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Description of key information

Skin irritation: irritating (OECD 404, K, Rel.2)

Eye irritation: irritating (OECD 405, K, Rel.2)

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:
14 June to 12 July 2005
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Remarks:
study conducted according to OECD 404 Guideline - supposed to be GLP but not specified - with acceptable deviations
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
Deviations: information on animals, environmental conditions and method not reported
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
Deviations: information on animals, environmental conditions and method not reported
Principles of method if other than guideline:
Not applicable
GLP compliance:
not specified
Remarks:
supposed to be GLP but not specified
Specific details on test material used for the study:
Date of receipt: 08 June 2005
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Elevage de Gérome (Quartier Labaste – F40260 Linxe)
- Age at study initiation: not specified
- Weight during study: 2.30-3.09 kg
- Housing: Each animal was kept in an individual box installed in conventional air conditioned animal husbanding.
- Diet: not specified
- Water: not specified
- Acclimation period: 5 days minimum

ENVIRONMENTAL CONDITIONS
- Temperature: 18-23 °C
- Humidity: 53-68 %
- Air changes: not specified
- Photoperiod: not specified
IN-LIFE DATES: 14 June -12 July 2005
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
other: On the opposite flank an untreated area was used as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration (if solution): Undiluted
Duration of treatment / exposure:
supposed to be 4 h
Observation period:
Skin reactions were appreciated 1, 24, 48 and 72 h & Days 4 to 14 after removal of the patch.
Number of animals:
3 males
Details on study design:
TEST SITE
- Area of exposure: undamaged skin area of the right flank of each animal.
- Type of wrap if used: The patch was secured in position with an extensible adhesive tape.
- Initially, a single animal was treated. After consideration of the cutaneous responses produced in the first treated animal, two additional animals were treated.

SCORING SYSTEM: According to OECD guideline 404
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
2.7
Max. score:
4
Reversibility:
fully reversible within: 5 days
Remarks on result:
positive indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
2.3
Max. score:
4
Reversibility:
fully reversible within: 5 days
Remarks on result:
positive indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
2.3
Max. score:
4
Reversibility:
fully reversible within: 6 days
Remarks on result:
positive indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
2.3
Max. score:
4
Reversibility:
fully reversible within: 6 days
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Irritant / corrosive response data:
A moderate erythema associated to a moderate to severe oedema waere noted in the treated area 24 hours after exposure. These reactions are fully reversibles within Day 6 or 8.
Regarding the cutaneous structure, the skin become totally undamaged at Day 15 in one animal but a slight dryness is still noted in the remaining animals at the end of the observation period.
Other effects:
None

Table 7.3.1/1: Individual and average scores

Observations Scores
Skin reactions Observation time Animal no. A6723 (#1) Animal no. A6772 (#2) Animal no. A6773 (#3)
Erythema and eschar 1h 2 2 2
24h 2 2 2
48h 3 2 2
72h 3 3 3
4 d 3 3 3
5d 0 3 3
6d 0 0 0
7d 0 0 0
8d 0 0 0
9d 0 0 0
10d 0 0 0
11d 0 0 0
12d 0 0 0
13d 0 0 0
14d 0 0 0
Mean 24/48/72 h 2.7 2.3 2.3
Oedema 1h 4 3 2
24h 3 2 2
48h 2 2 2
72h 2 2 2
4 d 2 2 2
5d 0 2 2
6d 0 1 1
7d 0 0 0
8d 0 0 0
9d 0 0 0
10d 0 0 0
11d 0 0 0
12d 0 0 0
13d 0 0 0
14d 0 0 0
Mean 24/48/72 h 2.3 2.0 2.0

A6723: slight dryness from D3 to D4 and from D11 to D13; dryness from D9 to D10, loss of skin elasticity from D5 to D8

A6772: slight dryness from D12 to D14; dryness from D2 to D5 and at D11, loss of skin elasticity from D6 to D10

A6773: slight dryness from D13 to D14; dryness from D2 to D5 and from D11 to D12, loss of skin elasticity from D6 to D10

Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
Under the test conditions, the test substance is classified as skin irritation Category 2 (H315: Causes skin irritation) according to the Annex I of the Regulation (EC) No. 1272/2008 (CLP) and as Category 2 "irritant" according to the GHS.
Executive summary:

In a dermal irritation study performed according to the OECD Guideline No. 404, 0.5 mL of undiluted test item was applied on the undamaged skin of the right flanks of 3 male New Zealand White rabbits. On the opposite flank an untreated area was served as the control. Test sites were covered with a extensible adhesive tape for 4 h. Skin irritation was assessed and scored according to the Draize scale at 1, 24, 48 and 72 h and day 4 to 14 after the removal of the patch. Initially, a single animal was treated. After consideration of the cutaneous responses produced in the first treated animal, two additional animals were treated during 4 hours.

 

A moderate erythema associated to a moderate to severe oedema waere noted in the treated area 24 hours after exposure. These reactions are fully reversibles within Day 6 or 8.

Regarding the cutaneous structure, the skin become totally undamaged at Day 15 in one animal but a slight dryness is still noted in the remaining animals at the end of the observation period.

The individual scores for each animal within 3 scoring times (24, 48 and 72 h) were 2.7 / 2.3 / 2.3 for erythema and 2.3 / 2.0 / 2.0 for oedema.

Under the test conditions, test substance is classified as skin irritation Category 2 (H315: Causes skin irritation) according to the Annex I of the Regulation (EC) No. 1272/2008 (CLP) and as Category 2 "irritant" according to the GHS.

This study is considered as acceptable and satisfies the requirement for skin irritation endpoint.

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:
20 to 30 June 2005
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Remarks:
study conducted according to OECD 404 Guideline - supposed to be GLP but not specified - with acceptable deviations
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
Deviations: information on animals, environmental conditions and method not reported
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
Deviations: information on animals, environmental conditions and method not reported
Principles of method if other than guideline:
Not applicable
GLP compliance:
not specified
Remarks:
supposed to be GLP but not specified
Specific details on test material used for the study:
Date of receipt: 08 June 2005
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Elevage de Gérome (Quartier Labaste – F40260 Linxe)
- Age at study initiation: not specified
- Weight during study: 2.49-2.95 kg
- Housing: Each animal was kept in an individual box installed in conventional air conditioned animal husbanding.
- Diet: not specified
- Water: not specified
- Acclimation period: 5 days minimum

ENVIRONMENTAL CONDITIONS
- Temperature: 18–23 °C
- Humidity: 59-68 %
- Air changes: not speicified
- Photoperiod: not specified

IN-LIFE DATES: 20 to 30 June 2005
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated eye serving as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): Undiluted
Duration of treatment / exposure:
single instillation
Observation period (in vivo):
Ocular examinations were performed on both eyes 1, 24, 48 and 72 h & Days 4 to 9 after instillation, according to a numerical evaluation.
Number of animals or in vitro replicates:
3 males
Details on study design:
TREATMENT
- 0.1 mL of the test item was instilled, as supplied, into the conjunctival sac of one eye. The other eye remained untreated serving as control.
- Initially, a single animal was treated. After consideration of the ocular responses produced in the first treated animal, two additional animals were treated.

REMOVAL OF TEST SUBSTANCE
- Washing: Not specified

SCORING SYSTEM: According to OECD guideline 405
Irritation parameter:
cornea opacity score
Basis:
animal #1
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #1
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #1
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 9 days
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #1
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 6 days
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #2
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #2
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #2
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 9 days
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #2
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 5 days
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #3
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #3
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #3
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
1.3
Max. score:
3
Reversibility:
fully reversible within: 5 days
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #3
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
Slight to moderate conjunctival reactions were noted, fully reversible:
moderate redness recorded 1 hour after instillation and fully reversible between day 6 and day 10 associated with a slight chemosis recorded 1 hour after instillation and fully reversible between day 3 and day 7.
Other effects:
None

Table 7.3.2/1: Individual and mean scores of conjunctivae, iris and cornea

Time / Animal No. Cornea Iris Conjunctivae
redness chemosis
A6747 (#1) A6748 (#2) A6750 (#3) A6747 (#1) A6748 (#2) A6750 (#3) A6747 (#1) A6748 (#2) A6750 (#3) A6747 (#1) A6748 (#2) A6750 (#3)
1h 0 0 0 0 0 0 2 2 2 1 1 1
24h 0 0 0 0 0 0 2 2 2 1 1 1
48h 0 0 0 0 0 0 2 2 1 1 1 0
72h 0 0 0 0 0 0 2 2 1 1 1 0
4 days 0 0 0 0 0 0 2 1 1 1 1 0
5 days 0 0 0 0 0 0 1 1 0 1 0 0
6 days 0 0 0 0 0 0 1 1  - 0 0  -
7 days 0 0 0 0 0 0 1 1  - 0 0  -
8 days 0 0 0 0 0 0 1 1  - 0 0  -
9 days 0 0 0 0 0 0 0 0  - 0 0  -
mean 24/48/72h 0 0 0 0 0 0 2.0 2.0 1.3 1.0 1.0 0.3

-: not examined

Interpretation of results:
Category 2A (irritating to eyes) based on GHS criteria
Conclusions:
Under the test conditions, the test substance is classified as eye irritation Category 2 (H319: Causes severe eye irritation) according to Regulation (EC) N°1272-2008 (CLP) and as Category 2A "irritating to eyes" according to the GHS.
Executive summary:

In an eye irritation study conducted according to OECD 405/EU Method B.5 guidelines and in compliance with GLP, 3 New Zealand White male rabbits were exposed to 0.1 mL of test substance in one eye while the contralateral eye remained untreated and served as control. The eyes were examined and the changes were observed at 1, 24, 48 and 72 h and Days 4 to 9 following treatment and graded according to the Draize method.  

 

Fully reversible slight to moderate conjunctival reactions were noted during the observation period.

Mean individual scores at 24, 48 and 72 h after exposure for the 3 animals were 0.0 / 0.0 / 0.0 for cornea score; 0.0 / 0.0 / 0.0 for iris score; 2.0 / 2.0 / 1.3 for conjunctivae score and 1.0 / 1.0 / 0.3 for chemosis score.

Under the test conditions, test substance is classified as eye irritation Category 2 (H319: Causes severe eye irritation) according to Regulation (EC) N°1272-2008 (CLP) and as Category 2A "irritating to eyes" according to the GHS.

This study is considered as acceptable and satisfies the requirement for eye irritation endpoint.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation:

A key study was identified (Phycher, 2005). In this dermal irritation study performed according to the OECD Guideline No. 404, 3 male New Zealand White rabbits were exposed for 4 hours to a semi-occluded application of 0.5 mL of undiluted test material to the intact skin. Initially, a single animal was treated. After consideration of the cutaneous responses produced in the first treated animal, two additional animals were treated.

A very slight erythema was noted, in two animals, only at the reading time 1 hour. The individual scores for each animal within 3 scoring times (24, 48 and 72 h) were 2.7 / 2.3 / 2.3 for erythema and 2.3 / 2.0 / 2.0 for oedema. The substance is therefore classified for skin irritation.

Eye irritation:

A key study was identified (Phycher, 2005). In this eye irritation study performed according to the OECD guideline 405, 0.1 mL of undiluted test material was instilled into one eye of 3 male New Zealand White rabbits. The other eye remained untreated and served as control. Initially, a single animal was treated. After consideration of the cutaneous responses produced in the first treated animal, two additional animals were treated.

The calculated mean score for each animal within 3 scoring times (24, 48 and 72 h) were 0.0 / 0.0 / 0.0 for cornea score; 0.0 / 0.0 / 0.0 for iris score; 2.0 / 2.0 / 1.3 for conjunctivae score and 1.0 / 1.0 / 0.3 for chemosis score. The effects observed were all reversible within 9 days. The substance is therefore classified for eye irritation.

Justification for classification or non-classification

Harmonized classification:

The substance has no harmonized classification according to the Regulation (EC) No. 1272/2008.

Self classification:

Skin irritation:

Based on the available data, the subtance should be classified as skin irritation Category 2 (H315: Causes skin irritation) according to the criteria of Annex I to the Regulation (EC) No. 1272/2008 (CLP) and as Category 2 "irritant" according to the GHS.

Eye irritation:

Based on the available data, the substance should be classified as eye irritation Category 2 (H319:Causes serious eye irritation) according to the criteria of Annex I to the Regulation (EC) No. 1272/2008 (CLP) and as Category 2A "irritating to eyes" according to the GHS.

Respiratory irritation:

No data was available regarding respiratory irritation.