Registration Dossier

Administrative data

Description of key information

Eye irritation: Not irritating (based on result of 1 key study)
Skin irritation: Category 2: Irritant (based on a weight of evidence approach from 4 studies)

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1986-02-25 to 1986-03-04
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
Meets generally accepted scientific standards, well documented and acceptable for assessment.
Principles of method if other than guideline:
Test material applied semiocclusively to the skin of 4 rabbits for 4 hrs, at concentrations of 100% and 50 %. Skin reactions were reacorded after 1 hour, 24, 48, 72 hours and 7 days.
GLP compliance:
yes
Remarks:
no certificate
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: A Smith, Warlingham, Surrey, United Kingdom
- Age at study initiation: No data
- Weight at study initiation: No data
- Housing: Individually in anodised aluminium cages with grid floors and no bedding
- Diet: Ad libitum, rabbit pellets (680, Dalgety-Spillers Ltd)
- Water: Mains tap water, ad libitum.
- Acclimation period: ≥ 5 d.

ENVIRONMENTAL CONDITIONS
- Temperature: 18 °C to 24 °C
- Humidity: 40 % - 67 %
- Air changes per hr: No data
- Photoperiod: 12 hrs dark / 12 hrs light
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
other: 100 % solution - no vehicle. 50 % solution DEP
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Volume applied: 0.5 mL:
- Concentration of test substance: 100 %, 50 % in DEP
Duration of treatment / exposure:
4 hrs
Observation period:
7 d (observations at 1 hr, 24 hrs, 48 hrs, 72 hrs and 7 d after removal of test material)
Number of animals:
4 (each animal treated with both concentrations)
Details on study design:
TEST SITE
- Area of exposure: 2.5 cm²
- Type of wrap if used: Elastoplast elastic adhesive barrier, 10 cm width.

REMOVAL OF TEST SUBSTANCE
- Washing: Adhesive tapes removed, gentle swabbing with cotton wool soaked in warm water
- Time after start of exposure: 4 hrs

SCORING SYSTEM:
- Erythema and eschar formation:
-- 0: No erythema
-- 1: Very slighty erythema (barely perceptible)
-- 2: Well-defined erythema
-- 3: Moderate to severe erythema
-- 4: Severe erythema (beet redness) to slight eschar formation (injuries in depth)
- Oedema formation:
-- 0: No oedema
-- 1: Very slight oedema (barely perceptible)
-- 2: Slight oedema (edges of area well defined by definite raising)
-- 3: Moderate oedema (raised approximately 1 mm)
-- 4: Severe oedema (raised more than 1 mm and extending beyond area of exposure)
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Reversibility:
not fully reversible within: 7 d.
Remarks on result:
other: 50% solution. Desquamation at 7 d.
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Reversibility:
fully reversible within: 7 d
Remarks on result:
other: 50% solution. Marked desquamation at 7d.
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Reversibility:
not fully reversible within: 7 d
Remarks on result:
other: 50% solution. Marked desquamation at 7 d.
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
2.67
Reversibility:
not fully reversible within: 7 d
Remarks on result:
other: 50% solution. Marked desquamation at 7 d.
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.67
Reversibility:
fully reversible within: 7 d
Remarks on result:
other: 50% solution
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Reversibility:
fully reversible within: 7 d
Remarks on result:
other: 50% solution
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2.33
Reversibility:
fully reversible within: 7 d
Remarks on result:
other: 50% solution
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
3
Reversibility:
not fully reversible within: 7 d
Remarks on result:
other: 50% solution
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Reversibility:
not fully reversible within: 7 d
Remarks on result:
other: 100% solution. Marked desquamation at 7 d.
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Reversibility:
not fully reversible within: 7 d
Remarks on result:
other: 100% solution. Marked desquamation at 7 d.
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Reversibility:
not fully reversible within: 7 d
Remarks on result:
other: 100% solution. Marked desquamation at 7 d.
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
2.67
Reversibility:
not fully reversible within: 7 d.
Remarks on result:
other: 100% solution. Marked desquamation at 7 d.
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2.67
Reversibility:
not fully reversible within: 7 d.
Remarks on result:
other: 100% solution
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2.67
Reversibility:
not fully reversible within: 7 d
Remarks on result:
other: 100% solution
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2.33
Reversibility:
fully reversible within: 7 d
Remarks on result:
other: 100% solution
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
3
Reversibility:
not fully reversible within: 7 d
Remarks on result:
other: 100% solution
Irritation parameter:
erythema score
Basis:
mean
Remarks:
Of all animals
Time point:
24/48/72 h
Score:
2.2
Remarks on result:
other: 100% solution
Irritation parameter:
edema score
Basis:
mean
Remarks:
Of all animals
Time point:
24/48/72 h
Score:
2.67
Remarks on result:
other: 100% solution
Other effects:
Marked desquamation in rabbits 920, 922 and 923 at 7 d; desquamation in rabbit 916 at 7 d; no other comments.
Interpretation of results:
Category 2 (irritant)
Conclusions:
Two concentrations of cyclamen aldehyde were tested. Classification is based on the study performed with 100%. The study was performed with more than 3 animals. In this case specific provisions apply to the classification criteria in CLP Regulation (EC) no. 1272/2008. In accordance with this classification criteria the test substance is considered to be a Category 2 skin irritant.
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1984-05-01 to 1984-06-12
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
Meets generally accepted scientific standards, well documented and acceptable for assessment.
Principles of method if other than guideline:
Test material applied semiocclusively to the skin of 3 rabbits for 4 hrs, observed for 7 d.
GLP compliance:
yes
Remarks:
no certificate
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Recognised breeders whose standards are acceptable to the Animal Welfare Department of the testing facilities.
- Age at study initiation: No data
- Weight at study initiation:
- Housing: Individually in anodised aluminium cages with grid floors and no bedding materials.
- Diet: Ad libitum - SQC standard rabbit diet, Special Diet Services Ltd, Witham, Essex, United Kingdom.
- Water: Mains tap water ad libitum.
- Acclimation period: ≥ 5 d

ENVIRONMENTAL CONDITIONS
- Temperature: 18 °C - 23 °C
- Humidity: 40 % - 80 %
- Air changes (per hr): No data
- Photoperiod: 12 hrs dark / 12 hrs light
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Volume applied: 0.5 mL
Duration of treatment / exposure:
4 hrs
Observation period:
7 d (observations at 1 hr, 24 hrs, 48 hrs, 72 hrs, 7 d after removal of patch)
Number of animals:
3 females (each animal tested with multiple substances)
Details on study design:
TEST SITE
- Area of exposure: 2.5 cm²
- Type of wrap if used: Elastoplast elastic adhesive barrier, 10 cm width.

REMOVAL OF TEST SUBSTANCE
- Washing: Adhesive tapes removed, gentle swabbing with cotton wool soaked in warm water
- Time after start of exposure: 4 hrs

SCORING SYSTEM:
- Erythema and eschar formation:
-- 0: No erythema
-- 1: Very slighty erythema (barely perceptible)
-- 2: Well-defined erythema
-- 3: Moderate to severe erythema
-- 4: Severe erythema (beet redness) to slight eschar formation (injuries in depth)
- Oedema formation:
-- 0: No oedema
-- 1: Very slight oedema (barely perceptible)
-- 2: Slight oedema (edges of area well defined by definite raising)
-- 3: Moderate oedema (raised approximately 1 mm)
-- 4: Severe oedema (raised more than 1 mm and extending beyond area of exposure)
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2.67
Reversibility:
not fully reversible within: 7 d
Remarks on result:
other: Marked desquamation from skin surface at day 7
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Reversibility:
not fully reversible within: 7 d
Remarks on result:
other: Desquamation from skin surface at day 7
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Reversibility:
not fully reversible within: 7 d
Remarks on result:
other: Desquamation from skin surface at day 7
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
3
Reversibility:
not fully reversible within: 7 d
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
3
Reversibility:
not fully reversible within: 7 d
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2.67
Reversibility:
not fully reversible within: 7 d
Irritant / corrosive response data:
Rabbit 329 had marked desquamation from skin surface at 7 d; rabbits 331 and 337 had desquamation from skin surface at 7 d. No other abnormalities were detected. For full results please refer to the attached supporting materials.
Interpretation of results:
Category 2 (irritant)
Conclusions:
The test material is considered to be a category 2 irritant in accordance with CLP Regulation (EC) no. 1272/2008 .
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1986-07-22 to 1987-07-29
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
Meets generally accepted scientific standards, well documented and acceptable for assessment.
Principles of method if other than guideline:
Test material applied semiocclusively to the skin of 4 rabbits for 4 hrs, at concentrations of 100%, 50 %, 25 %, 10 %. Skin reactions were reacorded after 1 hour, 24, 48, 72 hours and 7 days.
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: A Smith, Warlingham, Surrey, United Kingdom
- Age at study initiation:
- Weight at study initiation:
- Housing: Individually in metal cages with grid floors and no bedding
- Diet: Ad libitum, commercial rabbit pellets (680 Dalgety-Spillers Ltd)
- Water: Mains tap water ad libitum
- Acclimation period: 10 d

ENVIRONMENTAL CONDITIONS
- Temperature: 16 °C - 22 °C
- Humidity: 55 % - 91 %
- Photoperiod: 12 hrs dark / 12 hrs light
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
other: 100 % concentration unchanged (no vehicle); 50 %, 25 % and 10 % solutions in DEP.
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Volume applied: 0.5 mL
- Concentrations: 100 %, 50 %, 25 %, 10 %.
Duration of treatment / exposure:
4 hrs
Observation period:
7 d (observations at 1 hr, 24 hrs, 48 hrs, 72 hrs and 7 d after removal of test material)
Number of animals:
4 females (each animal tested with each concentration)
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Reversibility:
not fully reversible within: 7 d
Remarks on result:
other: 100% solution. Marked desquamation at 7 d.
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Reversibility:
not fully reversible within: 7 d
Remarks on result:
other: 100% solution. Marked desquamation at 7 d.
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Reversibility:
not fully reversible within: 7 d.
Remarks on result:
other: 100% solution. Slight desquamation at 72 h. Marked desquamation at 7 d.
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
2
Reversibility:
not fully reversible within: 7 d
Remarks on result:
other: Marked desquamation at 7 d.
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.33
Reversibility:
fully reversible within: 7 d
Remarks on result:
other: 100% solution
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Reversibility:
fully reversible within: 7 d
Remarks on result:
other: 100% solution
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Reversibility:
fully reversible within: 7 d
Remarks on result:
other: 100% solution
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
1.67
Reversibility:
not fully reversible within: 7 d
Remarks on result:
other: 100% solution
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.33
Reversibility:
fully reversible within: 7 d
Remarks on result:
other: 50% solution. Marked desquamation at day 7.
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1.67
Reversibility:
fully reversible within: 7 d
Remarks on result:
other: 50% solution. Marked desquamation at day 7.
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Reversibility:
not fully reversible within: 7 d
Remarks on result:
other: 50% solution. Marked dequamation at day 7.
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
2
Reversibility:
not fully reversible within: 7 d
Remarks on result:
other: 50% solution. Marked desquamation at day 7
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.67
Reversibility:
fully reversible within: 7 d.
Remarks on result:
other: 50% solution.
Irritation parameter:
edema score
Basis:
animal: # 2 and # 3
Time point:
24/48/72 h
Score:
0
Remarks on result:
other: 50% solution
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
1.33
Reversibility:
fully reversible within: 7 d
Remarks on result:
other: 50% solution
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Reversibility:
fully reversible within: 7 d
Remarks on result:
other: 25% solution. Desquamation at day 7.
Irritation parameter:
erythema score
Basis:
animal: # 2, 3 and 4
Time point:
24/48/72 h
Score:
0
Remarks on result:
other: 25% solution
Irritation parameter:
edema score
Basis:
animal: #1, 2, 3 and 4
Time point:
24/48/72 h
Score:
0
Remarks on result:
other: 25% solution
Irritation parameter:
erythema score
Basis:
animal: # 1, 2, 3 and 4
Time point:
24/48/72 h
Score:
0
Remarks on result:
other: 10% solution
Irritation parameter:
edema score
Basis:
animal: # 1, 2, 3 and 4
Time point:
24/48/72 h
Score:
0
Remarks on result:
other: 10% solution
Irritant / corrosive response data:
At 100 % solution, marked desquamation was observed in all animals at 7d, and slight desquamation at 72 hrs in rabbit 568. At 50 % solution, marked desquamation was observed in all animals at 7d. At 25 % solution, desquamation was observed in rabbit 565. There were no other comments.

For full results please refer to the attached supporting materials.
Interpretation of results:
not irritating
Conclusions:
Four concentrations of cyclamen aldehyde were tested. Classification is based on the study performed with 100%. The study was performed with more than 3 animals. In this case specific provisions apply to the classification criteria in CLP Regulation (EC) no. 1272/2008. In accordance with this classification criteria the test substance is not considered to be classified for skin irritation.
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1985-04-16 to 1985-04-17
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
Meets generally accepted scientific standards, well documented and acceptable for assessment.
Principles of method if other than guideline:
Test material applied semiocclusively to the skin of 4 rabbits for 4 hrs, observed for 7 d.
GLP compliance:
yes
Remarks:
no certificate
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: A Smith, 7 Kydcomb Road, Warlingham, Surrey, United Kingdom.
- Age at study initiation: No data
- Weight at study initiation: No data
- Housing: Individually in anodised aluminium cages with grid floors and no bedding materials.
- Diet: Ad libitum, commercial pelleted rabbit diet (680, Dalgety-Spillers Ltd)
- Water: Mains tap water (presumably ad libitum)
- Acclimation period: ≥ 5 d.

ENVIRONMENTAL CONDITIONS
- Temperature: 18 °C - 22 °C
- Humidity: 42 % - 65 %
- Photoperiod: 12 hrs dark / 12 hrs light
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Volume applied: 0.5 mL
Duration of treatment / exposure:
4 hrs
Observation period:
7 d (observations at 1 hr, 24 hrs, 48 hrs, 72 hrs and 7 d after removal of patch).
Number of animals:
4, female.
Details on study design:
TEST SITE
- Area of exposure: 2.5 cm²
- Type of wrap if used: Elastoplast elastic adhesive barrier, 10 cm width.

REMOVAL OF TEST SUBSTANCE
- Washing: Adhesive tapes removed, gentle swabbing with cotton wool soaked in warm water
- Time after start of exposure: 4 hrs

SCORING SYSTEM:
- Erythema and eschar formation:
-- 0: No erythema
-- 1: Very slighty erythema (barely perceptible)
-- 2: Well-defined erythema
-- 3: Moderate to severe erythema
-- 4: Severe erythema (beet redness) to slight eschar formation (injuries in depth)
- Oedema formation:
-- 0: No oedema
-- 1: Very slight oedema (barely perceptible)
-- 2: Slight oedema (edges of area well defined by definite raising)
-- 3: Moderate oedema (raised approximately 1 mm)
-- 4: Severe oedema (raised more than 1 mm and extending beyond area of exposure)
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Reversibility:
not fully reversible within: 7 d
Remarks on result:
other: Marked desquamation at day 7
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Reversibility:
not fully reversible within: 7 d
Remarks on result:
other: Marked desquamation at day 7
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Reversibility:
not fully reversible within: 7 d
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
2
Reversibility:
not fully reversible within: 7 d
Remarks on result:
other: Desquamation at day 7
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2.33
Reversibility:
not fully reversible within: 7 d
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2.67
Reversibility:
not fully reversible within: 7 d
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Reversibility:
not fully reversible within: 7 d
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
1.67
Reversibility:
fully reversible within: 7 d
Irritation parameter:
erythema score
Basis:
mean
Remarks:
All animals
Time point:
24/48/72 h
Score:
2
Irritation parameter:
edema score
Basis:
mean
Remarks:
All animals
Time point:
24/48/72 h
Score:
2.2
Irritant / corrosive response data:
For full results please refer to attached supporting materials.
Interpretation of results:
slightly irritating
Conclusions:
The study was performed with more than 3 animals. In this case specific provisions apply to the classification criteria in CLP Regulation (EC) no. 1272/2008. In accordance with this classification criteria the test substance is considered to be a skin irritant.
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:
Application on 1979-04-04
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
Meets generally accepted scientific standards, well documented and acceptable for assessment.
Principles of method if other than guideline:
The test article as a 6% w/v concentration in propylene glycol (0.1 ml) was applied to right eyes of 6 rabbits. Eyes were examined before testing and at 24, 48 and 72 hours and at 4 and 7 days. The irritation was scored by the method of Draize.
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: CSE Colony, Branchville, New Jersey, United States
- Age at study initiation:
- Weight at study initiation: 2.0 to 2.75 kg
- Housing: No data
- Diet (e.g. ad libitum): No data
- Water (e.g. ad libitum): No data
- Acclimation period: 7 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data
- Humidity (%): No data
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): No data
Vehicle:
other: Propylene glycol
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL AND VEHICLE
- Volume applied: 0.1 mL
- Concentration of test material: 6 % w/v in propylene glycol
Duration of treatment / exposure:
Single exposure.
Observation period (in vivo):
7 d
Number of animals or in vitro replicates:
6
Details on study design:
NON-REMOVAL OF TEST SUBSTANCE
- No washing

SCORING SYSTEM:
- According to the FDA's "Illustrated guide for Grading Eye Irritation by Hazardous Substances" and the "Scale for Scoring Ocular Lesions". Please refer to attached supporting information for full system.

TOOLS USED TO ASSESS SCORE:
- Hand opthalmascope (1 d, 2 d, 3 d, 4 d, 7 d)
- Fluorescein (1 d, 7 d)
Irritation parameter:
cornea opacity score
Remarks:
opacity
Basis:
animal: # 1,4 and 6
Time point:
24/48/72 h
Score:
0
Irritation parameter:
cornea opacity score
Remarks:
opacity
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.67
Reversibility:
fully reversible within: 4 days
Irritation parameter:
cornea opacity score
Remarks:
opacity
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.33
Reversibility:
fully reversible within: 72 h
Irritation parameter:
cornea opacity score
Remarks:
opacity
Basis:
animal #5
Time point:
24/48/72 h
Score:
0.67
Reversibility:
fully reversible within: 72 h
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.33
Reversibility:
fully reversible within: 48 h
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.33
Reversibility:
fully reversible within: 72 h
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Irritation parameter:
iris score
Basis:
animal: # 4, 5 and 6
Time point:
24/48/72 h
Score:
0.33
Reversibility:
fully reversible within: 48 h
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.33
Reversibility:
fully reversible within: 72 h
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.33
Reversibility:
fully reversible within: 4 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #4
Time point:
24/48/72 h
Score:
0.33
Reversibility:
fully reversible within: 48 h
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #5
Time point:
24/48/72 h
Score:
0.67
Reversibility:
fully reversible within: 72 h
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #6
Time point:
24/48/72 h
Score:
1
Reversibility:
fully reversible within: 72 h
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.33
Reversibility:
fully reversible within: 4 days
Irritation parameter:
chemosis score
Basis:
animal: # 3, 4 and 6
Time point:
24/48/72 h
Score:
0
Irritation parameter:
chemosis score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0.67
Reversibility:
fully reversible within: 72 h
Irritant / corrosive response data:
- No pannus, blistering of the conjunctivae or other effects indicative of corrosive action.
- Ulceration of the corneal surface was observed in 5 rabbits (A421, A446, A431, A450 and A442) at 24 hrs. All had resolved by d 7, except for a pinhead area in A421 which was still retaining dye.
Other effects:
- Rabbit A446 broke its right hind leg while in restraint but remained healthy throughout the study.
- All animals struggled for a short time when the test article was instilled, and tightly closed the dosed eye for 1 hr.
- No other abnormalities of health, behaviour or appearance were observed during the remainder of the study.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test substance is not considered to be irritating to eyes according to CLP Regulation (EC) no. 1272/2008
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Additional information

Eye irritation:

The test article as a 6% w/v concentration in propylene glycol (0.1 ml) was applied to right eyes of 6 rabbits. Eyes were examined before testing and at 24, 48 and 72 hours and at 4 and 7 days. The irritation was scored by the method of Draize. Based on the classification criteria according to CLP Regulation (EC) no. 1272/2008 whererby 6 rabbits have been used in the study the substance is not considered to be classified.

Skin irritation:

4 studies have been conducted in total

Study conducted with 3 animals:

In study 307-338/8403, 0.5 ml of test material was applied semiocclusively to the skin of 3 rabbits for 4 hrs. Observations of skin reactions were observed at 1 hour, 24, 48, 72 hours and at 7 days. Based on the classification criteria set out in accordance with CLP Regulation (EC) no. 1272/2008 the test material is considered to be a category 2 irritant.

 

Studies conducted with 4 animals:

In study 70-101/8503 0.5 ml of test material was applied semiocclusively to the skin of 4 rabbits for 4 hrs. Observations of skin reactions were observed at 1 hour, 24, 48, 72 hours and at 7 days.

 

In study 150-173/8602 0.5 ml of test material was applied semiocclusively to the skin of 4 rabbits for 4 hrs, at concentrations of 100% and 50 %. Skin reactions were recorded after 1 hour, 24, 48, 72 hours and 7 days.

 

In study 53-64/8607 0.5 ml of test material was applied semiocclusively to the skin of 4 rabbits for 4 hrs, at concentrations of 100%, 50 %, 25 %, 10 %. Skin reactions were recorded after 1 hour, 24, 48, 72 hours and 7 days.

 

Whereby 4 animals rather than 3 animals are used in the study the criteria within the Guidance on the Application of the CLP Criteria section 3.2.2.3.2.2 In vivo data, subsection entitled "Tests that have been conducted with more than three animals" applies.

 

That specifies two methods for determining the conclusion:

Method 1: The overall average over all animals will be used.

Method 2: According to the second approach the average score is determined per animal ie Skin Irritant Category 2 is assigned if at least in 3 individuals the mean score exceeds the value of 2.3. 

The more stringent result has to be used if the evaluation according to the first method is different to that of the second method.

  

In study 70-101/8503 according to the first method of evaluation, the arithmetic mean after 24/48/72 hours for erythema ME= 24:12 = 2 and for oedema MO= 26:12 = 2.2. Both values are <2.3 therefore result is considered slightly irritating.

According to the second method a mean value of <2.3 was obtained for erythema in all animals and >2.3 for oedema in 2 animals therefore the result is considered to be negative. As both results are negative using the 2 methods in accordance with this study the substance does not need to be classified.

 

In study 150-173/8602 the results obtained from the 100% solution are used for evaluation. According to the first method of evaluation, the arithmetic mean after 24/48/72 hours for erythema ME= 26/12 = 2.2 and for oedema MO= 32:12 = 2.67. As the result for oedema is >2.3 the result is considered positive.

According to the second method a mean value of >2.3 was observed in 1 of the 4 animals for erythema and in 3 of the animals for oedema therefore the result is considered positive. Both results are positive and the substance should be classified as a Cat 2 skin irritant.

  

In study 53-64/8607 the results obtained from the 100% solution are used for evaluation. According to the first method of evaluation, the arithmetic mean after 24/48/72 hours for erythema ME= 24/12 = 2 and for oedema MO= 17:12 = 1.5. Both values are <2.3 therefore the result is considered negative.

According to the second method a mean value of <2.3 was observed in all animals for both erythema and oedema. As both results are negative using the 2 methods in accordance with this study the substance does not need to be classified.


Effects on skin irritation/corrosion: irritating

Justification for classification or non-classification

Eye irritation:

Based on the classification criteria set out in accordance with CLP Regulation (EC) no. 1272/2008 the test material is not considered to be an eye irritant.

Skin irritation:

Two of the four studies resulted in no classification and the other two resulted in a Category 2: Irritant classification. In this case the conservative apporach is taken and the substance should be classified as a Category 2: irritant.