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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: Acceptable, well documented NTP study, which meets general standards.

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Unnamed
Year:
1987
Reference Type:
publication
Title:
No information
Author:
NTP
Year:
1987
Bibliographic source:
NTP web page
Report Date:
1987

Materials and methods

Principles of method if other than guideline:
Testing was performed as reported by Mortelmans et al. (1986).
GLP compliance:
not specified
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): Diethylamine
- Analytical purity: 99 %

Method

Target gene:
Histidine operon
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:
rat and hamster S9-Mix (10% Aroclor 1254-induced)
Test concentrations with justification for top dose:
0, 33, 100, 333, 1000, 3333, 10000 µg/plate
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: water
Controls
Untreated negative controls:
yes
Remarks:
sterility control
Negative solvent / vehicle controls:
yes
Remarks:
water
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: without S9: Sodium azide (TA1535, TA100), 9-aminoacridine (TA1537), 4-nitro-o-phenylenediamine (TA98 ); with S9: 2-aminoanthracene
Details on test system and experimental conditions:
METHOD OF APPLICATION: preincubation

DURATION
- Preincubation period: 20 min
- Exposure duration: 2 days


NUMBER OF REPLICATIONS: Each trial consisted of triplicate plates and was done in a replicate.
Evaluation criteria:
Positive if a reproducible dose related response over the solvent control was obtained .

Results and discussion

Test results
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:
cytotoxicity
Remarks:
from 3333 µg/plate onwards in all strains tested
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'. Remarks: Salmonella typhimurium TA98, TA100, TA1535, TA1537

Any other information on results incl. tables

Strain: TA1535

Dose

No Activation
(Negative)

No Activation
(Negative)

10% HLI
(Negative)

10% HLI
(Negative)

10% RLI
(Negative)

10% RLI
(Negative)

ug/Plate

Mean ± SEM

Mean ± SEM

Mean ± SEM

Mean ± SEM

Mean ± SEM

Mean ± SEM

0     

31

0.7

37

6.4

42

3.6

14

2.3

41

5.5

23

3.8

33     

 

 

26

4

 

 

12

2.1

 

 

17

1.2

100     

22

2.1

25

0.9

47

1.2

13

0.7

40

6.1

12

1.8

333     

21

3.4

25

0.3

41

7.5

7

1.3

36

2.2

13

1.9

1000     

31

3.3

19

0.7

55

2.6

10

2.2

42

6.2

17

5.5

3333     

0s

0

20

4

30s

15.3

7

0.7

31

3.5

14

4.7

10000     

0s

0

 

 

0t

0

 

 

0s

0

 

 

Positive Control

443

29.1

399

18

645

25.2

563

28

331

13.7

266

33.5

 

Strain: TA100

Dose

No Activation
(Negative)

No Activation
(Negative)

10% HLI
(Negative)

10% HLI
(Negative)

10% RLI
(Negative)

10% RLI
(Negative)

ug/Plate

Mean ± SEM

Mean ± SEM

Mean ± SEM

Mean ± SEM

Mean ± SEM

Mean ± SEM

0     

108

3.2

101

8.7

134

8.3

117

10.4

116

7.8

95

1.5

33     

 

 

122

9.3

 

 

112

2.5

 

 

106

3

100     

158

14.7

109

3.7

160

9.1

119

4.7

152

4.3

111

3.3

333     

144

6.9

121

6.7

142

9

116

13.5

141

4.2

119

15.2

1000     

153

4.8

121

10.4

146

8

123

13.3

141

2.9

104

11.4

3333     

0s

0

111

8.4

104s

52.1

97

12.5

116

17.9

102

3.7

10000     

0t

0

 

 

t

 

 

 

0t

0

 

 

Positive Control

467

18

477

6.4

2355

34.5

1511

49.9

846

26.4

820

36.8

 

Strain: TA98

Dose

No Activation
(Negative)

No Activation
(Negative)

10% HLI
(Negative)

10% HLI
(Negative)

10% RLI
(Negative)

10% RLI
(Negative)

ug/Plate

Mean ± SEM

Mean ± SEM

Mean ± SEM

Mean ± SEM

Mean ± SEM

Mean ± SEM

0     

28

2.2

21

3.8

48

5.8

28

2.6

37

2.3

36

3.2

33     

 

 

20

2.3

 

 

23

2.4

 

 

31

4.9

100     

19

0.7

15

1.5

46

7

30

4.2

43

1.2

30

1.7

333     

16

1.5

17

2.3

52

0.7

24

2.6

34

4.7

31

5.2

1000     

15

0.6

20

2.1

57

2.6

22

2.7

37

6.1

35

4.1

3333     

1s

0.7

17

0.9

0s

0

23

1.5

43

4.2

26

0.3

10000     

0s

0.3

 

 

t

 

 

 

0s

0

 

 

Positive Control

758

14.2

722

8.2

1856

19.6

1102

66.6

436

5.1

591

44.4

 

Strain: TA1537

Dose

No Activation
(Negative)

No Activation
(Negative)

10% HLI
(Negative)

10% HLI
(Negative)

10% RLI
(Negative)

10% RLI
(Negative)

ug/Plate

Mean ± SEM

Mean ± SEM

Mean ± SEM

Mean ± SEM

Mean ± SEM

Mean ± SEM

0     

11

1.8

7

1.5

19

4.7

9

1.3

14

1.2

11

1

33     

 

 

7

1.2

 

 

6

1.5

 

 

9

0

100     

5

0.9

7

0.3

23

2.8

7

0.9

10

2.7

17

1.2

333     

7

2

9

1.5

27

1

5

0.6

13

2.9

13

3.5

1000     

6

0

10

1

21

6.7

10

2.1

13

0.7

15

1.8

3333     

0s

0

7

1.2

0s

0

5s

0.9

6

1.5

12

0.3

10000     

0s

0

 

 

t

 

 

 

0s

0

 

 

Positive Control

388

33.5

205

40.4

591

16.8

465

15.2

266

9.8

241

15.6

RLI = induced male Sprague Dawley rat liver S9
HLI = induced male Syrian hamster liver S9
s = Slight Toxicity; p = Precipitate; x = Slight Toxicity and Precipitate; T = Toxic; c = Contamination

Under the conditions tested, no mutagenic activity was observed in any strain/activation combination in the bacterial AMES-Test. The positive controls showed the expected values.

Applicant's summary and conclusion