1-methylpiperazine

Genetic toxicity: in vitro

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:

11. May 1997 - 01. Jul 1997

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline Study (OECD 471/472)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1997

Report date:

1997

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Version / remarks:

; OECD Guideline 472 (Genetic Toxicology: Escherichia coli, Reverse Mutation Assay)

Deviations:

no

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

1-methylpiperazine

EC Number:

203-639-5

EC Name:

1-methylpiperazine

Cas Number:

109-01-3

Molecular formula:

C5H12N2

IUPAC Name:

1-methylpiperazine

Details on test material:

- Name of test material (as cited in study report): N-Methylpiperazin
- Physical state: colorless liquid
- Analytical purity: 99.8 %
- Lot/batch No.: 25-0388
- Storage condition of test material: Room temperature (N2 conditions).

Method

Target gene:

Histidin operon

Species / strain

Species / strain 1

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Species / strain 2

Species / strain / cell type:

E. coli WP2 uvr A

Metabolic activation:

with and without

Metabolic activation system:

S9-mix from Aroclor 1254 treated male Sprague-Dawley rats.

Test concentrations with justification for top dose:

0, 20, 100, 500, 2500 and 5000 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: with S-9 mix: all strains 2-aminoanthracene; without S-9 mix: strains TA100, TA1535: N-methyl-N'-nitro-N-nitrosoguanidine; TA98: 4-nitro-o-phenylendiamine; TA1537: 9-aminoacridine; E.coli WP2 uvrA: N-ethyl-N'-nitro-N-nitrosoguanidine.

Details on test system and experimental conditions:

METHOD OF APPLICATION: preincubation

DURATION
- Preincubation period: 20 min
- Exposure duration: 48 - 72 h


NUMBER OF REPLICATIONS: 3

METHOD OF APPLICATION: standard plate test

DURATION
- Exposure duration: 48 - 72 h


NUMBER OF REPLICATIONS: 3

Evaluation criteria:

The test chemical is considered positive in this assay if the following criteria are met: A dose-related and reproducible increase in the number of revertant colonies, i.e. about doubling of the spontaneous mutation rate in at least one tester strain either without S-9 mix or after adding a metabolizing system.
A test substance is generally considered non-mutagenic in this test if: The number of revertants for all tester strains were within the historical negative control range under all experimental conditions in two experiments carried out independently of each other.

Results and discussion

Test results

Test results 1

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

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 2

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:

valid

Positive controls validity:

valid

Additional information on results:

TEST-SPECIFIC CONFOUNDING FACTORS
- Water solubility: Complete solubility of test substance in aqua dest.

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

Standart plate test:

Dose (µg/plate)

TA1535

TA100

TA1537

TA98

E. coli WP2 uvrA

-S9

+S9

-S9

+S9

-S9

+S9

-S9

+S9

-S9

+S9

0

20±2

20±1

153±17

158±9

13±4

12±3

31±3

45±3

37±7

36±5

20

18±1

17±1

147±12

161±9

13±2

12±2

34±3

42±1

31±1

26±3

100

17±1

16±1

163±5

157±12

11±1

16±2

32±2

37±2

34±4

30±2

500

14±3

20±1

153±7

157±16

11±2

14±2

34±3

38±6

34±3

32±3

2500

15±2

17±2

152±14

156±5

13±4

14±2

32±3

42±3

28±3

31±3

5000

14±2

17±3

154±6

163±5

11±2

12±1

33±2

40±2

29±1

34±7

2-AA

-

149±7

-

1474±62

-

179±2

-

1237±32

-

317±37

MNNG

955±36

-

858±42

-

-

-

-

-

-

-

AAC

-

-

-

-

750±6

-

-

-

-

-

NPD

-

-

-

-

-

-

1104±77

-

-

-

ENNG

-

-

-

-

-

-

-

-

1185±189

-

Mean ± SD

Preincubation-test:

Dose (µg/plate)

TA1535

TA100

TA1537

TA98

E. coli WP2 uvrA

-S9

+S9

-S9

+S9

-S9

+S9

-S9

+S9

-S9

+S9

0

20±2

20±2

129±2

124±19

11±2

11±2

30±1

41±3

29±1

35±3

20

21±3

17±1

146±16

151±21

8±2

10±1

26±7

39±6

25±3

29±4

100

17±1

17±2

143±11

195±18

10±1

10±1

25±3

41±6

25±6

30±4

500

17±3

18±1

150±20

153±7

9±1

9±1

21±1

30±10

26±3

32±3

2500

17±1

16±2

158±13

176±25

8±2

9±1

23±4

41±1

24±2

28±3

5000

12±1

14±3

130±4

173±25

7±2

7±2

20±1

35±6

19±8

33±3

2-AA

-

154±22

-

805±107

-

148±10

-

1173±41

-

242±8

MNNG

981±45

-

1232±70

-

971±34

-

-

-

-

-

AAC

-

-

-

-

-

-

-

-

-

-

NPD

-

-

-

-

-

-

1228±98

-

-

-

ENNG

-

-

-

-

-

-

-

-

875±45

-

Mean ± SD

2-AA: 2-aminoanthracene;

MNNG; N-methyl-N-nitro-N-nitrosoguanidine

ENNG; N-ethyl-N-nitro-N-nitrosoguanidine

NPD: 4-nitro-o-phenylendiamine

AAC: 9-aminoacridine chloride monohydrate

Under the conditions tested Diethylaminopropylamin is non mutagenic in the bacterial AMES-test with or without metabolic activation.

The positive control gave the expected values.