Registration Dossier

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
11 June 2008 to 18 June 2008
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2008
Report Date:
2008

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:
no
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: crystalline
Details on test material:
- Appearance: White crystalline solid
- Storage conditions: Room temperature in the dark

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: The animal was in the range 12 to 20 weeks old.
- Weight at study initiation: The animal was in the range 2.0 to 3.5 kg.
- Housing: The animal was housed individually in a suspended cage.
- Diet (e.g. ad libitum): Free access to Certified Rabbit Diet was allowed.
- Water (e.g. ad libitum): ad libitum access to mains drinking water.
- Acclimation period: At least 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23 °C.
- Humidity (%): 30 to 70 % (relative).
- Air changes (per hr): At least 15 per hour.
- Photoperiod (hrs dark / hrs light): The lighting was controlled by a time switch to give 12 hours continuous light (0600 to 1800) and 12 hours darkness.

IN-LIFE DATES:
- From: 11 June 2008
- To: 18 June 2008

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Remarks:
The test material was moistened with 0.5 mL of distilled water.
Controls:
not required
Amount / concentration applied:
0.5 g
Duration of treatment / exposure:
3 minutes
Observation period:
24 hours
Number of animals:
1
Details on study design:
INITIAL CONSIDERATIONS
Available information indicated that the test material had the potential to produce severe irritation/corrosion (10 % w/w aqueous preparation had a pH of 13.8) and to confirm this initial assessment an ex vivo pre-screen test, the Transcutaneous Electrical Resistance Assay, was performed. The results of the pre-screen test indicated that the test material was considered not to be corrosive to the skin and the in vivo study was carried out.

TEST SITE
- Area of exposure: 2.5 x 2.5 cm. The test material was introduced under a 2.5 x 2.5 cm cotton gauze patch and placed in position on the shorn skin.
- Type of wrap if used: The patch was secured with a strip of surgical adhesive tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Any residual test material was removed by gentle swabbing with cotton wool soaked in distilled water.
- Time after start of exposure: 3 minutes.

SCORING SYSTEM:

Erythema and eschar formation:
0 = No erythema
1 = Very slight erythema (barely perceptible)
2 = Well-defined erythema
3 = Moderate to severe erythema
4 = Severe erythema (beef redness) to eschar formation preventing grading of erythema

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

Any other skin reactions, if present, were also recorded.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 1 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: Light green coloured dermal necrosis, Dermal haemorrhage surrounding dermal necrosis.
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24 h
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: Adverse reaction prevented accurate evaluation of erythema. Sunken, hardened dark brown.black coloured scab.
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 1 h
Score:
2
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24 h
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: Adverse reaction prevented accurate evaluation of edema
Irritant / corrosive response data:
Reactions noted at the treated skin site one hour after patch removal were light green coloured dermal necrosis (attributed a Draize score of 4 for injuries in depth), surrounded by dermal haemorrhage, and slight oedema. A sunken, hardened dark brown/black coloured scab, preventing accurate evaluation of erythema and oedema, was noted at the treated skin site at the 24-hour observation. The animal was killed for humane reasons immediately after the 24 hour observation, due to the irreversible effects. Due to the corrosive reactions following an exposure period of 3 minutes, the 1 and 4 hour exposure periods were not investigated.

Applicant's summary and conclusion

Interpretation of results:
other: Classified as Category 1A (corrosive) in accordance with EU criteria
Conclusions:
Under the conditions of this study, the test material was corrosive to rabbit skin and as such requires classification as Corrosive Category 1A in accordance with EU Criteria.
Executive summary:

A study was performed to assess the irritancy potential of the test material to the skin of the New Zealand White rabbit in accordance with the standardised guidelines OECD 404 and EU Method B.4.

Available information indicated that the test material had the potential to produce severe irritation/corrosion; to confirm this initial assessment, an ex vivo pre-screen test, the Transcutaneous Electrical Resistance (TER) Assay, was performed. The results of the pre-screen test indicated that the test material was considered not to be corrosive to the skin and the in vivo study was performed.

0.5 g of the test material, moistened with distilled water, was applied under a gauze patch to the clipped skin of one rabbit. The patch was removed 3 minutes after application and any residual test material removed with cotton wool soaked in distilled water. The reaction of the skin was evaluated 1 hour and 24 hours following the removal of the patch.

The test material produced reactions indicative of dermal corrosion. The reactions included light green coloured dermal necrosis, surrounded by dermal haemorrhage, and a sunken, hardened dark brown/black coloured scab. The animal was killed for humane reasons immediately after the 24 hour observation, due to the irreversible effects.

Due to the corrosive reactions following an exposure period of 3 minutes, the 1 and 4 hour exposure periods were not investigated.

Under the conditions of this study, the test material was corrosive to rabbit skin and as such requires classification as Corrosive Category 1A in accordance with EU Criteria.