Registration Dossier

Administrative data

Description of key information

Skin irritation (OECD 404): not irritating
Eye irritation (OECD 405): not irritating

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
26 Feb - 02 Mar 2001
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP-Guideline study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
adopted 1992
Deviations:
yes
Remarks:
several test substance concentrations were applied on one animal
Qualifier:
equivalent or similar to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Version / remarks:
Jan 1997
Deviations:
yes
Remarks:
several test substance concentrations were applied on one animal
GLP compliance:
yes
Species:
rabbit
Strain:
other: SPF albino rabbits
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2.8 - 3.0 kg
- Housing: individually in PPO cages
- Diet: Altromin 2123 (Altromin, Lage, Germany), ad libitum
- Water: domestic quality drinking water acidified with hydrochloric acid to ph 2.5, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 55 ± 15
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
other: for test substance concentrations of 1, 10, 25 and 50% ethanol/diethylphthalat (1:1) was used as vehicle
Controls:
yes, concurrent vehicle
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.5 mL
- Concentrations: 1, 10, 25, 50 and 100%
Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Reading time points: 1, 24, 48 and 72 hours
Number of animals:
4 females
Details on study design:
TEST SITE
- Area of exposure: 10 x 10 cm on the back (divided into six fields)
- Type of wrap: The test substance or vehicle was applied to 16-layer gauze patches (2.5 x 2.5 cm) and the patches placed on the appropriate test sites on the back of each rabbit. The gauze patches were secured with adhesive Gothaplast tape (2.5 cm wide) and fixed with Gothaplast tape (5 cm wide) loosely wound round the trunk.

REMOVAL OF TEST SUBSTANCE
- Washing: After application the skin sites were cleaned with mild soap and lukewarm water.
- Time after start of exposure: 4 hours

SCORING SYSTEM: Draize scoring system
Irritation parameter:
erythema score
Basis:
animal: #2, #3 and #4
Time point:
other: mean after 24, 48 and 72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: test concentration: 100%
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: mean after 24, 48 and 72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: test concentration: 100%
Irritation parameter:
edema score
Basis:
mean
Remarks:
of 4 animals
Time point:
other: mean after 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: reversiblitiy: not applicable
Remarks on result:
other: test concentration: 100%
Irritant / corrosive response data:
One hour after termination of exposure none of the 4 animals showed skin reactions at any concentration. 24 hours after termination of exposure a very slight erythema (score 1) was observed in all animals at 100%. 48 hours after termination of exposure a very slight erythema (score 1) was observed in one animal at 100%. The other animals were free of any signs of skin irritation after 48 hours at 100%. No skin reactions were observed at 1, 10 and 50% test substance concentration at any reading time point. Only very slight erythema (score 1) was observed in one animal 24 hours after removal of the patch at 25% test substance concentration. The animal was free of signs after 48 hours.

Table 1: Individual skin examination scores with the undiluted test substance

Skin effect

Erythema

Edema

Scoring

24h

48h

72h

Meana

24h

48h

72h

Meana

Animal 1

1

1

0

0.67

0

0

0

0

Animal 2

1

0

0

0.33

0

0

0

0

Animal 3

1

0

0

0.33

0

0

0

0

Animal 4

1

0

0

0.33

0

0

0

0

aMean of 24, 48 and 72 h scores

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this skin irritation study in rabbits the undiluted test substance (100%) was not irritating to the skin. Also the test substance concentrations of 1, 10, 25 and 50% in ethanol/diethylphthalat (1:1) did not show an irritation potential.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
12 - 16 Feb 2001
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP-Guideline study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
adopted Feb 1987
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
Jan 1997
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
other: SPF albino rabbits
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 1.9 - 3.3 kg
- Housing: during a pre-period of at least one week and throughout the experiment the rabbits were caged individually in PPO cages (floor area: 2576 cm²) with perforated floor.
- Diet: Altromin 2123 (Altromin 2123, Lage, Germany), ad libitum
- Water: domestic quality drinking water acidified with hydrochloric acid to pH 2.5, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 55 ± 15
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12 / 12

Vehicle:
unchanged (no vehicle)
Controls:
other: the untreated eye served as control
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.1 mL
Duration of treatment / exposure:
24 hours
Observation period (in vivo):
72 hours
Reading time points: 1, 24, 48 and 72 hours
Number of animals or in vitro replicates:
4 females
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: The treated eye was rinsed with 20 mL 0.9% sodium chloride solution.
- Time after start of exposure: 24 hours

SCORING SYSTEM: Draize scoring system

TOOL USED TO ASSESS SCORE: fluorescein
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
of 4 animals
Time point:
other: mean after 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
iris score
Basis:
mean
Remarks:
of 4 animals
Time point:
other: mean after 24, 48 and 72 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
of 4 animals
Time point:
other: mean after 24, 48 and 72 h
Score:
0.3
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
of 4 animals
Time point:
other: mean after 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritant / corrosive response data:
One hour after application of the test substance 2 animals showed an iris with markedly deepened folds, congestion, swelling, moderate circumcorneal injection and existence of reaction to light, a diffuse, crimson red conjunctiva with individual vessels not easily discernible, a swelling above normal and a discharge with moistening of the lids and hairs, and considerable area around the eye. An iris with markedly deepened folds, congestion, swelling, moderate circumcorneal injection and existence of reaction to light, a diffuse, crimson red conjunctiva with individual vessels not easily discernible , a swelling above normal and a discharge with moistening of the lids and hairs just adjacent to lids were observed in the other 2 animals. 24 hours alter application of the test substance all animals showed some conjunctival vessels definitely injected. 48 and 72 hours after application of the test article all four animals were free of any signs of eye irritation.

Table 1. Results of the eye irritation study

Animal

Time (h)

Conjunctivae

Cornea

Iris

Redness

Chemosis

1

1

2

1

0

1

24

1

0

0

0

48

0

0

0

0

72

0

0

0

0

Average 24+48+72

0.3

0

0

0

2

1

2

1

0

1

24

1

0

0

0

48

0

0

0

0

72

0

0

0

0

Average 24+48+72

0.3

0

0

0

3

1

2

1

0

1

24

1

0

0

0

48

0

0

0

0

72

0

0

0

0

Average 24+48+72

0.3

0

0

0

4

1

2

1

0

1

24

1

0

0

0

48

0

0

0

0

72

0

0

0

0

Average 24+48+72

0.3

0

0

0

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this eye irritation study in rabbits the test substance was not irritating to the eye.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin

The skin irritation potential of the test substance was determined by an in vivo skin irritation test in rabbits according to OECD Guideline 404 and in compliance with GLP (2001). A dose of 0.5 mL of the test substance at concentrations of 1, 10, 25, 50 and 100% was applied to the skin of four rabbits under semi-occlusive conditions for 4 hours. After the exposure period the patch was removed and the skin sites were evaluated using the Draize scaling system. Scores were taken 1, 24, 48 and 72 hours after patch removal. An erythema (score 1) was observed in all animals treated with undiluted test substance only 24 hours after patch removal, in one animal until 48 hours. No skin reactions were observed 72 hours after patch removal. The overall mean score after 24, 48 and 72 hours for erythema out of 3 rabbits was 0.3 and for one animal 0.67. The overall mean scores for edema after 24, 48 and 72 h out of 4 rabbits was 0. Based on the results, the undiluted test substance as well as 1, 10, 25 and 50% dilutions were not irritating to the skin under the conditions of the test.

 

Eye

The eye irritation potential of the test substance was investigated in four albino rabbits according to OECD Guideline 405 and in compliance with GLP (2001). 0.1 mL of the test material was placed in one eye of each animal. The other eye remained untreated and served as control. The eyes were examined and scored according to Draize 1, 24, 48 and 72 hours after application. Conjunctival redness (score 2), discharge (score 2 or 3), chemosis (score 1) and iris (score 1) was observed in all animals 1 hour after treatment. At 24 hours after application, conjunctival redness (score 1) was noted in all animals. All effects were fully reversible within 48 hours. The overall mean score after 24, 48 and 72 hours out of four rabbits for conjunctival redness was 0.3. The overall mean irritation score over 24, 48 and 72 hours for chemosis, iris and corneal effects was 0. Based on the results of this study, the test substance was not irritating to the eyes under the conditions of the test.


Justification for selection of skin irritation / corrosion endpoint:
The reliable GLP compliant OECD Guideline study was chosen.

Justification for selection of eye irritation endpoint:
The reliable GLP compliant OECD Guideline study was chosen.

Justification for classification or non-classification

The available data on skin and eye irritation of the test substance do not meet the criteria for classification according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.