

m-Amino benzene sulfonic acidis not mutagenic to theSalmonella typhimurium TA100, TA1535, TA97 and TA98 in the presence and absence of rat and hamster liver S9 metabolic activation system and hence it is not likely to classify as a gene mutant in vitro.