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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Between 2003-08-19 and 2003-10-28
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline and GLP study with no deviations.
Cross-reference
Reason / purpose for cross-reference:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2003
Report date:
2003

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
Principles of method if other than guideline:
NA
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Reference substance name:
-
EC Number:
451-530-8
EC Name:
-
Cas Number:
736150-63-3
Molecular formula:
Not applicable
IUPAC Name:
Not allocated
Details on test material:
Name of test material (as cited in study report): TS-ED 532
- Lot/batch No.: batch 10102
- Expiration date of the lot/batch: 2003-11-23

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: rabbit
- Age at study initiation: 10-11 weeks (male) and 12 weeks (female)
- Weight at study initiation: 2276 g (male), 2309 g and 2185 g (both female)
- Housing: individually
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: yes

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23 °C
- Humidity (%): 30-70%
- Air changes (per hr): 10-15 changes per h
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Type of coverage:
semiocclusive
Preparation of test site:
other:
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration (if solution): undiluted

Duration of treatment / exposure:
4 h
Observation period:
The scoring of skin reactions was performed at 1, 24, 48 and 72 h, as well as 7 days after removal of the dressing. Observations of viability/mortality and clinical signs were performed daily from acclimatization to termination. The bodyweight was measured at start of acclimatization, on the days of application and at termination.
Number of animals:
3 (1 male and 2 females)
Details on study design:
TEST SITE
- Area of exposure: ca. 4x4 cm on a clipped area of 10x10 cm.
- % coverage: in accordance with guideline.
- Type of wrap if used: semi-occlusive dressing

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: 4 h

SCORING SYSTEM:
The skin reaction was assessed according to the numerical scoring system listed in the EEC Commision Directive 92/69/EEC, July 31, 1992 at approximately 1, 24, 48, 72 h, as well as 7 days after the removal of the dressing, gauze patch and test item.

Grading of Skin Reactions:

ERYTHEMA AND ESCHAR FORMATION
No erythema 0
Very slight erythema: 1
Well-defined erythema: 2
Moderate to severe erythema: 3
Severe erythema (beet 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:
animal #1
Remarks:
mean score 1
Time point:
other: overall at 24, 48 and 72 h
Score:
1.33
Max. score:
2
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
mean score 2
Time point:
other: overall at 24, 48 and 72 h
Score:
1
Max. score:
2
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
mean score 3
Time point:
other: overall at 24, 48 and 72 h
Score:
1
Max. score:
1
Irritation parameter:
erythema score
Max. score:
2
Remarks on result:
other: max. duration: 3 days; max. value at end of observation period: 0 (related to all animals)
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
mean score 1
Time point:
other: overall at 24, 48 and 72 h
Score:
0.33
Max. score:
1
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
mean score 2
Time point:
other: overall at 24, 48 and 72 h
Score:
0.33
Max. score:
1
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
mean score 3
Time point:
other: overall at 24, 48 and 72 h
Score:
0
Max. score:
0
Irritation parameter:
edema score
Max. score:
1
Remarks on result:
other: max. duration: 1 d; max. value at end of observation period: 0 (related to all animals)
Irritant / corrosive response data:
Reversibility of any observed effect: Changes fully reversible within 7 days
Overall assessment of skin irritation scores for erythema: Not irritating
Overall assessment of skin irritation scores for oedema: Not irritating
Other effects:
No staining of the treated skin was observed. Neither alterations of the treated skin were observed nor were corrosive effects evident.

Any other information on results incl. tables

Table 1 Skin irritation scores – individual scores

Animal Number

Sex

Evaluation interval

Erythema

Oedema

82

83

84

M

F

F

 

1 hour

2

1

1

0

0

0

82

83

84

M

F

F

 

24 hours

2

2

1

1

1

0

82

83

84

M

F

F

 

48 hours

1

1

1

0

0

0

82

83

84

M

F

F

 

72 hours

1

0

1

0

0

0

82

83

84

M

F

F

 

7 days

0

0

0

0

0

0

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The primary skin irritation potential of TS-ED 532 was tested in 3 rabbits by topical semi-occlusive application.
Based on the results, it is concluded that TS-ED 532 is not irritating.
Executive summary:

The primary skin irritation potential of TS-ED 532 was tested in 3 rabbits by topical semi-occlusive application of 0.5 mL TS-ED 532 to clipped skin using a patch. The duration of treatment was 4 h. The scoring of skin reaction was performed at 1, 24, 48 and 72 h, as well as 7 days after removal of the dressing. The mean score was calculated across 3 scoring times (24, 48 and 72 h after patch removal) for each animal for erythema/eschar grades and for oedema grades, separately.

The mean erythema/eschar score of the 3 animals was 1.33, 1.00 and 1.00 respectively and the mean oedema score was 0.33, 0.33 and 0.00, respectively. 

The application of TS-ED 532 resulted in moderate signs of irritation which included erythema and oedema. These effects were reversible and were no longer evident 7 days after treatment. TS-ED 532 caused no staining of the treated skin and no corrosive effects were observed. No clinical signs of TS-ED 532 related effects were observed.

Overall, TS-ED 532 did not induce significant or irreversible damage to the skin. Hence, TS-ED 532 is considered to be “not irritating” to rabbit skin.