Triethoxy(3-isocyanatopropyl)silane

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1987-12-15 to 1988-01-22

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods

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

Test material information

Constituent 1

Reference substance name:

3-aminopropyltriethoxysilane

EC Number:

213-048-4

EC Name:

3-aminopropyltriethoxysilane

Cas Number:

919-30-2

Molecular formula:

C9H23NO3Si

IUPAC Name:

3-triethoxysilylpropan-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: lethality 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 erythro-cytes	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 erythro-cytes	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 erythro-cytes	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 erythro-cytes	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 erythro-cytes	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:

3-Aminopropyl(triethoxy)silane (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 in compliance with GLP. No treatment related increases in numbers of micronuclei in polychromatic erythrocytes in Swiss-Webster mice were observed. Relatively high dose levels of 3-aminopropyl(triethoxy)silane were tested up to 80% of the LD50 with no indication of a positive induction of micronuclei. 3-Aminopropyl(triethoxy)silane 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.