1,3,5-tris[3-(trimethoxysilyl)propyl]-1,3,5-triazine-2,4,6(1H,3H,5H)-trione

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1996-08-13 to 1996-09-24

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Report date:

1996

Materials and methods

Test guideline

Qualifier:

equivalent or similar 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:

1,3,5-tris[3-(trimethoxysilyl)propyl]-1,3,5-triazine-2,4,6(1H,3H,5H)-trione

EC Number:

247-465-8

EC Name:

1,3,5-tris[3-(trimethoxysilyl)propyl]-1,3,5-triazine-2,4,6(1H,3H,5H)-trione

Cas Number:

26115-70-8

Molecular formula:

C21H45N3O12Si3

IUPAC Name:

tris[3-(trimethoxysilyl)propyl]-1,3,5-triazinane-2,4,6-trione

Method

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:

E. coli WP2 uvr A

Metabolic activation:

with and without

Metabolic activation system:

Aroclor induced rat liver S9

Test concentrations with justification for top dose:

Pre-test: 6.7, 10, 33, 67, 100, 333, 667, 1000, 3333, 5000, with and without metabolic activation
Experiment 1: 100, 333, 1000, 3333, 5000, with and without metabolic activation
Experiment 2: 33, 100, 333, 1000, 5000, with and without metabolic activation

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: DMSO

- Justification for choice of solvent/vehicle: Sponsor indicated that the test article is stable in DMSO

Controls

Controls 1

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 2-aminoanthracene

Remarks:

All salmonella strains (with activation)

Controls 2

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

2-nitrofluorene

Remarks:

TA 98 (without activation)

Controls 3

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

sodium azide

Remarks:

TA 100, TA 1535 (without activation)

Controls 4

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

9-aminoacridine

Remarks:

TA 1537 (without activation)

Controls 5

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

methylmethanesulfonate

Remarks:

WP2 uvrA (without activation)

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar ; preincubation


DURATION
- Preincubation period: 60 minutes

- Expression time (cells in growth medium): 48 - 72 hours

NUMBER OF REPLICATIONS: 3 plates for each test concentration

DETERMINATION OF CYTOTOXICITY
- Method: Background lawn assessment, revertant colony counts

Evaluation criteria:

For a test substance to be considered positive, it must cause at least a doubling in the mean revertants per plate of at least one tester strain with a minimum of two increasing concentrations of test article.

A result is positive if the number of revertants is significantly increased compared with the solvent control to at least 2-fold of the solvent control for TA 98, TA 100 and WP2 uvrA and 3-fold of the solvent control for TA 1535 and TA 1537.

Cytotoxicity is defined as a reduction in the number of colonies by >50% compared with the solvent control and/or at least a moderate reduction in
the background lawn (background code 3,4 or 5).

Results and discussion

Test results

Test results 1

Key result

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Test results 2

Key result

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Test results 3

Key result

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Test results 4

Key result

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Test results 5

Key result

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

3333 - 5000 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Test results 6

Key result

Species / strain:

E. coli WP2 uvr A

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Additional information on results:

TEST-SPECIFIC CONFOUNDING FACTORS

- Precipitation: Interfering precipitate noted at 5000 µg/plate in TA 98 and TA 1535 (+/-MA), TA 1537 (-MA) and WP2 uvrA (-MA) 1000 - 5000 (+MA)

COMPARISON WITH HISTORICAL CONTROL DATA: Results were within range of historical control data

Remarks on result:

other: No mutagenic potential

Any other information on results incl. tables

Table 2: Dose range-finding study Number of revertants per plate (2 plates per strain)

	TA 100			WP2 uvrA
Concentration (µg/Plate)	Plate 1 + MA	Plate 2 - MA	Cytotoxic (Yes/No)	Plate 1 + MA	Plate 2 - MA	Cytotoxic (Yes/No)
0	133	98	No	16	23	No
6.7	128	110	No	13	8	No
10	123	95	No	28	17	No
33	134	98	No	13	9	No
67	150	84	No	19	19	No
100	147	111	No	17	15	No
333	146	107	No	11	20	No
667	134	104	No	22	26	No
1000	148	123	No	32	16	No
3333	146	116	No	15	18	No
5000	168	113	No	24	16	No

*solvent control with DMSO

Table 3: Experiment 1 Mutagenicity Assay Number of revertants per plate (mean of 3 plates)

	TA98			TA100			TA1535
Conc. (µg/plate)	— MA	+ MA	Cytotoxic (yes/no)	— MA	+ MA	Cytotoxic (yes/no)	— MA	+ MA	Cytotoxic (yes/no)
0*	16	27	No	134	161	No	11	12	No
100	21	30	No	131	156	No	11	11	No
333	11	24	No	134	163	No	10	14	No
1000	20	24	No	129	164	No	12	13	No
3333	20	32	No	141	167	No	9	11	No
5000	15	28	No	126	172	No	10	15	No
Positive control	367	873	No	720	1035	No	637	129	No

*solvent control with DMSO

Table 3: Experiment 1 Mutagenicity Assay Number of revertants per plate (mean of 3 plates)

	TA1537			WP2uvrA
Conc. (µg/plate)	— MA	+  MA	Cytotoxic (yes/no)	— MA	+  MA	Cytotoxic (yes/no)
0*	5	12	No	17	19	No
100	4	8	No	14	18	No
333	6	8	No	17	13	No
1000	4	9	No	10	16	No
3333	6	8	Yes	16	15	No
5000	6	6	Yes	17	14	No
Positive control	1070	119	No	292	108	No

*solvent control with DMSO

Table 4: Experiment 2 Mutagenicity Assay Number of revertants per plate (mean of 3 plates)

	TA98			TA100			TA1535
Conc. (µg/plate)	— MA	+ MA	Cytotoxic (yes/no)	— MA	+ MA	Cytotoxic (yes/no)	— MA	+ MA	Cytotoxic (yes/no)
0*	26	44	No	106	129	No	10	12	No
33	26	39	No	121	131	No	11	11	No
100	24	46	No	136	153	No	9	16	No
333	26	35	No	117	142	No	11	14	No
1000	25	39	No	119	166	No	11	11	No
5000	19	38	No	138	167	No	11	10	No
Positive control	292	901	No	534	945	No	446	106	No

*solvent control with DMSO

Table 4: Experiment 2 Mutagenicity Assay Number of revertants per plate (mean of 3 plates)

	TA1537			WP2 uvrA
Conc. (µg/plate)	— MA	+ MA	Cytotoxic (yes/no)	— MA	+ MA	Cytotoxic (yes/no)
0*	6	5	No	21	14	No
33	5	6	No	16	14	No
100	5	7	No	21	15	No
333	4	6	No	18	15	No
1000	5	9	No	19	18	No
5000	3	7	Yes	22	15	No
Positive control	598	97	No	430	118	No

*solvent control with DMSO

Applicant's summary and conclusion

Conclusions:

Under test conditions, no mutagenic effect was observed for the test substance tested up to cytotoxic concentration in any of the test strains in two independent experiments without and with metabolic activation. The test substance is non-mutagenic in test strains used.