Dichloro(dimethyl)silane

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1981-02-04 to 1981-12-21

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

mitotic index was determined in only 500 cells per animal, results are not presented in compliance with current guideline.

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1982

Report date:

1982

Reference 2

Reference Type:

publication

Title:

No information

Author:

Isquith et al

Year:

1988

Bibliographic source:

Fd Chem Toxic 26 (3) 263-266

Materials and methods

Test guideline

Test guideline 1

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)

Deviations:

yes

Remarks:

number of cells evaluated; only male animals used

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: EPA TAP 22: 269-275, 1972 modified 12/3 to 12/5 1980

Deviations:

not specified

GLP compliance:

yes

Type of assay:

chromosome aberration assay

Test material

Test material information

Constituent 1

Reference substance name:

Dichloro(dimethyl)silane

EC Number:

200-901-0

EC Name:

Dichloro(dimethyl)silane

Cas Number:

75-78-5

Molecular formula:

C2H6Cl2Si

IUPAC Name:

dichlorodimethylsilane

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Gofmoor Farms, Westboro, MA (range-finding study); Charles River, Wilmington, MA USA (main study)
- Age at study initiation: 10-14 weeks
- Weight at study initiation: 200-250 g
- Assigned to test groups randomly: not reported
- Fasting period before study:
- Housing: 5 per cage
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: not reported


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20
- Humidity (%): 50

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

- Vehicle(s)/solvent(s) used: paraffin oil
- Justification for choice of solvent/vehicle: none given
- Concentration of test material in vehicle: not reported
- Purity: laboratory grade

Duration of treatment / exposure:

single injection

Frequency of treatment:

Once

Post exposure period:

sacrifice at 6, 24 and 48 hours after exposure.

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

5 mg/kg bw/day

Remarks:

Criteria for selection of MTD based on the results of a range-finding study

Doses / concentrations 2

Dose / conc.:

11 mg/kg bw/day

Remarks:

Criteria for selection of MTD based on the results of a range-finding study

Doses / concentrations 3

Dose / conc.:

22 mg/kg bw/day

Remarks:

Criteria for selection of MTD based on the results of a range-finding study

Doses / concentrations 4

Dose / conc.:

32 mg/kg bw/day

Remarks:

Criteria for selection of MTD based on the results of a range-finding study

No. of animals per sex per dose:

5

Control animals:

yes, concurrent vehicle

Positive control(s):

- cyclophosphamide;
- Justification for choice of positive control(s): none given
- Route of administration: not reported
- Doses / concentrations: 22 mg/kg

Examinations

Tissues and cell types examined:

Bone marrow

Details of tissue and slide preparation:

CRITERIA FOR DOSE SELECTION: Based on range finding study

TREATMENT AND SAMPLING TIMES ( in addition to information in specific fields):

DETAILS OF SLIDE PREPARATION: Cells were centrifuged and resuspended three times in fixative (3:1 methanol:acetic acid). Aliquots of suspended cells were air dried. Slides of acceptable quality were stained with 5% Giesma, and photographed using x100 objective.

METHOD OF ANALYSIS: Negatives were projected onto a white counter and examined for chromosomal breaks or gaps, chromatid breaks or gaps, complex rearrangements, pulverised cells or chromosomes, acentric fragments, polyploidy and large translocations or deletions.

Evaluation criteria:

None given in report

Statistics:

Chi squared test and Wilcoxon test.

Results and discussion

Test results

Sex:

male

Genotoxicity:

negative

Toxicity:

yes

Remarks:

deaths at 22 mg/kg and above

Vehicle controls validity:

valid

Negative controls validity:

not applicable

Positive controls validity:

valid

Any other information on results incl. tables

Table 1: Results of range-finding studies   Dose level mg/kg Number dead/number animals 54 3/10 43 5/10 32 0/10 22 2/10 11 0/10 5 0/10

Table 2: Results of chromosome analysis in bone marrow(5 animals per dose, approx 110 cells per animal evaluated)

 

-	Positive control	Vehicle control			11mg/kg			22 mg/kg			32 mg/kg
Sampling time (h)	24	6	24	48	6	24	48**	6	24	48	6	24	48
Gaps	46-60	0-4	0-6	0-4	2-6	1-7	0-1	1-5	0-4	0-2	2-10	1-7	1-5
Breaks	ND	0-4	0-2	0-3	0-5	0-7	0-2	0-2	0-2	0-2	1-5	0-5	1-2
Other	3-<23	0-2*	0-1*	0-1*	0	0-2*	0-2*	0	3	0-2*	0	0-2*	0
Mitotic index %	1.3-3.1	1.7-5.0	1.4-3.7	1.2-4.9	0.8-5.8	2.1-5.8	1.0-4.3	2.0-4.7	1.8-5.8	1.4-3.6	2.3-4.5	1.8-4.3	1.7-3.4
Polyploidy	0	0	0		0	0	0	0	0	0	0	0	0
Endo reduplication	0	0	0		0	0	0	0	0	0	0	0	0

Numbers in table represent the range of the mitotic index or the total number of gaps, breaks or other aberrations recorded for each test animal

ND Not determined

* deletions

** 7 animals used at this dose and time, 2 with under 50 analysable cells.

Applicant's summary and conclusion

Conclusions:

Dichloro(dimethyl)silane has been tested according to a protocol similar to OECD TG 475. The test substance did not induce chromosome aberrations when tested in male rats by ip injection at doses up to 32 mg/kg bw. Appropriate positive and vehicle controls were included and gave expected results. It is concluded that the test substance is not genotoxic under the conditions of the test.