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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2006-12-19 to 2007-01-25
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Basic data given: comparable to guideline/standards

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2007
Report Date:
2007

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
no
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent

Method

Target gene:
his (Salmonella strains), trp (E. coli strain)
Species / strain
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2
Metabolic activation:
with and without
Metabolic activation system:
S9 mix
Test concentrations with justification for top dose:
Experiment 1: 0, 4.88, 19.5, 78.1, 313, 1250, 5000 µg/plate
Experiment 2: 0, 156, 313, 625, 1250, 2500, 5000 µg/plate
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: DMSO
Controlsopen allclose all
Negative solvent / vehicle controls:
yes
Positive controls:
yes
Positive control substance:
other: 2-Aminoanthracene
Remarks:
with metabolic activation
Positive controls:
yes
Positive control substance:
9-aminoacridine
sodium azide
other: 2-(2-Furyl)-3-(5-nitro-2-furyl)acrylamide
Remarks:
without metabolic activation
Details on test system and experimental conditions:
METHOD OF APPLICATION: in agar (plate incorporation)

DURATION
- Exposure duration: 48 h

NUMBER OF REPLICATIONS: 2

DETERMINATION OF CYTOTOXICITY
- Method: reduced bacterial growth
Evaluation criteria:
Although not given in the study report, according to OECD guideline 471 a test item is considered mutagenic if:
- a clear and dose-related increase in revertant number occurs
- a biologically relevant positive response for at least one dose group occurs: in TA 100 and E. coli uvrA number of revertants at least twice as high as in solvent control; TA 98, TA 1535, TA 1537 at least three times higher number of revertants as in solvent control

Results and discussion

Test results
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Vehicle controls validity:
valid
Positive controls validity:
valid
Additional information on results:
ADDITIONAL INFORMATION ON CYTOTOXICITY:
cytotoxic effects were observed in strains TA98, TA100, TA1535 and TA1537 at 5000 µg/plate without metabolic activation and in strains TA100 and TA1535 at 5000 µg/plate with metabolic activation
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

 

 

S9 mix

test item concentration [µg/plate]

mean number revertants/plate

TA100

TA1535

E. coli WP2uvrA-

TA98

TA1537

without

0

117

12

28

10

5

4.88

92

8

23

17

9

19.5

99

10

23

13

7

78.1

107

11

26

15

7

313

91

12

23

16

4

1250

109

10

20

17

5

5000

80*

8*

28

11*

5*

positive control

722

404

257

414

138

with

0

112

9

32

26

10

4.88

105

12

33

23

15

19.5

92

7

33

29

12

78.1

111

9

30

26

7

313

110

10

38

30

8

1250

124

7

34

24

10

5000

87*

11*

30

22

9

positive control

1341

256

1017

421

124

 

S9 mix

test item concentration [µg/plate]

mean number revertants/plate

TA100

TA1535

E. coli WP2uvrA-

TA98

TA1537

without

0

106

13

16

14

7

156

113

14

24

12

4

313

108

11

24

18

5

625

88

15

21

18

10

1250

110

13

20

12

7

2500

114

20

18

16

7

5000

65*

4*

18

10*

9*

positive control

679

454

188

520

195

with

0

112

10

26

26

12

156

109

5

28

21

11

313

99

8

28

29

10

625

104

7

30

26

11

1250

112

11

36

22

10

2500

110

12

33

21

12

5000

99*

10*

37

25

12

positive control

1311

276

981

426

132

 

* cytotoxic, reduced bacterial growth

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative

THFMA was not mutagenic in the bacterial reverse gene mutation assay when tested up to cytotoxic or limit concentrations (5000 µg/plate).
Executive summary:

In a reverse gene mutation assay in bacteria similar to OECD guideline 471, S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2 strains were exposed to THFMA in DMSO at concentrations of 0, 4.88, 19.5, 78.1, 313, 1250, 5000 µg/plate in the first experiment and 0, 156, 313, 625, 1250, 2500, 5000 µg/plate in the second experiment in the presence and absence of mammalian metabolic activation (S9 mix).  THFMA was tested up to limit concentrations (5000 µg/plate).

Cytotoxic effects (reduced bacterial growth) were observed in strains TA98, TA100, TA1535 and TA1537 at 5000 µg/plate without metabolic activation and in strains TA100 and TA1535 at 5000 µg/plate with metabolic activation.

There was no evidence of induced mutant colonies over background. 

THFMA was not mutagenic in this bacterial reverse gene mutation assay when tested up to cytotoxic or limit concentrations (5000 µg/plate).

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