Caesium fluoride

Endpoint summary

Description of key information

CsF is acutely toxic via the oral route as LD50 oral was determined to be 300 mg/kg bw> LD50 < 2000 mg/kg bw.

CsF is not acutely toxic via the dermal route as LD50 dermal > 2000 mg/kg bw based on WoE assessment of read-across data.

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:

15 February 2017 to 22 March 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

OECD Guideline for the Testing of Chemicals No. 423 “Acute Oral Toxicity – Acute Toxic Class Method” (adopted 17 December 2001)

Deviations:

yes

Remarks:

Due to a technician error, the food for animals 2-0, 2-1 and 2-2 was returned earlier than 3 to 4 hours after dosing, as stated in the General Study Plan. This deviation was considered not to have affected the integrity or validity of the study.

Principles of method if other than guideline:

No analysis was conducted to determine the homogeneity, concentration or stability of the test item formulation. This is an exception with regard to GLP and has been reflected in the GLP compliance statement.

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Specific details on test material used for the study:

Identification: Cesium fluoride
Batch: 216091B008
Purity: =>99.9%
Physical state/Appearance: white powder
Expiry Date: 01 September 2018
Storage Conditions: room temperature in the dark over silica gel

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

Female Wistar (RccHan™:WIST) strain rats were supplied by Envigo RMS (UK) Limited, Oxon, UK. On receipt the animals were randomly allocated to cages. The females were nulliparous and non pregnant. After an acclimatization period of at least 5 days the animals were selected at random and given a number unique within the study by indelible ink marking on the tail and a number written on a cage card. At the start of the study the animals were 8 to 12 weeks of age. The body weight variation did not exceed ±20% of the mean body weight of any previously dosed animals. The animals were housed in groups of three in suspended solid floor polypropylene cages furnished with woodflakes. With the exception of an overnight fast immediately before dosing and for approximately 2 to 4 hours after dosing, free access to mains drinking water and food (2014C Teklad Global Rodent diet supplied by Envigo RMS (UK) Limited, Oxon, UK) was allowed throughout the study. The diet, drinking water and bedding were routinely analyzed and were considered not to contain any contaminants that would reasonably be expected to affect the purpose or integrity of the study.
The temperature and relative humidity were set to achieve limits of 19 to 25 °C and 30 to 70% respectively. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give 12 hours continuous light and 12 hours darkness. The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

All animals were dosed once only by gavage, using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to the fasted body weight at the time of dosing. Treatment of animals was sequential. Sufficient time was allowed between each group to confirm the survival of the previously dosed animals.

Doses:

One fasted female was treated with the test item at a dose level of 5000 mg/kg body weight. This was followed by a group of three fasted females was treated with the test item at a dose level of 2000 mg/kg body weight. A further group of three fasted females was treated with the test item at a dose level of 300 mg/kg body weight. Based on the results from this dose level, a further group of fasted females was treated at a dose level of 300 mg/kg body weight. Dosing was performed sequentially.

No. of animals per sex per dose:

Dose level 5000 mg/kg 1 female rat
Dose level of 2000 mg/kg 3 female rats
Dose level of 300 mg/kg 6 female rats

Control animals:

no

Details on study design:

Specific regulatory requirements justified a starting dose of 5000 mg/kg. All animals were dosed once only by gavage, using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to the fasted body weight at the time of dosing. Treatment of animals was sequential. Sufficient time was allowed between each group to confirm the survival of the previously dosed animals.
Clinical observations were made 30 minutes, 1, 2, and 4 hours after dosing and then daily for up to 14 days. Morbidity and mortality checks were made twice daily, early and late during normal working days, and once daily at weekends and public holidays. Individual body weights were recorded prior to dosing and 7 and 14 days after treatment or at death. At the end of the observation period the surviving animals were killed by cervical dislocation. All animals were subjected to gross pathological examination. This consisted of an external examination and opening of the abdominal and thoracic cavities for examination of major organs. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

ca. 500 mg/kg bw

Based on:

test mat.

Mortality:

Dose Level - 5000 mg/kg - The animal was killed for humane reasons, approximately 2 hours 30 minutes after dosing, due to the occurrence of clinical signs of toxicity that were considered likely to exceed the severity limit set forth in the UK Home Office Project Licence.

Dose Level - 2000 mg/kg - During the day of dosing, one animal was found dead and the two animals were killed for humane reasons due to the occurrence of clinical signs of toxicity that were considered likely to exceed the severity limit set forth in the UK Home Office Project Licence.

Dose Level - 300 mg/kg - There were no deaths.

Clinical signs:

other: Dose Level - 5000 mg/kg - Signs of systemic toxicity noted hunched posture, lethargy, pilo erection, prostration, decreased respiratory rate, labored and gasping respiration, ptosis, pallor of the extremities, hypothermia and increased lachrymation Dose

Gross pathology:

At dose level 5000 mg/kg - Abnormalities noted at necropsy were patchy pallor of the liver, liquid present in the stomach and hemorrhagic gastric mucosa.
At dose level 2000 mg/kg - Abnormalities noted at necropsy were dark liver or patchy pallor of the liver, dark kidneys, hemorrhage and epithelial sloughing of the gastric mucosa and non glandular epithelium of the stomach and hemorrhagic small intestine.
At dose level 300 mg/kg - No abnormalities were noted at necropsy.

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was approximately 500 mg/kg body weight (Globally Harmonized Classification System – Category 4, >300 - 2000 mg/kg body weight).

Executive summary:

The oral toxicity of the test substance was determined according the acute toxic class method (OECD 423) in female Wistar rats. One fasted female was treated with the test item at a dose level of 5000 mg/kg body weight. This was followed by a group of three fasted females treated with the test item at a dose level of 2000 mg/kg body weight. A further group of three fasted females was treated with the test item at a dose level of 300 mg/kg body weight. Based on the results from this dose level, a further group of fasted females was treated at a dose level of 300 mg/kg body weight. Dosing was performed sequentially. The test item was administered orally as a solution in distilled water. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy.

 

Mortality. During the day of dosing, one animal treated at a dose level of 2000 mg/kg was found dead. The two other animals treated with 2000 mg/kg and the animal treated with 5000 mg/kg were killed for humane reasons due to the occurrence of severe clinical signs. There were no deaths at a dose level of 300 mg/kg.

 

Clinical Observations. Signs of systemic toxicity noted at dose levels of 2000 and 5000 mg/kg included hunched posture, lethargy, pilo‑erection, prostration, decreased respiratory rate and ptosis, labored and gasping respiration, pallor of the extremities, hypothermia, increased lachrymation, ataxia and occasional body tremors, with an isolated incident of increased salivation. Hunched posture was also noted in one animal treated at a dose level of 300 mg/kg. No further clinical signs were observed in the remaining animals.

 

Body Weight. Two animals treated at a dose level of 300 mg/kg showed expected gain in body weight during the first week but body weight loss during the second week. The remaining animals showed expected gains in body weight over the study period.

 

Necropsy. Abnormalities noted at necropsy of the animal treated at a dose level of 5000 mg/kg were patchy pallor of the liver, liquid present in the stomach and hemorrhagic gastric mucosa.  At 2000 mg/kg dark liver or patchy pallor of the liver, dark kidneys, hemorrhage and epithelial sloughing of the gastric mucosa and non-glandular region of the stomach and hemorrhagic small intestine were observed. No abnormalities were noted at a dose level of 300 mg/kg.

 

Conclusion The acute oral median lethal dose (LD₅₀) of the test item in the female Wistar strain rat was approximately 500 mg/kg body weight (Globally Harmonized Classification System – Category 4, >300 - 2000 mg/kg body weight).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

300 mg/kg bw

Quality of whole database:

One key study conducted according GLP and rated as KL1 is available.

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:

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

Adequacy of study:

key study

Justification for type of information:

Please refer to read-across justification attached to IUCLID section 13.

Reason / purpose for cross-reference:

read-across source

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

other: CsOH

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

read-across to GLP and guideline compliant study

Additional information

Acute oral

Acute oral toxicity was determined according to the acute toxic class method (OECD 423) in female Wistar rats. The acute oral median lethal dose (LD50) of cesium fluoride in the female rats was approximately 500 mg/kg body weight.

The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was approximately 500 mg/kg body weight (Globally Harmonized Classification System – Category 4, >300 - 2000 mg/kg body weight).

 

Acute dermal

An acute dermal toxicity study with cesium fluoride is not available.

Consequently, data from the source substance CSNO3 and NaF were used.

CsNO₃ was tested up to the limit dose of 2000 mg/kg bw. No test item related toxic effects or other changes were observed. Analogous, it is assumed that cesium fluoride has no acute dermal effects, particularly considering the fact that bioavailability of the ions formed will be very low via the skin.

A dermal LD50 of > 2000 mg/kg bw was determined with NaF in the disseminated dossier of on the ECHA homepage (ECHA, 2021).

Taken together, it can be concluded that there is no concern in terms of acute dermal toxicity for CsF and classification in this regards is not warranted.

Justification for classification or non-classification

According to data for the acute oral toxicity endpoint, the LD50 for the test item was found to be >300 but < 2000 mg/kg bw. Therefore, the test item is classified as category 4 according to Regulation (EC) No 1272/2008 (CLP/GHS) for acute oral toxicity.

 

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) for acute dermal toxicity.