Registration Dossier

Administrative data

Description of key information

The test substance demonstrated no persistent skin irritation in a reliable study with rabbits. Furthermore, no notable eye irritation was observed in the key study for eye irritation, minor changes were fully reversible. Due to these findings the test substance is considered to be 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:
1997
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study meets generally accepted scientific principles and is acceptable for assessment.
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Qualifier:
according to
Guideline:
EPA OTS 798.4470 (Acute Dermal Irritation)
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Ace Animals, Boyertown, PA
- Age at study initiation: 4 - 5 months
- Weight at study initiation: 2.0 - 2.4 kg
- Housing: 1/cage in suspended wire cages. Bedding was placed beneath the cages and changed at least three times per week.
- Diet: Fresh Purina Rabbit Chow (Diet #5321) was provided daily
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: controlled
- Photoperiod (hrs dark / hrs light): 12 / 12
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.5 g/rabbit
Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
6 females
Details on study design:
TEST SITE
- Area of exposure: dorsal area of the trunk
- Type of wrap if used: 2.5 x 2.5 cm surgical gauze patch; the patch was secured with non-irritating tape. The torso was wrapped with plastic in a semi-occlusive manner and secured with non-irritating tape which completely covered the plastic.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Residual test article was removed from the test site by gentle washing with distilled water at the end of the exposure period, prior to scoring for dermal reactions
- Time after start of exposure: 4 hours

SCORING SYSTEM: according to the Draize system
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24, 48 and 72 h
Score:
0
Max. score:
4
Remarks on result:
other: Erythema with max. score of 1 in two animals was noted at 60 min time point, reversible within 24 hours.
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24, 48 and 72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
In two animals, slight erythemas (score = 1) were noted 30 - 60 minutes after patch removal and cleared by 24 hours. Edema was absent at all observation intervals.
Other effects:
There were no abnormal systemic signs noted during the observation period.
Interpretation of results:
not irritating
Remarks:
Migrated information
Conclusions:
The test article caused only minimal skin reactions in 2/6 animals and is therefore considered to be not irritating to the rabbit skin.
Executive summary:

In a primary dermal irritation study according to OECD guideline 404, six female New Zealand White rabbits were dermally exposed to the test item for four hours in a semi-occlusive manner. 0.5 g of the test substance was placed on a clipped but intact area of the torso and held in place by a gauze patch moistened with distilled water. After 4 hours the wrappings were removed and residual test article was removed from the test site by gentle washing with distilled water. Dermal reactions were then scored according to the Draize scoring system at 30-60 min, 24, 48 and 72 hours after removal of the test substance. Only minimal erythema reactions were observed in two animals, reversible within 24 hours. All other scores for erythema and edema were zero. There were no abnormal systemic signs noted during the observation period. Therefore, based on this result, the test substance is considered to be not irritating to the rabbit skin.

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:
1997
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study meets generally accepted scientific principles and is acceptable for assessment
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Qualifier:
according to
Guideline:
EPA OTS 798.4500 (Acute Eye Irritation)
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand Black
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Ace Animals, Boyertown. PA
- Age at study initiation: 4-5 months
- Weight at study initiation: 2.0 - 2.2 kg
- Housing: 1/cage in suspended cages, bedding was placed beneath the cages and changed at least three times per week.
- Diet: Fresh Purina Rabbit Chow (Diet #5321) was provided daily
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: controlled
- 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 equivalent (12 mg)
Duration of treatment / exposure:
single instillation
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
3 males and 3 females
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

SCORING SYSTEM: according to Draize

TOOL USED TO ASSESS SCORE: hand-held lamp and fluorescein
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
2
Remarks on result:
other: Iritis noted in 2/6 animals, cleared by 24 hours
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0.39
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0.25
Max. score:
4
Reversibility:
fully reversible within: 24 hours
Irritant / corrosive response data:
There was no corneal opacity noted at any observation period. Iritis noted in 2/6 eyes, cleared by 24 hours. Minimal conjunctival irritation noted in 6/6 eyes, cleared by 72 hours the latest.
Other effects:
There were no abnormal systemic signs noted during the observation period.
Interpretation of results:
not irritating
Remarks:
Migrated information
Conclusions:
The test substance caused only minimal ocular reactions below the level of regulatory significance and is therefore classified as not irritating to the rabbit eye.
Executive summary:
In an eye irritation study performed according to OECD guideline 405, six New Zealand White rabbits were treated with 12 mg (equivalent to 0.1 ml) of the test article. The test article was placed into the conjunctival sac of one eye of each animal; the lids were then held together for about one second in order to prevent loss of the test material. The untreated eye served as a control. The ocular reactions were evaluated 1, 24, 48, and 72 hours after instillation and animals were checked daily for signs of systemic toxicity. In two animals iritis was noted at the 1 hour time point, reversible within 24 hours. Additional ocular reactions were recorded for the conjunctivae of all animals. However, the reactions were only minimal and reversible within 72 hours the latest. Since all reactions were well below the threshold of regulatory significance, the test article is considered as not irritating.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

The test article's potential to cause dermal irritation was assessed in an irritation study following OECD guideline 404 (MB Research Labs, MB 975706.03, 1997). An amount of 0.5 g of the test substance was applied topically to the intact skin of six female New Zealand White rabbits for 4 hours under semi-occlusive dressing. In two animals slight erythema reactions were observed 30 -60 minutes after removing of the dressing, reversible within 24 hours. All scores at 24, 48 and 72 hour time points were zero. There were no abnormal systemic signs noted during the observation period. Overall, only minimal skin reactions could be observed and in conclusion, under the test conditions chosen, the test substance is not considered to be irritating to the skin.

 

Eye irritation

To assess the acute eye irritation potential of the test substance in vivo, an irritation study with six New Zealand white rabbits was performed according to OECD guideline 405 (MB Research Labs, MB 975706.04, 1997). An amount of 12 mg (equivalent of 0.1 ml) of the test substance was applied into the conjunctival sac of one eye of each animal and the ocular reactions were evaluated 1, 24, 48, and 72 hours after instillation. All animals displayed minimal reactions to the conjunctivae (reddening, chemosis and discharge), all of which were reversible to normal within 72 hours the latest. Average scores for conjunctival redness and chemosis were 0.39 and 0.25, respectively. In two animals, iritis was observed at the 1 hour time point, reversible within 24 hours. The scores for edema were zero at any time point. Since the observed reactions were minimal and below the regulatory threshold of significance, the test article is considered to be not irritating to the rabbit eye.

Respiratory Irritation

No data


Justification for selection of skin irritation / corrosion endpoint:
Study acceptable for assessment

Justification for selection of eye irritation endpoint:
Study acceptable for assessment

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available experimental test data is reliable and suitable for the purpose of classification under Directive 67/548/EEC. 

Based on the data, the test substance is not classified as skin or eye irritant.

 

Classification, Labeling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for the purpose of classification under Regulation (EC) No.1272/2008.

Based on the data, the test substance is not classified as skin or eye irritant