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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2020
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2020
Report date:
2020

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
GLP compliance:
yes
Test type:
acute toxic class method

Test material

Constituent 1
Chemical structure
Reference substance name:
Lithium bis[ethanedioato(2-)-κO1,κO2]difluorophosphate(1-)
EC Number:
695-938-6
Cas Number:
678966-16-0
Molecular formula:
F2C4PLiO8
IUPAC Name:
Lithium bis[ethanedioato(2-)-κO1,κO2]difluorophosphate(1-)

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
Age at First Dose 8 - 12 weeks; female animals were non-pregnant and nulliparous
Animal Health The health condition of animals was examined by a veterinarian
before initiation of the study.
Acclimation The animals were acclimated to the condition identical to the condition during the experiment at least 5 days prior to the start of treatment. The acclimation was according to standard operation procedures.
Housing Condition The animals were housed in plastic cages suspended on stainless steel racks, up to 3 animals per cage, in a room equipped with central air-conditioning. The room temperature was maintained within the range of 22 ± 2 °C. The relative humidity will be 55 ± 10 %. The light regime was set to a 12-hour light / 12-hour dark cycle. The sanitation was performed according to standard operation procedures.

Administration / exposure

Route of administration:
oral: drinking water
Vehicle:
olive oil
Details on oral exposure:
Diet A standard laboratory food KKZ-P/M (UEFT CEM SAS) was available ad libitum. The certificate of analysis is included in the raw data.
Water The animals received tap water for human consumption. Supply of drinking water was unlimited. The quality of drinking water is periodical monitored (including microbiological control) and recorded; certificate of analysis is included in raw data.
Bedding AlpenSpan Eco, Johann Pabst Holzindustrie GmbH, Zeltweg, Austria
Animals Identification Each animal was marked with an ID number. Each cage was affixed with a cage card containing pertinent animal and study information. The animals in cages were marked by a line on the tail with an ink marker.
Doses:
The starting dose can be selected from the fixed dose levels of 5, 50, 300, and 2000 mg/kg body weight. Available information indicated that the test item was likely to be non-toxic regarding acute toxicity therefore we chose a dose of 2000 mg Lithium difluorobis(oxalate)phosphate/kg body weight to be used as a starting dose. In the first step, one group of 3 females was dosed. The test item in limit dose caused mortality of all three animals within 48 hours after administration. In a second step, 3 females were treated at dose of 300 mg/kg body weight. Test item-related mortality was not observed for 48 hours and therefore, in a third step, another 3 females were treated at the same dose level.
No. of animals per sex per dose:
15

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 300 - < 2 000 mg/kg bw
Clinical signs:
other: Mortality of 3/3 females at limit dose of 2000 mg/kg body weight was observed. Four out of six female animals survived and two animals (Animal No 8 and No 9) died 2-4 hours after administration at the dose of 300 mg/kg body weight. No animal died after do
Other findings:
All animals were necropsied. In animals No 1 - 3 dosed with 2000 mg/kg body weight we did not observe obvious pathological changes. No visible pathological findings were observed in animals dosed with 300 mg/kg and 50 mg/kg body weight except hyperemia of gastric corpus in Animal No 6. All necropsy results are in Table 6.

Any other information on results incl. tables

Table1.Clinical observation - 2000 mg/kg body weight, Animal No 1-3.

Observation

Time After Administration

Hour

Day

I

0.5

1

2

4

1

2

3

4

5

6

7

8

9

10

11

12

13

14

Skin and Hair**

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

Eyes

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

Mucosa

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

Respiratory

System*

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

Circulatory

System

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

CNS

1,2,3

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

Somatomotoric

Activity

1,2,3

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

Tremor

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

Spasms

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

Salivation

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

Diarrhoea

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

Lethargy

1,2,3

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

Sleep

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

Coma

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

Death

-

1,2,3

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

Sacrificed

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

Others

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

- No observed signs, I - immediately. * - dyspnoe, ** - vein vasodilatation in hindlimb soles and tail

Sex

Dose

ID

Administration

 Result

Clinical Observation

2000 mg/kg

1

death

- lethargy and sleep/sedative behavior immediately after administration of test item, ½ an hour later: death of animal

2

death

- lethargy and sleep/sedative behavior immediately after administration of test item, ½ an hour later: death of animal

3

death

- lethargy and sleep/sedative behavior immediately after administration of test item, ½ an hour later: death of animal

Table 2.Clinical observation - 300 mg/kg body weight, Animal No 4-9.

Observation

Time After Administration

Hour

Day

I

0.5

1

2

4

1

2

3

4

5

6

7

8

9

10

11

12

13

14

Skin and Hair**

--

4,5,6

7,8,9

4,5,6

7,8,9

4,5,6

7,8

4,5,6

7

-

-

-

-

-

-

-

-

-

-

-

-

-

-

Eyes

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

Mucosa

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

Respiratory

System*

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

Circulatory

System

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

CNS

-

4,5,6

7,8,9

4,5,6

7,8,9

4,5,6

7,8

6

7

-

-

-

-

-

-

-

-

-

-

-

-

-

-

Somatomotoric

Activity

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

Tremor

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

Spasms

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

Salivation

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

Diarrhoea

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

Lethargy

-

4,5,6

7,8,9

4,5,6

7,8,9

4,5,6

7,8

6

7

-

-

-

-

-

-

-

-

-

-

-

-

-

-

Sleep

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

Coma

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

Death

-

-

-

9

8

-

-

-

-

-

-

-

-

-

-

-

-

-

-

Sacrificed

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

Others

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

- No observed signs, I - immediately. * - dyspnoe, ** - vein vasodilatation in hindlimb soles and tail

Table 3.Clinical observation - 50 mg/kg body weight, Animal No 10-15.

Sex

Dose

ID

Administration

Result

Clinical Observation

50

mg/kg

10

alive

no signs of intoxication, change of health, nor any other adverse reactions during 24 hours and 14-days observation period

11

alive

no signs of intoxication, change of health, nor any other adverse reactions during 24 hours and 14-days observation period

12

alive

lethargy and sleep/sedative behavior ½ an hour after administration and persisted for 1 hour

13

alive

no signs of intoxication, change of health, nor any other adverse reactions during 24 hours and 14-days observation period

14

alive

no signs of intoxication, change of health, nor any other adverse reactions during 24 hours and 14-days observation period

15

alive

no signs of intoxication, change of health, nor any other adverse reactions during 24 hours and 14-days observation period

Table 4.Clinical observation - 50 mg/kg body weight, Animal No 10-15.

Observation

Time After Administration

Hour

Day

I

0.5

1

2

4

1

2

3

4

5

6

7

8

9

10

11

12

13

14

Skin and Hair**

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

Eyes

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

Mucosa

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

Respiratory

System*

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

Circulatory

System

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

CNS

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

Somatomotoric

Activity

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

Tremor

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

Spasms

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

Salivation

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

Diarrhoea

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

Lethargy

-

12

12

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

Sleep

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

Coma

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

Death

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

Sacrificed

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

Others

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

- No observed signs, I - immediately. * - dyspnoe, ** - vein vasodilatation in hindlimb soles and tail

Table 5.Body Weight

Sex

Dose

ID

Body Weight (g)

Body Weight Difference (g)

Initial

Week 1

Week 2

Week 1 - Initial

Week 2 - Initial

Week 2 - Week 1

2000 mg/kg

1

191

-

-

-

-

-

2

188

-

-

-

-

-

3

193

-

-

-

-

-

 

 

300 mg/kg

4

160

189

209

29

49

20

5

192

230

250

38

58

20

6

167

206

223

39

56

17

7

169

182

203

13

34

21

8

201

-

-

-

-

-

9

201

-

-

-

-

-

 

50 mg/kg

10

207

227

242

20

35

15

11

196

226

250

30

54

24

12

197

216

235

19

38

19

13

210

231

240

21

40

19

14

221

236

240

15

19

4

15

201

227

246

26

45

19

Table 6.Necropsy Results

Sex

Dose

ID

Result

2000 mg/kg

1

No obvious pathological changes in gastrointestinal tract were found

2

No obvious pathological changes in gastrointestinal tract were found

3

No obvious pathological changes in gastrointestinal tract were found

300 mg/kg

4

No findings

5

No findings

6

No findings

7

No findings

8

No obvious pathological changes in gastrointestinal tract were found

9

No obvious pathological changes in gastrointestinal tract were found

50 mg/kg

10

No findings

11

No findings

12

No findings

13

No findings

14

No findings

15

No findings

Applicant's summary and conclusion

Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
The LD50 of the test item Lithium difluorobis(oxalate)phosphate is greater than 300 mg/kg and lower than 2000 mg/kg body weight after single oral administration to Wistar rats.
Based on Annex 2d Test Procedure with a Starting Dose of 2000 mg/kg body weight of OECD Guideline 423 it can be concluded that the test item Lithium difluorobis(oxalate)phosphate is classified in GHS Category 3 with a LD50 cut off value 300 mg/kg body weight, after single oral administration to Wistar rats.