Reaction mass of 4,4,13,13-tetraethoxy-3,14-dioxa-8,9-dithia-4,13-disilahexadecane and 4,4,14,14-tetraethoxy-3,15-dioxa-8,9,10-trithia-4,14-disilaheptadecane

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:

1 September 1998 - 3 October 1998

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1998

Report date:

1998

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

Deviations:

no

GLP compliance:

yes

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

4,4,13,13-tetraethoxy-3,14-dioxa-8,9-dithia-4,13-disilahexadecane

EC Number:

260-350-7

EC Name:

4,4,13,13-tetraethoxy-3,14-dioxa-8,9-dithia-4,13-disilahexadecane

Cas Number:

56706-10-6

Molecular formula:

C18H42O6S2Si2

IUPAC Name:

4,4,13,13-tetraethoxy-3,14-dioxa-8,9-dithia-4,13-disilahexadecane

Constituent 2

Reference substance name:

S2

IUPAC Name:

S2

Test animals

Species:

mouse

Strain:

NMRI

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS

- Source: Harlan-Winkelmann GmbH, D-33176 Borchen

- Age at study initiation: approx 7 weeks

- Weight at study initiation: males: 27.4-33.8 g; female: 22.0-26.1g

- Assigned to test groups randomly: yes, under following basis: computerised random number generator.

- Fasting period before study:

- Housing: Macrolon cages type II, 1 animal per cage

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

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

- Acclimation period: at least 6 days


ENVIRONMENTAL CONDITIONS

- Temperature (°C): 21.0-21.5°C

- Humidity (%): 50-57%

- Air changes (per hr):

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


IN-LIFE DATES: From: To: 3 Sept 1998

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

- Vehicle(s)/solvent(s) used: peanut oil
- Lot/batch no. (if required): 1936301

Details on exposure:

Route of exposure: intraperitoneal

Duration of treatment / exposure:

46-48 hours

Frequency of treatment:

2 intraperitoneal administrations of 10 ml/kg bw with an interval of approximately 24 hours (test material and negative control group). Positive control group received a single injection of 10 ml/kg bw

Post exposure period:

Animals were sacrificed 22-24h after second (test and negative control) or single (positive control) administration.

Doses / concentrations

Remarks:

Doses / Concentrations:
2000 mg/kg bw
Basis:
nominal conc.

No. of animals per sex per dose:

7

Control animals:

yes, concurrent vehicle

Positive control(s):

- cyclophosphamide
- Justification for choice of positive control(s): standard guideline positive control
- Route of administration: intraperitoneal
- Doses / concentrations: 10 ml/kg bw of 0.9% solution in physiological saline

Examinations

Tissues and cell types examined:

See table 2

Details of tissue and slide preparation:

CRITERIA FOR DOSE SELECTION: limit dose
TREATMENT AND SAMPLING TIMES ( in addition to information in specific fields):no further information


DETAILS OF SLIDE PREPARATION: centrifuged cells were suspended n a thin layer of serum, and a small drop was smeared on a slide and air-dried overnight. The dried slides were stained using the panoptic stain method of Pappenheim (Queisser W (1978) Das Knochenmark, Georg Thieme Verlag, Stuttgart)


METHOD OF ANALYSIS: microscopic examination. 2000 PCE scored for incidence of polychromatic erythrocytes with micronuclei. Ratio of PCE/NCE was scored based on 1000 erythrocytes (PCE+NCE)

Statistics:

Frequencies of PCE with micronuclei of test material and of positive control group were compared with those of the negative control group. A Poisson test was applied. Data from each treatment group for each sex and for the sexes combined were compared with appropriate negative control using software from ASTA medica AG and an Alpha computer (Digital Equipment Corp)

Results and discussion

Test results

Key result

Sex:

male/female

Genotoxicity:

negative

Toxicity:

no effects

Vehicle controls validity:

valid

Negative controls validity:

not applicable

Positive controls validity:

valid

Additional information on results:

See table 3
RESULTS OF DEFINITIVE STUDY

- Induction of micronuclei (for Micronucleus assay): negative

- Ratio of PCE/NCE (for Micronucleus assay): see table 3. The PCE/NCE ratio was unchanged in treated animals, so there is no evidence that the test substance reached the target tissue.

- Appropriateness of dose levels and route: appropriate dose and route

- Statistical evaluation: no statistically significant induction of micronuclei occurred

Any other information on results incl. tables

Table 3: Results of in vivo micronucleus test with Silane Si 266

 

		Vehicle Control	Positive control	2000 mg/kg bw
Number of cells evaluated		2000	2000	2000
Sampling time (h)		24	24	24
Number of erythrocytes per animal	normo­chromatic	NR	NR	NR
	poly­chromatic	2000	2000	2000
	polychromatic with micronuclei	3.4	38.1	3.4
Ratio of erythro­cytes	polychromatic / normochromatic	1.9*	1.5*	1.8*
	polychromatic with micro­nuclei / normochromatic	NR	NR	NR

 * Mean calculated from data for individual animals

PCE polychromatic erythrocyte

NR not recorded

Applicant's summary and conclusion

Conclusions:

4,4,13,13-tetraethoxy-3,14-dioxa-8,9-dithia-4,13-disilahexadecane has been tested in an in vivo mouse micronucleus assay to OECD 474 and under GLP. No evidence of the induction of micronuclei was observed. It should be noted that the PCE/NCE ratio was unchanged in treated animals, so there is no evidence that the test substance reached the target tissue. It is concluded that the test substance is negative for the induction of micronuclei in vivo under the conditions of the test.