Registration Dossier

Administrative data

Description of key information

Skin irritation. No irritation. Not classified as a skin irritant. Reliability = 1
Eye irritation. Mild, fully reversible signs of irritation. Not classified as an eye irritant. Reliability = 1.
Respiratory irritation. Inhalation 4-hour LC50 rat. No irritation observed up to 0.89 mg/L (890 mg/m3). 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)
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: Young adult
- Weight at study initiation: 2082-2350 grams
- Housing: The animals were singly housed in suspended stainless steel caging with mesh floors.
- Diet (e.g. ad libitum): Not reported
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 6 or 13 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-23 ºC
- Humidity (%): 65-70 %
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration (if solution): undiluted

Duration of treatment / exposure:
4 hours
Observation period:
30-60 min and at 24, 48, and 72 hours
Number of animals:
3 animals: 1 male , 2 female
Details on study design:
TEST SITE
- Area of exposure: 6-cm2 dose site on dorsal area and the trunk
- Type of wrap if used: A 1-inch x 1-inch, 4-ply gauze pad covered the test area. The pad and entire trunk of each animal were then wrapped with semi-occlusive 3-inch Micropore tape to avoid dislocation of the pad.
REMOVAL OF TEST SUBSTANCE
- Washing (if done): The test sites were gently washed.
- Time after start of exposure: 4 hours
SCORING SYSTEM: Draize scale
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
There was no dermal irritation observed at any treated dose site during the study.

See Table 1 for complete individual rabbit scores

Table 1: Results are listed as ERYTHEMA/EDEMA

Animal No.

Sex

Time After Patch Removal

30-60 mins

24 hrs

48 hrs

72 hrs

1

M

0/0

0/0

0/0

0/0

2

F

0/0

0/0

0/0

0/0

3

F

0/0

0/0

0/0

0/0

Interpretation of results:
GHS criteria not met
Remarks:
not classified as an irritant
Conclusions:
There was no dermal irritation observed at any treated dose site during 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. The study was conducted in a stepwise manner using a single patch applied initially to one rabbit for 4-hours. Five-tenths of a millilitre of the test substance was applied to the skin of one healthy rabbit for 4-hours. The dose site was evaluated for dermal irritation by the method of Draize immediately following patch removal, and at 30-60 minutes and 24, 48, and 72 hours after patch removal. Since no dermal irritation was noted in this animal, the test was completed on two additional animals, as described above. There was no dermal irritation observed at any treated dose site during the study. According to the Globally Harmonized System (GHS) of classification and labelling of chemicals and under the conditions of this study, classification is not required.

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)
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Age at study initiation: Young adult
- Weight at study initiation: 2132-2717 g
- Housing: Singly in suspended, stainless steel, wire-mesh cages
- Diet (e.g. ad libitum): Not reported
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 or 12 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-23 ºC
- Humidity (%): 61-73%
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light):12 hour light/dark cycle
Vehicle:
unchanged (no vehicle)
Controls:
other: The left eye of each rabbit was not treated and served as a control.
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): undiluted
Duration of treatment / exposure:
Single exposure
Observation period (in vivo):
1, 24, 48, and 72 hours and/or at 4 days post-instillation.
Number of animals or in vitro replicates:
3 animals: 2 male, 1 female
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): The eyes remained unwashed.

SCORING SYSTEM: Draize scale

TOOL USED TO ASSESS SCORE: Ocular irritation was evaluated using a high-intensity white light (Mag Lite)
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0.33
Max. score:
2
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
1.33
Max. score:
3
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible
Irritant / corrosive response data:
Corneal opacity was evident in two treated eyes at one hour after dosing, and all three treated eyes exhibited iritis and conjunctivitis. All animals were free of ocular irritation by Day 4. See Table 1 for complete rabbit scores

Table 1: Individual Scores for Ocular irritation

 

Rabbit No.:3401

(male)

Rabbit No.:3402 (male)

Rabbit No.:3403 (female)

Hours

Hours

Hours

1

24

48

72

4 days

1

24

48

72

1

24

48

72

I. Cornea

 

 

A. Opacity

1

0

0

0

0

1

0

0

0

0

0

0

0

B. Area

4

4

4

4

4

4

4

4

4

4

4

4

4

II. Iris

 

A. Values

1

1

0

0

0

1

0

0

0

1

1

0

0

III. Conjunctivae

 

A. Redness

2

2

1

1

0

2

1

1

0

2

2

1

0

B. Chemosis

1

1

0

0

0

1

0

0

0

1

1

0

0

C. Discharge

2

1

1

1

0

1

1

0

0

2

1

1

0

Interpretation of results:
GHS criteria not met
Remarks:
not classified as an irritant
Conclusions:
Corneal opacity was evident in two treated eyes at one hour after dosing, and all three treated eyes exhibited iritis and conjunctivitis. All animals were free of ocular irritation by Day 4.

Executive summary:

A primary eye irritation test was conducted with rabbits to determine the potential for the test substance to produce irritation from a single instillation via the ocular route. The study was conducted in a stepwise fashion. Initially, 0.1 mL of the test substance was instilled into the conjunctival sac of the right eye of one healthy rabbit by pulling the lower lid away from the eyeball. The upper and lower lids were then gently held together for about one second before releasing to minimize loss of the test substance. The left eye remained untreated and served as a control. Ocular irritation was evaluated by the method of Draize. Since irritation cleared by Day 4 and there was no significant irritation observed in this animal, the test was completed on two additional animals, as described above. Corneal opacity was evident in two treated eyes at one hour after dosing, and all three treated eyes exhibited iritis and conjunctivitis. All animals were free of ocular irritation by Day 4. According to the Globally Harmonized System (GHS) of classification and labelling of chemicals and under the conditions of this study, classification is not required.

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

Respiratory irritation

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

Additional information

Justification for classification or non-classification

The test substance produced no skin irritation and evidence of minimal to mild, transient eye irritation.  No irritation was observed in an acute inhalation study. The substance does not need to be classified for skin, eye, or respiratory irritation according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.