Registration Dossier

Administrative data

Description of key information

The test item did not reveal any remarkable irritation potential on the skin of rabbits, tested according to OECD test guideline no. 404 and GLP conditions.

The test item did not reveal any remarkable irritation potential on the eyes of rabbits, tested according to OECD test guideline no. 405 and GLP conditions.

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 28 Jun 2006 to 13 JUL 2006
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study (OECD TG 404)
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan Netherlands BV, Horst, The Netherlands
- Age at study initiation: 11-12 weeks
- Housing: Individually in stainless steel cages equipped with feed hoppers and drinking water bowls.
- Diet: Pelleted standard Provimi Kliba 3418 rabbit maintenance diet (batch no. 24/06; provided by Provimi Kliba AG, CH-4303 Kaiseraugst); ad libitum
- Water: Community tap water from Füllinsdorf, ad libitum
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23
- Humidity (%): 30-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
other: clipped
Vehicle:
other: purified water
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.5 g/animal (mixed with 0.5 ml of purified water)
VEHICLE
- Amount applied: about 0.5 mL/animal
Duration of treatment / exposure:
4 h
Observation period:
10 days
Number of animals:
3 (1 male, 2 females)
Details on study design:
TEST SITE
- Area of exposure: 4 cm x 4 cm

REMOVAL OF TEST SUBSTANCE
- Washing (if done): flushed with lukewarm tap water
- Time after start of exposure: 4 h

SCORING SYSTEM:
Grading of Skin Reactions according to COMMISSION DIRECTIVE 2004/73/EC, APRIL 29, 2004
ERYTHEMA AND ESCHAR FORMATION
No erythema.......................................................................................................................0
Very slight erythema............................................................................................................1
Well-defined erythema........................................................................................................2
Moderate to severe erythema.............................................................................................3
Severe erythema (beef redness) or eschar formation (injuries in depth preventing erythema) reading.................................................4

OEDEMA FORMATION
No oedema.........................................................................................................................0
Very slight oedema (barely perceptible)..............................................................................1
Slight oedema (edges of area well-defined by definite raising)..........................................2
Moderate oedema (edges raised approximately 1 mm).....................................................3
Severe oedema (raised more than 1 mm and extending beyond the area of exposure)...4

Skin reaction was assessed at approximately 1, 24, 48 and 72 hours, as well as 7 and 10 days after exposure.
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility not applicable
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible
Remarks:
within 7 days
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible
Remarks:
with 72 hours
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility not applicable
Irritant / corrosive response data:
Individual animal data for animal #1, #2, #3 at time point 1h / 24h / 48h / 72 h / 7days / 10 days.

Edema score: 0/0/0/0/0/0, 0/0/0/0/0/0, 0/0/0/0/0/0
Erythema score: 1/1/1/1/0/0, 1/1/1/0/0/0, 0/0/0/0/0/0
Interpretation of results:
GHS criteria not met
Remarks:
Regulation (EC) no 1272/2008
Conclusions:
The test item did not reveal any remarkable irritation potential on the skin of rabbits, tested in this study according to OECD test guideline no. 404 and GLP conditions.
Executive summary:

The primary skin irritation potential of the test item was investigated according to OECD test guideline no. 404. The test item was applied by topical semi-occlusive application of 0.5 g mixed with 0.5 ml of purified water to the intact flank of each of three young adult New Zealand White rabbits. The duration of treatment was four hours. The scoring of skin reactions was performed 1, 24, 48 and 72 hours, as well as 7 and 10 days after removal of the dressing.

The mean score was calculated across 3 scoring times (24, 48 and 72 hours) for each animal for erythema/eschar grades and for oedema grades, separately. The mean erythema/eschar score of the three animals was 1.00, 0.67 and 0.00, respectively, and the mean oedema score was 0.00 for each of the three rabbits.

The application of test item to the skin resulted in very slight erythema. These effects were reversible and were no longer evident 7 days after treatment. The test item caused a yellow staining of the treated skin which persisted up to 7 days after treatment. No corrosive effects were noted on the treated skin of any animal at any of the measuring intervals and no clinical signs were observed.

Thus, the test item did not induce significant or irreversible damage to the 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
Study period:
From 12 JUL 2006 to 24 JUL 2006
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study (OECD TG 405)
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: 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: Harlan Netherlands BV, Horst, The Netherlands
- Age at study initiation: 10-14 weeks
- Housing: Individually in stainless steel cages equipped with feed hoppers and drinking water bowls.
- Diet: Pelleted standard Provimi Kliba 3418 rabbit maintenance diet (batch no. 24/06; provided by Provimi Kliba AG, CH-4303 Kaiseraugst); ad libitum
- Water: Community tap water from Füllinsdorf, ad libitum
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23
- Humidity (%): 30-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.1 g
Duration of treatment / exposure:
7 days (single application, the treated eyes were not rinsed after application)
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
3 (1 male, 2 females)
Details on study design:
SCORING SYSTEM: Reading was done at time point 1, 7, 24, 48 and 72 h as well as 7 days.
Grading of Ocular Lesions according to COMMISSION DIRECTIVE 2004/73/EC, APRIL 29, 2004; comparable to Draize system

CORNEA
Opacity: degree of density (area most dense taken for reading)
No ulceration or opacity.......................................................................................................0
Scattered or diffuse areas of opacity (other than slight dulling of normal luster),
details of iris clearly visible..................................................................................................1
Easily discernible translucent area, details of iris slightly obscured...................................2
Nacreous area, no details of iris visible, size of pupil barely discernible............................3
Opaque cornea, iris not discernible through the opacity.....................................................4

IRIS
Normal................................................................................................................................0
Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperemia, or injection, any of these or combination of any thereof, iris still reacting to light (sluggish reaction is positive)..............................................................................................1
No reaction to light, hemorrhage, gross destruction (any or all of these)...........................2

CONJUNCTIVAE
Redness (refers to most severe reading of palpebral and bulbar conjunctivae when compared with control eye)
Blood vessels normal..........................................................................................................0
Some blood vessels definitely hyperemic (injected)...........................................................1
Diffuse, crimson color, individual vessels not easily discernible.........................................2
Diffuse beefy red.................................................................................................................3

Chemosis: lids and/or nictitating membranes
No swelling.........................................................................................................................0
Any swelling above normal (including nictitating membranes)...........................................1
Obvious swelling with partial eversion of lids......................................................................2
Swelling with lids about half-closed.....................................................................................3
Swelling with lids more than half-closed.............................................................................4

TOOL USED TO ASSESS SCORE:
Eye examinations were made with a Varta Cliptrix diagnostic-lamp (Roth AG, Reinach/Switzerland).
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility not applicable
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
ca. 0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: reversibility not applicable
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal: #1 and #2 each
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 72 h
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 72 h
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 48 h
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility not applicable
Irritant / corrosive response data:
Individual animal data for animal #1, #2, #3 at time point 1h / 24h / 48h / 72 h / 7 days

cornea score: 1/0/0/0/0, 1/1/0/0/0, 1/0/0/0/0
iris score: 0/0/0/0/0, 0/0/0/0/0, 0/0/0/0/0
conjunctivae redness: 1/1/1/1/0, 1/1/1/1/0, 1/1/0/0/0
chemosis: 1/0/0/0/0, 1/0/0/0/0, 0/0/0/0/0
Interpretation of results:
GHS criteria not met
Remarks:
Regulation (EC) no 1272/2008
Conclusions:
The test item did not reveal any remarkable irritation potential on the eyes of rabbits, tested in this study according to OECD test guideline no. 405 and GLP conditions.
Executive summary:

The primary eye irritation potential of the test item was investigated according to OECD test guideline no 405.The test item was applied by instillation of 0.1 g into the left eye of each of three young New Zealand White rabbits. The scoring of irritating effects was performed 1, 24, 48 and 72 hours as well as 7 days after test item instillation.

The mean score was calculated across 3 scoring times (24, 48 and 72 hours after instillation) for each animal for corneal opacity, iris, redness and chemosis of the conjunctivae, separately. The individual mean scores for corneal opacity were 0.00, 0.33 and 0.00 for the three animals. The individual mean score for iris was 0.00 for all three animals. The individual mean scores for the conjunctivae were 1.00, 1.00 and 0.33 for reddening, respectively and 0.00 for chemosis for each of the three animals. A slight corneal opacity affecting the whole area was observed in the treated eyes of all three animals 1 hour after the instillation and was still present in one animal at the 24-hour reading. Slight reddening of the conjunctivae was noted in all three animals from the 1-hour reading on and persisted up to the 24- or 72-hour reading. A slight swelling of the conjunctivae was observed in two animals 1 hour after instillation. Slight reddening of the sclerae was present in all three animals one hour after the instillation and persisted up to the 24-, 48- or 72-hour reading. Slight ocular discharge was observed in all three animals 1 hour after the treatment and still at the 24-hour reading in one animal. Remnants of the test item were noted in the treated eyes of the three animals 1 hour after test item instillation and still at the 24- and 48-hour readings in one animal. No abnormal findings were observed in the treated eye of any animal 7 days after treatment, the end of the observation period for all animals. No corrosion of the cornea was observed at any of the reading times.

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

No classification - No adverse effects observed