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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:
1999
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1999
Report Date:
1999

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: solid
Details on test material:
- Name of test substance (as cited in study report): FAT 93450/A
- Physical state: Orange solid
- Analytical purity: ca. 96 %
- Ident-Nr.: 188719.4
- Expiration date: November 2003
- Stability of the test substance bidistilled water: 24 h at room temperature
- Storage condition of test substance: at room temperature (ca. 20 °C) away from direct sunlight.
- Safety precautions: Gloves, goggles and face mask were sufficient to assure personnel health and safety
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 188719.4
- Expiration date of the lot/batch: November 2003

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: at room temperature (ca. 20 °C) away from direct sunlight.
- Stability under test conditions: 24 hours at room temperature in bidistilled water

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Elevage Scientifique des Dombes F-01400 Chatillon sur Chalaronne
- Age at study initiation: 15 weeks
- Weight at study initiation: One male: 2715 g, Two females: 2631 and 2750 g
- Housing: Individually in stainless steel cages with an automatic cleaning system equipped with feed hoppers, drinking water bowls, with wood and haysticks for gnawing.
- Diet: Pelleted standard Provimi Kliba 3410 rabbit maintenance diet, ad libitum (batch no. 63/98).
- Water: Community tap water from Itingen, ad libitum, in water bowls
- Acclimation period: Five days

ENVIRONMENTAL CONDITIONS
- Temperature: 20 ± 3 °C
- Humidity: 40-70 % (values above 70 % during cleaning process possible)
- Air changes: Air-conditioned with 10-15 air changes/h
- Photoperiod: 12 h light/12 h dark cycle

IN-LIFE DATES: From January 18, 1999 to January 21, 1999

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Remarks:
with an electric clipper
Vehicle:
unchanged (no vehicle)
Remarks:
test substance was moistened with bidistilled water before application
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.5 g (per animal)
Duration of treatment / exposure:
4 h
Observation period:
Up to 72 h (The skin reaction was assessed at approximately 1, 24, 48 and 72 h after the removal of the dressing, gauze patch and test substance)
Number of animals:
One male and two females
Details on study design:
Test substance preparation
0.5 g (per animal) of the test substance was weighed and then moistened with bidistilled water before application. Prior to the application the pH of the test substance was determined with pH-Test-Strip (E. Merck, D-64271 Darmstadt / Germany) and was found to be not assessable.

TREATMENT
Approximately three d before treatment, the dorsal fur 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 approximately 24 h before treatment, and, if necessary, regrown fur was again clipped. 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. On the day of treatment, the test substance was applied to approx. 6 cm² of the intact skin of the clipped area. It was covered with a 2.5 cm x 2.5 cm patch of surgical gauze and the gauze was covered with a semi-occlusive dressing. The dressing was wrapped around the abdomen and anchored with tape.

REMOVAL OF TEST SUBSTANCE
The duration of treatment was 4 h. Then the dressing was removed and the skin was flushed with lukewarm tap water to clean the application site so that any reactions (erythema) were clearly visible at that time.

SCORING SYSTEM: The skin reaction was assessed according to the numerical scoring system listed in the EEC Commission Directive 92/69/EEC, July 31, 1992

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
IRRITATION: Application of the test substance to healthy intact rabbit skin resulted in a primary irritation score of 0.00. Local signs (mean values from 24 to 72 h) consisted of grade 0.00 erythema and grade 0.00 edema. No signs of irritation were observed.
CORROSION: No irreversible alterations of the treated skin were observed nor were corrosive effects evident on the skin.
Other effects:
VIABILITY/MORTALITY AND CLINICAL SIGNS: No clinical signs of systemic toxicity were observed in the animals during the test and observation period, and no mortality occurred.
COLORATION: Orange staining by the test substance of the treated skin was observed.
BODY WEIGHTS: The body weight of all animals were considered to be within the normal range of variability.

Any other information on results incl. tables

SKIN IRIRITATION SCORES - INDVIDUAL VALUES

Animal Number

Erythema

Edema

 

24 h

48 h

72 h

24 h

48 h

72 h

34 (M)

0

0

0

0

0

0

35 (F)

0

0

0

0

0

0

36 (F)

0

0

0

0

0

0

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
FAT 93450/A was considered to be non-irritating to Rabbit skin.
Executive summary:

An in vivo study was conducted to evaluate the skin irritation potential of the test substance, FAT 93450/A (of ca. 96 % purity) in New Zealand White rabbits according to EU Method B.4 and OECD Guideline 404 in compliance with GLP. 500 mg of test substance was applied to a clipped intact skin area of 6 cm2 in each animal under a 2.5 x 2.5 cm2 patch of surgical gauze. The patch was allowed to remain in contact with the skin for 4 h. Then, the dressing was removed and the skin was flushed with lukewarm tap water to clean the application site. Animals were scored for irritation reactions after 1, 24, 48 and 72 h. Animals were also monitored daily for viability, mortality and clinical signs. Body weights were recorded pre-test and at study termination. No dermal reactions (erythema or edema) were observed at 24, 48 and 72 h. No signs of body weight variability, toxicity or mortality were observed in any animal during the study period. Orange staining by the test substance of the treated skin was observed during the study period. Under the study conditions, FAT 93450 was considered to be non-irritating to rabbit skin.