Lithium difluoro(oxalato)borate(1-)

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2021.01-2021.03

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2021

Report date:

2021

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

GLP compliance:

yes (incl. QA statement)

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Lithium difluoro(oxalato)borate(1-)

EC Number:

803-919-2

Cas Number:

409071-16-5

Molecular formula:

C2BF2LiO4

IUPAC Name:

Lithium difluoro(oxalato)borate(1-)

Test material form:

solid: particulate/powder

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source (i.e. manufacturer or supplier) and lot/batch number of test material:
Provided by sponsor, Batch No.:G200810043

- Purity, including information on contaminants, isomers, etc.:
99.80%


STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material:
Refrigeration (+2 to +8°C)

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source:
In-vivo Biosciences
Shed No. 23, Khata No. 3169,
Assessment No. 154, Kodigehalli Village,
Magadi Road, Bengaluru – 560091, Karnataka

- Females (if applicable) nulliparous and non-pregnant: [yes/no]
yes

- Age at study initiation:
8 to 12 weeks

- Weight at study initiation:
218.6 to 259.9g

- Fasting period before study:
not specified

- Housing:
Rats were housed individually in standard polysulfone cages
(size: approximately L 425 x B 266 x H 185 mm), with stainless steel top grill
having facilities for pelleted food and drinking water in polycarbonate bottle.
Additionally, polycarbonate rat huts were placed inside the cage as an
enrichment object and were changed along with the cage once a week.
Bedding: steam sterilized corn cob was used and changed once a week along
with the cage.

- Diet (e.g. ad libitum):
ad libitum

- Water (e.g. ad libitum):
ad libitum

- Acclimation period:
After physical examination for good health and
suitability for experiment, the animals were
acclimatized for 6 days for G1-FTS, 21 days for G2-
FTS and 23 days for G2-STS before start of treatment.
Animals were observed once daily during
acclimatization period. Females were nulliparous and
non-pregnant.



ENVIRONMENTAL CONDITIONS
- Temperature (°C):
21 to 24 °C

- Humidity (%):
65 to 67%,

- Air changes (per hr):
13.1 to 14.5 per hour

- Photoperiod (hrs dark / hrs light):
12 hours light and 12 hours dark cycle

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

Milli-Q water

Details on oral exposure:

VEHICLE
Based on the solubility / suspendability test, the test item is miscible and
formed homogeneous suspension with Milli-Q water. Hence Milli-Q water was
used as vehicle for oral administration. The Milli-Q water was commonly used
for toxicological studies in our laboratory and was found to be non-toxic in
several animal species upon single and repeat dose administration.

MAXIMUM DOSE VOLUME APPLIED:
50 ml

Doses:

0, 50, 50, 300 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

yes

Details on study design:

- Duration of observation period following administration:
14 days

- Frequency of observations and weighing:
The body weights were recorded on test Day 1 (pre-administration), Day 8
(7 days post administration), Day 15 (14 days post administration) and Preterminally
dead rats.

- Necropsy of survivors performed:
yes

- Clinical signs including body weight
At each step, the animals were observed five times on test Day 1 (day of
administration) i.e. at 30 minutes and four times at hourly intervals and once daily during Day 2 to 15 post administration. Due to clinical signs of toxicity observed during treatment day an additional observation was carried out at the end of the treatment day.

Observations included changes in skin and fur, eyes and mucous membranes, and also respiratory, circulatory, autonomic and central nervous systems and somatomotor activity and behaviour pattern. Attention was directed to the observations of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma and all observed clinical signs were recorded.

- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:
none

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

200 mg/kg bw

Based on:

test mat.

Mortality:

300 mg/kg gourp G1: two rats died on day 1, 1 rats died on day 3
50 mg/kg groups G2 and G4: no mortality
control: no mortality

Clinical signs:

bodyweight loss

Body weight:

lower than 10% body weight loss

Applicant's summary and conclusion

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

The test item, Lithium difluoro (oxalato) borate (1-) is classified as follows:
• The test item is classified as “Category 3” (LD50 range >50 to 300 mg/kg
bodyweight) as per Globally Harmonized Classification system of Annex
2c of the Guideline OECD 423 .
• The test item is classified as “Category 3” (oral LD50 in the range of >50
to 300 mg/kg bodyweight) as per Globally Harmonized System of
Classification and Labelling of Chemicals (GHS) Eighth Revised Edition,
United Nations (2019). ST/SG/AC.10/30/Rev.8, as there was no mortality
observed at 50 mg/kg body weight .

Executive summary:

The acute oral toxicity study with Lithium difluoro (oxalato) borate (1-) in Wistar rats was conducted to assess the toxicological profile of the test item.

The dose formulation was prepared by using Milli-Q water and administered as a single oral gavage to overnight fasted (16 to 18 hours) three female rats (G1-FTS) at the dose of 300 mg/kg body weight. The clinical signs of hypoactivity, recumbent, abdominal respiration and slight piloerection were observed during
2nd hour post dose observation to end of the treatment day 1 and two rats died on day 2. Hypoactivity, slight piloerection, perineum wet with urine and weakness were observed in one rat during 2nd hour post dose observation to day 2 and rat died on day 3. Hence as per Annex 2c (OECD Guideline 423), the treatment was continued by dosing three additional female rats at the next lower dose of 50 mg/kg body weight (G2-FTS). All rats were normal and there were no pre-terminal deaths observed. As per Annex 2c (OECD Guideline 423), the treatment was continued by dosing three additional female rats at the same dose of 50 mg/kg body weight (G2-STS). All rats were normal and there were no pre-terminal deaths observed.

As per scheme, the dosing was stopped at this stage.

The prepared dose formulation was administered at the dose volume of 10 mL/kg bodyweight.

The rats were observed for mortality and clinical signs for 14 days post treatment. Body weights were recorded shortly prior to dosing on Day 1 and again on Day 8, 15 and at death. Necropsy was performed for all the survived and dead rats. All survived rats gained weight when compared to their initial body weight. There were no gross pathological changes at necropsy for survived and dead rats.

Based on the results of the present study, the LD50 of the test item Lithium difluoro (oxalato) borate (1-) is 200 mg/kg bodyweight as per the LD50 cut-off value.

The test item Lithium difluoro (oxalato) borate (1-) is classified as follows:
• The test item is classified as “Category 3” (LD50 range >50 to 300) as per Globally Harmonized Classification system of Annex 2c of the Guideline OECD 423.
• The test item is classified as “Category 3” (oral LD50 in the range of >50 to 300 mg/kg) as per Globally Harmonized System of Classification and Labelling of Chemicals (GHS) Eighth Revised Edition, United Nations
(2019). ST/SG/AC.10/30/Rev.8.