Registration Dossier

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
from 10 August 2009 to 20 November 2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Compliant to GLP and testing guideline; adequate coherence between data, comments and conclusions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009
Report date:
2009

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. QA statement)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Physical state: brown black liquid
- Lot/batch No.: prélévement SR320 du 1 juillet 2009
- Expiration date of the lot/batch: 01/07/2011
- Storage condition of test material: at room temperature
- Purity/Impurities: not applicable (complex composition)

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Breeder: Grimaud Frères Sélection S.A.S, Roussay, France
- Age at study initiation: 2 to 4 months old
- Weight at study initiation: 2.976 +- 0.109 kg
- Housing: Individual Pajon cages (50 cm x 57 cm x 75 cm).
- Diet: 112C pelleted diet, provided ad libitum
- Water: drinking water filtered by a FG Millpore membrane, provided ad libitum
- Acclimation period: at least 5 days before the beginning of the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 +- 3°C
- Humidity (%): 30 to 70%
- Air changes (per hr): 12 cycles/hour of filtered, non-recycled air
- Photoperiod (hrs dark / hrs light): 12h/12h (7:00 - 19:00)

IN-LIFE DATES: From: 18 August 2009 To: 31 August 2009

Test system

Type of coverage:
semiocclusive
Preparation of test site:
other: clipped
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied : 0.5 mL
- Concentration (if solution): not applicable


Duration of treatment / exposure:
3 minutes, 1 hour, 4 hours
Observation period:
1 hour, 24, 48 and 72 hours after removal of the dressing and daily until Day 8 at the latest.
Number of animals:
3 males
Details on study design:
TEST SITE
- Area of exposure: anterior left flank: application for 3 minutes, anterior right flank: application for 1 hour, or the posterior right
flank: application for 4 hours of the animals.
- % coverage: 6 cm2
- Type of wrap if used: gauze pad 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): a moistened cotton pad
- Time after start of exposure: at removal of each dressing

SCORING SYSTEM:
Dermal irritation was evaluated for each animal according to the following scoring scale:

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) to slight eschar formation (injuries in depth) 4
Edema formation
. no edema 0
. very slight edema (barely perceptible) 1
. slight edema (edges of area well-defined by definite raising) 2
. moderate edema (raised approximately 1 millimeter) 3
. severe edema (raised more than 1 millimeter and extending beyond area of exposure) 4

Any other lesions were noted.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 24h, 48h, 72h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 24h, 48h, 72h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 1h, 24h, 48h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 6 days
Irritation parameter:
edema score
Basis:
other: animal #1, 2 and 3
Time point:
other: 24h, 48h, 72h
Score:
0
Max. score:
4
Irritant / corrosive response data:
After a 3-minute exposure (one animal):
A very slight or well-defined erythema (grade 1 or 2) was noted from day 1 until day 7. A very slight edema (grade 1) was observed on days 1 and 2.
After a 1-hour exposure (one animal):
A very slight erythema (grade 1) was noted from day 1 until day 7.

After a 4-hour exposure (three animals):
A very slight or well-defined erythema (grade 1 or 2) was noted in all animals on day 1. A very slight erythema (grade 1) persisted in two of them until day 5 (No. 938) or 6 (No. 935). Dryness of the skin was noted in animal No. 938 on days 5 and 6

Applicant's summary and conclusion

Interpretation of results:
slightly irritating
Remarks:
Migrated information Criteria used for interpretation of results: other: REGULATION (EC) No 1272/2008
Conclusions:
The test item was slightly irritant when applied topically to rabbits.
Executive summary:

The potential of the test item to induce skin irritation was evaluated following a single topical applications to rabbits according to OECD (No. 404, 24th April 2002) and Council Regulation (EC) (No. 440/2008, B.4, 30 May 2008) guidelines. The study was conducted in compliance with the principles of Good Laboratory Practice Regulations. The test item was first applied for periods of 3 minutes, 1 hour and 4 hours to a single male New Zealand White rabbit. Since the test item was neither severely irritant nor corrosive on this first animal, it was then applied simultaneously for 4 hours to two other animals. A single dose of 0.5 mL of the undiluted test item was applied to the closely-clipped skin of one flank. The test item was held in contact with the skin by means of a semi-occlusive dressing. Cutaneous reactions were observed approximately 1 hour, 24, 48 and 72 hours after removal of the dressing and then daily until reversibility of cutaneous reactions (at least day 8). The mean values of the scores for erythema and edema were calculated for each animal. After a 3-minute exposure (one animal), a well-defined then very slight erythema was noted from day 1 until day 7. A very slight edema was observed on days 1 and 2. After a 1-hour exposure (one animal), a very slight erythema was noted from day 1 until day 7. After a 4-hour exposure (three animals), a very slight or well-defined erythema was noted in all animals on day 1. A very slight erythema persisted in two of them until day 5 (No. 938) or 6 (No. 935). Dryness of the skin was noted in animal No. 938 on days 5 and 6. Mean scores over 24, 48 and 72 hours for each animal were 1.0, 0.0 and 1.0 for erythema and 0.0, 0.0 and 0.0 for edema. The test item was slightly irritant when applied topically to rabbits.