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:
21 - 30 Jan 2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
No analytical purity is given.
Reference:
Composition 0
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
GLP compliance:
yes (incl. certificate)
Remarks:
THE DEPARTEMENT OF HEALTH OF THE GOVERNMENT OF THE UNITED KINGDOM:
Test material information:
Composition 1
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories UK Limited, Bicester, Oxon, UK
- Age at study initiation: 12 - 20 weeks old
- Weight at study initiation: 2.0 - 3.5 kg
- Housing: The animals were individually housed in suspended cages.
- Diet: 2030 Teklad Global Rabbit diet supplied by Harlan Teklad, Blackthorn, Bicester, Oxon, UK; ad libitum
- Water: drinking water; ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23
- Humidity (%): 30-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
other: Not required, untreated sites of the same animal served as control.
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
Duration of treatment / exposure:
3 min, 1 and 4 h
Observation period:
72 h
Reading time points: 1, 24, 48 and 72 h
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 3 suitable sites were selected on the back of the rabbit. The test substance was introduced under a 2.5cm x 2.5cm cotton gauze patch.
- Type of wrap if used: Each patch was secured in position with a strip of surgical adhesive tape. To prevent the animal interfering with the patches, the trunk of the rabbit was wrapped in an elasticated corset for the duration of the exposure period.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Any residual test material was removed by gentle swabbing with cotton wool soaked in distilled water.
- Time after start of exposure: 3 min, 1 h and 4 h

SCORING SYSTEM: Draize scoring system
Irritation parameter:
erythema score
Basis:
mean
Remarks:
out of all 3 animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
mean
Remarks:
out of all 3 animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritant / corrosive response data:
Following 3 min, 1 h and 4 h exposure, there were no signs of skin irritation at the treated skin sites. All scores at any observation time point were 0.

Other effects:
All animals showed expected gain in body weight during the study.
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008
Conclusions:
Under the conditions of the Acute Dermal Irritation/Corrosion Test in rabbits the test substance does not possess any skin irritating 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:
02 - 12 Feb 2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
No analytical purity is given.
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
THE DEPARTMENT OF HEALTH OF THE GOVERNMENT OF THE UNITED KINGDOM
Test material information:
Composition 1
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories UK Limited, Bicester, Oxon, UK
- Age at study initiation: 12 - 20 weeks old
- Weight at study initiation: 2.53 - 2.95 kg
- Housing: individually housing in suspended cages
- Diet: 2030 Teklad Global Rabbit diet supplied by Harlan Teklad, Blackthorn, Bicester, Oxon, UK: ad libitum
- Water: drinking water; ad libitum
- Acclimation period: att least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 - 23
- Humidity (%): 30 - 70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
other: The untreated left eye served as control.
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
Duration of treatment / exposure:
single application without washing
Observation period (in vivo):
Reading time points: 1, 24, 48 and 72 h
Number of animals or in vitro replicates:
3
Details on study design:
SCORING SYSTEM: Draize scoring system

TOOL USED TO ASSESS SCORE: Examination of the eyes was facilitated by the use of the light source from a standard ophthalmoscope.
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
out of all 3 animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
iris score
Basis:
mean
Remarks:
out of all 3 animals
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
out of all 3 animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.3
Max. score:
3
Reversibility:
fully reversible within: 48 h
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.3
Max. score:
3
Reversibility:
fully reversible within: 48 h
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.3
Max. score:
3
Reversibility:
fully reversible within: 48 h
Irritant / corrosive response data:
Ocular Reactions
At 1 h post application, conjunctival redness (score 2) and chemosis (score 1) were noted in all animals. However, the effects were fully reversible within 24 h for chemosis and within 48 h for redness (see table 2). No effects on iris or cornea were observed during the study period.
Other effects:
Body weight
All animals showed expected gain in body weight during the study (table 3).

Table 2. Results of the eye irritation study.

Rabbit #

 

Time [h]

 

conjunctivae

 

iris

 

cornea

 

 

conjunctivae

 

iris

 

cornea

 

redness

swelling

redness

swelling

1

 

 

 

 

1

2

1

0

0

 

24

1

0

0

0

48

0

0

0

0

72

0

0

0

0

average

0.3

0.0

0.0

0.0

Time to reversion

48.0

24.0

0.0

0.0

2

 

 

 

 

1

2

1

0

0

 

 

24

1

0

0

0

48

0

0

0

0

72

0

0

0

0

average

0.3

0.0

0.0

0.0

Time to reversion

48.0

24.0

0.0

0.0

3

 

 

 

 

1

2

1

0

0

 

 

24

1

0

0

0

48

0

0

0

0

72

0

0

0

0

average

0.3

0.0

0.0

0.0

Time to reversion

48.0

24.0

0.0

0.0

 

Table 3: Individual body weights and body weight changes

Rabbit Number

Individual body weight [kg]

Body weight change [kg]

Day 0

Day 3

#1

2.95

3.05

0.10

#2

2.82

2.90

0.08

#3

2.53

2.61

0.08

All animals showed expected gain in body weight during the study.

Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008
Conclusions:
Under the conditions of this eye irritation study in rabbits the test substance was not irritating to the eye according to Regulation (EC) No 1272/2008.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

The skin irritation/corrosion study was performed in accordance with OECD 404 (Pooles, 2009). The undiluted test substance was applied to the intact skin of rabbits and covered with a gauze patch. Under semi-occlusive conditions, the gauze patch was held in place with an adhesive tape for exposure periods of 3 min, 1 h or 4 h. After the respective exposure, the gauze patch was removed and the treated skin site was cleaned with distilled water. Evaluation of the treated skin sites was done 1, 24, 48 and 72 h after patch removal. There were no signs of skin irritation at the treated skin sites. All scores at any observation time points were 0. Under the test conditions, the test substance was not irritating to the skin.

Eye irritation

According to OECD 405, the undiluted test substance was placed into the conjunctival sac of the right eye of each rabbit (Pooles, 2009). The left eye remained untreated and was used as control. 1, 24, 48 and 72 h after test substance instillation, the grades of ocular reaction (conjunctivae redness, conjunctivae chemosis, cornea, iris) were assessed. 1 h post application, conjunctival redness and chemosis (score 1-2) were noted in all animals. However, the effects were fully reversible within 24 h for chemosis and within 48 h for redness. No effects on iris or cornea were observed during the study period. Under the test conditions, the test substance was not irritating to the eyes.

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 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.