Registration Dossier

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:
1987-12-15 to 1988-01-22
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to a national standard method, and in compliance with GLP. Read-across to the related substance is considered scientifically justified.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1988
Report date:
1988

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
Deviations:
yes
Remarks:
some details not included
GLP compliance:
yes
Type of assay:
micronucleus assay

Test material

Constituent 1
Reference substance name:
3-aminopropyltriethoxysilane
EC Number:
213-048-4
EC Name:
3-aminopropyltriethoxysilane
Cas Number:
919-30-2
IUPAC Name:
3-(triethoxysilyl)propan-1-amine

Test animals

Species:
mouse
Strain:
Swiss Webster
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS

- Source: Charles Rivers Laboratories

- Age at study initiation: Five weeks

- Assigned to test groups randomly: [yes, by computer generated randomization]

- Housing: Shoe-box type plastic cages (30 x 20 x 12.5 cm)

- Diet (e.g. ad libitum): Agway PROLAB (ad libitum)

- Water (e.g. ad libitum): ad libitum

- Acclimation period: 5 to 6 days prior to dosing


ENVIRONMENTAL CONDITIONS

- Photoperiod (hrs dark / hrs light): 12 hours dark / 12 hours light

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
- Vehicle(s)/solvent(s) used: corn oil

- Justification for choice of solvent/vehicle: sponsor indicated the sample reacts with water
Details on exposure:
Intraperitoneal injection
Duration of treatment / exposure:
single dose
Frequency of treatment:
single dose
Post exposure period:
30, 48 and 72 hours
Doses / concentrations
Remarks:
Doses / Concentrations:
90, 56 and 28 mg/kg bw
Basis:
nominal conc.
No. of animals per sex per dose:
5 males and 5 females per dose group
Control animals:
yes, concurrent vehicle
Positive control(s):
triethylenemelamine

- Route of administration: IP injection

- Doses / concentrations: 0.3 mg/kg

Examinations

Tissues and cell types examined:
Blood
Details of tissue and slide preparation:
CRITERIA FOR DOSE SELECTION: Pre toxicity study (tested to find LD50 using 160, 128 and 102 mg/kg; Doses calculated using this value)

TREATMENT AND SAMPLING TIMES ( in addition to information in specific fields): Blood samples taken 30, 48, and 72 hours after injection

DETAILS OF SLIDE PREPARATION: 2 blood smear slides prepared for each animal per sampling time

METHOD OF ANALYSIS: A minimum of 1000 polychromatic erythrocytes were examined microscopically for each animal per sample time.
Evaluation criteria:
A positive result in the micronucleus test was concluded if at least one statistically significant (p ≤ 0.01) increase above the vehicle control was observed with an indication of a dose-related effect of treatment.
Statistics:
Statistical significance determined using Fisher's Exact Test.

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative
Toxicity:
yes
Remarks:
> 112 mg/kg; no effects in bone marrow
Vehicle controls validity:
valid
Negative controls validity:
not applicable
Positive controls validity:
valid
Additional information on results:
RESULTS OF RANGE-FINDING STUDY
- Dose range in range finding study: 160, 128 and 102 mg/kg;
- Solubility: no information
- Clinical signs of toxicity in test animals: lethalities at 160, and 128 mg/kg, no clinical observations made during study
- Rationale for exposure: 25, 50 and 80% LD50 (28, 56 and 90 mg/kg bw)
- Harvest times: 30, 48 and 72 hours

RESULTS OF DEFINITIVE STUDY
- Induction of micronuclei (for Micronucleus assay): negative
- Ratio of PCE/NCE (for Micronucleus assay): not affected by test substance
- Appropriateness of dose levels and route: appropriate dose levels and route
- Statistical evaluation: Analysis of variance

Any other information on results incl. tables

Analysis of variance testing indicated significant sex-related differences in the incidence of micronuclei so data were analysed and reported separately. No statistically significant increases in any treatment group sampled at 30 and 72 hours. Statistically significant increases were observed with female mice sampled at 48 hours, but these were the result of an unusually low value in the vehicle control group compared with historical values, and so were not considered to be of biological significance. The positive control group produced highly significant increases in numbers of micronuclei. The vehicle control values were low and within an acceptable range.

Table 1:Results of in vivo micronucleus test with male Swiss-Webster mice (30 hours) 

 

Solvent Control

Positive Control

Low dose

28 mg/kg

Mid dose

56 mg/kg

High dose

90 mg/kg

Number of cells evaluated

1000

1000

1000

1000

1000

Sampling time (h)

30

30

30

30

30

Number of erythrocytes

normo­chromatic

-

-

-

-

-

poly­chromatic

10,000

10,000

10,000

10,000

10,000

polychromatic with micronuclei

13

159

16

10

9

Ratio of erythrocytes

polychromatic / normochromatic

22.6

20.2

24

26.6

24.4

polychromatic with micro­nuclei / normochromatic

2.6

31.8

3.2

2

1.8

Table 2:Results of in vivo micronucleus test with female Swiss-Webster mice (30 hours) 

 

Solvent Control

Positive Control

Low dose

28 mg/kg

Mid dose

56 mg/kg

High dose

90 mg/kg

Number of cells evaluated

1000

1000

1000

1000

1000

Sampling time (h)

30

30

30

30

30

Number of erythrocytes

normo­chromatic

-

-

-

-

-

poly­chromatic

10,000

10,000

10,000

10,000

10,000

polychromatic with micronuclei

5

86

13

9

8

Ratio of erythrocytes

polychromatic / normochromatic

25.6

26.2

25.8

38.6

25.8

polychromatic with micro­nuclei / normochromatic

1

17.2

2.6

1.8

1.6

 

Table 3:Results of in vivo micronucleus test with male Swiss-Webster mice (48 hours) 

 

Solvent Control

Positive Control

Low dose

28 mg/kg

Mid dose

56 mg/kg

High dose

90 mg/kg

Number of cells evaluated

1000

1000

1000

1000

1000

Sampling time (h)

48

48

48

48

48

Number of erythrocytes

normo­chromatic

-

-

-

-

-

poly­chromatic

5,000

5,000

5,000

5,000

5,000

polychromatic with micronuclei

15

Not evaluated

23

13

15

Ratio of erythrocytes

polychromatic / normochromatic

31.4

Not evaluated

27.2

31

29.4

polychromatic with micro­nuclei / normochromatic

3

Not evaluated

4.6

2.6

3

Table 4:Results of in vivo micronucleus test with female Swiss-Webster mice (48 hours) 

 

Solvent Control

Positive Control

Low dose

28 mg/kg

Mid dose

56 mg/kg

High dose

90 mg/kg

Number of cells evaluated

1000

1000

1000

1000

1000

Sampling time (h)

48

48

48

48

48

Number of erythrocytes

normo­chromatic

-

-

-

-

-

poly­chromatic

5,000

5,000

5,000

5,000

5,000

polychromatic with micronuclei

3

Not evaluated

10

11

10

Ratio of erythrocytes

polychromatic / normochromatic

31.2

Not evaluated

24

31.2

21.8

polychromatic with micro­nuclei / normochromatic

0.6

Not evaluated

2

2.2

2

 

Table 5:Results of in vivo micronucleus test with male Swiss-Webster mice (72 hours) 

 

Solvent Control

Positive Control

Low dose

28 mg/kg

Mid dose

56 mg/kg

High dose

90 mg/kg

Number of cells evaluated

1000

1000

1000

1000

1000

Sampling time (h)

72

72

72

72

72

Number of erythrocytes

normo­chromatic

-

-

-

-

-

poly­chromatic

5,000

5,000

5,000

5,000

5,000

polychromatic with micronuclei

15

Not evaluated

14

6

12

Ratio of erythrocytes

polychromatic / normochromatic

26

Not evaluated

33

30.6

27.6

polychromatic with micro­nuclei / normochromatic

3

Not evaluated

2.8

1.2

2.4

 

Table : Results of in vivo micronucleus test with female Swiss-Webster mice (72 hours) 

 

Solvent Control

Positive Control

Low dose

28 mg/kg

Mid dose

56 mg/kg

High dose

90 mg/kg

Number of cells evaluated

1000

1000

1000

1000

1000

Sampling time (h)

72

72

72

72

72

Number of erythrocytes

normo­chromatic

-

-

-

-

-

poly­chromatic

5,000

5,000

5,000

5,000

5,000

polychromatic with micronuclei

8

Not evaluated

1

3

5

Ratio of erythrocytes

polychromatic / normochromatic

25.2

Not evaluated

26.6

27.2

26.6

polychromatic with micro­nuclei / normochromatic

1.6

Not evaluated

0.2

0.6

1

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
3-aminopropyltriethoxysilane (Silane A-1100 CAS No. 919-30-2) has been tested in a reliable mouse micronucleus assay according to a protocol that is similar to OECD TG 474 and under GLP. No treatment related increases in numbers of micronuclei in PCEs in Swiss-Webster mice were observed. Relatively high dose levels of the substance were tested by intraperitoneal administration up to 80% of the LD50 with no indication of a positive induction of micronuclei. The test substance was considered to be inactive as a clastogenic agent under the statistical criteria used. It is concluded that the test substance is negative for the induction of chromosome aberrations under the conditions of the test.