Registration Dossier

Administrative data

Description of key information

Skin: OECD 404; no skin irritation was observed in rabbits. Reliability = 1
Eye: OECD 405; eye damage was observed in rabbits. Reliability = 1
Respiratory: No signs of respiratory tract irritation were observed in a rat acute inhalation study up to 5200 mg/m3.

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:
other: This study was selected as the key study because the information provided for the hazard endpoint is sufficient for the purpose of classification and labeling and/or risk assessment.
Qualifier:
according to
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:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
Remarks:
The study was conducted according to the guideline in effect dated 2002.
Qualifier:
according to
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.
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: Not reported
- Weight at study initiation: 3033, 3167, 3044 g
- Housing: singly in stainless steel, wire-mesh cages suspended above cage boards
- Diet (e.g. ad libitum): 125 grams of rabbit food daily
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16-22ºC
- Humidity (%): 30-70%
- 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:
other: The adjacent areas of untreated skin were used for comparison.
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 m/L
Duration of treatment / exposure:
4 hours
Observation period:
up to 72 hours
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: approximately 6 cm2
- % coverage: 100
- Type of wrap if used: 2-ply gauze pad which was held in place with non-irritating tape and the trunk of each rabbit was wrapped with porous tape and further secured with waterproof tape


REMOVAL OF TEST SUBSTANCE
- Washing (if done): gently washed with warm water to remove excess test substance and gently patted dry
- Time after start of exposure: 4 hours


SCORING SYSTEM: Draize Scale
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 0 minutes to 72 hours
Score:
>= 1 - <= 2
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 0 minutes to 72 hours
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
Erythema (score of 1 or 2) but no edema was observed in the 3 rabbits on the day of dosing. No dermal irritation was observed at 24, 48/50, or 72 hours after removal of the test substance. No clinical signs were observed, and no body weight loss occurred. See Table 1 below.

Table 1: Dermal Responses Observed in Individual Rabbits

ERYTHEMA

Rabbit

Number

Evaluation after Removal of Test Substance

0 Minutes

60 Minutes

24 Hours

48 Hours

72 Hours

264

2

2

0

0

0

275

--

2

0

0

0

276

--

1

0

0

0

 

EDEMA

Rabbit

Number

Evaluation after Removal of Test Substance

0 Minutes

60 Minutes

24 Hours

48 Hours

72 Hours

264

0

0

0

0

0

275

--

0

0

0

0

276

--

0

0

0

0

Interpretation of results:
other: no classification is required
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study, the test substance produced erythema, which cleared by 24 hours, when applied to the skin of rabbits. I
This study and the conclusions which are drawn from it fulfill the quality criteria (validity, reliability, repeatability).
Executive summary:

The test substance was applied as a single 0.5-mL 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 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 and scored by the method of Draize for signs of dermal irritation approximately 60 minutes, and 24, 48/50, and 72 hours after test substance removal. The rabbit that was initially treated was also examined immediately after test substance removal. Erythema (score of 1 or 2) but no edema was observed in the 3 rabbits on the day of dosing. No dermal irritation was observed at 24, 48/50, or 72 hours after removal of the test substance. No clinical signs were observed, and no body weight loss occurred. Under the conditions of this study, the test substance produced erythema, which cleared by 24 hours, when applied to the skin of rabbits.

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:
other: This study was selected as the key study because the information provided for the hazard endpoint is sufficient for the purpose of classification and labeling and/or risk assessment.
Qualifier:
according to
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:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Deviations:
no
Remarks:
The study was conducted according to guideline in effect at time of study conduct.
Qualifier:
according to
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.
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: 2846 g
- Housing: singly in a stainless steel, wire-mesh cage suspended above a cage board.
- Diet: 125 grams of PMI® Nutrition International, LLC Certified Rabbit LabDiet® 5322 daily
- Acclimation period: 7 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16-22°C
- Humidity (%): 30-70%
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12-hour light/dark cycle
Vehicle:
unchanged (no vehicle)
Controls:
other: control was untreated eye of test animal
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL


Duration of treatment / exposure:
28 hours
Observation period (in vivo):
at dosing, 1, 24 and 28 hours
Number of animals or in vitro replicates:
1
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: unwashed



SCORING SYSTEM: Draize Scale


TOOL USED TO ASSESS SCORE: illumination and magnification, fluorescein stain examinations were conducted on the day after instillation.
Irritation parameter:
cornea opacity score
Remarks:
opacity
Basis:
animal #1
Time point:
24/48 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 28 hours
Remarks on result:
other: 1 - 28h
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48 h
Score:
>= 1
Max. score:
2
Reversibility:
not fully reversible within: 28 hours
Remarks on result:
other: 1-28h
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48 h
Score:
0
Max. score:
3
Reversibility:
not fully reversible within: 28 hours
Remarks on result:
other: Brown and white discoloration of the conjunctival membrane of the treated rabbit eye was observed at 1, 24, and 28 hours after instillation of the test substance.
Remarks:
1-28h
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48 h
Score:
>= 2 - <= 4
Max. score:
4
Reversibility:
not fully reversible within: 28 hours
Remarks on result:
other: 1-28h
Irritation parameter:
other: Discharge
Basis:
animal #1
Time point:
other: 1 hour to 28 hours
Score:
>= 2 - <= 3
Max. score:
3
Reversibility:
not fully reversible within: 28 hours
Irritant / corrosive response data:
Brown and white discoloration of the conjunctival membrane of the treated rabbit eye was observed at 1, 24, and 28 hours after instillation of the test substance. Corneal opacity (score of 2), iritis (score of 1), conjunctival chemosis (score of 2 or 4), and discharge (score of 2 or 3) were also observed. Fluorescein stain examinations were positive for corneal injury in the treated eye. The rabbit was euthanized the day after treatment for humane reasons.
The ocular scores from the animal with respect to observation time are presented in Table 1.

Table 1: Individual Animal Ocular Effects

 

 

Rabbit No.

Cornea

Iritis

Conjunctiva

Fluorescein Stain

Other

Opacity

Area

Redness

Chemosis

Discharge

1 Hour

279

2

4

0

0

2

3

NA

-

24 Hours

279

2

2

1

0

4

2

POS

*

28 Hours

279

2

4

1

0

4

2

POS

*

POS= positive for corneal injury

NA = not applicable

- = No other effects

* = Brown and white discoloration of the conjunctiva

Interpretation of results:
irritating
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
Under the conditions of this study, the test substance produced ocular effects in a rabbit.
This study and the conclusions which are drawn from it fulfill the quality criteria (validity, reliability, repeatability).
Executive summary:

An aliquot of 0.1 mL 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, and 28 hours following administration of the test substance. Brown and white discoloration of the conjunctival membrane of the treated rabbit eye was observed at 1, 24, and 28 hours after instillation of the test substance. Corneal opacity (score of 2), iritis (score of 1), conjunctival chemosis (score of 2 or 4), and discharge (score of 2 or 3) were also observed. Fluorescein stain examinations of the treated eye were positive for corneal injury. The rabbit was euthanized the day after treatment for humane reasons. Under the conditions of this study, the test substance produced ocular effects in a rabbit.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

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

Additional information

After application of a single 0.5-mL dermal dose to the shaved intact skin of rabbits for 4 hours, erythema (score of 1 or 2) but no edema was observed on the day of dosing. No dermal irritation was observed at 24, 48/50, or 72 hours after removal of the test substance.

After instillation of 0.1 mL of test substance into the lower conjunctival sac of the eye of 2 rabbits, brown and white discoloration of the conjunctival membrane was observed at 1, 24, and 28 hours. Corneal opacity (score of 2), iritis (score of 1), conjunctival chemosis (score of 2 or 4), and discharge (score of 2 or 3) were also observed. Fluorescein stain examinations of the treated eye were positive for corneal injury. The rabbit was euthanized the day after treatment for humane reasons. Under the conditions of this study, the test substance produced ocular effects in a rabbit.

No signs of respiratory tract irritation were observed in an acute inhalation study in rats at a concentration of 5200 mg/m3.

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

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

Effects on eye irritation: highly irritating

Justification for classification or non-classification

Based on the observations following eye exposure, the substance is classified as Irritation Category 1 (Causes serious eye damage) according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.

There was no evidence of irritation in skin irritation studies or respiratory irritation during inhalation exposures. Therefore, the substance does not need to be classified for skin or respiratory tract irritation according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.