Registration Dossier

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
20/11/2008 to 23/11/2008
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted to GLP in accordance with recognised guideline

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:
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:
No further information required.

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories UK Limited, Bicester, Oxon, UK.
- Age at study initiation: Twelve to twenty weeks old
- Weight at study initiation: Range of 2.0 to 3.5 kg
- Housing: The animals were individually housed in suspended cages.
- Diet (e.g. ad libitum): Free access to food (2030 Teklad Global Rabbit diet supplied by Harlan Teklad, Blackthorn, Bicester, Oxon, UK) was allowed throughout the study.
- Water (e.g. ad libitum): Free access to mains drinking water was allowed throughout the study.
- Acclimation period: Minimum of 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23°C
- Humidity (%): 30 to 70%
- Air changes (per hr): The rate of air exchange was at least fifteen changes per hour.
- Photoperiod (hrs dark / hrs light): Lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
water
Controls:
no
Amount / concentration applied:
TEST MATERIAL/VEHICLE
- Amount(s) applied:
A quantity of 0.5 g of the test material, moistened with 0.5 ml of distilled water, was introduced under a 2.5 cm x 2.5 cm cotton gauze patch and placed in position on the shorn skin.
Duration of treatment / exposure:
4 hours
Observation period:
Approximately 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
Details on study design:
TEST SITE
- Area of exposure:
On the day of the test a suitable test site was selected on the back of each rabbit. A quantity of 0.5 g of the test material, moistened with 0.5 ml of distilled water, was introduced under a 2.5 cm x 2.5 cm area.

- Type of wrap if used:
Cotton gauze patch. The patch was secured in position with a strip of surgical adhesive tape. To prevent the animals interfering with the patches, the trunk of each rabbit was wrapped in an elasticated corset and the animals were returned to their cages for the duration of the exposure period.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Any residual test material removed by gentle swabbing with cotton wool soaked in distilled water.
- Time after start of exposure: 4 hours

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

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

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

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 1 hr
Score:
0
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24 hrs
Score:
0
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 48 hrs
Score:
0
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 72 hrs
Score:
0
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 1 hr
Score:
0
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24 hrs
Score:
0
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 48 hrs
Score:
0
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 72 hrs
Score:
0
Irritant / corrosive response data:
No evidence of skin irritation was noted during the study.
Other effects:
Blue coloured staining was noted at all treated skin sites throughout the study but did not affect evaluation of skin responses. All animals showed expected bodyweight gain during the study.

Any other information on results incl. tables

The scores for erythema and oedema at the 24 and 72-hour readings were totalled for the three test rabbits (12 values) and this total was divided by six to give the primary irritation index of the test material. The test material was classified according to the following scheme devised by Draize J H (1959) "Dermal Toxicity" In: Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics. Association of Food and Drug Officials of the United States, Austin, Texas, p.46-59.

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: other: Draize classification scheme
Conclusions:
The test material produced a primary irritation index of 0.0 and was classified as NON-IRRITANT to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.
Executive summary:

In an Acute dermal irritation in the rabbit study (Harlan project number: 0959/0228) the test material was found to be non-irritating to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.

The study was performed to assess the irritancy potential of the test material following a single, 4-hour, semi-occluded application to the intact rabbit skin. The method was designed to meet the requirements of the following:

 - OECD Guidelines for the Testing of Chemicals No. 404 "Acute Dermal Irritation/Corrosion" (adopted 24 April 2002).

 - Method B4 Acute Toxicity (Skin Irritation) of Commission Directive 2004/73/EC.

Blue coloured staining was noted at all treated skin sites throughout the study but did not affect evaluation of skin responses.

No evidence of skin irritation was noted during the study. All animals showed expected gain in bodyweight during the study.