Registration Dossier

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2009-11-18 till 2009-12-09
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline-conform study under GLP without deviations

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report Date:
2010

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): FAT 40849/A TE
- Substance type: reactive dyestuff for cellulose fibers
- Physical state: blue powder
- Analytical purity: 76.9% of all colored components
- Lot/batch No.: TZ 5463 / BOP 03-09
- Expiration date of the lot/batch: 2014-06-30
- Storage condition of test material: At room temperature at about 20 °C

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS Young Adult New Zealand White Rabbit, SPF
- Source: Charles River Deutschland GmbH Stolzenseeweg 32-36 88353 Kisslegg / Germany
- Age at study initiation: 18 weeks (male), 12-13 weeks (females)
- Weight at study initiation: 3046 g (male), 2783 - 2896 g (females)
- Housing: Individually in stainless steel cages equipped with feed hoppers and drinking water bowls. Haysticks and wood blocks were provided for gnawing.
- Diet: Pelleted standard Kliba Nafag 3418 rodent maintenance diet available ad libitum.
- Water: Community tap water from Füllinsdorf ad libitum.
- Acclimation period:.18-Nov-2009 to 22-Nov-2009 (one female), 18-Nov-2009 to 24-Nov-2009 (one male and one female)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23 °C
- Humidity (%): relative humidity between 30-70% (values above 70% during cleaning process possible),
- Air changes (per hr): Air-conditioned with 10-15 air changes per hour
- Photoperiod: automatically controlled light cycle of 12 hours light and 12 hours dark, music during the daytime light period.

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied : 0.5 g/animal, the dose specified in the test guidelines for a solid test item. the test item was moistened with approximately
0.5 mL of purified water before application
Duration of treatment / exposure:
4h
Observation period:
14d
Number of animals:
1 male and 2 females
Details on study design:
TEST SITE
- Area of exposure: approximately 100 cm2 (10 cm x 10 cm). Four days before treatment, the left flank was clipped with an electric clipper The skin of the animals was examined one day before treatment, and regrown fur of all animals was clipped again.
- % coverage:surgical gauze patch (ca. 2.5 cm x 2.5 cm) held in contact with the skin by means of an adhesive hypoallergenic aerated semiocclusive dressing and a restrainer bandage wrapped around the abdomen.


REMOVAL OF TEST SUBSTANCE
- Washing: 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.
- Time after start of exposure: 4h

SCORING SYSTEM:
Commission Regulation (EC) No 440/ 2008, 30 May 2008
Grading of Skin Reactions

Erythema and Eschar Formation
No erythema 0
Very slight erythema (barely perceptible) 1
Well-defined erythema 2
Moderate to severe erythema 3
Severe erythema (beef 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:
other: 1h
Score:
ca. 0
Max. score:
0
Reversibility:
other: not applicable
Remarks on result:
other: not assessable due to the marked blue staining produced by the test item.
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24h
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 48h
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 72h
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 7d
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 10d
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 14d
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 1h
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24h
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 48h
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 72h
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 7d
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 10d
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 14d
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritant / corrosive response data:
no irrtation effects observed, all scores (erythema and edema) = 0
Other effects:
Skin reaction
1h, erythema (all animals): not assessable due to the marked blue staining produced by the test item
24h erythema (all animals): no abnormal findings noted, slight blue staining produced by the test item
10d erythema (all animals): no abnormal findings noted, slight blue staining produced by the test item
14d erythema (male and one female): no abnormal findings noted, no staining present
14d erythema (animal 89, female): no abnormal findings noted, slight blue staining produced by the test item

Any other information on results incl. tables

Skin Irritation Scores - Assessment According to EC Guidelines

Evaluated

Intervals

Erythema

Oedema

24 hours

Not Classified

Not Classified

48 hours

Not Classified

Not Classified

72 hours

Not Classified

Not Classified

Viability / Mortality

No intercurrent deaths occurred during the course of the study.

 

Clinical Signs

No clinical signs were recorded in any of the animals throughout the complete observation period.

 

Body Weights

The body weights of all rabbits were considered to be within the normal range of variability for this strain and age.

 

Skin Reactions

Irritation

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. The individual mean score for erythema/eschar and oedema for each of the three animals was 0.

The application of FAT 40849/A TE to the skin resulted in no signs of irritation as far as the skin reactions were assessable (a possible erythema was not assessable in all three animals at the 1- hour reading after treatment due to marked blue staining produced by the test item.)

 

Coloration

Marked blue staining produced by the test item on the treated skin was observed in all three animals at the 1-hour reading after treatment and persisted as slight 10 (in the male and one female No. 88) to 14 days (female No. 89) after removal of the dressing. The study was closed thereafter.

 

Corrosion

Neither alterations nor corrosive effects were observed on the treated skin.

 

Pathology

Macroscopic Findings

No necropsy was performed at the end of the study.

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
According to the referred classification (Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008), FAT 40849/A TE does not have to be classified in respect to the skin irritation study in rabbits.
Executive summary:

The primary skin irritation potential of FAT 40849/A TE was investigated according to OECD test guideline No. 404 and Commission Regulation (EC) No. 440/2008, B.4. 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, as well as 7, 10 and 14 days 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. The individual mean score for erythema/eschar and oedema for each of the three animals was 0.

 

The application of FAT 40849/A TE to the skin resulted in no signs of irritation as far as the skin reactions were assessable (a possible erythema was not assessable in all three animals at the 1- hour reading after treatment due to marked blue staining produced by the test item.)

 

No corrosive effects were noted on the treated skin of any animal at any of the measuring intervals and no clinical signs were observed.

 

The test item caused slight to marked blue staining of the treated skin in all animals up to 10 days after removal of the dressing and persisted in one animal up to the last day of observation (test day 15).

 

According to the referred classification (Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008), FAT 40849/A TE does not have to be classified in respect to the skin irritation study in rabbits.