3-(trimethoxysilyl)propyl isocyanate

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:

1994-07-06 - 1994-10-08

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:

1994

Report date:

1994

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

range of strains does not comply with current guideline

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

3-(trimethoxysilyl)propyl isocyanate

EC Number:

239-415-9

EC Name:

3-(trimethoxysilyl)propyl isocyanate

Cas Number:

15396-00-6

Molecular formula:

C7H15NO4Si

IUPAC Name:

(3-isocyanatopropyl)trimethoxysilane

Test material form:

liquid

Details on test material:

.

Method

Target gene:

Histidine

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:

Aroclor induced rat liver S9

Test concentrations with justification for top dose:

Test 1: 0.003 - 0.30 µg/plate. Test 2: 0.03 - 3.0 µg/plate

Vehicle / solvent:

DMSO

Controls

Controls 1

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 4-Nitro-o-Phenylenediamine 0.01 µg/plate

Remarks:

TA98, TA1538 without metabolic activation

Controls 2

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

sodium azide

Remarks:

TA100, TA1535 without metabolic activation; 0.01 µg/plate

Controls 3

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

9-aminoacridine

Remarks:

TA1537 without metabolic activation 0.06 µg/plate

Controls 4

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 2-Aminoanthracene 2.5 µg/plate

Remarks:

TA 98, TA100, TA1535, TA1537 and TA1538 with metabolic activation

Details on test system and experimental conditions:

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

DURATION
- Preincubation period: ?
- Exposure duration: 48 - 72 hours


SELECTION AGENT (mutation assays):

NUMBER OF REPLICATIONS:
3 plates per dose, experiment repeated


DETERMINATION OF CYTOTOXICITY
- Method: Revertant colonies were counted


OTHER:

Evaluation criteria:

A chemical is considered positive if it shows a statistically significant dose dependent and reproducible increase in the number of revertants relative to the solvent control.

Statistics:

None used

Results and discussion

Test results

Test results 1

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 2

Species / strain:

S. typhimurium TA 98

Metabolic activation:

without

Genotoxicity:

positive

Remarks:

Produced a weak but consistent mutagenic effect

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

Species / strain:

S. typhimurium TA 98

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 4

Species / strain:

S. typhimurium TA 1537

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 5

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 6

Species / strain:

S. typhimurium TA 1538

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

Any other information on results incl. tables

Table 1a Experiment 1 Number of revertants per plate (mean of 3 plates)

Concentration µg/plate	TA98		TA100		TA1535
	-MA	+MA	-MA	+MA	-MA	+MA
Solvent control	7	18	90	88	25	8
Positive control	294	1500	645	1310	596	90
3	10	-	1	-	3*	-
10	10	14	64	80	134	5
30	12	15	69	72	3*	6
100	17	14	60	71	9*	6
300	12	9	69	50	4*	2*
3000	-	3*	-	8*	-	0*

* Toxic, absence of background lawn, or mean number of colonies < ½ solvent control values.

 

Table 1b Experiment 1 Number of revertants per plate (mean of 3 plates)

Concentration	TA1537		TA1538
µg/plate	-MA	+MA	-MA	+MA
Solvent control	4	3	9	14
Positive control	76	150	451	1285
3	4	-	5	3
10	4	4	11	11
30	4	5	7	9
100	3	5	12	12
300	2	3	2	6*
3000	-	*	2*	0*

* Toxic: absence of background lawn, or mean number of colonies < ½ solvent control values.

 

Table 2a Experiment 2 Number of revertants per plate (mean of 3 plates)

Concentration	TA98		TA100		TA1535
µg/plate	-MA	+MA	-MA	+MA	-MA	+MA
Solvent control	11	17	59	83	3	5
Positive control	341	1508	688	1572	664	101
3	12	-	59	-	4	-
10	13	20	53	65	4	7
30	15	17	66	74	5	4
100	22	18	65	76	2	1*
300	6	15	57	40*	1*	4
3000	-	0*	-	14*	-	3*

* Toxic, absence of background lawn, or mean number of colonies < ½ solvent control values.

 

Table 2b Experiment 2 Number of revertants per plate (mean of 3 plates)

Concentration	TA1537		TA1538
µg/plate	-MA	+MA	-MA	+MA
Solvent control	3	6	10	9
Positive control	100	175	338	1340
3	2	-	9	-
10	4	5	9	9
30	5	3	11	11
100	5	5	10	12
300	2	3	4*	6
3000	-	2*	-	2*

* Toxic, absence of background lawn, or mean number of colonies < ½ solvent control values.

Applicant's summary and conclusion

Conclusions:

3-(trimethoxysilyl)propyl isocyanate has been tested according to a protocol that is similar to OECD 471, and under GLP in Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA 1537 and TA 1538. A slight increase in the number of revertants was observed in strain TA 98 in the absence of metabolic activation, in the initial experiment at a single dose. This result was reproducible in the second experiment, in which the response appeared to be weakly dose-dependent. This was considered to be evidence of a weak mutagenic potential. It is concluded that the test substance is positive for mutagenicity to Salmonella typhimurium TA 98 in the absence of metabolic activation under the conditions of the test.