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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2009-11-25 to 2009-12-04
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted in compliance with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive and done to a valid guideline.

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
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

Test material

Constituent 1
Chemical structure
Reference substance name:
1-Propanesulfonamide, N-[3-[[5-bromo-1-(2,6-dichlorobenzoyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]carbonyl]-2,4-difluorophenyl]-
EC Number:
806-756-5
Cas Number:
1262985-24-9
Molecular formula:
C24 H16 Br Cl2 F2 N3 O4 S
IUPAC Name:
1-Propanesulfonamide, N-[3-[[5-bromo-1-(2,6-dichlorobenzoyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]carbonyl]-2,4-difluorophenyl]-
Test material form:
other: solid
Details on test material:
Purity: >99% (w/w)
Description: Solid

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
1 male aged 13 weeks and 2 females aged 15-16 weeks at start of treatment.
Standard Laboratory Conditions. Air-conditioned with 10-15 air changes per hour, with target ranges for room temperature 17-23°C and relative humidity 40-70% (values above 70% during cleaning process possible). Room environment was monitored continuously. The room was illuminated on a 12 hour light/dark cycle. Recorded music was played during the daytime light period.
Accommodation: Individually in stainless steel cages equipped with feed hoppers and drinking water bowls and wood for environmental enrichment. Standard pelleted diet and access to community tap water.
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 one day before treatment, and regrown fur of all animals was clipped again. 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 the test item moistened with approximately 0.5 mL PEG 300 was placed on a surgical gauze patch (ca. 2.5 cm x 2.5 cm) held in contact with the skin by means of an adhesive hypoallergenic aerated semi-occlusive dressing and a restrainer bandage wrapped around the abdomen.

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
other: PEG 300
Controls:
no
Amount / concentration applied:
0.5 g per animal
Duration of treatment / exposure:
4 hours. Then the dressing was removed and the skin was flushed with lukewarm tap water to clean the application site. As it was suspected that the test item might produce irritancy, a single animal (one female) was treated first. As neither a corrosive effect nor a severe irritant effect was observed after the 4- hour exposure, the test was completed using the two remaining animals for an exposure period of four hours.
Observation period:
After 4 hours, then daily for 3 days
Number of animals:
3
Details on study design:
The skin reaction was assessed according to the numerical scoring system listed in the Commission Regulation (EC) No. 440/2008, B.4, at approximately 1, 24, 48 and 72 hours after exposure (removal of the dressing, gauze patch and test item).
Data were summarized in tabular form, showing for each individual animal the irritation scores for erythema and oedema at all measurement intervals. Any lesions were described, including the degree and nature of irritation, corrosion or any other toxic effects observed, and their reversibility.
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. An animal is positive when the mean score is 2 or greater. The test is positive for irritation when at least 2 animals are positive for the same endpoint (erythema/eschar or oedema).

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
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.
Local signs (mean values from 24 to 72 hours) consisted of grade 0 erythema and grade 0 edema.

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: other: CLP - EC 1272/2008
Conclusions:
Based upon the referred classification criteria (Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008), the test item is not classified with respect to skin irritation
Executive summary:

Introduction: The test item was investigated according to OECD test guideline No. 404 and Commission Regulation (EC) No. 44012008 to assess its primary skin irritation potential.

Method: The test item was applied by topical semi-occlusive application of 0.5 g (moistened with PEG300) 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 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.

Results: The test item did not elicit any skin reactions at the application site of any animal at any of the observation times (all scores 0). The individual mean score for erythema/eschar and oedema for each of the three animals was therefore 0.

Conclusion: Based upon the referred classification criteria (Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008), the test item is not classified with respect to skin irritation.