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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: Comparable to guideline study with acceptable restriction (missing strain for crosslinking/oxidizing agents)

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Unnamed
Year:
1990
Reference Type:
publication
Title:
Comparative mutagenicity of aliphatic epoxides in Salmonella.
Author:
Canter DA, Zeiger E, Haworth S, Lawlor T, Mortelmans K, Speck W
Year:
1986
Bibliographic source:
Mutat. Res. 172: 105-138

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
yes
Remarks:
missing strain for crosslinking/oxidizing agents
GLP compliance:
no
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Allyl Glycidyl Ether
- Physical state: clear colorless liquid
- Analytical purity: 99 %

Method

Target gene:
his+
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:
S9 from Aroclor 1254-induced male Sprague-Dawley rat and Syrian hamster liver
Test concentrations with justification for top dose:
0, 100, 333, 1000, 3333, 10000 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 for all strains
Remarks:
with S9 mix
Negative solvent / vehicle controls:
yes
Positive controls:
yes
Positive control substance:
other: 4-nitro-o-phenylenediamine for TA98, sodium azide for TA100 and TA1535, and 9-aminoacridine for TA1537
Remarks:
without S9 mix
Details on test system and experimental conditions:
METHOD OF APPLICATION: preincubation

DURATION
- Preincubation period: 20 minutes

METABOLIC ACTIVATION:
The test was conducted with and without metabolic activation. In this study metabolic activation enzymes and cofactors from Aroclor 1254-induced male Sprague-Dawley rat and Syrian hamster liver were used.

REPEAT STUDY: One repeat was performed for TA 100 and TA 1535.
Evaluation criteria:
- A positive response was defined as a reproducible, dose-related increase in histidine-independent (revertant) colonies in any one strain/activation combination.
- An equivocal response was defined as an increase in revertants which was not dose related, not reproducible, or of insufficient magnitude to support a determination of mutagenicity.
- A response was considered negative when no increase in revertant colonies was observed after chemical treatment.

Results and discussion

Test resultsopen allclose all
Species / strain:
other: Salmonella typhimurium TA100, TA1535
Metabolic activation:
with and without
Genotoxicity:
positive
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
10000 µg/plate
Vehicle controls validity:
valid
Positive controls validity:
valid
Species / strain:
other: Salmonella typhimurium TA1537, TA98
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
10000 µg/plate in TA1537, from 3333 µg/plate in TA98 without S9
Vehicle controls validity:
valid
Positive controls validity:
valid
Additional information on results:
TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation: No precipitation was observed at any of the doses tested

Others: Mutagenic response was observed in every positive control tested. The solvent control did not induce any mutagenic response.
Remarks on result:
other:
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

Mean Revertants (±SE) from three plates

TA1535

Dose

No Activation
(Positive)

No Activation
(Positive)

10% HLI
(Positive)

10% HLI
(Positive)

10% RLI
(Positive)

10% RLI
(Positive)

Protocol

Preincubation

Preincubation

Preincubation

Preincubation

Preincubation

Preincubation

ug/Plate

Mean

± SEM

Mean

± SEM

Mean

± SEM

Mean

± SEM

Mean

± SEM

Mean

± SEM

0

23

3.8

26

2.7

10

1.8

10

1.5

18

1.2

13

2.3

100

63

10.2

54

5.4

9

1.2

17

2.2

13

0.6

17

3.5

333

125

10.3

166

1

27

3.8

42

5.2

19

7.2

29

2.1

1000

250

45.1

347

9

119

9.1

195

5.7

49

9.8

128

7.2

3333

759

20.2

783

22

444

27.8

516

12

442

43.6

495

12.2

10000

525s

84.6

1019s

26.4

454s

15.3

577s

11.9

521

33.2

406s

91.8

Positive Control

1373

108.5

1604

61.8

115

13.6

139

1.7

119

0.7

63

0.6

 

TA100

Dose

No Activation
(Positive)

No Activation
(Positive)

10% HLI
(Positive)

10% HLI
(Positive)

10% RLI
(Positive)

10% RLI
(Positive)

Protocol

Preincubation

Preincubation

Preincubation

Preincubation

Preincubation

Preincubation

ug/Plate

Mean

± SEM

Mean

± SEM

Mean

± SEM

Mean

± SEM

Mean

± SEM

Mean

± SEM

0

105

1.7

159

9

105

9.8

130

5.8

116

13.9

135

5.8

100

177

2.9

211

7.9

84

10.7

137

6.8

123

1.5

143

7.8

333

326

15.3

371

9

147

8.8

172

0.9

161

8.4

155

10.7

1000

904

198.3

814

30.5

329

14.3

399

5.8

382

13.6

417

10.5

3333

2178

119.4

2047

79.8

1382

21.7

1571

14.9

1478

50.1

1388

150.7

10000

3312s

135.3

3431s

15.9

3569

85.7

3705s

91.3

3726

133.3

3654s

63.6

Positive Control

2407

63.5

2397

25.7

2160

50.6

1491

37

1125

41.3

395

17.1

 

TA98

Dose

No Activation
(Negative)

10% HLI
(Negative)

10% RLI
(Negative)

Protocol

Preincubation

Preincubation

Preincubation

ug/Plate

Mean

± SEM

Mean

± SEM

Mean

± SEM

0

16

1.8

28

2.3

29

3.1

100

18

2.1

27

3.6

28

1.2

333

19

0.9

25

2.7

27

2

1000

18

1.2

26

1.5

31

5.5

3333

17s

1.2

25

5.8

29

2.6

10000

t

 

34

5.5

30

2.6

Positive Control

1579

37.9

970

40.2

874

39.3

 

TA1537

Dose

No Activation
(Negative)

10% HLI
(Negative)

10% RLI
(Negative)

Protocol

Preincubation

Preincubation

Preincubation

ug/Plate

Mean

± SEM

Mean

± SEM

Mean

± SEM

0

7

0.7

6

0

7

1

100

7

2.3

8

1.5

10

3.2

333

8

2.6

8

1

7

2.1

1000

8

1.3

11

2.2

4

1.5

3333

9

1.7

7

0.6

5s

1

10000

5s

1.2

11

0.9

10s

2.4

Positive Control

346

115

76

20.7

114

13.2

 

RLI = induced male Sprague Dawley rat liver S9
HLI = induced male Syrian hamster liver S9
s = Slight Toxicity; t = Toxic

Applicant's summary and conclusion