Registration Dossier

Administrative data

Description of key information

Based on an in vitro skin irritation test, conducted according to OECD 439 and GLP principles, and based on an in vivo skin irritation test, conducted according to OECD 404 and GLP principles, it was concluded that the substance is not irritating to the skin. Based on an in vivo eye irritation study, conducted in accordance with OECD 405 and according to GLP principles, it was concluded that the substance is also not irritating to the eyes.

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:
November 16, 2010 - November 20, 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study has been performed in accordance with OECD 404 (2002), EU Method B.4 (2008), EPA OPPTS 870.2500 (1998) and according to GLP principles.
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
(2002)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Version / remarks:
(2008)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Version / remarks:
(1998)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, 97633 Sulzfeld, Germany
- Age at study initiation: approx. 16 - 17 weeks
- Weight at study initiation: 3.2-3.6 kg
- Housing: individually in ABS - plastic rabbit cages
- Diet: ad libitum (autoclaved hay and Altromin 2123 maintenance diet)
- Water: ad libitum (tap water)
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3
- Humidity (%): 55 ± 10
- Air changes (per hr): at least 10
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
other: approx. 26 hours before the test, the fur was removed from the dorsal area of the trunk by using an electric clipper
Vehicle:
other: the substance was moistened with aqua ad injectionem
Controls:
other: the untreated right side of the dorsal area served as control
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.5 g

VEHICLE
- Vehicle: aqua ad injectionem (Delta Select, lot no. 05007A, expiry date: June 2013)
Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
3 females (1 female subsequently followed by 2 females)
Details on study design:
TEST SITE
The test item was applied to a gauze patch and was moistened with aqua ad injectionem.
The patch was then applied to the skin on a small area (approx. 6 cm^2) on the left side of the dorsal area.
The gauze was held in place with non-irritating tape. The patch was fixed with a semi-occlusive dressing.

REMOVAL OF TEST SUBSTANCE
- Washing: yes, using tap water
- Time after start of exposure: 4 hours

OBSERVATIONS
- Clinical signs: approximately 1, 24, 48 and 72 hours after patch removal
- Body Weight: at the start of the study and 72 hours after patch removal
- Irritation: the skin reactions were assessed at approximately 1, 24, 48 and 72 hours after patch removal. The irritation scores and a description of all other (local) effects were recorded.

SCORING SYSTEM
The irritation was assessed according to the numerical scoring system according to OECD 404.
Irritation parameter:
erythema score
Basis:
mean
Remarks:
(of all 3 animals)
Time point:
other: Mean value of score at 24, 48 and 72h after patch removal
Score:
0.22
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: Individual scores: 0.66-0-0
Irritation parameter:
edema score
Basis:
mean
Remarks:
(of all 3 animals)
Time point:
other: Mean value of score at 24, 48 and 72h after patch removal
Score:
0
Max. score:
4
Remarks on result:
other: Individual scores: 0-0-0
Irritant / corrosive response data:
See section "Any other information on results incl. tables"
Other effects:
- No significant clinical signs of toxicity were observed
- No mortalities were observed
- No significant body weight changes were observed

Animal No.

 

Irritation (hours after patch removal)

1 hour

24 hours

48 hours

72 hours

1

Erythema

1

1

1

0

Oedema

0

0

0

0

2

Erythema

0

0

0

0

Oedema

0

0

0

0

3

Erythema

1

0

0

0

Oedema

0

0

0

0

 

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on a skin irritation study with rabbits, performed in accordance with OECD 404 (2002), EU Method B.4 (2008), EPA OPPTS 870.2500 (1998) and according to GLP principles, the substance does not need to be classified for skin irritation.
Executive summary:

In an in vivo skin irritation study in rabbits, conducted in accordance with OECD 404 (2002), EU Method B.4 (2008), EPA OPPTS 870.2500 (1998) and according to GLP principles, 3 female rabbits were semi-occlusively exposed for 4 hours to 0.5 g of the (moistened) substance. In 2 animals slight redness was observed, which reversed within 24 or within 72 hours. No significant clinical signs of toxicity nor mortalities were observed. Based on the result of this study, the substance does not need to be classified for skin irritation/corrosion in accordance with the CLP Regulation.

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:
November 17, 2010 - January 19, 2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study has been performed in accordance with OECD 405 (2002), EU Method B.5 (2008), EPA OPPTS 870.2400 (1998) and according to GLP principles.
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
(2002)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
(2008)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Version / remarks:
(1998)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutsschland, 97633 Sulzfeld, Germany
- Age at study initiation: approximately 11 weeks old
- Weight at study initiation: >2 kg
- Housing: individually housed in ABS - plastic rabbit cages, floor 4200 cm^2
- Diet: autoclaved hay and Altromin 2123 maintenance diet (lot no. 0955), ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3 °C
- Humidity (%): 55 ± 10%
- Air changes (per hr): at least 10 per hour
- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light

IN-LIFE DATES: From: December 12, 2010 To: December 17, 2010
Vehicle:
unchanged (no vehicle)
Controls:
other: the untreated eye served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g
Duration of treatment / exposure:
Not applicable (the treated eyes were not rinsed)
Observation period (in vivo):
Not applicable (after 72 hours no ocular lesions were found in any animal)
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE: Not applicable
SCORING SYSTEM: in accordance with OECD 405
TOOL USED TO ASSESS SCORE: fluorescein (only 72 hours after installation)
Irritation parameter:
cornea opacity score
Basis:
other: Mean for animals #1, #2 and #3
Time point:
other: Mean value of score at 24, 48 and 72 h after installation
Score:
0
Max. score:
4
Remarks on result:
other: Individual mean scores: 0-0-0
Irritation parameter:
iris score
Basis:
other: Mean for animals #1, #2 and #3
Time point:
other: Mean value of score at 24, 48 and 72 h after installation
Score:
0
Max. score:
2
Remarks on result:
other: Individual mean scores: 0-0-0
Irritation parameter:
conjunctivae score
Basis:
other: Mean for animals #1, #2 and #3
Time point:
other: Mean value of score at 24, 48 and 72 h after installation
Score:
0.6
Max. score:
3
Reversibility:
fully reversible within: 72 hours (in all animals)
Remarks on result:
other: Individual mean scores: 0.7-0.7-0.3
Irritation parameter:
chemosis score
Basis:
other: Mean for animals #1, #2 and #3
Time point:
other: Mean value of score at 24, 48 and 72 h after installation
Score:
0
Max. score:
4
Remarks on result:
other: Individual mean scores: 0-0-0
Irritant / corrosive response data:
- In none of the animals, any effects on the cornea were observed
- In all animals, an iris score of 1 was observed after 1 hour
- In all animals, conjunctival redness (score: 1) was observed after 1 and 24 hours and in animals #1 and #2 also after 48 hours
- In animal # 1 and #2 chemosis (score: 1) was observed after 1 hour
- In animal #3, chemosis (score: 2) was observed after 1 hour
Other effects:
- Animal #2 and #3 had a slight discharge after 1 hour

- No mortalities nor significant clinical signs of toxicity were observed

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In an acute eye irritation study in 3 rabbits, conducted in accordance with OECD 405 (2002), EU Method B.5 (2008), EPA OPPTS 870.2400 (1998) and according to GLP principles, irritant effects were observed which were fully reversible within 72 hours. Based on the results of this study, the substance does not need to be classified for eye irritation.
Executive summary:

An acute eye irritation study was conducted in 3 rabbits in accordance with OECD 405 (2002), EU Method B.5 (2008), EPA OPPTS 870.2400 (1998) and according to GLP principles. In none of the animals, any effects on the cornea were observed. In all animals, an iris score of 1 was observed after 1 hour. Conjunctival redness (score: 1) was observed in all animals after 1 and 24 hours and in two animals also after 48 hours. In these two animals, chemosis (score: 1) was observed after 1 hour and in the other animal chemosis (score: 2). All ocular effects fully reversed within 72 hours. Based on the results of this study, the substance does not need to be classified for eye irritation.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

In an in vitro skin irritation test using a human skin model ( EPISKIN Standard Model), according to current OECD/EC guidelines, the influence of L579 on the viability of human skin was tested. The test substance was applied directly to cultured skin. After 15 minutes, the substance was removed and cells were cultured for 42 hours. Survival of unexposed skin was set at 100%, the positive control had a mean cell viability of 17% whereas L579 showed cell viability of 88%. Since the mean relative tissue viability after exposure to L579 was above 50%, it can be concluded that L579 is not an irritant in the in vitro skin irritation test.

In an in vivo skin irritation study in rabbits, conducted in accordance with OECD 404 (2002), EU Method B.4 (2008), EPA OPPTS 870.2500 (1998) and according to GLP principles, 3 female rabbits were semi-occlusively exposed for 4 hours to 0.5 g of the (moistened) substance. In 2 animals slight redness was observed, which reversed within 24 or within 72 hours. No significant clinical signs of toxicity nor mortalities were observed. Based on the result of this study, the substance does not need to be classified for skin irritation/corrosion in accordance with the CLP Regulation.

Eye irritation

An eye irritation study was conducted in 3 rabbits in accordance with current OECD/EC guidelines and according to GLP principles. In none of the animals, any effects on the cornea were observed. In all animals, an iris score of 1 was observed after 1 hour. Conjunctival redness (score 1) was observed in all animals after 1 and 24 hours and in two animals also after 48 hours. In these two animals, chemosis (score 1) was observed after 1 hour and in the other animal chemosis (score 2). All ocular effects fully reversed within 72 hours.


Justification for selection of skin irritation / corrosion endpoint:
There are 2 studies available, an in vitro and an in vivo study. Both studies are suitable for the endpoint conclusion, the in vivo study is selected.

Justification for selection of eye irritation endpoint:
Only one study available

Justification for classification or non-classification

Based on the results of an in vitro skin irritation study, an in vivo skin irritation study and an in vivo eye irritation study, the substance does not need to be classified for skin or eye irritation according to CLP Regulation (EC) No 1272/2008.