N-[3-(methoxydimethylsilyl)propyl]ethylenediamine

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was conducted according to an appropriate OECD test guideline, and in compliance with GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2002

Report date:

2002

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Freie und Hansestadt Hamburg, Behörde für Arbeit, Gesundheit uns Soziales, Germany

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

N-[3-(methoxydimethylsilyl)propyl]ethylenediamine

EC Number:

221-337-1

EC Name:

N-[3-(methoxydimethylsilyl)propyl]ethylenediamine

Cas Number:

3069-33-8

Molecular formula:

C8H22N2OSi

IUPAC Name:

(2-aminoethyl)[3-(methoxydimethylsilyl)propyl]amine

Details on test material:

- Name of test material (as cited in study report): VP 50991
- Physical state: colourless liquid
- Stability under test conditions: > 1 day (4°C, in the dark) if vehicle is free of water
- Storage condition of test material: at room temperature, dry, tightly closed, dark

Method

Target gene:

his operon

Species / strain

Species / strain / cell type:

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

Metabolic activation:

with and without

Metabolic activation system:

cofactor supplemented post-mitochondrial fraction (S9 mix), prepared from the livers of rats treated with Aroclor 1254.

Test concentrations with justification for top dose:

plate incorporation test: 10, 31.6, 100, 316, 1000 µg/plate
preincubation test: 3.16, 10, 31.6, 100, 316 µg/plate

Vehicle / solvent:

DMSO

Controls

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

9-aminoacridine

2-nitrofluorene

sodium azide

cyclophosphamide

methylmethanesulfonate

other: 2-anthracene amide

Remarks:

+S9: CP (TA 100, TA 1535; 1500 µg/plate); 2-anthracene amide (TA 98, TA 102, TA 1537; 2 µg/plate); -S9: Sodium azide (TA 100, TA 1535; 10 µg/plate); MMS (TA 102; 1300 µg/plate); 2-NF (TA 98; 10 µg/plate); amino acridine (TA 1537; 100 µg/plate)

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation); preincubation

DURATION
- Preincubation period: 60 min (only in preincubation test)
- Exposure duration: 48 h

NUMBER OF REPLICATIONS: 2 independent experiments with 3 plates/concentration.

DETERMINATION OF CYTOTOXICITY
- Method: reduction in the number of colonies and/or scarce background lawn

Evaluation criteria:

Cytotoxicity: reduction of colonies by more than 50%
Mutagenicity:
No significant effects: number of colonies after treatment with test substance is less than 2-fold the number of colonies of the solvent control.
Significant effects:
- number of colonies after treatment with test substance is at least 2-fold (TA 98, TA 100, TA 102) or 3-fold (TA 1535, TA 1537) the number of colonies of the solvent control (with statistical significance),
- and a significant concentration-releated effect is observed,
- positive results were reproducible and histidine independence of the revertants was confirmed.

Statistics:

Number of revertants: U-test according to MANN and WHITNEY
Trend test: Spearman´s rank correlation coefficient

Results and discussion

Test results

Species / strain:

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

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Additional information on results:

TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation: no

RANGE-FINDING/SCREENING STUDIES: In the preliminary test cytotoxicity was observed from 1000 µg/plate onwards.

ADDITIONAL INFORMATION ON CYTOTOXICITY:
Plate incorporation test:
Without S9: Cytotoxicity was observed at 1000 µg/plate in all strains, from 100 µg/plate onwards in test strain TA 102 and at concentrations of 316 and 1000µg/plate in test strains TA 1535 and TA 1537.
With S9: Cytotoxicity was observed at 1000 µg/plate in all strains and at 316 and 1000 µg/plate in test strains TA 102 and TA 1537.
Preincubation test:
Without S9: Cytotoxicity was observed at 316 µg/plate in all strains, but in the test strains TA 98, TA 102 and TA 1535 it was noticed at 100 and 316 µg/plate.
With S9: Cytotoxicity was observed at 316 µg/plate in strains TA 102, TA 1537, and TA 1535.

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

Table 1: Test results of main test 1 (plate incorporation).

With or without S9-Mix	Test substance concentration	Mean number of revertant colonies per plate in the plate incorporation test
	(μg/plate)	(average of 3 plates±standard deviation)
		Base-pair substitution type			Frameshift type
		TA 100	TA1535	TA 102	TA98	TA1537
–	Solvent control	118.3±2.9	9.0±3.0	288.7±52.8	20.3±4.5	9.0±3.0
–	10	140.7±40.5	11.0±1.0	268.3±3.2	22.3±4.0	11.0±1.0
–	31.6	104.3±3.2	6.7±2.1	277.3±17.3	22.3±3.1	6.7±2.1
–	100	112.7±12.6	9.7±4.5	200.0±18.7#	20.7±0.6	9.7±4.5
–	316	122.3±2.5	15.3±5.5	207.7±56.5#	27.7±6.0	4.3±2.1
–	1000	96.3±11.0#	#	154.0±49.0#	#	1.0±1.0#
Positive controls, –S9	Name	sodium azide	sodium azide	methyl methane sulfonate (MMS)	2-nitrofluorene (2 -NF)	amino-acridine
	Concentrations (μg/plate)	10	10	1300	10	100
	Average of 3 plates±sd	1123.0±61.3	291.7±74.4	983±35	755.3±22.9	246.7±12.7
+	Solvent control	143.0±7.8	14.3±0.6	299.3±13.0	35.3±3.8	15.0±7.0
+	10	139.7±15.9	10.0±3.0	274.0±22.6	39.3±1.5	8.0±2.0
+	31.6	180.7±48.9	12.0±2.0	278.3±10.1	39.0±6.0	6.3±3.1
+	100	133.3±17.6	14.7±6.0	159.0±14.2	41.3±4.0	8.0±2.6
+	316	146.0±33.8	16.0±3.5	113.3±47.6#	27.0±7.9	9.0±1.7#
+	1000	110.7±35.2#	5.3±5.0#	#	5.7±1.5#	#
Positive controls, +S9	Name	cyclophosphamide (CP)	cyclophosphamide (CP)	2-anthracene amide	2-anthracene amide	2-anthracene amide
	Concentrations (μg/plate)	1500	1500	2	2	2
	Average of 3 plates±sd	413.3±27.3	240.0±27.6	1061.0±49.3	758.7±31.8	254.3±10

#: scarce background lawn

Table 2: Test results of main test 2 (preincubation test). 

With or without S9-Mix	Test substance concentration	Mean number of revertant colonies per plate in the preincubation test
	(μg/plate)	(average of 3 plates±standard deviation)
		Base-pair substitution type			Frameshift type
		TA 100	TA1535	TA 102	TA98	TA1537
–	Solvent control	110.3±8.4	12.3±6.4	259.0±32.5	24.0±3.6	9.0±2.6
–	316	42.0±22.9#	0#	0#	5.0±5.0#	1.0±1.7#
–	100	97.3±7.1	18.7±4.9#	90.7±39.3#	14.0±5.6#	5.0±1.7
–	31.6	96.7±6.0	15.7±3.2	228.0±52.9	22.3±3.8	5.7±1.5
–	10	103.0±6.1	19.0±5.3	258.7±13.7	27.0±7.8	5.7±1.5
–	3.16	94.7±112.9	20.0±2.6	270.3±8.3	24.3±6.0	8.7±2.3
Positive controls, –S9	Name	2-nitrofluorene (2 -NF)	sodium azide (2 -NF)	methylmethane sulfonate (MMS)	2-nitrofluorene	amino-acridine
	Concentrations (μg/plate)	10	10	1300	10	100
	Average of 3 plates±sd	683.7±48.0	237.0±17.3	1076.3±97.2	683.7±48.0	287.3±48.2
+	Solvent control	102.3±13.1	12.7±2.5	336.0±67.1	49.0±10.1	11.3±3.5
+	316	106.0±5.3	12.0±4.4#	0#	28.3±1.2	0.3±0.6#
+	100	104.7±30.6	14.3±2.5	272.3±7.6	37.0±1.7	8.3±3.8
+	31.6	118.3±21.7	11.7±3.8	273.3±48.7	38.3±3.5	9.3±2.1
+	10	104.3±16.0	14.3±3.8	343.3±20.4	40.3±2.1	6.0±1.7
+	3.16	90.3±5.5	19.7±3.8	331.3±42.0	40.0±6.1	8.7±1.5
Positive controls, +S9	Name	cyclophosphamide (CP)	cyclophosphamide (CP)	2-anthracene amide	2-anthracene amide	2-anthracene amide
	Concentrations (μg/plate)	1500	1500	2	2	2
	Average of 3 plates±sd	1092.0±53.7	318±45.4	1101.0±94.0	676.0±252.0	283.3±58.5

#: scarce background lawn

 

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative

N-[3-(methoxydimethylsilyl)propyl]ethylenediamine has been tested for mutagenicity in bacteria, in a study which was conducted according to OECD 471 and in compliance with GLP. No evidence of a test substance related increase in the number of revertants was observed with or without metabolic activation in the plate incorporation and preincubation experiment. It is concluded that the test substance is negative for mutagenicity to bacteria under the conditions of the test.