Cesium formate

Endpoint summary

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

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

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

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

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.

Preliminary study:

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

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.

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

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).

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From January 7, 1997 to January 30, 1997

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OTS 798.1175 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMAL
-Source: Harlan Sprague Dawley, Inc. P. O. Box 29176, Indianapolis, IN 46229
- Age at study initiation: Adult
- Weight at study initiation: Males – 251-302 g, Females – 205-233 g (Day 0 body weights)
- Fasting period before study: None
- Housing: Wire mesh suspension cages
- Diet (e.g. ad libitum): Teklad 4 % Mouse/Rat Diet
- Water (e.g. ad libitum): Tap water
- Acclimation period: At least 5 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 64-79 ˚F
- Humidity (%): 30-70 %
- Air changes (per hr): 15 changes per h
- Photoperiod (hrs dark / hrs light): 12 h light/dark cycle

IN-LIFE DATES: From: January 7, 1997 To: January 30, 1997

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: The test substance was administered undiluted using the bulk density to determine the dose volume. Individual doses were calculated using post-fasting body weights.

DOSAGE PREPARATION (if unusual): Test substance was used undiluted

CLASS METHOD (if applicable): Not applicable
- Rationale for the selection of the starting dose: Not reported

Doses:

1250, 1580, 2000 and 5000 mg/kg

No. of animals per sex per dose:

Five

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 d
- Frequency of observations and weighing: All surviving animals were observed frequently for gross signs of systemic toxicity and mortality on the day of test material administration and at least twice daily.
- Necropsy of survivors performed: Yes
- Other examinations performed:
Clinical signs: Clinical signs were observed frequently on the day of dosing and at least twice daily from Day 2 until Day 14.
Body weight: Body weights were measured for each animal on the day of dosing, on Day 7 of the observation period, and at the ti me of necropsy (scheduled or in the event of death)
Organ weights: Not applicable
Histopathology: Not applicable
Other: Gross pathological observations were recorded for all necropsied animals.

Statistics:

Not reported

Preliminary study:

Not performed

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 1 780 other: mg/kg bw

95% CL:

ca. 200 - ca. 15 610

Mortality:

Males: 4/5 animals in 5000 mg/kg and 5/5 animals at 2000 mg/kg dose level died on Day 1. The surviving animal at 5000 mg/kg died by Day 1. There was no mortality at 1580 and 1250 mg/kg doses.
Females: 4/5 animals at 5000 mg/kg and 2/5 animals at 2000 mg/kg died on Day 0 of dosing. All the surviving animals at 5000 mg/kg and 4/5 animals at 2000 mg/kg died by Day 1. There were no mortalities in the lower doses.

Clinical signs:

Varying degrees of clinical signs like reduced activity, convulsions, respiratory distress, jaw movements, ataxia and external staining was observed across all dose levels from 1580 mg/kg. The only effect observed at 1250 mg/kg was fecal stains.

Body weight:

All surviving animals exhibited body weight gain at Day 14.

Gross pathology:

Presence of clear yellow fluid in the stomach and intestines, hemorrhagic lungs, congested kidneys and darkened spleen were observed in animals died at 2000 and 5000 mg/kg doses. Additionally, liver mottling were observed in 2/5 females at 5000 mg/kg dose. No gross pathological changes were observed at necropsy of the lower dose level animals.
External urine/fecal staining was observed in animals that died on Days 0 and 1.

Interpretation of results:

other: Acute oral LD50 = 1780 mg/kg

Conclusions:

Under the study conditions, the acute oral LD50 value was calculated to be 1780 mg/kg bw with 95 % confidence intervals of 200 and 15610 mg/kg bw.

Executive summary:

A study was conducted to determine the LD50 of the test substance in rats according to OECD Guideline 401 (acute oral toxicity test), in compliance with GLP. Male and female Sprague Dawley rats were exposed to a single dose of undiluted test substance at 0, 1250, 1580, 2000 and 5000 mg/kg bw and observed for 14 days. Clinical signs of reduced activity, convulsions, respiratory distress, ataxia and jaw movements were observed in animals of both sexes at 2000 and 5000 mg/kg bw. 100% mortality occurred in males at 2000 and 5000 mg/kg bw by Day 1. All animals at 5000 mg/kg and 4/5 animals at 2000 mg/kg bw in females died by Day 1. No mortality was observed at the lower doses in either sex. Gross pathological observations at necropsy/death revealed signs of stomach/small intestinal irritation. Under the study conditions, the acute oral LD50 value was calculated to be 1780 mg/kg bw with 95 % confidence intervals of 200 and 15610 mg/kg bw (Harrod, 1997).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 780 mg/kg bw

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:

experimental study

Adequacy of study:

key study

Study period:

From August 5, 2009 to September 3, 2009

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

humidity was outside the protocol range but did not affect study outcome

GLP compliance:

yes (incl. QA statement)

Test type:

other: Limit test

Limit test:

yes

Species:

other: albino rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Texas Animal Specialities, Humble, TX
- Weight at study initiation: Males: 232-269 g,
Females: 178-197 g
- Housing: Cage was suspended,wire bottom,stainless steel
- Diet (e.g. ad libitum): PMI feeds Inc. Formulab#5008,Ad libitum
- Water (e.g. ad libitum): Municipal water supply analysed by TCEQ water utilities division;tap water,ad libitum
- Acclimation period: 7 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-22 ⁰C
- Humidity (%): 54-92% (humidity was outside the protocol range but did not affect study outcome.
- Air changes (per hr): 10-12 air changes/h
- Photoperiod (hrs dark / hrs light): 12 h light/dark cycle

Type of coverage:

not specified

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: Dorsal surface of the trunk
- % coverage: 10%
- Type of wrap if used: Non-irritationg adhesive tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg (2528 mg/kg of the solution)
- Constant volume or concentration used: Yes

Duration of exposure:

24 h

Doses:

Single dose of 2000 mg/kg bw of test substance (2528 mg/kg bw of solution as received, consisting of 79.1 % test substance)

No. of animals per sex per dose:

5 males/dose
5 females/dose

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Three times on the day of dosing (day 0) and once daily for 14 days.
- Necropsy of survivors performed: Yes
- Other examinations performed: Clinical signs, body weight,organ weights, histopathology, other: Body weight were recorded just prior to dosing and on Day 7 and 14, Dermal irritation was measured at approx. 60 mins after removal of wrapping and on Day 4, 7, 11,14

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

act. ingr.

Mortality:

No mortality

Clinical signs:

The only clinical sign was red crusts around the eye of one animal on Days 7-14 (female).

Body weight:

No effect on the bodyweight gain, except one animal that lost weight during second week.

Gross pathology:

No observable abnormalities in gross necropsy, except an empty stomach in one animal.

Conclusions:

Under the study conditions the estimated LD50 of test substance was found to be greater than 2000 mg/kg bw.

Executive summary:

A study was conducted to determine the dermal toxicity and relative skin irritancy of the test substance according to OECD Guideline 402, in compliance with GLP.A single dose of 2000 mg/kg bw of test substance (2528 mg/kg bw of solution as received, consisting of 79.1% test substance) was applied to the intact skin of albino rats. No mortality occurred during the study. The only clinical sign was red crust around the eye of one animal on Days 7 - 14. There were no signs of dermal irritation and no effect on body weight gain (except one animal that lost weight during second week). No observable abnormalities in gross necropsy (except an empty stomach in one animal) were noted.Under the study conditions, the LD50 of the test substance was found to be greater than 2000 mg/kg bw (Kuhn, 2009).

 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

Oral

A study was conducted to determine the LD50 of the test substance in rats according to OECD Guideline 401 (acute oral toxicity test), in compliance with GLP. Male and female Sprague Dawley rats were exposed to a single dose of undiluted test substance at 0, 1250, 1580, 2000 and 5000 mg/kg bw and observed for 14 days. Clinical signs of reduced activity, convulsions, respiratory distress, ataxia and jaw movements were observed in animals of both sexes at 2000 and 5000 mg/kg bw. 100% mortality occurred in males at 2000 and 5000 mg/kg bw by Day 1. All animals at 5000 mg/kg and 4/5 animals at 2000 mg/kg bw in females died by Day 1. No mortality was observed at the lower doses in either sex. Gross pathological observations at necropsy/death revealed signs of stomach/small intestinal irritation. Under the study conditions, the acute oral LD50 value was calculated to be 1780 mg/kg bw with 95 % confidence intervals of 200 and 15610 mg/kg bw (Harrod, 1997).

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).

Dermal

A study was conducted to determine the dermal toxicity and relative skin irritancy of the test substance according to OECD Guideline 402, in compliance with GLP. A single dose of 2000 mg/kg bw of test substance (2528 mg/kg bw of solution as received, consisting of 79.1% test substance) was applied to the intact skin of albino rats. No mortality occurred during the study. The only clinical sign was red crust around the eye of one animal on Days 7 - 14. There were no signs of dermal irritation and no effect on body weight gain (except one animal that lost weight during second week). No observable abnormalities in gross necropsy (except an empty stomach in one animal) were noted. Under the study conditions, the LD50 of the test substance was found to be greater than 2000 mg/kg bw (Kuhn, 2009).

Justification for classification or non-classification

The available acute toxicity data (oral LD50 of 1780 mg/kg bw and dermal LD50 > 2000 mg/kg bw) suggests that the substance should be classified as Acute Tox. 4 - H302: Harmful if swallowed according to CLP (EC 1272/2008) criteria.