Caesium chloride

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

25.1 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Quality of whole database:

GLP and guideline study.

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

IUCLID Section 7.5.1 - KEY STUDY (90 -day oral gavage toxicity):

The aim of this 90-Day toxicity study with cesium hydroxide monohydrate was to obtain first information on the toxic potential of cesium salts 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. A sufficient stability of cesium hydroxide monohydrate in the chosen vehicle was analytically verified up front. Cesium hydroxide monohydrate was stable for 7 days at room temperature and in a refrigerator. Concentrations of the test item in the dosing formulations varied from 95 % to 97 % of nominal concentrations at all analytical occasions, thereby confirming proper dosing. Animals were observed for mortality twice a day in the course of the study. Daily general clinical observations and weekly detailed clinical observations were performed. A functional observation battery was conducted in the last week of treatment. The body weight and food consumption were measured and evaluated weekly. Clinical pathology examinations including hematology and clinical chemistry were conducted one day after the last treatment. Gross pathology was performed on animals on the day following the last treatment. The absolute and relative weights of selected organs were measured. Full histopathology was performed on the preserved organs or tissues of the animals of the control and high dose groups. Testes epididymides, prostate and seminal vesicles with coagulating gland were also evaluated histologically in all animals of the low and mid dose groups due to the necropsy and histopathological findings in these organs. The results of study were interpreted comparing test item treated groups with respect to controls, which were administered concurrently with vehicle (distilled water) only.

Results:

Mortality

There was no test item related mortality. One male and one female animal from the high dose group (250 mg/kg bw/day) died in the course of the study. In the female animal, clinical signs (irritability, piloerection, decreased activity and dyspnea) and severe body weight loss were observed before death. Histological examination revealed serious involution of thymus and signs of suffocation indicative of an individual metabolic disorder. The male animal died due to over anesthesia at the blood sampling at the termination of the study.

Clinical observations

Toxic signs related to the test item were not found at any dose level at the daily and detailed weekly clinical observations and in the course of functional observation battery.

Body weight and body weight gain

A test item related depression of the body weight development was detected in male animals at 250 and at 125 mg/kg bw/day during the entire study. The less body weight gain resulted in a less body weight compared to control group at 250 mg/kg bw/day from Day 21 and at 125 mg/kg bw/day from Day 35 up to the end of the treatment period.

Food consumption

The daily mean food consumption was reduced in male animals at 250 mg/kg bw/day during the entire observation period. Ophthalmological examination There were no abnormalities in the eyes of animals in the control and high dose groups at termination of the treatment.

Estrous cycle

A test item influence on the estrous cycle cannot be excluded with the results of this study. None of high dose (250 mg/kg bw/day) treated animal had regular cycle however the number of control animals with regular cycle was also significantly less than in the historical control data. There was no significant difference in the number of animals with an irregular estrous cycle in the low dose group as compared to the control group.

Hematology

A slightly higher mean white blood cell count and higher mean percentage of reticulocytes were detected in male and female animals at 250 and 125 mg/kg bw/day with respect to control group. Blood coagulation There were no test item induced pathologic changes in the examined blood coagulation parameters.

Clinical chemistry

Clinical chemistry evaluation revealed an elevated activity of aspartate aminotransferase at 250 and 125 mg/kg bw/day (male and female), as well as higher concentrations of urea, creatinine and less mean glucose concentration at 250 mg/kg bw/day (male and female) and at 125 mg/kg bw/day (male). These changes were indicative of the altered metabolic processes as histopathological examinations did not point out a damage in the relevant organs or tissues.

Necropsy

The testes and epididymides were judged to be smaller than normal in animals of 250 mg/kg bw/day group at the necropsy observations.

Organ weight

Significant reduction of the mean testes weights at 250 mg/kg bw/day and in epididymides weights at 250 and 125 mg/kg bw/day reflected a test item related influence. The significantly less liver weights in male animals administered with 250 or 125 mg/kg bw/day probably were in accordance with the body weight alteration. Slightly higher kidneys weights at 250 mg/kg bw/day (male and female), and at 125 mg/kg bw/day (female) with respect to controls were considered to be signs of adaptation of the organ to the altered demands. The mean thymus weight (absolute and relative to brain weight) in the male animals) and the absolute mean thymus weight in the female animals were less than the control in animals administered with 250 mg/kg bw/day.

Sperm analysis

Sperm analysis revealed lack of the sperm cells at 250 mg/kg bw/day and damage of the motility and morphology of the sperm cells at 125 mg/kg bw/day dose.

Histopathology

Histological examination detected decreased intensity of spermatogenesis, which was 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 in 250 mg/kg bw/day dose treated male animals.

Conclusion

Under the conditions of the present study, the 250 mg/kg bw/day dose of the test item caused reduced body weight, body weight gain, and reduced food consumption (male), and changes in hematology parameters (white blood cell count and percentage of reticulocyte – male and female). 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 considered to be toxicologically relevant.

 

A test item influence on the estrous cycle could not be excluded as none of the female animals in the dose group of 250 mg/kg bw/day had a regular estrous cycle. 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 considered to be equivocal.

 

At 125 mg/kg bw/day, depression of the body weight development (male), altered clinical pathology parameters (slightly higher mean white blood cell count and higher mean percentage of reticulocytes (male and female), reduced weight of epididymides and damage of sperm motility and morphology) were indicative of adverse test item related effects.

 

At 25 mg/kg bw/day, there were no test item related toxic alterations.

 

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

Based on these results the calculated NOAEL for cesium hydroxide anhydrous is 22.32 mg/kg bw/day.

Short description of key information:
Based on the result of the subchronic repeated dose oral toxicity study (see IULCID section 7.5.1 - key study) cesium hydroxide monohydrate caused interference with the male reproductive system (testis, epididymis, spermatogenesis) at dose levels of 250 and 125 mg/kg bw/day.
Based on this result cesium chloride is classified as Repr. 2 (H361f) according to Regulation (EC) No 1272/2008.

For this study 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
Based on these results the calculated NOAEL for cesium chloride is 25.1 mg/kg bw/day.

Justification for selection of Effect on fertility via oral route:
Based on the result of the subchronic repeated dose oral toxicity study (see IULCID section 7.5.1)

Effects on developmental toxicity

Description of key information

No developmental toxicity study with cesium chloride is available. Consequently, read-across with the structural analogous read-across substance cesium hydroxide monohydrate was performed. In a developmental toxicity study with cesium hydroxide monohydrate according to OECD guideline 414 no developmental toxicity was observed.
There are no studies on cesium chloride to cover the endpoint "Developmental toxicity / Teratogenicitiy" via respiratory or dermal route.

Link to relevant study records

Reference

Endpoint:

developmental toxicity

Type of information:

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

Adequacy of study:

key study

Study period:

2012-07-23 to 2013-01-09

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP and guideline compliant. An experimental study was performed with a structural analogous read-across substance. Please refer to IUCLID section 13 for read-across justification.

Reason / purpose for cross-reference:

reference to other study

Qualifier:

according to guideline

Guideline:

OECD Guideline 414 (Prenatal Developmental Toxicity Study)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.31 (Prenatal Developmental Toxicity Study)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.3700 (Prenatal Developmental Toxicity Study)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Limit test:

no

Species:

rat

Strain:

Wistar

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (Europe) Laboratories Inc., Toxi-Coop Zrt., Cserkesz u. 90., 1103 Budapest, Hungary
- Age at study initiation (start of mating): adult (males), 11-12 weeks old (females)
- Weight at study initiation: The group averages of the body weight were as similar as possible on the first day of gestation.
- Fasting period before study: no
- Housing: 1-2 males/cage and 1-3 females/cage before mating, 1 male and 1-3 female(s)/cage during mating, 2-3 or 1 sperm positive female(s)/cage during gestation; in type II polypropylene/polycarbonate cages.
- Diet: ssniff® SM R/M-Z+H "Autoclavable complete feed for rats and mice – breeding and maintenance" (ssniff Spezialdiäten GmbH, 59494 Soest, Germany), ad libitum.
- Water: tap water from municipal supply, from 500 mL bottles, ad libitum.
- Acclimation period: 96 days (males), 26 days (females)

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3 °C
- Humidity: 30 - 70 %
- Air changes: 8 - 12 air exchanges/hour by central air-condition system.
- Photoperiod: 12 hours dark / 12 hours light

Route of administration:

oral: gavage

Vehicle:

water

Details on exposure:

PREPARATION OF DOSING SOLUTIONS:
The test item was formulated in the vehicle water. Due to the corrosive properties of the test item, the pH value of the formulations was adjusted to pH 7-9 with HCl prior to gavage administration.

VEHICLE
- Concentration in vehicle: 1, 4 or 15 mg/mL
- Amount of vehicle: dose volume of 10 mL/kg bw

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Formulations were prepared in the formulation laboratory of the test facility daily to weekly. The suitability of the chosen vehicle for the test item at the intended concentrations was analytically verified up front. A sufficient stability and homogeneity in the chosen vehicle were verified over the range of relevant concentrations at the appropriate frequency of preparation (Toxi-Coop Study no.: 559.198.2751) analytical control (concentration, homogeneity) of dosing solutions was performed in the Laboratory of Toxi-Coop Zrt. twice during the treatment period. The cesium hydroxide monohydrate concentrations in the samples were found to be 94 – 95 % in comparison to the nominal values.

Details on mating procedure:

- Impregnation procedure: cohoused
- M/F ratio per cage: 1/1-3
- Length of cohabitation: 2-4 hours
- Verification of same strain and source of both sexes: yes
- Proof of pregnancy: sperm in vaginal smear referred to as day 0 of pregnancy

Duration of treatment / exposure:

Days 5-19 of gestation

Frequency of treatment:

Once per day

Duration of test:

15 treatment days

No. of animals per sex per dose:

At least 24 sperm positive females

Control animals:

yes, concurrent vehicle

Details on study design:

- Dose selection rationale: Dose setting was based on the results of a dose range finding prenatal developmental toxicity study (study number: 559.410.3533), under consideration of the results of a 14-day repeated dose oral gavage dose range finding toxicity study in rats (study number 559.400.2734) and a 28-day repeated dose oral gavage toxicity study in rats (study number 559.407.2735).

Maternal examinations:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Twice daily (mortality), once daily (clinical signs of systemic toxicity)

DETAILED CLINICAL OBSERVATIONS: No

BODY WEIGHT: Yes
- Time schedule for examinations: On gestation days 0, 3, 5, 8, 11, 14, 17 and 20

FOOD CONSUMPTION: Yes
- Time schedule for examinations: Between gestation days 0-3, 3-5, 5-8, 8-11, 11-14, 14-17 and 17-20
- Food consumption determined and mean daily diet consumption calculated as g food/kg bw/day: Yes

WATER CONSUMPTION: No

POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 20
- Organs examined: General macroscopical examination for gross lesions

OTHER:
- All sperm positive animals were examined for vaginal bleeding on days 13 and/or 14 of the gestation phase.

Ovaries and uterine content:

The ovaries and uterine content was examined after termination.
Examinations included:
- Gravid uterus weight
- Number of corpora lutea
- Number of implantations
- Number of early resorptions
- Number of late resorptions

Fetal examinations:

- External examinations: Yes, all per litter
- Soft tissue examinations: Yes, half per litter
- Skeletal examinations: Yes, half per litter
- Head examinations: Yes, half per litter (all animals assigned for soft tissue examinations)

Statistics:

The statistical evaluation of data was performed with the program package SPSS PC+4.0. The homogeneity of variance between groups was checked by Bartlett’s homogeneity of variance test. Where no significant heterogeneity was detected, a one-way analysis of variance (ANOVA) was carried out. If the obtained result was significant, Duncan’s Multiple Range test was used to access the significance of intergroup differences. If a significance was the result of the Bartlett’s test, the Kruskal-Wallis analysis of variance was used and the intergroup comparisons were performed using the Mann-Whitney U-test.

Indices:

Percent pre-implantation loss, post-implantation loss, sex distribution.
Percent external, visceral and skeletal abnormalities.

Clinical signs:

no effects observed

Dermal irritation (if dermal study):

not examined

Mortality:

no mortality observed

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

a statistically significantly lower body weight gain indicated in the 150 mg/kg bw/day dose group in the last three days of the study (p<0.01, -20%) and if the whole in-life phase was evaluated (p<0.05, -10%). A statically significant reduction in the corrected body weight gain was observed in the 40 mg/kg bw/day dose group (p<0.01, -17%) and in the 150 mg/kg bw/day dose group (p<0.05, -14%)

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Description (incidence and severity):

lower food consumption in the highest dose group was attributed to an effect of the test item.

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

no effects observed

Clinical biochemistry findings:

no effects observed

Endocrine findings:

not examined

Description (incidence and severity):

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Neuropathological findings:

not examined

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

not examined

Other effects:

no effects observed

Number of abortions:

no effects observed

Pre- and post-implantation loss:

no effects observed

Total litter losses by resorption:

no effects observed

Early or late resorptions:

no effects observed

Dead fetuses:

no effects observed

Changes in pregnancy duration:

no effects observed

Changes in number of pregnant:

no effects observed

Other effects:

no effects observed

Details on maternal toxic effects:

Maternal toxic effects:yes

Details on maternal toxic effects:
There were no significant differences indicated in the body weight and body weight gain of the dams in the 10 and 40 mg/kg bw/day dose groups.
There was a statistically significantly lower body weight gain indicated in the 150 mg/kg bw/day dose group in the last three days of the study (p<0.01, -20%) and if the whole in-life phase was evaluated (p<0.05, -10%). A statically significant reduction in the corrected body weight gain was observed in the 40 mg/kg bw/day dose group (p<0.01, -17%) and in the 150 mg/kg bw/day dose group (p<0.05, -14%), which corresponded with a lower food consumption and was attributed to an effect of the test item.

The food consumption of the dams was reduced slightly but statistically significantly in the mid dose group (40 mg/kg bw/day) between days 11 to 14 (p<0.01 without a dose response, -8%), 14 to 17 (p<0.05, -7%) and 17 to 20 (p<0.01, -12%). In the high dose group (150 mg/kg bw/day) the food consumption was reduced as well slightly but statistically significant from day 14 up to necropsy (p<0.01, -8 to -10%) if compared to the control. The reduction in the food consumption associated with a lower body weight gain in the 150 mg/kg bw/day dose group and with a reduced corrected body weight gain in the 40 and 150 mg/kg bw/day dose group.
A slight reduction in the food consumption (p<0.05, -8%) of the dams observed between days 17 to 20 in the 10 mg/kg bw/day dose group did not result in changes in the body weight parameters and was regarded to be incidental.

Key result

Dose descriptor:

NOAEL

Effect level:

10 mg/kg bw/day (nominal)

Based on:

test mat.

Remarks:

cesium hydroxide monohydrate

Basis for effect level:

body weight and weight gain

food consumption and compound intake

Key result

Dose descriptor:

NOAEL

Effect level:

150 mg/kg bw/day (nominal)

Based on:

test mat.

Basis for effect level:

dead fetuses

early or late resorptions

effects on pregnancy duration

endocrine findings

maternal abnormalities

necropsy findings

number of abortions

pre and post implantation loss

total litter losses by resorption

Key result

Dose descriptor:

NOAEL

Effect level:

7.9 mg/kg bw/day (nominal)

Based on:

test mat.

Remarks:

calculated for Cesium

Basis for effect level:

body weight and weight gain

food consumption and compound intake

Key result

Dose descriptor:

NOAEL

Effect level:

118.7 mg/kg bw/day (nominal)

Based on:

test mat.

Remarks:

calculated for Cesium

Basis for effect level:

changes in number of pregnant

changes in pregnancy duration

dead fetuses

early or late resorptions

effects on pregnancy duration

endocrine findings

maternal abnormalities

necropsy findings

number of abortions

pre and post implantation loss

total litter losses by resorption

Key result

Dose descriptor:

NOAEL

Effect level:

10 mg/kg bw/day (nominal)

Based on:

test mat.

Remarks:

calculated for cesium chloride

Basis for effect level:

body weight and weight gain

food consumption and compound intake

Key result

Dose descriptor:

NOAEL

Effect level:

150.4 mg/kg bw/day (nominal)

Based on:

test mat.

Remarks:

calculated for Cesium Chloride

Basis for effect level:

changes in number of pregnant

changes in pregnancy duration

early or late resorptions

effects on pregnancy duration

endocrine findings

maternal abnormalities

necropsy findings

number of abortions

pre and post implantation loss

total litter losses by resorption

Fetal body weight changes:

no effects observed

Reduction in number of live offspring:

no effects observed

Changes in sex ratio:

no effects observed

Changes in litter size and weights:

no effects observed

Anogenital distance of all rodent fetuses:

no effects observed

Description (incidence and severity):

None

Changes in postnatal survival:

no effects observed

External malformations:

no effects observed

Skeletal malformations:

no effects observed

Visceral malformations:

no effects observed

Other effects:

no effects observed

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
There was no effect related to the administration of the test item in the preimplantation loss, intrauterine mortality of the conceptuses, the number of implantations, viable fetuses and their sex distribution.

The mean fetal weight, placental and relative placental weight were similar across the control and test item treated groups.

The distribution of external, visceral and skeletal variations was homogenous among the experimental groups.

There were no malformations found during external and visceral evaluation of the fetuses and there were no significant differences in the skeletal malformations if compared to the control.

Dose descriptor:

NOAEL

Effect level:

150 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

fetal/pup body weight changes

Abnormalities:

no effects observed

Developmental effects observed:

no

Conclusions:

A prenatal development toxicity study with cesium chloride is not available. Consequently, read-across was applied using study results from cesium hydroxide monohydrate.
Based on the observations the No Observed Adverse Effect Level (NOAEL) for cesium hydroxide monohydrate was determined as follows:
NOAEL maternal toxicity: 10 mg/kg bw/day
NOAEL developmental toxicity: 150 mg/kg bw/day

Conclusively, the calculated NOAEL for cesium and cesium nitrate were determined as follows:
Cesium: NOAEL for maternal toxicity 7.9 mg/kg bw/day.
Cesium: NOAEL for developmental toxicity 118.72 mg/kg bw/day.
Cesium chloride: NOAEL for maternal toxicity 10.0 mg/kg bw/day.
Cesium chloride: NOAEL for developmental toxicity 150.4 mg/kg bw/day.

Executive summary:

A prenatal development toxicity study with cesium chloride is not available. Consequently, read-across was applied using study results from cesium hydroxide monohydrate.

Groups of 27 sperm- positive female Wistar rats were treated with the test item by oral administration daily at three dose levels of 10, 40 and 150 mg/kg bw/day from day 5 up to and including day 19 post coitum. A control group of 25 sperm positive females was included and the animals were given the vehicle distilled water. The treatment volume was 10 mL/kg bw. During the study, mortality was checked for and clinical observations were performed. Body weight and food consumption of the dams were also recorded. The day when sperm was detected in the vaginal smear was regarded as day 0 of gestation. A Caesarean section and gross pathology were performed on gestational day 20. The number of implantations, early and late resorption, live and dead fetuses in each uterine horn and the number of corpora lutea were recorded. Each fetus was weighed and examined for sex and gross external abnormalities. The placentas were weighed and examined externally. About half of each litter was preserved for visceral examination and the other half of the litters were preserved for skeletal evaluation. At visceral examination the bodies were micro dissected by means of a dissecting microscope. The heads were examined by Wilson's free-hand razor blade method. After cartilage-bone staining the skeletons were examined by means of a dissecting microscope. All abnormalities found during the fetal examinations were recorded. In total, there were 18, 20, 22 and 23 evaluated litters in the control, 10, 40 and 150 mg/kg bw/day groups, respectively. Oral treatment of pregnant rats from gestation days 5 to 19 (i.e. the day before Caesarean section) with the test item did not cause death, clinical signs or macroscopical alterations at necropsy at the dose levels of 10, 40 and 150 mg/kg bw/day. The test item did not reveal any adverse effect on the pregnancy of the dams, the pre-implantation loss, the intrauterine mortality of the conceptuses, the number of viable fetuses and their sex distribution. The development of fetuses evaluated at external, visceral and skeletal examination and determined by the fetal body weight was undisturbed. The test item caused no fetal malformation at the dose levels of 10, 40 and 150 mg/kg bw/day. The reduced food consumption from day 14 onwards and the lower corrected body weight gain of the dams at the dose levels of 40 and 150 mg/kg bw/day as well as the reduced body weight gain in the last three days of the in- life phase of the dams in the 150 mg/kg bw/day dose group were attributed to the treatment with the test item.

Based on these observations the No Observed Adverse Effect Level (NOAEL) was determined to be 10 mg/kg bw/day for maternal toxicity and 150 mg/kg bw/day for developmental toxicity.

Conclusively, the calculated NOAEL for cesium and cesium chloride were determined as follows:

Cesium: NOAEL for maternal toxicity 7.9 mg/kg bw/day.

Cesium: NOAEL for developmental toxicity 118.72 mg/kg bw/day.

Cesium chloride: NOAEL for maternal toxicity 10.0 mg/kg bw/day.

Cesium chloride: NOAEL for developmental toxicity 150.4 mg/kg bw/day.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Additional information

A prenatal development toxicity study with cesium chloride is not available. Consequently, read-across was applied using study results from cesium hydroxide monohydrate.

Groups of 27 sperm- positive female Wistar rats were treated with the test item by oral administration daily at three dose levels of 10, 40 and 150 mg/kg bw/day from day 5 up to and including day 19 post coitum. A control group of 25 sperm positive females was included and the animals were given the vehicle distilled water. The treatment volume was 10 mL/kg bw. During the study, mortality was checked for and clinical observations were performed. Body weight and food consumption of the dams were also recorded. The day when sperm was detected in the vaginal smear was regarded as day 0 of gestation. A Caesarean section and gross pathology were performed on gestational day 20. The number of implantations, early and late resorption, live and dead fetuses in each uterine horn and the number of corpora lutea were recorded. Each fetus was weighed and examined for sex and gross external abnormalities. The placentas were weighed and examined externally. About half of each litter was preserved for visceral examination and the other half of the litters were preserved for skeletal evaluation. At visceral examination the bodies were micro dissected by means of a dissecting microscope. The heads were examined by Wilson's free-hand razor blade method. After cartilage-bone staining the skeletons were examined by means of a dissecting microscope. All abnormalities found during the fetal examinations were recorded. In total, there were 18, 20, 22 and 23 evaluated litters in the control, 10, 40 and 150 mg/kg bw/day groups, respectively. Oral treatment of pregnant rats from gestation days 5 to 19 (i.e. the day before Caesarean section) with the test item did not cause death, clinical signs or macroscopical alterations at necropsy at the dose levels of 10, 40 and 150 mg/kg bw/day. The test item did not reveal any adverse effect on the pregnancy of the dams, the pre-implantation loss, the intrauterine mortality of the conceptuses, the number of viable fetuses and their sex distribution. The development of fetuses evaluated at external, visceral and skeletal examination and determined by the fetal body weight was undisturbed. The test item caused no fetal malformation at the dose levels of 10, 40 and 150 mg/kg bw/day. The reduced food consumption from day 14 onwards and the lower corrected body weight gain of the dams at the dose levels of 40 and 150 mg/kg bw/day as well as the reduced body weight gain in the last three days of the in- life phase of the dams in the 150 mg/kg bw/day dose group were attributed to the treatment with the test item.

Based on these observations the No Observed Adverse Effect Level (NOAEL) was determined to be 10 mg/kg bw/day for maternal toxicity and 150 mg/kg bw/day for developmental toxicity.

Conclusively, the calculated NOAEL for cesium and cesium chloride were determined as follows:

Cesium: NOAEL for maternal toxicity 7.9 mg/kg bw/day.

Cesium: NOAEL for developmental toxicity 118.72 mg/kg bw/day.

Cesium chloride: NOAEL for maternal toxicity 10.0 mg/kg bw/day.

Cesium chloride: NOAEL for developmental toxicity 150.4 mg/kg bw/day.

Justification for selection of Effect on developmental toxicity: via oral route:
GLP and guideline compliant study with the structural analogous read-across substance cesium hydroxide monohydrate. Please refer to IUCLID section 13 for read-across justification.

Justification for classification or non-classification

Based on the result of the subchronic repeated dose oral toxicity study (see IULCID section 7.5.1) cesium hydroxide monohydrate causes interference with the male reproductive system (testis, epididymis, spermatogenesis). Therefore also cesium chloride is classified as Repr. 2 (H361f) according to Regulation (EC) No 1272/2008.

Based on the results of a developmental toxicity study with the structural analogous substance cesium hydroxide monohydrate cesium chloride is not subject to classification as reproductive toxic according to the criteria EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No 1272/2008.