N-[3-(trimethoxysilyl)propyl]butylamine

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:

1989

Report date:

1989

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Version / remarks:

(1997)

Deviations:

yes

Remarks:

(no strain was included for detection of oxidising or cross-linking substances)

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

N-[3-(trimethoxysilyl)propyl]butylamine

EC Number:

250-437-8

EC Name:

N-[3-(trimethoxysilyl)propyl]butylamine

Cas Number:

31024-56-3

Molecular formula:

C10H25NO3Si

IUPAC Name:

butyl[3-(trimethoxysilyl)propyl]amine

Details on test material:

- Name of test material (as cited in study report): BRD 1155; 07651 J8 003
- Substance type: alkoxysilane
- Physical state: liquid
- Lot/batch No.: 1
- Storage condition of test material: at 4°C, in the dark under dry conditions

Method

Target gene:

his 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:

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

Test concentrations with justification for top dose:

0.05-5 mg/plate

Vehicle / solvent:

- Solvent: ethanol

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: +S9: 2-anthramine (TA 98, TA 100, TA 1535, TA 1537, TA 1538); -S9: 2-nitrofluorene (TA98); methyl methanesulfonate (TA 100); ethyl methanesulfonate (TA 1535); 9-aminoacridine (TA 1537); 2-nitrofluorene (TA 1538)

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation)

DURATION
- Exposure duration: 48 h

NUMBER OF REPLICATIONS: 3


DETERMINATION OF CYTOTOXICITY
- Cytotoxicity was determined in a preliminary study using strain TA 98 and also within the main study cytotoxicity was determined. No further information was given about the method applied.


POSITIVE CONTROLS:
+S9: 2-anthramine (TA 98, TA 100, TA 1535, TA 1537, TA 1538: 0.002 mg/plate)
-S9: 2-nitrofluorene (TA98: 0.001 mg/plate); methyl methanesulfonate (TA 100: 0.1 mg/plate); ethyl methanesulfonate (TA 1535: 10 mg/plate); 9-aminoacridine (TA 1537: 0.05 mg/plate); 2-nitrofluorene (TA 1538: 0.001 mg/plate)

Evaluation criteria:

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 the number of colonies of the solvent control.

Results and discussion

Test results

Species / strain:

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

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

-S9: TA 98, TA 1535 (5 mg/plate), TA 100, TA 1537, TA 1538 (1 and 5 mg/plate); +S9: TA 1537 (5 mg/plate)

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Additional information on results:

RANGE-FINDING/SCREENING STUDIES:
In a preliminary study the test substance was applied to bacteria (TA 98) from 0.5 to 100 mg/plate. Cytotoxicity was observed from 5 mg/plate upwards.

Any other information on results incl. tables

Table 1: Test results of experiment 1.

With or without S9-Mix	Test substance concentration	Mean number of revertant colonies per plate
	(μg/plate)	(average of 3 plates ± Standard deviation)
		TA 98	TA 100	TA1535	TA1537	TA1538
–	0	28±4	83±4	9±3	5±1	22±1
–	50	25±1	91±5	9±4	4±1	26±1
–	100	26±8	90±11	6±2	5±0	23±4
–	500	21±5	101±9	7±0	6±2	19±5
–	1000	21±2	78±6	11±4	8±5	26±4
–	5000	T	53±8	5±1	T	5±2
Positive controls, –S9	Name	2-NF	MMS	EMS	9-AA	2-NF
	Concentrations (μg/plate)	1	100	10000	50	1
	Mean No. of colonies/plate (average of 3)	472	299	1035	131	248
+	0	39±4	112±12	13±5	5±2	34±9
+	50	35±5	107±2	8±2	7±4	40±4
+	100	36±5	107±20	8±2	5±2	35±13
+	500	37±1	108±6	12±3	7±2	33±3
+	1000	34±7	102±8	10±3	4	33±8
+	5000	36±3	111±4	9±4	4±2	38±7
Positive controls, +S9	Name	2-A	2-A	2-A	2-A	2-A
	Concentrations (μg/plate)	2	2	2	2	2
	Mean No. of colonies/plate (average of 3)	554	1528	239	63	298

Table 2: Test results of experiment 2.

With or without S9-Mix	Test substance concentration	Mean number of revertant colonies per plate
	(μg/plate)	(average of 3 plates ± Standard deviation)
		TA 98	TA 100	TA1535	TA1537	TA1538
–	0	28±5	78±7	7±2	6±2	32±6
–	50	28±3	81±16	7±3	5±2	32±4
–	100	29±2	73±17	7±3	4±1	30±3
–	500	27±6	73±8	7±3	5±1	25±3
–	1000	28±6	T	5±3	2±1	7±6
–	5000	T	T	7±1	T	T
Positive controls, –S9	Name	2-NF	MMS	EMS	9-AA	2-NF
	Concentrations (μg/plate)	1	100	10000	50	1
	Mean No. of colonies/plate (average of 3)	573	270	835	116	548
+	0	43±10	118±4	9±5	6±1	38±3
+	50	41±5	107±13	11±2	5±3	47±11
+	100	43±2	101±14	8±2	5±1	38±10
+	500	44±14	101±11	9±5	5±3	42±9
+	1000	46±11	98±17	9±1	6±2	49±4
+	5000	43±8	109±5	11±2	6±1	41±12
Positive controls, +S9	Name	2-A	2-A	2-A	2-A	2-A
	Concentrations (μg/plate)	2	2	2	2	2
	Mean No. of colonies/plate (average of 3)	673	1337	185	35	579

 

MMS = methyl methanesulfonate

EMS = ethyl methanesulfonate

9AA = 9-aminoacridine

2-A = 2-anthramine

T = cytotoxic

Applicant's summary and conclusion

Conclusions:

Interpretation of results: negative

In a bacterial mutagenicity assay similar to OECD 471 and GLP, no mutagenic effect was observed for the test substance tested up to the top dose of 5000 µg/plate in any of the test strains in two independent experiments without and with metabolic activation. The test substance is non-mutagenic under the applied conditions.