Registration Dossier

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

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1982
Report Date:
1982
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 guidelineopen allclose all
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)
Deviations:
yes
Remarks:
number of cells evaluated; only male animals used
Qualifier:
according to
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

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals 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 / concentrationsopen allclose all
Dose / conc.:
5 mg/kg bw/day
Remarks:
Criteria for selection of MTD based on the results of a range-finding study
Dose / conc.:
11 mg/kg bw/day
Remarks:
Criteria for selection of MTD based on the results of a range-finding study
Dose / conc.:
22 mg/kg bw/day
Remarks:
Criteria for selection of MTD based on the results of a range-finding study
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.