Registration Dossier

Toxicological information

Genetic toxicity: in vivo

Currently viewing:

Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented publication which meets basic scientific principles. Comparable to guideline study.
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1974

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)
GLP compliance:
no
Type of assay:
chromosome aberration assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): FDA-Compound 71-41 = Silene, calcium silicate (hydrated)

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Flow laboratories
- Age at study initiation: 10-12 weeks
- Weight at study initiation: 300-350 g
- Fasting period before study: no data
- Housing: 1-5 rats / cage
- Diet (e.g. ad libitum): commercial 4% fat diet ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 4-11 days

ENVIRONMENTAL CONDITIONS: no data

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
- Vehicle(s)/solvent(s) used: 0.85% saline
Duration of treatment / exposure:
Single administration (acute) and repeated (5 days) administration (subacute)
Frequency of treatment:
Once per day
Post exposure period:
Observations 6, 24 and 48 hours, resp. after administration (acute study) and 6 hours after last administration (subacute study).
Doses / concentrations
Remarks:
Doses / Concentrations:
15, 150, 1500 and 5000 mg/kg bw
Basis:
actual ingested
gavage
No. of animals per sex per dose:
15, 150 and 1500 mg/kg: 15 animals
5000 mg/kg: acute test 5 animals, subacute 15 animals
negative control: 9 animals
Control animals:
yes, concurrent vehicle
Positive control(s):
0.3 mg/kg triethylene melamine

Examinations

Tissues and cell types examined:
Bone-marrow cell preparations were made and 50 cells per animal were counted in metaphase for aberrations. Mitotic indices were obtained by counting at least 500 cells.
Details of tissue and slide preparation:
DETAILS OF SLIDE PREPARATION: The cells were collected nd centrifuged and fixed with 3:1 absolute methanol:glacial acetic acid. After being resuspended a small amount of the suspension was pipetted on a slide. The slides were stained using Giemsa solution (5%), rinsed with solvents and mounted using Permount and coverglasses

METHOD OF ANALYSIS: The slides were examined microscopically.
Evaluation criteria:
The chromosomes of each cell were counted and only diploid cells were analyzed. They were scored for chromatid gaps and breaks, chromosome gaps and breaks, reunions, cells with >10 aberrations, polyploidy, pulverization, and any other chromosomal aberrations. The outcome were expressed as percentages.
50 metaphase spreads were scored per animal. The mitotic index was expressed as the ratio of number of cells in mitosis / the number of cells observed. At least 500 cells were counted.

Results and discussion

Test results
Sex:
male
Genotoxicity:
negative
Toxicity:
not examined
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
No significant bone marrow metaphase chromosomal aberrations were observed in any of the exposure groups.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
Calcium silicate was negative in an oral cytogenetic rat bone marrow test.
Executive summary:

The ability of calcium silicate to induce chromosomal aberrations was studied in male rats (Litton 1974). The rats were given doses of 15 -5000 mg/kg calcium silicate by gavage either as a single acute dose, or subacutely with one dose on five consecutive days. The induction of bone marrow metaphase chromosomal aberrations was measured, and the results showed that the outcome was at the same level as in the saline controls.