Registration Dossier

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
21 June 1995 to 3 July 1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, performed to valid guidelines and the study was conducted under GLP conditions.
Cross-reference
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1995
Report Date:
1995

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report): M-377
- Physical state: solid
- Appearance: garnet powder
- Storage condition of test material: room temperature and protected from light
- pH of substance: 8.3 (measured at a concentration of 10% w/w in distilled water)

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Sex: male
- Weight at study initiation: 2.4 ± 0.1 kg (mean)
- Housing: individually in polystyrene cages
- Diet: pelleted diet, ad libitum
- Water: filtered drinking water (0.22 µm), ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3 °C
- Humidity (%): 30 - 70 %
- Photoperiod (hrs dark / hrs light): 12 hours dark / 12 hours light

IN-LIFE DATES: From 21 June 1995 to 3 July 1995

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 500 mg
Duration of treatment / exposure:
4 hours
Observation period:
3 days post administration
Number of animals:
3 male animals
Details on study design:
TEST SITE
- Area of exposure: On the day prior to application, the flanks of each animal were clipped using electric clippers. A dose of 500 mg of test material was applied to a 6 cm² hydrophilic gauze pad moistened with 0.5 mL of distilled water and this was then applied to the right flank of the animals for 4 hours. The left flank did not receive any test material and served as an untreated control.
- Type of wrap if used: The test material and gauze pad were held in contact with the skin by means of an adhesive hypoallergenic aerated semi-occlusive dressing and a restraining bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): At the end of the exposure period, the dressing was removed and any residual test material was wiped off with a gauze pad moistened with water.
- Time after start of exposure: approximately 4 hours

SCORING SYSTEM:
The Draize scale, presented as table 1 in the field "Any other information on material and methods incl. tables" was used to assess the degree of erythema and oedema at the application sites approximately 1 hour and 1, 2 and 3 days after the removal of the dressings. Any other lesions were recorded.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: not applicable since no skin reaction was noted in any of the animals
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Max. score:
4
Reversibility:
no data
Remarks on result:
other: Scores for erythema could not be determined due to the skin colouration caused by the test material
Irritant / corrosive response data:
No oedema was noted at any time point.
Other effects:
Moderate to very slight purple colouration of the test site was noted on all animals which masked any observations of erythema of grades 1 to 3. The colouration persisted for 10 to 12 days post test material application.

Any other information on results incl. tables

Table 2: Results

Rabbit number

Dermal irritation

Scores

Mean irritation score

1 h

24 h

48 h

72 h

1

Erythema

C2

C2

C2

C2

(2)

Oedema

0

0

0

0

0

2

Erythema

C2

C2

C2

C2

(2)

Oedema

0

0

0

0

0

3

Erythema

C3

C3

C3

C2

(2)

Oedema

0

0

0

0

0

C2 = purple colouration of the skin would mask an erythema score of grades 1 or 2

C3 = purple colouration of the skin would mask an erythema score of grades 1 or 3

(2) = not calculated

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the test, the test material did not elicit any reaction in any of the animals during the course of the study that meant the test material required classification as a skin irritant. The study is considered to be reliable, relevant and adequate for risk assessment and classification and labelling purposes.
Executive summary:

The skin irritation potential of the test material was determined in accordance with standardised guidelines OECD 404 and EU Method B.4. Three rabbits received a single four hour application of 500 mg of the test material and were assessed for the following 3 days for any signs of skin irritation. The mean score over 24, 48 and 72 hours for each individual animal was 0.0 for oedema. Scores for erythema could not be calculated due to skin colouration. Due to skin colouration, evaluation of skin irritation could not be made. However, the absence of oedema in this study, the very weak ocular reactions observed in the acute eye irritation study (rabbits; de Jouffrey 1995b) and the absence of local effects observed in an acute dermal study (rat; de Jouffery 1996a) allows us to conclude that the test material is not a skin irritant based on expert judgment.