Registration Dossier

Administrative data

Description of key information

Skin irritation: not irritating (OECD 404, GLP)
Eye irritation: not irritating (OECD 405; GLP compliant)

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:
2005-12-20 to 2006-01-13
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
2002-04-24
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
dated 2005-12-13
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Elevage de Gérome (Quaratier Labaste - F40260 Linxe)
- Weight at study initiation: 2.35 kg - 2.73 kg
- Housing: each animal was kept in an individual box (dimensions: 61 cm X 46 cm X 34 cm) installed in conventional air conditioned animal husbanding.
- Diet (ad libitum): UAR 112 from UAR in 91360 Villemoisson s/Orge, France
- Water (ad libitum): tap-water from public distribution system
- Acclimation period: a minimal 5-day acclimatisation period

ENVIRONMENTAL CONDITIONS
- Temperature: between 18°C and 22°C
- Relative humidity: between 30% and 53%
- Air recycling: at least 10 cycles per hour
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): the test item was applied, as supplied, at a dose of 0.5 mL


Duration of treatment / exposure:
4 hours
Observation period:
1 hour and then 24, 48 and 72 hours as well as 4 to 14 days after removal of the patch
Number of animals:
3 male rabbits
Details on study design:
Initially, a single animal was treated. After consideration of cutaneous responses produced in the first treated animal, two additional animals were treated.
TEST SITE
- Area of exposure: approximately 24 hours before the test, the rabbits' backs and flanks are shorn using electric clippers equipped with a fine comb, so as to expose an area of skin about 6 cm^2. Any animal with skin lesions is replaced.
The test product is applied to a small area (approx. 6 cm^2) of shorn skin (unaffected zone) and covered with a gauze patch, which is maintained in position by a semi-occlusive dressing. The dressing is covered with an elastic strap taped in place around the animal's body, taking care not to impede its respiratory and abdominal movements.

SCORING SYSTEM: according to Draize scale

OBSERVATIONS:
The systemic toxicity, expressing by behavioural abnormalities, alteration of neuro-vegetative reactions or decrease feeding, and any toxic effects are to be logged and described.
The animals are weighed at the start and at the end of the test.
Irritation parameter:
erythema score
Basis:
mean
Remarks:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: Slight dryness from D2 to D14
Irritation parameter:
edema score
Basis:
mean
Remarks:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
mean
Remarks:
animal #2
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
edema score
Basis:
mean
Remarks:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
mean
Remarks:
animal #3
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: Slight dryness from D3 to D9
Irritation parameter:
edema score
Basis:
mean
Remarks:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
One hour after the test item application, very slight (barely perceptible) erythema was noted.
Twenty four hours after the test item application, it was noted, on the treated area, a very slight to well-definite erythema in the 3 animals. Moreover, it was noted a slight dryness on the cutaneous treated area, from the 2nd or 3rd day of the test in two animals. This reaction was ever noted at the end of the observation time (D14) in one animal.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test substance is not irritating to the skin.
According to the EC-Commission directive 67/548/EEC and its subsequent amendments, the test substance is not irritating to the skin.
According to the EC-Regulation 1272/2008 and subsequent regulations, the test item is not classified as skin irritant.
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:
2006-01-02 to 2006-01-06
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
2002-04-24
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
dated 2005-12-13
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Elevage de Gérome (Quaratier Labaste - F40260 Linxe)
- Weight at study initiation: 2.42 kg - 2.61 kg
- Housing: each animal was kept in an individual box (dimensions: 61 cm X 46 cm X 34 cm) installed in conventional air conditioned animal husbanding.
- Diet (ad libitum): UAR 112 from UAR in 91360 Villemoisson s/Orge, France
- Water (ad libitum): tap-water from public distribution system
- Acclimation period: a minimal 5-day acclimatisation period

ENVIRONMENTAL CONDITIONS
- Temperature: between 20°C and 22°C
- Relative humidity: between 35% and 44%
- Air recycling: at least 10 cycles per hour
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): a volume of 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.


Duration of treatment / exposure:
not applicable
Observation period (in vivo):
1 hour, 24, 48 and 72 hours as well as 4 days following treatment
Number of animals or in vitro replicates:
3 male rabbits
Details on study design:
Initially, a single animal was treated. After consideration of the ocular responses produced in the first treated animal, two additional animals were treated.
Both eyes of each experimental animal provisionally selected for testing should be examined before testing starts. Animals showing eye irritation, ocular defects, or pre-existing corneal injury should not be used.

SCORING SYSTEM: according to Draize scale
Any other lesions in the eye (e.g. pannus, staining) or adverse systemic effects should also be reported

TOOL USED TO ASSESS SCORE: examinations of reactions can be facilitated by use of a binocular loupe, had slit-lamp, biomicroscope or other suitable device. After recording the observations at 24 hours, the eyes may be further examined with the aid of fluorecein.

OBSERVATIONS: the systemic toxicity, expressing by behavioural abnormalities, alteration of neuro-vegetative reactions or decrease feeding, and any toxic effects are to be logged and described.
The animals are weighed at the start and at the end of the test.
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 4 days
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #1
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
animal #2
Time point:
24/48/72 h
Score:
0.67
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
animal #3
Time point:
24/48/72 h
Score:
0.67
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
It was only recorded slightly conjunctivae reactions, similar in the 3 animals and rapidly reversible: a slight redness noted 1 hour after the test item instillation and totally reversible between 4th and the 5th day of the test associated with a slight chemosis noted 1 hour after the test item instillation and totally reversible between 2nd and the 3rd day.
Interpretation of results:
GHS criteria not met
Conclusions:
The test material is not irritating to the eye.
According to 67/548/EC and subsequent regulations, the test substance is not classified as an eye irritant.
According to the EC Regulation No. 1272/2008 and subsequent regulations, the test substance is not classified as eye irritant.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Additional information

Skin irritation

One reliable in vivo study described by Richeux (2006) (OECD 404; GLP compliant) is considered to be reliable without restrictions. The substance was determined not to be irritating to the skin.

Eye irritation

One reliable in vivo study described by Richeux (2006) (OECD 405; GLP compliant) is considered to be reliable without restrictions. The substance was determined not to be irritating to the eyes.

Justification for classification or non-classification

Skin irritation

Reference Richeux (2006) is considered as the key study for in vivo skin irritation and will be used for classification. The skin irritation was scored according to the Draize scale. The mean score (24, 48, 72 h) for erythema and oedema for all three animals were as follows:

Erythema: 1, 0.67 and 0.67

Oedema: 0 (all animals)

Furthermore, it was noted a slight dryness on the cutaneous treated area, from the 2nd or 3rd day of the test in two animals. This reaction was ever noted at the end of the observation time (D14) in one animal.

According to regulation (EC) 1272/2008 and subsequent amendments the substance will not be classified as skin irritant.

Eye irritation

Reference Richeux (2006) is considered as the key study for in vivo eye irritation and will be used for classification. The eye irritation was scored according to the Draize scale. The mean score (24, 48, 72 h) for cornea, iris conjunctivae redness and chemosis all three animals were as follows:

Cornea: 0 (all animals)

Iris: 0 (all animals)

Conjunctivae redness: 1, 0.67 and 0.67

Chemosis: 0.33, 0 and 0

The study was terminated after 4 days. According to regulation (EC) 1272/2008 and subsequent amendments the substance will not be classified as eye irritant.