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Description of key information

PR185

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

The test item did not induce significant or irreversible damage to the rabbit eye in this study 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:
2006
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study (OECD TG 404), performed under GLP
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: Charles River Deutschland GmbH, Kisslegg, Germany
- 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. 85/05; 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:
water
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.5 g/animal moistened with appr. 0.5 mL purified water

VEHICLE
- Amount applied: 0.5 mL/animal
Duration of treatment / exposure:
4 h
Observation period:
14 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
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility not applicable since no effect
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility not applicable since no effect
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility not applicable since no effect
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility not applicable since no effect
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility not applicable since no effect
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility not applicable since no effect
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
At the first observation, 1 hour after the application, erythema was not assessable due to marked red staining by the test item. This staining persisted as a light staining until the end of the 14 day observation period. No irritant or corrosive effects were noted on the treated skin of any animal at any of the measuring intervals (all scores for erythema or edema = 0) and no clinical signs were observed.
Other effects:
no other effects observed
Interpretation of results:
GHS criteria not met
Conclusions:
The test item did not reveal any 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 to the intact left 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, 10 and 14 days after removal of the dressing. The mean score was calculated across 3 scoring times (24, 48 and 72 hours after patch removal) for each animal for erythema/eschar grades and for oedema grades, separately. The test item did not elicit any skin reactions at the application site of any animal at any of the observation times (all scores 0). The individual mean score for erythema/eschar and oedema for each of the three animals was therefore 0. At the first observation, 1 hour after the application, erythema was not assessable due to marked red staining by the test item. This staining persisted as a light staining until the end of the 14 day observation period. No irritant or corrosive effects were noted on the treated skin of any animal at any of the measuring intervals and no clinical signs were observed.

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:
2006
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study (OECD TG 405), performed under GLP
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, NM Horst, The Netherlands
- Age at study initiation: 11-12 weeks (male), 12-15 weeks (females)
- 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. 85/05; provided by Provimi Kliba AG, CH-4303 Kaiseraugst); ad libitum
- Water: Community tap water from Füllinsdorf, ad libitum
- Acclimation period: 5 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:
single application, the treated eyes were not rinsed after instillation
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
3 (1 male, 2 females)
Details on study design:
SCORING SYSTEM:
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:
other: 24-48-72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritation parameter:
cornea opacity score
Basis:
animal: #2 and #3 each
Time point:
other: mean of 24-48-72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility not applicable since no effect
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24-48-72 h
Score:
0
Max. score:
2
Reversibility:
other: reversibility not applicable since no effect
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #1
Time point:
other: mean of 24-48-72 h
Score:
0.67
Max. score:
3
Reversibility:
fully reversible within: 48 h
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal: #2 and #3 each
Time point:
other: mean of 24-48-72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24-48-72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility not applicable since no effect
Irritant / corrosive response data:
The mean score was calculated across 3 scoring times (24, 48 and72 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 0.33, 0.00 and 0.00 and for the iris 0.00 for all three animals. The individual mean scores for the conjunctivae were 0.67, 1.00 and 1.00 for reddening, respectively, and 0.00 for chemosis for each of the three animals.
A very slight corneal opacity affecting the whole area was noted in all treated animals 1 hour after the test item instillation and was still present in one animal at the 24 -hour reading. No abnormal findings were observed in the iris of any animal at any of the measurement intervals.
Moderate reddening of the conjunctivae was noted in all animals at the 1 -hour reading. 24 hours after instillation the reddening was still moderate in one animal and slight in two animals. Slight reddening was noted in two animals at the 48- and 72-hour readings.
Reddening of the sclerae was moderate in one animal and slight in two animals 1 hour after instillation. Slight reddening of the sclerae was observed in all animals at the 24-hour reading and was still present in two animals 48 and 72 hours after the treatment.
Slight ocular discharge was observed in all treated animals 1 hour after the instillation and was still present in two animals 24 hours after the test item instillation.
No abnormal findings were observed in the treated eye of anyanimal 7 days after treatment, the end of the observation period for all animals.
Other effects:
No clinical signs of systemic toxicity were observed in the animals during the study and no mortality occurred.
Interpretation of results:
GHS criteria not met
Conclusions:
The test item did not induce significant or irreversible damage to the rabbit eye in this study according to OECD test guideline no. 405 and GLP conditions.
Executive summary:

The eye irritating potential of the test item was assessed according to OECD TG 405. Three rabbits were exposed to 0.1 mg test item. The mean score was calculated across 3 scoring times (24, 48 and72 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 0.33, 0.00 and 0.00 and for the iris 0.00 for all three animals. The individual mean scores for the conjunctivae were 0.67, 1.00 and 1.00 for reddening,respectively, and 0.00 for chemosis for each of the three animals.

A very slight corneal opacity affecting the whole area was noted in all treated animals 1 hour after the test item instillation and was still present in one animal at the 24 -hour reading. No abnormal findings were observed in the iris of any animal at any of the measurement intervals.

Moderate reddening of the conjunctivae was noted in all animals at the 1 -hour reading. 24 hours after instillation the reddening was still moderate in one animal and slight in two animals. Slight reddening was noted in two animals at the 48- and 72-hour readings.

Reddening of the sclerae was moderate in one animal and slight in two animals 1 hour after instillation. Slight reddening of the sclerae was observed in all animals at the 24-hour reading and was still present in two animals 48 and 72 hours after the treatment.

Slight ocular discharge was observed in all treated animals 1 hour after the instillation and was still present in two animals 24 hours after the test item instillation.

No abnormal findings were observed in the treated eye of anyanimal 7 days after treatment, the end of the observation period for all animals.

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 for skin and eye irritation. No adverse effects observed.

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