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

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

December 1993

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1994

Report date:

1994

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

1992

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

1992

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

429-380-1

EC Name:

-

Cas Number:

133336-92-2

Molecular formula:

C29H28N4O2

IUPAC Name:

1-(4-methylphenyl)-3-{4-[(4-{[(4-methylphenyl)carbamoyl]amino}phenyl)methyl]phenyl}urea

Test material form:

solid: particulate/powder

Details on test material:

- Particle size distribution: 10%: < 23.94 µm
- Density: 1.32 g/cm3 (20°C)
- Test substance storage: at room temperature in the dark
- Stability under storage conditions: stable

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

- Source: Broekman Institute, Someren, The Netherlands.
- Age at study initiation: approx. 12 weeks old.
- Weight at study initiation: 2374 - 2772 grams.
- Housing: Animals were housed individually in cages with perforated floors.
- Diet: Free access to pelleted diet for rabbits (LKK-20, pellet diameter 4mm, Hope Farms, Woerden, The Netherlands).
- Water: Free access to tap water.
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
set to maintain:
- Temperature (°C): 21
- Humidity (%): 55
- Air changes (per hr): approx 15
- Photoperiod (hrs dark / hrs light): 12/12.

IN-LIFE DATES: From: 21 December 1993 to 24 December 1993

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 grams

Duration of treatment / exposure:

Single application.

Observation period:

3 days.

Number of animals:

3 males.

Details on study design:

TEST SUBSTANCE PREPARATION
A pre-test revealed that the test substance was hydrophobic. Therefore the skin of the animals was moistened with distilled water, to ensure close contact of the test substance to the skin.

TEST SITE
Approximately 24 hours before treatment, the dorsal fur was clipped with electric clippers, exposing an area of approximately 150 square centimeters (10x15 cm). To facilitate scoring, treated skin areas were re-clipped at least 3 hours before the observations.

The test substance was applied to the skin of one flank, using a patch of 2x3 cm.

REMOVAL OF TEST SUBSTANCE
Four hours after the application, the dressing was removed and the skin cleaned of residual test substance using tap water.

OBSERVATIONS
- Mortality/Viability: Twice daily.
- Toxicity: At least once daily.
- Body Weight: Day of treatment (prior to application).
- Necropsy: \\\tekst onder necropsy overnemen.
- Irritation:
The skin reactions were assessed at approximately 1, 24, 48 and 72 hours after the removal of the dressings and test substance. The irritation scores and a description of all other (local) effects were recorded.

SCORING SYSTEM:
The irritation was assessed according to the numerical scoring system according to OECD 404.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No skin irritation was caused by KY-AF after a 4 hour exposure. There was no evidence of a corrosive effect on the skin.

Other effects:

No staining of the treated skin by the test substance was observed.

Applicant's summary and conclusion

Interpretation of results:

other: Not irritating

Remarks:

According to Regulation (EC) No 1272/2008 and its amendments.

Conclusions:

In an skin irritation study with KY-AF in rabbits, performed according to OECD/EC test guidelines, no irritation was observed.

Executive summary:

An assessment of primary skin irritation/corrosion with KY-AF in the rabbit using a 4 hour semi-occlusive application was performed according to OECD/EC test guidelines and in accordance with GLP principles. No erythema or oedema was observed and there was no evidence of irritation or a corrosive effect on the skin.

Based on these results, KY-AF does not have to be classified and has no obligatory labelling requirement for dermal irritation or corrosion according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2015) (including all amendments) and Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments).