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

Acute Toxicity: oral

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

Test material information

Constituent 1

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.