Registration Dossier

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1985
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well performed GLP and OECD guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1985
Report Date:
1985

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Version / remarks:
84/449/EEC
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
- Animal specifics: Hoechst AG, conventional breed
- Source: Hoechst AG breeding colony
- Weight at study initiation: 1,9 kg to 2,1 kg
- Housing: Individually in cages equipped with feed hoppers and drinking water bowls
- Diet (e.g. ad libitum): standard laboratory diet (Albtromin 2123) ad libitum
- Water (e.g. ad libitum): deionized chlorinated water, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20° ± 3°C (air-condition)
- Humidity (%): 30-70%
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL

Duration of treatment / exposure:
4 hours
at the end of the exposure period removal of the test substance with lukewarm tap water
Observation period:
14 d post removal of the patch
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: approximately 2.5 cm x 2.5 cm
- Type of wrap if used: surgical gauze patch (Beiersdorf AG)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): flushed with lukewarm tap water
- Time after start of exposure: 4 hours

SCORING SYSTEM:
as in EU Method B.4, assessed approximately 30 - 60 min, 24, 48, and 72 h after the removal of the test item

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal: # 1, 2, 3 each
Time point:
other: mean of 24, 48 and 72 hours
Score:
1.8
Max. score:
4
Reversibility:
other: initial signs of irritation (erythema) were fully reversible within 14 d
Irritation parameter:
edema score
Basis:
animal: # 1, 2, 3 each
Time point:
other: mean of 24, 48 and 72 hours
Score:
0.2
Max. score:
4
Reversibility:
other: initial signs of irritation (edema) were fully reversible within 48 h
Irritant / corrosive response data:
Signs of irritation were not fully reversible after 72 h. Therefore additional assessments were performed after 7 and 14 days.
Until 7 days after removal of the test substance slight erythema and very slight edema were observed. After 2 days the skin of the animals was dry, rough and partly showed fine scales.

Any other information on results incl. tables

Table 1: individual scores

Animal no

Evaluation interval after removal of dressing

Erythema score

Edema score

Skin surface

dry, rough

Skin surface

fine scales

1

 

30 – 60 min

2

1

 

 

2

1

0

 

 

3

2

0

 

 

1

 

24 h

2

0

 

 

2

2

1

 

 

3

2

1

 

 

1

 

48 h

1

0

X

 

2

2

0

X

 

3

2

0

X

 

1

 

72 h

1

0

X

 

2

2

0

X

 

3

2

0

X

 

1

 

7 d

1

0

X

X

2

1

0

X

X

3

1

0

X

 

1

 

14 d

0

0

X

 

2

0

0

X

 

3

0

0

X

X

Applicant's summary and conclusion

Interpretation of results:
Category 2 (irritant)
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
Regulation (EC) 1272/2008: skin irritation category 2

Starting with day 2 dry and rough skin, scaling and alopecia (limited region) was observed, still persisting at the end of the observation period of 14 days. Taking into account these irritant response the test item has to be regarded as skin irritating.

Directive 67/548/EEC: irritating to skin, R 38

In a OECD guideline and GLP compliant primary skin irritation test in rabbits, the test item caused grade 2 erythema in at least 2 animals after 24, 48 and 72 h respectively. These effects were fully reversible after 14 days. Thus, the test item has to be classified as "Irritating to skin", R 38.
Executive summary:

The primary skin irritation potential of the test item was investigated according to OECD test guideline no. 404. The test item was applied by topical semi-occlusive application of 0.5 mL to the intact 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 30 - 60 min, 24, 48 and 72 hours and additionally 7 and 14 days 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 edema grades, separately. The application of the test item to the skin resulted in early-onset signs of irritation persisting for more than 7 days . The test item caused grade 2 erythema in at least 2 animals at any of the 3 scoring times. These effects were reversible and were no longer evident 14 days after treatment for all animals.

Starting with day 2 dry, rough and skin surface, scaling and alopecia (eye region) was observed. No corrosive effects were noted on the treated skin of any animal at any of the measuring intervals. Thus, the test item did not induce significant or irreversible damage to the skin.

Based upon these findings, the test item is considered to be "irritating" to rabbit skin according to Directive 67/548/EEC and the test item has to be classified as "skin irritating category 2" according to Regulation (EC) 1272/2008.