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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:
2006-05-24 to 2006-06-02
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Remarks:
Comparable GLP guideline study according to OECD Guideline 404 and EU Method B.4.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2006
Report Date:
2006

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
The testing facility reported the following deviation from the protocol: the test substance was put on a surgical gauze patch of approximately 4 cm x 4 cm instead of 6 cm x 6 cm.
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
The testing facility reported the following deviation from the protocol: the test substance was put on a surgical gauze patch of approximately 4 cm x 4 cm instead of 6 cm x 6 cm.
GLP compliance:
yes (incl. certificate)
Remarks:
Swiss Federal Office of Public Health, Swiss Agency for Therapeutic Products and the Swiss Agency for the Environment, Forests and Landscape

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 report): JNJ-559728-AAA (T001250)
- Physical state: solid (powder)
- Appearance: White powder
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 00443418 RT001250G4a661
- Expiration date of the lot/batch: no data
- Purity test date: no data

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

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Final preparation of a solid: 0.5 g (per animal) of test item was weighed as delivered by the sponsor and then 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: 1 male and 2 female New Zeeland White rabbits; Harlan Netherlands BV, Kreuzelweg 53, 5961 NM Horst, The Netherlands
- Age at study initiation: 11-12 weeks (male), 7-10 weeks (females)
- Weight at study initiation: Male 2702 grams, females 1689 and 1801 grams
- Housing: Standard Laboratory Conditions; Individually in stainless steel cages equipped with feed hoppers and drinking water bowls. Wood blocks (RCC Ltd, Füllinsdorf) and haysticks 4642 (batch no. 77/05, Provimi Kliba AG) were provided for gnawing.
- Diet (e.g. ad libitum): Pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad libitum (batch no. 8/06)
- Water (e.g. ad libitum): Community tap water from Fullinsdorf, ad libitum
- Acclimation period: 5 days (one female) and 6 days (one female and one male), under laboratory conditions after health examination. Only animals without any visual signs of illness were used.


ENVIRONMENTAL CONDITIONS
- Temperature (deg C): 17-23
- Humidity (%): 30-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12, with music played during the daytime light period


IN-LIFE DATES: From: 2006-05-29 (one female), 2006-05-30 (one male and one female) To: 2006-06-02

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g, the test item was moistened with approximately 0.5 mL of purified water before application
Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
3 (one male, two females)
Details on study design:
TEST SITE
- Area of exposure: left flank
- % coverage: no data
- Type of wrap if used: the dressing was wrapped around the abdomen and anchored with tape
- On the day of treatment 0.5 g of test item was placed on a surgical gauze patch (ca. 4 cm x 4 cm). This gauze patch was applied to the intact skin of the clipped area (10 cm x 10 cm). The patch was covered with a semi-occlusive dressing.
- As it was suspected that the test item might produce irritancy, a single animal (one female) was treated first.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): 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: 4 hours

OBSERVATION TIME POINTS
- Viability/mortality and clinical signs: daily from acclimatization of the animals to the termination of test.
- Body weights: at start of acclimatization, on the day of application and at termination of observation.
- Skin reactions: at approximately 1, 24, 48 and 75 hours after exposure (removal of the dressing, gauze patch and test item).
- To allow further examination of the test site, animal no. 21 was re-clipped on completion of the 48-hour examination.

SCORING SYSTEM:
- The skin reaction was assessed according to the numerical scoring system listed in the Commission Directive 2004/73/EC, April 29, 2004.
- If evident, corrosive or staining properties of the test item were described and recorded.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Remarks:
animal 19
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
mean
Remarks:
animal 20
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
mean
Remarks:
animal 21
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
mean
Remarks:
animal 19
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
mean
Remarks:
animal 20
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
mean
Remarks:
animal 21
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
The test substance 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 erytherna/eschar and oedema for each of the three animals was therefore 0.
Neither alterations of the treated skin were observed, nor were corrosive effects evident on the skin.
Other effects:
No clinical signs of systemic toxicity were observed in the animals during the study and no mortality occurred.
No staining produced by the test substance of the treated skin was observed.
The body weights 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:
Based upon the referred classification criteria (Commission Directive 2001/59/EC of August 2001), T1250 is considered to be "not irritating" to the rabbit skin.