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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:
25 January, 2000 to 3 February, 2000
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2000
Report date:
2000

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
Swiss GLP

Test material

Constituent 1
Chemical structure
Reference substance name:
2-[(1-amino-9,10-dihydro-4-hydroxy-9,10-dioxo-2-anthryl)oxy]ethyl ethyl carbonate
EC Number:
254-959-7
EC Name:
2-[(1-amino-9,10-dihydro-4-hydroxy-9,10-dioxo-2-anthryl)oxy]ethyl ethyl carbonate
Cas Number:
40530-60-7
Molecular formula:
C19H17NO7
IUPAC Name:
2-[(1-amino-9,10-dihydro-4-hydroxy-9,10-dioxo-2-anthryl)oxy]ethyl ethyl carbonate
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
Identification: FAT 93503/A
Item N°: 0033275
Vers N°: 99 Labor Mischung 1
Purity: Approximately 96%
Color/Physical state: Red powder
pH (1g/L): 7-8
Expiry date: January 2005
Stability of test article in bi-distilled water: Stable in bi-distilled water at leasr 24-hours.
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 99 Labor Mischung 1
- Expiration date of the lot/batch: January 2005

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: In the original container, at room temperature (range of 20 ± 3 °C), away from direct sunlight.
- Stability of the test substance in the solvent/vehicle: Stable in bi-distilled water for at least 24 h.

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: elevage scientifique des Dombes, F-01400 Chatillon sur Chalonne/France
- Age: 15 weeks (males), 16 weeks (females)
- Weight: 2.7 - 3.0 kg
- Housing:Individually in stainless steel cages equipped with feed hoppers, drinking water bowls, with wood (RCC Ltd, Füllinsdorf) and hay sticks
for gnawing.
- Diet: ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature:22 ± 3 °C
- Humidity: 35-54 %
- Air changes: air conditioned with 10-15 air changes per hour
- Photoperiod: light cycle of 12 hours light and 12 hours dark. Music was played during the light cycle.

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
other: Test item was moistened with bi-distilled water before application.
Controls:
yes, concurrent no treatment
Amount / concentration applied:
0.5 g/animal
The test article was moistened with bi-distilled water.
Duration of treatment / exposure:
4 h
Observation period:
72 h
Number of animals:
1 male and 2 females
Details on study design:
Approximately 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 approximately 24 h before treatment, and 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, 0.5 g of FAT 93503/A were put on a surgical gauze patch (ca. 2.5 cm x 2.5 cm). This gauze patch was applied to approximately 6 cm² of the intact skin of the clipped area. The patch was covered with a semi-occlusive dressing. The dressing was wrapped around the abdomen and anchored with tape. The duration of treatment was 4 hours. 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:
Grading of Skin Reactions
ERYTHEMA AND ESCHAR FORMATION:
- No erythema: 0
- Very slight erythema: 1
- Well-defined erythema: 2
- Moderate to severe erythema: 3
- Severe erythema (beet redness) or eschar formation (injuries in depth preventing erythema reading: 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 (edges raised approximately 1 mm): 3
- Severe oedema (raised more than 1 mm and extending beyond the area of exposure): 4

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 article 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 oedema.

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:
Light red staining by the test article of the treated skin was observed throughout the reading intervals.

BODY WEIGHTS:
The body weight of all rabbits were considered to be within the normal range of variability.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
FAT 93503/A is considered to be not irritating to the rabbit skin.
Executive summary:

The purpose of this primary skin irritation study was to assess the possible irritation potential when a single dose of the test article is placed on the skin of rabbits for approximately 4 h. This study was performed according to the OECD Guideline 404 (Acute Dermal Irritation / Corrosion). 0.5 g FAT 93503/A was applied topically to 6 cm² intact left flank of three young adult New Zealand White rabbits (1 male and 2 females). The duration of exposure was four hours. The scoring of skin reactions was performed 1, 24, 48 and 72 h, after removal of the dressing. The scores of each animal at the following reading times (24, 48, 72 h) were used in calculating the respective mean values for each type of lesion. No clinical signs of systemic toxicity were observed in the animals during the test and observation period, and no mortality occurred. The primary irritation score was calculated by totalling the individual cumulative scores at 24, 48 and 72 h and then dividing by the number of data points. The primary irritation score was 0.00 (max. 8.0). Local signs (mean values from 24 to 72 h) consisted of grade 0.00 erythema and grade 0.00 oedema. Light red staining by the test article of the treated skin was observed throughout the measuring intervals. No corrosive effects were noted on the treated skin of any animal at any measuring interval. In conclusion, the test article is considered to be "not irritating" to rabbit skin.