Registration Dossier

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Description of key information

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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The study was conducted in a contract research organization according to internationally accepted technical guidelines then at force, but without QA-statement. The study is scientifically valid and, despite limited documentation, fully adequate for assessment.
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
(of 1981)
Deviations:
no
Qualifier:
according to
Guideline:
other: Appraisal of Chemicals in Food, Drugs and Cosmetics. The Association of Food and Drug Officials of the United States.
Deviations:
not specified
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: adult
- Weight at study initiation: 3.0 kg (average weight)
- Housing: individual cages
- Diet: standard laboratory diet for rabbits, Altromin, Lage, Germany)
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 2°C
- Humidity (%):50-60
- Photoperiod (hrs dark / hrs light): 12 / 12
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
yes
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
Duration of treatment / exposure:
4 hours
Observation period:
7 days
Number of animals:
5
Details on study design:
TEST SITE
- Area of exposure: approx. 6 cm2 (gauze patches of 2.5 x 2.5 cm, fixed with adhesive plaster)

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: 4 hours

TIME POINTS OF SKIN EVALUATION
- 1, 24, 48 and 72 h and 7 days post patch removal

SCORING SYSTEM:
According to Draize 1959 (“Dermal toxicity,” Appraisal of Chemicals in Food, Drugs and Cosmetics. The Association of Food and Drug Officials of the United States):
Erythema and formation of scabs:
Score 0: No erythema
Score 1: Slight erythema (scarcely visible)
Score 2: Erythema clearly visible
Score 3: Moderate to significant erythema
Score 4: Severe erythema (red purple) with formation of slight scabs (deep lesions)

Formation of oedema:
Score 0: No oedema
Score 1: Very slight oedema (scarcely visible)
Score 2: Slight oedema (well defined outlines, swelling apparent)
Score 3: Moderate oedema (thickness about 1 mm)
Score 4: Severe oedema (thickness more than 1 mm and area larger than the treated skin square)

Only differences from controls were considered to be positive reactions.
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
no effects
Other effects:
No effects on mortality or clinical signs were reported.

Scoring of Erythema and Oedema Formation

Time point

  1 h

  24 h

  48 h

  72 h

  7 d

Animal No

1

2

3

4

5

1

2

3

4

5

1

2

3

4

5

1

2

3

4

5

1

2

3

4

5

Erythema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Oedema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the present experiment the test material was found to cause no irritation when applied to intact rabbit skin.
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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The study was conducted in a contract research organization according to internationally accepted technical guidelines then at force, but without QA-statement. The study is scientifically valid and, despite limited documentation, fully adequate for assessment.
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
of 1981
Deviations:
no
Qualifier:
according to
Guideline:
other: Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics, Division of Pharmacology, FDA
Deviations:
not specified
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Age at study initiation: adults
- Weight at study initiation: 2.5-3.0 kg
- Housing: individual cages
- Diet: standard laboratory diet for rabbits ( Altromin, Lage, Germany). The animals were starved for 16 hours prior to application.
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18±2°C
- Humidity (%): 50-60%
- Photoperiod (hrs dark / hrs light): 12 / 12
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.1 g of the test material was applied into the conjunctival pouch of one eye per rabbit. The contralateral eye remained untreated to serve as a control.
Duration of treatment / exposure:
single exposure
Observation period (in vivo):
- Readings of eye alterations were made after 1, 2, 4, and 24 hours and daily thereafter up to 7 days after administration.
- Grades attained at 24, 48 and 72 hours after administration were included in the mean gradings of ocular lesions used for eye irritation/corrosion classification.
Number of animals or in vitro replicates:
8
Details on study design:
Before and after the test the eyes of all animals were examained with fluorescin (2%) under UV light. After weighing (16 hours starved) 0.1 g of the substance was applicated into the conjunctival pouch of the left eye. The right one stayed untreated and served as control.

REMOVAL OF TEST SUBSTANCE
The test material was not removed.

SCORING SYSTEM:
Eye lesions were scored according to the system of Draize:
1. Cornea
- Degree of opacity:
Score 0: No opacity (nor loss of brilliancy or lustre)
Score 1: Presence of an irritated area of diffused or disseminated appearance, details of the iris clearly visible
Score 2: Presence of a translucid, irritated area easily identifiable, details of the iris slightly obscured
Score 3: Presence of an opalescent, irritated area, details of the iris visible, outline of the pupil can scarcely be observed
Score 4: Presence of opacity making the iris invisible

- Area of opacity:
Score 1: 1/4 (or less), but not zero
Score 2: Between 1/4 and 1/2
Score 3: Between 1/2 and 3/4
Score 4: From 3/4 to the whole area

2. Iris
Score 0: Normal
Score 1: Clearly more plicate than normal, congestion, swelling circumcorneal injection (one or several of these characteristics), iris still reacting to light (a slow reaction is a positive reaction)
Score 2: No reaction to light, haemorrhage, significant "destruction" (one, several or all of these characteristics)


3. Conjunctiva
- Reddening of the palpebral conjunvtiva:
Score 0: Vessels normal
Score 1: Vessels clearly more injected than normal
Score 2: Bright red colour, more diffuse, vessels difficult to distinguish
Score 3: Diffuse blood red colour

- Chemosis:
Score 0: No swelling
Score 1: Slight swelling, including the nictitating membrane
Score 2: Pronounced swelling, with inversion of the eyelid
Score 3: Swelling with eyelids half closed
Score 4: Swelling with eyelid closed more than half-way or completely closed

- Lacrimation:
Score 0: Absence
Score 1: Slight lacrimation (do not take into account slight secretions normally in the inside corner)
Score 2: Lacrimation with moistening of the eyelids and hairs around the eyelids
Score 3: Lacrimation with moistening of the eyelids and heirs on wide areas around the eye

TOOL USED TO ASSESS SCORE: fluorescein
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
over 8 animals and 3 time points
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
other: Area of opacity
Basis:
mean
Remarks:
over 8 animals and 3 time points
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Remarks:
over 8 animals and 3 time points
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
over 8 animals and 3 time points
Time point:
24/48/72 h
Score:
0
Max. score:
3
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
over 8 animals and 3 time points
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
other: lacrimation score
Basis:
mean
Remarks:
over 8 animals and 3 time points
Time point:
24/48/72 h
Score:
0
Max. score:
3
Irritant / corrosive response data:
Up to 4 hours after the application, the treated conjunctiva of all animals showed very slightly redness, chemosis and secretion (score 1). After 24 hours post application, no irritations have been observed at all.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the results and according to the EC criteria for classification and labelling (REGULATION (EC) 1272/2008, the test material does not have to be classified and has no obligatory labelling requirement as irritating to eyes.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

In the in vivo skin and eye irritation studies in rabbits no effects were observed in the presence of the test substance. Therefore, classification of WS400505 for skin or eye irritation is not required [REGULATION (EC) 1272/2008].