N,N''-(methylenedi-4,1-phenylene)bis[N'-octyl]urea

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

October 08, 2002 - October 13, 2002

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2003

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

451-060-3

EC Name:

-

Cas Number:

122886-55-9

Molecular formula:

Hill formula: C31H48N4O2 CAS formula: C31H48N4O2

IUPAC Name:

N,N’’-(methylenedi-4,1-phenylene)bis(N’-octylurea)

Constituent 2

Reference substance name:

N-{4-[(4-{[(octadecylamino)carbonyl]amino}phenyl)methyl]phenyl}-N’-octylurea

Cas Number:

117328-86-6

Molecular formula:

Hill formula: C41H68N4O2 CAS formula: C41H68N4O2

IUPAC Name:

N-{4-[(4-{[(octadecylamino)carbonyl]amino}phenyl)methyl]phenyl}-N’-octylurea

Constituent 3

Reference substance name:

3,3'-dioctadecyl-1,1'-methylenebis(4,1-phenylene)diurea

EC Number:

406-690-3

EC Name:

3,3'-dioctadecyl-1,1'-methylenebis(4,1-phenylene)diurea

Cas Number:

43136-14-7

Molecular formula:

Hill formula: C51H88N4O2 CAS formula: C51H88N4O2

IUPAC Name:

N,N’’-(methylenedi-4,1-phenylene)bis(N’-octadecylurea)

Test material form:

solid: particulate/powder

Details on test material:

- Name of test material (as cited in study report): KY-EU
- Appearance: white powder
- Storage condition of test material: in darkness at room temperature

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

- Source: CEGAV, Saint Mars d'Egrenne, France
- Age at study initiation: 2 to 4 months old
- Weight at study initiation: 2.7 ± 0.3 kg
- Housing: The animals were individually housed in polystyrene cages (48.2 cm x 58 cm x 36.5 cm).
- Diet (e.g. ad libitum): Free access to 110 pelleted diet (UAR, Villemoisson, Epinay-sur-Orge, France).
- Water (e.g. ad libitum): Free access to water filtered by a FG Millipore membrane (0.22 micron).
- Acclimation period: The acclimatization period was at least 5 days before the start of treatment.

Food was analysed regularly by the supplier for composition and contaminant levels. Bacteriological and chemical analyses of water were performed regularly by external laboratories. These analyses include the detection of possible contaminants (pesticides, heavy metals and nitrosamines).
No contaminants were known to have been present in the diet or drinking water at levels which may be expected to have interfered with or prejudiced the outcome of the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3
- Humidity (%): 30 - 70
The relative humidity recorded in the animal room was sometimes outside of the target ranges specified in the study plan. This minor deviation was not considered the validity or integrity of the study.
- Air changes (per hr): approximately 12
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: October 08, 2002 to October 13, 2002

Test system

Type of coverage:

semiocclusive

Preparation of test site:

other: clipped using electric clippers

Vehicle:

other: The test substance was moistened with purified water.

Controls:

other: The untreated skin of each animal served as controls.

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 grams

Duration of treatment / exposure:

Single application.

Observation period:

4 days.

Number of animals:

3 males.

Details on study design:

STUDY DESIGN
As no information was available on the irritant properties of the test item, in the first instance, the test item was evaluated on a single animal. The duration of exposure was 3 minutes on one flank and 4 hours on the other flank.
Since the test item was not corrosive/severely irritant on this first animal, it was than applied for 4 hours to two other animals.

TEST SITE
The day before treatment, both flanks of each animal were clipped using electric clippers and the skin of each animal was examined. Only animals with healthy intact skin were used. Clipping was repeated thereafter on day 2 or 3.
Doses of 500 mg of the test item in its original form were placed on a moistened gauze pad, which was then applied to the right flank (application for 4 hours) or the left flank (application for 3 minutes) of the animals.
The test item and the gauze pad were held in contact with the skin by means of an adhesive hypoallergic aerated semi-occlusive dressing and a restraining bandage.

REMOVAL OF TEST SUBSTANCE
After removal of the dressing, any residual test item was wiped off by means of a moistened or dry cotton pad.

OBSERVATIONS
- Mortality/Viability: No data
- Toxicity: No data
- Body Weight: No data
- Necropsy: No data
- Irritation:
The skin reactions were assessed at approximately 1, 24, 48 and 72 hours after the removal of the dressing and test substance. The irritation scores were recorded.

SCORING SYSTEM:
The irritation was assessed according to the following numerical scoring system. At each observation, the highest scores given were recorded:

Erythema and eschar formation:
0: No erythema
1: Very slight erythema (barely perceptible)
2: Well-defined erythema
3: Moderate to severe erythema
4: Severe erythema (beet redness) to slight eschar formation (injuries in depth)

Oedema formation:
0: No oedema
1; Very slight oedema (barely perceptible)
2: Slight oedema (edges of area well-defined by definite raising)
3: Moderate oedema (raised approximately 1 millimeter)
4: Severe oedema (raised more than 1 millimeter and extending beyond the area of exposure)

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 5

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

No cutaneous reactions were observed during the study.

Tables containing individual and mean irritation scores are specified in the attached table.

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

A primary skin irritation/corrosion study with KY-EU in the rabbit (4-hour semi-occlusive application, 3 males) was conducted according to OECD 404 and GLP guidelines. No skin irritation was observed, and based on these results KY-EU does not have to be classified and has no obligatory labelling requirement for skin irritation.

Executive summary:

In a skin irritation study performed according to OECD 404 and GLP principles, three male rabbits were exposed to 0.5 g of substance semi-occlusively for 4 hours. Skin reactions were assessed 1, 24, 48 and 72 hours after exposure.

No cutaneous reactions were observed during the study. No oedema was noted in any of the animals. Systemic effects were not described or recorded. KY-EU is considered to be not skin irritating.