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Description of key information

The skin irritating potential of the test substance was tested in an OECD guideline in-vivo study. An irritation potential to the skin of rabbits was found (BASF, 1999).
The eye irritating potential of the test substance was tested in an OECD guideline in-vivo study. An irritation potential to the eyes of rabbits was found (BASF, 1999).

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:
1999-06-14 to 1999-11-23
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP and guideline study
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
1992
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Version / remarks:
1992
Deviations:
no
GLP compliance:
yes
Test material information:
Composition 1
Species:
rabbit
Strain:
Himalayan
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Boehringer Ingelheim Pharma KG
- Age at study initiation: Young adult animals
- Weight at study initiation: 2.72 - 2.97 kg
- Housing: single housing in stainless steel wire mesh cages with grating, floor area : 3000 cm2. No bedding in the cages; wood shavings in the waste trays.
- Diet: Kliba-Labordiet, Klingentalmuehle AG, Kaiseraugst, Switzerland, (about 130 g per animal per day).
- Water: About 250 mL tap water per animal per day.
- Acclimation period: Acclimatization for at least 1 week.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Air changes (per hr): fully air-conditioned rooms
- Photoperiod: 12 h/12 h (6.00 a.m.- 6.00 p.m./6.00 p.m.- 6.00 a.m.)
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated skin sites of the same animal
Amount / concentration applied:
The test patch (2.5 cm x 2.5 cm) was moistened with 0 .5 mL of the unchanged liquid test substance.
Duration of treatment / exposure:
4 h
Observation period:
14 d
Number of animals:
3 males
Details on study design:
TEST SITE
- Area of exposure: Upper third of the back or flanks.
- Type of wrap: Idealbinde, Pfaelzische Verbandstoff-Fabrik, Kaiserslautern and Fixomull(R) stretch (adhesive fleece), Beiersdorf AG

REMOVAL OF TEST SUBSTANCE
- Washing: The test substance was removed at the end of the exposure period with Lutrol(R) = (Polyethylenglycol) and Lutrol(R)/water (1 :1).
- Time after start of exposure: 4 h

SCORING SYSTEM: according to OECD 404 (1992) and EEC directive 92/69 L383A B.4

- Body weight determination: Shortly before application of the test substance.
- Readings: 1 h, 24 h, 48 h, 72 h, 7 d and 14 d after removal of the patch.
- Mortality: A check for any dead or moribund animal was made twice each workday and once on saturdays, sundays and on public holidays.
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 24 h - 48 h - 72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 14 d
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 24 h - 48 h - 72 h
Score:
3.7
Max. score:
4
Reversibility:
not fully reversible within: 14 d
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 24 h - 48 h - 72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 14 d
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 24 h - 48 h - 72 h
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 14 d
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 24 h - 48 h - 72 h
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 14 d
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: 24 h - 48 h - 72 h
Score:
2.3
Max. score:
4
Reversibility:
not fully reversible within: 14 d
Irritant / corrosive response data:
Erythema and edema extending beyond the area of exposure were observed for all three animals from 24 h onward. All three animals showed eczematoid skin change extending beyond the area of exposure after 7 days. Edema were fully reversible for two of three animals, whereas erythema were not fully reversible within 14 days of observation.
Interpretation of results:
irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (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:
1999-06-24 to 1999-11-23
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP and guideline study
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
1987
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
1992
Deviations:
no
GLP compliance:
yes
Test material information:
Composition 1
Species:
rabbit
Strain:
Himalayan
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Boehringer Ingelheim Pharma KG
- Age at study initiation: Young adult animals
- Weight at study initiation: 2.41 - 2.70 kg
- Housing: Single housing in stainless steel wire mesh cages with grating, floor area : 3000 cm2. No bedding in the cages; wood shavings in the waste trays.
- Diet: Kliba-Labordiaet, Provimi Kliba SA, Kaiseraugst, Switzerland, ad libitum
- Water: Tap water ad libitum
- Acclimation period: For at least 1 week .

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Air changes (per hr): Fully air-conditioned rooms.
- Photoperiod (hrs dark / hrs light): 12 h/12 h (6 .00 a.m. - 6 .00 p.m./6 .00 p.m . - 6 .00 a .m.)
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated eye of the same animal
Amount / concentration applied:
0.1 mL (unchanged)
Duration of treatment / exposure:
single dose for 24 hours
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
1 female
2 males
Details on study design:
- Application: The test substance was applied in a single dose to the conjunctival sac of the right eyelid. Both eyes of the animal(s) were examined before application of the test material for signs of pre-existing irritation, reaction or abnormality which would prevent it from being used in the study.
- Readings: 1 h, 24 h, 48 h, 72 h and 7 d after application.
- Mortality: A check for any dead or moribund animal was made twice each workday and once on saturdays, sundays and on public holidays.

REMOVAL OF TEST SUBSTANCE
- Washing: the substance was washed out with tap water about 24 hours after application (before 24 hour reading).
- Time after start of exposure: 24 hours

SCORING SYSTEM: as specified in OECD 405 (1987) and EEC directive 92/69, L 383A, B.5 (1992)
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 24 h - 48 h - 72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 7 d
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: 24 h - 48 h - 72 h
Score:
2.3
Max. score:
3
Reversibility:
fully reversible within: 7 d
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: 24 h - 48 h - 72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 7 d
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 24 h - 48 h - 72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 7 d
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: 24 h - 48 h - 72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 7 d
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: 24 h - 48 h - 72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 7 d
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: 24 h - 48 h - 72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
other: 24 h - 48 h - 72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 d
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
other: 24 h - 48 h - 72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 d
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: 24 h - 48 h - 72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #2
Time point:
other: 24 h - 48 h - 72 h
Score:
0.3
Max. score:
2
Reversibility:
fully reversible within: 48 h
Irritation parameter:
iris score
Basis:
animal #3
Time point:
other: 24 h - 48 h - 72 h
Score:
0.3
Max. score:
2
Reversibility:
fully reversible within: 48 h
Irritant / corrosive response data:
One of three animals showed small retractions in the eyelid (24 h - 72 h). Loss of corneal tissue was observed for two of three animals (48 h - 72 h), aswell as discharge of blood and suppuration occured for one animal after 48 h. All symptons were reversible within 7 days.
Interpretation of results:
irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

The potential of the test item to cause acute dermal irritation or corrosion was assessed by a single topical application of 0.5 mL of the test substance to the intact skin of 3 Himalayan rabbits for 4 hours under semiocclusive dressing. The individual average scores (24 to 72 hours) for each animal for irritation was calculated to be 3.0, 3.7, and 3.0 for erythema and 3.0, 3.0, and 2.3 for edema, respectively. The skin findings were not reversible in all animals within 14 days after removal of the patches (study termination). Symptoms observed and together with the average scores for irritation indicate an irritant property of the test substance to the skin. Under the test conditions chosen and considering the described findings the test item gives indication of an irritant property to the skin.

Eye irritation

The potential of the test item to cause damage to the conjunctiva, iris or cornea was assessed in 3 Himalayan rabbits, subjected to a single ocular application of 0.1 mL of the test substance. The individual average scores (24 to 72 hours) for each animal for irritation was calculated to be 0.3,1.0, and 1.0 for corneal opacity, 0.0, 0.3, and 0.3 for iris, 2.0, 2.3, and 2.0 for conjunctival redness and 1.3, 1,3, and 1.3 for chemosis, respectively. The findings were reversible in all animals within 7 days after application; thus the study was terminated. Symptoms observed together with the average scores for irritation indicate an irritant property of the test substance to the eye. Under the test conditions chosen and considering the described findings the test item gives indication of an irritant property to the eye.


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

Justification for selection of eye irritation endpoint:
GLP and guideline study

Effects on skin irritation/corrosion: irritating

Effects on eye irritation: irritating

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008
The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. As a result the substance is considered to be classified as Category 2B (H319; causes serious eye irritation) and Category 2 (H315; causes skin irritation) under Regulation (EC) No 1272/2008, as amended for the seventh time in Regulation (EU) No 2015/491.