3-[[3-(dimethylamino)propyl]amino]propiononitrile

Genetic toxicity: in vitro

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:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1982

Report date:

1982

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

3-[[3-(dimethylamino)propyl]amino]propiononitrile

EC Number:

274-159-1

EC Name:

3-[[3-(dimethylamino)propyl]amino]propiononitrile

Cas Number:

69852-45-5

Molecular formula:

C8H17N3

IUPAC Name:

3-{[3-(dimethylamino)propyl]amino}propanenitrile

impurity 1

Reference substance name:

3,3'-[[3-(dimethylamino)propyl]imino]bispropiononitrile

EC Number:

275-331-9

EC Name:

3,3'-[[3-(dimethylamino)propyl]imino]bispropiononitrile

Cas Number:

71326-27-7

Molecular formula:

C11H20N4

IUPAC Name:

3,3'-{[3-(dimethylamino)propyl]imino}dipropanenitrile

Test material form:

liquid

Remarks:

colorless

Specific details on test material used for the study:

Batch no. Zd 429-10A III

Method

Species / strain

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2

Metabolic activation:

with and without

Metabolic activation system:

Rat liver microsomes and co-factors

Test concentrations with justification for top dose:

5, 10, 50, 100, 500 ,1000 and 5000 µg/0.1 ml

Vehicle / solvent:

Twice distilled water

Controls

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

9-aminoacridine

2-nitrofluorene

N-ethyl-N-nitro-N-nitrosoguanidine

other: DMSO

Details on test system and experimental conditions:

METHOD OF APPLICATION: Minimum agar, plus salts and glucose.

The plates were incubated for about 48 hours at 37°C in darkness.

Evaluation criteria:

When the colonies had been counted, the arithmetic mean was calculated. The test substance is generally considered to be non-mutagenic if the colony count in relation to the negative control is not doubled at any concentration.

Results and discussion

Test results

Key result

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Positive controls validity:

valid

Any other information on results incl. tables

Material	Concentration of testing sample (µg / plate)	Presence of S9 Mix	Back Mutation                 Number of colunies/plate (mean)
			Base Conversion Type			Frame Shift Type
			TA100	TS1535	WP2UBrA	TA98	TA1537	TA1538
Vehicle Control		-	91	15	20	19	15	14
TK12271	5	-	87	18	20	28	14	18
	10	-	89	20	26	29	14	14
	50	-	95	23	15	27	9	12
	100	-	100	15	19	25	14	20
	500	-	86	15	21	20	13	14
	1000	-	83	15	20	25	15	14
	5000	-	88	15	19	25	12	14
Vehicle Control		+	78	11	16	46	8	33
TK12271	5	+	71	12	24	44	7	30
	10	+	76	10	21	42	5	29
	50	+	83	12	13	44	5	27
	100	+	78	12	17	46	12	26
	500	+	81	15	18	51	6	30
	1000	+	81	12	13	44	6	28
	5000	+	69	7	19	45	9	30

Applicant's summary and conclusion

Conclusions:

In the experiments performed without and with microsomal activation, comparison of the number of histidine- or tryptophan-prototrophic mutants in the controls and after treatment with TK 12271 revealed no marked differences.

Executive summary:

TK 12271 was tested for mutagenic effects on histidine-auxotrophic strains of Salmonella typhimirium and on a tryptophan-auxotrophic strain of E. coli. The investigations were performed with the following concentrations of the trial substance without and with microsomal activation: 5, 10, 50, 100, 500, 1000 and 5000 µg/0.1 ml.

These tests permit the detection of point mutations in bacteria induced by chemical substances. Any mutagenic effects of the substances are demonstrable on comparison of the number of bacteria in the treated and control cultures that have undergone back- mutation to histidine- or tryptophan- prototrophism. To ensure that mutagenic effects of metabolites of the test substance formed in mammals would also be detected, experiments were performed in which the cultures were additionally treated with an activation mixture (rat liver microsomes and co-factors).

In the experiments performed without and with microsomal activation, comparison of the number of back-mutant colonies in the controls and the cultures treated with the various concentrations of TK 12271 revealed no marked deviations.

No evidence of the induction of point mutations by TK 12271 or by the metabolites of the substance formed as a result of microsomal activation was detectable in the strains ofS. typhimuriumandE. coliused in these experiments.