Registration Dossier

Administrative data

Description of key information

Skin irritation/corrosion

1) A primary skin irritation study (Daamen, 1989) is available which is key study. This study showed that the test substance is not irritating.

2) An abstract (Loeser, 1977) is available which demonstrated the test substance is not irritating.

Eye irritation

1) An acute eye irritation study (Daamen, 1989) is available which is key study. This study showed that the test substance is sufficiently irritating to warrant classification as Category 2 (Reversible eye effects).

2) Another abstract (Loeser, 1977) is available which demonstrated the test substance is 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:
From 03 to 06 May 1989
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
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)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga, Sulzfeld, West-Germany
- Age at study initiation: ±12 weeks
- Weight at study initiation: 2462-3094 gram
- Housing: Individually in cages with perforated floors equipped with an automatic drinking system
- Diet (e.g. ad libitum): Standard laboratory rabbit diet approx. 100 gram per day
- Water (e.g. ad libitum): Free access to tap-water diluted with decalcified water
- Acclimation period: At least five days under test conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21±3℃
- Humidity (%): 30-70%
- Air changes (per hr): 7.5-15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light/ 12 hours dark

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5g
- Concentration (if solution):
Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
3 females
Details on study design:
TEST SITE
- Area of exposure: Approximately 100 square centimeters (10 cm×10 cm)
- % coverage:
- Type of wrap if used: elastic bandage

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

SCORING SYSTEM: Draize
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
1
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: One of three animals appeared very slight erythema.
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritant / corrosive response data:
The test substance resulted in a primary irritation index of 0 (non-irritation) when applied to intact rabbit skin.

The observed skin irritation consisted of very slight erythema in one animal. The irritation was reversible within 24 hours after exposure.

No corrosive effect was evident on the skin.
Other effects:
No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Individual skin irritation scores

Time after exposure

Rabbit 2735

Rabbit 2736

Rabbit 2737

Erythema

Oedema

Erythema

Oedema

Erythema

Oedema

1 hour

24 hours

48 hours

72 hours

0

0

0

0

0

0

0

0

1

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test substance is not irritating when applied to the intact rabbit skin.
Executive summary:

This study was conducted under GLP according to OECD 404. Three rabbits were exposed to 0.5 g of the test substance, moistened with water, by application onto clipped skin for 4 hours using a semi-occlusive dressing. Skin reactions were assessed at 1, 24, 48 and 72 hours after the removal of the dressings and test article.

Under the conditions of this study, the test substance resulted in a primary irritation index of 0 when applied to the intact rabbit skin. No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred. In conclusion, the test substance is not irritating when applied to the intact rabbit skin.

The study represents a worst case situation as the treated skin area was 100 cm2 instead of 6 cm2 as required by the present version of OECD 404.

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:
From 10 to 24 May 1989
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
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)
Qualifier:
according to
Guideline:
EPA OPP 81-4 (Acute Eye Irritation)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Animal 2711 from Broekman Institute, Someren, The Netherlands. Animals 2717 and 2737 from Charles River Wiga, Sulzfeld, West-Germany.
- Age at study initiation: Approx. 12-14 weeks
- Weight at study initiation: 2654-3179 grams
- Housing: Individually in cages with perforated floors and equipped with an automatic drinking system.
- Diet (e.g. ad libitum): Pelleted standard rabbit maintenance diet approx. 100 g per day.
- Water (e.g. ad libitum): Free access to tap-water diluted with decalcified water.
- Acclimation period: At least five days under test conditions for animal 2711, four days for animal 2737 and two days for animal 2717.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21±3℃
- Humidity (%): 30-83%
- Air changes (per hr): 7.5-15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light / 12 hours dark
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): ±60 mg
Duration of treatment / exposure:
24 hours
Observation period (in vivo):
14 days
Number of animals or in vitro replicates:
3 females
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done):
- Time after start of exposure:

SCORING SYSTEM: Draize

TOOL USED TO ASSESS SCORE: Draize scale
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
1
Reversibility:
fully reversible within: 24 hours
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 2.44
Max. score:
3
Reversibility:
fully reversible within: 14 days
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 0.67
Max. score:
2
Reversibility:
fully reversible within: 72 hours
Irritant / corrosive response data:
The test substance appeared to be mildly irritating (M2) to the rabbit eye (Kay and Calandra interpretation of the Draize score: 9.3).

Instillation of the substance into one of the eyes of each of three albino rabbits affected the conjunctivae. The irritation of the conjunctivae was reversible within 14 days.

Treatment of the eyes with fluorescein 2%, 24 hours after test article instillation revealed no corneal epithelial damage in any of the animals.

No corrosion was observed.
Other effects:
No staining by the test article was observed.
No toxic symptoms were observed in the animals during the test period and no mortality occurred.

Individual eye irritation scores

Animal

Time after application

Cornea opacity

Iris

Conjunctivae

Redness

Chemosis

2711

1 hour

24 hours

48 hours

72 hours

7 days

14 days

0

0

0

0

0

0

1

0

0

0

0

0

1

2

3

3

2

0

1

1

1

0

0

0

2717

1 hour

24 hours

48 hours

72 hours

7 days

14 days

0

0

0

0

0

0

0

0

0

0

0

0

2

2

3

3

2

0

2

1

1

0

0

0

2737

1 hour

24 hours

48 hours

72 hours

7 days

14 days

0

0

0

0

0

0

0

0

0

0

0

0

1

2

2

2

1

0

1

1

1

0

0

0

Interpretation of results:
slightly irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test substance is mildly irritating to the rabbit eye, sufficient to warrant classification as Category 2 (Reversible eye effects).
Executive summary:

This study was conducted under GLP according to OECD 405. Three rabbits were exposed to 60 mg of the test substance, by instilling the test substance into the eye. The eyes of each animal were examined approx. 1, 24 ,48 and 72 hours, and 7 and 14 days after instillation of the test article.

Under the conditions of this study, the test substance resulted in adverse effects on the conjunctivae. The irritation of the conjunctivae was reversible within 14 days. No corrosion nor signs of systemic intoxication were observed. The test article should be considered mildly irritating to the rabbit eye.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Skin irritation/corrosion

1) A primary skin irritation study was conducted according to OECD 404 using rabbits (Daamen, 1989). Key study.

This study showed that the test substance is not irritating.

2) An abstract (Loeser, 1977) is available which demonstrated the test substance is not irritating.

Eye irritation

1) An acute eye irritation study was conducted according to OECD 405 using rabbits (Daamen, 1989). Key study.

This study showed that the test substance is sufficiently irritating to warrant classification as Category 2 (Reversible eye effects)

2) Another abstract (Loeser, 1977) is available which demonstrated the test substance is not irritating.

Justification for selection of skin irritation / corrosion endpoint:

This study was conducted under GLP according to OECD 404 using rabbits.

Justification for selection of eye irritation endpoint:

This study was conducted under GLP according to OECD 405 using rabbits.

Effects on eye irritation: slightly irritating

Justification for classification or non-classification

Skin irritation/corrosion: Mean scores at 24, 48 & 72 hours for erythema were < 2.3 (actual value 0) for oedema were < 2.3 (actual value 0). In addition all reactions were fully reversible within the observation period (worst case was full recovery within 24 hours).

Serious eye damage/eye irritation: Mean scores at 24, 48 & 72 hours for corneal opacity were < 1 (actual value 0), for iritis were < 1 (actual value 0), for conjunctival redness were ≥ 2 (actual value 2.44) and for conjunctival oedema were < 1 (actual value 0.67).

Therefore in accordance with Regulation (EC) No. 1272/2008 Tables 3.2.2 & 3.3.2 the substance is not classified for the skin corrosion/irritation endpoint and classified as "Category 2 (Reversible eye effects)" for the serious eye damage/eye irritation endpoint.