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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:
2 Feb 1989-20 Feb 1989
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study with GLP, acceptable with restriction (analytical purity of the test substance not reported).

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report Date:
1989

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
other: Guidelines for bacterial mutagenicity testing published by the major Japanese Regulatory Authorities including MITI, MHW, MOL and MAFF.
Deviations:
no
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
no
GLP compliance:
yes
Remarks:
(Safepharm Laboratories Limited, UK)
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material: N-vinylcaprolactam

Method

Species / strainopen allclose all
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Species / strain / cell type:
E. coli WP2 uvr A
Metabolic activation:
with and without
Metabolic activation system:
Aroclor 1254 induced rat liver S-9 mix
Test concentrations with justification for top dose:
Experiment 1: 8, 40, 200, 1000 and 5000 µg/plate;
Experiment 2: 312.5, 625, 1250, 2500 and 5000 µg/plate
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: DMSO
Controlsopen allclose all
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: 2-Aminoanthracene for all strains
Remarks:
with S9
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
9-aminoacridine
Remarks:
without S9

Migrated to IUCLID6: 50 µg/plate for TA1537
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: N-Methyl-N-nitro-N-nitrosoguanidine, 2 µg/plate for TA1535 and TA100
Remarks:
without S9
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: 4-Nitro-O-phenylenediamine, 10 µg/plate for TA98
Remarks:
without S9
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
4-nitroquinoline-N-oxide
Remarks:
without S9

Migrated to IUCLID6: 3.3 µg/plate for WP2uvrA
Details on test system and experimental conditions:
METHOD OF APPLICATION: in agar (plate incorporation)


DURATION
- Exposure duration: 48 h at 37°C

NUMBER OF INDEPENDENT EXPERIMENTS: 2

NUMBER OF REPLICATIONS: 3

DETERMINATION OF CYTOTOXICITY
Plates were scored for revertant colonies and examined for a thinning of the background lawn
Evaluation criteria:
For a substance to be considered positive in this test system, it should have induced a dose-related and statistically significant increase in mutation rate (of at least twice the spontaneous reversion rate) in one or more strains of bacteria in the presence and/or absence of the S-9 microsomal enzymes in both experiments. To be considered negative the number of induced revertants compared to spontaneous revertants should be less than two fold at each dose level employed, the intervals of which should be between 2 and 5 fold and extend to the limits imposed by toxicity or solubility or up to the maximum recommended dose of 5000 µg/plate. In this case, the limiting factor was the maximum recommended dose.

Results and discussion

Test resultsopen allclose all
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Species / strain:
E. coli WP2 uvr A
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
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

 

             TA 98

          TA 100

         TA 1535

        TA 1537

        WP2uvrA

Dose (µg/ml)

-S9

+S9

-S9

+S9

-S9

+S9

-S9

+S9

-S9

+S9

0

18

31

75

94

11

15

4

11

24

25

8

16

22

70

92

10

11

7

9

19

22

40

20

18

84

92

15

12

6

9

28

26

200

14

27

73

95

15

12

5

10

25

26

1000

19

24

65

85

12

11

5

8

22

25

5000

14

17

68

91

9

13

4

8

26

35

Positive control

643

503

774

814

304

77

288

74

589

198

             TA 98

          TA 100

         TA 1535

        TA 1537

        WP2uvrA

Dose (µg/ml)

-S9

+S9

-S9

+S9

-S9

+S9

-S9

+S9

-S9

+S9

0

13

23

75

97

13

12

5

9

21

22

312.5

17

25

67

99

13

12

4

6

20

21

625

17

22

74

93

9

14

6

4

24

25

1250

13

36

73

96

12

9

7

5

26

29

2500

16

29

98

81

12

14

4

7

21

28

5000

15

25

89

89

12

14

6

3

24

35

Positive control

751

551

519

970

45

65

316

41

670

123

Applicant's summary and conclusion