Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 12 September 2013 (Start of in-life phase) to 19 December 2013 (GLP compliance statement)
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 guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
not specified
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
not specified
Qualifier:
according to
Guideline:
other: Food and Agricultural Materials Inspection Centre (FAMIC), 12 Nohsan, Notification No. 8147, April 2011; including the most recent partial revisions.
Deviations:
not specified
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Details on test material:
- Name of test material : Lithium cryolite
- Molecular formula : Li3AlF6
- Molecular weight : 162
- Physical state: White powder
- Storage condition of test material: At room temperature in the dark

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: Young adult animals (approx. 10 weeks old)
- Weight at study initiation: mean weight for males was 288 g, mean weight for females was 199 g, Body weight variation did not exceed +/- 20% of the sex mean.
- Health inspection : At least prior to dosing. It was ensured that the animals were healthy and that the skin to be treated was intact and free from any abnormality
- Fasting period before study: none
- Housing: Individually housed in labeled Makrolon cages (MIII type, height 18 cm.) containing sterilized sawdust as bedding material (Litalabo, S.P.P.S., Argenteuil, France) and paper as cage-enrichment (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd), Surrey, United Kingdom).
- Diet : Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).
- Water : Free access to tap water.
- Acclimation period: at least 5 days before start of treatment under laboratory conditions. During the acclimatization period the animals were group housed in Makrolon cages (MIV type, height 18 cm).

ENVIRONMENTAL CONDITIONS
- Temperature (°C): from 18 to 24 °C
- Humidity (%): from 40 to 70 %
- Air changes (per hr): approximately 15 room air changes/hour
- Photoperiod (hrs dark / hrs light): a 12-hour light/12-hour dark cycle

IN-LIFE DATES: From: 12 September 2013 To: 26 September 2013.

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
propylene glycol
Details on dermal exposure:
TEST SITE
- Clipping : One day before exposure (Day -1) an area of approximately 5x7 cm on the back of the animal was clipped.
- Area of exposure: approx. 25 cm² for males and 18 cm² for females
- % coverage: approx. 10% of the total body surface
- Type of wrap if used: The formulation was held in contact with the skin with a dressing, consisting of a surgical gauze patch (Surgy 1D), successively covered with aluminum foil and Coban elastic bandage. A piece of Micropore tape was additionally used for fixation of the bandages in females only.

REMOVAL OF TEST SUBSTANCE
- Washing (if done) :the skin cleaned of residual test substance using tap water.
- Time after start of exposure: 24h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg (10 mL/kg) body weight

VEHICLE
Propylene glycol (Merck, Darmstadt, Germany) (specific gravity 1.036)
The vehicle was selected based on trial formulations performed at WIL Research Europe and on test substance data supplied by the sponsor.
The formulation (w/w) was prepared within 4 hours prior to dosing. Homogeneity was accomplished to a visually acceptable level. Adjustment was made for specific gravity of the vehicle. No correction was made for purity of the test substance.
Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 males and 5 females (females were nulliparous and non-pregnant).
Control animals:
not required
Details on study design:
- Duration of observation period following administration : 14 days
- Mortality/Viability : observation twice daily.
- Body weights : observation on days 1 (pre-administration), 8 and 15.
- Clinical signs : observations at periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15. The time of onset, degree and duration were recorded and the symptoms graded according to fixed scales:
Maximum grade 4: grading slight (1) to very severe (4)
Maximum grade 3: grading slight (1) to severe (3)
Maximum grade 1: presence is scored (1).
- Necropsy : observation at the end of the observation period, all animals were sacrificed by oxygen/carbon dioxide procedure and subjected to necropsy. Descriptions of all internal macroscopic abnormalities were recorded.
Statistics:
Not applicable (limit test).

Results and discussion

Preliminary study:
Not applicable.
Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
Chromodacryorrhoea was noted for all animals on Days 1 and 2. General erythema, erythema maculate, scales and/or scabs were noted among the female animals between Days 3 and 15.
Body weight:
The changes noted in mean body weight gain in males and females were within the range expected for rats used in this type of study and were therefore considered not indicative of toxicity.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.
Other findings:
None.

Any other information on results incl. tables

Deviations:

There were no deviations from the protocol.

Any deviations from standard operating procedures were evaluated and filed in the study file. There were no deviations from standard operating procedures that affected the integrity of the study.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The dermal LD50 value of Lithium cryolite in Wistar rats was established to exceed 2000 mg/kg body weight.
Based on these results, Lithium cryolite does not have to be classified for acute dermal toxicity according to the CLP and the UN GHS.
Executive summary:

The acute dermal toxicity of Lithium cryolite in the rat was investigated according to the OECD Testing Guideline 402 and under GLP.

Lithium cryolite was administered to five Wistar rats of each sex by a single dermal application at 2000 mg/kg body weight for 24 hours. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (Day 15).

No mortality occurred.

Chromodacryorrhoea was noted for all animals on Days 1 and 2. General erythema, erythema maculate, scales and/or scabs were noted among the female animals between Days 3 and 15.

The mean body weight gain during the observation period was within the range expected for rats used in this type of study.

No abnormalities were found at macroscopic post mortem examination of the animals.

The dermal LD50 value of Lithium cryolite in Wistar rats was established to exceed 2000 mg/kg body weight.

Based on these results, Lithium cryolite does not have to be classified according to the CLP and the UN GHS.