Pentamethylenediamine

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1988

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Read-across

GLP compliance:

no

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

3-aminopropyldimethylamine

EC Number:

203-680-9

EC Name:

3-aminopropyldimethylamine

Cas Number:

109-55-7

Molecular formula:

C5H14N2

IUPAC Name:

N,N-Dimethyl-1,3-diaminopropane

Details on test material:

- Name of test material (as cited in study report): N,N-dimethylpropane-1,3-diamine
- Molecular formula (if other than submission substance): C5H14N2
- Molecular weight (if other than submission substance): 102.1781
- Smiles notation (if other than submission substance): CN(C)CCCN
- InChl (if other than submission substance): InChI=1/C5H14N2/c1-7(2)5-3-4-6/h3-6H2,1-2H3
- Structural formula attached as image file (if other than submission substance): see Fig.2
- Substance type: organic
- Physical state: liquid

Method

Target gene:

Histidine 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:

S. typhimurium TA 1538

Metabolic activation:

with and without

Metabolic activation system:

S9 from Aroclor 1254-induced rat liver (10%)

Test concentrations with justification for top dose:

Bacterial toxicity: 100, 250, 500, 750 µg/plate (TA98) and 500, 1000, 5000, 10000 µg/plate (TA100)
Genotoxicity: 0, 50, 100, 250, 500, 750 µg/plate

Vehicle / solvent:

water

Controls

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 1342 -S9 : Na azide: 5 pg/plate (TA 100, TA1535), 2-nitrofluorene: 5 pg/plate (TA98, TA 1538), 9-aminoacridine: 100 pg/plate (TA 1537). + S9: 2-aminoanthracene: 5 pg/plate

Details on test system and experimental conditions:

DETERMINATION OF CYTOTOXICITY (preliminary range-finding test)
- Test: in TA 98 and TA 100 strains, with or without S9 mix ; 4 dose-levels (three plates/dose level)
- Method: relative total growth (decrease in the number of revertant colonies and/or a thinning of the bacterial lawn);

METHOD OF APPLICATION:
- Preincubation
DURATION
- Preincubation period: 60 min
- Exposure duration: 48H
NUMBER OF REPLICATIONS: triplicates

Evaluation criteria:

Reproducible increase in the number of revertant colonies compared with vehicle controls in any strain at any dose-level and/or evidence of a dose-relationship. Reference to historical data and consideration to biological relevance may also be taken into account.

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:

cytotoxicity

Remarks:

As seen in the preliminary tests, cytotoxicity was observed for the highest doses (500 µg/plate and above) with and without metabolic activation in all strains.

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Test results 2

Species / strain:

S. typhimurium TA 1538

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

As seen in the preliminary tests, cytotoxicity was observed for the highest doses (500 µg/plate and above) with and without metabolic activation in all strains.

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

Mean results:

		Without metabolic activation			With metabolic activation
Strain	Doses (µg/plate)	mean	SD	ratio	mean	SD	ratio
TA 98	0	26	3	1,00	21,7	1,76	1,00
	50	19	1,53	0,73	26,7	3,18	1,23
	100	26	4,51	1,00	33,7	4,41	1,55
	250	20,7	3,018	0,80	24	2,65	1,11
	500	23	5,13	0,88	26,7	2,73	1,23
	750	12,3	3,71	0,47	26,3	1,45	1,21
	Positive control	827,5	8,5	31,83	2178,5	392,5	100,39
TA 100	0	151	10,58	1,00	134,5	12,5	1,00
	50	160	4,73	1,06	151,3	4,63	1,12
	100	151,7	3,93	1,00	152,3	8,97	1,13
	250	0		0,00	0		0,00
	500	112,5	45,5	0,75	157,7	7,54	1,17
	750	0		0,00	0		0,00
	Positive control	614	32	4,07	1508	23	11,21
TA 1535	0	11,7	1,76	1,00	12,7	1,2	1,00
	50	13,3	0,88	1,14	11	0,58	0,87
	100	16,3	0,88	1,39	10,3	1,86	0,81
	250	10,3	2,4	0,88	13,3	0,67	1,05
	500	8	0,58	0,68	12,7	2,03	1,00
	750	3,3	1,67	0,28	11,7	2,33	0,92
	Positive control	971	54	82,99	286	32	22,52
TA 1537	0	6,7	1,2	1,00	7	1,15	1,00
	50	9,7	2,91	1,45	4,3	0,33	0,61
	100	7	0,58	1,04	8,7	1,45	1,24
	250	0		0,00	0		0,00
	500	3,3	0,33	0,49	7	0,58	1,00
	750	2,7	0,88	0,40	6,3	1,33	0,90
	Positive control	931	39	138,96	358,5	5,5	51,21
TA 1538	0	7	1	1,00	12,7	2,03	1,00
	50	5	0,58	0,71	10,3	1,45	0,81
	100	8,3	0,33	1,19	11,3	2,33	0,89
	250	6,7	1,67	0,96	14	2,52	1,10
	500	5	1	0,71	10,7	2,73	0,84
	750	4,7	1,2	0,67	12	2	0,94
	Positive control	702,5	19,5	100,36	1257,5	63,5	99,02

No noteworthy increase in the number of revertants was observed for all doses with and without metabolic activation on the 5 tested strains.

Under the experimental conditions, DMAPA did not show any mutagenic activity in the bacterial reverse mutation test with Salmonella typhimurium. The positive controls gave the expected values.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative