N'-(3-aminopropyl)-N,N-dimethylpropane-1,3-diamine

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:

date report 1993-08-19

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP, OECD N°471 (1983 May 26th and draft proposal of 1991)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1993

Report date:

1993

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial 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:

N'-(3-aminopropyl)-N,N-dimethylpropane-1,3-diamine

EC Number:

234-148-4

EC Name:

N'-(3-aminopropyl)-N,N-dimethylpropane-1,3-diamine

Cas Number:

10563-29-8

Molecular formula:

C8H21N3

IUPAC Name:

{3-[(3-aminopropyl)amino]propyl}dimethylamine

Details on test material:

- Name of test material (as cited in study report): Dimethyldipropylenetriamine
- Physical state: liquid
- Analytical purity: 99.10%
- Purity test date: 1993-02-01
- Lot/batch No.: P9011
- Expiration date of the lot/batch: no data
- Stability under test conditions: no data
- Storage condition of test material: at room temperature
- Other: analysis sheet number: 9301P0355

Method

Target gene:

Histidine

Species / strain

Species / strain / cell type:

S. typhimurium, other: TA 1535, TA 1537, TA 98, TA 100 and TA 102

Metabolic activation:

with and without

Metabolic activation system:

S9 Mix

Test concentrations with justification for top dose:

1st test: 156.25, 312.5, 625, 1250, 2500µg/plate
2nd test: 125, 250, 500, 1000, 2000µg/plate

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: water
- Justification for choice of solvent/vehicle: no data

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: -S9: TA1538 TA100 (sodium azide 1µg/plate); -S9: TA1537 (9-aminoacridine 50µg/plate); -S9: TA98 (2-nitrofluorene 0.5µg/plate); -S9: TA102 (mitomycin C 0.5µg/plate); +S9: TA1535 TA1537 TA98 TA100 (2-anthramine 2µg/plate); +S9: TA102 (danthron 30µg/plate)

Details on test system and experimental conditions:

METHOD OF APPLICATION: plate incorporation; preincubation

Direct incorporation method:
The test substance solution, 0.5mL S9mix (when required) and 0.1mL strain are added to 2mL agar containing traces of histidine and biotin at 45°C.
For the preincubation method:
The test substance solution, 0.5mL S9mix (when required) and 0.1mL strain are incubated for 60min at 37°C prior adding the overlay agar.
After 48 and 78 hours of incubation at 37°C, revertants are scored with an automatic counter (Artek counter, model 880, O.S.I, 750185 Paris, France)

DETERMINATION OF CYTOTOXICITY
- Method: relative total growth; number of revertants

Evaluation criteria:

The following criteria were used as an aid for determining a positive response:
a reproductible and significant dose relationship using a linear regression analysis, considered as significant if p<0.05 ( for n=18 values, the correlation coefficient must be r>0.47)
and
a reproductible and significant increase (i.e. a doubling in the number of revertants and/or solvent controls) for a least one of the tested strains when compared to that of the negative and/or solvent controls) for at least one of the tested concentrations.

Results and discussion

Test results

Species / strain:

S. typhimurium, other: TA 1535, TA 1537, TA 98, TA 100 and TA 102

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

high doses (2500µg/plate)

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative

DIMETHYLDIPROPYLENETRIAMINE did not show mutagenic activity in the Ames test.

Executive summary:

The potential of Dimethyldipropylenetriamine (DMAPAPA) to induce reverse mutation in bacteria Salmonella typhimurium was evaluated during an Ames test according to the 471 OECD guideline. Two experiments have been realized, according to two methods:

. the direct plate incorporation method: both experiments without S9 mix, first experiment with S9 mix.

. the preincubation method (1 hour, 37°C): second experiment with S9 mix.

Five strains of bacteria Salmonella typhimurium: TA 1535, TA 1537, TA 98, TA 100 and TA 102 were used.

The concentrations tested were:

. in the first test: 156.25, 312.5, 625, 1250 and 2500 µg/plate,

. in the second test: 125, 250, 500, 1000 and 2000 µg/plate, 2500 µg/plate being the concentration which showed moderate toxicity and being the limit of solubility in the molten agar.

The negative and solvent control results were equivalent to historical controls. The number of revertants induced by the positive controls was statistically higher than the controls, indicating the sensitivity of the test system.

The test substance DMAPAPA did not induce any significant increase in the number of revertants, with or without S9 mix, in any of the 5 strains. In conclusion, DIMETHYLDIPROPYLENETRIAMINE did not show mutagenic activity in the Ames test.