Caesium carbonate

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

A bacterial reverse mutation assay in vitro with the target substance provided a negative result. The available chromosome aberration test in vitro demonstrated clastogenic properties in human lymphocytes with 24 h continuous exposure in the absence of S9-mix. All other test conditions (3 hour or 48 hour with or without S9-mix) did not reveal genotoxic effects. No effects of test item were found on the number of polyploid cells. Therefore the target substance does not disturb mitotic processes. The positive in vitro result was not confirmed in vivo (see below).

A mammalian cell gene mutation test in vitro with the source substance cesium hydroxide monohydrate did not show mutagenic properties.

Link to relevant study records

Reference

Reference 1

Endpoint:

in vitro gene mutation study in mammalian cells

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

HYPOTHESIS FOR THE ANALOGUE APPROACH
Cesium carbonate completely dissociates in water forming cesium cation and the corresponding carbonate anion. Thus, cesium salts with different anion moieties were found to be suitable candidates for read-across. (Eco)toxicological properties were extrapolated to different endpoints by using the lowest effect concentration.
For further information, please refer to the read-across justification in IUCLID section 13.

Reason / purpose for cross-reference:

read-across source

Key result

Species / strain:

Chinese hamster Ovary (CHO)

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

True negative controls validity:

not examined

Positive controls validity:

valid

Remarks on result:

other: Based on CsOH monohydrate

Reference 2

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2006-04-14 to 2006-04-28

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP and Guideline compliant study

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Version / remarks:

adopted 1997

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Target gene:

The Salmonella typhimurium strains are constructed to differentiate between base pair (TA 1535, TA 100) and frameshift (TA 1537, TA 98) mutations. The Escherichia coli WP2 uvrA detect mutagens that cause other base-pair substitutions.

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2

Metabolic activation:

with and without

Metabolic activation system:

Phenobarbital (PB) and ß-naphthoflavone (BNF) induced rat liver S 9-mix

Test concentrations with justification for top dose:

3, 10 33, 11, 333, 1000, 3330, 5000 µg/plate

Vehicle / solvent:

Milli-Q water

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

4-nitroquinoline-N-oxide

9-aminoacridine

2-nitrofluorene

sodium azide

benzo(a)pyrene

methylmethanesulfonate

Details on test system and experimental conditions:

An initial mutation test was performed. Bacteria were exposed to the test item, both in the presence and absence of an appropriate metabolic activation system. Freshly grown cultures were used. It were used Agarplates with 25 ml glucose agar medium. Agar plates for test with Salmonella typhimurium strains also con tained 12.5 µg/plate biotin and 15 µg/plate tryptophan.

The entire test consisted of non-activated and activated test conditions (without S9 Mix and with addition of S9 Mix) and each of them with the addition of negative and positive controls.
Top agar in top agar tubes was molten and heated to 45°C. Following solutions were added to 3 ml top agar: 0.1 ml bacterial culture of one of the tester strains, 0.1 ml of a dilution (tests substance in Milli-Q-water and either 0.5 ml S9 mix (for activation assay) or 0.5 ml 0.1 M phosphate buffer (for non activation assay). Ingredients were mixed and poured onto a selective agar plate.
After solidification the plates were inverted and incubated at 37 °C for at least 48 hours in the dark and revertant colonies (Histidin independent for Salmonella typhimurium and tryptophan independent for Escherichia coli) were counted manually or with a Protos model 50000 counter.
The colony numbers on the control, positive control and the test plates were determined, the mean values, standard deviations and the mutation rates were calculated.

Evaluation criteria:

Cesium Carbonat is considered negativ (not mutagenic) if the total number of revertants in tester strain TA 100 is no greater than two times in the concurrent control, in tester strain TA 1535, TA1537, TA 98 or WP2uvrA is not greater than 3 times in concurrent control. Negative response shold be reproducible in one independentliy repeated experiment.
Cesium Carbonat is considered positve (mutagenic) if the total number of revertants in tester strain TA 100 is greater than two times in the concurrent control, in tester strain TA 1535, TA1537, TA 98 or WP2uvrA is not greater than 3 times in concurrent control. Positive response will be repeated, and reproducible in one independentliy repeated experiment.

Statistics:

not applicable

Key result

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

True negative controls validity:

not examined

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

True negative controls validity:

not examined

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

True negative controls validity:

not examined

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

True negative controls validity:

not examined

Positive controls validity:

valid

Key result

Species / strain:

E. coli WP2 uvr A

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

True negative controls validity:

not examined

Positive controls validity:

valid

Additional information on results:

Dose range finding test was reported as a part of the first experiment of the mutation assay.

Conclusions:

The test item was investigated for its mutagenic potential in vitro via an Ames assay with and without metabolic activation. Based on the results, Cesium carbonate is considered to be non-mutagenic.

Executive summary:

The mutagenic potential of cesium carbonat was investigated in five bacterial strains: Salmonella typhimurium (TA 98, TA 100, TA 1535, TA1537 and Escherichia coli WP2 uvrA), according to OECD Guideline No. 471 and EU Method B 13/14. The test item was investigated in vitro via an Ames assay with and without metabolic activation. Therefor concentrations up to 5000 µg Cesium carbonate/plate were tested in two independent experiments in absence and presence of S9 -mix.

Based on the results, the test item is considered to be non-mutagenic. The bacterial background lawn was not reduced at any tested concentration and no increase in the number of revertants was observed up on treatment with Cesium Carbonate. Negativ and the strain-specific positiv control values indicate that test conditions were adequate.

Reference 3

Endpoint:

in vitro cytogenicity / chromosome aberration study in mammalian cells

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2006-05-01 to 2007-01-16

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

A respective in vivo study on the substance and an in vivo study on a structural analogous substance do not confirm the positive result from this in vitro study. Therefore, the biological relevance of this in vitro study is questionable.

Qualifier:

according to guideline

Guideline:

OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)

Version / remarks:

, 9th Addendum, 21 July 1997

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.10 (Mutagenicity - In Vitro Mammalian Chromosome Aberration Test)

Version / remarks:

08 June 2000

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.5375 - In vitro Mammalian Chromosome Aberration Test

Version / remarks:

, August 1998

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of assay:

in vitro mammalian chromosome aberration test

Target gene:

not applicable

Species / strain / cell type:

lymphocytes: Cultured peripheral human lymphocytes from healthy adult, non-smoking male volunteers

Metabolic activation:

with and without

Metabolic activation system:

phenobarbital and ß-naphtoflavone

Test concentrations with justification for top dose:

Dose range finding test:
33, 100, 333, 1000, 3528 µg/mL culture medium with and without metabolic activation

First cytogenetic assay:
333, 1000, 3528 µg/mL culture medium with and without metabolic activation; 3h exposure, 24h fixation

Second cytogenetic assay:
33, 100, 333, 666, 1000, 1333, 1666, 2000 µg/mL culture medium without metabolic activation; 24h exposure, 24h fixation
100, 333, 666, 1000, 1333, 1666, 2000 µg/mL culture medium without metabolic activation; 48h exposure, 48h fixation
333, 1000, 3258 µg/mL culture medium with metabolic activation; 3h exposure, 48h fixation

Cytogenetic assay 2A:
3, 10, 33, 100, 333, 1000, 2000, 3258 µg/mL culture medium without metabolic activation; 24h/48h exposure, 24h/48h fixation
1000, 2000, 3258 µg/mL culture medium with metabolic activation; 3h exposure, 48h fixation

Cytogenetic assay 2B:
100, 333, 1000, 1250, 1500, 1750, 2000, 2250, 2500, 2750, 3000, 3258 µg/mL culture medium without metabolic activation; 48h exposure, 48h fixation

Third cytogenetic assay: With pH-adjustment with HCl
3, 10, 33, 100, 333, 1000, 2000, 3258 µg/mL culture medium without metabolic activation; 24h exposure, 24h fixation

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: RPMI 1640 medium
- Justification for choice of solvent/vehicle: test item is water soluble

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Remarks:

RPMI 1640 medium as vehicle

Positive controls:

yes

Remarks:

Mytomycin C

Positive control substance:

cyclophosphamide

mitomycin C

Remarks:

Mitomycin C (without metabolic activation); Cyclophosphamide (with metabolic activation); Solvent for positive control was HBSS

Details on test system and experimental conditions:

METHOD OF APPLICATION: in medium; in agar (plate incorporation); preincubation; in suspension; as impregnation on paper disk

DURATION
- Preincubation period:
- Exposure duration:
- Expression time (cells in growth medium):
- Selection time (if incubation with a selection agent):
- Fixation time (start of exposure up to fixation or harvest of cells):

SELECTION AGENT (mutation assays):
SPINDLE INHIBITOR (cytogenetic assays):
STAIN (for cytogenetic assays):

NUMBER OF REPLICATIONS:

NUMBER OF CELLS EVALUATED:

DETERMINATION OF CYTOTOXICITY
- Method: mitotic index

OTHER EXAMINATIONS:
- Determination of polyploidy:
- Determination of endoreplication:
- Other:

OTHER:

Evaluation criteria:

The assay was considered acceptable if it met the following criteria:
- number of chromosome aberrations found in the solvent control culture should be within the laboratory historical control data range
- positive control should produce statistically significant increase of cells with chromosome aberrations.
- homogeneous response between the replicate cultures
- possible precipitate present should not interfere with the scoring of chromosome aberrations

Statistics:

A test substance was considered positive (clastogenic) in the chromosome aberration test if:
- dose-related statistically significance (Chi-Square test, one-sided, p < 0.05)
- statistically significant effects were observed in the absence of a clear dose-response relationship

Key result

Species / strain:

lymphocytes: human

Metabolic activation:

with and without

Genotoxicity:

positive

Remarks:

only to the 24 h continuous exposure in absence of S9-mix at the highest tested concentration

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: strain/cell type: peripheral human lymphocytes

Remarks:

Migrated from field 'Test system'.

Conclusions:

The valid test results demonstrate that Cesium Carbonate is clastogenic in human lymphocytes under the experimental conditions. The clastogenic activity is confirmed only to the 24 h continuous exposure time in the absence of S9-mix at the highest concentration. All other test conditions (3 hour or 48 hour with or without S9-mix) did not reveal genotoxic effects. No effects of test item were found on the number of polyploid cells. Therefore Cesium Carbonate does not disturb mitotic processes.

Executive summary:

Potentiell genotoxic effects of Cesium carbonate on peripheral human lymphoctes were determined regarding OECD Guideline No. 473, EEC B.10 and EPA OPPTS 870.5375. Therefore cultured stimulated lymphocytes were exposed to Cesium Carbonate in absence and presence of a metabolic activation system (phenobarbital and ß-naphtoflavone induced rat liver S9 -mix) for 3h, 24h and 48h. After exposure cell devision was arrested in metaphase stage by the addition of colchicine. Chromosome aberrations (breaks, gabs, dicentrics and exchange figures) were compared with control treated cultures and were analysed after chromosome preparation and the preparation of slides. The mitotic index of each culture was determined.

It can be concluded that Cesium Carbonate is clastogenic in human lymphocytes at specific test conditions (24h continuous exposure, presence of S9 -mix and 3258 µg/ml test item).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (positive)

Genetic toxicity in vivo

Description of key information

The target substance did not induce chromosome mutations as determined by the chromosome aberration test with bone marrow cells of the rat in vivo. Another study with the source substance cesium hydroxide monohydrate further supports the lack of clastogenicity.

Link to relevant study records

Reference

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)

Qualifier:

according to guideline

Guideline:

OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

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

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.

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

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

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.

Key result

Sex:

male/female

Genotoxicity:

negative

Toxicity:

no effects

Vehicle controls validity:

valid

Negative controls validity:

not examined

Positive controls validity:

valid

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).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

in vitro tests

Bacterial reverse mutation

The mutagenic potential of cesium carbonate was investigated in five bacterial strains: Salmonella typhimurium (TA 98, TA 100, TA 1535, TA1537 and Escherichia coli WP2 uvrA), according to OECD Guideline No. 471 and EU Method B 13/14 in an Ames assay with and without metabolic activation. Concentrations up to 5000 µg cesium carbonate/plate were tested in two independent experiments in absence and presence of S9 -mix.

The bacterial background lawn was not reduced at any tested concentration and no increase in the number of revertants was observed upon treatment with cesium carbonate. Negative and the strain-specific positive control values indicate that test conditions were adequate. Based on the results, the test item is considered to be non-mutagenic.

Chromosome aberration

Potential genotoxic effects of cesium carbonate on peripheral human lymphocytes were determined according to OECD Guideline No. 473, EEC B.10 and EPA OPPTS 870.5375. Cultured stimulated lymphocytes were exposed to cesium carbonate in absence and presence of a metabolic activation system (phenobarbital and ß-naphtoflavone induced rat liver S9 -mix) for 3h, 24h and 48h. After exposure cell division was arrested in metaphase stage by the addition of colchicine. Chromosome aberrations (breaks, gabs, dicentrics and exchange figures) were compared with control treated cultures and were analysed after chromosome preparation and the preparation of slides. The mitotic index of each culture was determined.

It can be concluded that cesium carbonate is clastogenic in human lymphocytes in vitro at specific test conditions (24h continuous exposure, absence of S9 -mix and 3258 µg/mL test item).

Mammalian cell gene mutation

No data on mammalian cell gene mutation is available for the target substance. Consequently, data from the structural analogous substance CsOH monohydrate was used. As the carbonate ion does not contribute to the overall toxicity of the metal salt (please refer to the counterion file attached to the read across statement in IUCLID section 13) the study data with cesium hydroxide is suitable to cover this endpoint.

The source substance was tested in a HPRT Mammalian Gene Mutation Test in CHO-K1 cells according to OECD guideline 476 and EU method B.17.

The test item was dissolved in Ham's F12 medium and the following concentrations and intervals (without and with metabolic activation using S9 mix) were tested in two independent experiments (both run in duplicate):

Experiment 1, 5-hour treatment period without and with S9 mix:

625, 1250, 2500, 3125, 3750, 4200, 4600*, and 5000*µg/mL

Experiment 2, 20-hour treatment period without S9 mix:

625, 1250, 2500, 3125, 3750, 4000, 4200*, 4600*, and 5000*µg/mL

Experiment 2, 5-hour treatment period with S9 mix:

625, 1250, 2500, 3125, 3750, 4000, 4200, 4600*, and 5000*µg/mL

*These concentrations were very toxic when cesium hydroxide monohydrate were applied and there was not enough cells to start the phenotypic expression period after the treatment.

In Experiment 1, there were no biologically or statistically significant increases in mutation frequency at any concentration tested, either in the absence or in the presence of metabolic activation. There were no statistical differences between treatment and control groups and no dose-response relationships were noted.

In Experiment 2, the mutant frequency of the cells did not show significant alterations compared to the concurrent control, when the test item was tested without S9 mix over a prolonged treatment period (20 hours). Furthermore, a five-hour treatment with in the presence of S9 mix did not cause significant increases in mutant frequency, further indicating that the findings in Experiment 1 were within the normal biological variation.

As in Experiment 1, in Experiment 2 no statistical differences between treatment and solvent control groups and no dose response relationships were noted. The sensitivity of the test and the efficacy of the S9 mix were demonstrated by large increases in mutation frequency in the positive control cultures.

Cesium hydroxide monohydrate tested both without and with metabolic activation (S9 mix), did not induce increases in mutant frequency in this test in Chinese hamster ovary cells. The source substance was not mutagenic in this in vitro mammalian cell gene mutation test performed with CHO-K1 cells. It is concluded that cesium carbonate has no mutagenic effects on mammalian cell genes.

 

in vivo tests

The study with the target substance was performed to investigate the potential 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 damage. 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. The results were comparable to vehicle control. The 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 Basic toxicokinetics).

The above negative result with the target substance is further supported by a chromosome aberration assay performed with the source substance cesium hydroxide monohydrate in vivo according to OECD guideline No. 475 and EU method B.11. The single oral administration of the source substance did not induce statistically or biologically significant increases in the number of bone marrow cells showing structural chromosome aberrations compared to concurrent controls with harvest at 18 or 42 hours following treatment start. No statistically significant decreases in the number of mitotic cells compared to concurrent controls were induced. Therefore, according to the results achieved in this in vivo mammalian bone marrow chromosome aberration test cesium hydroxide monohydrate is not considered to be clastogenic.

Justification for classification or non-classification

Based on the results obtained in in vitro and in vivo studies cesium carbonate is not considered to be genotoxic/mutagenic or clastogenic and thus has not to be classified according to Regulation (EC) No 1272/2008. The positive findings in the in vitro chromosome aberration test were shown to be not biologically relevant based on the results of in vivo chromosome aberration assays on cesium carbonate and the structural analogue cesium hydroxide monohydrate.