Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Skin irritation: not irritating (OECD 404, GLP, K, Rel.2)

Eye irritation: irritating (OECD 405, GLP, 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:
31 January to 14 February 2012
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
GLP study conducted in compliance with OECD Guideline No. 404 without any deviation. The substance is adequately identified, but some data on composition is missing. Therefore validation applies with restrictions.
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
24 April 2002.
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:
Inspected on 2010-12-07 / Signed on 2011-03-07.
Specific details on test material used for the study:
- Physical state: Colourless gel
- Date received: 13 January 2012
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).
- Weight at study initiation: 2.74 - 3.06 kg
- Housing: Each animal was kept in an individual box installed in conventional air conditioned animal husbanding.
- Diet: foodstuff (SDS - C15), ad libitum
- Water: tap-water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 17-23 °C
- Humidity: 30-70 %
- Air changes: between ten and fifteen changes per hour.
- Photoperiod: 12 hours light/12 hours dark.

IN-LIFE DATES: From 31 January to 14 February.
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
yes
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration (if solution): Test item was applied, as supplied.
Duration of treatment / exposure:
4 hours
Observation period:
Skin reactions were appreciated 1, 24, 48 and 72 hours after removal of the patch and observations were continued from Days 4 to 14 (in case of persistent reactions were observed).
Number of animals:
3 females
Details on study design:
PRETEST
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: Undamaged skin area of the right flank of each animal
- Type of wrap if used: Patch was secured in position with a strip of surgical adhesive tape.

REMOVAL OF TEST SUBSTANCE
- Washing: After removal of the patch, the treated area was rinsed with distilled water.
- Time after start of exposure: 4 h

OBSERVATION TIME POINTS
1, 24, 48 and 72 hours after removal of the patch and observations were continued from Days 4 to 14 (in case of persistent reactions were observed).

SCORING SYSTEM:
- Method of calculation: Skin irritant reaction was scored as per Draize scale according to OECD guideline 404
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
probability of mild irritation
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
probability of mild irritation
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 2 days.
Remarks on result:
probability of weak 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: 2 days.
Remarks on result:
probability of weak irritation
Irritation parameter:
erythema 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:
edema score
Basis:
animal #3
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 2 days
Remarks on result:
probability of weak irritation
Irritant / corrosive response data:
- A very slight to well defined erythema was noted on the treated area of all animals, 1 hour after the patch removal.
- A very slight to moderate oedema was noted on the treated area of all animals, 1 or 24 hours after the patch removal.
- The erythematous reactions were totally reversible between days 1 and 7.
- The oedematous reactions were totally reversible between days 2 and 7. Dryness was noted from day 2 or day 3 in the three animals and was totally reversible on day 7.
Other effects:
None

Table 7.3.1/1: Individual and mean skin reactions/Erythema - Eschar formation following 4 hour exposure

Skin reaction

Observation time (following patch removal)

Individual Scores – Rabbit Number and Sex

A1812/Female

A1817/Female

A1818/Female

Erythema/Eschar formation

1 h

2

1

1

24 h

2

1

0

48 h

2

0

0

72 h

2

0

0

Day 7

0

0

0

Total (24, 48 and 72 hours)

6

1

0

Mean (24, 48 and 72 hours)

2

0.3

0

Table 7.3.1/2: Individual and mean skin reactions/Oedema formation following 4 hour exposure

Skin reaction

Observation time (following patch removal)

Individual Scores – Rabbit Number and Sex

A1812/Female

A1817/Female

A2166/Female

Oedema formation

1 h

3

1

0

24 h

3

2

2

48 h

2

0

0

72 h

1

0

0

Day 7

0

0

0

Total (24, 48 and 72 hours)

6

2

0

Mean (24, 48 and 72 hours)

2

0.7

0.7

Note:

A1812: dryness from D2 to D3

A1817: dryness at D3

A1818: dryness at D3.

Interpretation of results:
GHS criteria not met
Conclusions:
Under the test conditions, the test material is not classified as irritant to skin according to the annex I of the Regulation (EC) No. 1272/2008 and 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 undiluted test item was applied on an undamaged skin area of the flank of 3 female New Zealand White rabbits. On the other flank an untreated area was served as the control. Test sites were covered with a semi-occlusive dressing for 4 h. Skin irritation was assessed and scored according to the Draize scale at 1, 24, 48 and 72 hours after removal of the patch and observations were continued from Days 4 to 14. 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 to well defined erythema was noted on the treated area of all animals, 1 hour after the patch removal. A very slight to moderate oedema was noted on the treated area of all animals, 1 or 24 hours after the patch removal. The erythematous reactions were totally reversible between days 1 and 7. The oedematous reactions were totally reversible between days 2 and 7. Dryness was noted from day 2 or day 3 in the three animals and was totally reversible on day 7.

 

 

The mean scores for each animal within 3 scoring times (24, 48 and 72 h) were 2 / 0.3/ 0.0 for erythema and 2.0 / 0.7 / 0.7 for oedema. These effects are reversible between days 2 and 7.

 

Therefore the test material is not classified as irritant to skin according to the annex I of the Regulation (EC) No. 1272/2008 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:
Between 06 February and 05 March 2012.
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
GLP study conducted in compliance with OECD Guideline No. 405 without any deviation. The substance is adequately identified, but some data on composition is missing. Therefore validation applies with restrictions.
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
24 April 2002.
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:
Inspected on 2010-12-07 / Signed on 2011-03-07.
Specific details on test material used for the study:
- Physical state: Colourless gel
- Date received: 13 January 2012
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: 2.73 - 3.19 kg
- Housing: Each animal was kept in an individual box installed in conventional air conditioned animal husbanding.
- Diet: foodstuff (SDS - C15), ad libitum
- Water: tap-water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 17-23 °C
- Humidity: 30-70 %
- Air changes: between ten and fifteen changes per hour.
- Photoperiod: 12 hours light/12 hours dark.

IN-LIFE DATES: from 06 February to 05 March 2012
Vehicle:
unchanged (no vehicle)
Controls:
yes
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL

- Concentration (if solution): Test item was instilled, as supplied
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 7, 14 and 21 following treatment, 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: 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:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
probability of mild irritation
Irritation parameter:
iris score
Basis:
animal #1
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
0.3
Max. score:
2
Reversibility:
fully reversible within: 2 days.
Remarks on result:
probability of weak irritation
Irritation parameter:
conjunctivae score
Basis:
animal #1
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 14 days
Remarks on result:
probability of weak 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: 7 days
Remarks on result:
probability of weak irritation
Irritation parameter:
cornea opacity score
Basis:
animal #2
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
probability of mild irritation
Irritation parameter:
iris score
Basis:
animal #2
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
0.3
Max. score:
2
Reversibility:
fully reversible within: 2 days.
Remarks on result:
probability of weak irritation
Irritation parameter:
conjunctivae score
Basis:
animal #2
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
1.3
Max. score:
3
Reversibility:
fully reversible within: 14 days
Remarks on result:
probability of weak irritation
Irritation parameter:
chemosis score
Basis:
animal #2
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 7 days.
Remarks on result:
probability of weak irritation
Irritation parameter:
cornea opacity 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:
probability of mild irritation
Irritation parameter:
iris score
Basis:
animal #3
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
0.3
Max. score:
2
Reversibility:
fully reversible within: 7 days
Remarks on result:
probability of weak 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: 7 days
Remarks on result:
probability of weak irritation
Irritation parameter:
chemosis score
Basis:
animal #3
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 21 days
Remarks on result:
probability of weak irritation
Irritant / corrosive response data:
The ocular reactions observed during the study have been slight to important and totally reversible:
- at the conjunctivae level: a slight to moderate redness noted 1 hour after the test item instillation and totally reversible between days 7 and 14, associated with a slight to moderate chemosis noted 1 hour after the test item instillation and totally reversible between days 7 and 21;
- at the iris level: a congestion, noted 1 or 24 hours after the test item instillation in all animals, and totally reversible between days 2 and 7;
- at the corneal level: a moderate corneal opacity, noted 24 hours after the test item instillation in all animals and totally reversible between days 3 and 7.
Other effects:
None

Table 7.3.2/1: Individual and Mean Scores for Cornea, Iris and Conjunctivae

Rabbit Number and Sex

 

Time After Treatment

 

Corneal Opacity

 

Iris lesion

Conjunctival Redness

 

Conjunctival Chemosis

 

A1789 Male

 

1 h

0

0

1

1

24 h

2

1

1

1

48 h

2

0

1

1

72 h

2

0

1

1

Day 7

0

0

1

0

Day 14

0

0

0

0

Total (24, 48 and 72 h)

6

1

3

3

Mean (24, 48 and 72 h)

2

0.3

1

1

Rabbit Number and Sex

 

Time After Treatment

 

Corneal Opacity

 

Iris lesion

Conjunctival Redness

 

Conjunctival Chemosis

 

A1820 Male

 

1 h

0

1

2

2

24 h

2

1

2

2

48 h

2

0

1

1

72 h

0

0

1

1

Day 7

0

0

1

0

Day 14

0

0

0

0

Total (24, 48 and 72 h)

4

1

4

4

Mean (24, 48 and 72 h)

1.3

0.3

1.3

1.3

Rabbit Number and Sex

 

Time After Treatment

 

Corneal Opacity

 

Iris lesion

Conjunctival Redness

 

Conjunctival Chemosis

 

A1821 Male

 

1 h

0

1

2

2

24 h

2

0

2

2

48 h

2

0

1

1

72 h

2

1

1

1

Day 7

0

0

0

1

Day 14

0

0

0

1

Day 21

0

0

0

0

 

Total (24, 48 and 72 h)

6

1

4

4

  

Mean (24, 48 and 72 h)

 2  0.3  1.3  1.3
Interpretation of results:
Category 2A (irritating to eyes) based on GHS criteria
Conclusions:
Under the test conditions, test material is classified as irritating to eyes in category 2 according to the annex I of the Regulation (EC) No. 1272 /2008 (CLP) and in category 2A according to the GHS.
Executive summary:

In an eye irritation study conducted according to OECD 405 guideline and in compliance with GLP, 3 New Zealand White male rabbits were exposed to 0.1 mL of test item 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 from 4 to 21 days following treatment and graded according to the Draize method. Initially, a single animal was treated. After consideration of the ocular responses produced in the first treated animal, two additional animals were treated.

A slight to moderate redness noted 1 hour after the test item instillation and totally reversible between days 7 and 14, associated with a slight to moderate chemosis noted 1 hour after the test item instillation and totally reversible between days 7 and 21. At the iris level, a congestion was noted 1 or 24 hours after the test item instillation in all animals, and totally reversible between days 2 and 7. A moderate corneal opacity, noted 24 hours after the test item instillation in all animals and totally reversible between days 3 and 7.

 

 

Mean individual scores at 24, 48 and 72 h after exposure for the 3 animals were 2.0, 1.3, 2.0 for cornea score; 0.3, 0.3, 0.3 for iris score; 1.0, 1.3, 1.3 for conjunctivae score and 1.0, 1.3, 1.3 for chemosis score. These effects are reversible between days 2 and 21.

 

Under the test conditions, test material is classified as irritating to eyes in category 2 according to the annex I of the Regulation (EC) No. 1272 /2008 (CLP) and in category 2A 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, 2012). In this dermal irritation study performed according to the OECD Guideline No. 404, and in compliance with GLP, 3 female 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 to well defined erythema was noted on the treated area of all animals, 1 hour after the patch removal. A very slight to moderate oedema was noted on the treated area of all animals, 1 or 24 hours after the patch removal. The erythematous reactions were totally reversible between days 1 and 7. The oedematous reactions were totally reversible between days 2 and 7. Dryness was noted from day 2 or day 3 in the three animals and was totally reversible on day 7.

 

The mean scores for each animal within 3 scoring times (24, 48 and 72 h) were 2 / 0.3/ 0.0 for erythema and 2.0 / 0.7 / 0.7 for oedema. These effects are reversible between days 2 and 7.

 

 

Eye irritation:

A key study was identified (Phycher, 2012). 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 male New Zealand White rabbits. The other 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 7, 14 and 21 following treatment and graded according to the Draize method. Initially, a single animal was treated. After consideration of the ocular responses produced in the first treated animal, two additional animals were treated.

A slight to moderate redness noted 1 hour after the test item instillation and totally reversible between days 7 and 14, associated with a slight to moderate chemosis noted 1 hour after the test item instillation and totally reversible between days 7 and 21. At the iris level, a congestion was noted 1 or 24 hours after the test item instillation in all animals, and totally reversible between days 2 and 7. A moderate corneal opacity, noted 24 hours after the test item instillation in all animals and totally reversible between days 3 and 7.

 

 

Mean individual scores at 24, 48 and 72 h after exposure for the 3 animals were 2.0, 1.3, 2.0 for cornea score; 0.3, 0.3, 0.3 for iris score; 1.0, 1.3, 1.3 for conjunctivae score and 1.0, 1.3, 1.3 for chemosis score. These effects are reversible between days 2 and 21.

Justification for classification or non-classification

Harmonized classification:


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


 


Self classification:


Skin irritation:


Based on the available data, no additional self-classification is proposed regarding skin irritation according to the CLP and to the GHS.


 


Eye irritation:


Based on the available data:


- the substance should be classified in Category 2 (irritating to eyes) according to the CLP.


- the substance should be classified in Category 2A (irritating to eyes) according to the GHS.


 


Respiratory irritation:


No data was available regarding respiratory irritation.