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Toxicological information

Genetic toxicity: in vivo

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Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1985
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Remarks:
The restrictions were that only 1000 immature erythrocytes were scored for incidence of micronucleated immature erythrocytes: the current guideline requires 2000 to be scored.

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

Constituent 1
Chemical structure
Reference substance name:
Trimethoxyvinylsilane
EC Number:
220-449-8
EC Name:
Trimethoxyvinylsilane
Cas Number:
2768-02-7
Molecular formula:
C5H12O3Si
IUPAC Name:
ethenyltrimethoxysilane

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 / concentrationsopen allclose all
Dose / conc.:
300 mg/kg bw/day
Dose / conc.:
700 mg/kg bw/day
Dose / conc.:
1 125 mg/kg bw/day
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:
Fisher's exact test, males and female data combined as no statistically significant difference between them.

Results and discussion

Test results
Key result
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:
Trimethoxy(vinyl)silane has been tested in a reliable and valid micronucleus assay according to a protocol that is similar to the current OECD TG 474 and in compliance with 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 trimethoxy(vinyl)silane is negative for the induction of micronuclei under the conditions of this test.