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Diss Factsheets

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:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1988
Report date:
1998

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay

Test material

Constituent 1
Chemical structure
Reference substance name:
Methyl acetate
EC Number:
201-185-2
EC Name:
Methyl acetate
Cas Number:
79-20-9
Molecular formula:
C3H6O2
IUPAC Name:
methyl acetate
Details on test material:
Molecular formula: C3H6O2
Appearance: Colorless liquid
Melting Point: -98 C
Boiling Point: 57 C @ 1013 mbar
Molecular Weight: 74.1
Specific Gravity: 0.932 g/cm at 20C
Vapor Pressure: 217 mbar @ 20 C
pH - Value in water: Neutral
Storage Conditions: dark @ 22 C

Method

Species / strain
Species / strain / cell type:
other: S. typhimurium TA 1535, TA 1537, TA 98 and TA 100. Escherichia coli WP2uvrA
Metabolic activation:
with and without
Metabolic activation system:
S-9 from rat liver homogenate
Test concentrations with justification for top dose:
0, 4, 20, 100, 500, 2500 and 5000 ug/plate
Vehicle / solvent:
DMSO
Controls
Untreated negative controls:
yes
Positive controls:
yes
Positive control substance:
9-aminoacridine
2-nitrofluorene
sodium azide
N-ethyl-N-nitro-N-nitrosoguanidine
benzo(a)pyrene
other: 2-Aminoanthracene
Rationale for test conditions:
range finding test
Evaluation criteria:
statistically significant dose dependent increase

Results and discussion

Test results
Key result
Species / strain:
other: S. typhimurium TA 1535, TA 1537, TA 98 and TA 100 and E. coli WP2 uvr A
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Remarks:
non-toxic up to 5000 ug/plate
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

TA100

DOSE

Without Activation

With Activation

ug/Plate

Mean Value

Exp 1

Mean Value

Exp 2

Mean Value

Exp 1

Mean Value

Exp 2

0

168

129

168

148

4

178

137

178

136

20

170

133

170

137

100

169

140

169

146

500

185

139

185

135

2500

154

138

154

133

10000

157

148

157

139

+ ctrl

425

374

546

374

TA1535

DOSE

Without Activation

With Activation

ug/Plate

Mean Value

Exp 1

Mean Value

Exp 2

Mean Value

Exp 1

Mean Value

Exp 2

0

17

10

15

11

4

16

10

14

14

20

17

9

16

12

100

15

11

12

10

500

12

10

14

11

2500

14

9

15

13

10000

18

7

12

8

+ ctrl

350

297

114

102

TA1538

DOSE

Without Activation

With Activation

ug/Plate

Mean Value

Exp 1

Mean Value

Exp 2

Mean Value

Exp 1

Mean Value

Exp 2

0

16

10

19

13

4

16

10

16

15

20

16

11

19

14

100

19

11

19

16

500

14

11

21

12

2500

17

9

19

13

10000

14

9

19

15

+ ctrl

439

376

491

348

TA98

DOSE

Without Activation

With Activation

ug/Plate

Mean Value

Exp 1

Mean Value

Exp 2

Mean Value

Exp 1

Mean Value

Exp 2

0

24

22

30

28

4

22

24

32

28

20

23

21

19

30

100

25

24

32

29

500

23

24

32

31

2500

22

24

30

28

10000

24

24

31

28

+ ctrl

342

402

471

487

TA1537

DOSE

Without Activation

With Activation

ug/Plate

Mean Value

Exp 1

Mean Value

Exp 2

Mean Value

Exp 1

Mean Value

Exp 2

0

11

9

11

12

4

9

8

10

10

20

11

8

10

9

100

11

9

10

10

500

9

8

9

9

2500

11

11

11

9

10000

14

7

10

8

+ ctrl

98

126

98

106

 

WP2uvrA

DOSE

Without Activation

With Activation

ug/Plate

Mean Value

Exp 1

Mean Value

Exp 2

Mean Value

Exp 1

Mean Value

Exp 2

0

72

55

74

57

4

75

54

75

53

20

74

55

77

56

100

69

61

78

55

500

75

55

75

52

2500

75

57

79

52

10000

76

55

75

55

+ ctrl

280

509

216

446

Applicant's summary and conclusion

Conclusions:
Not Mutagenic with or without metabolic activation
Executive summary:

Methyl acetate was tested for mutagenicity with the strains TA 100, TA 1535, TA 1537, TA 1538, TA 98 of Salmonella typhimurium and Escherichia coli WP2uvrA.

The mutagenicity studies were conducted in the absence adn in the presence of a metabolizing system derived from rat liver homogenate. A dose range of 6 different doses from 4 micrograms/plate to 5000 micrograms/plate was used.

Control plates without mutagen showed that the number of spontaneous revertant colonies was similar to that described in the literature. All the positive control compounds gave the expected increase in the number of revertant colonies.

Toxicity: The test compound proved to be not toxic to the bacterial strains at 5000 micrograms/plate. 5000 micrograms/plate was chosen as the top dose level for the mutagenicity study.

Mutagenicity: In the absence of the metabolic activation system the test compound did not show a dose dependent increase in the number of revertants in any of the bacterial strains. Also in the presence of a metabolic activation system, treatment of the cells with Methyl acetate did not result in relevant increases in the number of revertant colonies.

Summarizing, it can be stated that Methyl acetate is not mutagenic in these bacterial test systems either with or without exogenous metabolic activation at the dose levels investigated.