Registration Dossier

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From April 23 to May 2, 2008.
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted according to internationally accepted testing guidelines and performed according to GLP.

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)
Version / remarks:
adopted Apri124, 2002
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Netherlands BV.
- Age at study initiation: 15 weeks (male) and 14 weeks (females).
- Allocation: Male No. 61, Female Nos. 62, 63.
- Diet: ad libitum, pelleted standard Provimi Kliba 3418 rabbit maintenance (batch no. 03/08) provided by Provimi Kliba AG, CH-4303 Kaiseraugst.
- Water: ad libitum, community tap water from Fullinsdorf.
- Acclimation period: under laboratory conditions after health examination. Only animals without any visual signs of illness were used for the study.

ENVIRONMENTAL CONDITIONS
- Temperature: continuously monitored environment with ranges for room temperature 17-23 °C.
- Humidity: between 30-70 % (values above 70 % during cleaning process possible).
- Air changes: air-conditioned with 10-15 air changes per hour.
- Photoperiod: automatically controlled light cycle of 12 hours light and 12 hours dark.
- Other: music during the daytime light period.

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
water
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.5 g (per animal) of test item was weighed as delivered by the Sponsor and then moistened with approximately 0.5 ml of purified water before application.
- Concentration: a formulation of a 1 % (w/w) solution in purified water was prepared. The pH was found to be 7-8.
Duration of treatment / exposure:
4 hours
Observation period:
The skin reaction was assessed at approximately 1, 24, 48 and 72 hours, after exposure (removal of the dressing, gauze patch and test item).
Number of animals:
Three: one male and two females.
Details on study design:
TEST SITE
- Area of exposure: four days before treatment, the left flank was clipped with an electric clipper, exposing an area of approximately 100 cm2 (10 cm x 10 cm). The skin of the animals was examined one day before treatment, and regrown fur of all animals was clipped again. Animals with overt signs of skin injury or marked irritation which may have interfered with the interpretation of the results were not used in the test.
- Application: on the day of treatment, 0.5 g of test item was placed on a surgical gauze patch (ca. 2.5 cm x 2.5 cm). This gauze patch was applied to the intact skin of the clipped area. The patch was covered with a semi-occlusive dressing.
- Type of wrap if used: the dressing was wrapped around the abdomen and anchored with tape.

REMOVAL OF TEST SUBSTANCE
- Washing: the dressing was removed after 4 hours and the skin was flushed with lukewarm tap water to clean the application site.

SCORING SYSTEM
The skin reaction was assessed according to the numerical scoring system listed in the Commission Directive 2004173/EC, April 29, 2004.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal: 3/3
Time point:
other: mean 24, 48 and 72 hrs
Score:
< 2.3
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal: 3/3
Time point:
other: mean 24, 48 and 72 hrs
Score:
< 2.3
Reversibility:
fully reversible
Irritant / corrosive response data:
A slight to well-defined erythema was observed in all animals I-hour after test item exposure and persisted as slight up to the 24-hour reading.
No abnormal findings were observed on the treated skin of any animal 48 hours after treatment.
Coloration: no staining produced by the test item of the treated skin was observed.
Corrosion: neither alterations of the treated skin were observed nor were corrosive effects evident on the skin.
Other effects:
No clinical signs of systemic toxicity were observed in the animals during the study and no mortality occurred.
The body weights of all rabbits were considered to be within the normal range of variability.

Any other information on results incl. tables

Skin irritation scores

Animal N. Sex Parameter 1 hr 24 hrs 48 hrs 72 hrs Mean*
61 M Erythema 1 1 0 0 0.33
Oedema 0 0 0 0 0.00
62 F Erythema 2 1 0 0 0.33
Oedema 0 0 0 0 0.00
63 F Erythema 2 1 0 0 0.33
Oedema 0 0 0 0 0.00

* Time point: 24, 48 and 72 hrs after patch removal.

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information according to the CLP Regulation Criteria used for interpretation of results: EU
Conclusions:
Not irritating.
Executive summary:

Method

The primary skin irritation potential of test item 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.

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.

Results

The mean erythema/eschar score of the three animals was 0.33 for all animals and the mean oedema score was 0.00 for all animals.

The application of test item to the skin resulted in very slight to well-defined erythema. This effect was reversible and was no longer evident 48 hours after treatment. 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.

Conclusion

According to the CLP Regulation (EC 1272/2008), test item is considered to be "not irritating" to rabbit skin.