Registration Dossier

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
April 04, 2006 - Juni 14, 2006
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2006
Report Date:
2006

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
other: 2004/73/EC B.4
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
, 2002
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
signed 2005-11-21

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Name: BIO 1031/1
Substance type: pure active substance
Physical state: solid
Storage condition of test material: ambient temp., dark, dry, in original container

other: The pH of the test material was determined prior to commencement of the study and found to be as follows: 10% (w/w) aqueous preparation of the test material = pH 4.4
No further details are given.

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Animals were supplied by David Percival Ltd., UK-
- Age at study initiation: 12 to 20 weeks
- Weight at study initiation: 2.0 to 3.5 kg
- Housing: The animals were individually housed in suspended cages.
- Diet: Certified Rabbit Diet (Code 5322) supplied by BCM IPS Limited, London, UK; ad libitum)
- Water: ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature: 17-23 °C
- Humidity: 30-70 %
- Air changes: 15 per hour
- Photoperiod: 12 hour light/dark cycle

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
water
Controls:
not required
Amount / concentration applied:
500 mg test material / 500 mL distilled water
Duration of treatment / exposure:
4 hours
Observation period:
Approx. one hour following the removal of the patches, and 24, 48 and 72 hours later, the test sites were examined for evidence of primary irritation.
Number of animals:
3 male rabbits
Details on study design:
TEST SITE
- Area of exposure: One rabbit was initially treated. Three suitable sites were selected on the back of the rabbit. At each test site a quantity of 0.5 g of the test material, moistened with 0.5 ml of distilled water was given .
- Type of wrap if used: Test material was introduced under a 2.5cm x 2.5cm cotten gauze patch and placed in position on the shorn skin. Each patch was secured in position with a strip of surgical adhesive tape. To prevent the animal interfering with the patches, the trunk of the rabbit was wrapped in an elasticated corset.

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: One patch was removed at each of three time points: 3 minutes, 1 hour and 4 hours after application. Any residual test material was removed by gentle swabbing with cotton wool soaked in distilled water.

After consideration of the skin reactions produced in the first animal, two additional rabbits were treated with 0.5g of the test material moistened with 0.5ml of distilled water. One patch was applied to the back of each rabbit, and was allowed to remain in contact with the skin for a period of 4 hours.

SCORING SYSTEM:
Erythema and Eschar Formation:
no erythema = 0
very slight erythema = 1
well-defined erythema = 2
moderate to serve erxthema = 3
serve erythema to eschar formation preventing grading of erythema = 4

Oedema Formation:
no oedema = 0
very slight oedema = 1
slight oedema = 2
moderate oedema = 3
serve oedema = 4

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: overall at 24, 48 and 72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: overall at 24, 48 and 72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: overall at 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 hours
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: overall at 24, 48 and 72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: overall at 24, 48 and 72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: overall at 24, 48 and 72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
4-hour exposure period: Very slight erythema was noted at all treated skin sites 1 hour after patch removal and 2 treated skin sites at the 24-hour observation.
1-hour exposure period: No evidence of skin irritation was noted during the study.
3-minutes exposure period: No evidence of skin irritation was noted during the study.
Reversibility of any observed effect: Changes fully reversible within 2 days
The test material produced a primary irritation index of 0.3 and was classified as a mild irritant to rabbit skin. No corrosive effects were noted.

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test item is regarded as not irritating to the skin. After an exposure time of 4 hours two of three animals show erythema/eschar formation (score 1). This effect was fully reversible within 48 hours.