Registration Dossier

Administrative data

Description of key information

The test substance did not produce skin or eye irritation/corrosion in OECD guideline, GLP studies.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study was selected as the key study because the information provided for the hazard endpoint is sufficient for the purpose of classification and labeling and/or risk assessment.
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Remarks:
The study was conducted according to the guideline in effect at the time of study conduct.
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: approximately three to four months old
- Weight at study initiation: 2.50 - 2.95 kg.
- Housing: They were individually housed in suspended stainless steel cages mounted in mobile batteries. The cages measured 61 x 76 x 46 cm high and were fitted with perforated counter-sunk floor panels. A tray beneath the floor was lined with absorbent crepe paper which was changed regularly.
- Diet: Animals had free access to a commercially available standard pelleted rabbit diet.
- Water: The rabbits had free access to tap water supplied to each cage by an automatic piped system.
- Acclimation period: at least seven days

ENVIRONMENTAL CONDITIONS
- The animals were housed in a lagomorph room within a limited-access building. The room was kept at slight positive pressure relative to the outside and had its own filtered air supply giving approximately 15 complete air changes per hour without re-circulation. A temperature range of 18-19°C and a relative humidity range of 46-62%. were achieved during the study. The achieved values were monitored daily. Electric time-switches operated a lighting cycle of 12 hours of artificial light per day. An emergency generator was available to maintain the electricity supply in the event of a power failure.
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
other: The right test site, acting as a control, was covered by a similar semi-occlusive dressing but otherwise remained untreated.
Amount / concentration applied:
TEST MATERIAL
Amount(s) applied: 0.5 g
Duration of treatment / exposure:
4 hours
Observation period:
one hour, 24, 48 and 72 hours after removal of the dressings
Number of animals:
3 males
Details on study design:
TEST SITE
- Two test sites (6 x 6 cm) were marked on either side of the clipped area of dorsum, and moistened by direct application of approximately 0.2 mL distilled water per test site. A single dose (0.5 g) was applied directly to the skin and covered by an unmedicated gauze patch (3 x 2 cm) which was held in place on the left test site by strips of Blenderm. The right test site, acting as a control, was covered by a similar semi-occlusive dressing but otherwise remained untreated. Pads of cotton 'wool' and elasticated bandage were used to protect the patches and ensure good contact between the skin and the test material during the four-hour exposure period. The elasticated bandage was held in place by thin strips of waterproof plaster at both edges.

REMOVAL OF TEST SUBSTANCE
- The dressings were removed after four hours exposure. Where necessary, the treatment sites were gently washed with warm water and dried with paper towels to remove excess test material adhering to the skin.

SCORING SYSTEM:
- according to the criteria of Draize
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 1 to 72 hours
Score:
0
Max. score:
4
Remarks on result:
other: no erythema observed in any animal
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 1 to 72 hours
Score:
0
Max. score:
4
Remarks on result:
other: no oedema observed in any animal
Irritant / corrosive response data:
No dermal response was observed at the test site of any animal at any time during the 72 hour observation period.
Other effects:
None
Interpretation of results:
GHS criteria not met
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
This study and the conclusions which are drawn from it fulfill the quality criteria (validity, reliability, repeatability).
Under the conditions of this test, the test item was classified as 'non-irritant' to the skin.
Executive summary:

The potential of the test substance to cause inflammatory or corrosive changes upon first contact with skin was assessed by semi-occluded application of 0.5 g of the test material to the closely-clipped dorsa of three New Zealand White rabbits for four hours. Dermal reactions were assessed 1, 24, 48 and 72 hours after removal of the dressings. No dermal response was observed at the test site of any animal at any time during the 72 hour observation period. Under the conditions of this test, the test substance was classified as 'non-irritant' to the skin.

Endpoint:
skin corrosion: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study was selected as the key study because the information provided for the hazard endpoint is sufficient for the purpose of classification and labeling and/or risk assessment.
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Remarks:
The study was conducted according to guideline in effect at time of study conduct.
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Age at study initiation: approximately three and a half to four months old
- Weight at study initiation: 2.76 - 3.30 kg
- Housing: They were individually housed in suspended stainless steel cages mounted in mobile batteries. The cages measured 61 x 76 x 46 cm high and were fitted with perforated counter-sunk floor panels. A tray beneath the floor was lined with absorbent crepe paper which was changed regularly.
- Diet: Animals had free access to a commercially available standard pelleted rabbit diet
- Water: The rabbits had free access to tap water supplied to each cage by an automatic piped system.
- Acclimation period: three or four weeks

ENVIRONMENTAL CONDITIONS
- The animals were housed in a lagomorph room within a limited-access building. The room was kept at slight positive pressure relative to the outside and had its own filtered air supply giving approximately 15 complete air changes per hour without re-circulation. A temperature range of 18-19°C and a relative humidity range of 39 - 56% were achieved during the study. The achieved values were monitored daily. Electric time-switches operated a lighting cycle of 12 hours of artificial light per day. An emergency generator was available to maintain the electricity supply in the event of a power failure.
Vehicle:
unchanged (no vehicle)
Controls:
other: The untreated eye was used as a comparison with the treated eye during assessment of ocular lesions.
Amount / concentration applied:
TEST MATERIAL
- Amount(s): 0.1 g



Duration of treatment / exposure:
72 hours
Observation period (in vivo):
Ocular reactions to treatment were assessed one hour, 24, 48 and 72 hours after treatment
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: no

SCORING SYSTEM: Draize, JH (1959). In "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics" p.47. Association of Food and
Drug Officials of the United States, Austin, Texas.

The Official Journal of the European Communities (L257/8-9, Vol. 26., 16/9/83 and L257/19, Vol.26., 16/9/83) Directive 83/467/EEC.

TOOL USED TO ASSESS SCORE: An ophthalmoscope was used to facilitate inspection of the eyes.
Irritation parameter:
conjunctivae score
Basis:
other: range
Time point:
other: 1 hour to 72 hours
Score:
0 - 2
Max. score:
4
Reversibility:
fully reversible within: 24 hours
Irritation parameter:
cornea opacity score
Basis:
other: range
Time point:
other: 1 hour to 72 hours
Score:
0
Max. score:
4
Remarks on result:
other: no corneal opacity observed in any animal
Irritation parameter:
iris score
Basis:
other: range
Time point:
other: 1 hour to 72 hours
Score:
0 - 1
Max. score:
2
Reversibility:
fully reversible within: 24 hours
Irritant / corrosive response data:
A diffuse crimson-red appearance to the conjunctiva and slight chemosis and/or discharge were observed in all animals one hour after
instillation. Iritis was also observed in two rabbits at this time. The eyes of all rabbits were overtly normal at the 24 hour observation.
Instillation of the test material caused a very slight initial pain response.

The mean values for ocular lesions recorded 24, 48 and 72 hours after treatment did not equal or exceed the EEC limit values for classifying the test material as irritant to the eye.
Interpretation of results:
GHS criteria not met
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
This study and the conclusions which are drawn from it fulfill the quality criteria (validity, reliability, repeatability).
Under the conditions of this test, the test item was classified as 'non-irritant' to the eye.
Executive summary:

The test substance was evaluated for acute eye irritation potential in 3 young adult New Zealand white rabbits. An aliquot of 0.1 g of the test substance was administered to 1 eye of each animal. The eyes remained unwashed following treatment. The untreated eye served as a control. The conjunctiva, iris, and cornea of each treated eye were evaluated and scored according to a numerical scale approximately 1, 24, 48, and 72 hours, following administration. A diffuse crimson-red appearance to the conjunctiva and slight chemosis and/or discharge were observed in all animals one hour after instillation. Iritis was also observed in two rabbits at this time. The eyes of all rabbits were overtly normal at the 24 hour observation. All ocular irritation reversed by 24 hours.

Endpoint:
eye irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The test substance did not produce skin or eye irritation/corrosion in OECD guideline, GLP studies.


Justification for selection of skin irritation / corrosion endpoint:
OECD Guideline, GLP study

Justification for selection of eye irritation endpoint:
OECD Guideline, GLP study

Justification for classification or non-classification

The test substance did not produce skin or eye irritation/corrosion in OECD guideline, GLP studies. The substance does not need to be classified for irritation according the EU Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.