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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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
According to OECD 471 requirements, If 2-aminoanthracene is used, each batch of S9 should also be characterised with a mutagen that requires metabolic activation by microsomal enzymes, e.g., benzo(a)pyrene, dimethylbenzanthracene. Aminoanthracene was used as the sole indicator of the efficacy of the S9-mix. Considering the clear negative results at all dose levels in all strains, this is an acceptable deviation.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991

Materials and methods

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

Test material

Constituent 1
Chemical structure
Reference substance name:
Butane-1,2-diol
EC Number:
209-527-2
EC Name:
Butane-1,2-diol
Cas Number:
584-03-2
Molecular formula:
C4H10O2
IUPAC Name:
butane-1,2-diol

Method

Target gene:
"his operon" (for S. typhimurium strains) and "trp operon" (for E. coli strains)
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:
cofactor supplemented post-mitochondrial fraction (S9 mix), prepared from the livers of rats treated with phenobarbital and 5,6-benzoflavone.
Test concentrations with justification for top dose:
First experiment: 50, 150, 500, 1500 and 5000 µg/plate with and without metabolic activation
Second experiment: 312.5, 500, 625, 1250 and 5000 µg/plate with and without metabolic activation
Vehicle / solvent:
- Vehicle/solvent used: distilled water
- Justification for choice of solvent/vehicle: 1,2-Butanediol is stable in an aqueous solution.
- Vehicle positive controls: DMSO for AF2, 9-AA and 2-AA; distilled water for SA
Controlsopen allclose all
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: 2-(2-Furyl)-3-(5-nitro-2-furyl)acrylamide
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
sodium azide
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
9-aminoacridine
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: 2-aminoanthracene
Details on test system and experimental conditions:
METHOD OF APPLICATION: in agar (plate incorporation)

DURATION
- Exposure duration: 48h

NUMBER OF REPLICATIONS: 3 replications each in 2 independent experiments

DETERMINATION OF CYTOTOXICITY
- Method: Cytotoxicity is detected by a reduction in the number of revertant colonies
- Other: The dose-finding study was carried out once
Evaluation criteria:
The test material may be considered positive in this test system if the following criteria are met: For the test item to be considered mutagenic, two-fold (or more) increases in mean revertant numbers must be observed at two consecutive dose levels or at the highest practicable dose level only. In addition, there must be evidence of a dose-response relationship showing increasing numbers of mutant colonies with increasing dose levels.

Results and discussion

Test resultsopen allclose all
Key result
Species / strain:
S. typhimurium TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Key result
Species / strain:
S. typhimurium TA 1535
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Key result
Species / strain:
S. typhimurium TA 98
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Key result
Species / strain:
S. typhimurium TA 1537
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Key result
Species / strain:
E. coli WP2 uvr A
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid

Any other information on results incl. tables

EXPERIMENT 1 (1,2-Butanediol)

S9-Mix

Without

Test item (µg/plate)

TA 100

TA 1535

TA 98

TA 1537

E. coli WP2uvrA

NC

131 131 128

(130 ± 1.7)

14 15 19

(16 ± 2.6)

29 22 14

(22 ± 7.5)

6 8 12

(9 ± 3.1)

11 18 15

(15 ± 3.5)

312.5

134 144 124

(134 ± 10.0)

9 13 12

(11 ± 2.1)

28 25 24

(26 ± 2.1)

11 13 11

(12 ± 1.2)

16 15 10

(14 ± 3.2)

500

118 128 116

(121 ± 6.4)

13 15 12

(13 ± 1.5)

35 27 31

(31 ± 4.0)

10 6 7

(8 ± 2.1)

18 14 9

(14 ± 4.5)

625

140 147 124

(137 ± 11.8)

17 15 14

(15 ± 1.5)

23 30 28

(27 ± 3.6)

10 6 11

(9 ± 2.6)

14 13 15

(14 ± 1.0)

1250

119 123 109

(117 ± 7.2)

21 11 15

(16 ± 5.0)

19 33 28

(27 ± 7.1)

4 12 6

(7 ± 4.2)

9 12 17

(13 ± 4.0)

5000

112 135 129

(125 ± 11.9)

16 12 17

(15 ± 2.6)

27 25 25

(26 ± 1.2)

17 8 8

(11 ± 5.2)

19 17 20

(19 ± 1.5)

AF2

698 665 691

(685 ± 17.4)

-

605 582 576

(588 ± 15.3)

-

286 252 239

(259 ± 24.3)

SA

-

204 250 196

(217 ± 29.1)

-

-

-

9AA

-

-

-

2597 2208 2554

(2453 ± 213.3)

-

S9-Mix

With

 

 

 

 

 

 

Test item (µg/plate)

TA 100

TA 1535

TA 98

TA 1537

E. coli WP2uvrA

NC

117 131 132

(127 ± 8.4)

13 10 24

(16 ± 7.4)

29 42 39

(37 ± 6.8)

11 14 19

(15 ± 4.0)

16 13 21

(17 ± 4.0)

312.5

172 133 138

(148 ± 21.2)

22 16 16

(18 ± 3.5)

47 49 40

(45 ± 4.7)

12 13 10

(12 ± 1.5)

14 15 16

(15 ± 1.0)

500

125 119 116

(120 ± 4.6)

17 15 17

(16 ± 1.2)

39 53 36

(43 ± 9.1)

15 9 12

(12 ± 3.0)

21 14 15

(17 ± 3.8)

625

146 133 149

(143 ± 8.5)

14 12 13

(13 ± 1.0)

41 37 39

(39 ± 2.0)

10 18 8

(12 ± 5.3)

14 17 24

(18 ± 5.1)

1250

130 118 124

(124 ± 6.0)

16 21 18

(18 ± 2.5)

44 43 33

(40 ± 6.1)

13 8 8

(10 ± 2.9)

14 23 19

(19 ± 4.5)

5000

114 129 117

(120 ± 7.9)

13 18 14

(15 ± 2.6)

47 41 42

(43 ± 3.2)

14 8 14

(12 ± 3.5)

19 19 10

(16 ± 5.2)

2AA

844 834 855

(844 ± 10.5)

231 194 242

(222 ± 25.1)

329 353 323

(335 ± 15.9)

189 242 167

(199 ± 38.6)

520 573 553

(549 ± 26.8)

NC = Negative/Vehicle Control

Respective positive control substances (for details see method description)

*, p<0.05; **, p<0.01

EXPERIMENT 2 (1,2-Butanediol)

S9-Mix

Without

Test item (µg/plate)

TA 100

TA 1535

TA 98

TA 1537

E. coli WP2uvrA

NC

111 117 124

(117 ± 6.5)

18 12 14

(15 ± 3.1)

29 22 21

(24 ± 4.4)

15 8 11

(11 ± 3.5)

23 19 24

(22 ± 2.6)

312.5

129 147 135

(137 ± 9.2)

11 16 14

(14 ± 2.5)

25 26 26

(26 ± 0.6)

8 7 6

(7 ± 1.0)

24 23 22

(23 ± 1.0)

500

124 120 114

(119 ± 5.0)

11 15 13

(13 ± 2.0)

17 18 32

(22 ± 8.4)

8 12 8

(9 ± 2.3)

17 18 12

(16 ± 3.2)

625

129 121 131

(127 ± 5.3)

7 12 8

(9 ± 2.6)

24 31 15

(23 ± 8.0)

7 6 6

(6 ± 0.6)

13 17 16

(15 ± 2.1)

1250

158 137 141

(145 ± 11.2)

12 10 10

(11 ± 1.2)

25 25 19

(23 ± 3.5)

8 6 9

(8 ± 1.5)

19 20 14

(18 ± 3.2)

5000

149 134 153

(145 ± 10.0)

14 16 17

(16 ± 1.5)

33 18 31

(27 ± 8.1)

11 11 9

(10 ± 1.2)

24 17 18

(20 ± 3.8)

AF2

607 607 657

(624 ± 28.9)

-

447 503 435

(462 ± 36.3)

-

168 158 163

(163 ± 5.0)

SA

-

166 177 189

(177 ± 11.5)

-

-

-

9AA

-

-

-

2644 2447 2009

(2367 ± 325.0)

-

S9-Mix

With

 

 

 

 

 

 

Test item (µg/plate)

TA 100

TA 1535

TA 98

TA 1537

E. coli WP2uvrA

NC

128 135 128

(130 ± 4.0)

24 22 21

(22 ± 1.5)

38 54 49

(47 ± 8.2)

14 15 7

(12 ± 4.4)

22 24 19

(22 ± 2.5)

312.5

148 135 155

(146 ± 10.1)

14 17 16

(16 ± 1.5)

44 51 45

(47 ± 3.8)

6 13 9

(9 ± 3.5)

23 24 21

(23 ± 1.5)

500

144 142 140

(142 ± 2.0)

18 12 10

(13 ± 4.2)

42 40 43

(42 ± 1.5)

8 7 8

(8 ± 0.6)

17 14 17

(16 ± 1.7)

625

144 148 147

(146 ± 2.1)

15 10 5

(10 ± 5.0)

48 42 48

(46 ± 3.5)

4 10 9

(8 ± 3.2)

14 18 13

(15 ± 2.6)

1250

141 155 147

(148 ± 7.0)

15 8 14

(12 ± 3.8)

37 52 55

(48 ± 9.6)

9 10 10

(10 ± 0.6)

13 13 15

(14 ± 1.2)

5000

131 139 162

(144 ± 16.1)

11 11 18

(13 ± 4.0)

30 30 39

(33 ± 5.2)

7 10 14

(10 ± 3.5)

12 15 21

(16 ± 4.6)

2AA

931 863 922

(905 ± 36.9)

215 193 181

(196 ± 17.2)

286 278 268

(277 ± 9.0)

191 210 185

(195 ± 13.1)

547 571 554

(557 ± 12.3)

NC = Negative/Vehicle Control

Respective positive control substances (for details see method description)

*, p<0.05; **, p<0.01

Applicant's summary and conclusion

Conclusions:
Negative