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Administrative data

Description of key information

Skin: Rabbit. No irritation. OECD 404; Reliability = 1

Eye: Rabbit. Irritation cleared by 7 days. OECD 405; Reliability = 1

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Deviations:
no
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: MAFF Japan Agricultural Chemicals Regulation Laws Notification 12 Nousan 8147 (2000)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Covance Research Products, Denver, Pennsylvania.
- Weight at study initiation: 3003 to 3583 g
- Housing: All animals were housed singly in stainless steel, wire-mesh cages suspended above cage boards.
- Diet: Approximately 125 grams/day
- Water: ad libitum
- Acclimation period: At least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature: 16-22°C
- Humidity: 30-70%
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
other: Deionized water
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount applied: Approximately 0.5 g of the test substance, moistened with 0.3 mL of deionized water to form a thick paste, was applied to the test site
Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
3 (males)
Details on study design:
TEST SITE
- Area of exposure: Approximately 6 cm²
- Type of wrap if used: The 2-ply gauze pad was held in place with non-irritating tape. The trunk of each rabbit was wrapped with porous tape. The tape was further secured with waterproof tape.

REMOVAL OF TEST SUBSTANCE
- Washing: Yes, with warm water
- Time after start of exposure: Approximately 4 hours

OBSERVATION TIME POINTS
Test sites were evaluated by Draize for signs of dermal irritation approximately 60 minutes, and 24, 48, and 72 hours after test substance removal.

SCORING SYSTEM:
- Method of calculation: Draize Scale for Scoring Skin Irritation, 1959
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
The rabbits exhibited no dermal irritation during the study.
Other effects:
No clinical signs of toxicity were observed, and no biologically important body weight loss occurred.
Interpretation of results:
GHS criteria not met
Conclusions:
Non irritant
Executive summary:

The test substance was applied as a single 0.5-g dermal dose to the shaved intact skin of a single New Zealand White rabbit. Since no corrosion occurred, 2 additional rabbits were treated. The test substance, moistened with 0.3 mL of deionized water, was applied to a 6 cm² area of skin. The application area was covered with a 2-ply gauze square which was held in place with non-irritating tape and covered with porous tape for a semi-occlusive dressing. The rabbits were exposed to the test substance for 4 hours after which the test substance was removed. Test sites were evaluated by Draize for signs of dermal irritation approximately 60 minutes, and 24, 48, and 72 hours after test substance removal. The rabbit that was initially treated was also examined immediately after test substance removal.

The rabbits exhibited no dermal irritation during the study. No clinical signs of toxicity were observed, and no biologically important body weight loss occurred.

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: MAFF Japan Agricultural Chemicals Regulation Laws Notification 12 Nousan 8147 (2000)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Covance Research Products, Denver, Pennsylvania
- Weight at study initiation: 2555 g
- Housing: The animal was housed singly in a stainless steel, wire-mesh cage suspended above a cage board.
- Diet: approximately 125 grams/day
- Water: ad libitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature: 16-22°C
- Humidity: 30-70%
- Photoperiod (hrs dark / hrs light): 12
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount applied: Approximately 59 mg (a weight equal to a 0.1 mL volume) of test substance
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
1 male
Details on study design:
REMOVAL OF TEST SUBSTANCE
The treated and control eye remained unwashed following treatment.

SCORING SYSTEM: Draize Scale

TOOL USED TO ASSESS SCORE: fluorescein
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
2.67
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 7 days
Other effects:
Fluorescein stain examination of the treated eye was positive for corneal injury at 24 hours after instillation of the test substance.
Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Conclusions:
Mildly irritant
Executive summary:

The test substance was evaluated for acute eye irritation potential in 1 young adult New Zealand White rabbit. A skin irritation study was previously conducted. The test substance was not a severe skin irritant or corrosive to the skin.

One rabbit was initially treated. Since severe irritation was observed, no further rabbits were treated. Approximately 59 mg (a weight equal to a 0.1 mL volume) of test substance was administered to 1 eye of the animal. The treated and control eye remained unwashed following treatment. The conjunctiva, iris, and cornea of the treated eye were evaluated and scored according to a numerical scale approximately 1, 24, 48, and 72 hours and 7 days following administration of the test substance.

Corneal opacity (score of 2), iritis (score of 1), conjunctival redness (score of 1, 2, or 3), conjunctival chemosis (score of 1, 2, or 3), and discharge (score of 2) were observed in the treated rabbit eye. Fluorescein stain examination of the treated eye was positive for corneal injury at 24 hours after instillation of the test substance. The treated eye of the rabbit was normal by 7 days after instillation.

No clinical signs of toxicity were observed, and no body weight loss occurred in the rabbit. Mean values were calculated for the animal by using numerical scores obtained from the quantitative evaluation of each ocular response observed approximately 24, 48, and 72 hours following treatment.

These values are as follows:

Corneal opacity: 0.67

Iritis: 1

Conjunctival redness: 2.67

Conjunctival chemosis: 1.33

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In an acute dermal irritation study, the test substance was applied as a single 0.5 g dermal dose, moistened with 0.3 mL deionised water, to the shaved intact skin of three male rabbits. The rabbits were exposed for 4 hours after which the test substance was removed. Test sites were evaluated for signs of dermal irritation up to 72 hours after test substance removal. Rabbits exhibited no dermal irritation during the study.

 

Approximately 100 mg of the test substance was applied to the conjunctival sac of the left eye of six New Zealand White rabbits. There were no signs of illness in any animal during the study. There was no corneal or iridic effects. Conjunctival effects, consisting of slight to mild chemosis (scores of 0 or 1), slight to moderate redness (scores of 1 or 2) and slight to severe discharge (only at 1 hour and then score of 1), were seen in all animals for up to 7 days.  Additional observations included mucoid discharge and Harderian gland discharge. All signs of irritation completely regressed 7 days after application.

Justification for classification or non-classification

The test substance produced no skin irritation and, therefore, does not need to be classified for skin irritation according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.

 

The test substance produced eye irritation in a rabbit at 24 to 72 hours, which cleared by 7 days after instillation. Therefore, the substance is classified as Cat 2 (H319: Causes serious eye irritation) according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.

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