Caesium carbonate

Endpoint summary

Description of key information

Based on the available 90 d studies with the structural analogues cesium hydroxide hydrate and cesium chloride NOAELs of 19.8 mg Cs/kg bw/d and 10.3 mg Cs/kg bw/d were determined, respectively. No effects were observed up to 19.8 mg Cs+/kg bw/d therefore the oral 90-day NOAEL of 25 mg CsOH*H2O/kg bw/d is used as source value. Re-calculation results in a NOAEL of 24.3 mg/kg bw/d for cesium carbonate which will be used as key value for risk assessment.

Key value for chemical safety assessment

Toxic effect type:

dose-dependent

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

sub-chronic toxicity: oral

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

Reason / purpose for cross-reference:

read-across source

Key result

Dose descriptor:

NOAEL

Effect level:

19.8 mg/kg bw/day (actual dose received)

Based on:

other: calculated for Cs

Sex:

male/female

Basis for effect level:

body weight and weight gain

food consumption and compound intake

haematology

sperm measures

Remarks on result:

other: based on CsOH monohydrate

Key result

Dose descriptor:

NOAEL

Effect level:

24.3 mg/kg bw/day (actual dose received)

Based on:

other: calculated for Cs2CO3

Sex:

male/female

Basis for effect level:

body weight and weight gain

food consumption and compound intake

haematology

sperm measures

Remarks on result:

other: Based on CsOH monohydrate

Dose descriptor:

NOAEL

Effect level:

10.3 mg/kg bw/day (actual dose received)

Based on:

other: calculated for Cs

Sex:

male/female

Basis for effect level:

sperm measures

Remarks on result:

other: Based on CsCl

Dose descriptor:

NOAEL

Effect level:

12.7 mg/kg bw/day (actual dose received)

Based on:

other: calculated for Cs2CO3

Sex:

male/female

Basis for effect level:

sperm measures

Remarks on result:

other: Based on CsCl

Key result

Critical effects observed:

yes

Lowest effective dose / conc.:

37 mg/kg bw/day (actual dose received)

System:

male reproductive system

Organ:

other: sperm cell number and morphology

Treatment related:

yes

Dose response relationship:

yes

Relevant for humans:

not specified

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

24.3 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Quality of whole database:

Read across from GLP and guideline compliant studies

System:

male reproductive system

Organ:

adrenal glands

kidney

testes

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

There is no repeated dose toxicity study for cesium carbonate available. Consequently, data from the structural analogous substances cesium hydroxide monohydrate and cesium chloride were used. As carbonate 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 and chloride are suitable to cover this endpoint. Both source substances were applied to male and female Wistar rats for 90 days. Relevant effects can be observed at a cesium dose of 30 mg/kg bw/d and above. This is shown in the 90 d study with CsCl as well as in the reproduction/developmental toxicity screening test with CsNO₃ (please refer to IUCLID section 7.8.1 for further information). The low NOAEL of Cs in the CsCl study is based on the dosing regimen. Therefore results from cesium hydroxide monohydrate were used for assessment of cesium carbonate. The key results of both 90 d studies are summarised below.

 

Key study

The aim of this 90-Day toxicity study was to obtain first information on the toxic potential of cesium hydroxide monohydrate in rats at three dose levels following 90-day oral administration. The study was performed in compliance with the OECD guideline No. 408, EU method B.26 and EPA guideline OPPTS 870.3100. The test item was administered orally (by gavage) to Hsd.Brl.Han: Wistar rats (n=10 animals/sex/group) once a day at 0 (vehicle control), 250, 125 and 25 mg/kg bw/day doses corresponding to concentrations of 0, 25, 12.5 and 2.5 mg/mL, applied in a dose volume of 10 mL/kg bw for 90 days. The dose levels correspond to 199, 99 and 19.8 mg Cs/kg bw/d.

Under the conditions of the present study, the 250 mg/kg bw/day dose of cesium hydroxide monohydrate caused reduced body weight, body weight gain, and reduced food consumption (male), and changes in haematology parameters (white blood cell count and percentage of reticulocyte – male and female).Clinical chemistry showed in an elevated activity of Aspartate Amino transferase in males and females of the 250 bw dose group as well as higher concentrations of urea and creatinine and lower mean glucose concentration in males and females. The latter findings are indicative of an impaired kidney function. Damage in spermatogenesis (smaller than normal testes, reduced weights of testes and epididymides, decreased intensity of spermatogenesis, accompanied with lack of mature spermatozoa in the seminiferous tubuli in the testes and in the ductuli of epididymides, and decreased number of spermatids in a proportion of seminiferous tubuli) after the 90-day oral (gavage) administration in Hsd.Brl.Han: Wistar rats was observed. These test item-related changes were toxicologically relevant.

 

A test item influence on the oestrous cycle could not be excluded as none of the female animals in the dose group of 250 mg/kg bw/day had a regular oestrous cycle. However, the concurrent control group showed significantly less animals with irregular oestrous cycle then the historical controls. At this dose level, slight changes in thymus weights were noted in male and female animals, which were associated with an accelerated involution process as compared with the controls. The toxicological significance of this finding was equivocal.

 

At 125 mg/kg bw/day, depression of the body weight development (male), altered hematology parameters (slightly higher mean white blood cell count and higher mean percentage of reticulocytes (male and female). Clinical chemistry showed in an elevated activity of Aspartate Amino transferase in males and females of the 125 mg/kg bw dose group as well as higher concentrations of urea and creatinine and lower mean glucose in males of this dose group.  reduced weight of epididymides, impaired sperm motility and changes in sperm morphology) were indicative of adverse test item related effects.

At 25 mg/kg bw/day, there were no test item related adverse effects.

Based on these observations the No Observed (Adverse) Effect Level (NO(A)EL) for cesium hydroxide monohydrate was determined as follows:

NOAEL: 25 mg/kg bw/day for male and female animals (equivalent to 19.8 mg Cs/kg bw/day and 24.3 mg Cs₂CO₃/kg bw/d).

 

 

Supporting study

A study was conducted to assess the systemic toxicity of cesium (Cs) in a 13-week oral gavage study in Han Wistar rats followed by a recovery period of up to 16 weeks (Webley, 2016). This study was designed to investigate in more detail the relationship between the toxicity produced by Cs (e.g. uremia, hypokalemia, alkalosis) and male reproductive effects (e.g. decrease in sperm motility, decrease in spermatogenesis and histopathological changes in the testes.

Four groups received the vehicle or cesium chloride (CsCl) at doses of 13, 38 and 127 mg/kg bw/day (equivalent to 10, 30 and 100 mg Cs/kg bw/day) for 13 weeks, followed by an 8, 12- or 16-week recovery period. A fifth treated group received cesium chloride (CsCl) at 253 mg/kg bw/day (equivalent to 200 mg Cs/kg/day) for a reduced treatment period of 59 days because of excessive toxicity, followed by an approximate 4- or 12-week recovery period.

 

Oral administration of cesium chloride (CsCl) to Han Wistar rats at doses of 13, 38, 127 or 253 mg/kg bw/day (equivalent to 10, 30, 100 or 200 mg Cs/kg bodyweight/day) resulted in pathological changes in the mandibular and sublingual salivary glands, heart, stomach, spleen, adrenals, mammary glands, skin and subcutis, epididymides and testes of animals treated at 253 mg/kg bw/day for 59 days or 127 mg/kg bw/day for 13 weeks. Additional changes were seen in the kidneys, skeletal muscles, extremities, ovaries and uterus of animals treated at 253 mg/kg bw/day. At 38 mg/kg bw/day, treatment-related changes were seen in the adrenals and testes. In addition, changes in the blood and urine indicative of an effect on kidney function were apparent at doses of 38 mg/kg bw/day and above; in particular, there was a clear increase in plasma urea and decrease in plasma potassium which was dose-related and marked at the 127 and 253 mg/kg bw/day dose levels. There was a dose-dependent detrimental effect on maturation of the sperm with most sperm breaking down within the epididymis. Treatment at 127 or 253 mg/kg bw/day resulted in most males showing no motile or normal sperm and significant reductions in sperm numbers. There was also a significant reduction in total sperm number in the cauda epididymis at 38 mg/kg bw/day and a slight effect on sperm morphology.

 

The dose of 253 mg/kg bw/day clearly exceeded the maximum tolerated dose and treatment at this dose level was stopped in Week 9. Recovery from all treatment-related changes was demonstrated, though one male receiving 127 mg/kg bw/day, still showed changes in the testes with associated low sperm numbers, all of which were immotile and abnormal after 16 weeks of recovery. No change on sperm numbers, morphology or motility or any pathological changes were seen at 13 mg/kg /day, nor were there any indications of an effect on the kidney. Consequently, based on these findings, the NOAEL was 13 mg CsCl/kg bw/day (equivalent to 10 mg Cs/kg bw/day and 12.7 mg Cs₂CO₃/kg bw/d).

 

Justification for classification or non-classification

Based on the above study data, cesium carbonate is classified into cat. 2 for single target organ toxicity upon repeated exposure according to Regulation (EC) 1272/2008. Kidneys, adrenals, testis and epididymis were identified as target organs.