Lithium bis[ethanedioato(2-)-κO1,κO2]difluorophosphate(1-)

Endpoint summary

Description of key information

Oral: 50 mg/kg bodyweight < LD50 < 300 mg/kg bodyweight (actual value: 50 mg/kg bodyweight < LD50 < 300 mg/kg bodyweight) (OECD Guideline 423)

Dermal: 200 mg/kg < LD50 < 1000 mg/kg (actual value: 501 mg/kg in female rats, 926 mg/kg in male rats) (OECD Guideline 402)

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 2009-03-05 to 2009-04-03

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.: 08111121
Purity: 98%

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: 213 - 239 g
- Fasting period before study: Yes (overnight prior to and approximately four hours after dosing)
- 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)
- Water: freely available
- Acclimation period: Minimum of five days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23 °C
- Humidity (%): 40 - 70%
- Photoperiod (hrs dark / hrs light): 12 hours light, 12 hours dark

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 5 mg/mL and 30 mg/mL

DOSE VOLUME APPLIED: 10 mL/kg bodyweight

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: 300 mg/kg chosen as the starting dose for compliance with the guidelines.

Doses:

Group 1: 300 mg/kg (3 females)
Group 2: 50 mg/kg (3 females)
Group 3: 50 mg/kg (3 females)

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Mortality: check the cages of rats at least twice daily for any mortalities
- Clinical observations: 14-day observation after dosing. 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. Individual weekly bodyweight changes and group mean bodyweights were calculated.
- Other examinations performed: necropsy, macropathology.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 50 - < 300 mg/kg bw

Based on:

test mat.

Mortality:

Two females dosed at 300 mg/kg died approximately 2 hours after dosing and a further female was killed for animal welfare reasons approximately 4 hours after dosing. Clinical signs prior to death comprised, underactive behaviour, seen in all animals. In addition loose faeces, hunched posture, piloerection, shallow respiration, reduced body temperature, unsteady gait, tremors and partially closed eyelids were all noted in two female. Reduced body tone and flat posture, were recorded for one female and increased respiration, chin rubbing, salivation and urine staining around the peri genital area in a further female . These signs were seen from approximately one hour after dosing. A loss in bodyweight was recorded for all three decedents. Macroscopic examination of the animals revealed yellow fluid contents of the stomach, duodenum, small and large intestines and caecum in all animals.

Clinical signs:

other: Clinical signs of reaction to treatment in animals dosed at 50 mg/kg comprised loose faeces, seen in five females. These signs were first noted approximately one hour after dosing. Recovery of animals, as judged by external appearance and behaviour, was c

Gross pathology:

Macroscopic examination at study termination on Day 15 revealed pallor of the lungs in three females treated at 50 mg/kg. No abnormalities were revealed in any other animal at the macroscopic examination at this time.

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

The acute median lethal oral dose (LD50) to rats of the test substance was demonstrated to be between 50 and 300 mg/kg bodyweight. The test substance is included in Category 3, according to the Globally Harmonised System (GHS), (UNITED NATIONS, 2005).

Executive summary:

The study was performed to assess the acute oral toxicity of the test substance to the rat according to OECD Guideline 423.

A group 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 300 mg/kg bodyweight. As results at this dose level indicated the acute median lethal dose to be below 300 mg/kg bodyweight, in compliance with the study guidelines, a further two groups of three fasted females were similarly dosed at 50 mg/kg bodyweight to complete the study.

Two females dosed at 300 mg/kg died approximately 2 hours after dosing and a further female was killed for animal welfare reasons approximately 4 hours after dosing. Clinical signs prior to death comprised, underactive behaviour, seen in all animals. In addition loose faeces, hunched posture, piloerection, shallow respiration, reduced body temperature, unsteady gait, tremors and partially closed eyelids were all noted in two females. Reduced body tone and flat posture, were recorded for one female and increased respiration, chin rubbing, salivation and urine staining around the peri genital area in a further female. These signs were seen from approximately one hour after dosing. A loss in bodyweight was recorded for all three decedents. Macroscopic examination of the animals revealed yellow fluid contents of the stomach, duodenum, small and large intestines and caecum in all animals.

Clinical signs of reaction to treatment in animals dosed at 50 mg/kg comprised loose faeces, seen in five females. These signs were first noted approximately one hour after dosing. Recovery of animals, as judged by external appearance and behaviour, was complete by Day 2. No clinical signs were seen in the remaining animal dosed at 50 mg/kg.

A low bodyweight gain was noted for two females on Day 15. All other animals were considered to have achieved satisfactory bodyweight gains throughout the study.

Macroscopic examination at study termination on Day 15 revealed pallor of the lungs in three females treated at 50 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 the test substance was demonstrated to be between 50 and 300 mg/kg bodyweight. The test substance is included in Category 3, according to the Globally Harmonised System (GHS), (UNITED NATIONS, 2005).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

50 mg/kg bw

Quality of whole database:

Guideline study, GLP study

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

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 2015-01-29 to 2015-04-16

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

2004

Deviations:

no

GLP compliance:

no

Remarks:

non GLP, but in compliance with China National Metrology Accreditation

Limit test:

no

Specific details on test material used for the study:

Batch No.: 141104
Purity: 95.4%

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 7 - 9 weeks.
- Weight at study initiation: 200 to 300 g.
- Housing: 5 per cage by sex
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum from bottled water
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-26 °C
- Humidity (%): 40 - 70%
- Air changes (per hr): 10-12
- Photoperiod (hrs dark / hrs light): 12-hour light / dark cycle.

Type of coverage:

occlusive

Vehicle:

vegetable oil

Details on dermal exposure:

TEST SITE
- Area of exposure: not less than 10% of the total body surface area
- Type of wrap if used: orthopedic stockinette.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes - washed with room temperature tap water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): four dosage levels (215, 464, 1000, 2150 mg/kg) in female rats and male rats
- Concentration (if solution): N/A - administered as supplied

Duration of exposure:

24 h

Doses:

four dosage levels (215, 464, 1000, 2150 mg/kg) in female rats and male rats

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality and clinical/behavioral signs of toxicity were made at least two times on the day of dosing (Day 0) and at least once thereafter for 14 days. Bodyweights were recorded just prior to dosing and on days 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: macroscopic pathology.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

501 mg/kg bw

Based on:

test mat.

95% CL:

> 344 - < 730

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

926 mg/kg bw

Based on:

test mat.

95% CL:

> 636 - < 1 350

Mortality:

Death occurred in female rats at 464, 1000, 2150mg/kg levels and male rats at 1000, 2150mg/kg levels. The acute dermal LD50 wás estimated to be 501 mg/kg in female rats (95% confidence interval is 344 to 730mg/kg) and 926 mg/kg in male rats (95% confidence interval is 636 to 1350mg/kg). according to Horn's method.

Clinical signs:

other: During experiment observation, clinical signs such as tremors and subject skin with varying degrees of poisoning symptoms (nigrescence, edema, necrosis, easy off) were found in 215, 464, 1000, 2150 mg/kg dose group of male and female rats, after 3 days th

Gross pathology:

No abnormal necropsy findings occurred in any test animal which could be suspected to be due to the test substance.

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

The acute dermal LD50 was estimated to be 501 mg/kg in female rats (95% confidence interval is 344 to 730 mg/kg) and 926 mg/kg in male rats (95% confidence interval is 636 to 1350 mg/kg). Based on these results, it was concluded that application of the test substance was moderately toxic by acute dermal route.

Executive summary:

The study was performed to assess the acute dermal toxicity of the test material in the Sprague-Dawley rat according to OECD Guideline 402: Acute Dermal Toxicity test (Ministry of Environmental Protection of the People's Republic of China, 2004).

The test material was evaluated for its acute dermal toxicity potential and relative skin irritancy in rats. 20 fernale and 20 male SD rats were randomly divided into 4 groups respectively for 24 hours by acute dermal route. Treated groups were dosed with the test material at 215, 464, 1000, 2150 mg/kg for female and male rat, respectively. Parameters measured during the exposure and observation period were body weight changes, clinical signs, mortality, and local irritation.

During experiment observation, clinical signs such as tremors and subject skin with varying degrees of poisoning symptoms (nigrescence, edema, necrosis, easy off) were found in 215, 464, 1000, 2150 mg/kg dose group of male and female rats, after 3 days the survivor appeared a black scab which was start off in 6 weeks and then returned to recovery. Death occurred in female rats at 464, 1000, 2150 mg/kg levels and male rats at 1000, 2150 mg/kg levels.

The acute dermal LD50 was estimated to be 501 mg/kg in female rats (95% confidence interval is 344 to 730 mg/kg) and 926 mg/kg in male rats (95% confidence interval is 636 to 1350 mg/kg). Based on these results, it was concluded that application of the test substance was moderately toxic by acute dermal route.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

501 mg/kg bw

Quality of whole database:

Guideline study, non GLP, but in compliance with China National Metrology Accreditation

Additional information

Acute oral toxicity:

The study was performed to assess the acute oral toxicity of the test substance to the rat according to OECD Guideline 423.

A group 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 300 mg/kg bodyweight. As results at this dose level indicated the acute median lethal dose to be below 300 mg/kg bodyweight, in compliance with the study guidelines, a further two groups of three fasted females were similarly dosed at 50 mg/kg bodyweight to complete the study.

Two females dosed at 300 mg/kg died approximately 2 hours after dosing and a further female was killed for animal welfare reasons approximately 4 hours after dosing. Clinical signs prior to death comprised, underactive behaviour, seen in all animals. In addition loose faeces, hunched posture, piloerection, shallow respiration, reduced body temperature, unsteady gait, tremors and partially closed eyelids were all noted in two females. Reduced body tone and flat posture, were recorded for one female and increased respiration, chin rubbing, salivation and urine staining around the peri genital area in a further female. These signs were seen from approximately one hour after dosing. A loss in bodyweight was recorded for all three decedents. Macroscopic examination of the animals revealed yellow fluid contents of the stomach, duodenum, small and large intestines and caecum in all animals.

Clinical signs of reaction to treatment in animals dosed at 50 mg/kg comprised loose faeces, seen in five females. These signs were first noted approximately one hour after dosing. Recovery of animals, as judged by external appearance and behaviour, was complete by Day 2. No clinical signs were seen in the remaining animal dosed at 50 mg/kg.

A low bodyweight gain was noted for two females on Day 15. All other animals were considered to have achieved satisfactory bodyweight gains throughout the study.

Macroscopic examination at study termination on Day 15 revealed pallor of the lungs in three females treated at 50 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 the test substance was demonstrated to be between 50 and 300 mg/kg bodyweight. The test substance is included in Category 3, according to the Globally Harmonised System (GHS), (UNITED NATIONS, 2005).

Acute inhalation toxicity:

No data were available for acute inhalation toxicity. However, given the extremely low vapour pressure of the substance, and there is acute dermal study is available, testing for acute inhalation toxicity is therefore not required.

Acute dermal toxicity:

The study was performed to assess the acute dermal toxicity of the test material in the Sprague-Dawley rat according to OECD Guideline 402: Acute Dermal Toxicity test (Ministry of Environmental Protection of the People's Republic of China, 2004).

The test material was evaluated for its acute dermal toxicity potential and relative skin irritancy in rats. 20 female and 20 male SD rats were randomly divided into 4 groups respectively for 24 hours by acute dermal route. Treated groups were dosed with the test material at 215, 464, 1000, 2150 mg/kg for female and male rat, respectively. Parameters measured during the exposure and observation period were body weight changes, clinical signs, mortality, and local irritation.

During experiment observation, clinical signs such as tremors and subject skin with varying degrees of poisoning symptoms (nigrescence, edema, necrosis, easy off) were found in 215, 464, 1000, 2150 mg/kg dose group of male and female rats, after 3 days the survivor appeared a black scab which was start off in 6 weeks and then returned to recovery. Death occurred in female rats at 464, 1000, 2150 mg/kg levels and male rats at 1000, 2150 mg/kg levels.

The acute dermal LD50 was estimated to be 501 mg/kg in female rats (95% confidence interval is 344 to 730 mg/kg) and 926 mg/kg in male rats (95% confidence interval is 636 to 1350 mg/kg). Based on these results, it was concluded that application of the test substance was moderately toxic by acute dermal route.

Justification for classification or non-classification

Oral: 50 mg/kg bodyweight < LD50 < 300 mg/kg bodyweight (actual value: 50 mg/kg bodyweight < LD50 < 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 this endpoint.

 

Specific target organ toxicity-single exposure:

No significant non-lethal toxic effects observed in acute oral toxicity study.

Therefore in accordance with Regulation (EC) No. 1272/2008 Table 3.8.1, this substance should not be classified for this endpoint.

 

Dermal: 200 mg/kg < LD50 < 1000 mg/kg (actual value: 501 mg/kg in female rats, 926 mg/kg in male rats)

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 this endpoint.