Registration Dossier

Administrative data

Description of key information

Skin irritation: not irritating (OECD 404, GLP, K, Rel.1)

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

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:
21 March to 07 April 2006
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
GLP study conducted according to OECD Guideline 404 with deviations: age at study initiation, feeding conditions not reported. These deviations do not affect the quality of the study and are not considered to be relevant.
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
age at study initiation, feeding conditions not reported
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. certificate)
Remarks:
13 December 2005
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS- Source: Elevage de Gérome, Quartier Labaste – F40260 Linxe- Weight at study initiation: 2.48-2.86 kg- Housing: Each animal was kept in an individual box installed in conventional air conditioned animal husbanding.- Diet: No data- Water: No data- Acclimation period: 5 daysENVIRONMENTAL CONDITIONS- Temperature: 19-23 °C- Humidity: 30-59 %IN-LIFE DATES: 21 March to 07 April 2006
Type of coverage:
semiocclusive
Preparation of test site:
not specified
Vehicle:
unchanged (no vehicle)
Controls:
other: On the left flank an untreated area was served as the 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:
4 h
Observation period:
Skin reactions were appreciated 1 hour and then 24, 48, 72 hours and Days 4 to 10 after removal of the patch.
Number of animals:
3 males
Details on study design:
Initially, a single animal was treated. After consideration of the cutaneous responses produced in the first treated animal, two additional animals were treated.TEST SITE - Area of exposure: The test item was applied, as supplied, at a dose of 0.5 mL, on an undamaged skin area of the right flank of each animal. - Type of wrap if used: The patch was secured in position with a strip of surgical adhesive tape. REMOVAL OF TEST SUBSTANCE - Time after start of exposure: 4 hOBSERVATION TIME POINTS- Skin reactions were appreciated 1 hour and then 24, 48, 72 hours and Days 4 to 10 after removal of the patch.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:
1
Max. score:
4
Reversibility:
fully reversible within: 4 days
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 4 days
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
1.7
Max. score:
4
Reversibility:
fully reversible within: 10 days
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 10 days
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 10 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:
0.3
Max. score:
4
Reversibility:
fully reversible within: 10 days
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
24 hours after the test item application, it was noted a well definite erythema, associated with a very slight oedema. The oedematous reactions were totally reversible between the 3rd and the 4th day of the test and the erythematous reactions were totally reversible between the 4th and the 7th day of the test.On the cutaneous aspect, the skin recovered a normal aspect, between the 5th and the 11th day of the test.
Other effects:
None

Table 7.3.1/1: Individual and average scores after 4 h exposure

Observations

Score

Skin

reactions

Observation

time

Animal no.A7286

Animal no.A7303

Animal no.A7304

Erythema

and eschar

1 h

2

2

2

24 h

2

2

2

48 h

1

2

2

72 h

0

1

2

Day 4

0

0

2

Day 5

-

0

1

Day 6

-

0

0

Day 7

-

0

0

Day 8

-

0

0

Day 9

-

0

0

Day 10

-

0

0

Mean (24, 48 and 72 h)

1.0

1.7

2.0

Oedema

formation

1 h

1

1

1

24 h

1

1

1

48 h

0

1

0

72 h

0

0

0

Day 4

0

0

0

Day 5

-

0

0

Day 6

-

0

0

Day 7

-

0

0

Day 8

-

0

0

Day 9

-

0

0

Day 10

-

0

0

Mean (24, 48 and 72 h)

0.3

0.7

0.3

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

In a dermal irritation study performed according to the OECD Guideline No. 404, and in compliance with GLP, undiluted test substance was applied at the dose of 0.5 mL, under semiocclusive dressing during 4 hours on an undamaged skin area of 3 rabbits. On the opposite flank an untreated area was served as the control. Skin irritation was assessed and scored according to the Draize scale at 1, 24, 48, 72 h and Days 4 to 10 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.

 

24 hours after the test item application, it was noted a well definite erythema, associated with a very slight oedema. The oedematous reactions were totally reversible between the 3rd and the 4th day of the test and the erythematous reactions were totally reversible between the 4th and the 7th day of the test. On the cutaneous aspect, the skin recovered a normal aspect, between the 5th and the 11th day of the test.The individual scores for each animal within 3 scoring times (24, 48 and 72 h) were 1.0 / 1.7 / 2.0 for erythema and 0.3 / 0.7 / 0.3 for oedema. 

 

Under the test conditions, the test substance is not classified according to the criteria of the annex VI of the Regulation EC No. 1272/2008 (CLP) and 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:
20-30 April 2006
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
GLP study conducted according to OECD Guideline 405 with deviations: age at study initiation, feeding conditions not reported. These deviations do not affect the quality of the study and are not considered to be relevant.
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
age at study initiation, feeding conditions not reported
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. certificate)
Remarks:
13 December 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- Weight at study initiation: 2.34-2.61 kg- Housing: Each animal was kept in an individual box installed in conventional air conditioned animal husbanding.- Diet: No data- Water: No data- Acclimation period: 5 daysENVIRONMENTAL CONDITIONS- Temperature: 19-23 °C- Humidity: 38-61 %IN-LIFE DATES: 20-30 April 2006
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:
No washing was done
Observation period (in vivo):
Ocular examinations were performed on both right and left eyes 1, 24, 48 and 72 h & Days 4, 5 and 6 following treatment, according to a numerical evaluation.
Number of animals or in vitro replicates:
3 males
Details on study design:
TREATMENTA volume of 0.1 mL of the pure test item was instilled 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: No 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:
0.7
Max. score:
4
Reversibility:
fully reversible within: 48 h
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:
1.3
Max. score:
3
Reversibility:
fully reversible within: 5 days
Remarks on result:
no 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: 72 h
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:
1
Max. score:
3
Reversibility:
fully reversible within: 72 h
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #2
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 h
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:
1.7
Max. score:
4
Reversibility:
fully reversible within: 6 days
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:
1.7
Max. score:
3
Reversibility:
fully reversible within: 4 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 h
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
The ocular reactions observed during the study have been moderate, and totally reversible in the three animals:- at the conjunctivae level: a moderate redness, noted 1 hour after the test item instillation and totally reversible between the 4th and the 6th day of the test, associated with a moderate chemosis, noted 1 hour after the test item instillation and totally reversible between the 3rd and the 4th day of the test;- at the corneal level: a moderate opacity, registered 24 hours after the test item instillation in two animals and totally reversible between the 3rd and the 7th day of the test.
Other effects:
None

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

 

Time / Animal

 

Cornea

 

Iris

 

Conjunctivae

 

redness

 

chemosis

 

1

2

3

1

2

3

1

2

3

1

2

3

1 h

0

0

0

0

0

0

2

2

2

2

2

2

24 h

2

0

2

0

0

0

2

2

2

2

1

1

48 h

0

0

2

0

0

0

1

1

2

1

0

0

72 h

0

0

1

0

0

0

1

0

1

0

0

0

D4

0

-

1

0

-

0

1

-

0

0

-

0

D5

0

-

1

0

-

0

0

-

0

0

-

0

D6

-

-

0

-

-

0

-

-

0

-

-

0

Total 24/48/72 h

2

0

5

0

0

0

4

3

5

3

1

1

Mean 24/48/72 h

0.7

0.0

1.7

0.0

0.0

0.0

1.3

1.0

1.7

1.0

0.3

0.3

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

In an eye irritation study conducted according to OECD 405 Guideline and in compliance with GLP, test substance was instilled as supplied, into the eye of 3 New Zealand rabbits at the dose of 0.1 mL, the other eye remained untreated serving as control. The lids were then gently held together for about one second in order to prevent loss of the test substance. The eyes were examined and the changes were observed at 1, 24, 48 and 72 h and 4, 5 and 6 days after treatment and graded according to the Draize method.  

 

The ocular reactions observed during the study have been moderate, and totally reversible in the three animals:

- at the conjunctivae level: a moderate redness, noted 1 hour after the test item instillation and totally reversible between the 4th and the 6th day of the test, associated with a moderate chemosis, noted 1 hour after the test item instillation and totally reversible between the 3rd and the 4th day of the test;

- at the corneal level: a moderate opacity, registered 24 hours after the test item instillation in two animals and totally reversible between the 3rd and the 7th day of the test.

 

Mean individual scores at 24, 48 and 72 h after exposure for the 3 animals were 0.7, 0.0, 1.7 for cornea score; 0.0, 0.0, 0.0 for iris score; 1.3, 1.0, 1.7 for conjunctivae score and 1.0, 0.3, 0.3 for chemosis score.

 

Under the test conditions, test substance is not classified as irritating to eyes according to the criteria of the annex VI of 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:

A key study was identified (Phycher, 2006). In this dermal irritation study performed according to the OECD Guideline No. 404, and in compliance with GLP, 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.

24 hours after the test item application, it was noted a well definite erythema, associated with a very slight oedema. The oedematous reactions were totally reversible between the 3rd and the 4th day of the test and the erythematous reactions were totally reversible between the 4th and the 7th day of the test. On the cutaneous aspect, the skin recovered a normal aspect, between the 5th and the 11th day of the test.The individual scores for each animal within 3 scoring times (24, 48 and 72 h) were 1.0 / 1.7 / 2.0 for erythema and 0.3 / 0.7 / 0.3 for oedema. The substance is therefore not classified for skin irritation.

Eye irritation:

A key study was identified (Phycher, 2006). In this eye irritation study performed according to the OECD guideline 405, and in compliance with GLP, 0.1 mL of undiluted test material was instilled into one eye of 3 female New Zealand White rabbits. The other eye remained untreated and served as control. The lids were then gently held together for about one second in order to prevent loss of the test substance. The eyes were examined and the changes were observed at 1, 24, 48 and 72 h and 4, 5 and 6 days after treatment and graded according to the Draize method.

The calculated mean score for each animal within 3 scoring times (24, 48 and 72 h) were 0.7/0.0/1.7 for the corneal opacity, 0.0/0.0/0.0 for iridial inflammation, 1.3/1.0/1.7 for conjunctival redness and 1.0/0.3/0.3 for chemosis. The effects observed were all reversible within 7 days. The substance is therefore not 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:

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

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