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Administrative data

Description of key information

Skin irritation/corrosion: not irritating (OECD 404, GLP, rel. 1, K)

Eye irritation: not irritating (OECD 405, GLP, rel. 1, K)

Respiratory irritation: No data was available, however the substance not being classified for skin and eye irritation, no classification is expected for respiratory irritation.

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:
From 25 May 2004 to 28 May 2004
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Study performed according to OECD test guideline No. 404 and in compliance with GLP
Reason / purpose for cross-reference:
reference to same study
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
Principles of method if other than guideline:
not applicable
GLP compliance:
yes (incl. QA statement)
Remarks:
UK GLP Compliance Programme (inspected on 2002-12-02)
Specific details on test material used for the study:
- Stability under test conditions: stable
- Storage condition of test material: ca. 4°C in the dark under nitrogen
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: David Percival Ltd, Moston, Sandbach, Cheshire, UK.
- Age at study initiation: twelve to twenty weeks old.
- Weight at study initiation: 2.0 to 3.5 kg
- Housing: individually housed in suspended metal cages
- Diet (e.g. ad libitum): free access (Certified Rabbit Diet (Code 5322) supplied by BCM IPS Limited, London, UK)
- Water (e.g. ad libitum): free access
- Acclimation period: at least five days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23°C
- Humidity (%): 30 to 70%
- Air changes (per hr): at least fifteen changes per hour
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 25 To: 28 May 2004
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
water
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g

VEHICLE (moistened with water)
- Amount(s) applied (volume or weight with unit): 0.5 mL
Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 2.5 cm x 2.5 cm
- Type of wrap if used: cotton gauze patch secured on position with a strip of surgical adhesive tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes (gentle swabbing with cotton wool soaked in distilled water)
- Time after start of exposure: 4 hours

SCORING SYSTEM: draize scale, as described in OECD Test Guideline 404.
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
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
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
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
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
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
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
Very slight erythema was noted at all treated skin sites one hour after patch removal. Reversibility of any observed effect: Changes fully reversible within 1 day
Other effects:
None

Very slight erythema was noted at all treated skin sites one hour after patch removal. All treated skin sites appeared normal at the 24 -hour observation.

Table 7.3.1: Individual Daily and Mean Scores for Dermal Irritation Following a 4-hour exposure

 

 

Individual Scores – Rabbit Number and sex

Skinreaction

Reading (hours)

1 male

2 male

3 male

Erythema/escharFormation

1

24

48

72

1

0

0

0

1

0

0

0

1

0

0

0

Mean Score (24 -48 -72 h)

0.0

0.0

0.0

Oedema Formation

1

24

48

72

0

0

0

0

0

0

0

0

0

0

0

0

Mean Score (24 -48 -72 h)

0.0

0.0

0.0

 

Interpretation of results:
GHS criteria not met
Conclusions:
Under the test conditions, test material is not classified as irritant to the skin according to the criteria of the Regulation (EC) No. 1272/2008 (CLP) and according to the GHS.
Executive summary:

In a dermal irritation study performed according to the OECD guideline No. 404, and in compliance with GLP, 0.5 mL of test material moistened with water was dermally applied on the clipped skin of the dorsal surface of 3 New Zealand White rabbits. Test sites were covered with a semi-occlusive dressing for 4 hours.

Skin irritation was assessed and scored according to the Draize scale at 1, 24, 48 and 72 h after the removal of the patch.

Slight erythema was observed 1 hour following patch removal. The individual scores calculated over all the animals tested within 3 scoring times (24, 48 and 72 h) were 0.0/0.0/0.0 for erythema and 0.0/0.0/0.0 for oedema.

Under the test conditions, test material is not classified as irritant to the skin according to the criteria of the Regulation (EC) No. 1272/2008 (CLP) and according to the GHS.

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

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:
From 02 June 2004 to 11 June 2004
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Study performed according to OECD test guideline No. 405 and in compliance with 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
Principles of method if other than guideline:
not applicable
GLP compliance:
yes (incl. QA statement)
Remarks:
UK GLP Compliance Programme (inspected on 2002-12-02)
Specific details on test material used for the study:
- Storage condition of test material: ca. 4°C in the dark under nitrogen
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: David Percival Ltd, Moston, Sandbach, Cheshire, UK.
- Age at study initiation: twelve to twenty weeks old.
- Weight at study initiation: 2.0 to 3.5 kg
- Housing: individually housed in suspended metal cages
- Diet (e.g. ad libitum): free access (Certified Rabbit Diet (Code 5322) supplied by BCM IPS Limited, London, UK)
- Water (e.g. ad libitum): free access
- Acclimation period: at least five days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23°C
- Humidity (%): 30 to 70%
- Air changes (per hr): at least fifteen changes per hour
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 02 June 2004 To: 11 June 2004
Vehicle:
unchanged (no vehicle)
Controls:
other: left eye (untreated eye)
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml
Duration of treatment / exposure:
72 hours
Observation period (in vivo):
1 hour and 24, 48 and 72 hours following treatment
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): no washing
- Time after start of exposure: N.A.

SCORING SYSTEM: Draize scale, as described in OECD Test Guideline 405.

TOOL USED TO ASSESS SCORE: light source from a standard ophtalmoscope
Irritation parameter:
conjunctivae score
Basis:
animal: #1, #2 and #3
Time point:
24/48/72 h
Score:
0.7
Max. score:
3
Reversibility:
fully reversible within: 72 h
Irritation parameter:
chemosis score
Basis:
animal: # 1 and #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritation parameter:
cornea opacity score
Basis:
animal: # 1, #2 and #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
animal: # 1, #2 and #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritant / corrosive response data:
No corneal or iridial effects were noted during the study. Minimal to moderate conjunctival irritation was noted in all treated eyes one hour after treatment with minimal conjunctival irritation noted in all treated eyes at the 24 and 48-hour observations. All treated eyes appeared normal at the 72-hour observation.
Other effects:
none

Table 7.3.2/1: Irritant/corrosive response data each animals at each observation time up to removal from the test

 

Score at time point / Reversibility

Cornea

Iris

(/2)

Conjunctivae

Opacity

(/4)

Area

(/4)

Redness

(/3)

Chemosis

(/4)

Discharge

(/3)

1 h

0 / 0 / 0

0 / 0 / 0

0 / 0 / 0

1 / 1 / 2

1 / 1 / 1

1 / 1 / 2

24 h

0 / 0 / 0

0 / 0 / 0

0 / 0 / 0

1 / 1 / 1

0 / 0 / 1

0 / 0 / 1

48 h

0 / 0 / 0

0 / 0 / 0

0 / 0 / 0

1 / 1 / 1

0 / 0 / 1

0 / 0 / 1

72 h

0 / 0 / 0

0 / 0 / 0

0 / 0 / 0

0 / 0 / 0

0 / 0 / 0

0 / 0 / 0

Average 24h, 48h, 72h

0 / 0 / 0

0 / 0 / 0

0 / 0 / 0

0.7 / 0.7 / 0.7

0 / 0 / 0.7

0 / 0 / 0.7

Reversibility*)

-

-

-

c.

c.

c.

Average time (unit) for reversion

-

-

-

72 h

72 h

72 h

*) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

Interpretation of results:
GHS criteria not met
Conclusions:
Under the test conditions, the test material is not classified as irritating to eyes according to the criteria of the Regulation (EC) No. 1272/2008 (CLP) and according the GHS.
Executive summary:

In an eye irritation study performed according to the OECD guideline No. 405, and in compliance with GLP, 0.1 mL of undiluted test material was instilled into the right eye of 3 New Zealand White Rabbit. The eyes were not rinsed after the instillation of the test item. The left eye of each rabbit served as control. Animals were observed at 1, 24, 48 and 72 hours after dosing under a standard light source. The reactions in the conjunctiva (redness, chemosis and discharge), the iris and the cornea (opacity and area involved) were scored according to the Draize scale. 

Minimal to moderate conjunctival irritation was noted in all treated eyes one hour after treatment.

All treated eyes appeared normal at the 72-hour observation.

The calculated mean score for each individual lesion for each animals within 3 scoring times (24, 48 and 72 h) were 0.7/0.7/0.7 for redness, 0.0/0.0/0.7 for chemosis and 0.0/0.0/0.0 for discharge, iris and corneal lesions.

 

Under the test conditions, the test material is not classified as irritating to eyes according to the Regulation (EC) No. 1272/2008 (CLP) and to the GHS.

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

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation/Corrosion

A key in vivo study was identified (Safepharm, 2004, rel. 1). This dermal irritation study was performed according to the OECD guideline No. 404, and in compliance with GLP. The mean scores calculated for each rabbits within 3 scoring times (24, 48 and 72 h) were 0.0/0.0/0.0 for erythema and 0.0/0.0/0.0 for oedema. The test material does not require classification for skin irritation.

Eye irritation:

A key in vivo study was identified (Safepharm, 2004, rel. 1). This eye irritation study was performed according to the OECD guideline No. 405, and in compliance with GLP. Minimal to moderate conjunctival irritation was noted in all treated eyes one hour after treatment. However, no signs of ocular irritation were apparent in any animal at all subsequent examinations. The calculated mean score for each individual lesion for each animals within 3 scoring times (24, 48 and 72 h) were 0.7/0.7/0.7 for redness, 0.0/0.0/0.7 for chemosis and 0.0/0.0/0.0 for discharge, iris and corneal lesions. The test material does not require classification 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 information, no additional self-classification is proposed regarding skin irritation according to the Regulation (EC) No. 1272/2008 (CLP) and according to the GHS.

Eye irritation:

Based on the available information, no additional self-classification is proposed regarding eye irritation according to the Regulation (EC) No. 1272/2008 (CLP) and according to the GHS.

Respiratory irritation:

No data was available, however the substance not being classified for skin and eye irritation, no classification is expected for respiratory irritation.

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