Registration Dossier

Administrative data

Description of key information

Skin:  OECD 404. Rabbits; no skin irritation. Reliability = 1
Eye: OECD 405. Rabbits; slight irritation which cleared in 24 hours. 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:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Remarks:
The study was conducted according to the guideline in effect at the time of study conduct.
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Deviations:
no
Remarks:
The study was conducted according to the guideline in effect at the time of study conduct.
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
Remarks:
The study was conducted according to the guideline in effect at the time of study conduct.
Qualifier:
according to guideline
Guideline:
other: JMAFF 12-Nousan-8147 (2000)
Deviations:
no
Remarks:
The study was conducted according to the guideline in effect at the time of study conduct.
GLP compliance:
yes
Species:
rabbit
Strain:
other: New Zealand albino.
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: 10-11 weeks
- Weight at study initiation: 2576-2706 g
- Housing: singly housed in suspended stainless steel caging
- Diet: Harlan Teklad Global High Fiber Rabbit Diet® #2031. A designated amount of the diet was available to each rabbit (approximately 150 grams/day).
- Water: Filtered tap water was supplied ad libitum
- Acclimation period: 6 or 13 days


ENVIRONMENTAL CONDITIONS
- Temperature: 19-22ºC
- Humidity: 40-50%
- Air changes (per hr): 12
- Photoperiod: 12-hour light/dark cycle
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
water
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): Five-tenths of a gram of the test substance (0.59 g of the test mixture)

VEHICLE
- Amount(s) applied (volume or weight with unit): dry paste containing 85% test substance and15% distilled water by weight

Duration of treatment / exposure:
4 hours
Observation period:
immediately following patch removal (initial rabbit only) and at approximately 30-60 minutes, 24, 48, and 72 hours after patch removal
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 6 cm2
- Type of wrap if used: a 1-inch x 1-inch, 4-ply gauze pad and wrapped with semi-occlusive 3-inch Micropore tape

REMOVAL OF TEST SUBSTANCE
After 4 hours of exposure to the test substance, the pads and collars were removed and the test sites were gently cleansed with a 3% soap solution followed by tap water and a clean paper towel to remove any residual test substance.

SCORING SYSTEM: Draize
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 1 to 72 hours
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 1 to 72 hours
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 1 to 72 hours
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 1 to 72 hours
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 1 to 72 hours
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: 1 to 72 hours
Score:
0
Max. score:
4

All animals appeared active and healthy and gained body weight during the study. There was no dermal irritation noted for any treated site during this study.

Interpretation of results:
GHS criteria not met
Conclusions:
This study and the conclusions which are drawn from it fulfil the quality criteria (validity, reliability, repeatability).
No skin irritation was observed throughout the study.
Executive summary:

A primary skin irritation test was conducted with rabbits to determine the potential for the test substance to produce irritation after a single topical application in accordance with OECD guideline 404. Five-tenths of a gram of the test substance was moistened with distilled water and applied to the skin of three healthy rabbits for 4 hours. The dose site was evaluated for dermal irritation by the method of Draize immediately after patch removal and at 30-60 minutes and 24, 48, and 72 hours after patch removal.

There was no dermal irritation noted for any treated site during this study.

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
Remarks:
The study was conducted according to guideline in effect at time of study conduct.
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
Remarks:
The study was conducted according to guideline in effect at time of study conduct.
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Deviations:
no
Remarks:
The study was conducted according to guideline in effect at time of study conduct.
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Age at study initiation: 10 weeks
- Weight at study initiation: 2285-2658 g
- Housing: singly housed in suspended stainless steel caging
- Diet: Food: Harlan Teklad Global High Fiber Rabbit Diet® 2031. A designated amount of the diet (approximately 150 grams/day) and a Premium Timothy CubeTM (Ontario Dehy Inc.) were available to each rabbit.
- Water: Filtered tap water was supplied ad libitum.
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature: 19-22ºC
- Humidity: 40-50%
- Air changes (per hr): 12
- Photoperiod: 12 hour light/dark cycle
Vehicle:
unchanged (no vehicle)
Controls:
other: The left eye of each rabbit remained untreated with the test substance and served as a control.
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): One-tenth of a millilitre (0.090 grams)
Duration of treatment / exposure:
single application
Observation period (in vivo):
1, 24, 48, and 72 hours post-instillation
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

SCORING SYSTEM: Draize

TOOL USED TO ASSESS SCORE: hand-slit lamp / biomicroscope / fluorescein: a white light source in accordance with Draize, the fluorescein dye evaluation procedure was used in the treated eye at 24 hours to verify the absence of corneal damage.
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: 1 to 72 hours
Score:
0
Max. score:
4
Remarks on result:
other: Calculated from the 24-, 48-, and 72-hour scores
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: 1 to 72 hours
Score:
0
Max. score:
2
Remarks on result:
other: Calculated from the 24-, 48-, and 72-hour scores
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 1 to 72 hours
Score:
0
Max. score:
3
Remarks on result:
other: Calculated from the 24-, 48-, and 72-hour scores
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 1 to 72 hours
Score:
0
Max. score:
4
Remarks on result:
other: Calculated from the 24-, 48-, and 72-hour scores
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
other: 1 to 72 hours
Score:
0
Max. score:
4
Remarks on result:
other: Calculated from the 24-, 48-, and 72-hour scores
Irritation parameter:
iris score
Basis:
animal #2
Time point:
other: 1 to 72 hours
Score:
0
Max. score:
2
Remarks on result:
other: Calculated from the 24-, 48-, and 72-hour scores
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: 1 to 72 hours
Score:
0
Max. score:
3
Remarks on result:
other: Calculated from the 24-, 48-, and 72-hour scores
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: 1 to 72 hours
Score:
0
Max. score:
4
Remarks on result:
other: Calculated from the 24-, 48-, and 72-hour scores
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
other: 1 to 72 hours
Score:
0
Max. score:
4
Remarks on result:
other: Calculated from the 24-, 48-, and 72-hour scores
Irritation parameter:
iris score
Basis:
animal #3
Time point:
other: 1 to 72 hours
Score:
0
Max. score:
2
Remarks on result:
other: Calculated from the 24-, 48-, and 72-hour scores
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: 1 to 72 hours
Score:
0
Max. score:
3
Remarks on result:
other: Calculated from the 24-, 48-, and 72-hour scores
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: 1 to 72 hours
Score:
0
Max. score:
4
Remarks on result:
other: Calculated from the 24-, 48-, and 72-hour scores
Irritant / corrosive response data:
All animals appeared active and healthy and gained body weight during the study. Apart from the eye irritation noted below, there were no other clinical signs observed.
No corneal opacity, iritis, or conjunctival chemosis was observed. Conjunctival redness (score of 1) was noted in the treated eye of one rabbits and discharge (score of 1) was noted in the treated eye of all three rabbits. Irritation cleared in the treated eye of all rabbits at 24 hours.

 

#1

#2

#3

Hour

Hour

Hour

1

24

48

72

1

24

48

72

1

24

48

72

I. Cornea

 

 

 

 

 

 

 

 

 

 

 

 

A.Opacity

0

0

0

0

0

0

0

0

0

0

0

0

B.Area

4

4

4

4

4

4

4

4

4

4

4

4

II. Iris

 

 

 

 

 

 

 

 

 

 

 

 

A.Values

0

0

0

0

0

0

0

0

0

0

0

0

III.Conjunctivae

 

 

 

 

 

 

 

 

 

 

 

 

A.Redness

0

0

0

0

1

0

0

0

0

0

0

0

B.Chemosis

0

0

0

0

0

0

0

0

0

0

0

0

C.Discharge

1

0

0

0

1

0

0

0

1

0

0

0

Interpretation of results:
GHS criteria not met
Conclusions:
This study and the conclusions which are drawn from it fulfil the quality criteria (validity, reliability, repeatability).
Conjunctival redness (score of 1) was noted in the treated eye of one rabbit and discharge (score of 1) was noted in the treated eye of all three rabbits. Irritation cleared in the treated eye of all rabbits at 24 hours.
Executive summary:

The test substance was evaluated for acute eye irritation potential in 3 young adult New Zealand white rabbits. An aliquot of 0.1 mL of the test substance was administered to 1 eye of each animal. The eyes remained unwashed following treatment. The untreated eye served as a control. The conjunctiva, iris, and cornea of each treated eye were evaluated and scored according to a numerical scale approximately 1, 24, 48, and 72 hours following administration. No corneal opacity, iritis, or conjunctival chemosis was observed. Conjunctival redness (score of 1) was noted in the treated eye of one rabbit and discharge (score of 1) was noted in the treated eye of all three rabbits. Irritation cleared in the treated eye of all rabbits at 24 hours.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

A primary skin irritation test was conducted in 3 rabbits to determine the potential for the test substance to produce irritation after a single topical application. Five-tenths of a gram of the test substance was moistened with distilled water and applied to the skin of three healthy rabbits for 4 hours. The dose site was evaluated for dermal irritation by the method of Draize immediately after patch removal and at 30-60 minutes and 24, 48, and 72 hours after patch removal. There was no dermal irritation noted for any treated site during this study.

The test substance was evaluated for acute eye irritation potential in 3 rabbits. An aliquot of 0.1 mL of the test substance was administered to 1 eye of each animal. The eyes remained unwashed following treatment. The untreated eye served as a control. The conjunctiva, iris, and cornea of each treated eye were evaluated and scored according to a numerical scale approximately 1, 24, 48, and 72 hours following administration. No corneal opacity, iritis, or conjunctival chemosis was observed. Conjunctival redness (score of 1) was noted in the treated eye of one rabbit and discharge (score of 1) was noted in the treated eye of all three rabbits. Irritation cleared in the treated eye of all rabbits at 24 hours.


Justification for selection of skin irritation / corrosion endpoint:
OECD guideline, GLP study

Justification for selection of eye irritation endpoint:
OECD guideline, GLP study

Justification for classification or non-classification

The test substance produced slight eye irritation, but no skin irritation. The substance does not need to be classified for skin or eye irritation according to EU Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.