Registration Dossier

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1985-02-05 to 1985-02-08
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study (OECD 404) according to GLP Deficiencies by guideline updates: simultaneous administration of test item to three animals - no sequential approach of dosing. However, this did not compromise the quality of the study.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1985
Report Date:
1985

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
adopted May 12 , 1981
Deviations:
no
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Physical state: solid, insoluble in water
- Analytical purity: commercial grade

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS:
- The test was performed on 3 male New Zealand white rabbits (KFM-NZW), checked for normal skin conditions.
- Source: Kleintierfarm Madoerin AG, CH-4414 Füllinsdorf, Switzerland
- Age at study initiation: approx. 12-14 weeks old
- Weight at study initiation: 2 to 3 kg
- Housing: Individually in metal cages, identified with individually numbered ear tags
- Diet: ad libitum standard rabbit pellet - Nafag No. 814, Gossau, Switzerland
- Water: Fresh water ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: Constant room temperature of 20±3 °C
- Humidity: Relative humidity of 30-70 %
- Photoperiod: 12 hours light cycle day

All batches of the diet are assayed for nutritive ingredients and contaminant level by the manufacturer. Analytical results are available at the animal supply office. The quality of the drinking water was according to the specifications of the "Schweizerisches Lebensmittelbuch" (Edition 1972). Results of the routine chemical examination of water at source (Grundwasserfassung Stein) as conducted periodically by the water authority (Baudepartement des Kantons Aargau, Abteilung Gewaesserschutz) are available to Ciba-Geigy Ltd., as well as the results of in house chemical analysis by the analytical laboratories of the Pharmaceuticals Division, Ciba-Geigy Ltd.

Test system

Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
water
Controls:
other: A control gauze patch was applied to the contralateral flank
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.5 g

An area of about 6 sq.cm was shaved on both flanks of the animals approximately 24 hours before treatment. A gauze patch bearing 0.5 g of the test substance was applied to the flank. A control gauze patch was applied to the contralateral flank. Both gauze patches were moistened before application with distilled water. The patches were covered with an occlusive membrane and held in place for 4 hours by an adhesive tape (Isoplast, Isoplast AG, CH-5200 Brugg).
Duration of treatment / exposure:
4 hrs
Observation period:
The skin reactions were evaluated 1, 24, 48, and 72 hours after removing the gauze patches.
Number of animals:
3 males
Details on study design:
TEST SITE
- Area of exposure: about 6 sq cm on the flank
- Type of wrap if used: gauze patch covered with an occlusive membrane

SCORING SYSTEM: according to OECD

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 24, 48, 72 hrs (mean)
Score:
0.66
Max. score:
4
Reversibility:
fully reversible within: 72 hrs
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 24, 48, 72 hrs (mean)
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 24, 48, 72 hrs (mean)
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 24, 48, 72 hrs (mean)
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hrs
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 24, 48, 72 hrs (mean)
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: 24, 48, 72 hrs (mean)
Score:
0
Max. score:
4
Irritant / corrosive response data:
At the 1 hour timepoint, one animal showed mild edema and erythema reactions, reversible within 48 and 72 hours, respectively. The remaining two animals showed only minimal erythema reactions at the 1 hour time point. This effect was reversed to normal within 1 day.

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information
Conclusions:
The test article caused only minimal skin reactions and is therefore considered to be not irritating to the rabbit skin.
Executive summary:

In a GLP-compliant skin irritation study performed according to OECD guideline 404, three New Zealand White rabbits were treated occlusively with 0.5 g of the test article. The test article was applied with a moistened gauze patch to the clipped flank of the animals and held in place for 4 hours by an adhesive tape. Control patches were applied to the contralateral flank. The skin reactions were evaluated 1, 24, 48, and 72 hours after removing the gauze patches and animals were checked daily for signs of systemic toxicity. Under the experimental conditions employed the test article induced minimal to mild erythema and edema reactions well below the threshold of significance. All signs of irritations disappeared within 72 days the latest. The test article is therefore classified as non irritating.