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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:
comparable to guideline study with acceptable restrictions

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Unnamed
Year:
1987
Reference Type:
review article or handbook
Title:
Unnamed
Year:
2008

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Version / remarks:
Haworth S, Lawlor T, Mortelmans K, Speck W, Zeiger E (1983): Salmonella mutagenicity results for 250 chemicals. Environ Mutagen S[Suppl 1]:3-142.
Deviations:
yes
Remarks:
No E.coli strain or TA102 tested
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Aldrich
- Purity: 96.4%

Method

Target gene:
Strain Target Gene:
TA1537 hisC3076
TA1535 hisG46
TA100 hisG46
TA98 hisD3052
Species / strain
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Metabolic activation system:
The S9 fractions were prepared from the liver of Aroclor 1254-induced male Sprague-Dawley rats and male Syrian hamsters.
Test concentrations with justification for top dose:
33 - 4000 ug/plate
Vehicle / solvent:
water
Controls
Untreated negative controls:
not specified
Negative solvent / vehicle controls:
yes
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
9-aminoacridine
2-nitrofluorene
sodium azide
other: For strains tested with S9: All strains, 2-aminoanthracene.
Details on test system and experimental conditions:
METHOD OF APPLICATION: preincubation

DURATION
- Preincubation period: 20 min
- Exposure duration: 2 days
DURATION
- Preincubation period: 20 min
- Exposure duration: 48 h
Evaluation criteria:
According to Haworth et al. (1983).

Results and discussion

Test resultsopen allclose all
Species / strain:
S. typhimurium, other: TA98, TA100, TA1537
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
Slightly toxic at highest dose in the 3 strains.
Vehicle controls validity:
valid
Untreated negative controls validity:
not specified
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 1535
Metabolic activation:
without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
Slightly toxic at highest dose
Vehicle controls validity:
valid
Untreated negative controls validity:
not specified
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 1535
Metabolic activation:
with
Genotoxicity:
ambiguous
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
Slightly toxic at highest dose
Vehicle controls validity:
valid
Untreated negative controls validity:
not specified
Positive controls validity:
valid

Any other information on results incl. tables

Table 1-4: Results for the Ames-testing.

Strain TA100

Dose

No Activation
(Negative)

10% HLI
(Negative)

10% RLI
(Negative)

Dose units

Mean

± SEM

Mean

± SEM

Mean

± SEM

0         

135

2

141

6.8

139

5.6

33         

152

4

144

8.7

132

14.4

100         

141

3.8

140

12.2

138

5.8

333         

148

4.2

140

5.5

149

11.1

1000         

155

0.9

128

6.4

124

4.3

3333         

130S

7.8

159S

7

156S

6.5

Positive Control

1298

63.2

1452

83.5

947

33.3

Strain TA98

Dose

No Activation
(Negative)

10% HLI
(Negative)

10% RLI
(Negative)

Dose units

Mean

± SEM

Mean

± SEM

Mean

± SEM

0         

18

2

30

0.6

24

1.2

33         

19

2.6

36

1.5

25

4.4

100         

25

2.9

43

1.9

30

6.3

333         

17

2.3

25

2.1

33

0.7

1000         

21

3.3

31

4.5

26

4.1

3333         

8T

3.5

20S

4.3

20S

1.8

Positive Control

1475

103.9

935

33.9

637

42.8

Strain TA1537

Dose

No Activation
(Negative)

10% HLI
(Negative)

10% RLI
(Negative)

Dose units

Mean

± SEM

Mean

± SEM

Mean

± SEM

0         

8

1.7

10

1.7

8

0.9

33         

7

2.9

12

1.5

11

2.9

100         

7

0.3

13

1.7

9

0.9

333         

6

1.8

7

1.2

7

1

1000         

6

0.6

7

1.3

8

0.3

3333         

4S

1.2

4S

0.3

5S

0.3

Positive Control

87

12.3

124

6.1

97

2.9

Strain TA1535:

Dose

No Activation
(Negative)

No Activation
(Negative)

No Activation
(Negative)

No Activation
(Negative)

10% HLI
(Equivocal)

10% HLI
(Weak Positive)

10% HLI
(Negative)

10% HLI
(Positive)

10% RLI
(Negative)

10% RLI
(Positive)

10% RLI
(Negative)

10% RLI
(Positive)

Dose units

Mean

± SEM

Mean

± SEM

Mean

± SEM

Mean

± SEM

Mean

± SEM

Mean

± SEM

Mean

± SEM

Mean

± SEM

Mean

± SEM

Mean

± SEM

Mean

± SEM

Mean

± SEM

0         

27

5

54

6.4

7

1.2

36

3.6

9

0.9

11

3.2

9

2.5

5

1

9

1.5

9

0.7

7

1.5

11

0

33         

30

1.5

 

 

 

 

 

 

11

2.2

 

 

 

 

 

 

7

2.6

 

 

 

 

 

 

100         

30

4.4

51

4.2

7

0.9

34

0.9

11

1

9

1

8

1.2

10

2.3

11

1.2

10

0.6

7

1.9

11

1.3

333         

27

4.4

45

2.2

6

1.5

32

5

14

0.9

14

1.2

6

0.7

11

2

9

0.9

14

2.8

6

0.7

7

0.3

1000         

20

1.5

47

3.8

4

0.7

23

4.8

10

1.2

9

0.3

7

1.3

11

4.2

7

1.8

14

0.7

5

1.5

9

0.7

1800         

 

 

34

3.8

5

1.3

28

1.3

 

 

24

1.9

10

1.3

29

0.7

 

 

15

1.9

5

1.7

13

3.2

2800         

 

 

25S

0.9

4S

1

23S

2

 

 

30S

2.9

5

0.6

28

6.6

 

 

33S

4.3

8

2

32

2.1

3333         

12S

3.8

25S

4.5

4S

0.9

16S

3.2

27S

1.7

20S

1.8

8S

2.1

24S

2.7

17S

2.5

32S

2.6

6S

2.2

32S

2.2

3500         

 

 

16S

0.6

3S

0.6

21S

0.3

 

 

18S

2.7

6S

1.5

25S

4.7

 

 

20S

1.5

6S

1

26S

2.2

4000         

 

 

13S

1.7

2S

0.6

17S

2.1

 

 

21S

0.9

3S

0.3

15S

2.4

 

 

26S

5.1

4S

1.7

23S

3.3

Positive Control

1005

61

1484

111

869

23.8

1124

41.3

124

3.5

99

2.3

85

2.3

231

16.1

98

6.4

95

11.4

83

4.7

103

13.6

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; c = Contamination

Applicant's summary and conclusion

Conclusions:
Under the conditions tested the test substance was not mutagenic in the strains TA98, TA100 and TA1537.
However, with S9-activation the TA1535 strain presented some weak positive results. Therefore the test substance was rated as ambiguous.