Registration Dossier

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 1994-12-12 to 1994-12-15
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study performed according to OECD test guideline No. 404 and in compliance with GLP.
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1994
Report Date:
1994

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
Principles of method if other than guideline:
The study was extended to investigate 5 different concentrations of the test article and a vehicle control on each animal
GLP compliance:
yes (incl. certificate)
Remarks:
OECD GLP (inspection date: 6-7 April, 1994)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
- Name of test material (as cited in study report): HR 94/130966
- Physical state: Viscous clear liquid
- Storage condition of test material: at room temperature in the dark

Test animals

Species:
rabbit
Strain:
other: SPF albino
Details on test animals and environmental conditions:
TEST ANIMALS:
- Source: stock Mol:Russian from Mollegaard Breeding and Research Centre A/S, Ebjy, DK-4623 Lille Skensved
- Age at study initiation: no data
- Weight at study initiation: 2.0 - 2.1 kg bw
- Housing: individually, in 62 x 52 cm PPO cages with perforated floor
- Diet (e.g. ad libitum): pelleted complete diet ad libitum ("Altromin 2123" from Chr. Petersen, DK-4100 Ringsted)
- Water (e.g. ad libitum): domestic quality drinking water acidified with hydrochloric acid to pH 2.5 in order to prevent microbial growth
- Acclimation period: at least 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +/- 3 °C
- Humidity (%): 55 +/- 5 %
- Air changes (per hr): 10 per hr
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
other: ethanol:diethyl phtalate (1:1 w/w)
Controls:
other: a site of each animal served as vehicle control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit):
- Concentration (if solution): 100, 20, 10, 5, 1 and 0 % on each animal
Duration of treatment / exposure:
4 hours
Observation period:
1, 24, 48 and 72 h after termination of the exposure
Number of animals:
4 females
Details on study design:
TEST SITE
- Area of exposure: an area of 10 x 10 cm on the back was clipped and divided into 6 test sites: 2 anterior, 2 centrally and 2 posterior. Each site had an area of 2.5 x 2.5 cm
- Type of wrap if used: gauze patches were secured with a semi-occlusive dressing by means of a 1 cm wide adhesive tape and fixed with Scanpor tape, 4.5 cm width, loosely wound round the trunk

REMOVAL OF TEST SUBSTANCE
- Washing (if done): soap and lukewarm water
- Time after start of exposure: 4 h

SCORING SYSTEM: Draize scale according to the OECD 404

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Remarks:
4 animals
Time point:
other: mean 24-48-72h
Score:
0
Max. score:
4
Remarks on result:
other: for each test concentration
Irritation parameter:
edema score
Basis:
mean
Remarks:
4 animals
Time point:
other: mean 24-48-72h
Score:
0
Max. score:
4
Remarks on result:
other: for each test concentration
Irritant / corrosive response data:
Slight dose related (100 %, 20 % and 10 % test concentrations) skin erythema was observed 1 hour after termination of exposure. Thereafter no abnormalities were observed.
Other effects:
none

Any other information on results incl. tables

Table 7.3.1/1: Irritant/corrosive response data for each animal at each observation time up to removal of animals from the test – 100 %

 

Score at time point / Reversibility

Erythema

Max. score 4

Oedema

Max. score 4

1 h

1 / 1 / 1 / 1

0 / 0 / 0 / 0

24 h

0 / 0 / 0 / 0

0 / 0 / 0 / 0

48 h

0 / 0 / 0 / 0

0 / 0 / 0 / 0

72 h

0 / 0 / 0 / 0

0 / 0 / 0 / 0

Average 24h, 48h, 72h

0.0 / 0.0 / 0.0

0.0 / 0.0 / 0.0

Reversibility*)

-

-

Average time (day) for reversion**

-

-

 *) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

**): correspond to the last day for which skin irritation signs in the last animal were observed

Table 7.3.1/2: Irritant/corrosive response data for each animal at each observation time up to removal of animals from the test – 20 %

 

Score at time point / Reversibility

Erythema

Max. score 4

Oedema

Max. score 4

1 h

1 / 1 / 1 / 0

0 / 0 / 0 / 0

24 h

0 / 0 / 0 / 0

0 / 0 / 0 / 0

48 h

0 / 0 / 0 / 0

0 / 0 / 0 / 0

72 h

0 / 0 / 0 / 0

0 / 0 / 0 / 0

Average 24h, 48h, 72h

0.0 / 0.0 / 0.0

0.0 / 0.0 / 0.0

Reversibility*)

-

-

Average time (day) for reversion**

-

-

 *) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

**): correspond to the last day for which skin irritation signs in the last animal were observed

Table 7.3.1/3: Irritant/corrosive response data for each animal at each observation time up to removal of animals from the test – 10 %

 

Score at time point / Reversibility

Erythema

Max. score 4

Oedema

Max. score 4

1 h

1 / 1 / 1 / 0

0 / 0 / 0 / 0

24 h

0 / 0 / 0 / 0

0 / 0 / 0 / 0

48 h

0 / 0 / 0 / 0

0 / 0 / 0 / 0

72 h

0 / 0 / 0 / 0

0 / 0 / 0 / 0

Average 24h, 48h, 72h

0.0 / 0.0 / 0.0

0.0 / 0.0 / 0.0

Reversibility*)

-

-

Average time (day) for reversion**

-

-

 *) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

**): correspond to the last day for which skin irritation signs in the last animal were observed

Table 7.3.1/4: Irritant/corrosive response data for each animal at each observation time up to removal of animals from the test – 5 %

 

Score at time point / Reversibility

Erythema

Max. score 4

Oedema

Max. score 4

1 h

0 / 0 / 0 / 0

0 / 0 / 0 / 0

24 h

0 / 0 / 0 / 0

0 / 0 / 0 / 0

48 h

0 / 0 / 0 / 0

0 / 0 / 0 / 0

72 h

0 / 0 / 0 / 0

0 / 0 / 0 / 0

Average 24h, 48h, 72h

0.0 / 0.0 / 0.0

0.0 / 0.0 / 0.0

Reversibility*)

-

-

Average time (day) for reversion**

-

-

 *) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

**): correspond to the last day for which skin irritation signs in the last animal were observed

Table 7.3.1/1: Irritant/corrosive response data for each animal at each observation time up to removal of animals from the test – 1 %

 

Score at time point / Reversibility

Erythema

Max. score 4

Oedema

Max. score 4

1 h

0 / 0 / 0 / 0

0 / 0 / 0 / 0

24 h

0 / 0 / 0 / 0

0 / 0 / 0 / 0

48 h

0 / 0 / 0 / 0

0 / 0 / 0 / 0

72 h

0 / 0 / 0 / 0

0 / 0 / 0 / 0

Average 24h, 48h, 72h

0.0 / 0.0 / 0.0

0.0 / 0.0 / 0.0

Reversibility*)

-

-

Average time (day) for reversion**

-

-

 *) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

**): correspond to the last day for which skin irritation signs in the last animal were observed

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the condition of the study the test material does not require a classification as irritant to the skin according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) and the Directive 67/548/EC.
Executive summary:

A dermal irritation study was performed according to the OECD guideline No. 404 and in compliance with GLP. The study was extended to investigate 5 different concentrations of the test material (100, 20, 10; 5, 1 %) and a vehicle control on each animal. 4 SPF rabbits were exposed to different concentrations of the test article (as provided or diluted in ethanol:DEP) at 6 skin sites on the back.

Test sites were covered with a semi-occlusive dressing for 4 hours. Skin irritation was assessed and scored according to the Draize scale at 1, 24, 48 and 72 h after the removal of the patch.

The mean scores calculated over the 4 animals tested within 3 scoring times (24, 48 and 72 h) were 0.00 for erythema and 0.00 for oedema.

 

Slight dose related (100 %, 20 % and 10 % test concentrations) skin erythema was observed 1 hour after termination of exposure. Thereafter no abnormalities were observed.

 

Therefore the test material does not require a classification as irritant to the skin according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) and the Directive 67/548/EC.

This study is considered as acceptable and satisfies the requirement for skin irritation endpoint.