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

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2009-11-04 to 2010-01-28

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

2002

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

2008

Deviations:

no

Principles of method if other than guideline:

NA

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

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

EC Number:

406-370-3

EC Name:

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

Cas Number:

58890-25-8

Molecular formula:

C27 H36 N4 O2

IUPAC Name:

1-cyclohexyl-3-[4-({4-[(cyclohexylcarbamoyl)amino]phenyl}methyl)phenyl]urea

Details on test material:

- Name of test material (as cited in study report): Thickener TH28
- Chemical name: 3,3’-dicyclohexyl-1,1’-methylenebis(4,1-phenylene)diurea
- Physical state: white solid, odourless
- Analytical purity: > 95 %
- Lot/batch No.: AH-1290/2009-02
- Expiration date of the lot/batch: 07 September 2012
- Stability under test conditions: stable for at least 3 years
- Storage condition of test material: room temperature

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: S&K-LAP Kft., 2173 Kartal, Császár út 135, Hungary
- Age at study initiation: Young adult rabbits, 10 weeks old
- Weight at study initiation: 3098-3218 g
- Housing: Rabbits were individually housed in AAALAC approved metal wire rabbit cages (65 x 65 cm with height of 45 cm, on 2 levels with a shelf to allow rabbits to climb up and to stretch out). Cages were of an open wire structure and were placed together to allow some social interaction with rabbit(s) in adjoining cages.
- Diet (e.g. ad libitum): The animals received PURINA Base – Lap gr. diet for rabbits produced by AGRIBRANDS Europe Hungary PLC, H-5300 Karcag, Madarasi road, Hungary, ad libitum.
- Water (e.g. ad libitum): The animals received tap water as for human consumption from an automatic watering system ad libitum.
- Acclimation period: 13 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17.3 - 21.2 degree C
- Humidity (%): 30 - 67 %
- Air changes (per hr): 15 - 20 air exchanges/hour.
- Photoperiod: 12 hours light daily, from 6.00 a.m. to 6.00 p.m.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

other: clipped

Vehicle:

unchanged (no vehicle)

Controls:

other: The untreated skin of each animal served as a control.

Amount / concentration applied:

TEST MATERIAL
The test item was used undiluted and a single dose of 0.5 g of the test item was applied to the test area.

Duration of treatment / exposure:

4 hours

Observation period:

Animals were examined for signs of erythema and oedema, and the responses scored at 60 minutes, and then at 24, 48 and 72 hours after the patch removal. As no sign of irritation was observed at 72 hours, the study was terminated following the observation at 72 hours.

Number of animals:

3 male animals

Details on study design:

TEST SITE
- Area of exposure: Back and flanks of the animals
- % coverage: The test item was applied to an area of approximately 6 cm² of intact skin.
- Type of wrap if used: Semi-occlusive plastic wrap


REMOVAL OF TEST SUBSTANCE
- Washing (if done): The remaining test item was removed with water of body temperature
- Time after start of exposure: After 4 hours

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:

0.33

Max. score:

4

Reversibility:

fully reversible

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 4

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0.11

Max. score:

4

Reversibility:

fully reversible

Results 5

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Other effects:

There was no mortality or systemic clinical changes related to the test item administration.
There was no effect of treatment on body weight.

Any other information on results incl. tables

Mean values of skin irritation scores (24, 48, 72 hours reading):

Animal Number	Sex	Erythema	Oedema
00399	male	0.00	0.00
00381	male	0.33	0.00
00382	male	0.00	0.00

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this acute skin irritation/corrosion study with rabbits, the test item did not cause any skin irritating effect.

Executive summary:

In this skin irritation study, albino New Zealand White rabbits were treated with the test item.

A semi-occlusive application procedure was used. The test item was administered undiluted, at a single dose of 0.5 g for a period of 4 hours. Gauze was placed onto the hairless skin of the rabbit, test item was applied to the gauze, additional gauze was placed over the test item and an adhesive clear plastic patch was applied. The trunk was wrapped in clear plastic with medical tubing used to hold the patch in place. The untreated skin of each animal served as control.

 

There was no mortality or systemic clinical changes related to the test item administration.

There was no effect of treatment on body weight.

 

At 1 hour after patch removal, well defined erythema (score 2) was observed in 1/3 animals. At 24 hours after patch removal, very slight erythema(score 1) was observed in 1/3 animals. At 48 and 72 hours after patch removal, there were no observed signs on the skin of the treated animals. Accordingly, the study was terminated after the observation performed at 72 hours.

 

The individual mean scores of the 3 animals (considering readings at 24, 48 and 72 hours) for erythema were 0.00, 0.33 and 0.00. The individual mean scores of the 3 animals (considering readings at 24, 48 and 72 hours) for oedema were 0.00, 0.00 and 0.00.

Under the conditions of this acute skin irritation/corrosion study with rabbits, the test item did not cause any skin irritating effect.