Registration Dossier

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2008
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The study was performed under GLP according to OECD guidelines for testing of Chemicals, Section 4, number 404, Acute Dermal Irritation/Corrosion (adopted April 24, 2002), and according to Commission Directive 2004/73/EC B.4, Acute Toxicity: Dermal Irritation/Corrosion (April 29,2004).

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
Details on test material:
- Name of test material (as cited in study report): Allantoin
- Physical state: solid
- Analytical purity: 99.5%
- Impurities (identity and concentrations): no data
- Composition of test material, percentage of components: not applicable
- Isomers composition: not applicable
- Purity test date: no data
- Lot/batch No.: 06052
- Expiration date of the lot/batch: 2009-03-07
- Stability under test conditions: stable under storage conditions
- Storage condition of test material: at room temperature (20°C +/- 5 °C), light protected.
- Other: routine hygienic procedures were used to ensure the health and safety of the personnel.

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Netherlands BV, Horst, the Netherlands
- Age at study initiation: 14 weeks (male), 15 weeks (female)
- Weight at study initiation: 2490 g (male) and 2274 - 2385 g (females)
- Housing: Individually in stainless steel cages equipped with feed hoppers and drinking water bowls. Wood blocks and haysticks were provided for gnawing.
- Diet: Pellet standard rabbit maintenance diet ad libitum.
- Water: Community tap water ad libitum.
- Acclimation period: Under laboratory conditions after health examination. Only animals without any visual signs of illness were used for the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23°C
- Humidity (%): 30-70%
- Air changes (per hr): 10-15 air changes per hour (air-conditioning)
- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light (automatically controlled).

IN-LIFE DATES: From: 13 May 2008 To: 19 May 2008

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
water
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 gram Allantoin
- Concentration (if solution): Allantoin moistened with approximately 0.5 mL of purified water

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.5 mL purified water
- Concentration (if solution): not applicable
- Lot/batch no. (if required): no data
- Purity: no data
Duration of treatment / exposure:
4 hours
Observation period:
1, 24, 48 and 72 hours.
Number of animals:
1 male, 2 females
Details on study design:
TEST SITE
- Area of exposure: 2.5 cm x 2.5 cm
- % coverage: no data
- Type of wrap if used: surgical gauze patch (2.5 x 2.5 cm), semi-occlusive dressing wrapped around abdomen.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): treated skin was flushed with lukewarm tap water to clean the application site after treatment.
- Time after start of exposure: 4 hrs

SCORING SYSTEM:
The skin reaction was assessed according to the numerical scoring system listed in the Commission Directive 2004/73/EC, April 29 2004.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Remarks on result:
other: The test item did not elicit any skin reactions at the application site of any animal at any of the observation times (all scores 0).
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Remarks on result:
other: The individual mean score for erythema for each of the three animals was 0.
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Remarks on result:
other: The individual mean score for edema for each of the three animals was 0.
Irritant / corrosive response data:
The mean score was calculated across 3 scoring times (24, 48 and 72 hours after patch removal) for each animal for erythema/eschar grades and for oedema grades, separately. The test item did not elicit any skin reactions at the application site of any animal at any of the observation times (all scores 0). The individual mean score for erythema/eschar and oedema for each of the three animals was therefore 0.
Other effects:
Coloration: No staining produced by the test item of the treated skin was observed.
Body weights: The body weights of all rabbits were considered to be within normal range of variability.

Any other information on results incl. tables

In the tested animals, no abnormal findings were noted (erythema, edema or flaking) and no staining was present at any of the observation intervals (1, 24, 48 or 72 hours).

Skin Irritation Scores - Individual Values

 Animal number  Sex  Evaluation Interval  Erythema  Oedema  Scaling
39/40/41 M/F/F 1 hour 0/0/0 0/0/0  0/0/0 
39/40/41 M/F/F  24 hours 0/0/0 0/0/0  0/0/0
39/40/41 M/F/F  48 hours 0/0/0  0/0/0  0/0/0 
39/40/41 M/F/F   72 hours 0/0/0  0/0/0  0/0/0 

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based upon referred classification criteria /Commission Directive 2001/59/EC of August 2001), Allantoin is considered to be "non irritating" to rabbit skin.
Executive summary:

The primary skin irritation potential of Allantoin was investigated according to OECD test guideline no. 404. The test item was applied by topical semi-occlusive application of 0.5 g to the intact left flank of each of three young adult New Zealand White rabbits. The duration of treatment was four hours. The scoring of skin reactions was performed 1, 24, 48 and 72 hours after removal of the dressing. Each animal was assessed for erythema/eschar grades and for oedema grades, separately.

The test item did not elicit any skin reactions at the application site of any animal at any of the observation times (all scores 0). The test item caused no staining of the treated skin. No corrosive effects were noted on the treated skin of any animal at any of the measuring intervals and no clinical signs were observed. Thus, the test item did not induce significant or irreversible damage to the skin.

Based upon the referred classification data (Commission Directive 2001/59/EC of August 2001), Allantoin is considered to be "not irritating" to rabbit skin.