Dichloro(methyl)(vinyl)silane

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

1985

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The study was conducted according to an appropriate national test guideline, and under GLP, with acceptable restrictions. The restrictions were that only 1000 immature erythrocytes were scored for incidence of micronucleated immature erythrocytes: the current guideline requires 2000 to be scored. It is considered that read-across to the registered substance is scientifically justified.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1985

Report date:

1985

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: EPA Health effects guidelines 560/6-83-001

Principles of method if other than guideline:

Method: other: BRRC Standard Operating Procedures 7.2.18A, 7.2.19A and 7.2.20A

GLP compliance:

yes

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

Trimethoxyvinylsilane

EC Number:

220-449-8

EC Name:

Trimethoxyvinylsilane

Cas Number:

2768-02-7

IUPAC Name:

trimethoxy(vinyl)silane

Test animals

Species:

mouse

Strain:

Swiss Webster

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hilltop laboratory animals
- Age at study initiation: 4 weeks
- Weight at study initiation: 24.0-28.9 g (male); 18.2-22.4 g (female)
- Assigned to test groups randomly: yes
- Fasting period before study: no
- Housing: 5 mice per sex per cage in shoe-box type plastic cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 5-6 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): monitored, not recorded
- Humidity (%): monitored, not recorded
- Air changes (per hr): no information
- Photoperiod (hrs dark / hrs light): 12 hours


IN-LIFE DATES: From March 26 1985 to April 5 1985:

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

- Vehicle(s)/solvent(s) used: corn oil;

- Justification for choice of solvent/vehicle: instability in water
- Concentration of test material in vehicle:

Details on exposure:

Intraperitoneal injection

Duration of treatment / exposure:

30, 48 and 72 hours

Frequency of treatment:

Single treatment

Post exposure period:

up to 72 hours

Doses / concentrations

Remarks:

Doses / Concentrations:
300, 700 and 1125 mg/kg bw
Basis:

No. of animals per sex per dose:

5

Control animals:

yes, concurrent vehicle

Positive control(s):

- triethylenemelamine
- Justification for choice of positive control(s): standard positive control
- Route of administration: ip injection
- Doses / concentrations: 500 μg/kg bw

Examinations

Tissues and cell types examined:

Peripheral erythrocytes

Details of tissue and slide preparation:

CRITERIA FOR DOSE SELECTION: based on LD 50

DETAILS OF SLIDE PREPARATION:Stained with Giesma

METHOD OF ANALYSIS: micronuclei were identified as darkly stained spherical inclusion in PCEs; PCEs were identified by pale blue staining of cytoplasm

OTHER: PCE/NCE ratio was calculated for approximately 1000 cells as a measure of cytotoxicity.

Evaluation criteria:

A positive result would be interpreted by a statistically significant (p < 0.05) increase above vehicle control with indication of dose response.

Statistics:

Fishcer's exact test, males and female data combined as no statistically significant difference between them.

Results and discussion

Test results

Sex:

male/female

Genotoxicity:

negative

Toxicity:

yes

Remarks:

decrease in PCE/NCE ratio at 1125 mg/kg bw

Vehicle controls validity:

valid

Negative controls validity:

not valid

Positive controls validity:

valid

Additional information on results:

RESULTS OF RANGE-FINDING STUDY
- Dose range: 500-2000 mg/kg
- Solubility: no information
- Clinical signs of toxicity in test animals: no information
- Evidence of cytotoxicity in tissue analyzed: slight decrease in PCE/NCE ratio
- Rationale for exposure: based on LD50 determined in an acute toxicity study
- Harvest times:
- Other:


RESULTS OF DEFINITIVE STUDY
- Induction of micronuclei (for Micronucleus assay): no evidence for induction of micronuclei
- Ratio of PCE/NCE (for Micronucleus assay): ratio was slightly decreased at the highest dose level
- Appropriateness of dose levels and route: appropriate dose and route
- Statistical evaluation: appropriate evaluation

Any other information on results incl. tables

Table 1 Results of toxicity assay: males

Dose mg/kg bw	No of animals tested	No of animals dead	% mortatlity	Mean PCE/NCE ratio	Percent of control
2000	5	4	80%	42.5	91.6%
1414	5	3	60%
1000	5	1	20%
707	5	0	0%
500	5	0	0%
Solvent control	5	0	0%	46.4	100%

 

Table 2 Results of toxicity assay: females

Dose mg/kg bw	No of animals tested	No of animals dead	% mortatlity	Mean PCE/NCE ratio	Percent of control
2000	5	3	60%	39.3	80.0%
1414	5	3	60%
1000	5	2	40%
707	5	0	0%
500	5	0	0%
Solvent control	5	0	0%	49.0	100%

 

Table 3 Micronucleus frequency and PCE/NCE ratio (mean of 5 animals for each sex)

Dose mg/kg bw	Sampling Timehours	Sex	Mean PCE/NCE ratio	Percent of control	Total micronuclei*	Mean+/- SD	% PCE with MN
350	30	M	46.6	92.4	18	3.6+/-2.19	0.36
		F	41.0		12	2.4+/-1.52	0.24
700		M	38.8	88.6	18	3.6+/-1.52	0.36
		F	45.2		21	4.2+/-1.30	0.42
1125		M	48.8	103.0	22	3.7+/-2.50	0.37
		F	49.0		23	3.3+/-1.11	0.33
Vehicle control		M	55.0	100	15	3.0+/-2.0	0.30
		F	42.8		14	2.8+/-0.84	0.28
Positive control		M	26.2	54.2	126	25.2+/-8.56	2.52
		F	25.2		149	29.5+/-16.02	2.98
350	48	M	44.4	110.2	21	4.2+/-1.92	0.42
		F	42.4		13	2.6+/-1.14	0.26
700		M	34.0	93.9	12	2.4+/-1.67	0.24
		F	40.0		7	1.4+/-0.55	0.14
1125		M	40.8	106.3	22	3.7+/-1.75	0.37
		F	43.0		20	3.3+/-2.16	0.33
Vehicle control		M	39.4	100	12	2.4+/-1.52	0.24
		F	45.4		14	2.8+/-2.17	0.28
Positive control		M	10.4	27.2	174	34.8+/-3.48	3.48
		F	11.0		176	35.2+/-9.63	3.52
350	72	M	46.2	92.0	16	3.32+/-1.64	0.32
		F	41.0		7	1.4+/-1.14	0.14
700		M	43.0	83.3	9	1.8+/-0.84	0.18
		F	36.0		6	1.2+/-1.10	0.12
1125		M	29.3	62.7	14	2.3+/-1.51	0.23
		F	30.0		9	1.5+/-1.38	0.15
Vehicle control		M	50.2	100	22	4.4+/-1.14	0.44
		F	47.0		15	3.0+/-1.73	0.30
Positive control		M	13.0	29.3	25	6.2+/-3.59	0.62
		F	15.0		14	3.5+/-3.70	0.35

*in 1000 PCE

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative
Trimethoxvinylsilane has been tested in a reliable and valid micronucleus assay according to a protocol that is similar to the current OECD TG 474 and under GLP. No statistically significance increase in the frequency of micronucleated polychromatic erythrocytes was observed in peripheral erythrocytes of mice treated with the test substance by ip injection. There was indication of slight toxicity to bone marrow at the highest dose in female mice, which is evidence that the test substance had reached the target cells. It is concluded that trimethoxyvinylsilane is negative for the induction of micronuclei under the conditions of this test.