Registration Dossier

Administrative data

Description of key information

Skin irritation:
One study is available (Latour, 2014). The test substance is not irritating to rabbit skin with a 4-hour semi-occlusive application.
Eye irritation:
One study is available (Latour, 2014). The test substance is slightly irritating to rabbit eyes.

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:
From 06 to 16 May 2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study run to a method comparable with current guidelines and to GLP
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River France, L’Arbresle Cedex, France
- Age at study initiation: between 12 and 24 weeks old
- Weight at study initiation: body weights were at least 1.5 kg
- Housing: labeled cages with perforated floors and shelters
- Diet (e.g. ad libitum): Pelleted diet
- Water (e.g. ad libitum): tap water
- Acclimation period: at least 5 days before start of treatment

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 24°C
- Humidity (%): 40 to 70%
- Air changes (per hr): at least 10 air changes/hour
- Photoperiod (hrs dark / hrs light): a 12-hour light/12-hour dark cycle

IN-LIFE DATES: From 06 to 16 May 2014
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): 0.5 grams of the test substance

VEHICLE
- Amount(s) applied (volume or weight with unit): 1 mL
Duration of treatment / exposure:
4 h
Observation period:
72 hours after the removal of the dressings and test substance
Number of animals:
3 males
Details on study design:
TEST SITE
- Area of exposure: approximately 150 square centimeters (10x15 cm)
- Type of wrap if used: metalline patch mounted on Micropore tape, which was wrapped around the abdomen and secured with Coban elastic bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): tap water
- Time after start of exposure: Four hours

OBSERVATION:
-Mortality/Viability: Twice daily.
-Toxicity: At least once daily.
-Body Weight: Day of treatment (prior to application) and after the final observation.
-Necropsy: No necropsy was performed according to protocol.
-Irritation: The skin reactions were assessed at approximately 1, 24, 48 and 72 hours after the removal of the dressings and test substance. The irritation scores and a description of all other (local) effects were recorded. Adjacent areas of the untreated skin of each animal served as controls.

SCORING SYSTEM: Draize
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0
Max. score:
0
Irritation parameter:
edema score
Basis:
mean
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0
Max. score:
0
Irritant / corrosive response data:
No skin irritation was caused by 4 hours exposure.
There was no evidence of a corrosive effect on the skin.
Other effects:
No staining of the treated skin by the test substance was observed and no test substance remnants were seen.
No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Individual skin irritation scores

Animal

682

684

685

Time after exposure

Erythema

(0-4)

Oedema

(0-4)

Erythema

(0-4)

Oedema

(0-4)

Erythema

(0-4)

Oedema

(0-4)

1 hour

0

0

0

0

0

0

24 hours

0

0

0

0

0

0

48 hours

0

0

0

0

0

0

72 hours

0

0

0

0

0

0

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test substance is not irritating to rabbit skin with a 4-hour semi-occlusive application.
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:
From 12 to 22 May 2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study run to a method comparable with current guidelines and to GLP
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Charles River France, L’Arbresle Cedex, France
- Age at study initiation: between 12 and 24 weeks old
- Weight at study initiation: at least 1.5 kg
- Housing: labeled cages with perforated floors and shelters
- Diet (e.g. ad libitum): Pelleted diet
- Water (e.g. ad libitum): tap water
- Acclimation period: at least 5 days before start of treatment

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 24°C
- Humidity (%): 40 to 70%
- Air changes (per hr): at least 10 air changes/hour
- Photoperiod (hrs dark / hrs light): a 12-hour light/12-hour dark cycle

IN-LIFE DATES: From 12 to 22 May 2014
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 41.2 mg
Duration of treatment / exposure:
1 hour
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
3 males
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): approx. 50 mL tepid tap water, using a velocity of flow which did not affect the eye, to remove any visible residual test substance.
- Time after start of exposure: Immediately after the 1 hour observation

OBSERVATION
-Mortality/Viability: Twice daily.
-Toxicity: At least once daily.
-Body Weight: Day of treatment (prior to instillation) and after the final observation.
-Necropsy: No necropsy was performed according to protocol.
-Irritation: The eyes of each animal were examined approximately 1, 24, 48 and 72 hours after instillation of the test substance. The irritation scores and a description of all other (local) effects were recorded.

SCORING SYSTEM: Draize
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
mean
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0
Max. score:
0
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: Mean of 24, 48 and 72 hours
Score:
ca. 0.67
Max. score:
2
Reversibility:
fully reversible within: 72 h
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0
Max. score:
1
Reversibility:
fully reversible within: 24 h
Irritant / corrosive response data:
Irritation:
Instillation of approximately 41 mg of the test substance (a volume of approximately 0.1 mL) into one eye of each of three rabbits resulted in irritation of the conjunctivae, which consisted of redness, chemosis and discharge. The irritation had completely resolved within 72 hours in all animals.
No iridial irritation or corneal opacity were observed, and treatment of the eyes with 2% fluorescein 24 hours after test substance instillation revealed no corneal epithelial damage.

Corrosion:
There was no evidence of ocular corrosion.
Other effects:
Remnants of the test substance were present in the eye of one animal on Day 1.
No staining of (peri) ocular tissues by the test substance was observed and no test substance remnants were seen in the eyes of the other two animals.
No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Individual eye irritation scores

Animal

Time after dosing

Cornea opacity

Iris

Conjunctivae redness

Conjunctivae Chemosis

680

1 hour

0

0

1

1

24 hour

0

0

1

0

48 hour

0

0

1

0

72 hour

0

0

0

0

691

1 hour

0

0

2

1

24 hour

0

0

1

0

48 hour

0

0

1

0

72 hour

0

0

0

0

692

1 hour

0

0

1

1

24 hour

0

0

1

0

48 hour

0

0

1

0

72 hour

0

0

0

0

Interpretation of results:
slightly irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test substance is slightly irritating to rabbit eye.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Skin irritation:

One study is available which was conducted according to OECD Guideline 404 under GLP (Latour, 2014). The test substance is not irritating to rabbit skin with a 4-hour semi-occlusive application.

Eye irritation:

One study is available which was conducted according to OECD Guideline 405 under GLP (Latour, 2014). The test substance is slightly irritating to rabbit eyes.


Justification for selection of skin irritation / corrosion endpoint:
Study run to a method comparable with current guidelines and to GLP

Justification for selection of eye irritation endpoint:
Study run to a method comparable with current guidelines and to GLP

Effects on eye irritation: slightly irritating

Justification for classification or non-classification

Skin irritation/corrosion: Mean scores at 24, 48 and 72 hours for erythema were < 2.3 (actual value 0) and for edema were < 2.3 (actual value 0).

Serious eye damage/eye irritation: Mean scores at 24, 48 and 72 hours for corneal opacity were < 1 (actual value 0), for iris were < 1 (actual value 0), for conjunctival redness were < 2 (actual value ca.0.67) and for chemosis were < 1 (actual value 0).

Therefore in accordance with Regulation (EC) No. 1272/2008 Table 3.2.2 & 3.3.2, this substance should not be classified for skin irritation/corrosion and serious eye damage/eye irritation endpoints.