Caesium carbonate

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian germ cell study: cytogenicity / chromosome aberration

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2008-03-18 to 2008-04-22

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.11 (Mutagenicity - In Vivo Mammalian Bone-Marrow Chromosome Aberration Test)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.5380 (In Vivo Mammalian Cytogenetics Tests: Spermatogonial Chromosomal Aberrations)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of assay:

chromosome aberration assay

Test material

Test material information

Constituent 1

Reference substance name:

Caesium carbonate

EC Number:

208-591-9

EC Name:

Caesium carbonate

Cas Number:

534-17-8

Molecular formula:

CCs2O3

IUPAC Name:

caesium carbonate

Constituent 2

Reference substance name:

Cesiumcarbonate technical grade

IUPAC Name:

Cesiumcarbonate technical grade

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Test animals

Species:

rat

Strain:

other: Wistar Hanlbm: WIST (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Winkelmann GmbH, D-33178 Borchen
- Age at study initiation:6 - 10 weeks
- Weight at study initiation: males 163.4 +- 8.6 g; females: 153.1 +- 6.0 g
- Assigned to test groups randomly: [no/yes, under following basis: ] yes
- Fasting period before study:
- Housing: single, Makrolon Type II with wire mesh top granulated soft wood bedding
- Diet (e.g. ad libitum): pelleted standard diet ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +- 3°C
- Humidity (%): 30 - 70%
- Photoperiod (hrs dark / hrs light): artificial light 6.00 a.m. - 6.00 p.m.

Administration / exposure

Route of administration:

oral: drinking water

Vehicle:

deionised water

Details on exposure:

As estimated by a pre-experiment 1750 mg/kg b.w. was suitable as the high dose ( toxic reactions like reduction of spontaneours activity, tremor apathy) .

Duration of treatment / exposure:

- 24h and 48 h (only the high dose group)

Frequency of treatment:

Single application

Post exposure period:

None

Doses / concentrations

Remarks:

Doses / Concentrations:
437.5, 875 and 1750 mg/kg b.w.
Basis:
actual ingested

No. of animals per sex per dose:

5 animals per sex per test group

Control animals:

yes, concurrent vehicle

Positive control(s):

CPA; Cyclophosphamide
- Route of administration: orally, once
- Doses / concentrations: 15 mg/kg (Volume administered 10 ml/kg b.w.)
- Solution prepared on day of administration

Examinations

Tissues and cell types examined:

Bone marrow.

Details of tissue and slide preparation:

The marrow was flushed out with 5 ml hypotonic potassium chloride solution and incubated for 20 min at 37°C. The cells were sedimented, the supernatant was discarded and the cell pellet was fixed (60 min). The cell pellet was gently resuspended to make a relatively thin cell suspension. Suspension was spread by flame-drying. One slide was made from each bone marrow sample.

Evaluation criteria:

- positive control with statistical response
- vehicle control with aberration rate < 2 %
- dose-related increase in the number of chromosomal aberrations and reproducible statistically significant positive response is classified as mutagenic

Statistics:

The statistical evaluation of appropriate data was performed with non-parametric Mann-Whithey test.

Results and discussion

Test results

Key result

Sex:

male/female

Genotoxicity:

negative

Toxicity:

no effects

Vehicle controls validity:

valid

Negative controls validity:

not examined

Positive controls validity:

valid

Applicant's summary and conclusion

Conclusions:

Cesium carbonate did not induce chromosome mutations as determined by the chromosome aberration test with bone marrow cells of the rat in vivo.

Executive summary:

The study was performed to investigate the potential of Cesium carbonate to induce chromosome aberrations in bone marrow cells of the rat according to OECD Guideline 475 (1997) and US EPA OPPTS 870.5385. The test item was formulated in deionised water. The volume administered orally was 10 mL/kg b.w. Rats were treated once with 437.5 mg/kg or 875 mg/kg or 1750 mg/kg. After 24 h and 48h (only the high dose group) spindle inhibitor colcemide was injected intraperitoneal, bone marrow cells were collected for chromosome aberration analysis and 10 animals (5 males/5 females) per test group were evaluated for occurrence of cytogenetic demage. No relevant reduction of mitotic indices could be observed. Therefore Test item was not cytotoxic in the bone marrow. No statistically significant increase in the frequency of aberrant cells occurred. Results are comparable to vehicle control. In addition positive control showed a significant increase of induced aberration frequency. Systemic bioavailability after oral administration was shown in an additional study investigating the plasma levels of the test item in male rats (IUCLID section 7.1.1).