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:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Comparable to a guideline study; not GLP. There was no indication of toxicity of test substance to bone marrow, so it cannot be confirmed that the test substance reached the target organ, so this study is not key. It is considered that read across to the registered substance is scientifically justified.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1982
Report date:
1982

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
Principles of method if other than guideline:
Rodent Bone Marrow Cytogenetic Assay as recommended by the Ad Hoc Committee on Chromosome Methodologies in Mutagen Testing (TAP 22: 269-275, 1972) with modifications per the EPA Gene-Tox Program Cytogenetics Committee (12/3 to 12/5, 1980), Washington, D.C.
GLP compliance:
no
Type of assay:
micronucleus assay

Test material

Constituent 1
Reference substance name:
Trichloro(methyl)silane
EC Number:
200-902-6
EC Name:
Trichloro(methyl)silane
Cas Number:
75-79-6
IUPAC Name:
trichloro(methyl)silane
Details on test material:
Purity: 99.4 %

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals or test system and environmental conditions:
Weight/Age at study initiation: 280-440 g (7-12 weeks)

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
Paraffin oil
Duration of treatment / exposure:
6, 24 or 48 hours
Frequency of treatment:
Frequency of treatment: One injection/rat
Doses / concentrations
Remarks:
Doses / Concentrations:
12, 16 and 23 mg/kg
Basis:
other: i.p. injection
No. of animals per sex per dose:
No. of animals per dose: Cytogenetic study: 5 animals/dose group/time point; only 3 dose groups were used for the chromosomal analysis
Control animals:
yes, concurrent vehicle
Positive control(s):
Positive: Cyclophosphamide

Examinations

Tissues and cell types examined:
Organs examined at necropsy (macroscopic and microscopic): Bone marrow collected from one femur of each animal
Details of tissue and slide preparation:
CRITERIA FOR DOSE SELECTION: Not provided

TREATMENT AND SAMPLING TIMES ( in addition to information in specific fields): For the cytogenetic studies, four doses of trichloromethylsilane were used, but only the following three dose groups were used for cytogenetic analysis: 12, 16, and 23 mg/kg. Animals were sacrificed at 6, 24, or 48 hours after injection. The negative control, paraffin oil, was used in each assay, but the positive control, cyclophosphamide (22 mg/kg) was included only in the 24-hour group. Colchicine was injected 2 to 2.5 hours before sacrifice at a final dose of approximately 1.5 mg/kg. Rats were sacrificed at the scheduled times and bone marrow was aspirated from the femur.

DETAILS OF SLIDE PREPARATION: Approximately four slides were prepared from each animal. Slides were fixed, stained and permanently mounted. Suitable cells were photographed using a 100X objective. Suitable cell spreads were those with both properly condensed and well-spread chromosomes. In general, a minimum of 100 metaphase cells was analyzed per animal, and 5 animals were analyzed for each dose.

METHOD OF ANALYSIS: A comparison of the expected and observed distribution values was performed using the Chi2 test as a measure of “goodness of fit”. The Wilcoxon test was used as a non parametric test to compare the distribution of breaks per animal between the negative controls and the highest dose animals.
Statistics:
Statistical method: A comparison of the expected and observed distribution values was performed using the Chi2 test as a measure of "goodness of fit". The Wilcoxon test was used as a non parametric test to compare the distribution of breaks per animal between the negative controls and the highest dose animals.

Results and discussion

Test results
Sex:
male
Genotoxicity:
negative
Toxicity:
not specified
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
There was no evidence that trichloromethylsilane induced chromosomal damage in rats following IP injection. No complex rearrangements such as quardriradicals, triradicals or ring chromosomes were detected in the test substance dosed animals. A comparison of the frequency of breaks for the trichloromethylsilane dose groups and the negative controls at 3 time points showed no significant differences. Animals injected with the positive control had both a large number of breaks and complex rearrangements.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
Appropriate concurrent negative and positive controls were included, and the expected responses were observed. The test substance, trimethylchlorosilane (CAS No. 75-79-6), did not cause an increase in the frequency of chromosomal breaks or aberrations in bone marrow cells of rats. There was no substance related effect on the mitotic index, so it was not demonstrated that the test substance reached the target organ.