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Description of key information

In the rat acute oral toxicity study, a single 300 mg/kg dose proved lethal, and necropsy revealed damage to the stomach mucosa.  No deaths followed dosing at 50 mg/kg.

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:
15 April 2008-13 May 2008
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study has been performed according to OECD and EC guidelines and according to GLP principles.
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Strain: Wistar strain Crl:WI(Han)
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: approx. 9-12 weeks old
- Weight at study initiation: 166-189 g
- Fasting period before study: Food was withheld overnight (for a maximum of 20 hours) prior to dosing until 3-4 hours after administration of the test substance.
- Housing: Group housing of 3 animals per cage in labelled Macrolon cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.5 – 21.6
- Humidity (%): 31 - 71
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 5 mg/mL and 30 mg/mL
- Amount of vehicle (if gavage): 10mL/kg bw
- Justification for choice of vehicle: The vehicle was selected based on trial formulations performed at NOTOX and on test substance data supplied by the sponsor.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw


DOSAGE PREPARATION (if unusual): The formulations (w/w) were prepared within 4 hours prior to dosing. The concentration of the test substance in vehicle was varied to allow constant dosage volume in terms of ml/kg body weight. Adjustment was made for specific gravity of the vehicle. Homogeneity was accomplished to a visually acceptable level.
In order to obtain homogeneity, the formulations were heated in a water bath with a maximum temperature of 42 °C for a maximum of 13 minutes. The formulations were allowed to cool down to a temperature of maximally 40 °C prior to dosing.


CLASS METHOD (if applicable)
The toxicity of the test substance was assessed by stepwise treatment of groups of 3 females. The first group was treated at a dose level of 300 mg/kg. The absence or presence of mortality of animals dosed at one step determined the next step, based on the test procedure defined in the guidelines. The onset, duration and severity of the signs of toxicity were taken into account for determination of the time interval between the dose groups.

Doses:
300, 50 and 50 mg/kg bw
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality/Viability: Twice daily.
Body weights: Days 1 (pre-administration), 8 and 15.
Clinical signs: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
No statistical analysis was performed (The method used is not intended to allow the calculation of a precise LD50 value).
Sex:
female
Dose descriptor:
LD50
Effect level:
50 - 300 mg/kg bw
Mortality:
Two females at 300 mg/kg were found dead and one female at 300 mg/kg was sacrificed for ethical reasons on Day 1.
No mortality occurred among the animals at 50 mg/kg.
Clinical signs:
Clinical signs observed during the study period were as follows:

300 mg/kg: Lethargy, hunched posture, uncoordinated movements, piloerection.
50 mg/kg: Hunched posture, piloerection.

The surviving animals had recovered from the symptoms by Day 3.
Body weight:
The mean body weight gain shown by the surviving animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain.
Gross pathology:
Macroscopic post mortem examination of the animals that were found dead or sacrificed for ethical reasons during the study revealed dark red and/or black discolouration of the glandular mucosa of the stomach.

No abnormalities were found at macroscopic post mortem examination of the animals at 50 mg/kg.
Other findings:
None.
Interpretation of results:
toxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The oral LD50 value of LiPF6 in Wistar rats was established to be within the range of 50-300 mg/kg body weight.
According to the OECD 423 test guideline, the LD50 cut-off value was considered to be 200 mg/kg body weight.

Based on these results:
- according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2004), LiPF6 should be classified as: Toxic if swallowed (Category 3) for acute toxicity by the oral route.
- according to the EC criteria for classification and labelling requirements for dangerous substances and preparations (Council Directive 67/548/EEC), LiPF6 should be labelled as: toxic if swallowed (R25).
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
200 mg/kg bw
Quality of whole database:
Klimisch 1

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for selection of acute toxicity – oral endpoint
Key study giving a reliable result.

Justification for selection of acute toxicity – inhalation endpoint
Study not required: substance is corrosive.

Justification for selection of acute toxicity – dermal endpoint
Study not required: substance is corrosive.

Justification for classification or non-classification

Evidence of an acute oral LD50 between 50 and 300 mg/kg triggers classification as Acute Toxicity 3, H301 under CLP regulation (1272/2008).