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Description of key information

The test substance was investigated in vivo in rabbits for its skin irritation/corrosion and eye irritation/ corrosion potential according to international accepted guidelines. 
Skin irritation: For the skin, no irritation potential was observed under selected testing conditions.
Eye irritation: For the eye, a single application produced slight but transient effects which were fully reversible within the observation period. Therefore the test substance was considered to be not irritant to the eye.

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:
2006-12-06 to 2006-12-18
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP and guideline compliant
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
(2002)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Version / remarks:
(2004)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan Netherlands BV, Kreuzelweg 53, NL-5961 NM Horst/ The Netherlands
- Age at study initiation: 12 weeks (male), 13 and 14 weeks (females)
- Weight at study initiation: 2.3 - 2.6 kg
- Housing: Individually in stainless steel cages equipped with feed hoppers and drinking water bowls. Wood blocks (RCC Ltd, Füllinsdorf) and haysticks 4642 (batch no. 77/05, Provimi Kliba AG) were provided for gnawing.
- Diet: Pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad libitum (batch no. 66/06) provided by Provimi Kliba AG, CH-4303 Kaiseraugst.
- Water: Community tap water from Füllinsdorf, ad libitum. Results of bacteriological, chemical and contaminant analyses are archived at RCC Ltd.

ENVIRONMENTAL CONDITIONS
- Temperature: 17-23 °C
- Humidity: 30- 70 %
- Air changes: 10- 15/ hour
- Photoperiod: 12 hours light and 12 hours dark
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.5 mL
- Concentration: Undiluted
Duration of treatment / exposure:
4 hours
Observation period:
The skin reaction was assessed at approximately 1, 24, 48 and 72 hours after exposure
Number of animals:
One male and two female animals
Details on study design:
TEST SITE
- Area of exposure: Left flank
- % coverage: 100 % of a test site with 10 cm x 10 cm
- Type of wrap if used: 0.5 mL of test item was placed on a surgical gauze patch (2.5 cm x 2.5 cm).This gauze patch was applied to the intact skin of the clipped area. The patch was covered with a semi-occlusive dressing. The dressing was wrapped around the abdomen and anchored with tape.

REMOVAL OF TEST SUBSTANCE
- Washing: The dressing was removed and the skin was flushed with lukewarm tap water to clean the application site
- Time after start of exposure: 4 hours

SCORING:
According to the numerical scoring system listed in the Commission Directive 2004/73/EC, April 29, 2004.
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 24, 48 and 73 hours
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Irritant / corrosive response data:
One hour after the treatment a very slight erythema was noted in one of the test animals. Otherwise no signs of irritation were observed in any animal at any observation. No abnormal findings were observed on the treated skin of any animal 24 hours after treatment.
Other effects:
none
Interpretation of results:
not irritating
Remarks:
Migrated information
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:
2006/12/20-2007/01/02
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP and guideline compliant.
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
(2002)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
(2002)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Harlan Netherlands BV, Kreuzelweg 53, NL-5961 NM Horst / The Netherlands
- Age at study initiation: 11 weeks (male), 11−12 weeks (females)
- Housing: Individually in stainless steel cages equipped with feed hoppers and drinking water bowls. Wood blocks (RCC Ltd, Füllinsdorf) and haysticks 4642 (batch no. 77/05, Provimi Kliba AG) were provided for gnawing.
- Diet: Pelleted standard Provimi Kliba 3418 rabbit maintenance diet, ad libitum, provided by Provimi Kliba AG, 4303 Kaiseraugst Switzerland
- Water: tap water

ENVIRONMENTAL CONDITIONS
- Temperature: 17 - 23 °C
- Humidity: 30 - 70 %
- Air changes: 10 - 15 air changes per hour
- Photoperiod: 12 hours light and 12 hours dark
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
0.1 mL (per animal) of test item was measured with a syringe and applied undiluted. The pH of the test item was measured and was found to be 10.69.
Duration of treatment / exposure:
0.1 mL of test item was placed in the conjunctival sac of the left eye of each animal after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second to prevent loss of test item. The right eye remained untreated and served as the reference control. The treated eyes were not rinsed after instillation. As it was suspected that the test item might produce irritancy, a single animal (one female) was treated first.
Observation period (in vivo):
24 hours
Number of animals or in vitro replicates:
3 males and 3 females
Details on study design:
SCORING SYSTEM: The eye reactions were assessed according to the numerical scoring system listed in the Commission Directive 2004/73/EC, April 29, 2004. Scleral reddening and ocular discharge were also assessed.

TOOL USED TO ASSESS SCORE: Eye examinations were made with a Varta Cliptrix diagnostic-lamp (Roth AG, CH-4153 Reinach/Switzerland).
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal 1,2,3
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal 1, 2, 3
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 24, 48 and 72 hours
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: 24, 48 and 72 hours
Score:
0.66
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: 24, 48 and 72 hours
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 24, 48 and 72 hours
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Irritant / corrosive response data:
No abnormal findings were observed in the cornea or iris of any animal at any of the measurement intervals. Moderate reddening of the conjunctivae was noted in the treated eyes of all animals one hour after test item instillation. The reddening persisted as moderate in two animals on the following day and had faded into slight in one animal at this time. Slight reddening of the conjunctivae was still present in the treated eyes of the three animals at the 48- hour reading. Obvious swelling (chemosis) of the conjunctivae with partial eversion of the lids was observed in two of the animals one hour after the treatment. The swelling persisted as slight in one animal at the 24- hour examination. Moderate or slight reddening of the sclerae was present in all test animals at the 1- hour reading and persisted in two animals still in the 24- hour evaluation. Slight or moderate ocular discharge was noted in the three test animals one hour after instillation was still present in one animal at the 24- hour reading. No abnormal findings were observed in the treated eye of any animal 72 hours after treatment at the end of the observation period for all animals. No staining of the eyes or test item remnants were noted at any examination. No corrosion of the cornea was observed at any of the reading times. The bod weights of all rabbits were considered to be within the normal range of variability.
Other effects:
none
Interpretation of results:
not irritating
Remarks:
Migrated information
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

The primary skin irritation potential of the test substance was investigated according to OECD 404, adopted in 2002. The test substance was applied by topical semiocclusive application of 0.5 mL 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 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 mean erythema/ eschar score and the mean oedema score were 0.00 for each of the three animals. The application of the test item to the skin resulted in a very slight erythema in one animal. This effect was reversible and no longer evident 24 hours after treatment. Two animals remained completely negative. The test item caused no staining of the treated skin. 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 substance did not induce significant or irreversible damage to the skin.

Eye irritation

The primary eye irritation potential of the test substance was investigated according to OECD 405, adopted in 1997. The test substance was applied by instillation of 0.1 mL into the left eye of each of three young adult New Zealand White rabbits. Scoring of irritation effects was performed approximately 1, 24, 48 and 72 hours 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 and iris were 0.00 for all three animals. The individual mean scores for the conjunctivae were 1.00, 0.67 and 1.00 for reddening and 0.33, 0.00 and 0.00 for chemosis, respectively. The instillation of the test item into the eye resulted in mild to moderate, early- onset and transient ocular changes, such as reddening of the conjunctivae and sclerae, discharge and chemosis. These effects were reversible and were no longer evident 72 hours after treatment, the end of the observation period for all animals. No abnormal findings were observed in the cornea or iris of any animal at any of the examinations. No corrosion was observed at any of the measuring intervals. No staining of the treated eyes by the test substance was observed and no clinical signs were observed. Thus, the test substance did not induce significant or irreversible damage to the rabbit eye.


Justification for selection of skin irritation / corrosion endpoint:
GLP and guideline compliant.

Justification for selection of eye irritation endpoint:
GLP and guideline compliant.

Justification for classification or non-classification

Based on the available data the test substance is considered to be “not irritating” to rabbit skin. Therefore there is no need for classification and labeling acorrding to Directive 67/548/EEC (DSD) and Regulation (EC) No 1272/2008 (CLP).

Based on the available data the test substance is considered to be “not irritating” to rabbit eye. Therefore there is no need for classification and labeling acorrding to Directive 67/548/EEC (DSD) and Regulation (EC) No 1272/2008 (CLP).