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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1993
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report Date:
1993

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
Principles of method if other than guideline:
None
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
not specified
Details on test material:
None

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
- The albino rabbit is the recommended species for skin irritation/corrosion studies.
- Animal strain: New Zealand white rabbits (Chbb:NZW)
- Breeder: Dr. K. Thomae GMBH, Chemisch-pharmazeutische Fabrik, D-7950 Biberach/Riss
- Acclimatisation period: at least 5 days

Group size and husbandry
The test was performed on 3 male rabbits, checked for normal skin conditions, weighing between 2320 to 2530 g. The animals were housed individually in metal cages, identified by ear tattoo, kept at a constant room temperature of 20 ± 3 °C, at a relative humidity of 30-70 % and on a 12 hours light cycle day. The rabbits received ad libitum standard rabbit pellet - Nafag No. 814, Gossau, Switzerland - and fresh water. 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 drinking water quality fulfilled the critical parameters in the specifications of the "Schweizerisches Lebensmittelbuch" (Edition 1972). The results of the routine chemical examination of water at source (Grundwasserfassung Stein) as conducted periodically by the water authority (Baudepartement des Kantons Aargau, Abteilung Gewaesserschütz) are available to CIBA-GEIGY Limited, as well as the results of inhouse chemical analysis by the analytical laboratories of the Pharmaceutical Division, CIBA-GEIGY Limited.

Test system

Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
other: 0.5 % (w/v) Carboxymethylcellulose in 0.1% (w/v) aqueous polysorbate 80.
Controls:
other: The contrelateral flank of each rabbit served as control.
Amount / concentration applied:
0.5 g of FAT 36038/F
Duration of treatment / exposure:
4 hours
Observation period:
72 hours; the skin reactions were evaluated 1, 24, 48, 72 hours after removing the gauze patches.
Number of animals:
3 male rabbits
Details on study design:
An area of at least 36 sq cm was shaved on both flanks of the animals approximately 24 hours before treatment. A gauze patch (approx. 12-16 sq cm) bearing 0.5 g of the test article was applied to the right flank of each animal. The skin area exposed directly to the test article was approx. 6 sq cm.
A control gauze patch was applied to the contralateral flank. Before application both patches were moistened with 0.5 % (w/v) carboxymethylcellulose in 0.1 % (w/v) aqueous polysorbate 80.

The patches were loosely covered with an aluminum foil (approx. 36 sq cm) and held in place for 4 hours by an adhesive tape (Isoplast, Isoplast AG, CH-5200 Brugg).
The animals were checked daily for systemic symptoms and mortality (only findings reported).
The skin reactions were evaluated 1, 24, 48, and 72 hours after removing the gauze patches according to the OECD scoring system.

SCORING SYSTEM:
Erythema and eschar formation
- No e rythema 0
- Very slight erythema (barely perceptible) 1
- Well defined erythema 2
- Moderate to severe erythema 3
- Severe erythema (beet redness) to slight eschar formation ( injuries in depth) 4
Total possible erythema score 4


Edema formation
- No edema 0
- Very slight edema (barely perceptible) 1
- Slight edema (edges of area well defined by definite raising) 2
- Moderate edema (raised approximately 1 mm) 3
- Severe edema (raised more than 1 mm and extending beyond area of exposure) 4
Total possible edema score 4

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Remarks:
3 rabbits males
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 h
Remarks on result:
other: slight erythema reactions in one animal only when applied to the clipped albino rabbit skin. The reactions were observed only one hour after removing the bandages.
Irritation parameter:
edema score
Basis:
mean
Remarks:
3 rabbits males
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
Under the experimental conditions employed FAT 36038/F induced slight erythema reactions in one animal only when applied to the clipped albino rabbit skin. The reactions were observed only one hour after removing the bandages.
Because no reactions were observed at 24 hours to 72 hours after removing the bandages, the test was ended after the 72 hours evaluation.
Other effects:
None

Any other information on results incl. tables

Individual Skin Reaction Scores:

Animal No. ERYTHEMA EDEMA
567/M   CF/TF 547/M   CF/TF 573/M   CF/TF 567/M   CF/TF 547/M   CF/TF 573/M   CF/TF
After 1 hour 0/1 0/0 0/0 0/0 0/0 0/0
After 24 hours 0/0 0/0 0/0 0/0 0/0 0/0
After 48 hours 0/0 0/0 0/0 0/0 0/0 0/0
After 72 hours 0/0 0/0 0/0 0/0 0/0 0/0
Mean 24-72 hours 0/0 0/0 0/0 0/0 0/0 0/0

CF = Control Flank

TF = test Flank

M = Male

Body Weights (g)

Animal no. 567/M 547/M 573/M
At start of test 2530 2320 2500
After 3 days (end) 2620 2390 2590

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
FAT 36038/F can be classified as non-irritant to skin.
Executive summary:

An acute skin irritiation / corrosion study in albino rabbits was performed to determine the irritant or corrosive potency of FAT 36038/F on the albino rabbit skin. This test was based on the OECD Guideline No. 404, adopted by the OECD council, and 79/831/EEC (Commission May 12, 1981, adapted July 17, 1992 on Annex V, part B of Council Directive Directive 92/69/EEC of July 31, 1992).

Three male rabbits were used for the experiment. An area of at least 36 cm² was shaved on both flanks of the animals approximately 24 hours before treatment. A gauze patch bearing 0.5 g of the test article was applied to the right flank of each animal. A control gauze patch was applied to the contralateral flank. Before application both patches were moistened with 0.5 % (w/v) carboxymethylcellulose in 0.1 % (w/v) aqueous polysorbate 80.

The skin reactions were evaluated 1, 24, 48, and 72 hours after removing the gauze patches according to the OECD scoring system.

Under the experimental conditions employed FAT 36038/F induced slight erythema reactions in one animal only when applied to the clipped albino rabbit skin. The reactions were observed only one hour after removing the bandages.

Because the mean values of the recordings 24 to 72 hours after application are scored zero, FAT 36038/F can be classified as non-irritant.