Registration Dossier

Administrative data

Description of key information

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Strain: Crl:NZW/Kbl.BR
- Sex: males
- Source: Charles River Ltd., Margate, UK
- Age at study initiation: approx. 14-17 weeks
- Weight at study initiation: 2.64-3.21 kg
- Housing: singly in floor-pens with minimum floor area of 0.6 m².
- Diet and water: ad libitum
- Acclimation period: at least 27 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16-22°C
- Humidity (%): within the range 40-80%
- Air changes (per hr): at least 10
- Photoperiod (hrs dark / hrs light): 10/14
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
other: The untreated skin served as control.
Amount / concentration applied:
500 mg
Duration of treatment / exposure:
4 h
Observation period:
According to guideline, but given that no skin reactions at all were observed in the depicted study, the observation period was terminated on Day 4.
Number of animals:
3
Details on study design:
The test article was applied to a 30 x 20 mm area on the clipped and moistened (with approx. 0.1 ml distilled water) dorsum on Day I. The designated area was then covered by a dense gauze patch (30 x 20 mm). This in turn was covered by a larger gauze patch (40 x 40 mm) and an open weave, elasticated adhesive bandage "Steroban" from Steroplast Ltd, Bredbury which was wrapped firmly around the torso to secure the applied dose and patch in the correct position. The dressings were considered to be semi-occlusive. The test patch was removed after four hours and the treated skin was lightly brushed clean of any solid residues and swabbed with moist cotton wool .
For reasons of animal welfare the test substance was applied to the skin of a single rabbit initially. The treated skin was assessed for a period of not less than three days to ensure the test article did not cause severe dermal changes. Subsequently, two further rabbits were similarly subjected to the testing.

Further details on study: A detailed account of any clinical signs of ill health or systemic toxicity was maintained. Each rabbit was weighed on the day before dosing commenced. The condition of all dermal test sites was recorded one hour, 24, 48 and 72 hours after removal of the patch and dressing.
Irritation parameter:
erythema score
Basis:
animal: #1, #2, #3
Time point:
other: 24, 48 and 72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal: #1, #2, #3
Time point:
other: 24, 48 and 72 h
Score:
0
Max. score:
4
Other effects:
There was no indication of any adverse effect on the rabbits.
Executive summary:

An acute dermal irritation/ corrosion study according to OECD TG 404 was performed with the test substance applied under semiocclusive dressings for 4 hours to the intact but shaved skin of a group of 3 male rabbits. No dermal reactions were observed at all after 24, 48 and 72 hours. Furthermore no indication of any adverse effect on the rabbits could be seen.

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
(1987)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Strain: Crl:NZW/Kbl.BR
- Sex: males
- Source: Charles River Ltd., Margate, UK
- Age at study initiation: approx. 11-14 weeks
- Weight at study initiation: 2.74-3.09 kg
- Housing: singly in floor-pens with minimum floor area of 0.6 m².
- Diet and water: ad libitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16-22°C
- Humidity (%): within the range 40-80%
- Air changes (per hr): at least 10
- Photoperiod (hrs dark / hrs light): 10/14
Vehicle:
unchanged (no vehicle)
Controls:
other: The right eye remained untreated and served as a control.
Amount / concentration applied:
22 mg (weight equivalent to compacted volume of 0.1 ml)
Duration of treatment / exposure:
After instillation the eyelids were held closed for a few seconds to prevent loss of the dose.
Observation period (in vivo):
As ocular changes persisted, further observations were recorded daily until resolution of the changes occurred or until Day 22.
Number of animals or in vitro replicates:
3
Details on study design:
One dose consisting of the above specified amount of powdered test substance, dispensed from a spatula, was instilled into the left conjunctival sac of a single rabbit. The lower eyelid was gently prised away from the eyeball to create a receptacle for the dose. After instillation the eyelids were held closed for a few seconds to prevent loss of the dose. The condition of the treated eye of the rabbit was assessed for a period of not less than three days to ensure the test article did not cause marked ocular damage. Subsequently, two further rabbits were subjected to a single instillation of the test article into the left conjunctival sac as described above.

Further details on study: Any clinical signs of ill health or systemic toxicity was maintained. The weight of each rabbit was determined on the day before dosing commenced. Ocular changes were assessed and recorded immediately, one half hour, one and four hours after treatment on Day 1 and 24, 48 and 72 hours after treatment.

TOOL USED TO ASSESS SCORE: pencil-beam torch. At examinations carried out 24 hours after treatment, and on subsequent daily examinations, the cornea was subject to application of 2% aqueous fluorescein solution followed by irrigation with water for irrigation. The corneal surface was then illuminated by an ultraviolet source.
Irritation parameter:
cornea opacity score
Remarks:
(opacity)
Basis:
animal #1
Time point:
other: 24, 48 and 72 h
Score:
>= 1 - <= 2
Max. score:
4
Reversibility:
fully reversible within: 12 days
Remarks on result:
other: mean score after 72 h: 1.3
Irritation parameter:
cornea opacity score
Remarks:
(opacity)
Basis:
animal #2
Time point:
other: 24, 48 and 72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
cornea opacity score
Remarks:
(opacity)
Basis:
animal #3
Time point:
other: 24, 48 and 72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 22 days
Irritation parameter:
iris score
Basis:
animal: #1, #2, #3
Time point:
other: 24, 48 and 72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #1
Time point:
other: 24, 48 and 72 h
Score:
>= 1 - <= 2
Max. score:
3
Reversibility:
fully reversible within: 11 days
Remarks on result:
other: mean score after 72 h: 1.7
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #2
Time point:
other: 24, 48 and 72 h
Score:
>= 0 - <= 2
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: mean score after 72 h: 0.7
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #3
Time point:
other: 24, 48 and 72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 20 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 24, 48 and 72 h
Score:
>= 1 - <= 2
Max. score:
4
Reversibility:
fully reversible within: 8 days
Remarks on result:
other: mean score after 72 h: 1.3
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: 24, 48 and 72 h
Score:
>= 0 - <= 2
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: mean score after 72 h: 0.7
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: 24, 48 and 72 h
Score:
>= 1 - <= 2
Max. score:
4
Reversibility:
fully reversible within: 6 days
Remarks on result:
other: mean score after 72 h: 1.7
Irritant / corrosive response data:
The treated eye of one animal showed corneal damage (circa 10% of corneal surface affected) which persisted for three weeks after instillation of the test article.
Other effects:
There was virtually no initial sting response. No observations indicative of systemic toxicity or ill health were noted for any rabbits during the course of the study.
Executive summary:

An acute eye irritation/ corrosion test according to OECD TG 405 was performed on three male rabbits. Ocular reactions were assessed for up to 21 days after treatment.

Within 24, 48 and 72 hours after instillation of the test substance areas of corneal opacity, conjunctival reactions and chemosis affected all rabbits (at maximum score 2). All conjunctival irritation resolved before completion of the observation period, but corneal changes persisted in one rabbit until the end of the study. There were no signs indicative of systemic toxicity or ill health noted during the course of the study.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

The test substance was not irritating to the skin of rabbits (OECD TG 404).

An eye irritation test (OECD TG 405) revealed effects of the test substance on corneal opacity and conjunctiva (redness and chemosis) on all rabbits (maximum score 2). All conjunctival irritation resolved before completion of the observation period, but corneal changes persisted in one rabbit until the end of the study.

Acute inhalation testing with substance (dust aerosol) revealed at the limit concentration (5790 mg(m³) findings that might be indicative for a local irritant effect (shallow respiration, slight increase in lung weights, impairment of general condition).


Justification for selection of skin irritation / corrosion endpoint:
Only one study available

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

Effects on eye irritation: corrosive

Justification for classification or non-classification

Not classified for Skin Irritation/Corrosion according to Regulation (EC) No 790/2009 (Amendment to Regulation (EC) No 1272/2008) and based on the criteria set out in Annex I to Regulation (EC) No 1272/2008 or in Annex VI to Council Directive 67/548/EEC (June 1967).

Not classified for Respiratory Irritation according to Regulation (EC) No 790/2009 (Amendment to Regulation (EC) No 1272/2008) and based on the criteria set out in Annex I to Regulation (EC) No 1272/2008 or in Annex VI to Council Directive 67/548/EEC (June 1967).

Classified for Eye Irritation as Eye Dam. 1 (H318: Causes serious eye damage) or as Xi, R41 (Risk of serious damage to eyes)

according to Regulation (EC) No 790/2009 (Amendment to Regulation (EC) No 1272/2008) and based on the criteria set out in Annex I to Regulation (EC) No 1272/2008 or in Annex VI to Council Directive 67/548/EEC (June 1967), respectively.