Registration Dossier

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:
2009-03-23 to 2009-03-26
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Well documented GLP study according to OECD guideline 404 en EU Method B.4.
Justification for type of information:
The study was performed in 2009 to investigate further the results obtained in the in vitro test. The report was finalized in 2015.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2015
Report Date:
2015

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:
solid: particulate/powder
Details on test material:
- Name of test material (as cited in study reports): JNJ-39453193-AAA (T003063)
- Physical state: solid (powder)
- Appearance: white to almost white powder
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 507652
- Expiration date of the lot/batch: 2009-04-03 (retest date)
- Purity test date: no data

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: at room temperature (20 +/- 5°C), light portected
- Stability under test conditions: no data

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: the test item was used as delivered by the sponsor and was moistened with approximately 0.5 mL of purified water before application.

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: young adult New Zealand White rabbits, SPF; from Harlan Laboratories B.V., Kreuzelweg 53, 5961 NM Horst, The Nertherlands
- Age when treated: 15 weeks (male), 15 weeks (females)
- Weight when treated: 2631 grams (male), 2831 - 2852 grams (females)
- Housing: Standard Laboratory Conditions; individually in stainless steel cages equipped with feed hoppers and drinking water bowls. Wood blocks (Harlan Laboratories Ltd., Füllinsdorf) and haysticks 4642 (batch no. 69/08, Provimi Kliba AG) were provided for gnawing.
- Diet (e.g. ad libitum): pelleted standard Provimi Kliba 3418 rabbit maintenance diet, ad libitum
- Water (e.g. ad libitum): Community tap water from Füllinsdorf, ad libitum
- Acclimation period: 5 days (from 2009-03-18 to 2009-03-22) under laboratory conditions after health examination. Only animals without any visual signs of illness were used for the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 - 23 °C
- Humidity (%): 30 - 70% (values above 70% during cleaning process possible)
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12, automatically controlled light cycle, music during the daytime light period

IN-LIFE DATES: From: 2009-09323 To: 2009-03-26

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Remarks:
purified
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g/animal, as delivered by the sponsor
- The pH of the test item was measured before the study initiation date in a 1 % (w/w) solution in purified water and was found to be 5.
Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
1 male and 2 females
Details on study design:
TEST SITE
- Area of exposure: left flank, 100 cm² (10 cm x 10 cm)
- % coverage: no data, ca. 2.5 cm x 2.5 cm
- Type of wrap if used: 0.5g of T003063 on a surgical gauze patch was held in contact with the skin by means of an adhesive hypoallergenic aerated semi-occlusive dressing and a restrainer bandage wrapped around the abdomen.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the skin was flushed with lukewarm tap water to clean the application site.
- Time after start of exposure: 4 hours after treatment

SCORING SYSTEM:
- 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).

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Remarks:
male 60
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Remarks:
male 60
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
other: scaling
Basis:
mean
Remarks:
male 60
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
mean
Remarks:
female 61
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Remarks:
female 61
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
other: scaling
Basis:
mean
Remarks:
female 61
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
mean
Remarks:
female 62
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Remarks:
female 62
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
other: scaling
Basis:
mean
Remarks:
female 62
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
Irritation:
- 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).

Corrosion:
- Neither alterations of the treated skin were observed nor were corrosive effects evident on the skin.
Other effects:
Mortality/Viability:
- No mortality occurred.

Clinical signs:
- No clinical signs were observed during the course of the study.

Body Weights:
- The body weights of all rabbits were considered to be within the normal range of variability.

Pathology:
- Macroscopic findings: no necropsy was performed at the end of the study.

Coloration:
- No staining produced by the test item of the treated skin was observed.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Based upon the referred classification criteria (Commission Directive 2001/59/EC of August 2001), T003063 is considered to be “not irritating” to rabbit skin. According to the CLP classification, the test item should not be classified.