Registration Dossier

Administrative data

Description of key information

Skin irritation:
An acute dermal irritation study (Pooles, 2009) is available which is key study. This study showed that the test substance is slightly irritating.
Eye irritation:
An acute eye irritation study (Pooles, 2009) is available which is key study. This study showed that the test substance is slightly irritating.

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:
From 14 to 24 Jan 2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study run to a method comparable with current guidelines and to GLP
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Test material information:
Composition 1
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories UK Limited, Bicester, Oxon, UK.
- Age at study initiation: 12 to 20 weeks old
- Weight at study initiation: 2.0 to 3.5 kg
- Housing: Individually housed in suspended cages.
- Diet (e.g. ad libitum): Free access to mains food.
- Water (e.g. ad libitum): Free access to mains drinking water.
- Acclimation period: At least five days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23℃
- Humidity (%): 30 to 70%
- Air changes (per hr): At least 15 changes per hour.
- Photoperiod (hrs dark / hrs light): 12 hours continuous light (06:00 to 18:00) and 12 hours darkness.

IN-LIFE DATES: From: 14 Jan 2009 To: 24 Jan 2009
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
water
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g
- Concentration (if solution):

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration (if solution):
- Lot/batch no. (if required):
- Purity:
Duration of treatment / exposure:
For the first animal: 3 mins, 1 hour and 4 hours
For the other two animals: 4 hours
Observation period:
72 hours
Number of animals:
3 males
Details on study design:
One rabbit was initially treated. Three suitable sites were selected on the back of the rabbit. At each test site a quantity of 0.5 g of the test material, moistened with 0.5 mL of distilled water, was introduced under a 2.5 cm × 2.5 cm cotton gauze patch and placed in position on the shorn skin. Each patch was secured in position with a strip of surgical adhesive tape. To prevent the animal interfering with the patches, the trunk of the rabbit was wrapped in an elasticated corset for the duration of the exposure period.
One patch was removed at each of three time points: 3 minutes, 1 hour and 4 hours after application. Any residual test material was removed by gentle swabbing with cotton wool soaked in distilled water.
After consideration of the skin reactions produced in the first animal, two additional animals were treated with 0.5 g of test material moistened with 0.5 mL of distilled water. One patch was applied to the back of each rabbit, and was allowed to remain in contact with the skin for a period of four hours.
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: Mean of 24, 48 and 72 hours
Score:
ca. 0.44
Max. score:
2
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: The exposure period is 4 hours.
Irritation parameter:
edema score
Basis:
mean
Time point:
other: Mean of 24, 48 and 72 hours
Score:
ca. 0.11
Max. score:
1
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: The exposure period is 4 hours.
Irritant / corrosive response data:
3-minute exposure period:
No evidence of skin irritation was noted during the study.

1-hour exposure period:
No evidence of skin irritation was noted during the study.

4-hour exposure period:
Very slight erythema was noted at one treated skin site one hour after patch removal. Well-defined erythema and very slight oedema were noted at one treated skin site and very slight erythema was noted at one other treated skin site at the 24-hour observation. Very slight erythema was noted at one treated skin site at the 48-hour observation.
One treated skin site appeared normal at the 48-hour observation and one other treated skin site appeared normal at the 72-hour observation. One treated skin site appeared normal throughout the test.
Other effects:
All animals showed expected gain in bodyweight during the study.

Individual skin reactions following 4-hour exposure

Skin reaction

Observation time

Individual scores-Rabbit number and sex

68120 Male

68163 Male

68164 Male

Erythema/Eschar formation

1 hour

24 hours

48 hours

72 hours

0

0

0

0

1

2

1

0

0

1

0

0

Oedema formation

1 hour

24 hours

48 hours

72 hours

0

0

0

0

0

1

0

0

0

0

0

0

Interpretation of results:
slightly irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test substance was mildly irritating to rabbit skin.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (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:
From 27 Jan to 05 Feb 2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study run to a method comparable with current guidelines and to GLP
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Test material information:
Composition 1
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories UK Limited, Bicester, Oxon, UK.
- Age at study initiation: 12 to 20 weeks old
- Weight at study initiation: 2.0 to 3.5 kg
- Housing: Individually housed in suspended cages.
- Diet (e.g. ad libitum): Free access to mains food.
- Water (e.g. ad libitum): Free access to mains drinking water.
- Acclimation period: At least five days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23℃
- Humidity (%): 30 to 70%
- Air changes (per hr): At least 15 changes per hour.
- Photoperiod (hrs dark / hrs light): 12 hours continuous light (06:00 to 18:00) and 12 hours darkness.

IN-LIFE DATES: From: 27 Jan 2009 To: 05 Feb 2009
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL (approx. 51 mg)
- Concentration (if solution):
Duration of treatment / exposure:
One second
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
3 males
Details on study design:
Initially, a single rabbit was treated. A volume of 0.1 mL of the test material, which was found to weigh approx. 51 mg was placed into the conjunctival sac of the right eye, formed by gently pulling the lower lid away from the eyeball. The upper and lower eyelids were held together for about one second immediately after treatment, to prevent loss of the test material, and then released. The left eye remained untreated and was used for control purposes. Immediately after administration of the test material, an assessment of the initial pain reaction was made according to the six point scale.
After consideration of the ocular responses produced in the first treated animal, two additional animals were treated.
Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment, according to the numerical evaluation.
Any other ocular effects were also noted. Examination of the eye was facilitated by the use of the light source from a standard ophthalmoscope.
Individual bodyweights were recorded on Day 0 ( the day of dosing) and at the end of the observation period.
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
mean
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0
Max. score:
0
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: Mean of 24, 48 and 72 hours
Score:
ca. 0.33
Max. score:
2
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: Mean of 24, 48 and 72 hours
Score:
ca. 0.33
Max. score:
2
Reversibility:
fully reversible within: 48 hours
Irritant / corrosive response data:
No corneal or iridial effects were noted during the study.
Moderate conjunctival irritation was noted in all treated eyes one hour after treatment with minimal conjunctival irritation noted at the 24-hour observation.
All treated eyes appeared normal at the 48-hour observation.

All animals showed expected gain in bodyweight during the study.

Individual eye irritation scores

Rabbit

Time after treatment

Cornea

Iris

Conjunctivae

Redness

Chemosis

Discharge

68200

1 hour

24 hours

48 hours

72 hours

0

0

0

0

0

0

0

0

2

1

0

0

2

1

0

0

2

1

0

0

68215

1 hour

24 hours

48 hours

72 hours

0

0

0

0

0

0

0

0

2

1

0

0

2

1

0

0

2

1

0

0

68216

1 hour

24 hours

48 hours

72 hours

0

0

0

0

0

0

0

0

2

1

0

0

2

1

0

0

2

1

0

0

Interpretation of results:
slightly irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test substance was slightly irritating to rabbit eye.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Skin irritation:

An acute dermal irritation study was conducted according to OECD 404 using rabbits (Pooles, 2009). Key study.

This study showed that the test substance is slightly irritating to rabbit skin.

Eye irritation:

An acute eye irritation study was conducted according to OECD 405 using rabbits (Pooles, 2009). Key study.

This study showed that the test substance is slightly irritating to rabbit eye.


Justification for selection of skin irritation / corrosion endpoint:
Study run to a method comparable with current guidelines and to GLP

Justification for selection of eye irritation endpoint:
Study run to a method comparable with current guidelines and to GLP

Effects on skin irritation/corrosion: slightly irritating

Effects on eye irritation: slightly irritating

Justification for classification or non-classification

Skin irritation/corrosion: Mean scores at 24, 48 & 72 hours for erythema were < 2.3 (actual value 0.44) for oedema were < 2.3 (actual value 0.11). In addition all reactions were fully reversible within the observation period (actual value within 72 hours).

Serious eye damage/eye irritation: Mean scores at 24, 48 & 72 hours for corneal opacity were < 1 (actual value 0), for iritis were < 1 (actual value 0), for conjunctival redness were < 2 (actual value 0.33) and for conjunctival oedema were < 1 (actual value 0.33).

Therefore in accordance with Regulation (EC) No. 1272/2008 Tables 3.2.2 & 3.3.2 the substance is not classified for the skin corrosion/irritation and serious eye damage/eye irritation endpoint.