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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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Preguideline study. Similar to GLP guideline study. Purity of TS not reported; not tested in TA102 or E.coli WP2.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1979
Report Date:
1979

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
no
Principles of method if other than guideline:
adopted 1983
GLP compliance:
yes
Remarks:
(Litton Bionetics, Inc.; quality control comparable to GLP)
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Methyl vinyl ether (MVE)
no information on
purity reported

Method

Target gene:
His-
Species / strain
Species / strain / cell type:
S. typhimurium, other: TA98, TA100, TA1535, TA1537, TA1538
Metabolic activation:
with and without
Metabolic activation system:
S9-mix; S-9 fraction from Arochlor 1254-induced male Sprague-Dawley rat liver was used
Test concentrations with justification for top dose:
vapour concentration:
0, 1, 5, 10, 25% 1st trial
0, 0.5, 1, 2.5, 5, 10% 2nd trial
Vehicle / solvent:
no vehicle, exposure to vapour
Controls
Untreated negative controls:
yes
Remarks:
(no solvent used; exposure to vapour)
Positive controls:
yes
Positive control substance:
other: Without metabolic activation: sodium azide (1 µg/plate; TA1535, TA100); 2-nitrofluorene (10 µg/plate TA1538, TA98); 9-aminoacridine (50 µg/plate; TA1537); With metabolic activation: 2-anthramine (2.5 µg/plate for all strains)
Details on test system and experimental conditions:
Standard plate test with and without metabolic activation using a gas-tight incubation chamber. Tests were run in duplicate. Plates with the test organisms were placed into a gas-tight incubation chamber. A flowmeter was used to introduce known amounts of gas from yielding atmosphere MVE concentrations of 0.5 to 25%. The chamber containing the plates was incubated at 37°C for 2 days.
Second trial with TA98, TA100 and TA1535
Evaluation criteria:
Strains TA-1535, TA-1537 and TA-1538
If the solvent control value is within the normal range, a test material that produces a positive dose response over three concentrations with the highest increase equal to three times the solvent control value will be considered to be mutagenic.
Strains TA-98 and TA-100
If the solvent control value is within the normal range, a test material that produces a positive dose response over three concentrations with the highest increase equal to twice the solvent control value for TA-98 and TA-100 will be considered to be mutagenic.
Reproducibility.
Statistics:
no

Results and discussion

Test results
Species / strain:
S. typhimurium, other: TA1535 TA1537 TA1538 TA98 TA100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
(at a vapour concentration of 25%)
Untreated negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
MVE did not increase the number of revertants in any tester strain at 1, 5, 10, or 25% with or without metabolic activation. The substance was cytotoxic at 25% with all strains; in TA98 and TA1535 also at 10% vapour concentration in the 2nd trial. Negative and positive control plates gave results as expected. Repeat tests with and without activation with test strains TA 1535 and TA100 at concentrations of 0.5, 1, 2, 5, and 10% were also negative. TA98 was also included in this series because of unacceptable control values and gave equally negative results.
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

Revertants in the Ames test after exposure to MVE vapour

Vapour concentration

TA1535

TA1537

TA1538

TA98

TA100

Plate1

Plate2

Plate1

Plate2

Plate1

Plate2

Plate1

Plate2

Plate1

Plate2

Without metabolic activation, 1st trial

Neg. control

20

16

11

7

21

17

130

151

274

249

Pos. control

1045

939

279

422

929

1137

602

1289

1186

1149

1%

19

29

4

3

5

14

109

93

229

C

5%

13

9

6

6

8

11

82

100

205

265

10%

14

18

9

4

8

7

94

95

211

217

25%

0

0

0

0

0

0

0

0

0

0

With metabolic activation, 1st trial

Neg. control

5

10

18

20

18

21

123

121

257

268

Pos. control

468

434

360

478

1918

2084

2174

1161

2170

2220

1%

3

7

5

11

12

16

109

148

C

C

5%

12

11

10

9

12

15

119

C

252

C

10%

5

9

7

6

12

14

94

114

249

C

25%

1

0

0

0

1

1

0

0

0

0

Without metabolic activation, 2nd  trial

Neg. control

10

14

No data

No data

28

27

162

154

Pos. control

829

944

954

922

938

977

0.5%

15

9

Nd

Nd

150

170

1%

13

10

22

30

189

177

2.5%

9

14

Nd

Nd

189

209

5%

3

9

10

11

216

192

10%

0

0

5

6

104

98

With metabolic activation, 2nd  trial

Neg. control

16

10

34

23

199

179

Pos. control

379

382

1273

1075

991

902

0.5%

16

21

Nd

Nd

275

200

1%

20

11

31

21

183

206

2%

9

8

Nd

Nd

290

296

5%

9

12

16

19

234

251

10%

0

0

2

4

45

87

C: contaminated; Nd: no data

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative

Methyl vinyl ether was not mutagenic in S. typhimurium TA98, TA100, TA1535, TA1537, TA1538 in the presence or absence of metabolic activation
at vapour concentrations from 0.5 to 25%. Atmospheres containing
25% of the test substance were cytotoxic.