Lithium [ethanedioato-O,O’]tetrafluorophosphate

Endpoint summary

Description of key information

Oral:

The acute oral toxicity of test item to the rat was assessed based on the method as described in OECD 423.

The acute median lethal oral dose (LD50) to rats of test item was demonstrated to be between 50 and 300 mg/kg bodyweight.

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:

From 2012-04-19 to 2012-05-17

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:

2001

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Specific details on test material used for the study:

Batch No.: 111202
Purity: 95.5%

Species:

rat

Strain:

other: CD (Crl:CD ‘SD’)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Ltd.
- Females nulliparous and non-pregnant: yes
- Age at study initiation: approximately eight to twelve weeks
- Weight at study initiation: 199 to 250 g
- Fasting period before study: yes, overnight
- Housing: housed in groups of up to three rats of the same sex, in solid bottomed polycarbonate cages with a stainless steel mesh lid. Each cage contained a quantity of autoclaved wood flake bedding.
- Diet: free access to a standard rodent diet (Rat and Mouse No. 1 Maintenance Diet), except for overnight prior to and approximately four hours after dosing.
- Water: ad libitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 23°C
- Humidity (%): 40 to 70%
- Air: The animal room was kept at positive pressure with respect to the outside by its own supply of filtered fresh air, which was passed to atmosphere and not re-circulated.
- Photoperiod: 12 hrs dark / 12 hrs light

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 5 and 30 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg bodyweight

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: The dose levels for the study were chosen in compliance with the study guidelines. Based on information provided by the Sponsor the initial dose was 50 mg/kg.

Doses:

50 and 300 mg/kg

No. of animals per sex per dose:

6 females for 50 mg/kg, 3 females for 300 mg/kg

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
- Mortality: at least twice daily
- Clinical observations: Animals were observed soon after dosing and at frequent intervals for the remainder of Day 1. On subsequent days, surviving animals were observed once in the morning and again at the end of the experimental day (with the exception of Day 15 - morning only). The nature and severity, where appropriate, of the clinical signs and the time were recorded at each observation.
- Bodyweight: recorded on Days 1 (prior to dosing), 8 and 15 or at death
- Necropsy of survivors performed: yes, All surviving animals were humanely killed on Day 15 by carbon dioxide asphyxiation and subject to a macroscopic examination which consisted of opening the cranial, thoracic and abdominal cavities.

Sex:

female

Dose descriptor:

LD50

Effect level:

> 50 - < 300 mg/kg bw

Based on:

test mat.

Mortality:

Two females (2/3) dosed at 300 mg/kg were found dead or died on Day 2.
Clinical signs prior to death comprised piloerection, loose faeces, underactive behaviour, hunched posture, increased body tone all seen in both decedents, in addition salivation, reduced body tone, irregular breathing, deep breathing, unsteady gait, unresponsive behaviour were all seen in one decedent. These signs were seen from approximately 30 minutes after dosing. A loss in bodyweight was noted for both decedents. Macroscopic examination of the decedents revealed congestion (characterised by darkened tissues/organs) of the subcutaneous tissue, heart, liver, spleen and kidneys, small (atrophy) ceacum and yellow/clear fluid contents seen in the stomach, duodenum, small intestines and large intestines and were seen in all decedents. Pallor of the lungs was noted in one decedent.

Clinical signs:

other: Clinical signs of reaction to treatment in the surviving animal dosed at 300 mg/kg comprised piloerection, loose faeces, underactive behaviour, hunched posture, salivation, increased body tone, reduced body tone , partially closed eyelids, red staining on

Gross pathology:

Macroscopic examination at study termination on Day 15 revealed a small (atrophy) stomach in two females dosed at 50 mg/kg and pallor of the kidneys in one animal treated at 300 mg/kg. No abnormalities were revealed in any other animal at the macroscopic examination.

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

The acute median lethal oral dose (LD50) to rats of test item was demonstrated to be between 50 and 300 mg/kg bodyweight.

Executive summary:

The acute oral toxicity of test item to the rat was assessed based on the method as described in OECD 423.

Two groups of three fasted female rats received a single oral gavage dose of the test substance, formulated in dried corn oil, at a dose level of 50 mg/kg bodyweight. As results at this dose level indicated the acute (median) lethal oral dose of the test substance to be greater than 50 mg/kg bodyweight, in compliance with the study guidelines a further group of three fasted females were similarly dosed at 300 mg/kg bodyweight to complete the study.

Two females dosed at 300 mg/kg were found dead or died on Day 2. Clinical signs prior to death comprised piloerection, loose faeces, underactive behaviour, hunched posture, increased body tone all seen in both decedents, in addition salivation, reduced body tone, irregular breathing, deep breathing, unsteady gait, unresponsive behaviour were all seen in one decedent. These signs were seen from approximately 30 minutes after dosing. A loss in bodyweight was noted for both decedents. Macroscopic examination of the decedents revealed congestion (characterised by darkened tissues/organs) of the subcutaneous tissue, heart, liver, spleen and kidneys, small (atrophy) ceacum and yellow/clear fluid contents seen in the stomach, duodenum, small intestines and large intestines and were seen in all decedents. Pallor of the lungs was noted in one decedent.

Clinical signs of reaction to treatment in the surviving animal dosed at 300 mg/kg comprised piloerection, loose faeces, underactive behaviour, hunched posture, salivation, increased body tone, reduced body tone , partially closed eyelids, red staining on fore paws and head, unsteady gait, wet urine staining (ventral) and hairloss (perigenital area). These signs were first noted approximately from 30 minutes to three hours after dosing.

Piloerection was seen in three females dosed at 50 mg/kg. These signs were first noted approximately from three hours after dosing. No clinical signs were seen in the remaining three animals dosed at 50 mg/kg.

A low bodyweight gain was noted for one female dosed at 50 mg/kg on Day 15. All other surviving animals were considered to have achieved satisfactory bodyweight gains throughout the study.

Macroscopic examination at study termination on Day 15 revealed a small (atrophy) stomach in two females dosed at 50 mg/kg and pallor of the kidneys in one animal treated at 300 mg/kg. No abnormalities were revealed in any other animal at the macroscopic examination at this time.

The acute median lethal oral dose (LD50) to rats of test item was demonstrated to be between 50 and 300 mg/kg bodyweight.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

50 mg/kg bw

Quality of whole database:

1 (reliable without restriction), guideline study, complied with GLP

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Acute toxicity:

Oral: OECD 423, LD50: between 50 and 300 mg/kg bodyweight.

 

Therefore in accordance with Regulation (EC) No. 1272/2008 (amended by 286/2011) Table 3.1.1, this substance should be classified as Category 3 for acute oral and no conclusion can be drawn for the classification of acute inhalation and dermal toxicity due to data lacking.

 

Specific target organtoxicity-single exposure:

Oral:

Acute oral toxicity test, OECD 423:

Mortality: 2/3 died at 300 mg/kg

Clinical observations:

Clinical signs of reaction to treatment in the surviving animal dosed at 300 mg/kg comprised piloerection, loose faeces, underactive behaviour, hunched posture, salivation, increased body tone, reduced body tone, partially closed eyelids, red staining on fore paws and head, unsteady gait, wet urine staining (ventral) and hairloss (perigenital area). These signs were first noted approximately from 30 minutes to three hours after dosing.

Piloerection was seen in three females dosed at 50 mg/kg. These signs were first noted approximately from three hours after dosing. No clinical signs were seen in the remaining three animals dosed at 50 mg/kg.

Necropsy:a small (atrophy) stomach in two females dosed at 50 mg/kg and pallor of the kidneys in one animal treated at 300 mg/kg

 

In accordance with Regulation (EC) No. 1272/2008 section 3.8.2.1.7., the effects observed are not considered as adverse effects that support classification, therefore this substance should be not classified.