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Description of key information

According to the results from the acute oral toxicity study, the LD50 obtained for the test item was found to be between 300 and 2000 mg/kg bw. Therefore, the test item is classified as harmful if swallowed (category 4) according to Regulation (EC) No 1272/2008 (CLP/GHS).
According to the results of acute dermal toxicity studies with two structural analogous read-across substances the test item is not classified according to Regulation (EC) No 1272/2008 (CLP/GHS) or Directive 67/548/EEC (DSD).

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2011-03-24 to 2011-04-13
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP and guideline compliant
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
other: Crl(WI)Br
Sex:
female
Details on test animals and environmental conditions:
Test animals
- Source: Toxi-Coop Zrt. 1103 Budapest, Cserkesz u. 90.
- Age at study initiation: young adult rats, 11/12 weeks old
- Weight at study initiation: 223-229 g
- Fasting period before study: food but not water was withheld overnight
- Housing: 3 animals/sex/cage
- Diet: ad libitum (ssniff® SM R/M-Z+H complete diet)
- Water: ad libitum
- Acclimation period: 35 days in first step, 36 days in second step and 40 days in third step

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3 °C
- Humidity: 30 - 70 %
- Air changes: 8 - 12 air exchanges/hour by central air-condition system
- Photoperiod: artifical light, from 6 a.m. to 6 p.m.
Route of administration:
oral: gavage
Vehicle:
physiological saline
Control animals:
no
Details on study design:
Testing Procedure
A single oral administration - followed by a fourteen-day observation period - was performed by gavage. The day before treatment the animals were
fasted. The food but not water was withheld overnight. Animals were weighed before the application and the food was given back 3 hours after the treatment.

Dose Level
Starting dose was selected on the basis of the available information about the test item.
The acute toxic class method was carried out involving a stepwise procedure with the use of 2000 mg/kg bw as the starting dose in three female rats.

Observations
Mortality
Inspection for signs of morbidity and mortality were made twice daily at the beginning and end of the working day.
Clinical Observations
Individual observations were performed on the skin and fur, eyes and mucous membranes and also respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
Body weight
The body weight were recorded on day 0 (shortly before the treatment), at day 7 and at day 15 on all animals with a precision of 1 g.
Pathology
All animals were subjected to gross pathology. All animals were exsanguinated under isoflurane anaesthesia. After examination of the external appearance the cranial, thoracic and abdominal cavities were opened and the appearance of the tissues and organs were observed. All gross pathological changes were recorded for each animal on the post mortem record sheets.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 300 - < 2 000 mg/kg bw
Based on:
test mat.
Mortality:
All rats dosed at 2000 mg/kg Cesiumsulfat 99,99 died between the treatment day and Day 1.
No death occurred at 300 mg/kg single oral dose of the test item. All rats survived until the end of the 14-day observation period.
Clinical signs:
2000 mg/kg bw:
In group 1 treated with 2000 mg/kg dose clinical sign of reaction comprised of decreased activity and general reaction (14 cases out of 14 observations), prostration (10/14), clonic convulsion (1/14), decreased righting reflex (8/14), decreased grip- and limb tone (8/14), decreased body tone (8/14), piloerection (14/14), dyspnoea (1/14), abnormal gait (2/14), incoordination (2/14), decreased plantary reflex (2/14), crouching (2/14), diuresis (2/14) and bloody urine (2/14). Decreased activity and general reaction (score -2; -3; -4), prostration (score +2; +3), decreased righting reflex (score -1; -2), decreased grip- and limb tone (score -1; -2), decreased body tone (score -2; -1) and piloerection (score +1; +2; +3) occurred in all animals. Abnormal gait (score +2), incoordination (score +3), decreased plantary reflex (score -2; -3), crouching (score +3) and diuresis (score +2) were found in two animals (No.: 8116, 8117). However, dyspnoea (score +2) was recorded in one animal and bloody urine (score +2; +3) and clonic convulsion (score +1) were detected in another animal.

300 mg/kg bw:
No treatment related symptoms were observed throughout the 14-day post-treatment period in all animals of group 2 and 3 treated with 300 mg/kg dose.
Body weight:
The body weight and body weight gain data of group 1 (2000 mg/kg) could not be evaluated, because all rats died in this group.
In group 2 and 3 (300 mg/kg) the mean body weight of the animals corresponded to their species and age throughout the study.
Gross pathology:
All rats treated with 2000 mg/kg dose of the test item spontaneously died during the study. There was no any macroscopic alteration in died animals.
All animals treated with 300 mg/kg dose of test item survived until the scheduled necropsy on Day 15. Slight hydrometra was found in two females of the group 3. Hydrometra is physiological finding and connected to the cycle of the animal. No pathological changes were found related to the effect of the test item during the macroscopic examination of animals.
Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral LD50 obtained for the test item was found to be between 300 and 2000 mg/kg bw. Therefore, the test item is classified as category 4 according to Regulation (EC) No 1272/2008 (CLP/GHS).
Executive summary:

This study was conducted to assess the acute oral toxicity of the test item in Rats (Crl(WI)Br) according to OECD Guideline 423 and EU Method B.1 tris. The acute toxic class method was carried out involving a stepwise procedure with the use of 2000 mg/kg bw as the starting dose in three female rats. Since three female animals died the test was continued at 300 mg/kg bw dose level on further three female rats. No animal died in the second step at 300 mg/kg bw dose level, three further female rats were treated with the same (300 mg/kg bw) dose. No animal died in the third step, too, so the test was finished, the stopping criteria of Annex 2d of OECD Guideline No. 423 (presented in Annex VII) were met. Animals were weighed, observed for lethality and toxic symptoms for 14 days after the treatment. Gross pathological examination was carried out on the 15th day after the treatment.

According to the results from this study the LD50 obtained for the test item was found to be between 300 and 2000 mg/kg bw. Therefore, the test item is classified as category 4 according to Regulation (EC) No 1272/2008 (CLP/GHS).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
300 mg/kg bw
Quality of whole database:
CLP, guideline and GLP compliant study.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
2012-01-24 to 2012-02-22
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: CLP, guideline and GLP compliant study. An experimental study was performed with a structural analogous read-across substance.
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
, adopted 1987
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
, adopted 1992
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Version / remarks:
,adopted 1998
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Toxi-Coop Zrt. 1103 Budapest, Cserkesz u. 90.
- Age at study initiation: Young adult rats, 11 /12 weeks old
- Weight at study initiation: Male 272-300 g, Female 217-242 g
- Fasting period before study: food but not water was withheld overnight
- Housing: 5 animals/sex/cage
- Diet: ad libitum (ssniff® SM R/M-Z+H complete diet )
- Water: ad libitum
- Acclimation period: 5 days for the pre-study, 19 days for the main study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 30 - 70 %
- Air changes (per hr): 8-12 air exchanges/hour by central air-condition system.
- Photoperiod: Artificial light, from 6 a.m. to 6 p.m.
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: approximately 10 % of the total body surface
- Type of wrap if used: sterile gauze pad below a semi-occlusive plastic wrap

REMOVAL OF TEST SUBSTANCE
- Washing: water pre-warmed to body temperature
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount applied: Main-tests: 2000 mg/kg bw; pre-test: Pre-test: 5 mg/kg bw, 50 mg/kg bw, 300 mg/kg bw, 2000 mg/kg bw
- Constant volume or concentration used: yes
Duration of exposure:
single administration for 24 hours
Doses:
Main-test
2000 mg/kg bw
No. of animals per sex per dose:
Main-test: 5 males and 5 females
Pre-tests: 2 females per dose
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: For the main study, the body weight of all animals were recorded on day 0 (shortly before the treatment), on day 7 and on day 15 (with a precision of 1 g)
- Necropsy of survivors performed: yes
- Other examinations performed: Animals were observed individually 1 h and 5 h after dosing, and once each day for 14 days thereafter. Observations included the skin and fur, eyes and mucous membranes, and also respiratory, circulatory, autonomic and central nervous system, and somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
All animals were subjected to gross pathology. All animals were exsanguinated under isoflurane anaesthesia. After examination of the external appearance the cranial, thoracic and abdominal cavities were opened and the appearance of the tissues and organs were observed. All gross pathological changes were recorded for each animal on the post mortem record sheets. The animals of preliminary study were humanely sacrificed on day 7.
Statistics:
not applicable
Preliminary study:
No mortalities occured during the preliminary study
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks:
cesium nitrate
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 1 856.7 mg/kg bw
Based on:
other: calculated for cesium sulphate
Mortality:
no mortality occured
Clinical signs:
In males treated with 2000 mg/kg bw, blood around the nose (4 cases of 80 observations) was observed. This symptom (score +2) was found in two animals. It was detected between 1 and 5 hours after the treatment. However, this effect cannot be related to the test item. Three animals were free of symptoms during the study. All animals were free of symptoms between Day 1 and Day 14. No behavioural changes or general systemic toxic signs were noted in females during the study. No local symptoms (dermal irritation) were observed on the treated skin of animals as redness and oedema.
Body weight:
The mean body weight of the male animals corresponded to their species and age throughout the study.
Body weight loss was observed in one female treated with 2000 mg/kg bw cesium nitrate between Day 0 and Day 7. This body weight loss was very low (approx. 0.9 %) and the animal's body weight exceeded the original body weight by the end of study. Thus, this effect can be interpreted as an individual variation without toxicological meaning.
Gross pathology:
All animals survived until the scheduled necropsy on Day 15. Slight hydrometra was observed in one female and moderate hydrometra was found in a second female. Hydrometra was an indication for the sexual cycle of female animals and is a frequent observation in experimental rats with no toxicological meaning.
No macroscopic alterations due to the systemic toxic effects of the test item were found.
Other findings:
none
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
An acute dermal toxicity study with cesium sulphate is not available. Consequently, read-across was applied using study data from cesium nitrate. The acute dermal LD50 value of the test item cesium nitrate was greater than 2000 mg/kg bw in male and female Crl:(WI)BRrats.
Since cesium nitrate has a higher molecular weight due to the molecular weight of the counter ion the calculated value for cesium sulphate is > 1857 mg/kg bw. Due to the fact that no test item related toxic effects or other changes occurred in this limit test of the structural analogous read-across substance cesium sulphate was not classified as harmful category 4.
Executive summary:

An acute dermal toxicity study with cesium sulphate is not available. Consequently, read-across was applied using study data from cesium nitrate.

An acute dermal toxicity study was performed with the test item cesium nitrate in Crl:(WI)BR rats, in compliance with OECD Guideline No. 402 and EU Method B.3. A limit test was carried out. A single group of male and female animals (n=5 animals/sex) was exposed to the test item at 2000 mg/kg bw by dermal route. The test item was applied in its original form and left in contact with the skin for 24 hours, followed by a 14-day observation period.

No mortality occurred after the single dermal administration of cesium nitrate at a dose of level 2000 mg/kg bw with an exposure period of 24 h. No test item related systemic toxic clinical signs were observed and no test item related effects on the animal’s body weights were established throughout the study. The general symptoms observed could not be connected to a toxic effect of the test item but may be related to the induced stress during the treatment procedure (for example due to the presence of the bandage etc.). Autopsy revealed no treatment related pathological changes. The test item did not cause dermal irritation symptoms as erythema, oedema or other signs.

In this acute dermal toxicity study with the test item cesium nitrate, the obtained acute dermal LD50 valuewas greater than 2000 mg/kg bw in male and female Crl:(WI)BRrats.

Since cesium nitrate has a higher molecular weight due to the molecular weight of the counter ion the calculated value for cesium sulphate is > 1857 mg/kg bw. Due to the fact that no test item related toxic effects or other changes occurred in this limit test of the structural analogous read-across substance cesium sulphate was not classified as harmful category 4.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
An acute dermal toxicity study with cesium sulphate is not available. Consequently, data from two structural analogous read-across substances were used. Both substances were tested up to the limit concentration. No test item related toxic effects or other changes were observed. Since both substances, cesium nitrate and cesium iodide, have a higher molecular weight due to the molecular weight of the counter ions the calculated value for cesium sulphate is e.g. > 1857 mg/kg bw. Due to the fact that no test item related toxic effects or other changes occurred in limit tests of two structural analogous read-across substance the cesium sulphate was not classified as harmful category 4.

Additional information

Oral:

This study was conducted to assess the acute oral toxicity of the cesium sulphate in Rats (Crl(WI)Br) according to OECD Guideline 423 and EU Method B.1 tris. The acute toxic class method was carried out involving a stepwise procedure with the use of 2000 mg/kg bw as the starting dose in three female rats. Since three female animals died the test was continued at 300 mg/kg bw dose level on further three female rats. No animal died in the second step at 300 mg/kg bw dose level, three further female rats were treated with the same (300 mg/kg bw) dose. No animal died in the third step, too, so the test was finished, the stopping criteria of Annex 2d of OECD Guideline No. 423 (presented in Annex VII) were met. Animals were weighed, observed for lethality and toxic symptoms for 14 days after the treatment. Gross pathological examination was carried out on the 15th day after the treatment.

According to the results from this study the LD50 obtained for the test item was found to be between 300 and 2000 mg/kg bw. Therefore, the test item is classified as category 4 according to Regulation (EC) No 1272/2008 (CLP/GHS).

The key LD50 value for the chemical safety assessment was set at 300 mg/kg bw in order to obtain a numerical figure to allow for CSA calculations. However, it must be highlighted that this value is based on a worst case scenario and does not truly reflect the results obtained from this study where the actual LD50 was in the range between 300 and 2000 mg/kg bw.

Further information: A review article issue by “The British Industrial Biological Research Associations” (bibra), titled “Toxicity Profile of Cesium Compounds (2000)”, states an oral LD50 values for cesium sulphate determined in rats of 2800 mg/kg bw and in mice of 3200 mg/kg bw.

Inhalation:

According to REACH Regulation (EC) No 1907/2006, Annex VIII, 8.5 data for a maximum of two routes of exposure need to be provided. Testing for acute toxicity via the inhalation route was not applicable as data on acute oral and acute dermal toxicity were available. Based on the results of the particle size distribution study (d10: 170 µm, d50: 258 µm, d90: 384 µm) no inhalable particles are expected. Inhalation exposure is thus expected to be negligible.

Dermal:

Key Study:

An acute dermal toxicity study with cesium sulphate is not available. Consequently, read-across was applied using study data from cesium nitrate.

An acute dermal toxicity study was performed with the test item cesium nitrate in Crl:(WI)BR rats, in compliance with OECD Guideline No. 402 and EU Method B.3. A limit test was carried out. A single group of male and female animals (n=5 animals/sex) was exposed to the test item at 2000 mg/kg bw by dermal route. The test item was applied in its original form and left in contact with the skin for 24 hours, followed by a 14-day observation period.

No mortality occurred after the single dermal administration of cesium nitrate at a dose of level 2000 mg/kg bw with an exposure period of 24 h. No test item related systemic toxic clinical signs were observed and no test item related effects on the animal’s body weights were established throughout the study. The general symptoms observed could not be connected to a toxic effect of the test item but may be related to the induced stress during the treatment procedure (for example due to the presence of the bandage etc.). Autopsy revealed no treatment related pathological changes. The test item did not cause dermal irritation symptoms as erythema, oedema or other signs.

In this acute dermal toxicity study with the test item cesium nitrate, the obtained acute dermal LD50 valuewas greater than 2000 mg/kg bw in male and female Crl:(WI)BRrats.

Since cesium nitrate has a higher molecular weight due to the molecular weight of the counter ion the calculated value for cesium sulphate is > 1857 mg/kg bw. Due to the fact that no test item related toxic effects or other changes occurred in this limit test of the structural analogous read-across substance cesium sulphate was not classified as harmful category 4.

Supporting Study:

An acute dermal toxicity study with cesium sulphate is not available. Consequently, read-across was applied using study data from cesium iodide.

An acute dermal toxicity study was performed with the test item cesium iodide in Crl(WI)Br rats, in compliance with OECD Guideline No. 402 and EU Method B.3. A limit test was carried out. A single group of male and female animals (n=5 animals/sex) was exposed to the test item at 2000 mg/kg bw by dermal route. The test item was applied in its original form and left in contact with the skin for 24 hours, followed by a 14-day observation period.

No mortality occurred after the single dermal administration of cesium iodide at a dose of level 2000 mg/kg bw with an exposure period of 24 h. No test item related systemic toxic clinical signs were observed and no test item related effects on the animal’s body weights were established throughout the study. The general symptoms observed could not be connected to a toxic effect of the test item but may be related to the induced stress during the treatment procedure (for example due to the presence of the bandage etc.). Autopsy revealed no treatment related pathological changes.

In this acute dermal toxicity study with the test item cesium iodide, the obtained acute dermal LD50 value was greater than 2000 mg/kg bw in male and female Crl(WI)Br rats. Since cesium iodide has a higher molecular weight due to the molecular weight of the counter ion the calculated value for cesium sulphate is > 1393 mg/kg bw. Due to the fact that no test item related toxic effects or other changes occurred in this limit test of the structural analogous read-across substance cesium sulphate was not classified as harmful category 4.


Justification for selection of acute toxicity – oral endpoint
Most reliable study

Justification for selection of acute toxicity – inhalation endpoint
According to REACH Regulation (EC) No 1907/2006, Annex VIII, 8.5 data for a maximum of two routes of exposure need to be provided. Testing for acute toxicity via the inhalation route was not applicable as data on acute oral and acute dermal toxicity were available. Based on the results of the particle size distribution study (d10: 119 µm, d50: 214 µm, d90: 339 µm) no inhalable particles are expected. In addition, the vapour pressure is expected to be low. Inhalation exposure is thus expected to be negligible.

Justification for selection of acute toxicity – dermal endpoint
Most reliable study with a structural analogous substance. Please refer to IUCLID section 13 for read-across justification.

Justification for classification or non-classification

According to the results from the acute oral toxicity study, the LD50 obtained for the test item was found to be between 300 and 2000 mg/kg bw. Therefore, the test item is classified as harmful if swallowed (category 4) according to Regulation (EC) No 1272/2008 (CLP/GHS).

According to the results of acute dermal toxicity studies with two structural analogous read-across substances the test item is not classified according to Regulation (EC) No 1272/2008 (CLP/GHS).