Registration Dossier

Administrative data

Description of key information

An in vivo skin irritation/corrosion study is available.  The study was conducted on a single male New Zealand White rabbit according to OECD Guideline 404. The results of this single rabbit investigation following a 3-minute exposure indicated corrosive effects of acute exposure and no additional animals were exposed. 

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study was compliant with the relevant guidelines and was conducted in accordance with GLP.
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
The temperature and relative humidity recorded in the animal room were sometimes outside of the target ranges. This minor deviation was not considered to have compromised the validity or integrity of the study.
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
see above
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: CEGAV, Saint Mars d'Egrenne, France
- one male animal
- Age at study initiation: 2 to 4 months old
- Weight at study initiation: 3.2 kg
- Housing: polystyrene cage (48.2 cmx 58cmx 36.5cm)
- Diet : free access to 110 pelleted diet (UAR, Villemoisson, Epinay sur Orge, France)
- Water : drinking water filtered by a FG millipore membrane (0.22 micron), ad libitum
- Acclimation period: at least 5 days before the beginning of the study


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18+/-3
- Humidity (%): 30 to 70
- Air changes (per hr): approximately 12 cycles/ hour of filterd, non-recycled air
- Photoperiod (hrs dark / hrs light): 12h/12h
Type of coverage:
semiocclusive
Preparation of test site:
other: The day before the treatment, both flanks of the animal were clipped using electric clippers and the skin of the animal was examined in order to ensure that the animal has healthy intact skin at the beginning of the study.
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.5 ml of the test substance were placed on a dry gauze pad.
Duration of treatment / exposure:
3-minute and 4-hour applications
Observation period:
1h and 24 h
The animal was killed on day 2 for ethical reasons.
Number of animals:
1
Details on study design:
TEST SITE
- Area of exposure: right and left flank of the animal

REMOVAL OF TEST SUBSTANCE
After removal of the dressing, any residual test item was wipped off by means of moistened cotton pad.

SCORING SYSTEM:
Irritation evaluated according to the grading scale originally proposed by Draize and adopted by OECD test guideline 404.
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 1 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 1 h
Score:
0
Max. score:
4
Irritation parameter:
other: lesion
Basis:
animal #1
Time point:
other: 1 h
Remarks on result:
other: brown coloration of the skin
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 24 h
Remarks on result:
other: Necrosis
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 24 h
Remarks on result:
other: Scoring masqued by necrosis
Irritant / corrosive response data:
After a 3-minute or a 4-hour exposure, necrosis was noted at the application site 24 hours after removal of the dressing (day 2). The animal was then killed for ethical reasons.

Since the test item showed corrosive properties on the first animal, the study was considered complete and the test item was not evaluated on other animals.

Interpretation of results:
corrosive
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under our experimental conditions, the test substance is corrosive when applied topically to rabbits.
According to the classification criteria laid down in Council Directive 67/548/EEC (and subsequent adaptations), the test substance should be classified as corrosive and assigned the symbol C, the indication of danger “Corrosive” and the risk phrase R35: “Causes severe burns”. In accordance with CLP Regulation 1272/2008, the test substance should be classified as Category 1 B corrosive substance with the signalword Danger and the hazard statement "H314: Causes severe skin burns and eye damage" associated with it.
Executive summary:

The potential of the test substance to induce skin irritation was evaluated in rabbits according to OECD (No. 404, 17th July 1992) and EC (96/69/EEC, B.4, 31 July 1992) guidelines. The study was conducted in compliance with the principles of Good Laboratory Practice Regulations. In the first instance, the test substance was applied for a period of 3 minutes and 4 hours to a single male New Zealand White rabbit. As the test substance showed corrosive properties on this first animal, the study was considered complete and the test item was not evaluated on other animals. A single dose of 0.5ml of the undiluted test substance was applied to the closely-clipped skin of one flank. The test substance was held in contact with the skin by means of a semi-occlusive dressing. Cutaneous reaction were observed approximately 1 hour and 24 hours after removal of the dressing. After a 3-minute or a 4-hour exposure, necrosis was noted at the application site 24  hours after removal of the dressing (day 2) The animal was then killed for ethical reasons. Under our experimental conditions, the test substance is corrosive when applied topically to rabbits. According to the classification criteria laid down in Council Directive 67/548/EEC (and subsequent adaptations), the test substance should be classified as corrosive and assigned the symbol C, the indication of danger “Corrosive” and the risk phrase R35: “Causes severe burns”. In accordance with CLP Regulation 1272/2008, the test substance should be classified as Category 1 B corrosive substance with the signalword Danger and the hazard statement "H314: Causes severe skin burns and eye damage" associated with it.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The potential of the test substance to induce skin irritation was evaluated in rabbits according to OECD (No. 404, 17thJuly 1992) and EC (96/69/EEC, B.4, 31 July 1992) guidelines. The study was conducted in compliance with the principles of Good Laboratory Practice Regulations.

In the first instance, the test substance was applied for a period of 3 minutes and 4 hours to a single male New Zealand White rabbit. As the test substance showed corrosive properties on this first animal, the study was considered complete and the test item was not evaluated on other animals.A single dose of 0.5ml of the undiluted test substance was applied to the closely-clipped skin of one flank.

The test substance was held in contact with the skin by means of a semi-occlusive dressing. Cutaneous reaction were observed approximately 1 hour and 24 hours after removal of the dressing.

After a 3-minute or a 4-hour exposure, necrosis was noted at the application site 24  hours after removal of the dressing (day 2) The animal was then killed for ethical reasons. Under our experimental conditions, the test substance is corrosive when applied topically to rabbits.

In accordance with CLP Regulation 1272/2008, the test substance should be classified as Category 1 B corrosive substance with the signal word Danger and the hazard statement "H314: Causes severe skin burns and eye damage" associated with it. According to Directive 67/548/EEC, the test substance should be classified as Corrosive (C) and have the risk phrase "R35: Causes severe burns" associated with it.

The corrosive results obtained in rabbit dermis preclude conducting an in vivo assessment of ocular reactions. It is assumed that serious damage or ocular corrosion would occur from single exposure of the eye. This hazard is recognised in the GHS classification of H314.


Effects on skin irritation/corrosion: corrosive

Justification for classification or non-classification

In accordance with CLP Regulation 1272/2008, the test substance should be classified as Category 1 B corrosive substance with the signal word Danger and the hazard statement "H314: Causes severe skin burns and eye damage" associated with it. According to Directive 67/548/EEC, the test substance should be classifed as Corrosive (C) and have the risk phrase "R35: Causes severe burns" associated with it.

The corrosive results obtained in rabbit dermis preclude conducting an in vivo assessment of ocular reactions. It is assumed that serious damage or ocular corrosion would occur from single exposure of the eye. This hazard is recognised in the GHS classification of H314.