Registration Dossier

Administrative data

Description of key information

Skin irritation: Key study: Experimental result: According to OECD 404. GLP study. 
In the 4 hour rabbit skin irritancy test, the test material caused no skin reactions and is therefore not a skin irritant.
Eye irritation: Key study: Experimental result: According to OECD 405. GLP study.
In the rabbit eye irritancy test, the test material caused slight conjunctival redness within 1 hour of dosing which had cleared by 24 hours. The test material is therefore not an eye irritant in rabbits.

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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: According to OECD 404. GLP study. The dose level applied to the skin of the animals was 250 mg instead of 500 mg for solids, as recommended in the guideline. However, it is considered that this deviation does not affect the outcome of the study.
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
(However, it is considered that this deviation does not affect the outcome of the study).
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Sittingbourne Research Centre Breeding unit
- Age at study initiation: 4-9 months old
- Weight at study initiation: males: 3888-4462 g; females: 4966-4994 g
- Housing: Animals were singly housed in hanging, stainless-steel cages with all-mesh floors and tops and half-mesh fronts; each cage measured 67 cm x 43 cm x 45 cm.
- Diet (e.g. ad libitum): Standard Rabbit Diet, S.Q.C., Special Diet Services Ltd., Essex, ad libitum.
- Water (e.g. ad libitum): Filtered from the public supply , ad libitum.
- Acclimation period: At least, two weeks.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16-19 ºC
- Humidity (%): Not documented.
- Air changes (per hr): Not documented.
- Photoperiod (hrs dark / hrs light): Lighting was automatically switched on for the day (06.00 to 18.00 hours GMT) and off for the night (18.00 to 06.00 hours GMT).


Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
other: moistened with water
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 250 mg
Duration of treatment / exposure:
4 hours
Observation period:
30 minutes after the removal of the patch and at 24, 48 and 72 hours and 7 days after patch removal.
Number of animals:
Three per sex
Details on study design:
TEST SITE
- Area of exposure: Dorsal hair between the shoulders and hindquarters was closely shorn with fine electric clippers. A 2 cm x 2 cm lint patch was applied.
- Type of wrap if used: The patch and surrounding skin were covered by a single layer of gauze and held in place by means of an elastic adhesive bandage.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): After 4 hours the wrapping and patch were removed and the test site washed with water and gently dried.


SCORING SYSTEM: Erythema and oedema on a graded scale of 0 to 4.
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24-72 h
Score:
0
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24-72 h
Score:
0

Table 7.3.1: Dermal irritation scores

Erythema

Oedema

Animal No

1

2

3

4

5

6

1

2

3

4

5

6

after 4 h

0

0

0

0

0

0

0

0

0

0

0

0

after 24 h

0

0

0

0

0

0

0

0

0

0

0

0

after 48 h

0

0

0

0

0

0

0

0

0

0

0

0

after 72 h

0

0

0

0

0

0

0

0

0

0

0

0

after 7 days

0

0

0

0

0

0

0

0

0

0

0

0

Mean score 24 – 72 h

0.0

0.0

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In the 4 hour rabbit skin irritancy test, the test material caused no skin reactions and is therefore not a skin irritant.
Executive summary:

Six New Zealand White rabbits (3 per sex) were exposed via the dermal route to 250 mg of the test substance. After a 4 hour exposure the dresssings were removed, the skin washed with water and dried. After treatment, animals were examined for erythema, oedema and other lesions at 4, 24, 48 and 72 hours and at 7 days after patch removal. The test material caused no skin reactions and was therefore considered as not irritanting to skin.

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: According to OECD 405. GLP study.
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Sittingbourne Research Centre Breeding unit
- Age at study initiation: 4-9 months old
- Weight at study initiation: males: 3872-4184 g; females: 3276-4806 g
- Housing: Animals were singly housed in hanging, stainless-steel cages with all-mesh floors and tops and half-mesh fronts; each cage measured 67 cm x 43 cm x 45 cm.
- Diet (e.g. ad libitum): Standard Rabbit Diet, S.Q.C., Special Diet Services Ltd., Essex, ad libitum.
- Water (e.g. ad libitum): Filtered from the public supply , ad libitum.
- Acclimation period: At least, two weeks.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16-19 ºC
- Humidity (%): Not documented.
- Air changes (per hr): Not documented.
- Photoperiod (hrs dark / hrs light): Lighting was automatically switched on for the day (06.00 to 18.00 hours GMT) and off for the night (18.00 to 06.00 hours GMT).


Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 25 mg
Duration of treatment / exposure:
The eyes were not washed.
Observation period (in vivo):
A visual assessment of eye irritancy was made at 1, 4, 24, 48 and 72 hours and 7 days after instillation.
Number of animals or in vitro replicates:
Three per sex
Details on study design:
SCORING SYSTEM: Irritancy was scored for the cornea, iris and conjunctivae using the standard scores included in the study report.


TOOL USED TO ASSESS SCORE: At 24 hours and in the event of any corneal damage visualization was aided by the instillation of one drop of 2% fluorescein solution.
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24-72 h
Score:
0
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24-72 h
Score:
0
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24-72 h
Score:
0
Irritation parameter:
other: Conjunctivae redness
Basis:
mean
Time point:
other: 24-72 h
Score:
0
Irritant / corrosive response data:
The instillation of the test substance powder into the conjunctival sac of one eye of each of six rabbits resulted in slight initial pain. The only occular effect was slight conjunctival redness in all rabbits within 1 hour of dosing which had cleared by 24 hours.

Table 7.3.2: Mean eye irritation scores

Redness

Chemosis

Discharge

Opacity

Iris

24 hours

0

0

0

0

0

48 hours

0

0

0

0

0

72 hours

0

0

0

0

0

7 days

0

0

0

0

0

Mean score

24-72 h

0.0

0.0

0.0

0.0

0.0

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In the rabbit eye irritancy test, the test material caused slight conjunctival redness within 1 hour of dosing which had cleared by 24 hours. The test material is therefore not an eye irritant in rabbits.
Executive summary:

The test material (25 mg) was applied to the eyes of six New Zealand White rabbits (3 per sex). A visual assessment of eye irritancy was made at 1, 4, 24, 48 and 72 hours and 7 days after instillation. The test material caused slight conjunctival redness within 1 hour of dosing which had cleared by 24 hours.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation: Key study: Experimental result: According to OECD 404. GLP study.

In the 4 hour rabbit skin irritancy test, the test material caused no skin reactions and is therefore not a skin irritant.

Eye irritation: Key study: Experimental result: According to OECD 405. GLP study.

In the rabbit eye irritancy test, the test material caused slight conjunctival redness within 1 hour of dosing which had cleared by 24 hours. The test material is therefore not an eye irritant in rabbits.


Justification for selection of skin irritation / corrosion endpoint:
Only one study available. Klimisch 2.

Justification for selection of eye irritation endpoint:
Only one study available. Klimisch 2.

Justification for classification or non-classification

Based on the available data, the substance is not classified as irritating.