Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report date:
2013

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Lithium phosphorodifluoridate
EC Number:
643-080-8
Cas Number:
24389-25-1
Molecular formula:
LiPO2F2
IUPAC Name:
Lithium phosphorodifluoridate
Test material form:
solid: particulate/powder
Details on test material:
Batch number: 8252153

Test animals

Species:
rat
Strain:
Wistar
Remarks:
CRL:(WI) rats
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7, D-97633 Sulzfeld
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: Young adult rats
- Weight at study initiation: Males between 259g and 293g, Females between 205g and 256g
- Fasting period before study: none
- Housing :Individual caging (Cage type: Type II. polypropylene/polycarbonate Bedding: Laboratory bedding:
Lignocel Hygienic Animal Bedding produced by J. Rettenmaier & Söhne GmbH+Co.KG
- Diet (e.g. ad libitum): ssniff® SM R/M "Autoclavable complete diet for rats and mice – breeding and maintenance" produced by ssniff Spezialdiäten GmbH, D-59494 Soest, Germany ad libitum
- Water (e.g. ad libitum): tap water from the municipal supply, as for human consumption from 500 ml bottle ad libitum.
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.1 - 25°C
- Humidity (%): 30-51%
- Air changes (per hr): 15-20
- Photoperiod (hrs dark / hrs light): 12h dark' / 12h light

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: back of each animal
- % coverage: 10
- Type of wrap if used: semi-occlusive plastic wrap

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: 24h

TEST MATERIAL
- For solids, paste formed: moisten with water when applied to skin

Duration of exposure:
20 hours
Doses:
Sighting study: 50, 200, 1000, 2000 mg/kg bw
Main study: 1000 mg/kg bw
No. of animals per sex per dose:
Sighting study: 1 animal per dose
Main study: 4 females, 5 males
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were performed on the day of treatment at 1 and 5 hours after application of the test item and once each day for 14 days thereafter. Observations included the skin and fur, eyes and mucous membranes, the respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma. The body weights were recorded on Day 0 (before test item administration) and on Days 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology
Statistics:
None

Results and discussion

Preliminary study:
As the animal treated at a dose level of 2000 mg/kg bw in the sighting period, showed severe signs of a corrosive effect, the animal was euthanized and the dose level for the main period was defined as 1000 mg/kg bw.
Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 1 000 - < 2 000 mg/kg bw
Based on:
test mat.
Mortality:
Administration of the test item at a dose level of 1000 mg/kg body weight did not cause mortality, however due to the severe corrosive effects caused by the administration of the test item, two male animals were euthanized due to ethical reasons.
Clinical signs:
No systemic clinical signs were observed after treatment with the test item or during the 14-day observation period. Piloerection observed in case of 2 animals is suspected to be associated with the general bad condition of the animal caused by the severe skin injury rather than a systemic effect.
Body weight:
The body weight and body weight gain of surviving animals did not show any test item-related effect.
Gross pathology:
Test-item related, diffuse, grey discoloration of the skin at the site of application could be detected in 2/3 male and 1/5 female rats. In 1/5 male and 4/5 female rats, there was no evidence of the test item-related observations at a dose level of 1000 mg/kg bw at necropsy.
Other findings:
LOCAL DERMAL SIGNS
Administration of the test item at a dose level of 1000 mg/kg bw caused necrotic skin surface, wounds, scabs, erythema, oedema and scaled skin. Full recovery of the local signs was observed in case of 1/5 male and 4/5 females. Local signs were irreversible within the observation period in case of one female and two males. In case of two male animals, necrotic tissues on an extended surface was observed on the exposed skin area, therefore the animals were euthanized for animal welfare reasons in consultation with the clinical veterinarian.

Any other information on results incl. tables

Severe corrosive effects were seen in the 2000 mg/kg bw test group and irreversible local effects on the skin within the observation period in case of one female and two males (1000 mg/kg bw).

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The acute dermal median lethal dose (LD50) of the test item was found to be higher than 1000 mg/kg body weight in male and female CRL:(WI) rats. Severe corrosive effects were seen in the 2000 mg/kg bw test group and irreversible local effects on the skin was observed.