Cesium formate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From February 21, 2007 to March 29, 2007

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2007

Report date:

2007

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Cesium formate

EC Number:

222-492-8

EC Name:

Cesium formate

Cas Number:

3495-36-1

Molecular formula:

HCO2.Cs, Cs+HCOO-, CH2O2.Cs

IUPAC Name:

Caesium formate

Details on test material:

- Name of test material (as cited in study report): Cesium Formate
- Physical state: Colorless liquid
- Stability under test conditions: Stable during the test period
- Storage condition of test material: Stored in a dry, cool place with the container tightly closed

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Ltd, Margate, Kent, UK
- Age at study initiation: Eight to twelve weeks of age
- Weight at study initiation: Since the animals are 8-12 weeks old, hence weight should be approximately 200-250 g
- Housing: Propylene cages furnished with woodflakes
- Diet (e.g. ad libitum): Certified rat and mouse diet
- Water (e.g. ad libitum): Drinking water
- Acclimation period: 5 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25 ˚C
- Humidity (%): 30-70 %
- Air changes (per hr): 15 changes per h
- Photoperiod (hrs dark / hrs light): 12 h continuous light (06:00 to 18:00) and 12 h darkness

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: For 300 mg/kg – 30 mg/mL; For 2000 mg/kg – 2127.7 mg/mL (calculated from the dose volume 0.94 ml/kg)
- Amount of vehicle (if gavage): No data
- Justification for choice of vehicle: Test substance is highly soluble in water. Moreover distilled water is an inert vehicle and will not interfere with the subsequent evaluation of results
- Lot/batch no. (if required): No data
- Purity: No data

MAXIMUM DOSE VOLUME APPLIED: For 300 mg/kg - 10 ml/kg; For 2000 mg/kg – 0.94 ml/kg

DOSAGE PREPARATION (if unusual): The specific gravity was determined and used to calculate the appropriate dose volume for the required dose level. The test substance was freshly prepared as a solution in distilled water.

For 300 mg/kg, the test substance was dissolved in the distilled water at a concentration of 30 mg/ml.
For 2000 mg/kg, the test substance was dissolved in distilled water to achieve a dose volume of 0.94 ml/kg.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Using available information on toxicity of test material, 300 mg/kg was chosen as the starting dose.

Doses:

300 and 2000 mg/kg

No. of animals per sex per dose:

Sighting test: 1 animal per dose group of 300 and 2000 mg/kg
Main test: 4 animals per dose group of 300 and 2000 mg/kg

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 d
- Frequency of observations and weighing: Daily for observations and weekly for weighing
- Necropsy of survivors performed: Yes
- Other examinations performed:
Clinical signs: Clinical observations were performed ½, 1, 2 and 4 h after dosing and then daily for up to 14 d.
Body weight: Body weights were recorded on Day 0 (the day of dosing) and on Days 7 and 14 or at death.
Organ weights: Not applicable
Histopathology: Not applicable
Other: Mortality and morbidity checks were performed twice daily.

Results and discussion

Preliminary study:

No toxicity was observed in the two animals treated with 300 and 2000 mg/kg

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Mortality:

Dose level: 2000 mg/kg
4/5 were found dead during the day of dosing or one day after dosing
Dose level: 300 mg/kg
There was no mortality

Clinical signs:

Dose level: 2000 mg/kg
Treatment related clinical signs were observed in 1/5 animals at 4 h after dosing followed which the animal was found dead. The clinical signs included reduced activity, hunched posture, ataxia and piloerection.

Dose level: 300 mg/kg
No signs of systemic toxicity were observed during the observation period.

Body weight:

Dose level: 2000 mg/kg
The only surviving animal gained body weight normally throughout the observation period.

Dose level: 300 mg/kg
All animals showed expected gains in body weight over the observation period.

Gross pathology:

Dose level: 2000 mg/kg
The necropsy of animals (4/5 rats) that died during the observation period showed abnormally red lungs, dark liver and kidneys and haemorrhage in gastric mucosa. No abnormalities were observation at necropsy of the surviving animal.

Dose level: 300 mg/kg
No gross pathological abnormalities were observed at necropsy in any animal.

Any other information on results incl. tables

Using the mortality data obtained an estimate of the acute oral median lethal dose (LD50) of the test material was made.

Applicant's summary and conclusion

Conclusions:

Under the study conditions, the LD50 of the test substance in Sprague Dawley rats was greater than 300 mg/kg bw but lower than 2000 mg/kg bw.

Executive summary:

A study was conducted to determine the acute oral toxicity of the test substance to Sprague-Dawley CD (crl: CD®(SD) IGS BR) rats according to OECD Guideline 420, in compliance with GLP. A sighting test was performed with a single female rat at 300 mg/kg bw. In the absence of toxicity at this dose level, another female rat was treated with 2000 mg/kg bw. In the absence of toxicity at 2000 mg/kg, an additional group of 4 female rats were treated with the same dose level, i.e. 2000 mg/kg bw. Due to the absence of mortality and signs of systemic toxicity at 2000 mg/kg bw, an additional 4 animals were treated at 300 mg/kg bw. At the end of the observation period, the surviving animals were killed by cervical dislocation and subjected to gross necropsy. All four animals at 2000 mg/kg bw were found dead on the day of dosing or one day after dosing. There were no mortalities or clinical signs observed at 300 mg/kg bw. The surviving animal at 2000 mg/kg bw showed clinical signs such as hunched posture, lethargy, ataxia and piloerection. All surviving animals showed expected gain in bodyweight over the observation period. No abnormalities were recorded at necropsy of the animals that were killed at the end of the study. Under the study conditions, the LD50 of the test substance in Sprague Dawley rats was greater than 300 mg/kg bw but lower than 2000 mg/kg bw (Sanders, 2007).