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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:
weight of evidence
Study period:
2006-05-10 to 2006-06-01
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
GLP study performed according to OECD Guideline 404 (Acute Dermal Irritation / Corrosion) and EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion) without deviations that would impact the results.

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 deviations from the protocol: 1) the test substance was put on a surgical gauze patch of approx. 4 cm x 4 cm (instead of 6 cm2); 2) the pH of the test substance was measured before the study initiation date.
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
: The testing facility reported the following deviations from the protocol: 1) the test substance was put on a surgical gauze patch of approx. 4 cm x 4 cm (instead of 6 cm2); 2) the pH of the test substance was measured before the study initiation date.
GLP compliance:
yes (incl. certificate)
Remarks:
: Certificate from the Swiss GLP Monitoring Authorities

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-117676-AAA (T000263)
- Physical state: solid (powder)
- Appearance: White, slight beige amorphous, crystalline, micropowder
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 8693
- Expiration date of the lot/batch: 2007-12-31
- 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
- Solubility and stability of the test substance in the solvent/vehicle: not applicable

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: the test item 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: Harlan France (ZI Le Malcourlet, 03800 Gannat, France)
- Age at study initiation: 12 weeks (male), 13-15 weeks (females)
- Weight at study initiation: male 2297 grams; female 2402 g; female 2280 g
- Housing: Individually in stainless steel cages equipped with feed hoppers and drinking water bowls. Wood blocks and haysticks 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: 4 days (one female); 7 days (one male and one female), 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): approximately 10-15
- Photoperiod (hrs dark / hrs light): 12/12, music was played during the daytime light period


IN-LIFE DATES: From: 2006-05-10 To: 2006-06-01

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 grams per animal was delivered and then moistened with approximately 0.5 mL purified water before application
- Concentration (if solution): not applicable
Duration of treatment / exposure:
4 hours
Observation period:
1, 24, 48 and 72 hrs; 7, 10 and 14 days after exposure (removal of the dressing, gauze patch and test item)
Number of animals:
3 (1 male, 2 females)
Details on study design:
TEST SITE
- Area of exposure: 4 cm x 4 cm
- % coverage: no data
- Type of wrap if used: surgical gauze, covered with semi-occlusive dressing and anchored with tape


REMOVAL OF TEST SUBSTANCE
- Washing (if done): the dressing was removed and the skin was flushed with lukewarm tapwater
- Time after start of exposure: 4 hrs


SCORING SYSTEM:
- according to the numerical scoring system listed in the Commission Directive 2004/73/EC, April 29, 2004

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
other: animal #91 mean score
Time point:
other: 24, 48 and 72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
erythema score
Basis:
other: animal #92 mean score
Time point:
other: 24, 48 and 72 h
Score:
2.67
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
erythema score
Basis:
other: animal #93 mean score
Time point:
other: 24, 48 and 72 h
Score:
1.67
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
other: animal #91 mean score
Time point:
other: 24, 48 and 72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
other: animal #92 mean score
Time point:
other: 24, 48 and 72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
other: animal #93 mean score
Time point:
other: 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 hours
Irritant / corrosive response data:
The test substance was found to be irritating based on erythema. The test substance was found to be not irritating based on edema.
Other effects:
No clinical signs of systemic toxicity were observed during the study and no mortality occurred. No staining produced by the test item was observed. Neither alterations of the treated skin were observed nor were corrosive effects evident. Body weights of all rabbits were considered to be within the normal range of variability.

Scaling was observed in all three test animals on days 7 and 10; scaling was observed in test animal numbers 91 and 93 at day 14.

Any other information on results incl. tables

Table 1: Skin Irritation Scores - Individual Values

Animal Number

Sex

Evaluation Interval*

Erythema

Oedema

Scaling

91

M

 1 hour

2

2

0

92

F

1 hour

4

3

0

93

F

1 hour

2

2

0

91

M

24 hours

2

1

0

92

F

24 hours

3

2

0

93

F

24 hours

2

0

0

91

M

48 hours

2

1

0

92

F

48 hours

3

1

0

93

F

48 hours

2

0

0

91

M

72 hours

2

1

0

92

F

72 hours

2

1

0

93

F

72 hours

1

0

0

91

M

7 days

1

0

X

92

F

7 days

1

0

X

93

F

7 days

1

0

X

91

M

10 days

1

0

X

92

F

10 days

1

0

X

93

F

10 days

1

0

X

91

M

14 days

0

0

X

92

F

14 days

0

0

0

93

F

14 days

0

0

X

*Examinations were performed at the specified times after removal of the dressing.

x=scaling present

 

 

Applicant's summary and conclusion

Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
The test substance was found to be irritating based on erythema, but not irritating based on edema. Based upon the referred classification criteria (Commission Directive 2001/59/EC of August 2001), T263 is considered to be "irritating" to rabbit skin.
The test substance is found to be category 2 'irritating' based on the persistance of scaling in 2 out of 3 animals up to the end of the 14 days observation period.