Registration Dossier

Administrative data

Description of key information

To evaluate the irritation potential of the test article, skin or eyes of New Zealand White rabbits were treated with the test substance or structural analogues (according OECD guideline 404 and 405) and reactions were observed and scored up to 72h. Application onto skin provoked slight to well defined erythema and very slight edema which resolved within 72h. In contact with eyes, slight reactions in conjunctiva and cornea were observed. All reactions were reversible within 72h and are below the threshold of significance. The test substance is considered to be as non-irritating to skin or eyes.

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:
comparable to guideline study with acceptable restrictions
Remarks:
details about test substance, animal source/breeder, in life dates and animal enviroment (air changes per hour) are missing
Qualifier:
equivalent or similar to
Guideline:
other: "Hazardous Substances Regulations" under the U.S. Federal Hazardous Substances Labelling Act
Version / remarks:
Sect. 191.11 (February 1965)
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
12 May 1981 / The study was performed before the guideline was published.
Deviations:
yes
Remarks:
exposure duration (24h instead of 6h), no washing step, no readings after 30-60 minutes and 48 hours, different scoring
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: /
- Age at study initiation: 17-20 weeks
- Weight at study initiation: 3.09 kg male and 3.10 kg female
- Housing: singly
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum, sterile
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 1
- Humidity (%): 50-70
- Air changes (per hr): /
- Photoperiod (hrs dark / hrs light): 10h, 8-18.00 hours
Type of coverage:
occlusive
Preparation of test site:
other: shaved and right hand site abraded
Vehicle:
other: PEG 50 % aqueous solution
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1 ml containing 0.5 g
- Concentration (if solution): 50 %

VEHICLE
- Amount(s) applied (volume or weight with unit): 1 ml
- Concentration (if solution): 50 %

10 g of the test compound mixed with 12 ml of a 50 % aqueous solution of polyethylene glycol to make a suspension of 20ml, 10 ml of which was applied to each test site on a 2.5 cm square gauze pad.
Duration of treatment / exposure:
24h
Observation period:
72h
Number of animals:
5 male, 1 female
Details on study design:
TEST SITE
- Area of exposure: back/flanks
- % coverage: 10
- Type of wrap if used: aluminium foil secured with "Sleek" adhesive tape

SCORING SYSTEM: Draize
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72h
Remarks on result:
other: intact skin
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24h
Score:
1.17
Max. score:
4
Reversibility:
fully reversible within: 72h
Remarks on result:
other: abraded skin
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24h
Score:
1.17
Max. score:
4
Reversibility:
fully reversible within: 72h
Remarks on result:
other: intact skin
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 72h
Remarks on result:
other: abraded skin
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: all time points
Score:
1.2
Max. score:
8
Remarks on result:
other: slightly irritating according Draize system
Irritant / corrosive response data:
24 hours.
Slight to well defined erythema was seen on all sites and very slight to slight oedema on 5/6 intact and 4/6 abraded.sites.
72 hours.
All sites were normal.

Generally, there was very little difference seen in the reactions between intact and abraded sites.

The primary irritation score was 1.2.

Interpretation of results:
GHS criteria not met
Conclusions:
Based on the results of the test and the primary irritation score of 1.2, no indication for classification according to GHS is indicated.
Executive summary:

In the primary skin irritation test, similar to OECD 404, male and female New Zealand White rabbits were dermally treated with the test substance.

Five male and one female were singly housed and shaved (and partially abraded) before the substance was applied as a aqueous solution with polyethylene glycol as vehicle.

The test substance was covered by an occlusive coverage and the test site was treated for 24 hours.

After the removal of the coverage, the site was observed for further 72 hours.

There was very little difference seen in the reactions between intact and abraded sites and the primary irritation score was 1.2.

The test substance is not considered to be skin irritant to rabbits.

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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
details about test substance, animal source/breeder, in life dates and animal enviroment (air changes per hour) are missing
Qualifier:
according to
Guideline:
other: "Hazardous Substances Regulations" under the U.S.A. Federal Hazardous Substances Labelling Act
Version / remarks:
Sect.191.12 (February 1965)
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
12 May 1981 / The study was performed before the guideline was published.
Deviations:
yes
Remarks:
period of treatment different to guideline, slightly different scoring system
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: /
- Age at study initiation: 17-20 weeks
- Weight at study initiation: 3.09 kg male and 3.10 kg female
- Housing: singly
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum, sterile
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 1
- Humidity (%): 50-70
- Air changes (per hr): /
- Photoperiod (hrs dark / hrs light): 10h, 8-18.00 hours
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 mg
Duration of treatment / exposure:
1 s eye held closed, 30 s treatment with open eye
Observation period (in vivo):
1, 24, 48 and 72 h
Number of animals or in vitro replicates:
5 male, 1 female
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): warm water 200 ml
- Time after start of exposure: 30 sec

SCORING SYSTEM:
Appraisal of the Safety of Chemicals in Food Drugs and Cosmetics" page 51, published by the Association of Food and Drug Officials of the U.S.A.

The eye reactions were assessed as follows:

Score : Assessment
0 non irritant
>0 - 10 minimally irritant
11 - 25 slightly irritant
26 - 56 moderately irritant
57 - 84 markedly irritant
> 84 extremely irritant


TOOL USED TO ASSESS SCORE: fluorescein
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 1h
Score:
10
Max. score:
80
Remarks on result:
other: washed and unwashed
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24h
Score:
5
Max. score:
80
Remarks on result:
other: 3 unwashed, 1 washed
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 48h
Score:
5
Max. score:
80
Reversibility:
fully reversible within: 72h
Remarks on result:
other: unwashed only
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 1h
Score:
ca. 5
Max. score:
20
Remarks on result:
other: washed and unwashed
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24h
Score:
2
Max. score:
20
Remarks on result:
other: washed
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24h
Score:
5
Max. score:
20
Remarks on result:
other: unwashed
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 48h
Score:
2
Max. score:
20
Remarks on result:
other: washed and unwashed
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 72h
Score:
ca. 1
Max. score:
20
Reversibility:
fully reversible within: 6d
Remarks on result:
other: unwashed
Irritant / corrosive response data:
Conjunctiva.
A very slight to slight reaction was seen in all treated eyes one hour after the application of the compound. There was very little change by 24 hours. These had returned to normal as follows: 48 hours (one washed eye), 72 hours (one unwashed and 2 washed eyes) and 6 days (2 unwashed eyes).
Cornea.
Slight opacity with damage to the surface epithelium was seen in all treated eyes at one hour. This was still present in the 3 unwashed and one washed eye at 24 hours. These had returned to normal as follows: 48 hours (one washed eye), 72 hours (2 unwashed eyes) and 6 days (one unwashed eye).

Generally, washed eyes tended to show a slightly less severe reaction than unwashed eyes.
Interpretation of results:
GHS criteria not met
Conclusions:
The test substance is a minimal eye irritant but based on the results, there is no indication for an irritating effect based on GHS.
Executive summary:

In the eye irritation test, similar to OECD 405, male and female New Zealand White rabbits were treated with the test substance as such.

Five male and one female were singly housed.

After the test substance was applied to one eye, the lid was closed for 1 second and left open for 30 seconds. Afterwards, the eye was washed with warm water and observed 1, 24, 48 and 72 hours after application. The right eye of each animal seved as control.

The slight reactions were reversible within 24 hours after application. Generally, washed eyes tended to show a slightly less severe reaction than unwashed eyes.

The test substance is not considered to be eye irritant to rabbits.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

In the primary skin irritation test, similar to OECD 404, male and female New Zealand White rabbits were dermally treated with the test substance.

Five male and one female were singly housed and shaved (and partially abraded) before the substance was applied as a aqueous solution with polyethylene glycol as vehicle.

The test substance was covered by an occlusive coverage and the test site was treated for 24 hours.

After the removal of the coverage, the site was observed for further 72 hours.

There was very little difference seen in the reactions between intact and abraded sites and the primary irritation score was 1.2.

The test substance is not considered to be skin irritant to rabbits.

Eye irritation

In the eye irritation test, similar to OECD 405, male and female New Zealand White rabbits were treated with the test substance as such.

Five male and one female were singly housed.

After the test substance was applied to one eye, the lid was closed for 1 second and left open for 30 seconds. Afterwards, the eye was washed with warm water and observed 1, 24, 48 and 72 hours after application. The right eye of each animal seved as control.

The slight reactions were reversible within 24 hours after application. Generally, washed eyes tended to show a slightly less severe reaction than unwashed eyes.

The test substance is not considered to be eye irritant to rabbits.

Justification for classification or non-classification

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008, as amended for the thirteenth time in Regulation (EU) No 2018/1480. As a result the substance is not considered to be classified for irritation under Regulation (EC) No. 1272/2008.