3-trimethoxysilylpropyl methacrylate

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1986

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1986

Report date:

1986

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

GLP compliance:

yes

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

3-trimethoxysilylpropyl methacrylate

EC Number:

219-785-8

EC Name:

3-trimethoxysilylpropyl methacrylate

Cas Number:

2530-85-0

Molecular formula:

C10H20O5Si

IUPAC Name:

3-trimethoxysilylpropyl methacrylate

Test animals

Species:

mouse

Strain:

Swiss Webster

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Breeding Laboratories
- Age at study initiation: not stated
- Weight at study initiation: 15-5 g (female); 20-30 g (male)
- Assigned to test groups randomly: yes
- Fasting period before study: no
- Housing: shoe-vox type plastic cages.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 5 to 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): controlled but not specified in report
- Humidity (%): controlled but not specified in report
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 hours dakr / 12 hours light

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

Corn oil; all solutions made just before dosing.
Substance reacted slowly with water.

Duration of treatment / exposure:

30, 48 and 72 hour

Frequency of treatment:

One treatment

Post exposure period:

Samples taken 30,48 and 72 hours after treatment

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

2 500 mg/kg bw/day

Doses / concentrations 2

Dose / conc.:

4 000 mg/kg bw/day

Doses / concentrations 3

Dose / conc.:

5 000 mg/kg bw/day

No. of animals per sex per dose:

5 males and 5 females per dose

Control animals:

yes, concurrent vehicle

Positive control(s):

- Positive control substance: triethylenemelamine
- Route of administration: ip injection
- Doses / concentrations: 0.3 and 0.5 mg/kg bw

Examinations

Tissues and cell types examined:

Peripheral blood; 1000 Polychromatic erythrocytes (PCE) examined for micronuclei; PCE/NCE (normochromatic erythrocyte) ratio calculated for approximately 1000 total cells

Evaluation criteria:

Results were considered positive under the following conditions:
- at least one statistically significant increase above the control was obtained and there was a statistically significant indication of a dose-related effect of treatment;
- at least two dose level from the same sample period produced micronucleus frequencies which were significantly above the control values;
- at least two dose level from the same sample period produced micronucleus frequencies which were significantly above the control values and there was an indication of a significant dose-related increase in at least one of the sample intervals

Results and discussion

Test results

Key result

Sex:

male/female

Genotoxicity:

negative

Toxicity:

yes

Remarks:

25% reduction in proportion of PCEs at MTD 72h post dose

Vehicle controls validity:

valid

Negative controls validity:

not applicable

Positive controls validity:

valid

Any other information on results incl. tables

Table 1 Results of micronucleus assay

Dose mg/kg	Collection interval (hours)	%Micronucleated PCE’s^1 Mean ± S.D		Ratio PCE : NCE^2 Mean ± S.D
		Males	Females	Males	Females
2500	30	0.46± 0.35	0.34± 0.34	41.4± 11.8	46.4± 20.8
	48	0.50± 0.49	0.20± 0.29	38.6± 14.9	34.5± 9.8
	72	0.18± 0.05	0.28± 0.38	21.4±4.4	27.2± 2.9
4000	30	0.52± 0.27	0.20± 0.10	43.6± 11.3	53.2± 16.4
	48	0.42± 0.33	0.26± 0.23	37.2± 4.8	44.6± 14.7
	72	0.14± 0.11	0.18± 0.18	23.2± 6.4	24.6± 8.7
5000	30	0.24± 0.11	0.38± 0.15	43.6± 10.1	40.8± 12.2
	48	0.34± 0.15	0.22± 0.05	32.2± 11.1	38.3± 6.2
	72	0.26± 0.17	0.18± 0.18	19.8± 5.4	21.0± 12.3
Vehicle (corn oil)	30	0.30±0.12	0.36±0.11	44.6± 12.4	47.6± 11.3
	48	0.34± 0.18	0.14± 0.11	42.4± 10.9	44.2± 11.4
	72	0.24± 0.17	0.04± 0.06	29.4±6.7	32.0± 8.5
Positive control 0.3 mg/kg	30	2.92± 0.9	2.84± 1.00	34.4± 10.0	29.8± 8.2
	48	NE	NE	NE	NE
		NE	NE	NE	NE

1 Polychromatic erythrocytes

2 Normochromatic erythrocytes

Applicant's summary and conclusion

Conclusions:

In a mouse micronucleus assay, conducted in a similar manner to OECD TG 474 and in compliance with GLP, 3-trimethoxysilylpropyl methacrylate did not produce treatment-related or statistically significant increases in the incidence of micronuclei in the peripheral blood polychromatic erythrocytes when administered by intraperitoneal injection up to limit concentrations. A decrease in the PCE/NCE ratio at 72 hours was considered to be evidence that the test substance had reached the target tissue. Positive and vehicle controls produced appropriate responses. It is concluded that the test substance is negative for the induction of micronuclei under the conditions of the test.