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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 03 September 2013 (Start of in-life phase) to 09 December 2013 (GLP compliance statement and Quality assurance 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 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
not specified
Qualifier:
according to
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
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 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:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Source: Charles River France, L’Arbresle Cedex, France
- Age at study initiation: between 12 and 24 weeks old
- Weight at study initiation: body weights were at least 1.5 kg
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.
- Housing: Animals were individually housed in labeled cages with perforated floors (Ebeco, Germany, dimensions 67 x 62 x 55 cm) and shelters (Ebeco, Germany, dimensions 40 x 32 x 23 cm).
- Diet : Pelleted diet for rabbits (Global Diet 2030 from Harlan Teklad®, Mucedola, Milanese, Italy) approximately 100 grams per day. Hay (TecniLab-BMI BV, Someren, The Netherlands) and wooden sticks (Swedish aspen wood, Bioservices, Uden, The Netherlands) were available during the study period.
- Water : Free access to tap water.
- Acclimation period: at least 5 days before start of treatment under laboratory conditions.
- End of treatment: After the final observation, the animals were sacrificed by intra-venous injection of Euthasol® 20% (AST Farma BV, Oudewater, The Netherlands).

ENVIRONMENTAL CONDITIONS
- Temperature : 18-24°C
- Humidity : 40-70 %
- Air changes : approximately 15 room air changes/hour
- Photoperiod : 12-hour light/12-hour dark cycle

IN-LIFE DATES: From: 03 September 2013 To: 20 September 2013.

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
water
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
Amount(s) applied : Each animal was treated by dermal application of 0.5 grams of the test substance which was moistened with 0.3 mL of the vehicle (i.e. water).

VEHICLE
The powdery test substance was moistened with water (Elix, Millipore S.A.S., Molsheim, France), immediately before application, to ensure close contact with the animal's skin.
No corrections were made for the purity/composition of the test substance, since the guidelines requires a fixed amount that has to be applied.
Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
3 males : The study was performed in a stepwise manner and was started by treatment of a single rabbit (sentinel). The two other animals were treated in a similar manner 14 days later, after considering the degree of skin irritation observed in the first animal.
Details on study design:
TEST SITE
Approximately 24 hours before treatment, the dorsal fur was clipped with electric clippers, exposing an area of approximately 150 square centimeters (10x15 cm). To facilitate scoring, treated skin areas were re-clipped at least 3 hours before the observations.
The test item was applied to the skin of one flank, using a metalline patch of 2x3 cm. The patch was mounted on Micropore tape, which was wrapped around the abdomen and secured with Coban elastic bandage.


REMOVAL OF TEST SUBSTANCE
Four hours after the application, the dressing was removed and the skin cleaned of residual test substance using tap water.

OBSERVATION AND SCORING SYSTEM:
Mortality/Viability : observation twice daily.
Toxicity : observation at least once daily.
Body Weight : observation the day of treatment (prior to application) and after the final observation.
Necropsy : No necropsy was performed according to protocol.
Irritation : The skin reactions were assessed at approximately 1, 24, 48 and 72 hours after the removal of the dressings and test substance. The irritation scores and a description of all other (local) effects were recorded. Adjacent areas of the untreated skin of each animal served as controls.
The irritation was assessed according to the following numerical scoring system. At each observation, the highest scores given were recorded:

Erythema and eschar formation:
No erythema .......................................................................................................................... 0
Very slight erythema (barely perceptible) ............................................................................... 1
Well-defined erythema ........................................................................................................... 2
Moderate to severe erythema................................................................................................. 3
Severe erythema (beet redness) *.......................................................................................... 4
*. Where signs of necrosis or corrosion (injuries in depth) prevent erythema scoring, the
maximum grade for erythema (= 4) is given.

Oedema formation:
No oedema ............................................................................................................................ 0
Very slight oedema (barely perceptible) ................................................................................. 1
Slight oedema (edges of area well-defined by definite raising) ............................................... 2
Moderate oedema (raised approximately 1 millimeter) ........................................................... 3
Severe oedema (raised more than 1 millimeter and extending beyond the area of exposure) 4

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Remarks:
all the 3 animals showed the same score
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Remarks:
first reading at 1h
Irritation parameter:
edema score
Basis:
mean
Remarks:
all the 3 animals showed the same score
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Remarks:
first reading at 1h
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Irritant / corrosive response data:
Irritation:
No skin irritation was caused by 4 hours exposure to Lithium cryolite.
Corrosion:
There was no evidence of a corrosive effect on the skin.
Coloration / Remnants:
No staining of the treated skin by the test substance was observed and no test substance remnants were seen.
Toxicity / Mortality :
No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.
Other effects:
No histopathology was performed.

Any other information on results incl. tables

Deviations:

- protocol deviations : Deviations from the minimum and maximum level of daily mean relative humidity occurred.

Evaluation: Laboratory historical data do not indicate an effect of the deviations.

The study integrity was not adversely affected by the deviations.

- standard operating procedures deviations : 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:
Lithium cryolite does not have to be classified for skin irritation according to the CLP and the UN GHS.
Executive summary:

The primary skin irritation/corrosion of Lithium cryolite in the rabbit (4-hour semi-occlusive application) was investigated in a study performed according to the OECD Testing Guideline No.404 and under GLP.

Three rabbits were exposed to 0.5 grams of Lithium cryolite, moistened with water by application onto clipped skin for 4 hours using a semi-occlusive dressing. Skin reactions were assessed 1, 24, 48 and 72 hours after exposure.

No skin irritation was caused by 4 hours exposure to Lithium cryolite.

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