Cordierite (Mg2[Al4O3(SiO3)5])

Genetic toxicity: in vivo

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

Study period:

1974

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study was conducted using a method similar to OECD Testing Guideline 475 and meets acceptable scientific standards.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1974

Report date:

1974

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)

Deviations:

yes

Remarks:

higher dose limit, 500 cells evaluated per animal instead of 1000

GLP compliance:

no

Type of assay:

chromosome aberration assay

Test material

Test material information

Constituent 1

Reference substance name:

Silicic acid, aluminum sodium salt

EC Number:

215-684-8

EC Name:

Silicic acid, aluminum sodium salt

Cas Number:

1344-00-9

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): FDA 71-45 (Sodium silicoaluminate)
- Physical state: Fine white powdered material
- Lot/batch No.: SR-1621

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Not provided
- Age at study initiation: 10 to 12 weeks
- Weight at study initiation: 280 to 350 g
- Assigned to test groups randomly: Yes
- Fasting period before study: Not provided
- Housing: Five per cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: Quarantine for 4 - 11 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Not provided
- Humidity (%): Not provided
- Air changes (per hr): Not provided
- Photoperiod (hrs dark / hrs light): Not provided

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

- Vehicle: 0.85 saline

Details on exposure:

PREPARATION OF DOSING SOLUTIONS:

DIET PREPARATION
- Rate of preparation of diet (frequency): Not provided
- Mixing appropriate amounts with (Type of food): Not provided
- Storage temperature of food: Not provided

Duration of treatment / exposure:

Acute toxicity: single administration
Subacute toxicity: five days (five administrations)

Frequency of treatment:

Acute toxicity: one exposure at three time points (6 hours, 24 hours, 48 hours)
Subacute toxicity: one exposure per concentration per day

Post exposure period:

Termination after administration

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
subacute: 4.25, 42.5, 425 mg/kg bw
Basis:
nominal conc.

Doses / concentrations 2

Remarks:

Doses / Concentrations:
acute: 5000 mg/kg bw
Basis:
nominal conc.

No. of animals per sex per dose:

Acute toxicity: five per dose per time points (45) + negative control three per time points (9) + positive control five only for the last time point (5)
Subacute toxicity: five per dose (15) + negative control

Control animals:

yes, concurrent vehicle

other: positive control: TEM 0.3 mg/kg

Positive control(s):

triethylenemelamine (TEM)
- Route of administration: oral gavage
- Doses / concentrations: 0.3 mg/kg bw

Examinations

Tissues and cell types examined:

Bone marrow diploid cells
Fifty metaphase spreads scored per animal.
Mitotic indices obtained by counting at least 500 cells

Details of tissue and slide preparation:

DETAILS OF SLIDE PREPARATION:
- Slides dried at room temperature. Duplicate slides prepared. Slides stained using a 5% Giemsa solution (Giemsa buffer pH 7.2) for 20 minutes, rinsed in acetone, 1:1 acetone:xylene, and placed in fresh xylene for 30 minutes.

METHOD OF ANALYSIS:
- Chromosomes of each cell counted and only diploid cells analyzed.

OTHER:
- Intraperitoneal administration of 4 mg/kg of colcemid two hours prior to killing.

Evaluation criteria:

Chromatid gaps and breaks, polyploidy, chromosome gaps and breaks, reunions, pulverization, cells with greater than ten aberrations, and any other chromosomal aberrations.

Results and discussion

Test results

Sex:

male

Genotoxicity:

negative

Toxicity:

not examined

Vehicle controls validity:

valid

Negative controls validity:

not applicable

Positive controls validity:

valid

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative
The test item was considered to be non-mutagenic under the conditions of the test.

Executive summary:

The in vivo cytogenicity of the read-across substance sodium silicoaluminate branded as FDA 71-45 was determined according to a method similar to the OECD Guideline for Testing of chemicals 475. Chromosome aberrations were evaluated in Sprague-Dawley rats.

Two methods of dosing were used. In the acute method, one dose of 5000 mg/kg bw was administrated. In the subacute, doses of 4.25, 42.5, and 425 mg/kg were administrated daily for five days.

Each animal was intraperitoneally administrated 4 mg/kg of colcemid two hours prior to killing in order to stop the mitosis. Bone marrow slides were prepared and stained with 5% Giemsa solution in order to score pulverization, achromatid gaps and breaks, chromosome gaps and breaks, cells with greater than ten aberrations, reunions, polyploidy, and any other chromosomal aberrations in diploid cells.

No significant numbers of aberration were observed for each tested concentration.

The test item was considered to be non-mutagenic under the conditions of the test.